Doxorubicin (DOX) is limited in clinical application because of its cardiotoxicity. Oxidative stress and apoptosis are crucial in DOX-induced cardiac injury. Dimethyl fumarate (DMF) is an FDA-approved oral drug with powerful effects to reduce oxidative stress and apoptosis through the Nrf2 pathway. This study was aimed to determine whether DMF can protect against DOX-induced cardiac injury. We used both neonatal rat cardiomyocytes (NRCMs) in vitro and DOX-induced cardiac toxicity in vivo to explore the effects of DMF. The results showed that DMF significantly improved cell viability and morphology in NRCMs. In addition, DMF alleviated DOX-induced cardiac injury in rats, as evidenced by decreased CK-MB, LDH levels, improved survival rates, cardiac function, and pathological changes. Moreover, DMF significantly inhibited cardiac oxidative stress by reducing MDA levels and increasing GSH, SOD, and GSH-px levels. And DMF also inhibited DOX-induced cardiac apoptosis by modulating Bax, Bcl-2 and cleaved caspase-3 expression. Moreover, DMF exerted its protective effects against DOX by promoting Nrf2 nuclear translocation, which activated its downstream antioxidant gene Hmox1. Silencing of Nrf2 attenuated the protective effects of DMF in NRCMs as manifested by increased intracellular oxidative stress, elevated apoptosis levels, and decreased cell viability. In addition, DMF showed no protective effects on the viability of DOX-treated tumor cells, which suggested that DMF does not interfere with the antitumor effect of DOX in vitro. In conclusion, our data confirmed that DMF alleviated DOX-induced cardiotoxicity by regulating oxidative stress and apoptosis through the Nrf2 pathway. DMF may serve as a new candidate to alleviate DOX-related cardiotoxicity in the future.

BackgroundThe COVID-19 pandemic has led to concerns around its subsequent impact on global health.ObjectiveTo investigate the health-seeking behavior, reflected by ECG utilization patterns, of patients with non-COVID-19 diseases during and after COVID-19 epidemic.MethodsTaking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of medical visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-SARS-CoV-2 (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019).ResultsCompared with the same period during pre-COVID years, the number of medical visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level in post-SARS-CoV-2 period. The number of new COVID-19 cases announced on a given day significantly correlated negatively with the numbers of medical visits during the following 7 days. Medical visit dynamics differed for various arrhythmias. Whereas medical visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, medical visits for atrial fibrillation did not fall during the lockdown but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period.ConclusionThe ECG utilization patterns of patients with arrhythmias exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Medical visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.