Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the action and detailed mechanism of pterostilbene on DOX-treated cardiomyocytes. We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 μM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Pterostilbene markedly alleviated the DOX exposure-induced acute myocardial injury. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) in vivo. Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.

Cardiovascular disease (CVD) is a heavy burden on cancer patients worldwide. This study aimed to evaluate the prevalence and influence of cardiovascular risk factors (CVRF) and CVD on the all-cause mortality among Chinese cancer patients. Overall, 13.0% of all cancer patients had at least one type of CVRFs and 5.0% with CVDs. Patients with CVRF or CVD presented more frequently at later stages and received higher percentage of oncotherapy. During 1,782,527 person-years of follow-up, the all-cause mortality in cancer patients with CVDs and with CVRFs was higher compared with those without (182.6/1000, 109.5/1000 and 93.3/1000 person-years, respectively). Cox regression analysis showed that patients with heart failure (HR 1.79, 95% CI 1.61-1.99), myocardial infarction (HR 1.50, 95% CI 1.16-1.95), atrial fibrillation (HR 1.30, 95% CI 1.09-1.53), stroke (HR 1.21, 95% CI 1.11-1.32), hypertension (HR 1.10, 95% CI 1.04-1.16) and diabetes (HR 1.16, 95% CI 1.08-1.24) had increased all-cause mortality, whereas dyslipidemia patients had better prognosis (HR 0.73, 95% CI 0.64-0.83). Stratified by cancer type, the prognostic impact of specific CVRF or CVD varied. We consecutively recruited 710,170 cancer patients between Feb. 1995 and Jun. 2018. A stratified Cox proportional hazards model was used to analyze the effect of comorbidities on the overall survival of patients stratified by cancer type. Cancer patients are vulnerable to comorbidity related to heart and cerebral disease. The influence of comorbidities on prognosis is noticeable and specific both for the type of cancer and comorbidities.

Aging may aggravate the damage and dysfunction of different components of multiorgan and thus increasing multiorgan ischemia/reperfusion (IR) injury. IR injury occurs in many organs and tissues, which is a major cause of morbidity and mortality worldwide. The kinase mammalian target of rapamycin (mTOR), an atypical serine/threonine protein kinase, involves in the pathophysiological process of IR injury. In this review, we first briefly introduce the molecular features of mTOR, the association between mTOR and aging, and especially its role on autophagy. Special focus is placed on the roles of mTOR during ischemic and IR injury. We then clarify the association between mTOR and conditioning phenomena. Following this background, we expand our discussion to potential future directions of research in this area. Collectively, information reviewed herein will serve as a comprehensive reference for the actions of mTOR in IR injury and may be significant for the design of future research and increase the potential of mTOR as a therapeutic target.

The aim of this study was to explore the most updated changing trends of non-rheumatic calcific aortic valve disease (nrCAVD) and reveal possible improvements. We analyzed the age-standardized rates (ASRs) of prevalence, incidence, disability-adjusted life-years (DALYs), and mortality trends of nrCAVD from 1990 to 2019 using data from the Global Burden of Disease (GBD) study 2019. The relations between ASRs and socio-demographic index (SDI) were analyzed with Pearson’s correlation coefficients. Decomposition and frontier analysis were employed to reveal the contribution proportion of influence factors and regions where improvement can be achieved. In 2019, there were 9.40 million (95% uncertainty interval (UI): 8.07 to 10.89 million) individuals with nrCAVD globally. From 1990 to 2019, the prevalence rate of nrCAVD increased by 155.47% (95% IU: 141.66% to 171.7%), with the largest increase observed in the middle SDI region (821.11%, 95% UI: 709.87% to 944.23%). Globally, there were no significant changes in the mortality rate of nrCAVD (0.37%, 95% UI: −8.85% to 7.99%). The global DALYs decreased by 10.97% (95% UI: −17.94% to −3.46%). The population attributable fraction (PAF) of high systolic blood pressure increased in the population aged 15–49 years, while it declined slightly in population aged 50+ years. Population growth was the main contributing factor to the increased DALYs across the globe (74.73%), while aging was the driving force in the high-SDI region (80.27%). The Netherlands, Finland, Luxembourg, Germany, and Norway could reduce DALY rates of nrCAVD using their socio-demographic resources. According to these results, we revealed that the burden of nrCAVD increased markedly from 1990 to 2019 in high-SDI and high-middle-SDI regions. There was a downward trend in the mortality due to nrCAVD since 2013, which is possibly owing to profound advances in transcatheter aortic valve replacement. Some countries may reduce burdens of nrCAVD using their socio-demographic resources.

Background: Atherosclerosis in diabetic patients progresses fast. Evidence on how to choose target vessels of percutaneous coronary interventions (PCIs) in diabetic patients post-coronary artery bypass graft (post-CABG) is insufficient. Methods: One hundred and fifty-seven patients with diabetes and previous CABG, who underwent PCI of either a graft vessel (GV) (n=44) or a native vessel (NV) (n=113) in the National Center for Cardiovascular Disease, China, were studied. In-hospital and long-term clinical outcomes were compared between the groups. Results: Diabetic patients with prior CABG had more PCI to native arteries, but the proportion of grafts PCI increased as time went on. Both groups had similar baseline characteristics. Group GV patients compared with group NV had more totally occluded NVs, less totally occluded grafts and more in-stent restenosis. However, there was no difference in in-hospital mortality and long-term incidence of major adverse cardiac event (MACE), cardiac death, nonfatal myocardial infarction (MI), or revascularization. Multivariate logistic regression analysis showed that PCI success [hazard ratio (HR), 11.488; 95% confidence interval (CI), 1.135–116.303; P<0.05] was independent predictor of MACE. Conclusions: It suggested similar long-term clinical outcomes after PCI in GV or NV in prior CABG patients with diabetes. Thus, the vessel with higher estimated PCI success rate should be prioritized by operators.