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.

Metformin: new applications for an old drug.

Metformin is a biguanide, evolved as one of the most widely used medicines. The applications of this component include but are not limited to reducing blood glucose, weight loss, and polycystic ovary syndrome. Studies about other probable indications have emerged, indicating that this agent can also be utilized for other purposes. In this review, applications of metformin are noticed based on the current evidence. Metformin commonly is used as an off-label drug in non-alcoholic fatty liver disease (NAFLD), but it worsens inflammation and should not be used for this purpose, according to the latest research. Metformin decreased the risk of death in patients with liver cirrhosis. It is an effective agent in the prevention and improvement of survival in patients suffering hepatocellular carcinoma. There is evidence of the beneficial effects of metformin in colorectal cancer, early-stage prostate cancer, breast cancer, urothelial cancer, blood cancer, melanoma, and bone cancer, suggesting metformin as a potent anti-tumor agent. Metformin shows neuroprotective effects and provides a potential therapeutic benefit for mild cognitive impairment and Alzheimer's disease (AD). It also has been shown to improve mental function and reduce the incidence of dementia. Another condition that metformin has been shown to slow the progression of is Duchenne muscular dystrophy. Regarding infectious diseases, tuberculosis (TB) and coronavirus disease (COVID-19) are among the conditions suggested to be affected by metformin. The beneficial effects of metformin in cardiovascular diseases were also reported in the literature. Concerning renal function, studies showed that daily oral administration of metformin could ameliorate kidney fibrosis and normalize kidney structure and function. This study reviewed the clinical and preclinical evidence about the possible benefits of metformin based on recent studies. Numerous questions like whether these probable indications of metformin can be observed in non-diabetics, need to be described by future basic experiments and clinical studies.

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.

Exosomes carrying immune checkpoints, a promising therapeutic approach in cancer treatment.

Exosomes are a subgroup of extracellular vesicles generated by distinct cells. Tumor-derived extracellular vesicles convey immunological checkpoint molecules. TEXs as critical mediators in tumor development, metastasis, and immune escape have recently become the focus of scientific research. Exosomes are involved in the regulation of the immune system. Exosomes interact with target cells in the tumor microenvironment, changing their function based on the cargo they contain. Exosomal immune checkpoints might be exploited to track tumor immune evasion, treatment response, and patient prognosis while enhancing tumor cell proliferation and spread. This review focuses on tumor-derived exosomes, their immunosuppressive effects in mice models, and their role in cancer immunotherapy. Exosomes are being studied as possible cancer vaccines, with numerous uses in tumor immunotherapy. Exosomes can carry chemotherapeutics, siRNA, and monoclonal antibodies. Exosomes produced by macrophages might be used to treat cancer. These and other clinical consequences provide new doors for cancer treatment.

Pharmacotherapy of Alzheimer's disease: an overview of systematic reviews.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. In this umbrella systematic review (SR), we summarized the efficacy of different pharmacological interventions in improving cognitive function in patients with AD. METHODS: A systematic search was performed through the PubMed, Scopus, Embase, and Cochrane databases for SRs of studies assessing the efficacy of pharmacological interventions versus placebo in improving cognitive function in AD or mild cognitive impairment due to AD. The risk of bias (RoB) was assessed using the Risk of Bias in SRs (ROBIS) tool. RESULTS: Out of 1748 articles found through the database survey, 33 SR articles were included. These studies assessed effects of immunotherapy, cholinesterase inhibitors (ChEIs), memantine, statins, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetic agents, Cerebrolysin, RAS-targeting antihypertensive drugs (ARBs and ACEIs), psychostimulants, glycogen synthase kinase 3 (GSK-3) inhibitors, melatonin, and herbal medications on cognitive function in AD patients. There was no notable overall RoB in 18 studies (54.5%), the RoB in 14 studies (42.4%) was high, and in one study (3.0%) it was unclear. CONCLUSIONS: The use of ChEIs, including rivastigmine, galantamine, and donepezil, as well as memantine has demonstrated a positive impact on improving cognitive outcomes of AD patients, but no considerable effects were found for immunotherapies. Melatonin, statins, antihypertensive drugs, antidiabetic agents, Cerebrolysin, psychostimulants, and some herbal drugs such as Danggui-Shaoyao-San and Ginkgo biloba seem to be effective in improving cognitive function of AD patients, but the evidence in this regard is limited.

Systematic Review and Meta-analysis of the Most Common Genetic Mutations in Esophageal Squamous Cell Carcinoma.

PURPOSE: Esophageal cancer is the second most common cancer among men and women. There is a need to systematically assess the current evidence to map out the contribution of genetic factors in the development of esophageal squamous cell carcinoma (ESCC). METHODS: A literature search was carried out on published and unpublished studies up to August 2021 in Medline (PubMed), Embase (Ovid), Scopus, Proquest, Web of Science, and Google scholar. Studies that have reported the frequency of genetic mutations in ESCC were included in this study. RESULTS: A total of 1238 titles were retrieved through searches, and finally, 56 articles, including 8114 samples, met our predefined inclusion criteria. Of the included studies, 31 were conducted in China, 12 in Japan, and the remaining were conducted in various nations, including Brazil, Korea, and Iran. Most of our included studies evaluated the TP53 (n = 37 studies) and PIK3CA (n = 30 studies) gene mutations. TP53 (68.6%; 95% CI: 61.6-74.9), CCND1 (39.3%; 95% CI: 26.2-54.1), MDM2 (24.9%; 95% CI: 9.5-51.0), NOTCH1/2/3 (17.9%; 95% CI: 15.0-21.2), KMT2D (17.4%; 95% CI: 12.4-23.8), CDKN2A (15.0%; 95% CI: 8.1-26.1), PIK3CA (13.8%; 95% CI: 10.3-18.1), FAT1 (13.3%; 95% CI: 11.7-15.0), and EGFR (9.9%; 95% CI: 5.6-17.0) were the most common involved genetic factors in developing ESCC. CONCLUSION: This systematic review and meta-analysis revealed that more than 10% of ESCC patients had changes in TP53, CCND1, MDM2, NOTCH1/2/3, KMT2D, CDKN2A, PIK3CA, and FAT1 genes, which can highlight their role in developing ESCC. TP53, CCND1, and MDM2 are the most prevalent, demonstrating 68.6%, 39.3%, and 24.9% of the mutations in ESCC 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.