MicroRNA-21: A critical underestimated molecule in diabetic retinopathy.

Diabetes mellitus (DM) has grown in attention in recent years as a result of its debilitating complications and chronic disabilities. Diabetic retinopathy (DR) is a chronic microvascular complication of DM and is considered as the primary reason for blindness in adults. Early diagnosis of diabetes complications along with targeted therapy options are critical in avoiding morbidity and mortality associated with complications of diabetes. miR-21 is an important and widely studied non-coding-RNA (ncRNA) with considerable roles in various pathologic conditions including diabetic complications. miR-21 is one of the most elevated miRNAs in response to hyperglycemia and its role in angiogenesis is a major culprit of a wide range of disorders including DR. The main role of miR-21 in DR pathophysiology is believed to be through regulating angiogenesis in retina. This article aims to outline miR-21 biogenesis and distribution in human body along with discussions about its role in DR pathogenesis and its biomarker value in order to facilitate understanding of the new characteristics of miR-21 in DR management.

Effects of underlying heart failure on outcomes of COVID-19; a systematic review and meta-analysis.

Background: The risk for worse outcomes of COVID-19 (Coronavirus 2019 disease) is higher in patients with cardiac conditions. In this study, we aim to investigate the risks of COVID-19-induced conditions in cases with underlying heart failure. Methods: We systematically searched PubMed, Scopus, Ovid, ProQuest, Web of Science, and the Cochrane library, to collect the English language articles that investigated patients with underlying heart failure who get infected by COVID-19. The second version of comprehensive meta-analysis (CMA.2) software was used to conduct the meta-analysis. Results: From 5997 publications, our eligibility criteria were met by 27 studies. Overall, outcomes investigated in all studies include but are not limited to mortality rate, length of hospitalization, need for Intensive care unit (ICU) admission, need for mechanical ventilation, and major cardiovascular conditions. Regarding mortality heart failure patients were more susceptible to death (OR:2.570, 95%CI: 2.085 to 3.169; p-value:<0.001). Also in heart failure patients, the risk of mechanical ventilation was higher (OR:1.707, 95%CI: 1.113 to 2.617; p-value: 0.014). Conclusion: Pre-existing heart failure is associated with the increased risk of mortality and the need for mechanical ventilation while getting infected with COVID-19. Finding an answer to determine the risk of hospitalization, length of stay, readmission rate, and multiorgan failure is necessary for further development of preventive care and making a plan for providing optimal healthcare facilities for these patients.

Tumor-derived exosomal PD-L1 in progression of cancer and immunotherapy.

Cancer is a gravely important health issue all over the world and has been spreading fast. In recent years immune checkpoint treatment options have been used extensively as a primary line of treatment for different cancer types. PD-1 and its ligand, PD-L1, are members of the immune-checkpoints superfamily. Anti-PD-L1 and anti-PD-1 antibodies have shown efficacy against different cancer types, but fewer than 30% of patients have shown robust therapeutic responses and, therefore, it is hypothesized that exosomal PD-L1 is the mechanism to blame for failure in primary immune checkpoint therapy. The identical membrane topology of exosomal PD-L1 with tumor cell membrane-type provides the possibility to mimic immunosuppressive effects of tumor cell membrane PD-L1. In this review, it is discussed whether exosomal PD-L1 binds to antibodies and hence resistance to immunotherapy will be developed, and targeting exosome biogenesis inhibition can provide a new strategy to overcome tumor resistance to anti-PD-L1 therapy. Diagnostic and prognostic values of exosomal PD-L1 in different cancer types are discussed. Multiple clinical studies conclude that the level of tumor-derived exosomes (TEXs) as a biomarker for diagnosis could distinguish cancer patients from healthy controls. Elevated exosomal PD-L1 levels may be predictive of advanced disease stages, cancer metastasis, lower response to anti-PD-1/PD-L1 therapy, lower overall survival rates, and poor tumor prognosis. These novel findings of TEXs serve as promising therapeutic targets for early diagnosis and prevention of cancer progression.