Project description:Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Previous publication showed the obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. The goal of this experiment was to compare genome wide enrichment of H3K9ac histone mark profile of white blood cells of healthy controls, patients with obesity and/or stroke in order to understand the histone modifications differences behind the different phenotypes. There were 3 subjects in each group.
Project description:BackgroundHashimoto's thyroiditis, an autoimmune thyroid disease, shows high morbidity worldwide, particularly in female. Patients with Hashimoto's thyroiditis have an increasing risk of hypothyroidism during the occurrence and progression of Hashimoto's thyroiditis. In recent years, metabolomics has been widely applied in autoimmune diseases, especially thyroid disorders. However, metabolites analysis in Hashimoto's thyroiditis is still absent.MethodsA total of 92 samples were collected, including 35 cases in the control group, 30 cases in the Hashimoto's thyroiditis with euthyroidism group, and 27 cases in the Hashimoto's thyroiditis with subclinical hypothyroidism group. SPSS 25.0 for statistical analysis and ROC curve, SIMCA 14.0, Metaboanalysis for multifactor analysis, and Origin 2021 for correlation analysis.Results21 metabolites were identified. 10 metabolites were obtained from control group versus HTE group, 8 serum metabolites were abnormal between control group and HTS group, 3 metabolites were derived from HTE group versus HTS. Kyoto Encyclopedia of Genes and Genomes Enrichment analysis showed that fatty acid degradation, Arginine, and proline metabolism have a significant impact on HTE, while lysine degradation, tyrosine metabolism play an important role HTS group, compared to control group. In the comparison between the HTE and HTS group, Valine, leucine, and isoleucine degradation and Valine, leucine, and isoleucine biosynthesis exists a key role. Correlation analysis shows clinical are not related to metabolites. ROC curve indicates SM, LPC, PC can efficiency in identification patients with HT in different clinical stage from healthy individuals.ConclusionSerum metabolites were changed in HT. Phospholipids such as SM, LPC, PC influence the pathogenesis of Hashimoto's thyroiditis. Fatty acid degradation and lysine degradation pathways have an impact on different clinical stage of HT.
Project description:Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established.
Project description:Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance. Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA). Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests. Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.
Project description:We investigated a panel of 21 genes by parallel sequencing on the Ion Torrent Personal Genome Machine platform. We sequenced 65 CRCs that were treated with cetuximab or panitumumab ( 37 samples were responsive and 28 were resistant).
Project description:Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, L-aspartic acid, L-ornithine, Ethanolamine, L-Serine, L-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.
Project description:Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders. Studies have shown the involvement of an abnormal immune system in MDS pathogenesis. The gut microbiota are known to influence host immunity and metabolism, thereby contributing to the development of hematopoietic diseases. In this study, we performed gut microbiome and plasma metabolomic analyses in patients with MDS and healthy controls. We found that patients with MDS had a different gut microbial composition compared to controls. The gut microbiota in MDS patients showed a continuous evolutionary relationship from the phylum to the species level. At the species level, the abundance of Haemophilus parainfluenzae, Streptococcus luteciae, Clostridium citroniae, and Gemmiger formicilis increased, while that of Prevotella copri decreased in MDS patients compared to controls. Moreover, abundance of bacterial genera correlated with the percentage of lymphocyte subsets in patients with MDS. Metabolomic analysis showed that the concentrations of hypoxanthine and pyroglutamic acid were increased, while that of 3a,7a-dihydroxy-5b-cholestan was decreased in MDS patients compared to controls. In conclusion, gut microbiome and plasma metabolomics are altered in patients with MDS, which may be involved in the immunopathogenesis of the disease.
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. MicroRNAs are small nucleatides that function as regulators of gene expression in almost any biological process. However, few microRNAs are reported to have a role in the pathological process of OPLL. Therefore, we performed high-throughput microRNA sequencing and transcriptome sequencing of primary OPLL and PLL cells in order to decipher the interacting network of microRNAs in OPLL. MRNA and microRNA profiles were done using primary culture cells of human ossification of the posterior longitudinal ligament (OPLL) tissue and normal posterior longitudinal ligament (PLL) tissue.