Metabolomics study reveals blood biomarkers for early diagnosis of chronic kidney disease and IgA nephropathy: A retrospective cross-sectional study.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) causes low quality of life and alarming morbidity and mortality. The crucial to retard CKD progression is to diagnose early for timely treatment. IgA nephropathy (IgAN) is a typical CKD and the most common glomerulonephritis. Both CKD and IgAN lack accurate and sensitive blood biomarkers for early diagnosis. Here we report the potential of plasma biomarkers for early diagnosis of CKD and IgAN. MATERIALS AND METHODS: Plasma levels of metabolites derived from tryptophan were quantified with an LC-MS/MS-based metabolomics for two cohorts. Based on the predictive probability of each metabolite, multivariate models including logistic regression and random forest were used to establish the early diagnostic biomarkers for CKD and IgAN. RESULTS: The plasma melatonin diagnosed early CKD (stages Ⅰ-Ⅱ) with an accuracy exceeding 95%, and a panel of melatonin and tryptophan achieved a remarkable 100% accuracy in diagnosing early CKD. Furthermore, indole-3-lactic acid had an excellent ability to distinguish IgAN among CKD patients. Based on the CKD screening and IgAN diagnosis primarily contributed by melatonin and indole-3-lactic acid, early IgAN could be diagnosed with an accuracy of over 85%. CONCLUSIONS: This study provides promising plasma biomarkers for early diagnosis of CKD and IgAN.

Effect of PPARγ agonist (rosiglitazone) on the secretion of Th2 cytokine in asthma mice.

OBJECTIVE: To explore the effect of PPARγ agonist (rosiglitazone) on the secretion of Th2 cytokines and the proportion of immune cell subsets in asthma mice. METHODS: Ovalbumin (OVA)-sensitized mice were used to build asthma models. Those mice were divided into the normal control group, model group and rosiglitazone group. Differences of the changes in lung histopathology of mice in the three groups were observed through hematoxylin and eosin (HE) strain, and the numbers of the total cells, eosinophils and neutrophils in BALF of mice in the three groups were compared. ELISA and real-time PCR were employed to detect the protein levels of interleukin (IL)-5, IL-13, IL-4 and IL-10 and mRNA level, respectively. Flow cytometry number was implied to analyze the proportion of immune cell subsets in peripheral blood of mice. RESULTS: Compared with the mice in the control group, and mice of the model group, the infiltration of inflammatory cells in BALF increased, bronchial smooth muscle became thickened, a large amount of collagen deposited, the secretion of Th2 cytokine increased significantly, the ratio of regulatory T cells (Treg) decreased, the ratio of T17 cells rose distinctly; while in mice of the rosiglitazone group, the changes of their lung histopathology were improved obviously, the number of infiltration of inflammatory cells declined, the thickened smooth muscle relieved, the deposition of collagen decreased, the secretion of Th2 cytokine was inhibited, the ratio of Treg went up, and the increased of the ratio of T17 cells was inhibited but still not return to normal level. CONCLUSIONS: Rosiglitazone can regulate the proportion of Treg and Th17 cells and inhibit the secretion of Th2 cytokines, which inhibit the airway inflammatory response for asthma mice effectively.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3.

OBJECTIVE: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. METHODS: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. RESULTS: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1ß. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. CONCLUSIONS: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

Tooth loss is associated with increased risk of esophageal cancer: evidence from a meta-analysis with dose-response analysis.

Epidemiological studies have revealed the association between tooth loss and the risk of esophageal cancer (EC); however, consistent results were not obtained from different single studies. Therefore, we conducted the present meta-analysis to evaluate the association between tooth loss and EC. We conducted electronic searches of PubMed until to February 10, 2015 to identify relevant observational studies that examined the association between tooth loss and the risk of EC. Study selection and data extraction from eligible studies were independently performed by two authors. The meta-analysis was conducted using Stata 12.0 software. Finally eight eligible publications with ten studies involving 3 cohort studies, 5 case-control studies, and 1 cross-sectional study were yielded. Meta-analysis identified tooth loss increased risk of EC 1.30 times (Relative risk = 1.30, 95% confidence interval = 1.06-1.60, I(2) = 13.5%). Dose-response analysis showed linear relationship between tooth loss and risk of EC (RR = 1.01, 95%CI = 1.00-1.03; P for non-linearity test was 0.45). Subgroup analysis proved similar results and publication bias was not detected. In conclusion, tooth loss could be considered to be a significant and dependent risk factor for EC based on the current evidence.

RELATIVE CONTRIBUTIONS OF ECTOPIC LIVER AND ABDOMINAL FAT ACCUMULATION TO ARTERIAL STIFFNESS.

OBJECTIVE: To compare the arterial stiffness between the abdominal obese population without nonalcoholic fatty liver disease (NAFLD) (referred to as abdominal fat accumulation), the normal-weight population with NAFLD (ectopic liver fat accumulation), and the population with both abdominal obesity and NAFLD (accumulation of both abdominal and ectopic liver fat). METHODS: A total of 111,552 Chinese adults who underwent the health checkups from January 2012 to December 2012 were screened. Clinical and biochemical parameters were measured in each subject. NAFLD was diagnosed by ultrasonography. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). RESULTS: Normal-weight subjects with NAFLD had significantly higher CAVI than subjects with abdominal obesity with or without NAFLD (8.12 ± 1.16 vs. 7.93 ± 1.38, 7.96 ± 1.20; P<.01). When the presence of abdominal obesity, NAFLD, and both diseases (abdominal obesity and NAFLD) were included in regression analyses individually, CAVI was independently associated with abdominal obesity or NAFLD or both after adjusting for confounders. When the presence of abdominal obesity and NAFLD and both diseases were included simultaneously in regression analyses, the association between NAFLD and CAVI and the association between both diseases and CAVI remained significant, whereas the association between abdominal obesity and CAVI was no longer significant. The presence of NAFLD conferred a greater odds ratios of having an elevated CAVI than did the presence of abdominal obesity or even the presence of both diseases. CONCLUSION: Ectopic liver fat accumulation is associated with greater risk of arterial stiffness compared with abdominal fat accumulation or accumulation of both abdominal and ectopic liver fat.

Cytochrome P450 2E1 RsaI/PstI polymorphism and risk of esophageal cancer: A meta-analysis of 17 case-control studies.

The aim of this study was to explore the cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and risk of esophageal cancer (EC) in mainland Chinese populations. A systematic search of PubMed, EMBASE, Web of Science, CBM, CNKI and VIP databases for publications on the CYP2E1 RsaI/PstI polymorphism and risk of EC was performed. and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity and assessment of publication bias were performed. The search yielded 17 studies including 18 trails involving 1,663 cases and 2,603 controls. The meta-analyses showed a significant association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population (c2 vs. c1: OR=0.64; 95% CI, 0.50-0.81; P<0.001; c2/c2 vs. c1/c1: OR=0.73; 95% CI, 0.57-0.93; c2/c2 vs. c1/c1+c1/c2: OR=0.76; 95% CI, 0.60-0.96; P=0.02; c1/c2 vs. c1/c1: OR=0.54; 95% CI, 0.38-0.75; P<0.001; c1/c2+c2/c2 vs. c1/c1: OR=0.48; 95% CI, 0.34-0.70; P<0.001). An increased cancer risk in all genetic models was identified following stratification by ethnicity, source of controls and tumor type. In conclusion, in all genetic models, the association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population was significant. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism is a risk factor for EC, and the c2 allele is a factor that lowers the possibility of EC in the mainland Chinese population and this association did not change due to ethnic differences in genetic backgrounds and the environment.