2024-03-29T12:57:40Zhttps://repositori.udl.cat/server/oai/requestoai:repositori.udl.cat:10459.1/648842023-02-10T19:05:09Zcom_10459.1_241com_10459.1_2col_10459.1_30324col_10459.1_49291
Granado-Serrano, Ana Belén
Martín, María Angeles
Haegeman, Guy
Goya, Luis
Bravo, Laura
Ramos, Sonia
2018-10-16T09:16:32Z
2018-10-16T09:16:32Z
2010
https://doi.org/10.1017/S0007114509991747
018373
0007-1145
http://hdl.handle.net/10459.1/64884
The dietary flavonoid epicatechin has been reported to exhibit a wide range of biological activities. The objective of the present study was to
investigate the time-dependent regulation by epicatechin on the activity of the main transcription factors (NF-kB, activator protein-1 (AP-1)
and nuclear transcription factor erythroid 2p45-related factor (Nrf2)) related to antioxidant defence and survival and proliferation pathways in
HepG2 cells. Treatment of cells with 10mM-epicatechin induced the NF-kB pathway in a time-dependent manner characterised by increased
levels of IkB kinase (IKK) and phosphorylated inhibitor of kB subunit-a (p-IkBa) and proteolytic degradation of IkB, which was
consistent with an up-regulation of the NF-kB-binding activity. Time-dependent activation of the AP-1 pathway, in concert with enhanced
c-Jun nuclear levels and induction of Nrf2 translocation and phosphorylation were also demonstrated. Additionally, epicatechin-induced NF-kB
and Nrf2 were connected to reactive oxygen species intracellular levels and to the activation of cell survival and proliferation pathways, being
phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) associated to Nrf2 modulation and ERK
to NF-kB induction. These data suggest that the epicatechin-induced survival effect occurs by the induction of redox-sensitive transcription factors
through a tight regulation of survival and proliferation pathways.
eng
info:eu-repo/semantics/openAccess
(c) Cambridge University Press, 2010
Epicatechin
NF-kB signalling
Activator protein-1
Nuclear factor-erythroid 2p45-related factor-2
Epicatechin induces NF-kB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/584452021-08-30T15:04:36Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Martínez, Ana Isabel
Castillo, Luis
Garcera, Ana
Elorza, M. Victoria
Valentín, Eulogio
Sentandreu, Rafael
2016-11-09T19:23:17Z
2016-11-09T19:23:17Z
2004-10
https://doi.org/10.1099/mic.0.27220-0
024765
1350-0872
http://hdl.handle.net/10459.1/58445
Searches in a Candida albicans database (http://genolist.pasteur.fr/CandidaDB/) identified two Individual Protein Files (IPF 15363 and 19968) whose deduced amino acid sequences showed 42% and 45% homology with Saccharomyces cerevisiae Pir4. The two DNA sequences are alleles of the same gene (CaPIR1) but IPF 19968 has a deletion of 117 bases. IPF 19968 encodes a putative polypeptide of 364 aa, which is highly O-glycosylated and has an N-mannosylated chain, four cysteine residues and seven repeats. Both alleles are expressed under different growth conditions and during wall construction by regenerating protoplasts. The heterozygous mutant cells are elongated, form clumps of several cells and are hypersensitive to drugs that affect cell wall assembly. CaPir1 was labelled with the V5 epitope and found linked to the 1,3-b-glucan of the C. albicans wall and also by disulphide bridges when expressed in S. cerevisiae.
eng
info:eu-repo/semantics/restrictedAccess
(c) SGM, 2004
Role of Pir1 in the construction of the Candida albicans cell wall
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/832202023-10-31T14:45:58Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Morales García, Lorena
González Alonso, Alba
Desfilis, Ester
Medina Hernández, Loreta Mª
2022-05-05T07:48:47Z
2022-05-05T07:48:47Z
2022
https://doi.org/10.3389/fncir.2022.831074
032412
1662-5110
http://hdl.handle.net/10459.1/83220
Taking advantage of two Otp-specific reporter lines of transgenic mice (Otp-eGFP and Otp-Cre; Rpl22-HA), we identify and describe different Otp cell populations across various pallial regions, including the pallial amygdala, the piriform cortex, the mesocortex, the neocortex, and the hippocampal complex. Some of these populations can be followed throughout development, suggesting migration from external sources (for example, those of the pallial amygdala and at least some of the cingulate cortex). Other cells become visible during postnatal development (some of those in the neocortex and hippocampal formation) or in adulthood (those of the parahippocampal lobe), and seem to be produced locally. We discuss the possible role of Otp in these different populations during different moments of ontogenesis. We also analyze the connectivity patterns of some of these cells and discuss their functional implications. For example, our data suggest that Otp cells of the pallial amygdala might be engaged in networks with other Otp cells of the medial amygdala with the same embryonic origin, and may regulate specific aspects of social behavior. Regarding Otp cells in the parahippocampal lobe, they seem to be projection neurons and may regulate hippocampal function during spatial navigation and memory formation. The two reporter transgenic mice employed here provide very powerful tools for high precision studies on these different Otp cells of the pallium, but careful attention should be paid to the age and to differences between lines.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Morales, González-Alonso, Desfilis and Medina, 2022
Basomedial amygdala
Cingulate bundle
Cingulate cortex
Cortical amygdala
Frontal cortex
Hippocampus
Pallium
Parahippocampal lobe
Precise Mapping of Otp Expressing Cells Across Different Pallial Regions Throughout Ontogenesis Using Otp-Specific Reporter Transgenic Mice
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/590542021-08-30T15:04:27Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Legaz, Isabel
Olmos, Luis
Real, M. Ángeles
Guirado, Salvador
Dávila, José Carlos
Medina Hernández, Loreta Mª
2017-01-20T10:04:16Z
2005
https://doi.org/10.1002/cne.20608
011376
0021-9967
http://hdl.handle.net/10459.1/59054
We studied the development of neurons and fibers containing calbindin, calretinin, and parvalbumin in the mouse pallial amygdala, with special emphasis on those of the basolateral amygdalar complex. Numerous calbindin-immunoreactive (CB+) cells were observed in the incipient basolateral amygdalar complex and cortical amygdalar area from E13.5. At E16.5, CB+ cells became more abundant in the lateral and basolateral nuclei than in the basomedial nucleus, showing a pattern very similar to that of γ-aminobutyric acid (GABA)ergic neurons. Many CB+ cells observed in the pallial amygdala appeared to originate in the anterior entopeduncular area/ganglionic eminences of the subpallium. The density of CB+ cells gradually increased in the pallial amygdala until the first postnatal week and appeared to decrease later, coinciding with the postnatal appearance of parvalbumin cells and raising the possibility of a partial phenotypic shift. Calretinin (CR) immunoreactivity could be observed in a few cells and fibers in the pallial amygdala at E14.5, and by E16.5 it became a good marker of the different nuclei of the basolateral amygdalar complex. Numerous CB+ and CR+ varicosities, part of which have an intrinsic origin, were observed in the basolateral amygdalar complex from E16.5, and some surrounded unstained perikarya and/or processes before birth, indicating an early formation of inhibitory networks. Each calcium binding protein showed a distinct spatiotemporal expression pattern of development in the mouse pallial amygdala. Any alteration in the development of neurons and fibers containing calcium binding proteins of the pallial amygdala may result in important disorders of emotional and social behavior. J. Comp. Neurol. 488:492–513, 2005. © 2005 Wiley-Liss, Inc.
eng
info:eu-repo/semantics/restrictedAccess
(c) Wiley-Liss, Inc. 2005
Calbindin
Calretinin
Parvalbumin
GABA
Development of neurons and fibers containing calcium binding proteins in the pallial amygdala of mouse, with special emphasis on those of the basolateral amygdalar complex
article
oai:repositori.udl.cat:10459.1/661592022-09-27T14:41:19Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Medina Hernández, Loreta Mª
Abellán Ródenas, Antonio
Vicario Andrade, Alba
Desfilis, Ester
2019-04-09T08:58:57Z
2019-04-09T08:58:57Z
2014-04-24
https://doi.org/10.1159/000357832
021324
0006-8977
http://hdl.handle.net/10459.1/66159
Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons containing LANT6). Based on the presence of neurons containing enkephalin or SP, it is possible that the pallidum of these animals also includes the Islet1 lineage cell subpopulation, and both neuron subtypes were likely present in the pallidum of the first jawed vertebrates. In contrast, lampreys (jawless fishes) appear to lack the pallidal embryonic domain and the Nkx2.1 lineage cell population that mainly characterize the pallidum in jawed vertebrates. In the absence of data in other jawless fishes, the ancestral condition in vertebrates remains to be elucidated. Perhaps, a major event in telencephalic evolution was the novel expression of Nkx2.1 in the subpallium, which has been related to Hedgehog expression and changes in the regulatory region of Nkx2.1.
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/3.0/
cc-by-nc (c) S. Karger AG, Basel, 2014
Forebrain evolution
Developmental regulatory genes
Enkephalin
Globus pallidus
Pallidostriatal projections
Evolutionary and developmental contributions for understanding the organization of the basal ganglia
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4642392024-01-12T09:21:54Zcom_10459.1_241com_10459.1_2col_10459.1_30324col_10459.1_49291
Ureta Velasco, Noelia
Montealegre-Pomar, Adriana
Keller, Kristin
Escuder Vieco, Diana
Fontecha, Javier
Calvo, Mª Victoria
Megino-Tello, Javier
Serrano Casasola, José Carlos Enrique
García Lara, Nadia Raquel
Pallás Alonso, Carmen R.
2023-10-25T07:53:27Z
2023-10-25T07:53:27Z
2023
https://doi.org/10.3390/nu15153486
033780
2072-6643
https://repositori.udl.cat/handle/10459.1/464239
The influence of the diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations between donors’ dietary intake and nutritional status and the micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a five-day weighed dietary record, and collected milk for five consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day DHA intake, an increase of 0.38% in DHA content and 0.78% in total omega-3 content was observed in DHM (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamin, free riboflavin, pyridoxal, dehydroascorbic acid, and the lipid profile in DHM. In conclusion, the diet and nutritional status of donors influence the fatty acid profile and micronutrient content of DHM.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Noelia Ureta-Velasco et al., 2023
Attribution 4.0 International
Breast milk
Human milk bank
Associations
Donors
Diet
Nutritional status
Associations of Dietary Intake and Nutrient Status with Micronutrient and Lipid Composition in Breast Milk of Donor Women
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4649412024-02-01T08:20:04Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Yeramian Hakim, Andree
Moreno Bueno, Gema
Dolcet Roca, Xavier
Catasus, L.
Abal Diaz, Leandro
Colás, Eva
Reventós, Jaume
Palacios, José
Prat, Jaime
Matias-Guiu, Xavier
2024-01-31T15:12:08Z
2024-01-31T15:12:08Z
2013
https://doi.org/10.1038/onc.2012.76
018539
1476-5594
0950-9232
https://repositori.udl.cat/handle/10459.1/464941
In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10–20 per 100 000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 10, PIK3CA, K-RAS and CTNNB1 (β-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors.
eng
info:eu-repo/semantics/openAccess
(c) Macmillan Publishers Limited, 2012
Endometrial carcinoma
Genetics
Microsatellite instability
PTEN
PIK3CA
K-RAS
Beta-catenin
Apoptosis
Chromosomal instability
E-cadherin
TP53
Endometrial carcinoma: molecular alterations involved in tumor development and progression
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/698402022-05-13T09:46:36Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Cunill, Joan
Babot, Clara
Santos, Liliana
Serrano Casasola, José Carlos Enrique
Jové Font, Mariona
Martín Garí, Meritxell
Portero Otín, Manuel
2020-11-11T09:30:16Z
2020-11-11T09:30:16Z
2020-09-04
https://doi.org/10.3390/nu12092699
030446
2072-6643
http://hdl.handle.net/10459.1/69840
Egg-yolk based supplements have demonstrated biological effects. We have developed a novel processed egg-yolk (PEY) complement, and we have tested whether it has inflammation modulatory properties. These were evaluated in a lipopolysaccharide (LPS)-challenge in 1-month male rats by in vivo circulating cytokine profiles measured by multiplexing techniques. Cell culture was used to explore ex vivo properties of derived serum samples. We explored growth factor composition, and mass-spectrometry metabolome and lipidome analyses of PEY to characterize it. PEY significantly prevented LPS-induced increase in IL-1 β, TNF-α, and MCP-1. Further, serum from PEY-treated animals abrogated LPS-induced iNOS build-up of the Raw 264.7 macrophage-like cell line. Immunochemical analyses demonstrated increased concentrations of insulin-like growth factor 1 (IGF-1), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF) in the extract. PEY vs. egg-yolk comparative metabolomic analyses showed significative differences in the concentrations of at least 140 molecules, and in 357 in the lipidomic analyses, demonstrating the complexity of PEY. Globally, PEY acts as an orally-bioavailable immunomodulatory extract that may be of interest in those conditions associated with disarranged inflammation, such as inflammaging.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es
cc-by (c) Cunill, Joan et al., 2020
Fecundation
Inflammation
Cytokine
Growth factors
Metabolomics
Lipidomics
In Vivo Anti-Inflammatory Effects and Related Mechanisms of Processed Egg Yolk, a Potential Anti-Inflammaging Dietary Supplement
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/833082022-10-05T19:03:28Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Jové Font, Mariona
Mota Martorell, Natàlia
Torres Cabestany, Pascual
Ayala Jové, Ma. Victoria (Maria Victoria)
Portero Otín, Manuel
Ferrer, Isidre
Pamplona Gras, Reinald
2022-05-17T12:28:54Z
2022-05-17T12:28:54Z
2021
https://doi.org/10.3390/life11050388
031694
2075-1729
http://hdl.handle.net/10459.1/83308
Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s disease (AD) pathology in the cerebrum. Compared with other cortical areas, the neurons from this brain region possess an inherent selective vulnerability derived from particular oxidative stress conditions that favor increased mitochondrial molecular damage with early bioenergetic involvement. This alteration of energy metabolism is the starting point for subsequent changes in a multitude of cell mechanisms, leading to neuronal dysfunction and, ultimately, cell death. These events are induced by changes that come with age, creating the substrate for the alteration of several neuronal pathways that will evolve toward neurodegeneration and, consequently, the development of AD pathology. In this context, the present review will focus on description of the biological mechanisms that confer vulnerability specifically to neurons of the entorhinal cortex, the changes induced by the aging process in this brain region, and the alterations at the mitochondrial level as the earliest mechanism for the development of AD pathology. Current findings allow us to propose the existence of an altered allostatic mechanism at the entorhinal cortex whose core is made up of mitochondrial oxidative stress, lipid metabolism, and energy production, and which, in a positive loop, evolves to neurodegeneration, laying the basis for the onset and progression of AD pathology.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Authors, 2021
Aging
ATP synthase
Energy metabolism
Entorhinal cortex
Lipoxidation-derived damage
Mitochondrial dysfunction
Neurodegeneration
Oxidative damage
The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer's Disease Pathology
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/602862017-10-20T00:19:34Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Brebi, Priscilla
Maldonado, Leonel
Noordhuis, Maartje G.
Ili, Carmen
Leal, Pamela
Garcia, Patricia
Brait, Mariana
Ribas i Fortuny, Judit
Michailidi, Christina
Perez, Jimena
Soudry, Ethan
Tapia, Oscar
Guzman, Pablo
Muñoz, Sergio
Van Neste, Leander
Van Criekinge, Wim
Irizarry, Rafael
Sidransky, David
Roa, Juan C.
Guerrero-Preston, Rafael
2017-10-05T16:04:06Z
2017-10-05T16:04:06Z
2014-02-01
https://doi.org/10.4161/epi.27120
021322
1559-2294
http://hdl.handle.net/10459.1/60286
Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide DNA methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarrays and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently corroborated in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples, after adjusting for age and HPV status. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.
eng
info:eu-repo/semantics/openAccess
(c) Taylor & Francis, 2014
Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/844642023-03-31T14:17:35Zcom_10459.1_241com_10459.1_2col_10459.1_30324col_10459.1_49291
Mota Martorell, Natàlia
Jové Font, Mariona
Pamplona Gras, Reinald
2022-12-03T16:31:17Z
2022-12-03T16:31:17Z
2022
https://doi.org/10.3390/ijms23158747
033106
1422-0067
http://hdl.handle.net/10459.1/84464
Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling
pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and
human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is respon sible, at least in part, for the longevous phenotype. Conversely, increased content and activity of
mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant
activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and
cancer. The downstream processes regulated through this network are diverse, and depend upon
nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity
and, consequently, delaying the ageing process and the development of age-related diseases, are
under continuous study. Among these, the restriction of calories is still the most studied and ro bust intervention capable of downregulating mTOR signalling and feasible for application in the
human population.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Natàlia Mota Martorell et al., 2022
mTORC1
Longevity
Ageing
Age-related diseases
Metabolism
mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/658262022-05-26T13:07:13Zcom_10459.1_56965com_10459.1_2com_10459.1_227com_10459.1_241com_10459.1_244col_10459.1_57707col_10459.1_314col_10459.1_30324col_10459.1_363col_10459.1_44504
Granado-Serrano, Ana Belén
Martín Garí, Meritxell
Sánchez, Virginia
Riart Solans, Marissa
Berdún Hernández, Rebeca
Ludwig, Iziar A.
Rubió Piqué, Laura
Vilaprinyo Terré, Ester
Portero Otín, Manuel
Serrano Casasola, José Carlos Enrique
2019-02-28T09:31:41Z
2019-02-28T09:31:41Z
2019
https://doi.org/10.1038/s41598-019-38874-3
028252
2045-2322
http://hdl.handle.net/10459.1/65826
Gut microbiota has been suggested to affect lipid metabolism. The objective of this study was to characterize the faecal microbiota signature and both short chain fatty acids (SCFAs) and bile acids (BA) profile of hypercholesterolemic subjects. Microbiota composition, SCFAs, BA and blood lipid profile from male volunteers with hypercholesterolemia (HC) and normocholesterolemia (NC) were determined by 16S rDNA sequencing, HPLC, GC and NMR, respectively. HC subjects were characterized by having lower relative abundance of Anaeroplasma (0.002% vs 0.219%, p-value = 0.026) and Haemophilus (0.041% vs 0.078%, p-value = 0.049), and higher of Odoribacter (0.51% vs 0.16%; p-value = 0.044). Correlation analysis revealed that Anaeroplasma and Haemophilus were associated to an unfavourable lipid profile: they correlated negatively to cholesterol and triglycerides related biomarkers and the ratio total to high density lipoprotein (HDL) cholesterol, and positively to HDL size. Odoribacter displayed an opposite behaviour. Faecal SCFAs profile revealed higher abundance of isobutyric (2.76% vs 0.82%, p-value = 0.049) and isovaleric acid (1.32% vs 0.06%, p-value = 0.016) in HC. Isobutyric acid correlated positively with Odoribacter and lipid parameters indicative of an unfavourable profile. BA profile did not show differences between groups. It was concluded that HC subjects showed a particular faecal bacterial signature and SCFAs profile associated with their lipid profile.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es
cc-by (c) Granado-Serrano, Ana Belén et al., 2019
Hypercholesterolemia
Faecal bacteria
short chain fatty acids
Branched short chain fatty acids
Bile acids
Faecal bacterial and short-chain fatty acids signature in hypercholesterolemia
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/585742021-08-30T15:04:29Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291
Gonzalo Benito, Hugo
Brieva Ruiz, Luis
Tatzber, Franz
Jové Font, Mariona
Cacabelos Barral, Daniel
Cassanyé, Anna
Lanau, Lucia
Boada Pallàs, Jordi
Serrano Casasola, José Carlos Enrique
González Mingot, Cristina
Hernández, Lourdes
Peralta Moncusí, Silvia
Pamplona Gras, Reinald
Portero Otín, Manuel
2016-11-18T09:37:52Z
2012
https://doi.org/10.1111/j.1471-4159.2012.07934.x
018290
0022-3042
http://hdl.handle.net/10459.1/58574
Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2α is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor γ (PPARγ). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS.
eng
info:eu-repo/semantics/restrictedAccess
(c) International Society for Neurochemistry, 2012
AItoimmunity
Lipid peroxidation
PPAR
Protein oxidation
Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism
article
oai:repositori.udl.cat:10459.1/832752023-06-02T09:33:16Zcom_10459.1_227com_10459.1_2com_10459.1_237com_10459.1_47453com_10459.1_241com_10459.1_240col_10459.1_314col_10459.1_354col_10459.1_59998col_10459.1_30324col_10459.1_333
Cambray Carner, Serafí
Ibarz Escuer, Mercedes
Bermúdez López, Marcelino
Martí Antonio, Manuel
Bozić Stanojević, Milica
Fernández i Giráldez, Elvira
Valdivielso Revilla, José Manuel
2022-05-13T07:32:33Z
2022-05-13T07:32:33Z
2020
https://doi.org/10.3390/nu12092631
032814
2072-6643
http://hdl.handle.net/10459.1/83275
Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Authors, 2020
Atherosclerosis
Cardiovascular risk
Cholesterol
First-order interaction
Magnesium
Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/626812023-03-15T12:36:12Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
Maiques Carlos, Oscar
Barceló Gómez, Carla
Panosa, Anais
Pijuan Marquilles, Jordi
Orgaz, Jose L.
Rodríguez Hernández, Irene
Matas Nadal, Clara
Tell, Gemma
Vilella, Ramón
Fabra, Angels
Puig, Susana
Sanz Moreno, Victoria
Matias-Guiu, Xavier
Cantí Nicolás, Carles
Herreros Danés, Judit
Martí Laborda, Rosa Ma.
Macià Armengol, Anna
2018-02-20T09:45:39Z
2019-02-18T23:24:51Z
2018
https://doi.org/10.1111/pcmr.12690
026992
1755-1471
http://hdl.handle.net/10459.1/62681
Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3.1 and LC3-II proteins are highly expressed in BRAFV600E compared with NRAS mutant melanomas, both in cell lines and biopsies. Chloroquine, pharmacological blockade, or gene silencing of TTCCs inhibit the autophagic flux and impair the migration and invasion capabilities, specifically in BRAFV600E melanoma cells. Snail1 plays an important role in motility and invasion of melanoma cells. We show that Snail1 is strongly expressed in BRAFV600E melanoma cells and patient biopsies, and its expression decreases when autophagy is blocked. These results demonstrate a role of Snail1 during BRAFV600E melanoma progression and strongly suggest that targeting macroautophagy and, particularly TTCCs, might be a good therapeutic strategy to inhibit metastasis of the most common melanoma type (BRAFV600E).
eng
info:eu-repo/semantics/openAccess
(c) Wiley, 2018
Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
article
oai:repositori.udl.cat:10459.1/584502022-10-18T18:47:29Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
López González, Irene
Schlüter, Agatha
Aso, Ester
García Esparcia, Paula
Ansoleaga, Belen
Llorens, Franc
Moreno, Jesús
Fuso, Andrea
Portero Otín, Manuel
Pamplona Gras, Reinald
Pujol, Aurora
Ferrer, Isidre
Carmona, Margarita
2016-11-10T08:41:48Z
2015
https://doi.org/10.1097/NEN.0000000000000176
023680
0022-3069
http://hdl.handle.net/10459.1/58450
To understand neuroinflammation-related gene regulation during normal aging and in sporadic Alzheimer disease (sAD), we performed functional genomics analysis and analyzed messenger RNA (mRNA) expression by quantitative reverse transcription–polymerase chain reaction of 22 genes involved in neuroinflammation-like responses in the cerebral cortex of wild-type and APP/PS1 transgenic mice. For direct comparisons, mRNA expression of 18 of the same genes was then analyzed in the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 of middle-aged human subjects lacking Alzheimer disease–related pathology and in older subjects with sAD pathology covering Stages I–II/0(A), III–IV/A–B, and V–VI/C of Braak and Braak classification. Modifications of cytokine and immune mediator mRNA expression were found with normal aging in wild-type mice and in middle-aged individuals and patients with early stages of sAD-related pathology; these were accompanied by increased protein expression of certain mediators in ramified microglia. In APP/PS1 mice, inflammatory changes coincided with β-amyloid (Aβ) deposition; increased levels of soluble oligomers paralleled the modified mRNA expression of cytokines and mediators in wild-type mice. In patients with sAD, regulation was stage- and region-dependent and not merely acceleration and exacerbation of mRNA regulation with aging. Gene regulation at first stages of AD was not related to hyperphosphorylated tau deposition in neurofibrillary tangles, Aβ plaque burden, concentration of Aβ1–40 (Aβ40) and Aβ1–42 (Aβ42), or fibrillar Aβ linked to membranes but rather to increased levels of soluble oligomers. Thus, species differences and region- and stage-dependent inflammatory responses in sAD, particularly at the initial stages, indicate the need to identify new anti-inflammatory compounds with specific molecular therapeutic targets.
Key Words
eng
info:eu-repo/semantics/restrictedAccess
(c) American Association of Neuropathologists, Inc., 2015
Beta-amyloid
Cytokines,
Genomics
Neuroinflammation
Neuroinflammatory Signals in Alzheimer Disease and APP/PS1 Transgenic Mice Correlations With Plaques, Tangles, and Oligomeric Species
article
oai:repositori.udl.cat:10459.1/681692022-10-07T11:24:30Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Gonzalo Benito, Hugo
Nogueras Penabad, Lara
Gil-Sánchez, Anna
Vicente Hervás, José
Valcheva, Petya
González Mingot, Cristina
Martin-Gari, Meritxell
Canudes Solans, Marc
Peralta Moncusí, Silvia
Solana Moga, M. José
Pamplona Gras, Reinald
Portero Otín, Manuel
Boada Pallàs, Jordi
Serrano Casasola, José Carlos Enrique
Brieva Ruiz, Luis
2020-03-09T09:52:59Z
2020-03-09T09:52:59Z
2019
https://doi.org/10.3389/fnins.2019.00938
029282
1662-4548 (Print)
1662-453X (Online)
http://hdl.handle.net/10459.1/68169
Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by, (c) Gonzalo et al., 2019
Multiple sclerosis
Oxidative stress
Mitochondria
Superoxide anion
Mitochondrial complexes
Impairment of Mitochondrial Redox Status in Peripheral Lymphocytes of Multiple Sclerosis Patients
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/489852023-01-27T18:07:13Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291
Naudí i Farré, Alba
Jové Font, Mariona
Aledo, Juan Carlos
Ayala Jové, Ma. Victoria (Maria Victoria)
Cabré Cucó, Rosanna
Portero Otín, Manuel
Barja, Gustavo
Pamplona Gras, Reinald
2015-11-18T11:17:32Z
2015-11-18T11:17:32Z
2013
https://doi.org/10.1038/srep03346
020183
2045-2322
http://hdl.handle.net/10459.1/48985
determination of their longevity. In the present work, the use of high-throughput technologies allowed us to
determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to
120 years. The non-targeted approach revealed a specie-specific lipidomic profile that accurately predicts the
animal longevity. The regression analysis between lipid species and longevity demonstrated that the longer
the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations,
peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These
results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
cc-by-nc-nd (c) Jové Font, Mariona et al., 2013
Longevity
Plasma long-chain
Metabolism
Plasma long-chain free fatty acids predict mammalian longevity
article
oai:repositori.udl.cat:10459.1/480932017-03-10T09:57:41Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Ribas i Fortuny, Judit
Boix Torras, Jacint
Meijer, Laurent
2015-03-23T18:37:36Z
2015-03-23T18:37:36Z
2006
https://doi.org/10.1016/j.yexcr.2006.04.021
009195
0014-4827
http://hdl.handle.net/10459.1/48093
In this study, we have analyzed the consequences, on several neuroblastoma cell lines, of combined treatments with (R)-roscovitine (CYC202, Seliciclib), a CDK inhibitory drug, and nutlin-3, a p53 activating drug. Both compounds were found to synergize, causing significant levels of apoptosis in cultured cells when combined at sublethal concentrations. In SH-SY5Y cells, Bcl-XL protein overexpression protected from apoptosis induced by either nutlin-3 alone or the (R)-roscovitine plus nutlin-3 association but failed to prevent apoptosis triggered by (R)-roscovitine alone. Moreover, Western blot studies showed that (R)-roscovitine increased nutlin-3-mediated p53 stabilization. Therefore, we conclude the contribution of (R)-roscovitine to the synergism is basically the sensitization of SH-SY5Y cells to the action of nutlin-3 on p53. The relevance of this pharmacological synergism with respect to the treatment of neuroblastoma is discussed.
eng
info:eu-repo/semantics/openAccess
(c) Elsevier, 2006
Apoptosis
Cell Cycle
Nutlins
p53
Roscovitine
(R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastorna cells to nutlin-3-induced apoptosis
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/594072021-05-25T10:50:31Zcom_10459.1_227com_10459.1_2com_10459.1_59360com_10459.1_47453com_10459.1_241com_10459.1_240col_10459.1_314col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_333
Betriu i Bars, M. Àngels
Farràs-Sallés, Cristina
Abajo, María
Martínez Alonso, Montserrat
Arroyo, David
Barbé Illa, Ferran
Buti, Miquel
Lecube Torelló, Albert
Portero Otín, Manuel
Purroy Garcia, Francisco
Torres, Gerard
Valdivielso Revilla, José Manuel
Fernández i Giráldez, Elvira
2017-03-29T10:23:36Z
2017-03-29T10:23:36Z
2016
https://doi.org/10.1016/j.nefro.2016.02.008
024182
0211-6995
http://hdl.handle.net/10459.1/59407
Antecedentes y objetivos: La enfermedad renal crónica (ERC) y la ateromatosis son 2 enfermedades interrelacionadas que aumentan el riesgo de morbimortalidad cardiovascular. Los objetivos del proyecto ILERVAS son: 1) conocer la prevalencia de enfermedad ateromatosa subclínica y de enfermedad renal oculta; 2) valorar el impacto de su diagnóstico precoz sobre la morbimortalidad cardiovascular y la progresión de la ERC; 3) disponer de una plataforma de datos y muestras biológicas. Métodos: Estudio de intervención aleatorizado. Entre 2015 y 2017 se incluirá a 19.800 personas (9.900 en el grupo de intervención y 9.900 en el grupo control) entre 45 y 70 años, sin antecedentes de enfermedad cardiovascular y que presenten al menos un factor de riesgo cardiovascular, seleccionadas aleatoriamente de los centros de atención primaria (AP) de la provincia de Lérida. Un equipo técnico experto se desplazará con una unidad móvil para realizar las exploraciones basales al grupo de intervención: ecografía arterial (carótida, femoral,transcraneal y aorta abdominal), medición del índice tobillo-brazo, espirometría, detección de los productos de glicación avanzada y analítica seca de sangre y orina. Adicionalmente, se recogerán muestras de sangre y orina que serán almacenadas en el biobanco para identificar nuevos biomarcadores con biología de sistemas. Los participantes serán seguidos hasta 2025 para la identificación de eventos cardiovasculares, cambios de tratamiento y modificación de estilos de vida.
Conclusiones: El proyecto ILERVAS permitirá conocer la prevalencia de enfermedad vascular y de enfermedad renal subclínicas, evaluar si su diagnóstico precoz tiene un beneficio en la salud e investigar factores de riesgo emergentes.
Background and objectives: Chronic kidney disease (CKD) and atherosclerosis are 2 interrelated diseases that increase the risk of cardiovascular morbidity and mortality. The objectives of the ILERVAS project are: 1) to determine the prevalence of subclinical arterial disease and hidden kidney disease; 2) to assess the impact of early diagnosis of both diseases on cardiovascular morbidity and mortality and also on the progression of CKD; 3) to have a platform of data and biological samples.
Methods: Randomized intervention study. From 2015 to 2017, 19,800 people (9,900 in the intervention group and 9,900 in the control group) aged between 45 and 70 years without previous history of cardiovascular disease and with at least one cardiovascular risk factor will be randomly selected from the primary health care centres across the province of Lérida. A team of experts will travel around in a mobile unit to carry out the following baseline tests on the intervention group: Artery ultrasound; (carotid, femoral, transcranial and abdominal aorta); ankle-brachial index; spirometry; determination of advanced glycation end products; dried blood spot and urine spot tests. Additionally, blood and urine samples will be collected and stored in the biobank to identify new biomarkers using omics studies. Participants will be followed up until 2025 for identification of cardiovascular events, treatment changes and changes in lifestyle.
Conclusions: The ILERVAS project will reveal the prevalence of subclinical vascular disease and hidden kidney disease, determine whether or not their early diagnosis brings health benefits and will also allow investigation of new risk factors.
spa
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
cc-by-nc-nd, (c) Sociedad Española de Nefrología, 2016
Enfermedad cardiovascular
Placa de ateroma
Enfermedad renal oculta
Diagnóstico precoz
Estudio de intervención aleatorizado para evaluar la prevalencia de enfermedad ateromatosa y renal ocultas y su impacto en la morbimortalidad: Proyecto ILERVA
article
oai:repositori.udl.cat:10459.1/586282021-08-30T15:04:29Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
Fourcade, Stéphane
Schlüter, Agatha
López Erauskin, Jone
Guilera, Cristina
Jové Font, Mariona
Naudí i Farré, Alba
García Arumí, Elena
Andreu, Antoni L.
Starkov, Anatoly A.
Pamplona Gras, Reinald
Ferrer, Isidre
Portero Otín, Manuel
Pujol, Aurora
2016-11-23T11:17:11Z
2011
https://doi.org/10.1089/ars.2010.3877
016999
1523-0864
http://hdl.handle.net/10459.1/58628
Aims: Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degeneration in spinal cords and motor disability. The disease is caused by loss of function of the ABCD1 transporter, involved in the import and degradation of very long-chain fatty acids (VLCFA) in peroxisomes. Oxidative stress due to VLCFA excess appears early in the neurodegenerative cascade. Results: In this study, we demonstrate by redox proteomics that oxidative damage to proteins specifically affects five key enzymes of glycolysis and TCA (Tricarboxylic acid) cycle in spinal cords of Abcd1− mice and pyruvate kinase in human X-ALD fibroblasts. We also show that NADH and ATP levels are significantly diminished in these samples, together with decrease of pyruvate kinase activities and GSH levels, and increase of NADPH. Innovation: Treating Abcd1− mice with the antioxidants N-acetylcysteine and α-lipoic acid (LA) prevents protein oxidation; preserves NADH, NADPH, ATP, and GSH levels; and normalizes pyruvate kinase activity, which implies that oxidative stress provoked by VLCFA results in bioenergetic dysfunction, at a presymptomatic stage. Conclusion: Our results provide mechanistic insight into the beneficial effects of antioxidants and enhance the rationale for translation into clinical trials for X-adrenoleukodystrophy. Antioxid. Redox Signal. 15, 2095–2107.
eng
info:eu-repo/semantics/restrictedAccess
(c) Mary Ann Liebert, Inc. 2011
Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-Adrenoleukodystrophy
article
oai:repositori.udl.cat:10459.1/729982022-02-15T00:18:25Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Milanesi, Elena
Manda, Gina
Dobre, Maria
Codrici, Elena
Neagoe, Ionela Victoria
Popescu, Bogdan Ovidiu
Bajenaru, Ovidiu Alexandru
Spiru, Luiza
Tudose, Catalina
Prada, Gabriel-Ioan
Davidescu, Eugenia Irene
Piñol Ripoll, Gerard
Cuadrado, Antonio
2022-02-14T11:23:30Z
2022-02-14T11:23:30Z
2021
https://doi.org/10.2147/JIR.S280328
1178-7031
http://hdl.handle.net/10459.1/72998
Purpose: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case–control study for assessing in whole blood the expression profile of inflammation and redox-related genes in elderly subjects with various comorbidities. Patients and Methods: In the blood of 130 elderly subjects with various pathologies (cardiovascular disease, hypertension, dyslipidemia including hypercholesterolemia, type 2 diabetes mellitus), kept under control by polyvalent disease-specific medication, we investigated by pathway-focused qRT-PCR a panel comprising 84 inflammation-related and 84 redox-related genes.
Results: The study highlights a distinctive expression profile of genes critically involved in NF-κB-mediated inflammation and redox signaling in the blood of patients with cardiovascular disease, characterized by significant down-regulation of the genes NFKB2, NFKBIA, RELA, RELB, AKT1, IRF1, STAT1, CD40, LTA, TRAF2, PTGS1, ALOX12, DUOX1, DUOX2, MPO, GSR, TXNRD2, HSPA1A, MSRA, and PDLIM1. This gene expression profile defines the transcriptional status of blood leukocytes in stable disease under medication control, without discriminating between disease- and therapy-related changes.
Conclusion: The study brings preliminary proof on a minimally invasive strategy for monitoring disease in patients with cardiovascular pathology, from the point of view of inflammation or redox dysregulation in whole blood.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/4.0/
cc-by-nc (c) MIlanesi et al., 2021
Aging-related diseases
Cardiovascular disease
Inflammation
NF-κB signaling
Redox metabolism
Oxidative stress
Distinctive Under-Expression Profile of Inflammatory and Redox Genes in the Blood of Elderly Patients with Cardiovascular Disease
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/492622017-02-08T14:38:14Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Medina Hernández, Loreta Mª
Desfilis, Ester
2015-12-12T11:35:56Z
2015-11-15
023584
1576-074X
http://hdl.handle.net/10459.1/49262
Los avances en el campo de la investigación biomédica se están produciendo a un ritmo vertiginoso, y esto ha llevado a una necesaria discusión sobre las perspectivas éticas de su posible aplicación en humanos y al nacimiento de la bioética y sus diferentes subdisciplinas. Dicha discusión no solo ocurre en el ámbito profesional de los investigadores y los médicos, sino que ha llegado a la sociedad y la política, siendo relativamente frecuente la aparición de noticias e incluso la publicación de leyes relacionadas con el uso médico de, por ejemplo, la clonación humana, las células madre de origen humano, la prolongación artificial o no de la vida (en la Unión Europea: http://conventions.coe.int/Treaty/en/Treaties/Html/164.htm). Otras preguntas que han ido surgiendo son los límites de las interfaces máquina-cuerpo, la creación de una raza humana mejorada o la pertinencia o no de alcanzar la inmortalidad. Esto ha llevado a la creación por la UNESCO de un Comité Internacional de Bioética (1993). Además, los gobiernos de varios países han creado comisiones internas mixtas para la discusión de asuntos de bioética (por ejemplo, en EE.UU. existe el President's Council on Bioethics, creado en 2001, y renovado cada pocos años; en estas comisiones participan científicos, médicos, expertos en ética, sociólogos, teólogos y abogados; en la Unión Europea existe una comisión similar (http://www.coe.int/en/web/bioethics/home).
spa
info:eu-repo/semantics/openAccess
(c) Col·legi Oficial de Metges de Lleida, 2015
Ética
Investigació
Biomedicina
Investigación biomédica y dilemas morales
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/602832017-10-20T00:19:31Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Zheng, Qizhi
Peskoe, Sarah B.
Ribas i Fortuny, Judit
Rafiqi, Fatema
Kudrolli, Tarana
Meeker, Alan K.
De Marzo, Angelo M.
Platz, Elizabeth A.
Lupold, Shawn E.
2017-10-05T13:08:56Z
2017-10-05T13:08:56Z
2014-12
https://doi.org/10.1002/pros.22883
021802
0270-4137
http://hdl.handle.net/10459.1/60283
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate a broad array of cellular and disease processes. Several miRNAs are differentially expressed in cancer and many are being considered as biomarkers for predicting clinical outcomes. Here we quantified the expression of three miRNAs, miR-21, miR-141, and miR-221, from prostate cancer surgical specimens and evaluated their association with disease recurrence after primary therapy. METHODSA pilot nested case-control study was designed from a large cohort of men who underwent radical prostatectomy between 1993 and 2001. Total RNA was extracted from malignant prostate tissue of 59 cases (recurrence) and 59 controls. Cases and controls were matched on age, race, pathologic stage, and grade. The relative expression of each miRNA was then determined for each sample by quantitative real-time RT-PCR. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of recurrence for tertiles of miRNA expression. We noted block storage time effects and thus, used separate tertile cutpoints based on the controls by calendar year of prostatectomy. RESULTSLower miR-221 expression was associated with a higher risk of recurrence; the ORs were 3.21 for the lowest tertile and 2.63 for the middle tertile compared with the highest tertile of expression (P-trend=0.02). This pattern was unchanged after multivariable adjustment (P-trend=0.05). No statistically significant trends were observed for miR-21 or miR-141 after multivariable adjustment. CONCLUSIONSBased on this small pilot study, men with localized prostate cancers with lower miR-221 expression may have a greater risk for recurrence after surgery
eng
info:eu-repo/semantics/openAccess
(c) John Wiley & Sons, Inc., 2014
Investigation of miR-21, miR-141, and miR-221 expression levels in prostate adenocarcinoma for associated risk of recurrence after radical prostatectomy
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/489732017-03-10T09:57:42Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Dolcet Roca, Xavier
Encinas Martín, Mario
Bozić Stanojević, Milica
Álvarez, Ángeles
Pablo, Carmen de
Sanchez-Niño, Maria-Dolores
Ortiz, Alberto
Fernández i Giráldez, Elvira
Valdivielso Revilla, José Manuel
2015-11-17T11:31:11Z
2015-11-17T11:31:11Z
2015
https://doi.org/10.1371/journal.pone.0136863
023350
1932-6203
http://hdl.handle.net/10459.1/48973
Endothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while its deficiency is a risk factor for the progression of cardiovascular damage.
Our aim was to assess the role of basal levels of vitamin D receptor (VDR) on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR) led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC) rolling velocity and increased PBMC rolling flux and adhesion to the endothelium. shVDR cells showed decreased IκBα levels and accumulation of p65 in the nucleus compared to shRNA controls. Inhibition of NF-κB activation with super-repressor IκBα blunted all signs of endothelial cell activation caused by downregulation of VDR in endothelial cells. In vivo, deletion of VDR led to significantly larger aortic arch and aortic root lesions in apoE-/- mice, with higher
macrophage content. apoE-/-VDR-/-mice showed higher aortic expression of VCAM-1, ICAM-1 and IL-6 when compared to apoE-/-VDR+/+ mice. Our data demonstrate that lack of VDR signaling in endothelial cells leads to a state of endothelial activation with increased leukocyte-endothelial cell interactions that may contribute to the more severe plaque accumulation observed in apoE-/-VDR-/- mice. The results reveal an important role for basal levels of endothelial VDR in limiting endothelial cell inflammation and atherosclerosis.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
cc-by (c) Valdivielso Revilla, José Manuel et al., 2015
Impaired Vitamin D Signaling in Endothelial Cell Leads to an Enhanced Leukocyte-Endothelium Interplay: Implications for Atherosclerosis Development
article
oai:repositori.udl.cat:10459.1/4642432023-10-26T03:00:25Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Martín Masot, Rafael
Jiménez-Muñoz, María
Herrador-López, Marta
Navas-López, Víctor Manuel
Obis Monné, Èlia
Jové Font, Mariona
Pamplona Gras, Reinald
Nestares, Teresa
2023-10-25T08:53:33Z
2023-10-25T08:53:33Z
2023
https://doi.org/10.3390/nu15132871
2072-6643
https://repositori.udl.cat/handle/10459.1/464243
Celiac disease (CD) is included in the group of complex or multifactorial diseases, i.e., those caused by the interaction of genetic and environmental factors. Despite a growing understanding of the pathophysiological mechanisms of the disease, diagnosis is still often delayed and there are no effective biomarkers for early diagnosis. The only current treatment, a gluten-free diet (GFD), can alleviate symptoms and restore intestinal villi, but its cellular effects remain poorly understood. To gain a comprehensive understanding of CD’s progression, it is crucial to advance knowledge across various scientific disciplines and explore what transpires after disease onset. Metabolomics studies hold particular significance in unravelling the complexities of multifactorial and multisystemic disorders, where environmental factors play a significant role in disease manifestation and progression. By analyzing metabolites, we can gain insights into the reasons behind CD’s occurrence, as well as better comprehend the impact of treatment initiation on patients. In this review, we present a collection of articles that showcase the latest breakthroughs in the field of metabolomics in pediatric CD, with the aim of trying to identify CD biomarkers for both early diagnosis and treatment monitoring. These advancements shed light on the potential of metabolomic analysis in enhancing our understanding of the disease and improving diagnostic and therapeutic strategies. More studies need to be designed to cover metabolic profiles in subjects at risk of developing the disease, as well as those analyzing biomarkers for follow-up treatment with a GFD.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Rafael Martín-Masot et al., 2023
Attribution 4.0 International
Celiac disease
Gluten-free diet
Metabolomics
Children
Immune
Intestinal
Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/734472022-10-07T10:50:35Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
de Rojas, Itziar
Hernández, Isabel
Montrreal, Laura
Quintela, Inés
Calero, Miguel
Royo, Jose Luís
Huerto Vilas, Raquel
González Pérez, Antonio
Franco Macías, Emilio
Macías, Juan
Menéndez González, Manuel
Frank García, Ana
Diez Fairen, Mónica
Lage, Carmen
García Madrona, Sebastián
Aguilera, Nuria
García González, Pablo
Puerta, Raquel
Sotolongo Grau, Oscar
Alonso Lana, Silvia
Rábano, Alberto
Arias Pastor, Alfonso
Pastor, Ana Belén
Corma Gómez, Anaïs
Martín Montes, Ángel
Martínez Rodríguez, Carmen
Buiza Rueda, Dolores
Rodríguez Rodríguez, Eloy
Álvarez, Ignacio
Rosas Allende, Irene
Pineda, Juan A.
Bernal Sánchez-Arjona, María
Fernández Fuertes, Marta
Mendoza, Silvia
Del Ser, Teodoro
García Ribas, Guillermo
Sánchez Juan, Pascual
Pastor, Pau
Bullido, María J.
Álvarez, Victoria
Real, Luis M.
Mir, Pablo
Piñol Ripoll, Gerard
García Alberca, Jose María
Medina, Miguel
Orellana, Adelina
Butler, Chris R.
Marquié, Marta
Sáez, María Eugenia
Carracedo, Angel
Tárraga, Lluís
Boada, Mercè
Ruiz, Agustín
2022-03-30T11:07:48Z
2022-03-30T11:07:48Z
2021
https://doi.org/10.3390/jpm11121318
2075-4426
http://hdl.handle.net/10459.1/73447
Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Authors, 2021
APOE
COVID-19
GR@ACE/DEGESCO
GWAS
SARS-CoV-2
Dementia
Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4636362023-07-06T03:00:21Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Berlana, David
Sabin, Pilar
Gimeno Ballester, Vicente
Romero Jiménez, Rosa
Zapatas Rojas, Amalia
Márquez, Esther
Martínez Cutillas, Julio
Schoenenberger, Joan Antoni
2023-07-05T07:15:28Z
2023-07-05T07:15:28Z
2013
https://doi.org/10.3305/nh.2013.28.6.6862
031618
1699-5198
0212-1611
https://repositori.udl.cat/handle/10459.1/463636
Background: Parenteral nutrition (PN) is a costly technology used widely to provide nutrition to patients who have an inaccessible or non-functioning intestine. Two all-in-one systems currently being used are customized formulations and three-compartment bags. Objective:To provide a systematic cost comparison of the two all-in-one PN systems: individualized (made from nutrient solutions) versus commercialized (made from three-compartment bag), both prepared in hospital pharmacies. Setting:This study was conducted in three public Spanish hospitals. Method:We conducted a cost-minimization study to analyze prospectively the total cost of PN bags, accounting for all of the processes involved in preparing and delivering PN bags (cost of manpower, nutrition solutions, medical supplies and quality controls) in three different healthcare settings. To compare therapeutic alternatives of equivalent nutritional value, the study was performed for the most frequently employed formulation and similar to commercial preparations. A univariate sensitivity analysis was performed to evaluate the impact of different rates of use of three-compartment PN bag. Results: 157 routine acts of PN bag preparation (65 customized and 92 three-compartment) were observed and timed over 9 days. Total costs of the 157 PN bags were included in the study. Mean costs of customized bags were higher than three-compartment bags, 51.16 ± 5.63 € versus 39.69 ± 3.00 € respectively (p < 0.01). Manpower costs were responsible for the majority of the differences found (70%). The time to complete an adult bag for the hospital compounded system was a mean of 25.9 minutes longer than the three-compartment system. In scenarios using a three-compartment system for 30%, 70% and 90% of PN provision, a cost savings of 4.3%, 10.1% and 12.9% respectively could be achieved. Greatest rates of changing from customized bags (70% and 90%), in a hospital with 1,800 PN bags/year, might reduce the annual budget by 9306 € and 11,964.8 €, respectively.
Meanwhile, in a large facility the savings for 8,000 TPN days would be 64,248 € and 82,605 €, respectively. Conclusions:Since seeking cost-reduction of effective treatments is needed, the use of three-compartment bags for standard adult PN could lead to cost savings. Our data should be helpful for health care providers to calculate their own cost of administer.
Antecedentes: La nutrición parenteral (NP) es una tecnología costosa que se usa ampliamente para proporcionar nutrición a los pacientes que tienen un intestino inaccesible o no funcional. Los dos sistemas todo en uno que se utilizan en la actualidad son las formulaciones individualizadas y las bolsas tri-compartimentales. Objetivo: Proporcionar una comparación de costes sistemática entre los dos sistemas todo en uno: los sistemas individualizados (preparados a partir de soluciones de nutrientes) frente a los comerciales (hechos a partir de una bolsa tri-compartimental). Contexto: Este estudio se realizó en tres hospitales públicos españoles. Método: Realizamos un estudio de minimización de costes para analizar prospectivamente el coste total de las bolsas de NP, considerando todos los procesos implicados en la preparación y suministro de las bolsas (coste de personal, soluciones de nutrición, material fungible y controles de calidad) en tres centros hospitalarios distintos. Para comparar alternativas terapéuticas de valor nutricional equivalente, el estudio se realizó con la formulación que se empleaba con mayor frecuencia y similar a los preparados comerciales. Se realizó un análisis de sensibilidad univariaante para evaluar el impacto de las diferentes tasas de uso de la bolsa de NP tri-compartimental. Resultados:Se analizaron 157 elaboraciones de bolsas de NP (65 individualizada y 92 tri-compartimentales) programadas durante 9 días. Los costes totales de las 157 bolsas de NP se incluyeron en el estudio. Los costes medios de las bolsas individualizadas fueron superiores a los costes de las bolsas tri-compartimentales, 51,16 ± 5,63 € frente a 39,69 ± 3,00 €, respectivamente (p < 0,01). Los costes de personal fueron los responsables de la mayor parte de las diferencias encontradas (70%). El tiempo para completar una bolsa de formulación individualizada fue en promedio 25,9 minutos superior que para el sistema tri-compartimental. En los supuestos en que se utilizase el sistema tri-compartimental un 30%, 70% y 90% del total de NP, se producirían unos ahorros del 4,3%, 10,1% y 12,9%, respectivamente. Con mayores tasas de cambio (70% y 90%), en un hospital con 1.800 bolsas de NP/año, se podría obtener un ahorro en el presupuesto anual de 9.306 € y 11.964.8 €, respectivamente. A su vez, en un centro hospitalario mayor, el ahorro para 8.000 bolsas de NP sería de 64.248 € y 82.605 €, respectivamente. Conclusiones: Dada la necesidad de buscar una reducción de costes de tratamientos efectivos, el uso de las bolsas tri-compartimentales para la NP estándar del adulto podría conllevar una reducción de costes. Nuestros datos pueden ayudar a los gestores sanitarios a calcular su propio coste de administración de la NPT.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
cc-by-nc-sa (c) Nutrición Hospitalaria, 2013
Attribution-NonCommercial-ShareAlike 4.0 International
Cost analysis
Parenteral nutrition
Parenteral nutrition methods
Parenteral nutrition economics
Análisis de costes
Nutrición parenteral
Métodos de nutrición parenteral
Economía de la nutrición parenteral
Cost analysis of adult parenteral nutrition systems: three-compartment bag versus customized
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/844662023-11-08T14:19:42Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Torres Cabestany, Pascual
Anerillas Aljama, Carlos
Ramírez Núñez, Omar
Encinas Martín, Mario
Povedano, Mònica
Andrés Benito, Pol
Ferrer, Isidre
Ayala Jové, Ma. Victoria (Maria Victoria)
Pamplona Gras, Reinald
Portero Otín, Manuel
2022-12-03T19:21:01Z
2022-12-03T19:21:01Z
2022
https://doi.org/10.1242/dmm.049059
032640
1754-8403
http://hdl.handle.net/10459.1/84466
To evaluate senescence mechanisms, including senescence associated secretory phenotype (SASP), in the motor neuron
disease model hSOD1-G93A, we quantified the expression of p16
and p21 and senescence-associated β-galactosidase (SA-β-gal) in
nervous tissue. As SASP markers, we measured the mRNA levels of
Il1a, Il6, Ifna and Ifnb. Furthermore, we explored whether an alteration
of alternative splicing is associated with senescence by measuring the
Adipor2 cryptic exon inclusion levels, a specific splicing variant
repressed by TAR DNA-binding protein (TDP-43; encoded by
Tardbp). Transgenic mice showed an atypical senescence profile
with high p16 and p21 mRNA and protein in glia, without the canonical
increase in SA-β-gal activity. Consistent with SASP, there was an
increase in Il1a and Il6 expression, associated with increased TNF-R
and M-CSF protein levels, with females being partially protected. TDP-
43 splicing activity was compromised in this model, and the senolytic
drug Navitoclax did not alter the disease progression. This lack of
effect was reproduced in vitro, in contrast to dasatinib and quercetin,
which diminished p16 and p21. Our findings show a non-canonical
profile of senescence biomarkers in the model hSOD1-G93A.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Pascual Torres Cabestany et al., 2022
Amyotrophic lateral sclerosis
Navitoclax
Senolytic
Neuroinflammation
Therapy
Cell cycle
Cryptic exon
A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/591352023-09-26T09:28:08Zcom_10459.1_59328com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59329col_10459.1_59998col_10459.1_30324col_10459.1_49291
Casanovas i Llorens, Anna
Salvany, Sara
Lahoz, Víctor
Tarabal Mostazo, Olga
Piedrafita Llorens, Lídia
Sabater, Raimundo
Hernández i Estanyol, Sara
Calderó i Pardo, Jordi
Esquerda Colell, Josep
2017-01-26T11:54:49Z
2017-01-26T11:54:49Z
2017
https://doi.org/10.1038/srep40155
025062
2045-2322
http://hdl.handle.net/10459.1/59135
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca2+ activated K+ [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown. We have previously suggested that neuregulin-1 (NRG1)/ErbBs-based retrograde signalling occurs at this synapse. To better understand signalling through C-boutons, we performed an analysis of the distribution of C-bouton-associated signalling proteins. We show that within SSC, S1R, Kv2.1 and NRG1 are clustered in highly specific, non-overlapping, microdomains, whereas ErbB2 and ErbB4 are present in the adjacent presynaptic compartment. This organization may define highly ordered and spatially restricted sites for different signal-transduction pathways. SSC associated proteins are disrupted in axotomised MNs together with the activation of microglia, which display a positive chemotactism to C-bouton sites. This indicates that C-bouton associated molecules are also involved in neuroinflammatory signalling in diseased MNs, emerging as new potential therapeutic targets.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Casanovas i Llorens, Anna., et al. 2017
Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury
article
oai:repositori.udl.cat:10459.1/659482023-10-04T12:11:06Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Gutiérrez Carrasquilla, Liliana
Sánchez Peña, Enric
Hernández García, Marta
Polanco Alonso, Dinora
Salas-Salvadó, Jordi
Betriu i Bars, M. Àngels
Gaeta, Anna Michela
Carmona, Paola
Purroy Garcia, Francisco
Pamplona Gras, Reinald
Farràs-Sallés, Cristina
López Cano, Carolina
Fernández i Giráldez, Elvira
Lecube Torelló, Albert
2019-03-13T09:26:02Z
2019-03-13T09:26:02Z
2019
https://doi.org/10.3390/nu11020329
028374
2072-6643
http://hdl.handle.net/10459.1/65948
A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87–109) vs. 94 (82–105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89–112) vs. 93 (80–107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88–107) vs. 94 (83–105) % of predicted, p = 0.027) and FEV1 (100 (89–110) vs. 95 (84–108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Liliana Gutiérrez et al., 2019
Forced vital capacity
Forced expiratory volume in the first second
Lung function
Mediterranean diet
Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/604532017-11-10T00:18:53Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Schoenenberger, Joan Antoni
Solanilla Puertolas, Montserrat
Acer Puig, Maria
Gómez Arbonés, Javier
2017-11-09T18:02:58Z
2017-11-09T18:02:58Z
2017-07-27
https://doi.org/10.2147/OAJCT.S134555
026076
1179-1519
http://hdl.handle.net/10459.1/60453
Background: Patients enrolled in clinical trials continue to have frequent contacts with primary care physicians because of comorbidities or toxicities. The aim of the present study was to analyze the information provided at different levels, when participants are included in clinical trials organized at a specialized care level. The purpose was to verify if informing the patient's primary care physician is contemplated in the inclusion process. Methods: The authors conducted a cross-sectional study that included the clinical trials approved in the last 2 years by the hospital's Institutional Review Board. In addition, some of the participants in the included clinical trials were interviewed in order to check their knowledge of the type of research taking place. Results: In total, 67 protocols and the accompanying informed consent documents were reviewed. Half of the reviewed protocols (48%) did not provide participants with an identification card. Regarding the role of the primary care physician, 68.6% of clinical trials (46/67) had taken it into account in different ways. In only four trials, the method used to contact the primary care physician was documented. In total, 20 participants were interviewed. Only 3 (15%) knew the title of the study in which they were participating, 14 (70%) were aware of their illness and 6 (30%) did not know how to answer any of these two questions. Almost all participants in the study knew the name of the physician who was the principal investigator in the trial. Conclusion: Information given to health care practitioners, who are not directly involved in clinical trials conducted by specialized medical staff, is still scarce. In our clinical setting, patients participating in clinical trials have a low awareness of such studies. Keywords: informed consent, clinical trials, family physician, wallet card
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/3.0/
cc-by-nc (c) Schoenenberger-Arnaiz JA, Solanilla-Puertolas M, Acer-Puig M, Gomez-Arbones J, 2017
Informing primary care physicians of patients' involvement in clinical trials carried out at a specialist care level
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4632502023-04-28T03:00:33Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Almenara Fuentes, Lidia
Rodríguez Fernández, Silvia
Rosell Mases, Estela
Kachler, Katerina
You, Axel
Salvado, Miriam
Andreev, Darja
Steffen, Ulrike
Bang, Holger
Bozec, Aline
Schett, Georg
Le Panse, Rozen
Verdaguer Autonell, Joan
Dalmases, Martí
Rodríguez Vidal, Silvia
Barneda Zahonero, Bruna
Vives Pi, Marta
2023-04-27T09:14:44Z
2023-04-27T09:14:44Z
2023
https://doi.org/10.1016/j.nano.2022.102635
032877
1549-9634
https://repositori.udl.cat/handle/10459.1/463250
Autoimmune diseases (AIDs) are caused by the loss of self-tolerance and destruction of tissues by the host's immune system. Several antigen-specific immunotherapies, focused on arresting the autoimmune attack, have been tested in clinical trials with discouraging results. Therefore, there is a need for innovative strategies to restore self-tolerance safely and definitively in AIDs. We previously demonstrated the therapeutic efficacy of phosphatidylserine (PS)-liposomes encapsulating autoantigens in experimental type 1 diabetes and multiple sclerosis. Here, we show that PS-liposomes can be adapted to other autoimmune diseases by simply replacing the encapsulated autoantigen. After administration, they are distributed to target organs, captured by phagocytes and interact with several immune cells, thus exerting a tolerogenic and immunoregulatory effect. Specific PS-liposomes demonstrate great preventive and therapeutic efficacy in rheumatoid arthritis and myasthenia gravis. Thus, this work highlights the therapeutic potential of a platform for several autoimmunity settings, which is specific, safe, and with long-term effects
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Authors, 2023
Attribution-NonCommercial-NoDerivatives 4.0 International
Immunotherapy
Autoimmune diseases
Nanomedicine
Myasthenia gravis
Rheumatoid arthritis
Preclinical mouse models
A new platform for autoimmune diseases. Inducing tolerance with liposomes encapsulating autoantigens
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/841112022-11-07T11:06:19Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Garay Sevilla, Ma. Eugenia
Rojas, Armando
Portero Otín, Manuel
Uribarri, Jaime
2022-11-06T17:08:27Z
2022-11-06T17:08:27Z
2021
https://doi.org/10.3390/nu13082802
031685
2072-6643
http://hdl.handle.net/10459.1/84111
Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated)
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Ma. Eugenia Garay Sevilla et.al., 2021
low-grade inflammation
inflammatory diet
Mediterranean diet
DASH diet
dietary inflammatory index (DII)
matrix glycation
Dietary AGEs as Exogenous Boosters of Inflammation
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/709302021-04-29T09:26:24Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Mota Martorell, Natàlia
Pradas Barriga, Irene
Jové Font, Mariona
Naudí i Farré, Alba
Pamplona Gras, Reinald
2021-04-07T07:17:52Z
2021-04-07T07:17:52Z
2019-03-30
https://doi.org/10.1016/j.regg.2018.05.006
029374
0211-139X
http://hdl.handle.net/10459.1/70930
Introducción. Entre los principales componentes lipídicos de las membranas celulares se encuentran los glicerofosfolípidos (GFL), que se sintetizan en una vía de novo a partir del diacilglicerol (DAG). El perfil lipídico es una característica optimizada asociada con la longevidad animal. En este contexto, hipotetizamos que la tasa de biosíntesis de DAGs y, por extensión, de GFL, guarda una relación con la longevidad de una especie animal.
Material y métodos. Se realiza un análisis lipidómico basado en espectrometría de
masas del plasma de 11 especies de mamíferos que cubren un rango de longevidad
máxima de 3,5 a 120 años. La identificación de especies lipídicas se basa en masa
exacta, tiempo de retención y distribución isotópica. Se aplica un test ANOVA para
obtener las especies lipídicas diferenciales entre las especies y la correlación de Spearman para establecer su asociación con la longevidad. Los análisis estadísticos se realizaron con el programa SPSS y el software para el análisis metabolómico
Metaboanalyst. Resultados. Entre las 1061 especies moleculares lipídicas diferenciales se
identifican 47 DAGs, 14 de los cuales presentan una correlación significativa y negativa con la longevidad animal. El análisis multivariante muestra que solamente con estos 14 DAGs somos capaces de discriminar una especie animal y su longevidad máxima. Conclusiones. Éstos resultados sugieren que las especies longevas tienen una menor tasa de biosíntesis de novo de GFL, posiblemente asociada a una menor tasa
de recambio de los lípidos de membrana, lo que conllevaría un menor coste energético.
spa
info:eu-repo/semantics/openAccess
(c) Sociedad Española de Geriatría y Gerontología, 2019
Diacilglicéridos
Espectrometría de masas
Lipidómica
Longevidad máxima
Biosynthesis de novo of glycerophospholipids and longevity
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/647352018-09-20T00:20:25Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Portero Otín, Manuel
Pamplona Gras, Reinald
Bellmunt i Curcó, Josepa
Cristina Ruiz, Maria
Prat, Joan
Salvayre, Robert
Nègre Salvayre, Anne
2018-09-19T17:43:51Z
2018-09-19T17:43:51Z
2002-05
https://doi.org/10.2337/diabetes.51.5.1535
004251
1939-327X
http://hdl.handle.net/10459.1/64735
Formation of advanced glycation end products (AGEs) is considered a potential link between hyperglycemia and chronic diabetic complications, including disturbances in cell signaling. It was hypothesized that AGEs alter cell signaling by interfering with growth factor receptors. Therefore, we studied the effects of two AGE precursors, glyoxal (GO) and methylglyoxal (MGO), on the epidermal growth factor receptor (EGFR) signaling pathway in cultured cells. Both compounds prevented tyrosine autophosphorylation induced by epidermal growth factor (EGF) in a time- and dose-dependent manner as well as phospholipase Cγ1 recruitment and subsequent activation of extracellular signal-regulated kinases. AGE precursors inhibit EGF-induced EGFR autophosphorylation and tyrosine kinase activity in cell membranes and in EGFR immunoprecipitates. In addition, AGE precursors strongly inhibited cellular phosphotyrosine phosphatase activities and residual EGFR dephosphorylation. AGE precursors induced the formation of EGFR cross-links, as shown by the cross-reactivity of modified EGFR with an anti-Nε(carboxymethyl)lysine antibody, suggesting that altered EGFR signaling was related to carbonyl-amine reactions on EGFR. Aminoguanidine, an inhibitor of AGE formation, partially prevented the EGFR dysfunction induced by GO and MGO. These data introduce a novel mechanism for impaired cellular homeostasis in situations that lead to increased production of these reactive aldehydes, such as diabetes.
The Maillard reaction comprises the nonenzymatic reaction of reducing sugars with molecules containing an amino group, including proteins, phospholipids, and DNA (1,2). After the reversible formation of a Schiff’s base between the reducing sugar and free amino group, this reaction proceeds to form advanced glycation end products (AGEs). Aldehydes such as glyoxal (GO) and methylglyoxal (MGO) are also able to induce AGE formation (3). GO and MGO can be generated during glycation of proteins by glucose (3); during lipid peroxidation (4); from metabolic processes, such as base-catalyzed phosphate elimination of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate; and also during the metabolism of acetone and threonine (5).
During chronic complications of diabetes and aging, the levels of AGEs derived from the reaction of GO and MGO with proteins rise in plasma proteins, extracellular matrix, and lens proteins (6–8). Modification of proteins through derivatization by GO and MGO may induce interaction with specific receptors, such as the RAGE and AGE-R family (9), or directly alter protein functions. For instance, MGO inhibits mitochondrial respiration, membrane ATPases and glyceraldehyde-3-phosphate dehydrogenases (10), and DNA and protein synthesis, thereby inducing growth arrest and cell death (11)
eng
info:eu-repo/semantics/openAccess
(c) American Diabetes Association, 2002
Advanced glycation end product precursors impair epidermal growth factor receptor signalin
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/661692019-05-16T10:46:04Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Reiner, Anton
Perkel, David J.
Bruce, Laura L.
Butler, Ann B.
Csillag, András
Kuenzel, Wayne J.
Medina Hernández, Loreta Mª
Paxinos, George
Shimizu, Toru
Striedter, George
Wild, Martin
Ball, Gregori F.
Durand, Sarah
Gütürkün, Onur
Lee, Diane W.
Mello, Claudio V.
Powers, Alice
White, Stephanie A.
Hough, Gerald
Kubikova, Lubica
Smulders, Tom V.
Wada, Kazuhiro
Dugas-Ford, Jennifer
Husband, Scott
Yamamoto, Keiko
Yu, Jing
Siang, Connie
Jarvis, Erich D.
2019-04-10T08:14:02Z
2019-04-10T08:14:02Z
2004
https://doi.org/10.1002/cne.20119
011368
0021-9967
http://hdl.handle.net/10459.1/66169
Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of avian brains have been based are in error, and as a result that terminology promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains. Recognizing this problem, a number of avian brain researchers began an effort to revise the terminology, which culminated in the Avian Brain Nomenclature Forum, held at Duke University from July 18 to 20, 2002. In the new terminology approved at this Forum, the flawed conception that the telencephalon of birds consists nearly entirely of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given names reflecting their now evident homologies. The telencephalic regions that were erroneously named to reflect presumed homology to mammalian basal ganglia were renamed as parts of the pallium, using prefixes that retained most established abbreviations (to maintain continuity with the replaced nomenclature). Details of this meeting and its major conclusions are presented in this paper, and the details of the new terminology and its basis are presented in a longer companion paper. We urge all to use this new terminology, because we believe it will promote better communication among neuroscientists.
eng
info:eu-repo/semantics/openAccess
(c) Wiley, 2004
Pallium
Basal ganglia
Telencephalon
Brainstem
Evolution
Terminology
Birds
Mammals
The Avian Brain Nomenclature Forum: Terminology for a New Century in Comparative Neuroanatomy.
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/567712017-07-24T12:20:32Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Junyent, Mireia
Martínez Alonso, Montserrat
Borràs, Mercè
Betriu i Bars, M. Àngels
Coll, Blai
Craver Hospital, Lourdes
Marco Mayayo, M. Paz
Sarró, Felipe
Valdivielso Revilla, José Manuel
Fernández i Giráldez, Elvira
2016-03-30T08:38:19Z
2016-03-30T08:38:19Z
2010
https://doi.org/10.3265/Nefrologia.pre2010.Jan.10216
017130
0211-6995
http://hdl.handle.net/10459.1/56771
Background: Cardiovascular disease (CVD) is the leading
cause of morbidity and mortality in patients with chronic
kidney disease (CKD). Cardiovascular risk assessment in this
population is hampered by the failure of traditional risk
factors to fully account for the elevated CVD risk, mainly
due to the reverse epidemiology effect, and the presence
of risk factors specifically related to uraemia. Hereby, we
present the protocol of a prospective study aimed to assess
the predictive value of imaging techniques and biomarkers
for CVD in patients with CKD. Methods: From November
2009, 2661 asymptomatic adult patients with stages 3-5D
CKD will be recruited from nephrology services and dialysis
units throughout Spain. Eight-hundred and forty-three
participants without CKD (control group) will be also
recruited. During the follow-up, CVD events and mortality
will be recorded from all CKD patients. One trained
itinerant team will carry out a carotid ultrasound to assess
intima-media thickness and presence of plaques. A
composite atherosclerosis score will be constructed based
on carotid ultrasound data and ankle-brachial index.
Presence and type of calcifications will be assessed in
carotid, femoral and brachial arteries, and in cardiac
valves, by ultrasound. Finally, blood samples will be
collected from all participants to study biomarkers.
Discussion: The NEFRONA study will allow us to examine
the usefulness of imaging techniques and biomarkers to
assess atherosclerosis development and their predictive
value in a Spanish population with CKD.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
cc-by-nc-nd (c) Nefrologia, 2010
Chronic kidney disease
Cardiovascular disease
Ultrasound
Usefulness of imaging techniques and novel biomarkers in the prediction of cardiovascular risk in patients with chronic kidney disease in Spain: The NEFRONA project
article
oai:repositori.udl.cat:10459.1/483802018-03-23T13:28:50Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Marsal Mora, Josep Ramon
Cruz Esteve, María Inés
Teixidó Armengol, Conxita
Díez, Olga
Martínez, Mireia
Galindo Ortego, Gisela
Real, Jordi
Schoenenberger, Joan Antoni
Pera, Helena
2015-06-26T09:23:11Z
2015-06-26T09:23:11Z
2011
https://doi.org/10.1186/1471-2334-11-278
019323
1471-2334
http://hdl.handle.net/10459.1/48380
Background: Molluscum contagiosum is a non-severe pediatric viral infection. Because it is highly contagious and
current treatments have negative aesthetic and psychological effects, we want to test an alternative treatment in
the primary care setting, consisting of two different concentrations of potassium hydroxide solution.
Methods/design: The study design is a double-blind, randomized clinical trial, using three types of topical treatment.
The treatment consist of daily applications of potassium hydroxide (KOH) in aqueous solution at 10% and 15%
concentration, and a placebo administered in the control group. Four follow-up visits (at 15, 30, 45 and 60 days) are
planned to evaluate treatment effectiveness and patient tolerance.
The main outcome measure of the trial will be the healing rate, defined as lesion disappearance in the affected zones
after the topic application of the experimental treatment. Secondary measures will be the principal characteristics and
evolution of the affected zone (surface area, number of lesions, size and density of lesions), treatment tolerance
(hyperpigmentation, itching, burning, pain), recurrence rate and the natural evolution of lesions in the control group.
Discussion: KOH can potentially be an effective and safe treatment for MC in primary care, and can also reduce
referrals to dermatologists and hospital pediatric departments. In addition, KOH may be a valid and less expensive
alternative to current invasive treatments (surgical excision).
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
cc-by, (c) Marsal et al., 2011
Efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscum contagiosum: Randomized clinical trial: Research protocol
article
oai:repositori.udl.cat:10459.1/4640462023-09-28T03:00:26Zcom_10459.1_241com_10459.1_2col_10459.1_30324
González, Luz María
Robles, Nicolás Roberto
Mota Zamorano, Sonia
Valdivielso Revilla, José Manuel
González‑Rodríguez, Laura
López Gómez, Juan
Gervasini, Guillermo
2023-09-27T10:09:31Z
2023-09-27T10:09:31Z
2023
https://doi.org/10.1038/s41598-022-27343-z
2045-2322
https://repositori.udl.cat/handle/10459.1/464046
Nephrosclerosis patients are at an exceptionally high cardiovascular (CV) risk. We aimed to determine whether genetic variability represented by 38 tag-SNPs in genes of the cyclooxygenase pathway (PTGS1, PTGS2, PTGES, PTGES2 and PTGES3) leading to prostaglandin E2 (PGE2) synthesis, modified CV traits and events in 493 nephrosclerosis patients. Additionally, we genotyped 716 controls to identify nephrosclerosis risk associations. The addition of three variants, namely PTGS2 rs4648268, PTGES3 rs2958155 and PTGES3 rs11300958, to a predictive model for CV events containing classic risk factors in nephrosclerosis patients, significantly enhanced its statistical power (AUC value increased from 78.6 to 87.4%, p = 0.0003). Such increase remained significant after correcting for multiple testing. In addition, two tag-SNPs (rs11790782 and rs2241270) in PTGES were linked to higher systolic and diastolic pressure [carriers vs. non-carriers = 5.23 (1.87–9.93), p = 0.03 and 5.9 (1.87–9.93), p = 0.004]. PTGS1(COX1) rs10306194 was associated with higher common carotid intima media thickness (ccIMT) progression [OR 1.90 (1.07–3.36), p = 0.029], presence of carotid plaque [OR 1.79 (1.06–3.01), p = 0.026] and atherosclerosis severity (p = 0.041). These associations, however, did not survive Bonferroni correction of the data. Our findings highlight the importance of the route leading to PGE2 synthesis in the CV risk experienced by nephrosclerosis patients and add to the growing body of evidence pointing out the PGE2 synthesis/activity axis as a promising therapeutic target in this field.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Luz M. González et al., 2023
Attribution 4.0 International
Cardiovascular diseases
Chronic kidney disease
Genetics research
Kidney diseases
Infuence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4633642023-12-20T14:06:12Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
Medina Hernández, Loreta Mª
Abellán Ródenas, Antonio
Morales García, Lorena
Pross, Alessandra
Hanafi-Metwalli, Alek
González Alonso, Alba
Freixes, Júlia
Desfilis, Ester
2023-05-18T10:54:10Z
2023-05-18T10:54:10Z
2023-01
https://doi.org/10.1159/000527512
033075
0006-8977
https://repositori.udl.cat/handle/10459.1/463364
The amygdala is a central node in functional networks regulating emotions, social behavior, and social cognition. It develops in the telencephalon and includes pallial and subpallial parts, but these are extremely complex with multiple subdivisions, cell types, and connections. The homology of the amygdala in nonmammals is highly controversial, especially for the pallial part, and we are still far from understanding general principles on its organization that are common to different groups. Here, we review data on the adult functional architecture and developmental genoarchitecture of the amygdala in different amniotes (mammals and sauropsids), which are helping to disentangle and to better understand this complex structure. The use of an evolutionary developmental biology (evo-devo) approach has helped distinguish three major divisions in the amygdala, derived from the pallium, the subpallium, and from a newly identified division called telencephalon-opto-hypothalamic domain (TOH). This approach has also helped identify homologous cell populations with identical embryonic origins and molecular profiles in the amygdala of different amniotes. While subpallial cells produce different subtypes of GABAergic neurons, the pallium and TOH are major sources of glutamatergic cells. Available data point to a development-based molecular code that contributes to shape distinct functional subsystems in the amygdala, and comparative genoarchitecture is helping to delineate the cells involved in same subsystems in non-mammals. Thus, the evodevo approach can provide crucial information to understand common organizing principles of the amygdala cells and networks that control behavior, emotions, and cognition in amniotes.
eng
info:eu-repo/semantics/emgargoedAccess
(c) S. Karger AG, Basel, 2022
Forebrain
Telencephalon
Dorsal ventricular ridge
Bed nucleus of the stria terminalis
Birds
Reptiles
Evolution and Development of Amygdala Subdivisions: Pallial, Subpallial, and Beyond
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/704412021-02-05T00:20:07Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Park, Min
Nishimura, Takanori
Baeza-Garza, Carlos D.
Caldwell, Stuart T.
Boon Li Pun, Pamela
Prag, Hiran A.
Young, Tim
Sauchanka, Olga
Logan, Angela
Forkink, Marleen
Gruszczyk, Anja V.
Prime, Tracy A.
Arndt, Sabine
Naudí i Farré, Alba
Pamplona Gras, Reinald
Coughlan, Melinda T.
Tate, Mitchel
Ritchie, Rebecca H.
Caicci, Federico
Kaludercic, Nina
Lisa, Fabio Di
Smith, Robin A. J.
Hartley, Richard C.
Murphy, Michael P.
Krieg,Thomas
2021-02-04T11:47:42Z
2021-02-04T11:47:42Z
2020-12-01
https://doi.org/10.1007/s10557-020-07086-7
030826
0920-3206
http://hdl.handle.net/10459.1/70441
Purpose HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide. Methods and Results A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial
oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls.
Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group.
Conclusion Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Diabetes
Heart failure with preserved ejection fraction (HFpEF)
Akita mice
Advanced glycation endproducts (AGE)
Mitochondria
cc-by (c) Park et al. 2020
Confirmation of the cardioprotective effect of MitoGamide in the diabetic heart
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/726972022-11-25T20:44:13Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Pessoa, Luiz
Medina Hernández, Loreta Mª
Hof, Patrick R.
Desfilis, Ester
2022-01-11T11:33:19Z
2022-01-11T11:33:19Z
2019
https://doi.org/10.1016/j.neubiorev.2019.09.021
028991
0149-7634
http://hdl.handle.net/10459.1/72697
Cognition is considered a hallmark of the primate brain that requires a high degree of signal integration, such as achieved in the prefrontal cortex. Moreover, it is often assumed that cognitive capabilities imply “superior” computational mechanisms compared to those involved in emotion or motivation. In contrast to these ideas, we review data on the neural architecture across vertebrates that support the concept that association and integration are basic features of the vertebrate brain, which are needed to successfully adapt to a changing world. This property is not restricted to a few isolated brain centers, but rather resides in neuronal networks working collectively in a context-dependent manner. In different vertebrates, we identify shared large-scale connectional systems involving the midbrain, hypothalamus, thalamus, basal ganglia, and amygdala. The high degree of crosstalk and association between these systems at different levels supports the notion that cognition, emotion, and motivation cannot be separated – all of them involve a high degree of signal integration.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Elsevier, 2019
Vertebrate brain
Integration
Basal ganglia
Amygdala
Emotion
Cognition
Neural architecture of the vertebrate brain: implications for the interaction between emotion and cognition
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/715762021-07-10T00:11:57Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Serrano Casasola, José Carlos Enrique
Goñi Cambrodón, Isabel
2021-07-09T10:46:08Z
2021-07-09T10:46:08Z
2004
015633
0004-0622
http://hdl.handle.net/10459.1/71576
En Guatemala existe un fenómeno de superposición
epidemiológica, en el que coexisten problemas de salud propios de
países desarrollados con otros característicos de poblaciones en
vías de desarrollo. Se observan deficiencias marcadas en algunos
macronutrientes tales como hierro y vitamina A. en simultaneidad
con enfermedades crónicas como diabetes tipo II o enfermedades
cardiovasculares. Se conoce muy bien la importancia del frijol negro
(.Phaseolus vulgaris) en la dieta habitual de Guatemala, en donde
el consum o p e r capita es de 70g al día. A dem ás del aporte
energético, los frijoles constituyen la principal fuente de proteína
en la dieta y contienen un alto porcentaje de carbohidratos
glicém icos de digestión lenta y carbohidratos no glicém icos
fermentables en el intestino grueso. Estos últimos, pueden ejercer
efectos fisiológicos beneficiosos relacionados con el control de la
respuesta glicém ica, de los niveles de colesterol sanguíneo y
disminución de los factores de riesgo de cáncer colónico debido a
la formación de productos de fermentación colónica (propiónico y
butírico). Sin embargo, el frijol negro contiene también diversos
factores antinutricionales (inhibidores enzimáticos, hemagluteninas,
saponinas, ácido fitico, etc.) muchos de ellos termolábiles que
pueden ser destruidos durante el procesado. La riqueza nutricional
del frijol negro, y especialmente los carbohidratos glicémicos de
digestión lenta, los compuestos no digestibles fermentados por las
bacterias intestinales y algunos factores antinutricionales, juegan
un papel importante en la etiología de numerosas enfermedades de
incidencia actual en Guatemala.
spa
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/4.0/
cc-by-nc (c) Sociedad Latinoamericana de Nutrición (SLAN), 2004
Frijol negro
Estado nutricional
Carbohidratos glicémicos
Carbohidratos no glicémicos
Fibra dietética
Proteína
Compuestos antinutricionales
Papel del frijol negro Phaseolus vulgaris en el estado nutricional de la población guatemalteca
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4643042023-10-31T03:00:25Zcom_10459.1_237com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_354col_10459.1_59998col_10459.1_30324
Carnes Vendrell, Anna
Barallat Gimeno, Eva
Lara Gallego, Beatriz
Lladó, A.
Escobar Bravo, Miguel Ángel
Reivan‑Ortiz, G. G.
Maxi‑Maxi, E. A.
Martínez‑Suárez, P. C.
Ramírez‑Coronel, A. A.
Piñol Ripoll, Gerard
2023-10-30T09:20:28Z
2023-10-30T09:20:28Z
2023
https://doi.org/10.1186/s12877-023-03904-3
1471-2318
https://repositori.udl.cat/handle/10459.1/464304
Introduction
Alzheimer’s disease (AD) is the most frequent cause of cognitive impairment. Improving knowledge of dementia management through health education for health professionals can improve clinical and community care in home and specialist settings. It is important to guarantee good dementia knowledge in health students, and it is necessary to evaluate it with a good standardized tool. The aim of the current study was to assess the psychometric properties of the DKAS-S with cohorts of Ecuadorian health students, to compare these results with a former validation in Spanish health students and to analyse the level of knowledge according to different variables.
Methods
We performed a cross-sectional study to assess the validity, reliability and feasibility of the DKAS-S by comparing two different cohorts of health students (nursing and psychologists).
Results
A total of 659 students from Spain (n = 233) and Ecuador (n = 426) completed the DKAS-S (mean age 24.02 (6.35) years old), and 52.80% were nursing students. The DKAS-S showed good internal consistency in the Ecuadorian cohort (Cronbach’s α = 0.76). No significant difference was found between Spanish and Ecuadorian students (p = 0.767) in the global scale score, but there were differences in some subscales. Psychologist students scored significantly higher on the global scale than nursing students (32.08 (9.51) vs. 27.49 (7.15); p < 0.001)). Students with a family history of cognitive impairment scored higher on the global scale, and those who had contact with people with dementia obtained better results on the global scale.
Conclusions
We confirmed that the DKAS-S is an adequate and useful instrument to measure levels of knowledge about dementia among health students in Spanish-speaking communities. It is a reliable and valid measure with good psychometric properties. Understanding health students’ knowledge about dementia will allow better adaptation of academic plans to train better health professionals.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) A. Carnes‑Vendrell et al., 2023
Attribution 4.0 International
Alzheimer’s disease
Dementia
Ecuador
Knowledge
DKAS
Spain
Validation studies
Students
Spanish-Dementia Knowledge Assessment Scale (DKAS-S): Ecuadorian validation and comparison among Spanish health students
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/709032021-03-26T00:30:42Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Gómez Arbonés, Javier
Salazar-Alarcon, E.
Solanilla Puertolas, Montserrat
Ortega Bravo, Marta
Vallez-Valero, L.
Schoenenberger, Joan Antoni
2021-03-25T13:04:12Z
2021-03-25T13:04:12Z
2020-07-20
030366
2637-7373
http://hdl.handle.net/10459.1/70903
Objectives: To evaluate Primary Care Physician's (PCP) awareness degree concerning their patient's participation in Clinical Trials (CT) analyze the communication methods used and obtain physicians personal views. Methods: Authors performed a cross-sectional observational study that included CTs approved by the Institutional Review Board at a Regional University Hospital (n=78). Among these 37 CTs were selected. PCPs involved in these trials received a questionnaire regarding aspects of the CTs in which their patients participated. The communication systems established in the study protocols were analyzed. Results: Out of 89 PCPs contacted, 82.1% were aware of their patient's participation in CTs. The information reached them through verbal communication from the participant (56.3%). PCPs also accessed it through electronic medical records (EMR) (34.0%). A majority (97.4%) considered being informed about the participation of their patients in CTs should be compulsory. Conclusion: Communication of patients' participation in CTs fundamentally takes place through a verbal interaction between patients and their doctor. PCPs consider that the preferred method of communication would be an alarm system in the patient's EMR. Keywords: Clinical research, Sponsor, Electronic medical record, Safety
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Gómez Arbonés, Javier et al., 2020
Clinical research
Sponsor
Electronic medical record
Safety
Informed Consent Procedure in Clinical Trials Promoted by the Hospital: Knowledge and Perceptions of Primary Care Physicians
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/701072022-10-05T11:35:54Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Jorge, C.
Cetó, M.
Arias Pastor, Alfonso
Blasco, E.
Gil Villar, M. Pilar
López, R.
Dakterzada, Farida
Purroy Garcia, Francisco
Piñol Ripoll, Gerard
2020-12-17T12:40:58Z
2020-12-17T12:40:58Z
2019-05-11
https://doi.org/10.1016/j.nrl.2018.03.004
028968
0213-4853
http://hdl.handle.net/10459.1/70107
Introducción El conocimiento de la enfermedad de Alzheimer es fundamental para el diagnóstico precoz y para reducir la sobrecarga del cuidador. El objetivo fue evaluar el grado de conocimiento de la enfermedad de Alzheimer mediante la Alzheimer's Disease Knowledge Scale en cuidadores informales y diferentes segmentos de población. Sujetos y métodos Se evaluó el conocimiento a cuidadores en diferente periodo de seguimiento (menor de un año, entre 1-5 y más de 5 años desde el diagnóstico) y sujetos de la población general. La puntuación Alzheimer's Disease Knowledge Scale se agrupó en distintos ítems: impacto vital, factores de riesgo, síntomas, diagnóstico, tratamiento, progresión de la enfermedad y cuidadores. Resultados Total de 419 personas; 215 cuidadores, 204 población general. Respecto a la puntuación global de la escala no se encontraron diferencias entre ambos grupos (19,1 vs. 18,8; p=0,9). Destaca un escaso conocimiento de los factores de riesgo de la enfermedad (49,3%) y de los cuidados necesarios (51,2%) mientras que los síntomas (78,6%) y el curso de la enfermedad (77,2%) fueron los aspectos mejor reconocidos. Entre las variables, la edad del cuidador se correlacionó con peor puntuación total de la escala Alzheimer's Disease Knowledge Scale, peor conocimiento sobre el impacto vital, síntomas, cuidados y de la progresión de la enfermedad (p<0,05). La duración de los cuidadores mejoró el conocimiento de los síntomas (p=0,00) y el diagnóstico de la enfermedad (p=0,05). Conclusión Evaluar el grado de conocimiento de la enfermedad es fundamental para poder elaborar estrategias de educación sanitaria tanto a nivel poblacional como en los cuidadores.
Introduction
Understanding of Alzheimer disease is fundamental for early diagnosis and to reduce caregiver burden. The objective of this study is to evaluate the degree of understanding of Alzheimer disease among informal caregivers and different segments of the general population through the Alzheimer's Disease Knowledge Scale.
Patients and methods
We assessed the knowledge of caregivers in different follow-up periods (less than one year, between 1 and 5 years, and over 5 years since diagnosis) and individuals from the general population. Alzheimer's Disease Knowledge Scale scores were grouped into different items: life impact, risk factors, symptoms, diagnosis, treatment, disease progression, and caregiving.
Results
A total of 419 people (215 caregivers and 204 individuals from the general population) were included in the study. No significant differences were found between groups for overall Alzheimer's Disease Knowledge Scale score (19.1 vs. 18.8, P = .9). There is a scarce knowledge of disease risk factors (49.3%) or the care needed (51.2%), while symptoms (78.6%) and course of the disease (77.2%) were the best understood aspects. Older caregiver age was correlated with worse Alzheimer's Disease Knowledge Scale scores overall and for life impact, symptoms, treatment, and disease progression (P < .05). Time since diagnosis improved caregivers’ knowledge of Alzheimer disease symptoms (P = .00) and diagnosis (P = .05).
Conclusion
Assessing the degree of understanding of Alzheimer disease is essential to the development of health education strategies both in the general population and among caregivers.
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Sociedad Española de Neurología (SEN), 2019
Enfermedad de Alzheimer
Conocimiento
Demencia
Educación sanitaria
Nivel de conocimiento de la enfermedad de Alzheimer en cuidadores y población general
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/650092018-11-01T00:22:09Zcom_10459.1_56965com_10459.1_2com_10459.1_47453com_10459.1_241com_10459.1_244col_10459.1_57707col_10459.1_59998col_10459.1_30324col_10459.1_363
Collazo Cordero, Cyrelys
Abadias i Sero, Mª Isabel
Colás Medà, Pilar
Iglesias Valenzuela, María Belén
Granado-Serrano, Ana Belén
Serrano Casasola, José Carlos Enrique
Viñas Almenar, Inmaculada
2018-10-31T08:27:51Z
2018-10-31T08:27:51Z
2017
https://doi.org/10.1016/j.ijfoodmicro.2017.09.003
025933
0168-1605
http://hdl.handle.net/10459.1/65009
To further gain insight into the mechanism by which the biopreservative bacterium Pseudomonas graminis CPA-7 develops its antimicrobial activity, we have examined the effect that the prior interaction stablished by this bacterium and two foodborne pathogens on fresh-cut pear, has on their capacity to colonize human epithelial cells (Caco-2 cell line) which is crucial for establishing infection. CPA-7 inhibited the growth of L. monocytogenes and S. enterica subsp. enterica ser. Enteritidis by 5.5 and 3.1 log10, respectively, after 7 d of interaction at 10 °C. Furthermore, CPA-7 attenuated the adherence of S. enterica to Caco-2 cells by 0.8 log10 regardless of the pre-adaptation on the fruit. Conversely, the adhesiveness of L. monocytogenes was not influenced by the interaction with the antagonist but it was reduced by 0.5 log10 after incubation on the food matrix. Pathogen-antagonist-food matrix interaction was associated to a significant reduction of the relative invasiveness of both pathogens, by 1.3 log10 in the case of L. monocytogenes and to an undetectable level (below 5 CFU/g fruit) for S. enterica. CPA-7 can adhere to and internalize into intestinal epithelium which enables it for competition. Its adherence positively correlates to the multiplicity of infection (MOI) with respect to Caco-2 cells, increasing by 0.6 log10 in an MOI range of 0.1:1 to 100:1. For the same levels of inoculum, internalized cells could only be detected after 7 d of pre-adaptation in the fruit (pH 4.5–5.0). However, the combination of gastrointestinal digestion and habituation on the fruit resulted in a significant reduction of CPA-7 populations (by 2 log10 more after 7d of incubation than on inoculation day) as well as in the decrease of its adhesiveness (by 0.8 log10) and invasiveness (to undetectable levels).
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Elsevier, 2017
Adhesion Invasion
Gastrointestinal simulation
Antagonist
Biological control
Effect of Pseudomonas graminis strain CPA-7 on the ability of Listeria monocytogenes and Salmonella enterica subsp. enterica to colonize Caco-2 cells after pre-incubation on fresh-cut pear
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/677522023-07-05T10:53:21Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Serrano Casasola, José Carlos Enrique
Baena-Fustegueras, Juan A
Martín Garí, Meritxell
Rassendren, Helene
Cassanyé, Anna
Naudí i Farré, Alba
López Cano, Carolina
Sánchez Peña, Enric
de la Fuente, Maricruz
Herrería González, Fernando
Olsina Kissler, Jorge Juan
Lecube Torelló, Albert
Portero Otín, Manuel
2019-12-19T11:20:25Z
2019-12-19T11:20:25Z
2019-05
https://doi.org/10.1002/oby.22501
028614
1930-7381
http://hdl.handle.net/10459.1/67752
Objective: This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight‐loss success.
Methods: A human model, in which sixty‐five individuals with obesity underwent bariatric surgery, and a diet‐induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model.
Results: The levels of carboxyethyl‐lysine (CEL) and 2‐succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106 μmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes.
Conclusions: CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/4.0/
cc-by-nc (c) Serrano et al.. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS). 2019
Adipose Tissue Protein Glycoxidation is Associated with Weight‐Loss Potential
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/675982020-07-13T10:33:47Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
Bhardwaj, Deepshikha
Nàger Grifo, Mireia
Visa Pretel, Anna
Crespí Sallán, Marta
Coopman, PJ
Cantí Nicolás, Carles
Herreros Danés, Judit
2019-11-25T09:23:25Z
2019-11-25T09:23:25Z
2018-04-01
https://doi.org/10.1002/jcb.26571
026372
0730-2312
http://hdl.handle.net/10459.1/67598
β-catenin is a central component of adherent junctions and a key effector of canonical Wnt signalling, in which dephosphorylated Ser/Thr β-catenin regulates gene transcription. β-catenin phosphorylation at Tyr142 (PTyr142 β-catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β- catenin switch from adhesive to migratory roles. In addition to classical β-catenin roles, phosphorylated Ser/Thr β-catenin and total β-catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation. Here we find that PTyr142 β-catenin is present in centrosomes in non-transformed and glioblastoma cells and that, in contrast to the Ser/Thr phosphorylated β-catenin, PTyr142 β-catenin centrosomal levels drop in mitosis. Furthermore, we show that the inhibitor of Spleen Tyrosine Kinase (Syk) piceatannol decreases centrosomal PTyr142 β-catenin levels, indicating that Syk regulates centrosome PTyr142 β-catenin. Our findings suggest that PTyr142 β-catenin negatively regulates mitotic progression and highlight the contribution of different phosphorylated β-catenin forms in the coordination of the cell and centrosome cycles.
eng
info:eu-repo/semantics/openAccess
(c) Wiley Periodicals, Inc., 2017
Phosphorylated Tyr142 β-catenin localizes to centrosomes and is regulated by Syk
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/635002018-06-18T13:04:18Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Izquierdo, Cristina
Zarama Ortiz, Angela
Presa, Maximiliano
Malo, Sara
Montoya, Anna
Garabatos, Nahir
Mora Giral, Concepció
Verdaguer Autonell, Joan
Stratmann, Thomas
2018-06-14T08:35:55Z
2018-06-14T08:35:55Z
2018
https://doi.org/10.1038/s41598-018-26161-6
027048
2045-2322
http://hdl.handle.net/10459.1/63500
Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3− CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3− regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Izquierdo et al., 2018
Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4645342023-11-16T03:00:40Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Le Guen , Yann
Luo, Guo
Ambati, Aditya
Damotte, Vincent
Jansen, Iris
Yu, Eric
Nicolas, Aude
de Rojas, Itziar
Peixoto Leal, Thiago
Miyashita, Akinori
Bellenguez, Céline
Mulan Lian, Michelle
Parveen, Kayenat
Morizono, Takashi
Park, Hyeonseul
Grenier- Boley, Benjamin
Naito, Tatsuhiko
Küçükali, Fahri
Talyansky, Seth D.
Piñol Ripoll, Gerard
2023-11-15T12:56:34Z
2023-11-15T12:56:34Z
2023
https://doi.org/10.1073/pnas.2302720120
1091-6490
https://repositori.udl.cat/handle/10459.1/464534
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Yann Le Guen et al., 2023
Attribution 4.0 International
HLA
Alzheimer’s dementia
Parkinson’s disease
Neurodegeneration
Autoimmunity
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4636412023-07-06T03:00:27Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Herrerías-González, Fernando
Yeramian Hakim, Andree
Baena-Fustegueras, Juan A
Bueno Díez, Marta
Fleitas Pérez, Catherine
de la Fuente, Maricruz
Serrano Casasola, José Carlos Enrique
Granado-Serrano, Ana Belén
Santamaría Gómez, Maite
Yeramian, Nadine
Zorzano-Martínez, Marta
Mora Giral, Concepció
Lecube Torelló, Albert
2023-07-05T09:01:36Z
2023-07-05T09:01:36Z
2023
https://doi.org/10.3390/nu15102414
033256
2072-6643
https://repositori.udl.cat/handle/10459.1/463641
Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c)Authors, 2023
Attribution 4.0 International
PKN1
Visceral adipose tissue
Insulin resistance
Type 2 diabetes
Adipocyte
Glucose metabolism
PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/586922021-08-30T15:04:30Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291
Martínez, Anna
Portero Otín, Manuel
Pamplona Gras, Reinald
Ferrer, Isidre
2016-11-29T12:59:12Z
2010
https://doi.org/10.1111/j.1750-3639.2009.00326.x
015603
1015-6305
http://hdl.handle.net/10459.1/58692
Human neurodegenerative diseases with abnormal protein aggregates are associated with aberrant post-translational modifications, solubility, aggregation and fibril formation of selected proteins which cannot be degraded by cytosolic proteases, ubiquitin–protesome system and autophagy, and, therefore, accumulate in cells and extracellular compartments as residual debris. In addition to the accumulation of “primary” proteins, several other mechanisms are involved in the degenerative process and probably may explain crucial aspects such as the timing, selective cellular vulnerability and progression of the disease in particular individuals. One of these mechanisms is oxidative stress, which occurs in the vast majority of, if not all, degenerative diseases of the nervous system. The present review covers most of the protein targets that have been recognized as modified proteins mainly using bidimensional gel electrophoresis, Western blotting with oxidative and nitrosative markers, and identified by mass spectrometry in Alzheimer disease; certain tauopathies such as progressive supranuclear palsy, Pick disease, argyrophilic grain disease and frontotemporal lobar degeneration linked to mutations in tau protein, for example, FTLD-tau, Parkinson disease and related α-synucleinopathies; Huntington disease; and amyotrophic lateral sclerosis, together with related animal and cellular models. Vulnerable proteins can be mostly grouped in defined metabolic pathways covering glycolysis and energy metabolism, cytoskeletal, chaperoning, cellular stress responses, and members of the ubiquitin–proteasome system. Available information points to the fact that vital metabolic pathways are hampered by protein oxidative damage in several human degenerative diseases and that oxidative damage occurs at very early stages of the disease. Yet parallel functional studies are limited and further work is needed to document whether protein oxidation results in loss of activity and impaired performance. A better understanding of proteins susceptible to oxidation and nitration may serve to define damaged metabolic networks at early stages of disease and to advance therapeutic interventions to attenuate disease progression.
eng
info:eu-repo/semantics/restrictedAccess
(c) Wiley, 2009
Alzheimer disease
Amyotrophic lateral sclerosis
Cytoskeleton
Energy metabolism
Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates
article
oai:repositori.udl.cat:10459.1/590362021-08-30T15:04:26Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Abellán Ródenas, Antonio
Legaz, Isabel
Vernier, Baptiste
Rétaux, Sylvie
Medina Hernández, Loreta Mª
2017-01-19T10:58:01Z
2009
https://doi.org/10.1002/cne.22102
013520
0021-9967
http://hdl.handle.net/10459.1/59036
We compared the combinatorial expression patterns of several
LIM domain-containing regulatory genes in the ventrolateral
pallium of mouse and chicken, in order to identify the
homologues of the ventral pallial amygdala and other olfactory
structures in birds. Lmo3, Lmo4, Lhx2, and Lhx9
showed comparable expression patterns in the telencephalon
of mouse and chicken, which allowed distinction of the
ventrolateral pallium and, particularly, the ventral pallial
amygdala and entorhinal cortex. Lmo3 was expressed in
most of the ventrolateral pallium in both species, including,
in chicken, the piriform cortex and dorsal ventricular ridge
(mesopallium, nidopallium, and arcopallium) and, in mouse,
the piriform cortex, most of the claustral complex, and the
pallial amygdala. Lhx9 was differentially expressed in the
ventral pallium, where it was restricted to its rostral (olfactory
bulb) and caudal (amygdalar and entorhinal) poles. In
the caudal pole, expression of Lhx9 overlapped that of its
paralog Lhx2. According to these expression patterns, the
chicken ventral pallial amygdala appears to include the caudal
dorsolateral pallium, the caudal nidopallium, and the
whole arcopallium, and each one relates to a distinct ventricular
sector. Finally, the combinatorial expression patterns
of Lmo3, Lhx9, and Lmo4 distinguished four distinct
subdivisions in the superficial, olfactorecipient area of the
chicken ventral pallium, which appear comparable to the
piriform, entorhinal, amygdalopiriform, and amygdalar cortices
of mammals. The results are discussed in the context
of the two existing, opposite views on the homology of the
dorsal ventricular ridge of sauropsids and in terms of the
evolution of pallial derivatives. J. Comp. Neurol. 516:
166–186, 2009.
eng
info:eu-repo/semantics/restrictedAccess
(c) Wiley-Liss, Inc. 2009
cLhx2
cLhx9
cLmo3
cLmo4
cCdh8
cCdh10
Olfactory and amygdalar structures of the chicken ventral pallium based on the combinatorial expression patterns of LIM and other developmental regulatory genes
article
oai:repositori.udl.cat:10459.1/4647242024-01-04T11:03:23Zcom_10459.1_241com_10459.1_2col_10459.1_30324
Barja, Gustavo
Pamplona Gras, Reinald
2023-12-11T13:33:16Z
2023-12-11T13:33:16Z
2023
https://doi.org/10.1016/j.exger.2023.112324
0531-5565
https://repositori.udl.cat/handle/10459.1/464724
What are the structural components and physiological mechanisms determining the aging process? Can the different mechanisms described in aging biology converge into a core of coordinated aging effectors? Why some human beings, for instance, can reach 115–122 years of age while rats can live at best a maximum of 4 years? Can the aging rate be modified? How much can human lifespan be extended? Is aging a programmed or non-programmed process? This special issue includes invited articles to explore the physiological mechanisms of aging, and both classical and updated hypotheses on the evolutionary meaning of aging.
eng
info:eu-repo/semantics/openAccess
cc-by-nc-nd (c) Gustavo Barja, Reinald Pamplona, 2023
Aging process
Introduction to special issue on ‘physiological and evolutionary mechanisms of aging’
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4642522023-10-26T03:00:33Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
García García, David
Gómez-Barroso, Diana
Hernando, Victoria
Ruiz-Algueró, Marta
Simón, Lorena
Sastre, María
Sierra, María José
Godoy i García, Pere
Diaz, Asunción
2023-10-25T11:03:54Z
2023-10-25T11:03:54Z
2023
https://doi.org/10.1017/S0950268823000985
1469-4409
https://repositori.udl.cat/handle/10459.1/464252
We analysed the transmission of the human mpox virus in Spain by estimating the effective reproduction number of the disease from official surveillance data. Our computations show that this decreased steadily after an initial burst phase, dropping below 1 on July 12, and thus the outbreak was expected to reduce in the following weeks. Differences in trends were found across geographical regions of the country and across MSM and heterosexual populations.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) David García-García et al., 2023
Attribution-NonCommercial-NoDerivatives 4.0 International
Monkeypox
Spain
Transmission
Estimates of mpox effective reproduction number in Spain, April–August 2022
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4642782023-10-27T03:00:33Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324col_10459.1_49291
Navaridas Fernández de Bobadilla, Raúl
Vidal Sabanés, Maria
Ruiz Mitjana, Anna
Perramon Güell, Aida
Megino-Luque, Cristina
Llobet Navàs, David
Matias-Guiu, Xavier
Egea Navarro, Joaquim
Encinas Martín, Mario
Bardia, Lídia
Colombelli, Julien
Dolcet Roca, Xavier
2023-10-26T11:38:31Z
2023-10-26T11:38:31Z
2023
https://doi.org/10.1002/cac2.12409
033221
2523-3548
2523-3548
https://repositori.udl.cat/handle/10459.1/464278
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) TheAuthors, 2023
Attribution-NonCommercial-NoDerivatives 4.0 International
Transient and DNA-free in vivo CRISPR/Cas9 genome editing for flexible modeling of endometrial carcinogenesis
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/659242023-06-28T10:50:55Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Pradas Barriga, Irene
Jové Font, Mariona
Huynh, Karina
Puig Farré, Josep
Inglés, Marta
Borrás, Consuelo
Viña Ribes, José
Meikle, Peter J.
Pamplona Gras, Reinald
2019-03-11T08:45:02Z
2019-03-11T08:45:02Z
2019
https://doi.org/10.1016/j.redox.2019.101127
029429
2213-2317
http://hdl.handle.net/10459.1/65924
A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content in alkenyl forms from phosphatidylethanolamine with longer chain length and higher double bonds. This compositional pattern suggests that ether lipids from centenarians are more resistant to lipid peroxidation, and that ether lipid signature expresses an optimized feature associated with exceptional human longevity. These results are in keeping with the free radical theory of aging.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc- by-nc-nd (c) Elsevier, 2019
Alkenyl phospholipids
Alkyl phospholipids
Centenarians
Fatty acid unsaturation
Exceptional human longevity is associated with a specific plasma phenotype of ether lipids
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/650432023-02-10T19:13:04Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Galván, Ismael
Naudí i Farré, Alba
Erritzøe, Johannes
Møller, Anders P.
Barja, Gustavo
Pamplona Gras, Reinald
2018-11-07T10:40:57Z
2018-11-07T10:40:57Z
2015
https://doi.org/10.1111/evo.12754
023679
0014-3820
http://hdl.handle.net/10459.1/65043
The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here, we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.
eng
info:eu-repo/semantics/openAccess
(c) Society for the Study of Evolution, 2015
Ageing
Birds
Homeoviscous longevity adaptation hypothesis
Longevity
Long lifespans have evolved with long and monounsaturated fatty acids in birds
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/676812023-11-15T10:29:55Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324col_10459.1_49291
Vaquero, Marta
Cuesta, Sara
Anerillas Aljama, Carlos
Altés Bargalló, Gisela
Ribera i Calvet, Joan
Basson, M. Albert
Licht, Jonathan D.
Egea Navarro, Joaquim
Encinas Martín, Mario
2019-12-09T12:07:37Z
2019-12-09T12:07:37Z
2019-08-01
https://doi.org/10.1681/ASN.2018111085
028598
1046-6673
http://hdl.handle.net/10459.1/67681
Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is a group of diseases that include a broad spectrum of developmental defects of the genitourinary system. Mouse models indicate that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of CAKUT. Sprouty1 is an intracellular Ret inhibitor whose mutation results in supernumerary kidneys, megaureters, and hydronephrosis in mice. Both the molecular mechanisms and the structural domains critical for Sprouty function are a matter of controversy, partly because studies pursuing this objective rely on ectopic overexpression in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for their function in vitro. Methods: We have generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We have characterized development of the genitourinary systems of these mice via different methods, including the use of reporter mice expressing EGFP form the Ret locus, and whole mount cytokeratin staining. Results: Mice lacking this tyrosine grow ectopic ureteric buds that ultimately will form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position. Conclusions: Tyrosine 53 is absolutely necessary to convey Sprouty1 function during genitourinary development.
eng
info:eu-repo/semantics/openAccess
Sprouty
Ret
Genitourinary Development
Wolffian Duct
Ureteric bud
Sprouty1 controls genitourinary development via its N-terminal tyrosine
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/710182022-03-16T12:23:19Zcom_10459.1_227com_10459.1_2com_10459.1_241col_10459.1_314col_10459.1_30324
Klionsky, Daniel J.
Cantí Nicolás, Carles
Garcera, Ana
Herreros Danés, Judit
Soler i Tatché, Rosa Ma.
others
2021-04-14T06:57:44Z
2022-02-08T23:21:46Z
2021-02-08
https://doi.org/10.1080/15548627.2020.1797280
031126
1554-8627
http://hdl.handle.net/10459.1/71018
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
eng
info:eu-repo/semantics/openAccess
(c) Taylor & Francis, 2021
Autophagosome
LC3
Cancer
Macroautophagy
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/603332017-10-24T12:14:47Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Serrano Casasola, José Carlos Enrique
Martín Garí, Meritxell
Cassanyé, Anna
Granado-Serrano, Ana Belén
Portero Otín, Manuel
2017-10-20T10:22:39Z
2017-10-20T10:22:39Z
2017
https://doi.org/10.1371/journal.pone.0182762
025934
1932-6203
http://hdl.handle.net/10459.1/60333
Soybean is recognized as rich source of bioactive compounds for the improvement of glucose homeostasis. However, the post-prandial mechanisms of action have not been extensively described. The aim of this study is to determine the changes in glucose homeostasis and related factors after acute intake of a soy beverage. Twenty-nine subjects (15 women and 14 men, with an average age of 19.5 ± 1.2) ingested 500 mL of water, glucose (20.5 g/500 mL) and soy beverage (20 g of carbohydrate) in three separate sessions. Capillary blood glucose was monitored every 15 min until 120 min post-prandial, and blood samples were collected at baseline and after 60 min for insulin, incretin, free amino acids, antioxidant capacity and inflammation marker analysis. The increase in capillary glucose after soy-beverage intake was negligible. This is explained in part by an increase in 83% in insulin levels than induced with glucose alone, which is mainly mediated by a low insulin degradation ratio (determined by c-peptide ratio), incretins and likely also by the modulation of the antioxidant environment. No associations were observed between the insulin levels and soy amino acid uptake. It could be concluded that the acute low glycaemic response of a soy beverage may involves a relationship between incretin and insulin secretion and insulin degradation.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Serrano et al., 2017
Characterization of the post-prandial insulinemic response and low glycaemic index of a soy beverage
article
oai:repositori.udl.cat:10459.1/570262022-10-17T20:37:49Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291
Naudí i Farré, Alba
Jové Font, Mariona
Cacabelos Barral, Daniel
Ayala Jové, Ma. Victoria (Maria Victoria)
Cabré Cucó, Rosanna
Caro, Pilar
Gómez, José
Portero Otín, Manuel
Barja, Gustavo
Pamplona Gras, Reinald
2016-05-13T08:21:20Z
2013
https://doi.org/10.1007/s00726-012-1339-2
020169
0939-4451
http://hdl.handle.net/10459.1/57026
Maillard reaction contributes to the chemical
modification and cross-linking of proteins. This process
plays a significant role in the aging process and determination
of animal longevity. Oxidative conditions promote
the Maillard reaction. Mitochondria are the primary site of
oxidants due to the reactive molecular species production.
Mitochondrial proteome cysteine residues are targets of
oxidative attack due to their specific chemistry and localization.
Their chemical, non-enzymatic modification leads
to dysfunctional proteins, which entail cellular senescence
and organismal aging. Previous studies have consistently
shown that caloric and methionine restrictions, nutritional
interventions that increase longevity, decrease the rate of
mitochondrial oxidant production and the physiological
steady-state levels of markers of oxidative damage to
macromolecules. In this scenario, we have detected
S-(carboxymethyl)-cysteine (CMC) as a new irreversible
chemical modification in mitochondrial proteins. CMC
content in mitochondrial proteins significantly correlated
with that of the lysine-derived analog Ne-(carboxymethyl)-
lysine. The concentration of CMC is, however, one order of
magnitude lower compared with CML likely due in part to
the lower content of cysteine with respect to lysine of the
mitochondrial proteome. CMC concentrations decreases in
liver mitochondrial proteins of rats subjected to 8.5 and 25 % caloric restriction, as well as in 40 and 80 %
methionine restriction. This is associated with a concomitant
and significant increase in the protein content of
sulfhydryl groups. Data presented here evidence that CMC,
a marker of Cys-AGE formation, could be candidate as a
biomarker of mitochondrial damage during aging.
eng
info:eu-repo/semantics/restrictedAccess
(c) Springer Verlag, 2013
Aging
Carboxymethylated proteins
Dietary restriction
Formation of S-(carboxymethyl)-cysteine in rat liver mitochondrial proteins: effects of caloric and methionine restriction
article
oai:repositori.udl.cat:10459.1/600102021-04-29T09:27:09Zcom_10459.1_227com_10459.1_2com_10459.1_59360com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59361col_10459.1_59998col_10459.1_30324
Cabré Cucó, Rosanna
Naudí i Farré, Alba
Dominguez Gonzalez, Mayelin
Ayala Jové, Ma. Victoria (Maria Victoria)
Jové Font, Mariona
Mota Martorell, Natàlia
Piñol Ripoll, Gerard
Gil Villar, M. Pilar
Rué i Monné, Montserrat
Portero Otín, Manuel
Ferrer, Isidre
Pamplona Gras, Reinald
2017-07-06T11:54:01Z
2017-12-31T23:27:49Z
2017
https://doi.org/10.1016/j.freeradbiomed.2016.12.010
025637
0891-5849
http://hdl.handle.net/10459.1/60010
Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional throughout a healthy adult lifespan, yet the mechanisms that maintain function and protect against neurodegenerative processes during aging are unknown. Here we show that protein oxidative and glycoxidative damage significantly increases during human brain aging, with a breakpoint at 60 years old. This trajectory is coincident with a decrease in the content of the mitochondrial respiratory chain complex I–IV. We suggest that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Elsevier, 2016
Cell survival pathways
Mechanistic target of rapamycin (mTOR)
Mitochondria respiratory chain
Mitochondrial stress
Protein oxidation
Repressor element 1-silencing transcription factor (REST)
Sixty years old is the breakpoint of human frontal cortex aging
article
oai:repositori.udl.cat:10459.1/695082023-02-03T10:09:05Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Sánchez Peña, Enric
Sánchez Pérez, Marta
Betriu i Bars, M. Àngels
Rius, Ferran
Torres, Gerard
Purroy Garcia, Francisco
Pamplona Gras, Reinald
Ortega, Marta
López Cano, Carolina
Hernández García, Marta
Bueno Díez, Marta
Fernández i Giráldez, Elvira
Salvador, Javier
Lecube Torelló, Albert
ILERVAS project collaborators
2020-09-18T09:36:52Z
2020-09-18T09:36:52Z
2020
https://doi.org/10.1159/000502696
029673
1662-4033
http://hdl.handle.net/10459.1/69508
Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease.
Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53-63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra - Body Adiposity Estimator [CUN-BAE], and Deurenberg's formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora's equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. -Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive.
Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd, (c) Sánchez, Enric et al., 2020
Obesity indices
Adipose tissue
Excess body weight
Subclinical atheromatosis
Are Obesity Indices Useful for Detecting Subclinical Atheromatosis in a Middle-Aged Population?
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/844842023-04-14T03:00:46Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
José, Viña
Escudero, Joaquín
Baquero, Miquel
Cebrián, Mónica
Carbonell Asíns, Juan Antonio
Muñoz, José Enrique
Satorres, Encarnación
Meléndez, Juan Carlos
Ferrer Rebolleda, José
Cózar Santiago, Mª Del Puig
Santabárbara Gómez, Jose Manuel
Jové Font, Mariona
Pamplona Gras, Reinald
Tarazona Santabalbina, Francisco José
Borrás, Consuelo
2022-12-07T10:58:33Z
2022-12-07T10:58:33Z
2022
https://doi.org/10.1186/s13195-022-01097-2
033110
1758-9193
http://hdl.handle.net/10459.1/84484
Background: Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet efective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defned
polyphenol that acts by multimodal specifc mechanisms. Our group previously showed that genistein supplementation is efective to treat the double transgenic (APP/PS1) AD animal model.
Methods: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the efect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloidbeta deposition was analyzed using 18F-futemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.
Results: We report that genistein treatment results in a signifcant improvement in two of the tests used (dichotomized direct TAVEC, p=0.031; dichotomized delayed Centil REY copy p=0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p=0.878), while placebo-treated did increase it (p=0.036). We did not observe signifcant changes in other brain areas studied.
Conclusions: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with prodromal Alzheimer’s disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) authors, 2022
Soy isofavones
Phytoestrogens
Cognitive impairment
Amyloid-beta cingulate gyrus
Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/585212022-10-18T18:43:42Zcom_10459.1_59360com_10459.1_2com_10459.1_241col_10459.1_59361col_10459.1_30324col_10459.1_49291col_10459.1_44504
Keipert, Susanne
Ost, Mario
Chadt, A.
Voigt, A.
Ayala Jové, Ma. Victoria (Maria Victoria)
Portero Otín, Manuel
Pamplona Gras, Reinald
Al-Hasani, H.
Klaus, Susanne
2016-11-16T08:50:59Z
2013
https://doi.org/10.1152/ajpendo.00518.2012
020173
0002-9513
http://hdl.handle.net/10459.1/58521
Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.
eng
info:eu-repo/semantics/restrictedAccess
(c) The American Physiological Society, 2013
Uncoupling protein 1
AMP-activated protein kinase
Oxidative
Stress
Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system
article
oai:repositori.udl.cat:10459.1/733192022-03-19T00:12:46Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Castelblanco Echavarría, Esmeralda
Sarrias, Maria-Rosa
Betriu i Bars, M. Àngels
Soldevila, Berta
Barranco Altirriba, María
Franch-Nadal, Josep
Valdivielso Revilla, José Manuel
Bermúdez López, Marcelino
Groop, Per-Henrik
Fernández i Giráldez, Elvira
Alonso, Núria
Mauricio Puente, Dídac
2022-03-18T09:12:47Z
2022-03-18T09:12:47Z
2021
https://doi.org/10.18632/aging.203615
1945-4589
http://hdl.handle.net/10459.1/73319
This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0-1.36), and all-cause mortality (1.22, 1.01-1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all-cause mortality in individuals with CKD.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by(c)Authors, 2021
CD5L
Cardiovascular events
Chronic kidney disease
Mortality
sCD36
Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/678782023-02-03T10:08:08Zcom_10459.1_47453com_10459.1_2com_10459.1_241com_10459.1_240col_10459.1_59998col_10459.1_30324col_10459.1_333
Sánchez Pérez, Marta
Sánchez Peña, Enric
Hernández García, Marta
González, Jessica
Purroy Garcia, Francisco
Rius, Ferran
Pamplona Gras, Reinald
Farràs-Sallés, Cristina
Gutiérrez Carrasquilla, Liliana
Fernández i Giráldez, Elvira
Bermúdez López, Marcelino
Salvador, Javier
Salas-Salvadó, Jordi
Lecube Torelló, Albert
2020-01-27T08:21:32Z
2020-01-27T08:21:32Z
2019-06-17
https://doi.org/10.3390/nu11061359
029433
2072-6643
http://hdl.handle.net/10459.1/67878
There is a close relationship between lifestyle behaviors and excess adiposity. Althoughbody mass index (BMI) is the most used approach to estimate excess weight, other anthropometricindices have been developed to measure total body and abdominal adiposity. However, littleis known about the impact of physical activity and adherence to a Mediterranean diet on theseindices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects withlow to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants’adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet(Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, ClínicaUniversidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg’s formula), centraladiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora’s equation,A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher valuesof total body fat and central adiposity. This result was constant regardless of the indices used toestimate adiposity. However, the association between MedDiet and obesity indices was much lessmarked and more dependent on sex than that observed for physical activity. Lean body mass wasinfluenced by neither physical activity nor MedDiet adherence. No joint effect between physicalactivity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion,physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDietshowed a slight impact on estimated anthropometric indices, with no joint effect when consideringboth lifestyle variables. ClinTrials.gov Identifier: NCT03228459.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es
cc-by (c) Sánchez, Marta et al., 2019
Adiposity
Body fat
Mediterranean diet
Obesity indices
Physical activity
Questionnaire
Dissimilar impact of Mediterranean diet and physical activity on estimated body composition: A cross-sectional study from the ILERVAS project
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/727542023-01-24T20:40:17Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Mota Martorell, Natàlia
Jové Font, Mariona
Berdún Hernández, Rebeca
Pamplona Gras, Reinald
2022-01-17T08:06:20Z
2022-01-17T08:06:20Z
2021-06-11
https://doi.org/10.1038/s42003-021-02254-3
031952
2399-3642
http://hdl.handle.net/10459.1/72754
Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content. The present study follows a comparative approach to analyse plasma methionine metabolic profile using a LC-MS/MS platform from 11 mammalian species with a longevity ranging from 3.5 to 120 years. Our findings demonstrate the existence of a species-specific plasma profile for methionine metabolism associated with longevity characterised by: i) reduced methionine, cystathionine and choline; ii) increased non-polar amino acids; iii) reduced succinate and malate; and iv) increased carnitine. Our results support the existence of plasma longevity features that might respond to an optimised energetic metabolism and intracellular structures found in long-lived species.
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/4.0
cc-by (c) authors, 2021
Plasma methionine metabolic profile is associated with longevity in mammals
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/677512022-10-18T18:51:39Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
Casasnovas, Carlos
Ruiz, Montserrat
Schlüter, Agatha
Naudí i Farré, Alba
Fourcade, Stéphane
Veciana, Misericordia
Castañer, Sara
Albertí, Antonia
Bargalló, Nuria
Johnson, Maria
Raymond, Gerald V.
Fatemi, Ali
Moser, Ann B.
Villarroya, Francesc
Portero Otín, Manuel
Artuch, Rafael
Pamplona Gras, Reinald
Pujol, Aurora
2019-12-19T10:06:02Z
2019-12-19T10:06:02Z
2019-05
https://doi.org/10.1007/s13311-019-00735-2
029454
1933-7213
http://hdl.handle.net/10459.1/67751
X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were
administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III
randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Casasnovas et al., 2019
Adrenomyeloneuropathy
Antioxidants
Biomarkers
Oxidative stress
Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4644812024-03-13T11:06:06Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
Cambray Carner, Serafí
Bermúdez López, Marcelino
Garcia Carrasco, Alicia
Valdivielso Revilla, José Manuel
2023-11-09T18:16:24Z
2023-11-09T18:16:24Z
2023-10-10
https://doi.org/10.1093/ckj/sfad257
2048-8513
2048-8505
https://repositori.udl.cat/handle/10459.1/464481
Background: Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism–related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort. Methods: A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression. Results: Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression [odds ratio 2.3 (95% confidence interval 1.06–4.9)] and higher risk of suffering a CVE [hazard ratio 2.16 (95% confidence interval 1.13–4.12)] compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample. Conclusions: The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) The Authors, 2023
Attribution 4.0 International
Atherosclerosis progression
Cardiovascular events
Chronic kidney disease
Matrix gamma-carboxy glutamic acid (Gla) protein
Polymorphisms
Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/483792022-11-25T20:33:00Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Abellán Ródenas, Antonio
Desfilis, Ester
Medina Hernández, Loreta Mª
2015-06-26T08:10:11Z
2015-06-26T08:10:11Z
2014
https://doi.org/10.3389/fnana.2014.00059
021239
1662-5129
http://hdl.handle.net/10459.1/48379
We carried out a study of the expression patterns of seven developmental regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination with topological position, to identify the medial pallial derivatives, define its major subdivisions, and compare them between mouse and chicken. In both species, the medial pallium is defined as a pallial sector adjacent to the cortical hem and roof plate/choroid tela, showing moderate to strong ventricular zone expression of Lef1, Lhx2, and Lhx9, but not Lhx5. Based on this, the hippocampal formation (indusium griseum, dentate gyrus, Ammon's horn fields, and subiculum), the medial entorhinal cortex, and part of the amygdalo-hippocampal transition area of mouse appeared to derive from the medial pallium. In the chicken, based on the same position and gene expression profile, we propose that the hippocampus (including the V-shaped area), the parahippocampal area (including its caudolateral part), the entorhinal cortex, and the amygdalo-hippocampal transition area are medial pallial derivatives. Moreover, the combinatorial expression of Lef1, Prox1, Lmo4, and Lmo3 allowed the identification of dentate gyrus/CA3-like, CA1/subicular-like, and medial entorhinal-like comparable sectors in mouse and chicken, and point to the existence of mostly conserved molecular networks involved in hippocampal complex development. Notably, while the mouse medial entorhinal cortex derives from the medial pallium (similarly to the hippocampal formation, both being involved in spatial navigation and spatial memory), the lateral entorhinal cortex (involved in processing non-spatial, contextual information) appears to derive from a distinct dorsolateral caudal pallial sector.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
cc-by, (c) Abellán et al., 2014
medial pallium
hippocampus
dentate gyrus
Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken
article
oai:repositori.udl.cat:10459.1/4634502023-10-05T13:39:00Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Sol, Joaquim
Obis Monné, Èlia
Mota Martorell, Natàlia
Pradas Barriga, Irene
Galo-Licona, José Daniel
Martín Garí, Meritxell
Fernández Bernal, Anna
Ortega Bravo, Marta
Mayneris Perxachs, Jordi
Borrás, Consuelo
Viña, José
Fuente, Monica de la
Mate, Ianire
Biarnés, Carles
Pedraza, Salvador
Vilanova, Joan Carles
Brugada, Ramon
Ramos, Rafel
Serena, Joaquín
Ramió Torrentà, Lluís
Pineda, Víctor
Daunis-i-Estadella, Pepus
Thió-Henestrosa, Santiago
Barretina Ginesta, Jordi
Garre Olmo, Josep
Portero Otín, Manuel
Fernández Real, José Manuel
Puig, Josep
Jové Font, Mariona
Pamplona Gras, Reinald
2023-06-05T07:42:18Z
2023-06-05T07:42:18Z
2023
https://doi.org/10.1111/acel.13821
1474-9726
https://repositori.udl.cat/handle/10459.1/463450
Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of “omic” techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30–100 years old; 2: n = 68, 70% females, 19–107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial β-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Joaquim Sol et al., 2023
Attribution 4.0 International
Aging
Aromatic amino acids
Bioenergetics
Liquid chromatography-mass spectrometry
Metabolomics
Sex/gender perspective
Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/721972023-02-02T13:12:07Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Toledano Magaña, Yanis
Flores-Santos, Leticia
Montes de Oca, Georgina
González Montiel, Alfonso
García Ramos, Juan Carlos
Mora Giral, Concepció
Saavedra Ávila, Noemí Alejandra
Gudiño Zayas, Marco
González Ramírez, Luisa Carolina
Laclette, Juan P.
Carrero, Julio C.
2021-11-03T11:47:58Z
2021-11-03T11:47:58Z
2021-10-27
https://doi.org/10.1021/acsomega.1c04367
031757
2470-1343
http://hdl.handle.net/10459.1/72197
Halloysite clay nanotubes (HNTs) have been proposed as highly biocompatible for several biomedical applications. Various polymers have been used to functionalize HNTs, but scarce information exists about polystyrene for this purpose. This work evaluated polystyrene-functionalized HNTs (FHNTs) by comparing its effects with non-FHNTs and innocuous talc powder on in vitro and in vivo models. Monocyte-derived human or murine macrophages and the RAW 264.7 cell line were treated with 0.01, 0.1, 1, and 100 μg mL-1 FHNTs, HNTs, or talc to evaluate the cytotoxic and cytokine response. Our results show that nanoclays did not cause cytotoxic damage to macrophages. Only the 100 μg mL-1 concentration induced slight proinflammatory cytokine production at short exposure, followed by an anti-inflammatory response that increases over time. CD1 mice treated with a single dose of 1, 2.5, or 5 mg Kg-1 of FHNTs or HNTs by oral and inhalation routes caused aluminum accumulation in the kidneys and lungs, without bodily signs of distress or histopathological changes in any treated mice, evaluated at 48 h and 30 days post-treatment. Nanoclay administration simultaneously by four different parenteral routes (20 mg Kg-1) or the combination of administration routes (parenteral + oral or parenteral + inhalation; 25 mg Kg-1) showed accumulation on the injection site and slight surrounding inflammation 30 days post-treatment. CD1 mice chronically exposed to HNTs or FHNTs in the bedding material (ca 1 mg) throughout the parental generation and two successive inbred generations for 8 months did not cause any inflammatory process or damage to the abdominal organs and the reproductive system of the mice of any of the generations, did not affect the number of newborn mice and their survival, and did not induce congenital malformations in the offspring. FHNTs showed a slightly less effect than HNTs in all experiments, suggesting that functionalization makes them less cytotoxic. Doses of up to 25 mg Kg-1 by different administration routes and permanent exposure to 1 mg of HNTs or FHNTs for 8 months seem safe for CD1 mice. Our in vivo and in vitro results indicate that nanoclays are highly biocompatible, supporting their possible safe use for future biomedical and general-purpose applications.
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) The Authors, 2021
Immunology
Anatomy
Rodent models
Peptides and proteins
Toxicity
Toxicological Evaluations in Macrophages and Mice Acutely and Chronically Exposed to Halloysite Clay Nanotubes Functionalized with Polystyrene
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/480872017-03-10T09:57:32Zcom_10459.1_59328com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59329col_10459.1_59998col_10459.1_30324
Garrofé Ochoa, Xènia
Melero Fernández de Mera, Raquel M
Fernández Gómez, Francisco J.
Ribas i Fortuny, Judit
Jordán Bueso, Joaquín
Boix Torras, Jacint
2015-03-20T19:03:24Z
2015-03-20T19:03:24Z
2008
https://doi.org/10.1158/1535-7163.MCT-08-0655
013097
1535-7163
http://hdl.handle.net/10459.1/48087
In previous reports we have shown in SH-SY5 cells that Olomoucine and Roscovitine, two inhibitory drugs of Cyclin Dependent Kinases, caused apoptosis independent of the extrinsic pathway. In this experimental paradigm, apoptosis was refractory to the protective effects of either Bcl-2 or Bcl-XL overexpression. We are now reporting the failure of Bcl-XL to prevent dell death was consistent with no effect on the kinetics of caspase activation and cytochrome c release. To further characterize this issue, we have discarded a direct effect of either Olomoucine or Roscovitine on mitochondrial permeability transition. Moreover, we have evidence that an intrinsic pathway took place in SH-SY5Y cells by demonstrating the mitochondrial translocation of a GFP-Bax construct upon transfection and treatment with CDK inhibitory drugs. Finally, we tested the effect of Olomoucine and Roscovitine on w.t., bax-/-, bak-/- and double bax-/-bak-/- MEFs. In w.t. MEFs, both drugs induced cell death by apoptosis in a dose-dependent manner. In bax-/-, bak-/- and, particularly, double bax-/-bak-/- MEFs, we observed the inhibition of apoptosis. In conclusion, Olomoucine and Roscovitine caused apoptosis through an intrinsic pathway with Bax and Bak proteins being involved.
eng
info:eu-repo/semantics/openAccess
(c) American Association for Cancer Research, 2008
Apoptosis
Olomoucine
Bcl-2
CDK
Roscovitine
BAX and BAK proteins are required for cyclin-dependent kinase inhibitory drugs to cause apoptosis
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/569322021-08-30T15:04:36Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Boix Torras, Jacint
Roca, Joaquim
2016-05-02T09:43:08Z
1993
https://doi.org/10.1002/cyto.990140418
004937
0196-4763
http://hdl.handle.net/10459.1/56932
By application of minor variations in
the usual method of centrifugal elutriation,
we have been able to separate a nuclear
suspension from rooster testes. We
have obtained a population of elongated
or late spermatid nuclei (98% purity), a Key terms: Centrifugal elutriation, nupopulation
of round or early spermatid clei separation, rooster spermatogenesis
nuclei (90% purity), and, finally, a mixed
population of meiotic and pre-meiotic
nuclei.
eng
info:eu-repo/semantics/restrictedAccess
(c) Wiley-Liss, Inc., 1993
Centrifugal elutriation
nuclei separation
rooster spermatogenesi
Separation of rooster spermatogenic nuclei by means of centrifugal elutriation
article
oai:repositori.udl.cat:10459.1/557132017-03-10T14:17:03Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241com_10459.1_240col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_333
Soler González, Jorge
Buti, Miquel
Boada Pallàs, Jordi
Ayala Jové, Ma. Victoria (Maria Victoria)
Peñascal Pujol, Eduard
Rodriguez, Toni
2016-02-15T08:32:43Z
2016-02-15T08:32:43Z
2016
https://doi.org/10.1016/j.aprim.2015.02.005
022516
0212-6567
http://hdl.handle.net/10459.1/55713
Objectives: The adaptation of the educational programmes of European faculties of medicine
to the European Higher Education Area guidelines has focused curricula design on competence acquisition. Competencies are defined as the achievements of a predetermined level of efficacy in real-world scenarios. Our objective was to assess whether performance on a common
competence evaluation test, the Objective Structured Clinical Examination (OSCE), resulted in different scores for second-year students after a practical medical training course took place in a primary health centre (PHC) or in a hospital.
Design: A descriptive study was conducted during the 2010---2014 academic year of the OSCE
test scores obtained by all second-year students.
Location: Faculty of Medicine at the University of Lleida (Catalonia, Spain).
Main measurements: We performed a correlation analysis between students who completed
their practical medical training at the PHC and hospitals utilising Student’s t-test for comparison
of means.
Results: 423 students who completed internships at the PHC and at hospitals obtained OSCE
mean scores of 7.32 (SD; IC) (0.82; 7.18---7.47) points and 7.17 (0.83; 6.07---7.26) points, respectively
(p = 0.07).
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
cc-by-nc-nd, (c) Elsevier España, 2014
Competencias
Educación médica
Innovación docente
Evaluación de competencias clínicas estructurada
Do primary health centres and hospitals contribute equally towards achievement of the transversal clinical competencies of medical students? Performance on the Objective Structured Clinical Examination (OSCE) in competency acquisition
article
oai:repositori.udl.cat:10459.1/726082023-10-26T14:22:18Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Berdún Hernández, Rebeca
Jové Font, Mariona
Sol, Joaquim
Cai, Weijing
He, John C.
Rodriguez Mortera, Reyna
Martín Garí, Meritxell
Pamplona Gras, Reinald
Uribarri, Jaime
Portero Otín, Manuel
2021-12-21T10:13:26Z
2021-12-21T10:13:26Z
2021
https://doi.org/10.1002/mnfr.202000499
031683
1613-4125
1613-4133
http://hdl.handle.net/10459.1/72608
Scope: Diets with low content in advanced glycation end products (AGEs) lead to beneficial properties in highly prevalent age-related diseases. To shed light on the mechanisms behind, the changes induced by a low AGE dietary intervention in the circulating metabolome are analyzed.
Methods and Results: To this end, 20 non-diabetic patients undergoing peritoneal dialysis are randomized to continue their usual diet or to one with a low content of AGEs for 1 month. Then, plasmatic metabolome and lipidomes are analyzed by liquid-chromatography coupled to mass spectrometry. The levels of defined AGE structures are also quantified by ELISA and by mass-spectrometry. The results show that the low AGE diet impinged significant changes in circulating metabolomes (166 molecules) and lipidomes (91 lipids). Metabolic targets of low-AGE intake include sphingolipid, ether-lipids, and glycerophospholipid metabolism. Further, it reproduces some of the plasma characteristics of healthy aging.
Conclusion : The finding of common pathways induced by low-AGE diets with previous metabolic traits implicated in aging, insulin resistance, and obesity suggest the usefulness of the chosen approach and supports the potential extension of this study to other populations.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) authors, 2021
Restriction of Dietary Advanced Glycation End Products Induces a Differential Plasma Metabolome and Lipidome Profile
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/587272021-08-30T15:04:30Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291
Terni, Beatrice
Boada Pallàs, Jordi
Portero Otín, Manuel
Pamplona Gras, Reinald
Ferrer, Isidre
2016-12-01T08:35:09Z
2010
https://doi.org/10.1111/j.1750-3639.2009.00266.x
013684
1015-6305
http://hdl.handle.net/10459.1/58727
Oxidative stress has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Several proteins have been identified as targets of oxidative damage in AD dementia (usually stages V/VI of Braak) and in subjects with mild cognitive impairment associated with middle stages of AD pathology (stage IV of Braak). In this study, we investigate whether brain proteins are locally modified by oxidative stress at the first stages of AD-related pathology when morphological lesions are restricted to the entorhinal and transentorhinal cortices of neurofibrillary pathology (stages I/II of Braak). Using a proteomic approach, we show that the α subunit of the mitochondrial adenosine triphosphate (ATP)-synthase is distinctly lipoxidized in the entorhinal cortex at Braak stages I/II compared with age-matched controls. In addition, ATP-synthase activity is significantly lower in Braak stages I/II than age-matched control, while electron transport chain, expressed by the mitochondrial complex I activity, remains not affected. This is the first study showing oxidative damage in the first stage, and clinically silent period, of AD-related pathology characterized by entorhinal and transentorhinal tauopathy.
eng
info:eu-repo/semantics/restrictedAccess
(c) International Society of Neuropathology, 2009
Alzheimer disease stage I/II
ATP-synthase α chain
Entorhinal cortex
Lipid peroxidation
Mitochondrial ATP-Synthase in the entorhinal cortex is a target of oxidative stress at stages I/II of Alzheimer's disease pathology
article
oai:repositori.udl.cat:10459.1/840432023-11-15T10:29:14Zcom_10459.1_227com_10459.1_2com_10459.1_241col_10459.1_314col_10459.1_30324col_10459.1_49291
Altés Bargalló, Gisela
Vaquero, Marta
Cuesta, Sara
Anerillas Aljama, Carlos
Macià Armengol, Anna
Espinet Mestre, Carme
Ribera i Calvet, Joan
Bellusci, Saverio
Klein, Ophir D.
Yeramian Hakim, Andree
Dolcet Roca, Xavier
Egea Navarro, Joaquim
Encinas Martín, Mario
2022-11-02T10:38:27Z
2022-11-02T10:38:27Z
2022
https://doi.org/10.1007/s00018-022-04546-1
032642
1420-682X
1420-9071
http://hdl.handle.net/10459.1/84043
The Wolffian ducts (WD) are paired epithelial tubules central to the development of the mammalian genitourinary tract. Outgrowths from the WD known as the ureteric buds (UB) generate the collecting ducts of the kidney. Later during development, the caudal portion of the WD will form the vas deferens, epididymis and seminal vesicle in males, and will degenerate in females. While the genetic pathways controlling the development of the UB are firmly established, less is known about those governing development of WD portions caudal to the UB. Sprouty proteins are inhibitors of receptor tyrosine kinase (RTK) signaling in vivo. We have recently shown that homozygous mutation of a conserved tyrosine (Tyr53) of Spry1 results in UB defects indistinguishable from that of Spry1 null mice. Here, we show that heterozygosity for the Spry1 Y53A allele causes caudal WD developmental defects consisting of ectopically branched seminal vesicles in males and persistent WD in females, without affecting kidney development. Detailed analysis reveals that this phenotype also occurs in Spry1+/- mice but with a much lower penetrance, indicating that removal of tyrosine 53 generates a dominant negative mutation in vivo. Supporting this notion, concomitant deletion of one allele of Spry1 and Spry2 also recapitulates the genital phenotype of Spry1Y53A/+ mice with high penetrance. Mechanistically, we show that unlike the effects of Spry1 in kidney development, these caudal WD defects are independent of Ret signaling, but can be completely rescued by lowering the genetic dosage of Fgf10. In conclusion, mutation of tyrosine 53 of Spry1 generates a dominant negative allele that uncovers fine-tuning of caudal WD development by Sprouty genes.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Altés et al., 2022
Dominant negative
Gartner cyst
Genitourinary development
Seminal vesicle
Wolffian duct
A dominant negative mutation uncovers cooperative control of caudal Wolffian duct development by Sprouty genes
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4649422024-02-01T09:07:09Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Yeramian Hakim, Andree
Santacana Espasa, Maria
Sorolla Bardají, Anabel
Llobet Navàs, David
Encinas Martín, Mario
Velasco Sánchez, Ana
Bahi i Pla, Núria
Eritja Sánchez, Núria
Domingo, Mónica
Oliva, E.
Dolcet Roca, Xavier
Matias-Guiu, Xavier
2024-01-31T15:38:30Z
2024-01-31T15:38:30Z
2011
https://doi.org/10.1038/labinvest.2011.58
016649
0023-6837
1530-0307
https://repositori.udl.cat/handle/10459.1/464942
Endometrial carcinoma (EC) is a common female cancer, treated mainly by surgery and adjuvant radiotherapy. Relapse following treatment is associated with increased risk of metastases. Hypoxia, a common microenvironment in solid tumors, correlates with malignant progression, rendering tumors resistant to ionizing therapy. Hence, we assessed here the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α) and members of the NF-κB family in 82 primary EC and 10 post-radiation recurrences of EC. Post-radiation recurrences were highly hypoxic, with a higher expression of HIF-1α and also RelA (p65) and p52 when compared with primary EC. We next investigated the effects of hypoxia on EC cell lines. We found that EC cell lines are highly resistant to hypoxia-induced apoptosis. We thus focused on the molecular mechanisms involved in conferring hypoxic cell death resistance. We show that in addition to the classical NF-κB, hypoxia activates the alternative NF-κB pathway. To characterize the upstream kinases involved in the activation of these pathways, we used lentiviral-mediated knockdown and mouse embryonic fibroblasts lacking IKKα and IKKβ kinases. Both IKKα and IKKβ kinases are required for RelA (p65) and p100 accumulation, whereas p52 processing under hypoxia is IKKα dependent. Furthermore, Ishikawa endometrial cell line harboring either RelA (p65) or p52 short-hairpin RNA was sensitive to hypoxia-induced cell death, indicating that, in addition to the known prosurvival role of RelA (p65) under hypoxia, alternative NF-κB pathway also enhances hypoxic survival of EC cells. Interestingly, although HIF-1α controlled classical NF-κB activation pathway and survival under hypoxia through RelA (p65) nuclear accumulation, the alternative pathway was HIF-1α independent. These findings have important clinical implications for the improvement of EC prognosis before radiotherapy.
eng
info:eu-repo/semantics/openAccess
(c) USCAP, 2011
Apoptosis
Hypoxia
IKKα
IKKβ
NF-κB
Nuclear factor-κB2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1α independent manner
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/681472022-11-25T20:43:06Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Medina Hernández, Loreta Mª
Abellán Ródenas, Antonio
Desfilis, Ester
2020-03-05T08:15:15Z
2020-03-05T08:15:15Z
2019
https://doi.org/10.3389/fphys.2019.00894
028995
1664-042X
http://hdl.handle.net/10459.1/68147
Birds are extremely interesting animals for studying the neurobiological basis of cognition and its evolution. They include species that are highly social and show high cognitive capabilities. Moreover, birds rely more on visual and auditory cues than on olfaction for social behavior and cognition, just like primates. In primates, there are two major brain networks associated to sociality: (1) one related to perception and decision-making, involving the pallial amygdala (with the basolateral complex as a major component), the temporal and temporoparietal neocortex, and the orbitofrontal cortex; (2) another one
related to affiliation, including the medial extended amygdala, the ventromedial prefrontal and anterior cingulate cortices, the ventromedial striatum (largely nucleus accumbens), and the ventromedial hypothalamus. In this account, we used an evolutionary developmental neurobiology approach, in combination with published comparative connectivity and functional data, to identify areas and functional networks in the sauropsidian brain comparable to those of mammals that are related to decision-making and affiliation. Both in mammals and sauropsids, there is an important interaction between these networks
by way of cross projections between areas of both systems.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Loreta Medina et al., 2019
Medial amygdala
BST
Social cognition
Affiliation
Dorsal ventricular ridge
Evolution of Pallial Areas and Networks Involved in Sociality: Comparison Between Mammals and Sauropsids
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/590502021-08-30T15:04:27Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Suárez, Juan
Dávila, José Carlos
Real, M. Ángeles
Guirado, Salvador
Medina Hernández, Loreta Mª
2017-01-20T09:35:09Z
2006
https://doi.org/10.1002/cne.21004
011377
0891-0618
http://hdl.handle.net/10459.1/59050
To better understand the formation and adult organization of the avian pallium, we studied
the expression patterns of gamma-aminobutyric acid (GABA), calbindin (CB), calretinin (CR),
and neuronal nitric oxide synthase (nNOS) in the hippocampal formation and hyperpallium of
developing and adult chicks. Each marker showed a specific spatiotemporal expression pattern
and was expressed in a region (area)-specific but dynamic manner during development. The
combinatorial expression of these markers was very useful for identifying and following the
development of subdivisions of the chicken hippocampal formation and hyperpallium. In the
hyperpallium, three separate radially arranged subdivisions were present since early development
showing distinct expression patterns: the apical hyperpallium (CB-rich); the intercalated
hyperpallium (nNOS-rich, CB-poor); the dorsal hyperpallium (nNOS-poor, CB-moderate). Furthermore,
a novel division was identified (CB-rich, CR-rich), interposed between hyper- and
mesopallium and related to the lamina separating both, termed laminar pallial nucleus. This
gave rise at its surface to part of the lateral hyperpallium. Later in development, the interstitial
nucleus of the apical hyperpallium became visible as a partition of the apical hyperpallium. In the
hippocampal formation, at least five radial divisions were observed, and these were compared
with the divisions proposed recently in adult pigeons. Of note, the corticoid dorsolateral area
(sometimes referred as caudolateral part of the parahippocampal area) contained CB immunoreactivity
patches coinciding with Nissl-stained cell aggregates, partially resembling the patches
described in the mammalian entorhinal cortex. Each neurochemical marker was present in
specific neuronal subpopulations and axonal networks, providing insights into the functional
maturation of the chicken pallium. J. Comp. Neurol. 497:751–771, 2006.
eng
info:eu-repo/semantics/restrictedAccess
(c) Wiley-Liss, Inc. 2006
Calbindin
Calretinin
Wulst
Cortical regions
Calcium-binding proteins, neuronal nitric oxide synthase, and GABA help to distinguish different pallial areas in the developing and adult chicken. I. Hippocampal formation and hyperpallium
article
oai:repositori.udl.cat:10459.1/590492023-01-02T18:52:25Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Dávila, José Carlos
Olmos, Luis
Legaz, Isabel
Medina Hernández, Loreta Mª
Guirado, Salvador
Real, M. Ángeles
2017-01-20T09:20:26Z
2008
https://doi.org/10.1016/j.jchemneu.2007.06.003
011380
0891-0618
http://hdl.handle.net/10459.1/59049
Calbindin cells represent a major interneuron subtype of the cortical/pallial regions, such as the basolateral amygdala, which are often analyzed
in studies of tangential migration of interneurons from the subpallial ganglionic eminences to the pallium/cortex. However, previous evidence
suggests that during development the calbindin cells may include more than one of the interneuron subtypes found in the adult pallium/cortex.
Furthermore, in the adult basolateral amygdala, calbindin cells include a subpopulation of non-GABAergic (non-interneuron) cells. To better
characterize these cells throughout development, in the present study we investigated the colocalization of calbindin, parvalbumin and GABA in
cells of the mouse basolateral amygdala during late embryonic (E16.5) and several postnatal ages from birth until 4 weeks after birth (P0, P10 and
P28). Our results indicate that CB, PV and GABA show a dynamic pattern of colocalization in cells of the mouse basolateral amygdalar nucleus
throughout development. From E16.5 through P28, the majority of CB+ neurons and virtually all PV+ neurons are GABAergic. However, after
P10, the percentage of GABAergic CB+ cells decline from 96% to 70%. Furthermore, while only 9% of CB+ neurons are PV+ at P10, this
percentage raises to 42% at P28. At all postnatal ages studied, the majority of the PV+ cells are CB+, suggesting that PV+ interneurons develop
postnatally mainly as a subpopulation within the CB+ cells of the basolateral amygdalar nucleus. These results are important for interpreting data
from interneuron migration.
eng
info:eu-repo/semantics/restrictedAccess
(c) Elsevier B.V., 2007
Interneurons
Calcium binding proteins
Pallial amygdala
Neuroanatomy
Immunohistochemistry
Dynamic patterns of colocalization of calbindin, parvalbumin and GABA in subpopulations of mouse basolateral amygdalar cells during development
article
oai:repositori.udl.cat:10459.1/658062022-02-01T09:47:29Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Rando, Amaya
Torre, Miriam de la
Martinez-Muriana, Anna
Zaragoza, Pilar
Musaro, Antonio
Hernández i Estanyol, Sara
Navarro, Xavier
Toivonen, Janne M.
Osta, Rosario
2019-02-27T10:33:21Z
2019-02-27T10:33:21Z
2019
https://doi.org/10.1371/journal.pone.0210752
028238
1932-6203
http://hdl.handle.net/10459.1/65806
Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Rando A. et al., 2019
Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/626032018-12-21T12:14:55Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Jové Font, Mariona
Pradas Barriga, Irene
Naudí i Farré, Alba
Rovira-Llopis, Susana
Bañuls, Celia
Rocha, Milagros
Portero Otín, Manuel
Hernández-Mijares, Antonio
Victor, Victor M.
Pamplona Gras, Reinald
2018-02-01T12:00:40Z
2018-02-01T12:00:40Z
2017
https://doi.org/10.18632/oncotarget.23393
027604
1949-2553
http://hdl.handle.net/10459.1/62603
Purpose: In this work, a non-targeted approach was used to unravel changes in the plasma lipidome of PCOS patients. The aim is to offer new insights in PCOS patients strictly selected in order to avoid confounding factors such as dyslipemia, obesity, altered glucose/insulin metabolism, cardiovascular disease, or cancer.
Results: Multivariate statistics revealed a specific lipidomic signature for PCOS patients without associated pathologies. This signature implies changes, mainly by down-regulation, in glycerolipid, glycerophospholipid and sphingolipid metabolism suggesting an altered biosynthetic pathway of glycerophospholipids and cell signaling as second messengers in women with PCOS.
Conclusions: Our study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls.
Methods: In a cross-sectional pilot study, data were obtained from 34 subjects, allocated to one of two groups: a) lean, healthy controls (n = 20), b) PCOS patients (n = 14) with diagnosis based on hyperandrogenaemia, oligo-anovulation and abnormal ovaries with small follicular cysts. A detailed biochemical characterization was made and lipidomic profiling was performed via an untargeted approach using LC-ESI-QTOF MS/MS.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Jové et al., 2017
Cell signaling molecules
Glycerophospholipids
Free fatty acids
Lipidomics
Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome
article
oai:repositori.udl.cat:10459.1/4634372023-06-03T03:00:41Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Planas Serra, Laura
Launay, Nathalie
Goicoechea, Leire
Heron, Bénédicte
Jou, Cristina
Juliá Palacios, Natalia
Ruiz, Montserrat
Fourcade, Stéphane
Casasnovas, Carlos
de la Torre Gómez, Carolina
Gelot, Antoinette
Marsal, Maria
Loza-Alvarez, Pablo
García-Cazorla, Àngels
Fatemi, Ali
Ferrer, Isidre
Portero Otín, Manuel
Area-Gómez, Estela
Pujol, Aurora
2023-06-02T09:12:06Z
2023-06-02T09:12:06Z
2023
https://doi.org/10.1172/JCI162957
0021-9738
1558-8238
https://repositori.udl.cat/handle/10459.1/463437
Sphingolipids function as membrane constituents and signaling molecules, with crucial roles in human diseases, from neurodevelopmental disorders to cancer, best exemplified in the inborn errors of sphingolipid metabolism in lysosomes. The dihydroceramide desaturase Δ4-dihydroceramide desaturase 1 (DEGS1) acts in the last step of a sector of the sphingolipid pathway, de novo ceramide biosynthesis. Defects in DEGS1 cause the recently described hypomyelinating leukodystrophy-18 (HLD18) (OMIM #618404). Here, we reveal that DEGS1 is a mitochondria-associated endoplasmic reticulum membrane-resident (MAM-resident) enzyme, refining previous reports locating DEGS1 at the endoplasmic reticulum only. Using patient fibroblasts, multiomics, and enzymatic assays, we show that DEGS1 deficiency disrupts the main core functions of the MAM: (a) mitochondrial dynamics, with a hyperfused mitochondrial network associated with decreased activation of dynamin-related protein 1; (b) cholesterol metabolism, with impaired sterol O-acyltransferase activity and decreased cholesteryl esters; (c) phospholipid metabolism, with increased phosphatidic acid and phosphatidylserine and decreased phosphatidylethanolamine; and (d) biogenesis of lipid droplets, with increased size and numbers. Moreover, we detected increased mitochondrial superoxide species production in fibroblasts and mitochondrial respiration impairment in patient muscle biopsy tissues. Our findings shed light on the pathophysiology of HLD18 and broaden our understanding of the role of sphingolipid metabolism in MAM function.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by ©Authors, 2023
Attribution 4.0 International
Bioenergetics
Demyelinating disorders
Lipid rafts
Metabolism
Neuroscience
Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/852372023-04-14T03:00:53Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_44504
Castillo Izquierdo, Ángela del
Moreno Navarrete, José María
Latorre, Jèssica
Arnoriaga Rodríguez, María
Ballanti, Marta
Monteleone, Giovanni
Paoluzi, Alessandro Omero
Mingrone, Geltrude
Puig, Josep
Ramos, Rafael
Garre Olmo, Josep
Jové Font, Mariona
Pamplona Gras, Reinald
Portero Otín, Manuel
Sol, Joaquim
Lefevre, Philippe
Staels, Bart
Federici, Massimo
Fernández Real, José Manuel
Mayneris Perxachs, Jordi
2023-01-13T09:04:29Z
2023-01-13T09:04:29Z
2022
https://doi.org/10.3390/antiox11112177
033109
033109
2076-3921
http://hdl.handle.net/10459.1/85237
Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family. Inhibition of DPP9 has recently been shown to activate the nucleotide-binding domain leucine-rich repeat 1 (NLRP1) inflammasome. NLRP1 is known to bind nucleic acids with high affinity and directly interact with double stranded RNA, which plays a key role in viral replication. DPP9 has also recently emerged as a key gene related to lung-inflammation in critical SARS-CoV-2 infection. Importantly, DPP9 activity is strongly dependent on the oxidative status. Here, we explored the potential role of DPP9 in the gastrointestinal tract. We performed transcriptomics analyses of colon (microarray, n = 37) and jejunal (RNA sequencing, n = 31) biopsies from two independent cohorts as well as plasma metabolomics analyses in two independent cohorts (n = 37 and n = 795). The expression of DPP9 in the jejunum, colon, and blood was significantly associated with circulating biomarkers of oxidative stress (uric acid, bilirubin). It was also associated positively with the expression of transcription factors (NRF-2) and genes (SOD, CAT, GPX) encoding for antioxidant enzymes, but negatively with that of genes (XDH, NOX) and transcription factors (NF-KB) involved in ROS-generating enzymes. Gene co-expression patterns associated with DPP9 identified several genes participating in antiviral pathways in both tissues. Notably, DPP9 expression in the colon and plasma was strongly positively associated with several circulating nucleotide catabolites (hypoxanthine, uric acid, 3-ureidopropionic acid) with important roles in the generation of ROS and viral infection, as well as other metabolites related to oxidative stress (Resolvin D1, glutamate-containing dipeptides). Gene-drug enrichment analyses identified artenimol, puromycin, anisomycin, 3-phenyllactic acid, and linezolid as the most promising drugs targeting these DPP9-associated genes. We have identified a novel potential pathogenic mechanism of viral infection in the digestive tract and promising existing drugs that can be repositioned against viral infection.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Ángela del Castillo Izquierdo et al., 2022
Viral infection
Gastrointestinal tract
Transcriptomics
Metabolomics
SARS-CoV-2
DPP9 as a Potential Novel Mediator in Gastrointestinal Virus Infection
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/705562023-09-26T09:28:30Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Salvany, Sara
Casanovas i Llorens, Anna
Piedrafita Llorens, Lídia
Tarabal Mostazo, Olga
Hernández i Estanyol, Sara
Calderó i Pardo, Jordi
Esquerda Colell, Josep
2021-02-19T09:24:06Z
2021-02-19T09:24:06Z
2021-01-02
https://doi.org/10.1002/glia.23959
030677
0894-1491
http://hdl.handle.net/10459.1/70556
Peripheral nerve section with subsequent disconnection of motor neuron (MN) cell bodies from their skeletal muscle targets leads to a rapid reactive response involving the recruitment and activation of microglia. In addition, the loss of afferent synapses on MNs occurs in concomitance with microglial reaction by a process described as synaptic stripping. However, the way in which postaxotomy‐activated microglia adjacent to MNs are involved in synaptic removal is less defined. Here, we used confocal and electron microscopy to examine interactions between recruited microglial cells and presynaptic terminals in axotomized MNs between 1 and 15 days after sciatic nerve transection in mice. We did not observe any bulk engulfment of synaptic boutons by microglia. Instead, microglial cells internalized small membranous‐vesicular fragments which originated from the acute disruption of synaptic terminals involving the activation of the necroptotic pathway. The presence of abundant extracellular vesicles in the perineuronal space after axotomy, together with the increased expression of phospho‐mixed lineage kinase domain‐like protein and, later, of extracellular vesicle markers, such as CD9, CD63, and flotillin, indicate that the vesicles mainly originated in synapses and were transferred to microglia. The upregulation of Rab7 and Rab10 in microglia interacting with injured MNs, indicated the activation of endocytosis. As activated microglia and synaptic boutons displayed positive C1q immunoreactivity, a complement‐mediated opsonization may also contribute to microglial‐mediated synaptic disruption. In addition to the relevance of our data in the context of neuroinflammation and MN disease, they should also be taken into account for understanding functional recovery after peripheral nerve injury.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Salvany et al., 2021
Afferent synapses
Extracellular vesicles
Exosomes
Microglia
Motor neuron
Nerve axotomy
Necroptosis
Microglial recruitment and mechanisms involved in the disruption of afferent synaptic terminals on spinal cord motor neurons after acute peripheral nerve injury
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/715792021-07-10T00:11:58Zcom_10459.1_237com_10459.1_2com_10459.1_241col_10459.1_354col_10459.1_30324
Ensenyat Solé, Assumpta
Espigares Tribó, Gemma
Machado, Leonardo
Verdejo Amengual, Francisco José
Rodríguez Arregui, Rosa
Serrano Casasola, José Carlos Enrique
Miret, Marta
Galindo Ortego, Gisela
Blanco Nespereira, Alfonso
Marsal Mora, Josep Ramon
Sarriegui, Susana
Sinfreu Bergués, Xènia
Serra Payà, Noemí
2021-07-09T12:54:08Z
2021-07-09T12:54:08Z
2017
https://doi.org/10.1186/s12889-017-4144-8
025579
1471-2458
http://hdl.handle.net/10459.1/71579
Background: The primary aim of this study is to evaluate the effectiveness of different doses (intensity) of supervised
exercise training — concomitant with lifestyle counselling — as a primary care intervention tool for the management
of metabolic syndrome risk factors in low-active adults with one or more such factors (programme name in Catalan:
Bellugat de CAP a peus).
Methods/Design: Three-arm, randomized controlled clinical trial implemented in the primary care setting, with a
duration of 40 weeks (16 weeks intervention and 24-week follow-up).
Adults aged 30 to 55 years with metabolic risk factors will be randomized into three intervention groups: 1) aerobic
interval training (16 supervised training lessons) plus a healthy lifestyle counselling programme (6 group and 3 individual
meetings); 2) low-to-moderate intensity continuous training (16 supervised training lessons) plus the same counselling
programme; or 3) the counselling- programme without any supervised physical exercise.
The main output variables assessed will be risk factors for metabolic syndrome (waist circumference, blood pressure, and
levels of plasma triglycerides, high-density lipoproteins and glucose), systemic inflammation, cardiorespiratory
fitness, physical activity and sedentary behaviour, dietary habits, health-related quality of life, self-efficacy and
empowerment. Economic factors will also be analysed in order to determine the cost-effectiveness of the programme.
These variables will be assessed three times during the study: at baseline, at the end of the intervention, and at followup.
We estimate to recruit 35 participants per group.
Discussion: The results of this study will provide insight into the immediate and medium-term effects on metabolic risk
and lifestyle of a combined approach involving aerobic interval training and a multidisciplinary behavioural intervention.
If effective, the proposed intervention would provide both researchers and practitioners in this field with a platform on
which to develop similar intervention programmes for tackling the repercussions of an unhealthy lifestyle.
Trial registration: Clinical trials.gov. NTC02832453. Registered 6 July 2016 (retrospectively registered).
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
cc-by (c) Ensenyat et al., 2017
Metabolic risk management
Physical exercise
Metabolic risk management, physical exercise and lifestyle counselling in low-active adults: controlled randomized trial (BELLUGAT)
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/415492020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2com_10459.1_59360com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59361col_10459.1_59998col_10459.1_30324
Jové Font, Mariona
Serrano Casasola, José Carlos Enrique
Bellmunt i Curcó, Josepa
Cassanyé, Anna
Anglès, Neus
Reguant, Jordi
Morelló, José R.
Pamplona Gras, Reinald
Portero Otín, Manuel
2011-07-19T10:19:25Z
2011-07-19T10:19:25Z
2010
https://doi.org/10.1186/1476-511X-9-65
015648
1476-511X
http://hdl.handle.net/10459.1/41549
Background: Experimental evidences demonstrate that vegetable derived extracts inhibit cholesterol absorption in the gastrointestinal tract. To further explore the mechanisms behind, we modeled duodenal contents with several vegetable extracts.
Results: By employing a widely used cholesterol quantification method based on a cholesterol oxidase-peroxidase coupled reaction we analyzed the effects on cholesterol partition. Evidenced interferences were analyzed by studying specific and unspecific inhibitors of cholesterol oxidase-peroxidase coupled reaction. Cholesterol was also quantified by LC/MS. We found a significant interference of diverse (cocoa and tea-derived) extracts over this method. The interference was strongly dependent on model matrix: while as in phosphate buffered saline, the development of unspecific fluorescence was inhibitable by catalase (but not by heat denaturation), suggesting vegetable extract derived H2O2 production, in bile-containing model systems, this interference also comprised cholesterol-oxidase inhibition. Several strategies, such as cholesterol standard addition and use of suitable blanks containing vegetable extracts were tested. When those failed, the use of a mass-spectrometry based chromatographic assay allowed quantification of cholesterol in models of duodenal contents in the presence of vegetable extracts.
Conclusions: We propose that the use of cholesterol-oxidase and/or peroxidase based systems for cholesterol analyses in foodstuffs should be accurately monitored, as important interferences in all the components of the enzymatic chain were evident. The use of adequate controls, standard addition and finally, chromatographic analyses solve these issues.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.0/es/deed.ca
cc-by, (c) Jové et al., 2010
When cholesterol is not cholesterol: a note on the enzymatic determination of its concentration in model systems containing vegetable extracts
article
oai:repositori.udl.cat:10459.1/663612020-06-02T09:45:51Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
Visa Pretel, Anna
Shaikh, Soni
Alza, Lía
Herreros Danés, Judit
Cantí Nicolás, Carles
2019-05-16T10:05:21Z
2020-04-25T22:09:31Z
2019
https://doi.org/10.1016/j.molmed.2019.03.001
028440
1471-4914
http://hdl.handle.net/10459.1/66361
T-Type calcium channels (TTCCs) are key regulators of membrane excitability, which is the reason why TTCC pharmacology is subject to intensive research in the neurological and cardiovascular fields. TTCCs also play a role in cancer physiology, and pharmacological blockers such as tetralols and dihydroquinazolines (DHQs) reduce the viability of cancer cells in vitro and slow tumor growth in murine xenografts. However, the available compounds are better suited to blocking TTCCs in excitable membranes rather than TTCCs contributing window currents at steady potentials. Consistently, tetralols and dihydroquinazolines exhibit cytostatic/cytotoxic activities at higher concentrations than those required for TTCC blockade, which may involve off-target effects. Gene silencing experiments highlight the targetability of TTCCs, but further pharmacological research is required for TTCC blockade to become a chemotherapeutic option.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Elsevier, 2019
The hard-to-close window of T-type calcium channels
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/709322023-03-06T14:36:35Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Hernández-Alvarez, María Isabel
Sebastián, David
Vives, Sara
Ivanova, Sa ka
Bartoccioni, Paola
Kakimoto, Pamela
Plana, Natalia
Veiga, Sónia R.
Hernández, Vanessa
Vasconcelos, Nuno
Gopalacharyulu, Peddinti
Adrover, Anna
Jové Font, Mariona
Pamplona Gras, Reinald
Berenguer-Llergo, Antonio
Gordaliza, Isabel
Calvo, Enrique
Cabré, Noemí
Castro, Rui
Kuzmanic, Antonija
Boutant, Marie
Sala, David
Hyotylainen, Tuulia
Oresic, Matej
Fort, Joana
Errasti-Murugarren, Ekaitz
Orozco, Modesto
Joven, Jorge
Cantó, Carles
Palacin, Manuel
Fernández-Veledo, Sonia
Vendrell, Joan
Zorzano, Antonio
2021-04-07T08:44:04Z
2021-04-07T08:44:04Z
2019-05-02
https://doi.org/10.1016/j.cell.2019.04.010
029375
0092-8674
http://hdl.handle.net/10459.1/70932
Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
eng
info:eu-repo/semantics/openAccess
(c) Elsevier, 2019
Mfn2
NASH
Phosphatidylserine
MAMs
Mitochondria
Phospholipid transfer
Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/4646092024-01-23T14:26:04Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Sisó, Pol
de la Rosa, Inés
Ríos, Christopher
Panosa, Anais
Verdaguer Autonell, Joan
Martí Laborda, Rosa Ma.
Macià Armengol, Anna
2023-11-28T07:58:56Z
2023-11-28T07:58:56Z
2023-12-15
https://doi.org/10.1016/j.xpro.2023.102690
033738
2666-1667
https://repositori.udl.cat/handle/10459.1/464609
Here, we present a protocol to study and describe immune cells that surround or infiltrate tumor cells or get through the body of a melanoma syngeneic mice model. We describe steps for creating and establishing the syngeneic mouse model, euthanasia, and tumor or organ harvest. We then detail procedures to rapidly achieve a single-cell suspension from different tissue samples to further quantify and analyze the phenotype of the immune cell population (lymphocytes T and B, tumor-associated macrophages, and myeloid-derived suppressor cells) by flow cytometry.
eng
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) 2023 The Authors
Cancer
Cell Isolation
Flow Cytometry
Single Cell
Immunology
Protocol to characterize the melanoma tumor immune microenvironment in mice from single cell to flow cytometry analysis
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/585172021-08-30T15:04:29Zcom_10459.1_59360com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_49291col_10459.1_44504
Jové Font, Mariona
Ayala Jové, Ma. Victoria (Maria Victoria)
Ramírez-Núñez, Omar
Serrano Casasola, José Carlos Enrique
Cassanyé, Anna
Arola i Ferrer, Lluís
Caimari, Antoni
Bas, Josep M. del
Crescenti, Anna
Pamplona Gras, Reinald
Portero Otín, Manuel
2016-11-16T08:20:03Z
2013
https://doi.org/10.1093/cvr/cvs368
020172
0008-6363
http://hdl.handle.net/10459.1/58517
Aims Atherosclerosis is the main pathological process contributing to cardiovascular disease, with diet being the most important factor involved. Although the lipidome of atheromatous plaque has been studied previously, the use of comparative lipidomics and metabolomics in plasma in early atherogenesis could lead to the discovery of plasma biomarkers that allow not only disease prediction but also measurement of disease progression.
eng
info:eu-repo/semantics/restrictedAccess
(c) Oxford Journals, 2012
Sphingolipids
Free cholesterol
Taurocholic acid
Cell senescence
Phospholipid oxidation
Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters
article
oai:repositori.udl.cat:10459.1/623092022-11-25T20:34:50Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324col_10459.1_49291
Desfilis, Ester
Abellán Ródenas, Antonio
Sentandreu, Vicente
Medina Hernández, Loreta Mª
2018-01-09T09:34:28Z
2018-01-09T09:34:28Z
2017
https://doi.org/10.1002/cne.24329
025894
0021-9967
http://hdl.handle.net/10459.1/62309
The comparison of gene expression patterns in the embryonic brain of mouse and chicken is being essential for understanding pallial organization. However, the scarcity of gene expression data in reptiles, crucial for understanding evolution, makes it difficult to identify homologues of pallial divisions in different amniotes. We cloned and analyzed the expression of the genes Emx1, Lhx2, Lhx9, and Tbr1 in the embryonic telencephalon of the lacertid lizard Psammodromus algirus. The comparative expression patterns of these genes, critical for pallial development, are better understood when using a recently proposed six-part model of pallial divisions. The lizard medial pallium, expressing all genes, includes the medial and dorsomedial cortices, and the majority of the dorsal cortex, except the region of the lateral cortical superposition. The latter is rich in Lhx9 expression, being excluded as a candidate of dorsal or lateral pallia, and may belong to a distinct dorsolateral pallium, which extends from rostral to caudal levels. Thus, the neocortex homolog cannot be found in the classical reptilian dorsal cortex, but perhaps in a small Emx1-expressing/Lhx9-negative area at the front of the telencephalon, resembling the avian hyperpallium. The ventral pallium, expressing Lhx9, but not Emx1, gives rise to the dorsal ventricular ridge and appears comparable to the avian nidopallium. We also identified a distinct ventrocaudal pallial sector comparable to the avian arcopallium and to part of the mammalian pallial amygdala. These data open new venues for understanding the organization and evolution of the pallium.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
cc-by-nc-nd (c) Desfilis et al., 2017
Forebrain evolution
Reptile
Developmental regulatory genes
Transcription factors
Expression of regulatory genes in the embryonic brain of a lizard and implications for understanding pallial organization and evolution
article
oai:repositori.udl.cat:10459.1/4649522024-02-02T03:00:41Zcom_10459.1_47453com_10459.1_2com_10459.1_241col_10459.1_59998col_10459.1_30324
Morales García, Lorena
Castro Robles, Beatriz
Abellán Ródenas, Antonio
Desfilis, Ester
Medina Hernández, Loreta Mª
2024-02-01T12:01:15Z
2024-02-01T12:01:15Z
2021-01-13
https://doi.org/10.1002/cne.25103
030839
0021-9967
https://repositori.udl.cat/handle/10459.1/464952
Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp‐eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a distinct telencephalon‐opto‐hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp‐lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic‐like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.
eng
info:eu-repo/semantics/openAccess
(c) Wiley Periodicals 2021
Forebrain development
Hypothalamus
Telencephalon
Glutamate
GABA
Social behavior
Neurodevelopmental disorders
A novel telencephalon‐opto‐hypothalamic morphogenetic domain coexpressing Foxg1 and Otp produces most of the glutamatergic neurons of the medial extended amygdala
info:eu-repo/semantics/article
oai:repositori.udl.cat:10459.1/463702022-10-27T10:05:59Zcom_10459.1_59328com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_59329col_10459.1_59998col_10459.1_30324col_10459.1_49291
Ribas i Fortuny, Judit
Ni, Xiaohua
Castanares, Mark
Liu, Minzhi M.
Esopi, David
Yegnasubramanian, Srinivasan
Rodriguez, Ronald
Mendell, Joshua T.
Lupold, Shawn E.
2012-12-11T11:22:06Z
2012-12-11T11:22:06Z
2012
https://doi.org/10.1093/nar/gks308
017838
0305-1048
http://hdl.handle.net/10459.1/46370
miR-21 is the most commonly over-expressed microRNA (miRNA) in cancer and a proven oncogene. Hsa-miR-21 is located on chromosome 17q23.2, immediately downstream of the vacuole membrane protein-1 (VMP1) gene, also known as TMEM49. VMP1 transcripts initiate ∼130 kb upstream of miR-21, are spliced, and polyadenylated only a few hundred base pairs upstream of the miR-21 hairpin. On the other hand, primary miR-21 transcripts (pri-miR-21) originate within the last introns of VMP1, but bypass VMP1 polyadenylation signals to include the miR-21 hairpin. Here, we report that VMP1 transcripts can also bypass these polyadenylation signals to include miR-21, thus providing a novel and independently regulated source of miR-21, termed VMP1–miR-21. Northern blotting, gene-specific RT-PCR, RNA pull-down and DNA branching assays support that VMP1–miR-21 is expressed at significant levels in a number of cancer cell lines and that it is processed by the Microprocessor complex to produce mature miR-21. VMP1 and pri-miR-21 are induced by common stimuli, such as phorbol-12-myristate-13-acetate (PMA) and androgens, but show differential responses to some stimuli such as epigenetic modifying agents. Collectively, these results indicate that miR-21 is a unique miRNA capable of being regulated by alternative polyadenylation and two independent gene promoters.
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/3.0/es/deed.ca
cc-by-nc, (c) Ribas et al., 2012
miR-21
A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts
article
mods///col_10459.1_30324/100