Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.

BACKGROUND: Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL). METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats. CONCLUSION: VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart. The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging.

Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNß compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNß1a and IFNß1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNß1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNß1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNß1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value = 0.031) while the IFNß1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNß1a group and 30% in the IFNß1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNß1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).