Search results for " 2"
showing 10 items of 10825 documents
Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men.
2016
Aims/hypothesis: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. Methods: Older Finnish men enriched with individuals having been athletes in y…
Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Tre…
2020
Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels o…
Insufficient generation of Th17 cells in IL-23p19-deficient BALB/c mice protects against progressive cutaneous leishmaniasis
2017
Healing of leishmaniasis-a parasitic skin disease-is associated with high levels of secreted interferon (IFN)γ and IL-12 in resistant C57BL/6 mice and humans. Susceptible BALB/c mice predominantly react with a Th17/Th2/Treg-related immune response and finally succumb to infection. Previously, we showed that BALB/c IL-17A-/- mice are protected against Leishmania (L.) major infections, indicating that IL-17A-predominantly produced by Th17 cells-plays an important role for disease outcome. We now investigated DC-derived cytokines and finally identified IL-23p19 as key cytokine responsible for induction of Leishmania-specific Th17 cells that play an important role for progressive disease in sus…
Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation
2016
IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha …
Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers
2016
A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the c…
Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses
2020
AbstractInterleukin-25 (IL-25) is recognized as the most relevant initiator of protective Th2 responses in intestinal helminth infections. It is well known that IL-25 induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. E. caproni has been extensively used as an experimental model to study the factors determining the resistance to intestinal infections. Herein, we assessed the role of IL-25 in the generation of resistance in mice to E. caproni infections. ICR mice are permissive hosts for E. caproni in which chronic infections are developed in relation to the lack of IL-25 production in response to primary infection and the consequ…
T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease
2017
International audience; IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy contro…
Autoantibodies in Spondyloarthritis, Focusing on Anti-CD74 Antibodies
2019
Spondyloarthritis (SpA) is an inflammatory rheumatic disease with diverse clinical presentation. The diagnosis of SpA remains a big challenge in daily clinical practice because of the limitation in specific biomarkers of SpA, more biomarkers are still needed for SpA diagnosis and disease activity monitoring. In the past, SpA was considered predominantly as auto-inflammatory disease vs. autoimmune disease. However, in recent years several researches demonstrated a broad autoantibody response in SpA patients. Study also indicated that mice lack of ZAP70 in T cell develop SpA featured inflammation. These studies indicated the autoimmune features of SpA and gave rise to the potential use of aut…
Microbiota-Mitochondria Inter-Talk: A Potential Therapeutic Strategy in Obesity and Type 2 Diabetes
2020
The rising prevalence of obesity and type 2 diabetes (T2D) is a growing concern worldwide. New discoveries in the field of metagenomics and clinical research have revealed that the gut microbiota plays a key role in these metabolic disorders. The mechanisms regulating microbiota composition are multifactorial and include resistance to stress, presence of pathogens, diet, cultural habits and general health conditions. Recent evidence has shed light on the influence of microbiota quality and diversity on mitochondrial functions. Of note, the gut microbiota has been shown to regulate crucial transcription factors, coactivators, as well as enzymes implicated in mitochondrial biogenesis and meta…
Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening
2020
Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut mic…