Causal effects of circulating vitamin levels on the risk of heart failure:a Mendelian randomization study

BACKGROUND Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure(HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization(MR) study to investigate the causal associations between genetically determined vitamin levels and HF.METHODS Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium(47,309 cases and 930,014controls) and FinnGen Study(30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis.RESULTS Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97(95% confidence interval [CI]: 0.85–1.09, P = 0.41) for vitamin C to 1.05(95% CI: 0.61–1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94(95% CI:0.75–1.19, P = 0.62) for α-tocopherol and 1.11(95% CI: 0.98–1.26, P = 0.09) for γ-tocopherol.CONCLUSION Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore,there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.

Therapeutic effect of a hydroxynaphthoquinone fraction on dextran sulfate sodium-induced ulcerative colitis

AIM: To evaluate the therapeutic effect of hydroxynaphthoquinone mixture (HM) on dextran sulfate sodium (DSS)-induced colitis and explore the underlying mechanisms.

Effectiveness of a hydroxynaphthoquinone fraction from Arnebia euchroma in rats with experimental colitis

AIM:To evaluate the potential effectiveness of hydroxynaphthoquinone mixture(HM)in rats with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Colitis was induced by intracolonic administration of TNBS(80 mg/kg,dissolved in 50%ethanol).Rats were treated daily for 7 d with HM(2.5,5,10 mg/kg)and mesalazine 100 mg/kg 24 h after TNBS instillation.Disease progression was monitored daily by observation of clinical signs and body weight change.At the end of the experiment,macroscopic and histopathologic lesions of rats were scored,and myeloperoxidase(MPO)activity was determined.We also determined inflammatory cytokine tumor necrosis factor(TNF)-αlevel by ELISA,Western blotting and immunochemistry to explore the potential mechanisms of HM.RESULTS:After intracolonic instillation of TNBS,animals developed colitis associated with soft stool,diarrhea and marked colonic destruction.Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner.It abrogated body weight loss,diarrhea and inflammation,decreased macroscopic damage score,and improved histological signs,with a significant reduction of inflammatory infiltration,ulcer size and the severity of goblet cell depletion(all P<0.05 vs TNBS alone group).HM could reduce MPO activity.In addition,it also decreased serum TNF-αlevel and down-regulated TNF-αexpression in colonic tissue.This reduction was statistically significant when the dose of HM was 10 mg/kg(P<0.05 vs TNBS alone group),and the effect was comparable to that of mesalazine and showed no apparent adverse effect.The underlying mechanism may be associated with TNF-αinhibition.CONCLUSION:These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis,which provides direct pharmacological evidence for its clinical application.

Synthesis and optoelectronic properties of a novel molecular semiconductor of dithieno[5,6-b:11,12-b']coronene-2,3,8,9-tetracarboxylic tetraester

A facile procedure for the synthesis ofdithieno[5,6-b：11,12-b＇]coronene-2,3,8,9-tetracarboxylic tetra（2- ethylhexyl）ester （DTCTI＇E-EH） from readily available perylene-3,4,9,10-tetracaroboxylic dianhydride is described. The electronic properties of DTCTTE-EH were elucidated on the basis of UV-vis spectra, emission spectrum and electrochemical measurement, which demonstrate that DTCTTE is a new class of components for promising semiconducting materials.