New insights into the effects of hydroxychloroquine in COVID-19

In late 2019 until 2021, the novel coronavirus disease (COVID-19) has become pandemic. This disease is related to severe inflammatory symptoms of the respiratory epithelial cells and the dysfunction of several organs. One of the suggested drugs to reduce the inflammation caused by COVID-19 is hydroxychloroquine. Studies have shown this drug blocks the inflammatory pathway of nuclear factor-kappaB by blocking P21 activated kinase 1. Also, nanoparticle vaccines Poly Lactide-Glycolide) Acid (PLGA) containing hydroxychloroquine are effective in cancer by stimulating CD8T + cells responses. This study assumed that hydroxychloroquine was effective in inhibiting COVID-19 with these mechanisms.Copyright © 2021 Health Biotechnology And Biopharma. All Rights Reserved.

The mechanisms of action of ivermectin against SARS-CoV-2-an extensive review

Considering the urgency of the ongoing COVID-19 pandemic, detection of new mutant strains and potential re-emergence of novel coronaviruses, repurposing of drugs such as ivermectin could be worthy of attention. This review article aims to discuss the probable mechanisms of action of ivermectin against SARS-CoV-2 by summarizing the available literature over the years. A schematic of the key cellular and biomolecular interactions between ivermectin, host cell, and SARS-CoV-2 in COVID-19 pathogenesis and prevention of complications has been proposed.Copyright © 2022 Japan Antibiotics Research Association. All rights reserved.

The Risk of COVID-19 in People Having a Particular Set of Gene

These risk factors of advancing age, male gender and co-existing health conditions like cancer, cardiovascular diseases, diabetes and obesity do not fully explain why some people have no or mild symptoms whereas others have severe symptoms. Genomewide association study (GWAS) identify a 3p21.31 gene cluster as a genetic susceptibility locus in patients with COVID-19 with respiratory failure. They also found a higher risk among persons with blood group A and protective effect for blood group O than among patients with other blood groups. The particular haplotype in a region of chromosome 3 is contributed to modern humans by neandertals. Another Neanderthal haplotype on chromosome 12 is associated with a 22% reduction in relative risk of becoming severely ill with COVID-19. The ApoE e4e4 homozygous genotype was found to increase the risk of severe COVID-19. Change in angiotensin converting enzyme (ACE) 2 gene was also found to be associated with increased risk of COVID-19, cardiovascular and pulmonary conditions. Copyright © 2021, Kathmandu University. All rights reserved.

New insights into the effects of hydroxychloroquine in COVID-19

In late 2019 until 2021, the novel coronavirus disease (COVID-19) has become pandemic. This disease is related to severe inflammatory symptoms of the respiratory epithelial cells and the dysfunction of several organs. One of the suggested drugs to reduce the inflammation caused by COVID-19 is hydroxychloroquine. Studies have shown this drug blocks the inflammatory pathway of nuclear factor-κB by blocking P21 activated kinase 1. Also, nanoparticle vaccines Poly Lactide-Glycolide) Acid (PLGA) containing hydroxychloroquine are effective in cancer by stimulating CD8T + cells responses. This study assumed that hydroxychloroquine was effective in inhibiting COVID-19 with these mechanisms. © 2021 Health Biotechnology And Biopharma. All Rights Reserved.

Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages.

Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1, CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.

Functional assessment of miR­1291 in colon cancer cells.

miR­1291 exerts an anti­tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR­1291 in CRC cells was investigated. It was identified that miR­1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR­1291 induced cell apoptosis. A luciferase reporter assay revealed that miR­1291 directly bound the 3'­untranslated region sequence of doublecortin­like kinase 1 (DCLK1). miR­1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR­1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR­1291 induced CDK inhibitors p21WAF1/CIP1 and p27KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21WAF1/CIP1 and p27KIP1. Intravenous administration of miR­1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD­1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21WAF1/CIP1 and p27KIP1 protein with treatment of miR­1291. Taken together, the results indicated that miR­1291 served an anti­tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR­1291 may be a promising nucleic acid medicine against CRC.

SARS-CoV-2 N Protein Induces Acute Kidney Injury via Smad3-Dependent G1 Cell Cycle Arrest Mechanism.

COVID-19 is infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can cause severe multiple organ injury and death. Kidney is one of major target organs of COVID-19 and acute kidney injury (AKI) is common in critically ill COVID-19 patients. However, mechanisms through which COVID-19 causes AKI remain largely unknown and treatment remains unspecific and ineffective. Here, the authors report that normal kidney-specifically overexpressing SARS-CoV-2 N develops AKI, which worsens in mice under ischemic condition. Mechanistically, it is uncovered that SARS-CoV-2 N-induced AKI is Smad3-dependent as SARS-CoV-2 N protein can interact with Smad3 and enhance TGF-ß/Smad3 signaling to cause tubular epithelial cell death and AKI via the G1 cell cycle arrest mechanism. This is further confirmed in Smad3 knockout mice and cells in which deletion of Smad3 protects against SARS-CoV-2 N protein-induced cell death and AKI in vivo and in vitro. Most significantly, it is also found that targeting Smad3 with a Smad3 pharmacological inhibitor is able to inhibit SARS-CoV-2 N-induced AKI. In conclusion, the authors identify that SARS-CoV-2 N protein is a key mediator for AKI and induces AKI via the Smad3-dependent G1 cell cycle arrest mechanism. Targeting Smad3 may represent as a novel therapy for COVID-19-asscoaited AKI.

Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties.

Artepillin C (ARC), a prenylated derivative of p-coumaric acid, is one of the major phenolic compounds found in Brazilian green propolis (BGP) and its botanical source Baccharis dracunculifolia. Numerous studies on ARC show that its beneficial health effects correlate with the health effects of both BGP and B. dracunculifolia. Its wide range of pharmacological benefits include antioxidant, antimicrobial, anti-inflammatory, anti-diabetic, neuroprotective, gastroprotective, immunomodulatory, and anti-cancer effects. Most studies have focused on anti-oxidation, inflammation, diabetic, and cancers using both in vitro and in vivo approaches. Mechanisms underlying anti-cancer properties of ARC are apoptosis induction, cell cycle arrest, and the inhibition of p21-activated kinase 1 (PAK1), a protein characterized in many human diseases/disorders including COVID-19 infection. Therefore, further pre-clinical and clinical studies with ARC are necessary to explore its potential as intervention for a wide variety of diseases including the recent pandemic coronaviral infection. This review summarizes the comprehensive data on the pharmacological effects of ARC and could be a guideline for its future study and therapeutic usage.