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showing 10 items of 15327 documents
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
2018
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…
Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.
2020
Summary De novo germline mutations in the RNA helicase DDX3X account for 1%–3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n = 107), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcom…
Marathon Race Affects Neutrophil Surface Molecules: Role of Inflammatory Mediators
2016
The fatigue induced by marathon races was observed in terms of inflammatory and immunological outcomes. Neutrophil survival and activation are essential for inflammation resolution and contributes directly to the pathogenesis of many infectious and inflammatory conditions. The aim of this study was to investigate the effect of marathon races on surface molecules related to neutrophil adhesion and extrinsic apoptosis pathway and its association with inflammatory markers. We evaluated 23 trained male runners at the Sao Paulo International Marathon 2013. The following components were measured: hematological and inflammatory mediators, muscle damage markers, and neutrophil function. The maratho…
Oestrus ovis external ophtalmomyiasis : a case report in Burgundy France
2018
Background External ophtalmomyiasis (EOM) is a zoonosis related to the presence of Oestrus ovis larvae at the ocular level in small ruminants (i.e. ovine, caprine). In humans, EOM is a rare cosmopolitan disorder, mostly described in warm and dry rural areas in patients living close to livestock areas. In metropolitan France (excluding Corsica), EOM is an exceptional disease with less than 25 cases recorded since 1917. Case presentation We report a case of EOM in a 19-years old man in the last week of September 2016 in Burgundy. Conclusion The diagnosis of an EOM in Burgundy, a French region described as cold and humid, is surprising and could be due to a more marked climatic warming during …
PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability
2020
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 express…
Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study.
2016
The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16–88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, v…
Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium
2017
AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infe…
Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patient…
2017
Background The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). Methods Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic–phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc pat…
Early miR-223 Upregulation in Gastroesophageal Carcinogenesis
2017
Objectives: To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis. Methods: miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas. miR-223 expression was also assessed in plasma samples from 30 patients with early stage (ie, stages I and II) gastroesophageal adenocarcinoma and relative controls. Res…
Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers
2015
// Giorgio Mauri 1 , Elena Jachetti 1 , Barbara Comuzzi 1 , Matteo Dugo 2 , Ivano Arioli 1 , Silvia Miotti 1 , Sabina Sangaletti 1 , Emma Di Carlo 3, 4 , Claudio Tripodo 5 , Mario P. Colombo 1 1 Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 20133, Milano, Italy 2 Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 20133, Milano, Italy 3 Department of Medicine and Science of Aging, Section of Anatomic Pathology and Molecular Medicine, “G. d’Annunzio” University, 66100, Chieti, Italy 4 Ce.S.I. Aging Research Center, “G…