Melatonin regulates mitochondrial dynamics and mitophagy: Cardiovascular protection.

Despite extensive progress in the knowledge and understanding of cardiovascular diseases and significant advances in pharmacological treatments and procedural interventions, cardiovascular diseases (CVD) remain the leading cause of death globally. Mitochondrial dynamics refers to the repetitive cycle of fission and fusion of the mitochondrial network. Fission and fusion balance regulate mitochondrial shape and influence physiology, quality and homeostasis. Mitophagy is a process that eliminates aberrant mitochondria. Melatonin (Mel) is a pineal-synthesized hormone with a range of pharmacological properties. Numerous nonclinical trials have demonstrated that Mel provides cardioprotection against ischemia/reperfusion, cardiomyopathies, atherosclerosis and cardiotoxicity. Recently, interest has grown in how mitochondrial dynamics contribute to melatonin cardioprotective effects. This review assesses the literature on the protective effects of Mel against CVD via the regulation of mitochondrial dynamics and mitophagy in both in-vivo and in-vitro studies. The signalling pathways underlying its cardioprotective effects were reviewed. Mel modulated mitochondrial dynamics and mitophagy proteins by upregulation of mitofusin, inhibition of DRP1 and regulation of mitophagy-related proteins. The evidence supports a significant role of Mel in mitochondrial dynamics and mitophagy quality control in CVD.

Melatonin effect on breast and ovarian cancers by targeting the PI3K/Akt/mTOR pathway.

Melatonin, the hormone of the pineal gland, possesses a range of physiological functions, and recently, its anticancer effect has become more apparent. A more thorough understanding of molecular alterations in the components of several signaling pathways as new targets for cancer therapy is needed because of current innate restrictions such as drug toxicity, side effects, and acquired or de novo resistance. The PI3K/Akt/mTOR pathway is overactivated in many solid tumors, such as breast and ovarian cancers. This pathway in normal cells is essential for growth, proliferation, and survival. However, it is an undesirable characteristic in malignant cells. We have reviewed multiple studies about the effect of melatonin on breast and ovarian cancer, focusing on the PI3K/Akt/mTOR pathway. Melatonin exerts its inhibitory effects via several mechanisms. A: Downregulation of downstream or upstream components of the signaling pathway such as phosphatase and tensin homolog (PTEN), phosphatidylinositol (3,4,5)-trisphosphate kinase (PI3K), p-PI3K, Akt, p-Akt, mammalian target of rapamycin (mTOR), and mTOR complex1 (mTORC1). B: Apoptosis induction by decreasing MDM2 expression, a downstream target of Akt, and mTOR, which leads to Bad activation in addition to Bcl-XL and p53 inhibition. C: Induction of autophagy in cancer cells via activating ULK1 after mTOR inhibition, resulting in Beclin-1 phosphorylation. Beclin-1 with AMBRA1 and VPS34 promotes PI3K complex I activity and autophagy in cancer cells. The PI3K/Akt/mTOR pathway overlaps with other intracellular signaling pathways and components such as AMP-activated protein kinase (AMPK), Wnt/ß-catenin, mitogen-activated protein kinase (MAPK), and other similar pathways. Cancer therapy can benefit from understanding how these pathways interact and how melatonin affects these pathways.

Variation in Mycobacterium tuberculosis population structure in Iran: a systemic review and meta-analysis.

BACKGROUND: Acquiring comprehensive insight into the dynamics of Mycobacterium tuberculosis (Mtb) population structure is an essential step to adopt effective tuberculosis (TB) control strategies and improve therapeutic methods and vaccines. Accordingly, we performed this systematic review and meta-analysis to determine the overall prevalence of Mtb genotypes/ sublineages in Iran. METHODS: We carried out a comprehensive literature search using the international databases of MEDLINE and Scopus as well as Iranian databases. Articles published until April 2020 were selected based on the PRISMA flow diagram. The overall prevalence of the Mtb genotypes/sublineage in Iran was determined using the random effects or fixed effect model. The metafor R package and MedCalc software were employed for performing this meta-analysis. RESULTS: We identified 34 studies for inclusion in this study, containing 8329 clinical samples. Based on the pooled prevalence of the Mtb genotypes, NEW1 (21.94, 95% CI: 16.41-28.05%), CAS (19.21, 95% CI: 14.95-23.86%), EAI (12.95, 95% CI: 7.58-19.47%), and T (12.16, 95% CI: 9.18-15.50%) were characterized as the dominant circulating genotypes in Iran. West African (L 5/6), Cameroon, TUR and H37Rv were identified as genotypes with the lowest prevalence in Iran (< 2%). The highest pooled prevalence rates of multidrug-resistant strains were related to Beijing (2.52, 95% CI) and CAS (1.21, 95% CI). CONCLUSIONS: This systematic review showed that Mtb populations are genetically diverse in Iran, and further studies are needed to gain a better insight into the national diversity of Mtb populations and their drug resistance pattern.