Stachydrine hydrochloride alleviates pressure overload-induced heart failure and calcium mishandling on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far. AIM OF THE STUDY: The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action. MATERIALS AND METHODS: In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells. RESULTS: Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2. CONCLUSION: Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.

Dietary protein intake and risk of type 2 diabetes: a dose-response meta-analysis of prospective studies.

PURPOSE: The association between dietary protein intake and type 2 diabetes risk has been inconsistent in the previous epidemiological studies. We aimed to quantitatively assess whether dietary total, animal, and plant protein would be associated with type 2 diabetes risk. METHODS: A comprehensive literature review was conducted to identify related articles by searching PubMed, Embase, Web of Science, and Wiley Online Library through 20th March 2018. Generalized least squares for trend estimation and restricted cubic spline regression model were applied in the dose-response analysis. RESULTS: Eight publications with ten prospective cohorts of 34,221 type 2 diabetes cases were included. After adjustment of potential confounders, a 5% of energy increment from dietary total and animal protein intake was related to a 9% (1.04, 1.13; I2 = 42.0%) and 12% (95% CI 1.08, 1.17; I2 = 14.0%) higher risk of type 2 diabetes respectively. However, for plant protein, a significant U-shaped curve was observed with the most risk reduction at intake of about 6% of energy intake from plant protein intake (Pnonlinearity = 0.001). The results were robust in sensitivity analysis and no publication bias was detected. CONCLUSIONS: These findings indicate that the consumption of protein particularly animal protein may be associated with an increased risk of type 2 diabetes.

Association between breastfeeding and risk of endometrial cancer: a meta-analysis of epidemiological studies.

Epidemiological studies have yielded inconsistent findings on the relationship between breastfeeding and the risk of endometrial cancer. Pertinent studies were identified by searching PubMed, Embase, and Web of Knowledge through February 2015 and by reviewing the reference lists of retrieved articles. Study-specific estimates were pooled using a random-effects model. Dose-response analysis was carried out for every 6-month increase in the duration of breastfeeding in relation to the risk of endometrial cancer. Three prospective and 11 case-control studies were included in this meta-analysis. The pooled estimates for ever compared with never breastfeeding and the longest duration of breastfeeding compared with the shortest were 0.91 [95% confidence interval (CI): 0.75-1.09] and 0.76 (95% CI: 0.59-0.98). The risk of endometrial cancer decreased by 7% for every 6-month increase in the duration of breastfeeding (relative risk: 0.93; 95% CI: 0.88-0.97). This study provides evidence that ever breastfeeding, particularly a longer duration of breastfeeding, is associated with a lower risk of endometrial cancer.

Association between whole grain intake and all-cause mortality: a meta-analysis of cohort studies.

Some observational studies have examined the association between dietary whole grain intake and all-cause mortality, but the results were inconclusive. We therefore conducted a meta-analysis to summarize the evidence from cohort studies regarding the association between whole grain intake and all-cause mortality. Pertinent studies were identified by searching PubMed, Embase and Web of Knowledge, up to February 28, 2016. Study-specific estimates were combined using random-effects models. Eleven prospective cohort studies involving 101,282 deaths and 843,749 participants were included in this meta-analysis. The pooled relative risk of all-cause mortality for the highest category of whole grain intake versus lowest category was 0.82 (95% confidence interval: 0.78, 0.87). There was a 7% reduction in risk associated with each 1 serving/day increase in whole grain intake (relative risk = 0.93; 95% confidence interval: 0.89, 0.97). No publication bias was found. This analysis indicates that higher intake of whole grain is associated with a reduced risk of all-cause mortality. The findings support current recommendations for increasing whole grain consumption to promote health and overall longevity.

Dietary, circulating beta-carotene and risk of all-cause mortality: a meta-analysis from prospective studies.

Observational studies evaluating the relation between dietary or circulating level of beta-carotene and risk of total mortality yielded inconsistent results. We conducted a comprehensive search on publications of PubMed and EMBASE up to 31 March 2016. Random effect models were used to combine the results. Potential publication bias was assessed using Egger's and Begg's test. Seven studies that evaluated dietary beta-carotene intake in relation to overall mortality, indicated that a higher intake of beta-carotene was related to a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.83, 95%CI: 0.78-0.88) with no evidence of heterogeneity between studies (I(2) = 1.0%, P = 0.416). A random-effect analysis comprising seven studies showed high beta-carotene level in serum or plasma was associated with a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.69, 95%CI: 0.59-0.80) with low heterogeneity (I(2) = 37.1%, P = 0.145). No evidence of publication bias was detected by Begg's and Egger's regression tests. In conclusion, dietary or circulating beta-carotene was inversely associated with risk of all-cause mortality. More studies should be conducted to clarify the dose-response relationship between beta-carotene and all-cause mortality.

Risk prediction models for hepatocellular carcinoma in different populations.

Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well.

A concise synthesis of benzimidazoles via the microwave-assisted one-pot batch reaction of amino acids up to a 10-g scale.

An efficient method for the synthesis of aminomethyl benzimidazoles is developed by using a one-pot batch reaction between amino acids and o-phenylenediamines. This reaction proceeds smoothly in an unmodified household microwave oven, even though scale-up is to 10 g. A desirable method for the quick synthesis of benzimidazoles, which are used as a kind of important intermediates in drug synthesis, is provided by the scale-up utilization of amino acid resource.

Incidence trends of urinary bladder and kidney cancers in urban Shanghai, 1973-2005.

OBJECTIVES: We examined the incidence trends of bladder and kidney cancers using a population-based cancer registration data. METHODS: Age-standardized incidence rates were analyzed using data from the Shanghai Cancer Registry during 1973 to 2005. Annual percentage changes and 95% confidence intervals were calculated to evaluate the incidence changes. Age-period-cohort analysis was further implemented to assess the contributions of age, period and cohort effects to the trends using the intrinsic estimator method. RESULTS: In total, 12,676 bladder and 5,811 kidney cancer patients were registered in urban Shanghai. The age-standardized rates of bladder cancer in males increased from 6.39 to 7.66 per 100,000, or 0.62% per year, whereas the rates in females increased from 1.95 to 2.09 per 100,000, or 0.33% per year. For kidney cancer, the age-standardized rates in males increased from 1.20 to 5.64 per 100,000, or 6.98% per year. Similarly in females, the rates increased from 0.85 to 3.33 per 100,000, or 5.93% per year. Age-period-cohort analysis showed increasing curves of age and period effects but generally decreasing cohort effects for bladder and kidney cancers. CONCLUSIONS: Our results show increasing incidence trends of bladder and kidney cancers in Chinese men and women, especially for kidney cancer.