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Chenodeoxycholic Acid as a Potential Prognostic Marker for Roux-en-Y Gastric Bypass in Chinese Obese Patients. - The Journal of clinical endocrinology and metabolism
Bile acids (BAs) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB).To test whether the individual or a group of BAs have potential value to predict diabetes remission after RYGB.A retrospective cohort of 38 Chinese obese patients with type 2 diabetes (T2DM) who had undergone RYGB and a cross-sectional cohort of 327 subjects from the Shanghai Obesity Study (SHOS) were involved in the study.We applied a targeted metabolomics approach to quantitatively measure 26 serum BAs. The relative proportion of each BA in total BAs was calculated.In the metabolic surgery study, RYGB was effective in the reduction of body weight in both remission and non-remission groups. The reductions of BMI in both groups were 7.34Â±2.10kg/m(2) and 6.31Â±2.38kg/m(2) respectively (p=0.14). Patients in the remission group had shorter duration of diabetes, lower glycated haemoglobin (HbA1c), higher C-peptide and chenodeoxycholic acid (CDCA) proportion at baseline compared with the non-remission group. Multiple logistic regression indicated that a higher level of CDCA relative to TBA (CDCA %) and shorter duration of diabetes at baseline were associated with a greater chance of diabetes remission. The odd ratios were 0.19 (95%CI, 0.05 to 0.74), 1.77 (95%CI, 1.13 to 2.76) respectively after adjusted for age, gender and BMI. In the cross-sectional study, CDCA% was significantly higher in obese individuals with T2DM than the NGT group. Correlation analysis showed CDCA% was positively correlated with BMI, HbA1c, TG, LDL-c, and negatively correlated with HDL-c and diabetes duration.Increased CDCA, a major primary bile acid, was correlated with shorter duration of T2DM which was associated with a higher possibility of remission after surgery. CDCA% might act as a potential prognostic marker of RYGB.
High Trap Formation and Low Metabolite Production by Disruption of the Polyketide Synthase Gene Involved in the Biosynthesis of Arthrosporols from Nematode-Trapping Fungus Arthrobotrys oligospora. - Journal of agricultural and food chemistry
A group of morphology regulatory arthrosporol metabolites have been recently characterized from carnivorous fungus Arthrobotrys oligospora that can develop trapping networks to capture their prey. A combination of genetic manipulation and chemical analyses was applied to characterize the function of one polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora, which was putatively involved in the production of 6-methylsalicylic acid. High-performance liquid chromatography analysis showed that the disruption of the PKS gene not only led to the total loss of the arthrosporol A but also resulted in significant reduction in the production of secondary metabolites in the cultural broth of the mutant Î”AOL_s00215g283 strain. Interestingly, the mutant strain displayed significant increases in the trap formation and the nematicidal activity by 10 and 2 times, respectively, higher than the wild-type strain. These findings revealed a pathogenicity-related biosynthetic gene of this agriculturally important biological agent and have implications for establishment of efficient fungal biocontrol agents.
Polymorphism of IL37 gene as a protective factor for autoimmune thyroid disease. - Journal of molecular endocrinology
Autoimmune thyroid disease (AITD) comprises Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL37 has been recently proved to be a natural suppressor for innate immunity and acquired immunity. Therefore, this study was conducted to identify the association of IL37 genetic polymorphisms with AITD in Chinese Han population. Polymorphisms of rs3811046/rs3811047/rs2723176/rs272186 in the IL37 gene were assessed in a case-control study comprising 701 GD patients, 301 HT patients and 939 controls. Genetic variants were genotyped by multiplex polymerase chain reaction and ligase detection reaction. The frequencies of the minor allele A of rs2723176 and A of rs2723186 were significantly lower in the GD patients than in the controls (P=0.014, OR=0.774; P=0.014, OR=0.777). After gender stratification, the rs3811046 G allele and the rs3811047/rs2723186 A allele were both significantly associated with a decreased risk of GD in female patients (P=0.030, OR=0.777; P=0.023, OR=0.774; P=0.029, OR=0.761). However, none of the four single nucleotide polymorphisms of IL37 gene showed any significant association with HT. Moreover, haplotype analysis revealed the GCG haplotype conferred increased risk for GD as a whole and in female GD patients (OR=1.213; OR=1.320). The ACG haplotype was associated with an increased risk of HT as a whole (OR=1.567) and in male GD patients (OR=1.820). In contrast, the AAA haplotype showed a protective role for GD as a whole (OR=0.760) and in female GD patients (OR=0.765). Our study strongly supports that the IL37 gene variants are associated with the susceptibility to AITD.Â© 2015 Society for Endocrinology.
Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system. - Journal of hazardous materials
In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO was the predominant radical in the system and that O2(-) played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO scavenger, supporting the hypothesis that HO was primarily responsible for PCE degradation. It is noteworthy that Cl(-) release was slightly delayed in the first 20min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater.Copyright Â© 2015 Elsevier B.V. All rights reserved.
Degradation of trichloroethene by siderite-catalyzed hydrogen peroxide and persulfate: Investigation of reaction mechanisms and degradation products. - Chemical engineering journal (Lausanne, Switzerland : 1996)
A binary catalytic system, siderite-catalyzed hydrogen peroxide (H2O2) coupled with persulfate (S2O8 (2-)), was investigated for the remediation of trichloroethene (TCE) contamination. Batch experiments were conducted to investigate reaction mechanisms, oxidant decomposition rates, and degradation products. By using high performance liquid chromatography (HPLC) coupled with electron paramagnetic resonance (EPR), we identified four radicals (hydroxyl (HOÂ·), sulfate (SO4 (-)Â·), hydroperoxyl (HO2Â·), and superoxide (O2 (-)Â·)) in the siderite-catalyzed H2O2-S2O8 (2-) system. In the absence of S2O8 (2-) (i.e., siderite-catalyzed H2O2), a majority of H2O2 was decomposed in the first hour of the experiment, resulting in the waste of HOÂ·. The addition of S2O8 (2-) moderated the H2O2 decomposition rate, producing a more sustainable release of hydroxyl radicals that improved the treatment efficiency. Furthermore, the heat released by H2O2 decomposition accelerated the activation of S2O8 (2-), and the resultant SO4 (-)Â· was the primary oxidative agent during the first two hours of the reaction. Dichloroacetic acid was firstly detected by ion chromatography (IC). The results of this study indicate a new insight to the reaction mechanism for the catalytic binary H2O2-S2O8 (2-) oxidant system, and the delineation of radicals and the discovery of the chlorinated byproduct provide useful information for efficient treatment of chlorinated-solvent contamination in groundwater.
In-situ activation of persulfate by iron filings and degradation of 1,4-dioxane. - Water research
Activation of persulfate by iron filings and subsequent degradation of 1,4-dioxane (dioxane) was studied in both batch-reactor and column systems to evaluate the potential of a persulfate-enhanced permeable reactive barrier (PRB) system for combined oxidative-reductive removal of organic contaminants from groundwater. In batch experiments, decomposition of persulfate to sulfate and degradation of dioxane both occurred rapidly in the presence of iron filings. Conversely, dioxane degradation by persulfate was considerably slower in the absence of iron filings. For the column experiments, decomposition and retardation of persulfate was observed for transport in the columns packed with iron filings, whereas no decomposition or retardation was observed for transport in columns packed with a reference quartz sand. Both sulfate production and dioxane degradation were observed for the iron-filings columns, but not for the sand column. The pH of the column effluent increased temporarily before persulfate breakthrough, and significant increases in both ferrous and ferric iron coincided with persulfate breakthrough. Multiple species of free radicals were produced from persulfate activation as determined by electron paramagnetic resonance (EPR) spectroscopy. The impact of the oxidation process on solution composition and iron-filings surface chemistry was examined using ICP-MS, SEM-EDS, and XRD analyses. A two-stage reaction mechanism is proposed to describe the oxidation process, consisting of a first stage of rapid, solution-based, radical-driven decomposition of dioxane and a second stage governed by rate-limited surface reaction. The results of this study show successful persulfate activation using iron filings, and the potential to apply an enhanced PRB method for improving in-situ removal of organic contaminants from groundwater.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Histone hypoacetylation and increased histone deacetylases in peripheral blood mononuclear cells from patients with Graves' disease. - Molecular and cellular endocrinology
The objective of this study was to investigate histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with Graves' disease (GD). Thirty GD patients and 20 healthy controls were enrolled in this study. Global histone H3/H4 acetylation levels of PBMCs in all subjects were detected by enzyme-linked immunosorbent assay. mRNA levels of histone-related chromatin modifier genes were measured by real-time quantitative reverse transcription-polymerase chain reaction. Global histone H4 acetylation level in PBMCs of GD patients was significantly decreased compared with controls (p=0.005). The mRNA expression of histone deacetylases HDAC1 and HDAC2 were significantly increased in PBMCs of GD patients compared with controls (p=0.004 and 0.018; respectively). No significant difference was observed either in SIRT1 or in HATs mRNA including p300, CREBBP between GD patients and controls (p>0.05). Our findings firstly suggested that histone acetylation modifications are aberrant in PBMCs of GD patients, possibly due to the deregulation of epigenetic modifier genes.Copyright Â© 2015 Elsevier Ireland Ltd. All rights reserved.
RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population. - BMC medical genetics
Polymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population.We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Three CCR6 single nucleotides polymorphisms (SNPs) (rs3093023/rs3093024/rs6902119) and one tagging SNP (rs9355610) within RNASET2 gene were selected for genotyping by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR).The frequency of rs9355610 genotypes in the patients with GD differed significantly from that in the controls (pâ€‰=â€‰0.017). The frequency of the minor G allele of rs9355610 was significantly higher in the GD patients than in the healthy controls (pâ€‰=â€‰0.005, ORâ€‰=â€‰1.225, 95% CI:1.063-1.412). However, we could not find significant differences in the genotype or allele frequencies of HT patients compared with healthy controls. After gender stratification, the frequency of the minor G allele in both male and female GD patients was significantly higher than that in the healthy controls (pâ€‰=â€‰0.036, ORâ€‰=â€‰1.308, 95% CI:1.017-1.684 ; pâ€‰=â€‰0.048, ORâ€‰=â€‰1.19, 95% CI:1.001-1.413; respectively);. Furthermore, the frequency of haplotype AT in GD patients was significantly lower than that in their control groups (pâ€‰=â€‰0.003) and showed a protective effect against GD (ORâ€‰=â€‰0.806, 95% CI: 0.699-0.929). The frequency of haplotype GT in GD patients was significantly higher than that in their control groups (pâ€‰=â€‰0.048), indicating that GT was the risk haplotype to GD (ORâ€‰=â€‰1.267, 95% CI: 1.001-1.603). There were no significant differences in the allele or genotype frequencies of three SNPs of CCR6 (rs3093023/rs3093024/ rs6902119) gene between GD patients, HT patients and controls.Our results suggest that the rs9355610 tag SNP of RNASET2 gene is positively associated with susceptibility to GD in the Chinese Han population. No association was found for the tested CCR6 SNPs.
Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay. - The AAPS journal
Programmed death-1 (PD-1) protein is a co-inhibitory receptor which negatively regulates immune cell activation and permits tumors to evade normal immune defense. Anti-PD-1 antibodies have been shown to restore immune cell activation and effector function-an exciting breakthrough in cancer immunotherapy. Recent reports have documented a soluble form of PD-1 (sPD-1) in the circulation of normal and disease state individuals. A clinical assay to quantify sPD-1 would contribute to the understanding of sPD-1-function and facilitate the development of anti-PD-1 drugs. Here, we report the development and validation of a sPD-1 protein assay. The assay validation followed the framework for full validation of a biotherapeutic pharmacokinetic assay. A purified recombinant human PD-1 protein was characterized extensively and was identified as the assay reference material which mimics the endogenous analyte in structure and function. The lower limit of quantitation (LLOQ) was determined to be 100Â pg/mL, with a dynamic range spanning three logs to 10,000Â pg/mL. The intra- and inter-assay imprecision were â‰¤15%, and the assay bias (percent deviation) was â‰¤10%. Potential matrix effects were investigated in sera from both normal healthy volunteers and selected cancer patients. Bulk-prepared frozen standards and pre-coated Streptavidin plates were used in the assay to ensure consistency in assay performance over time. This assay appears to specifically measure total sPD-1 protein since the human anti-PD-1 antibody, nivolumab, and the endogenous ligands of PD-1 protein, PDL-1 and PDL-2, do not interfere with the assay.
Metabonomics reveals metabolite changes in biliary atresia infants. - Journal of proteome research
Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.
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