Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis.

PURPOSE: Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis. MATERIALS AND METHODS: The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry. RESULTS: Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19. CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

The importance of predictors for in-hospital COVID-19 mortality changes over one month.

BACKGROUND: Risk stratification enables care providers to make the proper clinical decision for the management of patients with COVID-19 infection. We aimed to explore changes in the importance of predictors for inpatient mortality of COVID-19 over one month. METHODS: This research was a secondary analysis of data from in-hospital patients with COVID-19 infection. Individuals were admitted to four hospitals, New York, USA. Based on the length of hospital stay, 4370 patients were categorized into three mutually exclusive interval groups, day 1, day 2-7, and day 8-28. We measured changes in the importance of twelve confirmed predictors for mortality over one month, using principal component analysis. RESULTS: On the first day of admission, there was a higher risk for organ dysfunction, particularly in elderly patients. On day 1, serum aspartate aminotransferase and sodium were also associated with an increased risk of mortality, while normal troponin opposes in-hospital death. With time, the importance of high aspartate aminotransferase and sodium concentrations decreases, while the variable quality of high troponin levels increases. Our study suggested the importance of maintaining normal blood pressure early in the management of patients. High serum concentrations of creatinine and C-reactive protein remain poor prognostic factors throughout the 28 days. The association of age with mortality increases with the length of hospital stay. CONCLUSION: The importance of some patients' characteristics changes with the length of hospital stay. This should be considered in developing and deploying predictive models and the management of patients with COVID-19 infection.

The dual role of microRNA (miR)-20b in cancers: Friend or foe?

MicroRNAs, as non-coding transcripts, modulate gene expression through RNA silencing under normal physiological conditions. Their aberrant expression has strongly associated with tumorigenesis and cancer development. MiR-20b is one of the crucial miRNAs that regulate essential biological processes such as cell proliferation, apoptosis, autophagy, and migration. Deregulated levels of miR-20b contribute to the early- and advanced stages of cancer. On the other hand, investigations emphasize the tumor suppressor ability of miR-20b. High-throughput strategies are developed to identify miR-20b potential targets, providing the proper insight into its molecular mechanism of action. Moreover, accumulated results suggest that miR-20b exerts its effects through diverse signaling pathways, including PI3K/AKT/mTOR and ERK axes. Restoration of the altered expression levels of miR-20b induces cell apoptosis and reduces invasion and migration. Further, miR-20b can be used as a biomarker in cancer. The current comprehensive review could lead to a better understanding of the miR-20b in either tumorigenesis or tumor regression that may open new avenues for cancer treatment. Video Abstract.

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.

The progress of genetic engineering in the 1970s brought about a paradigm shift in genome editing technology. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system is a flexible means to target and modify particular DNA sequences in the genome. Several applications of CRISPR/Cas9 are presently being studied in cancer biology and oncology to provide vigorous site-specific gene editing to enhance its biological and clinical uses. CRISPR's flexibility and ease of use have enabled the prompt achievement of almost any preferred alteration with greater efficiency and lower cost than preceding modalities. Also, CRISPR/Cas9 technology has recently been applied to improve the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies and defeat tumor cell resistance to conventional treatments such as chemotherapy and radiotherapy. The current review summarizes the application of CRISPR/Cas9 in cancer therapy. We also discuss the present obstacles and contemplate future possibilities in this context.