Project description:Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, and inflammatory markers in patients with type 1 diabetes. In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed seven-day washout period. Each intervention period involved three study days: Day 0 (baseline measurements, a baseline abdominal adipose tissue biopsy and blood sampling), Day 1 (fasting blood sample after 24 hours infusion), and Day 6 (fasting blood sample, an abdominal adipose tissue biopsy).
Project description:In this project we will investigate the peptides present by HLA-DQ8. We will identify linear, spliced and PTM peptides from one cell line.
Project description:Type 2 diabetes (T2D) is a global public health issue characterized by excess weight, abdominal obesity, dyslipidemia, hyperglycemia, and a progressive increase in insulin resistance. Human population studies of T2D development and its effects on systemic metabolism are confounded by many factors that cannot be controlled, complicating the interpretation of results and the identification of early biomarkers. Aged, sedentary, and overweight/obese non-human primates (NHPs) are one of the best animal models to mimic spontaneous T2D development in humans. We sought to identify and distinguish a set of plasma and/or fecal metabolite biomarkers, that have earlier disease onset predictability, and that could be evaluated for their predictability in subsequent T2D studies in human cohorts. In this study, a single plasma and fecal sample was collected from each animal in a colony of 57 healthy and dysmetabolic NHPs and analyzed for metabolomics and lipidomics. The samples were comprehensively analyzed using untargeted and targeted LC/MS/MS. The changes in each animal's disease phenotype were monitored using IVGTT, HbA1c, and other clinical metrics, and correlated with their metabolic profile. The plasma and fecal lipids, as well as bile acid profiles, from Healthy, Dysmetabolic (Dys), and Diabetic (Dia) animals were compared. Following univariate and multivariate analyses, including adjustments for weight, age, and sex, several plasma lipid species were identified to be significantly different between these animal groups. Medium and long-chain plasma phosphatidylcholines (PCs) ranked highest at distinguishing Healthy from Dys animals, whereas plasma triglycerides (TG) primarily distinguished Dia from Dys animals. Random Forest (RF) analysis of fecal bile acids showed a reduction in the secondary bile acid glycoconjugate, GCDCA, in diseased animals (AUC 0.76[0.64, 0.89]). Moreover, metagenomics results revealed several bacterial species, belonging to the genera Roseburia, Ruminococcus, Clostridium, and Streptococcus, to be both significantly enriched in non-healthy animals and associated with secondary bile acid levels. In summary, our results highlight the detection of several elevated circulating plasma PCs and microbial species associated with fecal secondary bile acids in NHP dysmetabolic states. The lipids and metabolites we have identified may help researchers to differentiate individual NHPs more precisely between dysmetabolic and overtly diabetic states. This could help assign animals to study groups that are more likely to respond to potential therapies where a difference in efficacy might be anticipated between early vs. advanced disease.
Project description:Early prediction and prevention of type 1 diabetes (T1D) are currently unmet medical needs. Previous metabolomics studies suggest that children who develop T1D are characterised by a distinct metabolic profile already detectable during infancy, prior to the onset of islet autoimmunity. However, the specificity of persistent metabolic disturbances in relation T1D development has not yet been established. Here, we report a longitudinal plasma lipidomics dataset from (1) 40 children who progressed to T1D during follow-up, (2) 40 children who developed single islet autoantibody but did not develop T1D and (3) 40 matched controls (6 time points: 3, 6, 12, 18, 24 and 36 months of age). This dataset may help other researchers in studying age-dependent progression of islet autoimmunity and T1D as well as of the age-dependence of lipidomic profiles in general. Alternatively, this dataset could more broadly used for the development of methods for the analysis of longitudinal multivariate data.
Project description:To define the role of MAGE-A1 in melanoma growth and metastasis, we performed RNA-seq analysis on MAGE-A1 overexpression (OE) and knockdown (KD) models in A375 human melanoma cell line. Our results revealed that overexpression of MAGE-A1 dramatically promoted proliferation, migration, and invasion of human melanoma cells in vitro and down-regulated of MAGE-A1 inhibited tumor cell proliferation and invasion. Furthermore, MAGE-A1 exerts its tumor promoting activity via activating including ERK-MAPK signaling pathway by RNA-seq analysis. mRNA profiles of MAGE-A1 over expression (OE), knockdown (KD), pcDNA-vector control, and pRNAT-scramble control in A375 cell line were generated using Ion torrent
Project description:Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ?70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P?<?0.001) and 48.4% vs 9.3% (P?<?0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients with advanced vascular complications reduced cardiovascular death and nonfatal cardiovascular events.
Project description:H. seropedicae wild-type or ntrC mutant were grown on three different nitrogen conditions: nitrogen limiting, ammonium shock and nitrate shock.
Project description:Per- and polyfluorinated alkyl substances (PFAS) are pervasive environmental contaminants that bioaccumulate in tissues and pose risks to human health. Increasing evidence links PFAS to neurodegenerative and behavioral disorders, yet the underlying mechanisms of their effects on neuronal function remain largely unexplored. In this study, we utilized SH-SY5Y neuroblastoma cells, differentiated into neuronal-like cells, to investigate the impact of six PFAS compounds perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfonate (8:2 FTS), and 8:2 fluorotelomer alcohol (8:2 FTOH) neuronal health. Following a 30 μM exposure for 24 h, PFAS accumulation ranged from 40−6500 ng/mg of protein. Transcriptomic analysis revealed 721 differentially expressed genes (DEGs) across treatments (padj < 0.05), with 11 DEGs shared among all PFAS exposures, indicating potential biomarkers for neuronal PFAS toxicity. PFOA-treated cells showed downregulation of genes involved in synaptic growth and neural function, while PFOS, PFDS, 8:2 FTS, and 8:2 FTOH exposures resulted in the upregulation of genes related to hypoxia response and amino acid metabolism. Lipidomic profiling further demonstrated significant increases in fatty acid levels with PFDA, PFDS, and 8:2 FTS and depletion of triacylglycerols with 8:2 FTOH treatments. These findings suggest that the neurotoxic effects of PFAS are structurally dependent, offering insights into the molecular processes that may drive PFAS-induced neuronal dysfunction.
Project description:Metformin is the first-line oral medication for treating type 2 diabetes mellitus (T2DM). In the current study, an untargeted lipidomic analytical approach was used to investigate the alterations in the serum lipidome of a cohort of 89 participants, including healthy lean controls and obese diabetic patients, and to examine the alterations associated with metformin administration. A total of 115 lipid molecules were significantly dysregulated (64 up-regulated and 51 down-regulated) in the obese compared to lean controls. However, the levels of 224 lipid molecules were significantly dysregulated (125 up-regulated and 99 down-regulated) in obese diabetic patients compared to the obese group. Metformin administration in obese diabetic patients was associated with significant dysregulation of 54 lipid molecule levels (20 up-regulated and 34 down-regulated). Levels of six molecules belonging to five lipid subclasses were simultaneously dysregulated by the effects of obesity, T2DM, and metformin. These include two putatively annotated triacylglycerols (TGs), one plasmenyl phosphatidylcholine (PC), one phosphatidylglycerol (PGs), one sterol lipid (ST), and one Mannosyl-phosphoinositol ceramide (MIPC). This study provides new insights into our understanding of the lipidomics alterations associated with obesity, T2DM, and metformin and offers a new platform for potential biomarkers for the progression of diabetes and treatment response in obese patients.
Project description:AimsAging, obesity, and type 2 diabetes mellitus (T2DM) form a metabolic disease continuum that has a continuously increasing prevalence. Lipidomics explains the complex interactions between lipid metabolism and metabolic diseases. We aimed to systematically investigate the plasma lipidome changes induced by newly diagnosed impaired glucose tolerance (IGT) and T2DM in overweight/obese elderly individuals and to identify potential biomarkers to differentiate between the IGT, T2DM, and control groups.MethodsPlasma samples from 148 overweight/obese elderly individuals, including 52 patients with IGT, 47 patients with T2DM, and 49 euglycemic controls, were analyzed using a high-coverage nontargeted absolute quantitative lipidomics approach.ResultsWe quantified 1840 lipids from thirty-eight classes and seven lipid categories. Among overweight/obese elderly individuals, the lipidomic profiles of IGT and T2DM patients were significantly different from those of controls, while they were similar in the IGT and T2DM groups. The concentrations of diglycerides, triglycerides, phosphatidylcholines, and ceramides were obviously altered in the IGT and T2DM groups. Particularly, IGT and T2DM induced the accumulation of triglycerides with longer carbon atom numbers (C44-50) and saturated or lower double bond numbers (n (C=C) = 0-2). Furthermore, a total of 17 potential lipidic biomarkers were identified to successfully differentiate between the IGT, T2DM, and control groups.ConclusionsIn overweight/obese elderly patients, IGT and T2DM induced apparent lipidome-wide changes. This study's results may contribute to explaining the complex dysfunctional lipid metabolism in aging, obesity, and diabetes.