Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload-induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8-week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α-myosin heavy chain, downregulated the expression level of β-myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator-activated receptor-gamma co-activator-1 beta (PGC-1β) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II-induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC-1β using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC-1β.
Lophomonas blattarum, a rare protozoa, was involved in pulmonary infections of transplant recipients. We report 2 cases of late onset pulmonary L. blattarum infection in renal transplant recipients with normal graft function and relative normal immune function. The diagnosis in both cases was confirmed by bronchoscopy and broncho alveolar lavage (BAL) fluid examination. Both cases were sensitive to metronidazole treatment, but one case did not completely recover during the follow-up. The diagnosis and treatment were discussed to facilitate improvement in the recognition of this rare infection, especially in transplant recipients.
We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.
Aims/IntroductionThere is still no obvious evidence proving that androgen deprivation therapy (ADT) would increase the risk of diabetes. To determine if ADT is associated with diabetes in men with prostate cancer, we carried out the present study.Materials and MethodsWe systematically searched Medline, Embase and the Cochrane Library Central Register through 2014. Studies comparing ADT vs control aimed at treating prostate cancer reporting diabetes as outcome were included. Data were extracted independently by two reviewers. This meta‐analysis was reported based on the Preferred Reporting Items for Systematic reviews and Meta‐Analyses checklist. Observational studies were evaluated through the Meta‐analysis Of Observational Studies in Epidemiology checklist.ResultsEight studies were identified with 65,695 ADT users and 91,893 non‐ADT users. The pooled incidence of diabetes was 39% higher in ADT groups. A significant association was observed in the overall analysis (risk ratio [RR] 1.39, 95% confidence interval [CI] 1.27–1.53; P < 0.001). In subgroup analyses, diabetes was found to be significantly associated with gonadotropin‐releasing hormone (GnRH) alone (RR 1.45, 95% CI 1.36–1.54; P < 0.001), GnRH plus oral antiandrogen (RR 1.40, 95% CI 1.01–1.93; P = 0.04) and orchiectomy (RR 1.34, 95% CI 1.20–1.50; P < 0.001), but not with antiandrogen alone (RR 1.33, 95% CI 0.75–2.36; P = 0.33). Diabetes was strongly related to long duration of ADT (RR 1.43, 95% CI 1.22–1.68; P < 0.001), and was slightly associated with short duration of ADT (RR 1.29, 95% CI 1.12–1.49; P = 0.0004).Conclusions
ADT, especially long duration (>6 months) of this treatment, GnRH alone, GnRH plus antiandrogen and orchiectomy can increase the incidence of diabetes.
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