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showing 10 items of 22846 documents
The JAK2 pathway is activated in idiopathic pulmonary fibrosis
2018
Background: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. Methods and results: JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative …
KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.
2017
Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude…
Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.
2016
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…
SOX2 expression diminishes with ageing in several tissues in mice and humans.
2017
SOX2 (Sex-determining region Y box 2) is a transcription factor expressed in several foetal and adult tissues and its deregulated activity has been linked to chronic diseases associated with ageing. Nevertheless, the level of SOX2 expression in aged individuals at the tissue level has not previously been examined. In this work, we show that SOX2 expression decreases significantly in the brain with ageing, in both humans and rodents. The administration of resveratrol for 6 months in mice partly attenuated this reduction. We also identified an age-related decline in SOX2 mRNA and protein expression in several other organs, namely, the lung, heart, kidney, spleen and liver. Moreover, periphera…
Analysis of cold activation of the contact system in hereditary angioedema with normal C1 inhibitor.
2021
Hereditary angioedema (HAE) attacks are caused by excessive activation of the contact system. Understanding how the contact system is activated in HAE, especially in patients with normal C1 inhibitor (HAEnCI), is essential to effectively treat this disease. Contact system activation involves the cleavage of several proteins including Factor XII (FXII), high molecular weight kininogen (HK), prekallikrein, sgp120 (ITIH4) and C1 inhibitor (C1-INH) before the subsequent generation of bradykinin that mediates HAE. In this study, we evaluated the fragmentation and enzymatic activity of contact system proteins in HAEnCI plasma samples before and after contact system activation induced by incubatio…
Gene-environment interactions between education and body mass: Evidence from the UK and Finland
2017
More education is associated with a lower body mass index (BMI) and likelihood of being overweight. However, since a large proportion of the variation in body mass is due to genetic makeup, it has been hypothesized that education may moderate the genetic risk. We estimate main associations between (i) education, (ii) genetic risk, and (iii) interactions between education and genetic risk on BMI and the probability of being overweight in the UK and Finland. The estimates show that education is negatively associated with BMI and overweightness, and genetic risk is positively associated. However, the interactions between education and genetic risk are small and statistically insignificant. pee…
Malignant PEComa With Metastatic Disease at Diagnosis and Resistance to Several Chemotherapy Regimens and Targeted Therapy (m-TOR Inhibitor).
2017
Perivascular epithelioid cell tumors (PEComas) are infrequent neoplasms with peculiar myomelanocytic differentiation. The aggressive abdominopelvic variant is rare, with only a small number of published cases. We present an additional case of this unusual variant, which showed an aggressive histologic and clinical behavior with multiple liver metastases and resistance to several therapies. We also discuss the histological and immunohistochemical profiles as well as the differential diagnosis.
Safety of Novel Amino-5-laevulinate Photosensitizer Precursors in Photodynamic Therapy for Healthy Human Skin.
2015
Peer reviewed
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
2020
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…
Use of Medaka Fish as Vertebrate Model to Study the Effect of Cocoa Polyphenols in the Resistance to Oxidative Stress and Life Span Extension.
2018
Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of …