Two isoreticular metal-organic frameworks with chemical formulae [Cu(L)(4,4'-bipy)(H2O)]n 1.5nCH3CN (1) and [Cu(L)(4,4'-bipy)(H2O)]n·4nH2O (2) (H2L = diphenylmethane-4,4'-dicarboxylic acid) were synthesized and structurally characterized. They show the CdSO4 (6(5) 8) net and have an obvious 1D channel that is spread along the crystallographic c axis. More importantly, 1 shows high selectivity for H2 over N2 and CO2 at low pressure, which could be confirmed via computational calculations using the Connolly algorithm to reveal the size and shape of accessible voids. The incorporation of the drug 5-fluorouracil (5-FU) into the desolvated 1 was around 27.5 wt% per gram of the dehydrated 1. 5-FU is released in a highly controlled and progressive fashion with 61% of the drug released after 95 hours. In addition, we have applied molecular docking calculations to investigate the preferred conformation of 5-FU molecules upon binding to MOF 1. These calculations provide a structural basis to explain the 5-FU release from MOF 1.
Scope:We conducted a pooled analysis of randomized controlled trials to evaluate the effects of chromium supplementation on clinically relevant metabolic biomarkers in type 2 diabetes mellitus (T2DM) patients. Methods and results: Electronic searches were conducted and the bibliographies of located articles were searched, and 28 studies were suitable for statistical pooling. Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using fixed-effects or random-effects models. Statistical heterogeneity, publication bias, subgroup analyses, sensitivity analysis and meta-regression assessments were also assessed. Chromium reduced levels of fasting plasma glucose (WMD, −0.99 mmol/L; 95% CI, −1.72 to −0.25; p = 0.008), hemoglobin A1c (WMD, −0.54 %; 95% CI, −0.82 to −0.25; p = 0.0002), triglycerides (WMD, −11.71 mg/dL; 95% CI, −18.38 to −5.04; p = 0.0006). Chromium also increased levels of high-density lipoprotein cholesterol (WMD, 1.73 mg/dL; 95% CI, 0.50 to 2.96; p = 0.006). These results were robust in sensitivity analysis and were not dependent on the chromium dose and duration of supplementation. Subgroup analyses indicated that these notably favorable effects were presented in T2DM subjects ingesting chromium chloride and chromium picolinate formulations. Conclusion: Our pooled analysis suggested that chromium supplementation might be a candidate as an adjunct to pharmacological management in patients with T2DM.
Rotavirus (RV) is the most common cause of severe gastroenteritis and fatal dehydration in human infants and neonates of different species. However, the pathogenesis of rotavirus-induced diarrhea is poorly understood. Secretory diarrhea caused by rotavirus may lead to a combination of excessive secretion of fluid and electrolytes into the intestinal lumen. Fluid absorption in the small intestine is driven by Na-coupled transport mechanisms at the luminal membrane, including Na/H exchanger (NHE). Here, we performed qRT-PCR to detect the transcription of NHEs. Western blotting was employed for protein detection. Furthermore, immunocytochemistry was used to validate the NHE's protein expression. Finally, intracellular Ca concentration was detected by confocal laser scanning microscopy. The results demonstrated that the NHE6 mRNA and protein expressed in the human colon adenocarcinoma cell line (Caco-2). Furthermore, RV-Wa induced decreased expression of the NHE1 and NHE6 in Caco-2 cell in a time-dependent manner. In addition, intracellular Ca concentration in RV-Wa-infected Caco-2 cells was higher than that in the mock-infected cells. Furthermore, RV-Wa also can downregulate the expression of calmodulin (CaM) and calmodulin kinase II (CaMKII) in Caco-2 cells. These findings provides important insights into the mechanisms of rotavirus-induced diarrhea. Further studies on the underlying pathophysiological mechanisms that downregulate NHEs in RV-induced diarrhea are required.
BackgroundThe potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans.MethodsComprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (≥18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta-regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations.ResultsSixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, −0.6 mg/dL; 95% CI, −2.79 to 1.58; P=0.59), FBI (WMD, 0.29 μIU/mL; 95% CI, −1.16 to 1.75; P=0.70), HOMA-IR (WMD, −0.04; 95% CI, −0.53 to 0.46; P=0.88) or HbA1c (WMD, −0.11%; 95% CI, −0.39 to −0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis.ConclusionPomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results.Electronic supplementary materialThe online version of this article (10.1186/s12937-017-0290-1) contains supplementary material, which is available to authorized users.
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