Depinar, a drug that potentially inhibits the binding and entry of COVID-19 into host cells based on computer-aided studies.

BACKGROUND AND PURPOSE: The new coronavirus (Covid-19) has resulted in great global concerns. Due to the mortality of this virus, scientists from all over the world have been trying to employ different strategies to tackle down this concern. This virus enters cells via phagocytosis through binding to the angiotensin-converting enzyme II receptor. After invading the body, it can stay hidden in there for a period of up to 24 days (incubation period). EXPERIMENTAL APPROACH: In this report, by the use of in silico studies we selected several FDA-approved compounds that possess antiviral properties. We chose the viral Spike protein as the target of drug compounds and carried out the screening process for the FDA databank in order to find the most effective ligand. FINDINGS/RESULTS: The results from dock and MD revealed 10 compounds with high affinity to the receptor-binding domain motif of S protein. The best inhibitors were the ingredients of Depinar, which managed to effectively block the interactions between cells and virus. CONCLUSION AND IMPLICATION: The results of this study were approved by in silico studies and due to the lack of time; we did not test the efficiency of these compounds through in vitro and in vivo studies. However, the selected compounds are all FDA approved and some are supplements like vitamin B12 and don't cause any side effects for patients.

Gene Panel Testing in Hereditary Breast Cancer.

BACKGROUND: Breast cancer (BC) is a highly complex, heterogeneous and multifactorial disease and is the most commonly diagnosed cancer and the leading cause of cancer-related mortality in women worldwide. Family history and genetic mutations are important risk factors for BC. While studies in twins have estimated that about 10%-30% of BC are due to hereditary factors, only 4%-5% of them are due to mutations in BRCA1 or BRCA2 genes. Our aim was to investigate the role of other BC genes in familial BC among the Iranian population. METHODS: We selected 61 BC patients who were wild-type for BRCA1 and BRCA2 mutations but who met the criteria for hereditary BC based on the American College of Medical Genetics and Genomics (ACMG) and the National Comprehensive Cancer Network (NCCN) guidelines. We performed targeted sequencing covering the exons of 130 known cancer susceptibility genes based on the Cancer Gene Census list. RESULTS: We found seven mutations in seven known BC susceptibility genes (RAD50, PTEN, TP53, POLH, DKC1, WRN and CHEK2) in seven patients including two pathogenic frameshift variants in RAD50 and WRN genes, four pathogenic missense variants in TP53, PTEN, POLH, and DKC1 genes and a pathogenic splice donor variant in the CHEK2 gene. The presence of all these variants was confirmed by Sanger sequencing and Gap reverse transcription-polymerase chain reaction (RT-PCR) for the splice variant. In silico analysis of all of these variants predicted them to be pathogenic. CONCLUSION: Panel testing of BC patients who met the established criteria for hereditary BC but who were negative for BRCA1/2 mutations provided additional relevant clinical information for approximately 11.5% of the families. Our findings indicate that next generation sequencing (NGS) is a powerful tool to investigative putative mutagenic variants among patients who meet the criteria for hereditary BC, but with negative results on BRCA1/2 testing.

Effect of flavonoids rich extract of Capparis spinosa on inflammatory involved genes in amyloid-beta peptide injected rat model of Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Despite vast ongoing researches focusing on the area, little is known about novel treatments. In this study, we aimed to survey the effects of Capparis spinosa (C. spinosa) extract on amyloid-beta peptide (Aß)-injected rat. METHODS: For this purpose, hydroalcoholic extracts of caper leaf and fruit were prepared. Total phenolic content, DPPH, and FRAP assay were accomplished to determine antioxidant activity of C. spinosa. HPLC analysis was conducted to measure rutin and quercetin content of selected parts of the plant. Higher levels of flavonoids were observed in leaves of the plant. Twelve male Wistar Aß-induced rats were randomly divided in four groups of (1) Aß-/DW+: Sham-operated group (2) Aß+/DW+: Aß-injected group (3) Aß+/RU+: Standard rutin treatment (4) Aß+/CS+: C. spinosa extract treatment. After 6 weeks of oral administration, real-time qPCR were conducted to determine APP, BACE-1, PSEN-1, and PSEN-2 genes expression in the hippocampus of rats. RESULTS: HPLC analysis showed high levels of rutin and quercetin in leaves of Capparis. Rutin was 16939.2 ± 0.01 and quercetin was 908.93 ± 0.01 µg/g fresh weight. In fruit, 1019.52 ± 0.01 rutin and 97.86 ± 0.01 µg/g FW quercetin were measured. Expression of BACE-1, APP, PSEN-1, and PSEN-2 genes in comparison with the control group showed significant down regulation. DISCUSSION: Results of the study demonstrated that C. spinosa has the potential to down regulate inflammation-involved genes in AD, due to its high levels of flavonoids and could be beneficial as a dietary complement in AD patients.

Increase in mRNA Level of Orexin1 and 2 Receptors Following Induction of Experimental Autoimmune Encephalomyelitis in Mice.

Orexin A and B are hypothalamic peptides with a wide variety of effects such as anti-inflammation and neuroprotection. Impaired function of orexin system has been reported in some neurodegenerative diseases like Parkinson, Huntington and Alzheimer. In this study, the mRNA expression levels of some hypothalamic peptides were investigated in C57BL/6 female mice with experimental autoimmune encephalomyelitis (EAE). Animals were randomly divided into two control and EAE groups. EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG) with complete Ferund's adjuvant and pertussis toxin. Twenty-first days following immunization, mice were decapitated to remove the brains. Then, the expression profiles of prepro-orexin, orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) in hypothalamic region were assessed using real-time PCR method. In this study, we found a considerable increase in the mRNA expression of OX1R and OX2R following EAE induction in C57BL/6 mice. Elevation levels of OX1R and OX2R following EAE induction suggest that alteration in orexinergic system may involve in pathogenesis of multiple sclerosis.