355 results match your criteria: "Pfizer-University of Granada-Andalusian Regional Government[Affiliation]"

Pancreatic cancer is a highly lethal and metastatic malignancy, mainly because it often remains undetected until advanced stages due to the limitations of current diagnostic methods, rendering currently available therapies ineffective. Therefore, it is imperative to identify useful biomarkers for early diagnosis and new therapeutic targets for pancreatic cancer. Recently, extracellular vesicles have emerged as promising biomarkers for the diagnosis and prognosis of pancreatic cancer.

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  • Two natural -kaurene diterpenoids were extracted from a plant, and six new derivatives were synthesized for evaluation of their anti-tumor properties against three types of cancer cells (colon, liver, and melanoma).
  • One synthesized compound showed the strongest anti-proliferative effects across all cell lines, with a notable IC value of around 2.5 μM, and further studies indicated that some derivatives induced a selective G2/M cell cycle arrest.
  • Apoptosis analysis revealed that certain compounds led to high levels of cell death (up to 99% apoptosis), linked to mitochondrial dysfunction and the activation of the intrinsic apoptotic pathway, suggesting their potential as effective anticancer agents.
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Oxidation-sensitive cysteines drive IL-38 amyloid formation.

Cell Rep

November 2024

Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, Geneva, Switzerland.

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 family member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs).

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  • Systemic sclerosis (SSc) is a complicated disease with various manifestations, making it hard to manage, but autoantibodies may help identify different patient groups and their underlying mechanisms.
  • A study of 206 SSc patients used antibody status (ACA and SCL70) and various biological analyses to explore differences between groups.
  • Results showed that SCL70-positive patients had more severe symptoms and unique biological profiles, while ACA-positive patients had a different set of immune and metabolic features, highlighting the importance of serological status in understanding and treating the disease.
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Exploring the role of genetic variability and exposure to bisphenols and parabens on excess body weight in Spanish children.

Ecotoxicol Environ Saf

November 2024

Department of Nutrition and Food Science, Faculty of Pharmacy, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Institute of Nutrition and Food Technology "Jose Mataix Verdú," Biomedical Research Center, University of Granada, Granada, Spain.

Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3-12 years.

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  • - The study analyzed 64 patients with small cell lung cancer (SCLC) to assess the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers using immunohistochemistry and digital pathology tools; DLL3 was found expressed in 72.3% of patients.
  • - The majority of patients were older adults (median age over 71), and notable findings included high expression rates of ASCL1 (97%) and a potential new role for TTF-1 as a biomarker, as it was positive in half of the cases.
  • - The research highlights the variability of neuroendocrine marker expression in SCLC, suggesting that DLL3 could be a therapeutic target, while the
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  • - The study investigates the influence of genetic variations, specifically single nucleotide polymorphisms (SNPs) in autophagy-related genes, on the risk of developing pancreatic ductal adenocarcinoma (PDAC) using data from over 12,000 cases and 324,000 controls. - It identifies a new association between the BID gene variant and increased PDAC risk, as well as confirms previous links between TP63 gene variants and PDAC, highlighting their roles in promoting cell growth and regulating T regulatory cell populations. - The findings suggest that genetic variations in BID and TP63 may contribute to PDAC susceptibility and indicate potential new pathways for understanding the mechanisms behind this lethal cancer.
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Background: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure.

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Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study.

Artif Intell Med

October 2024

Department of Computer Science and Artificial Intelligence, Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI), University of Granada, Granada, 18071, Spain. Electronic address:

Pediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated comorbidities.

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Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Crit Rev Oncol Hematol

November 2024

Department of Medicine, Weill Cornell Medicine, Englander Institute for Precision Medicine, New York Presbyterian Hospital, New York, NY 10021, USA.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required.

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Variants in the autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

bioRxiv

October 2023

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.

Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including .

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Principal Bioactive Properties of Oleanolic Acid, Its Derivatives, and Analogues.

Molecules

July 2024

Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain.

Natural products have always played an important role in pharmacotherapy, helping to control pathophysiological processes associated with human disease. Thus, natural products such as oleanolic acid (OA), a pentacyclic triterpene that has demonstrated important activities in several disease models, are in high demand. The relevant properties of this compound have motivated re-searchers to search for new analogues and derivatives using the OA as a scaffold to which new functional groups have been added or modifications have been realized.

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Objective: Guided Bone Regeneration (GBR) is a dental surgical procedure that uses barrier membranes to prevent soft tissue invasion and conduct new bone growth. This study aimed to define a Prognosis Recovery score (PR score) to objectively classify post-surgery responders from non-responder patients who underwent GBR using Cone Beam Computed Tomography (CBCT).

Methods: This prospective-observational-longitudinal-cohort study recruited 250 individuals who were assigned to: Conventional-Apical-Surgery (CAS, n = 39), Apical-Surgery using human fascia lata Membrane placement (ASM, n = 42), and Apical-Surgery using human fascia lata Membrane placement and lyophilized allograft Bone powder (ASMB, n = 39); and Apical-Surgery using collagen membrane Porcine origin and Bovine Bone-matrix (ASPBB, n = 130), an independent external validation cohort.

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The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood DNA methylation from 213 SLE patients and 221 controls.

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Periodontitis and peri-implantitis are inflammatory diseases of infectious etiology that lead to the destruction of the supporting tissues located around teeth or implants. Although both pathologies share several characteristics, it is also known that they show important differences which could be due to the release of particles and metal ions from the implant surface. The activation of the inflammasome pathway is one of the main triggers of the inflammatory process.

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DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Eur J Med Chem

October 2024

Departamento de Biología Molecular, Instituto de Parasitología y Biomedicina López Neyra, CSIC, PTS Granada, Avenida Del Conocimiento, 17, Armilla, 18016 Granada, Spain. Electronic address:

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease.

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Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Biomed Pharmacother

August 2024

Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, Granada 18016, Spain. Electronic address:

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds.

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Introduction: Chimeric antigen receptor-expressing T cells (CAR T cells) have revolutionized cancer treatment, particularly in B cell malignancies. However, the use of autologous T cells for CAR T therapy presents several limitations, including high costs, variable efficacy, and adverse effects linked to cell phenotype.

Methods: To overcome these challenges, we developed a strategy to generate universal and safe anti-CD19 CAR T cells with a defined memory phenotype.

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Oral β-RA induces metabolic rewiring leading to the rescue of diet-induced obesity.

Biochim Biophys Acta Mol Basis Dis

October 2024

Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016 Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain; Instituto de Investigación Biosanitaria Ibs. Granada, 18016 Granada, Spain; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), 18016 Granada, Spain. Electronic address:

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Alu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1) ORF2-encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition.

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Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples.

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Background: Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery and efficacy for a successful cancer treatment. However, surface functionalization involves complex procedures that increase costs and timelines, presenting challenges for clinical implementation. Biomimetic nanoparticles (BNPs) have emerged as unique drug delivery platforms that overcome the limitations of actively targeted nanoparticles.

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Classification of systemic lupus erythematosus: From the development of classification criteria to a new taxonomy?

Best Pract Res Clin Rheumatol

December 2023

GENYO. Centre for Genomics and Oncological Research, Pfizer / University of Granada / Andalusian Regional Government, Granada, Andalusia, Spain; Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

SLE is a highly variable systemic autoimmune disease. Its immunopathological effector phase is partly understood. However, the background of its variability is not.

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