Articles publicats (Ciències Mèdiques Bàsiques)

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    Open Access
    Automatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum
    (Elsevier, 2018) Pereira, Tania; Muguruza, José; Virtu, Maria; Vilaprinyo Terré, Ester; Sorribas Tello, Albert; Fernández i Giráldez, Elvira; Fernández Armenteros, José Manuel; Baena-Fustegueras, Juan A; Rius, Ferran; Betriu i Bars, M. Àngels; Solsona Tehàs, Francesc; Alves, Rui
    Adventitial vasa vasorum are physiologic microvessels that nourish artery walls. In the presence of cardiovascular risk factors, these microvessels proliferate abnormally. Studies have reported that they are the first stage of atheromatous disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct, quantitative and non-invasive visualization of the adventitial vasa vasorum. Hence, the development of computer-assisted methods that speed image analysis and eliminate user subjectivity is important. We developed methods for automatic analyses and quantification of vasa vasorum neovascularization in CEUS and tested these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers. We implemented alternative automatic strategies for using the images to stratify patients according to their risk group and compare the strategies with respect to diagnostic performance. An automatic single-parameter strategy performs less effectively than the corresponding Arcidiacono method based on manual interpretation of the images (68 < area under the receiver operating characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC for the automatic single-parameter strategy < 63). However, by use of additional image parameters, an automatic multiparameter strategy has significantly improved performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The automatic multiparameter strategy is a valuable alternative to the manual Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.
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    Open Access
    Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach
    (Springer Nature, 2024-02-12) Bayona, Clara; Alza, Lía; Ranđelović, Teodora; Sallán, Marta C.; Visa Pretel, Anna; Cantí Nicolás, Carles; Ochoa, Ignacio; Oliván, Sara; Herreros Danés, Judit
    Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM.
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    Open Access
    Polygenic risk score comparator (PRScomp): Test population vs. worldwide populations
    (2024) Laplana Lafaja, Marina; López Ortega, Ricard; Fibla Palazón, Joan
    Background: Polygenic risk scores (PRS) are a powerful tool for predicting an individual's genetic risk for complex diseases. Methods: We have developed a web service (PRScomp) as a user-friendly tool to evaluate PRS of the user own population and compare it with worldwide populations. Results: A disease/trait database has been constructed from GWAS Catalog summary statistics. Genotype data of test population is uploaded and merged with the reference dataset (1000 Genome Project and Human Genome Diversity Project) to obtain a file including the common SNPs. The user can select a disease/trait from the database and a curated set of risk markers is used to calculate summatory PRS. Distribution of z-scored PRS values is presented in publication-ready plots and text files that can be downloaded. Discussion: PRScomp can be useful for public health decision-making by identifying population-specific genetic risk factors and informing the development of targeted interventions for at-risk populations.
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    Open Access
    Results of a Community-Based Screening Program for Chlamydia trachomatis Genital Infection in Young People Aged 18-25 Years
    (Springer, 2023) Espies, Noemi; Fernandez , Joan; Justribó Sánchez, Elena ; Aramburu, Jesus; Bernet, Albert; Marquez, Alicia; Godoy i García, Pere; Yuguero Torres, Oriol
    Introduction and aim Chlamydia trachomatis (CT) cases have increased in the last decade. The aim of the study was to assess the prevalence of CT genital infection in asymptomatic, sexually active young people and determine whether a community screening program would be effective in reducing the number of cases. Methods A descriptive cross-sectional studyof consecutive inclusion of asymptomatic people aged 18-25 years between September 2021 and May 2022. Community interventions in high schools, universities, and cultural events were planned to realize the screening. Sociodemographic variables of gender, age, country of origin, and educational level, as well as sexual habits, were recorded for each patient. CT was detected via urine samples. An estimate of the prevalence of CT genital infection and its 95% confidence interval (CI) was made based on the exact binomial distribution, assuming that the sample is representative of the study population. Results A total of 628 subjects participated in the study, of whom 33 had a CT infection, giving a prevalence of 5.2% (95% CI: 3.6%, 7.3%). 93.9% of subjects with CT infection were female (p≤0.019) and 85% of the participants were Spanish nationals. Among vocational training students, the prevalence was 8.1%. Having had four or more sexual partners in the last month and in the previous year was significantly associated with CT infection (p<0.001). Conclusion Screening for CT genital infection in young sexually active women should be implemented in our country, as recommended by the various guidelines.
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    Open Access
    Metformin exhibits antineoplastic effects on Pten-deficient endometrial cancer by interfering with TGF-β and p38/ERK MAPK signalling
    (Elsevier, 2023) Ruiz Mitjana, Anna; Vidal Sabanés, Maria; Navaridas Fernández de Bobadilla, Raúl; Perramon Güell, Aida; Yeramian Hakim, Andree; Nicholson Sabaté, Nathan; Egea Navarro, Joaquim; Encinas Martín, Mario; Matias-Guiu, Xavier; Dolcet Roca, Xavier
    Metformin is a widespread antidiabetic agent that is commonly used as a treatment against type 2 diabetes mellitus patients. Regarding its therapeutic potential, multiple studies have concluded that Metformin exhibits antineoplastic activity on several types of cancer, including endometrial carcinoma. Although Metformin’s antineoplastic activity is well documented, its cellular and molecular anticancer mechanisms are still a matter of controversy because a plethora of anticancer mechanisms have been proposed for different cancer cell types. In this study, we addressed the cellular and molecular mechanisms of Metformin’s antineoplastic activity by using both in vitro and in vivo studies of Pten-loss driven carcinoma mouse models. In vivo, Metformin reduced endometrial neoplasia initiated by Pten-deficiency. Our in vitro studies using Pten-deficient endometrial organoids focused on both cellular and molecular levels in Metformin’s tumor suppressive action. At cellular level, we showed that Metformin is involved in not only the proliferation of endometrial epithelial cells but also their regulation via a variety of mechanisms of epithelial-to-mesenchymal transition (EMT) as well as TGF-β-induced apoptosis. At the molecular level, Metformin was shown to affect the TGF-β signalling., a widely known signal that plays a pivotal role in endometrial carcinogenesis. In this respect, Metformin restored TGF-β-induced apoptosis of Pten-deficient endometrial organoids through a p38-dependent mechanism and inhibited TGF-β-induced EMT on no-polarized endometrial epithelial cells by inhibiting ERK/MAPK signalling. These results provide new insights into the link between the cellular and molecular mechanism for Metformin’s antineoplastic activity in Pten-deficient endometrial cancers.