A mitochondria-targeted fluorescent probe for monitoring endogenous cysteine in living cells and zebrafish.

At the organelle level, pathogenesis due to abnormal concentrations of cysteine (Cys) is of great significance for the early diagnosis and treatment of related diseases. Generally speaking, organelle localization requires the participation of specific target groups, which increases the difficulty of synthesis. Herein, through simple synthesis, a novel biflavone derivative (BFD) that exhibits excited-state intramolecular proton transfer (ESIPT) was obtained and successfully located in mitochondria without target groups. The probe BFD can distinguish Cys from Hcy and GSH with a rapid response (< 5 s) and showed visual detection for Cys with a large Stokes shift (about 260 nm). Because of its nanomorphology in solution and surface functional groups, the probe BFD can enter the cell smoothly and achieve mitochondrial localization. Owing to its excellent optical performance, the probe BFD was successfully applied to the imaging of endogenous Cys in HeLa cells and zebrafish.

Comparison of Drug-Eluting and Bare Metal Stents in Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Drug-eluting stents (DESs) and bare metal stents (BMSs) are both recommended to improve coronary revascularization and to treat coronary artery disease in patients with chronic kidney disease (CKD). However, the potential superiority of DESs over BMSs for reducing the incidence of long-term major adverse cardiovascular events and mortality in CKD patients has not been established, and the results remain controversial. We aimed to systematically assess and quantify the total weight of evidence regarding the use of DESs versus BMSs in CKD patients. METHODS AND RESULTS: In this systematic review and conventional meta-analysis, electronic studies published in any language until May 20, 2016, were systematically searched through PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials and observational studies comparing outcomes in CKD patients with DESs versus BMSs and extracted data in a standard form. Pooled odd ratios and 95% CIs were calculated using random- and fixed-effects models. Finally, 38 studies involving 123 396 patients were included. The use of DESs versus BMSs was associated with significant reductions in major adverse cardiovascular events (pooled odds ratio 0.75; 95% CI, 0.64-0.88; P<0.001), all-cause mortality (odds ratio 0.81; 95% CI, 0.73-0.90; P<0.001), myocardial infarction, target-lesion revascularization, and target-vessel revascularization. The superiority of DESs over BMSs for improving clinical outcomes was attenuated in randomized controlled trials. CONCLUSIONS: The use of DESs significantly improves the above outcomes in CKD patients. Nevertheless, large-sized randomized controlled trials are necessary to determine the real effect on CKD patients and whether efficacy differs by type of DES.

Clinical characteristics of drug-induced liver injury and related risk factors.

Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory-specific serological markers. In this study, we comprehensively assessed the clinical characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes concerning DILI, and explored the similarities in mechanisms between Chinese and Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for systematic retrospective study. Their clinical characteristics, clinical classification, risk factors, laboratory indices, hepatotoxic drugs and outcomes were analyzed. Cholestatic patients had the highest alkaline phosphatase (ALP) and prothrombin time activity (PTA) levels (P<0.05). Patients with medication time ≥30 days had significantly higher positive rate of autoantibodies than those with medication time <30 days. Odds ratio values for DILI-related factors such as hepatobiliary diseases, immune dysfunction, diabetes, hypertension, chronic alcohol consumption and age ≥45 years were 6.552, 6.130, 3.774, 2.801, 2.002 and 1.838, respectively. Pathogeneses of Chinese and Western drug-induced DILI may be substantially the same. DILI accompanied with autoantibody positivity may indicate severe liver injury outcome. Hepatobiliary diseases, diabetes and hypertension are likely to increase drug susceptibility, and more prone to cause liver injury.

Effects of mineralocorticoid receptor antagonists on left ventricular mass in chronic kidney disease patients: a systematic review and meta-analysis.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are used widely in treatment of heart failure, but their effects on cardiovascular complications and mortality of chronic kidney disease (CKD) are not well known. Thus, we aim to assess such therapeutic effects of MRAs on CKD. METHODS: Electronic literature published in any language until Dec 31, 2015, was systematically searched on PubMed, Embase, and Cochrane Central Register of Controlled Trials. Primary outcome was left ventricular mass (LVM) or LVM index (LVMI), and secondary outcome was all-cause mortality and major adverse cardiovascular events (MACEs). Results of continuous outcomes were pooled using mean difference (MD) and standard mean difference (SMD). Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled using a random- or fixed-effects model. RESULTS: Totally 12 studies (6 randomized controlled trials with 1003 participants) involving 4935 patients were included. MRA treatment versus non-MRA treatment resulted in a significant change of 0.93 SMD (standard mean difference) in LVM (LVMI), a significant reduction of 22 % in all-cause mortality, a significant reduction of incidence of MACEs (RR 0.65, P = 0.001), significantly higher prevalence rates of hyperkalemia (>5.5 mmol/L), but no significant change in prevalence rates of severe hyperkalemia (>6.0 mmol/L). CONCLUSION: MRA benefits CKD patients in terms of LVMI, all-cause mortality, and MACEs with no incidence of severe hyperkalemia. Nevertheless, the real effects of MRAs on cardiovascular events and mortality as well as their safety in CKD patients should be identified by further studies with prospective and large-sample clinical trials.

Association of vitamin D receptor BsmI gene polymorphism with risk of tuberculosis: a meta-analysis of 15 studies.

BACKGROUND: Genetic variations in vitamin D receptor (VDR) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a comprehensive meta-analysis of 15 publications with a total of 2309 cases and 3568 controls. We assessed the strength of the association between VDR BsmI gene polymorphism and TB risk and performed sub-group analyses by ethnicity, sample size and Hardy-Weinberg equilibrium (HWE). We found a statistically significant correlation between VDR BsmI gene polymorphism and decreased TB risk in four comparison models: allele model (b vs. B: OR = 0.78, 95% CI = 0.67, 0.89; Pheterogeneity = 0.004), homozygote model (bb vs. BB: OR = 0.61, 95% CI = 0.43, 0.87; Pheterogeneity = 0.001), recessive model (bb vs. Bb+BB: OR = 0.70, 95% CI = 0.56, 0.88; Pheterogeneity = 0.005) and dominant model (bb+Bb vs. BB: OR = 0.77, 95% CI = 0.61, 0.97; Pheterogeneity = 0.010), especially in studies based on Asian population. Sub-group analyses also revealed that there was a statistically decreased TB risk in "small" studies (<500 participants) and studies with PHWE>0.5. Meta-regression and stratification analysis both showed that the ethnicity and sample size contributed to heterogeneity. CONCLUSIONS: This meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.