Genotype and phenotype of COVID-19: Their roles in pathogenesis

COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3′-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses. keywords: COVID-19, Genotype, Pathogenesis, Phenotyp

Problems and dilemmas in decision-making in industry, mine & trade organization of West Azerbaijan Province

The decision-making is so important in administration of organization affairs that some authors defined the organization as “decision network” and management as “decision-making action”. In this study that with respect to the objective is an applied and with respect to the method is a survey study, considers the dilemmas and problems of decision-making in Industry, Mine and Trade Organization of West Azerbaijan Province. In order to identify the problems and dilemmas of decision-making, in addition to theoretical studies, the opinions of professors particularly advisors and counseling professors were used, and after identification thereof, a questionnaire including 10 main factors and 39 subfactors were designed as paired comparisons. After approval of questionnaire validity of questionnaire, upon obtaining the comments of professors and experts, 21 questionnaires distributed among skilled deputies and experts of organization. The collected data were analyzed by means of hierarchic analysis technique and prioritized. According to the research results, the elements including applying the personal opinion in decision-making and excessive rely on individual experiences, unwillingness to the future and tendency to early results and unwillingness to making decision are more significant and in fact there factors form the major problems of decision makers in the organization

Problems and dilemmas in decision-making in industry, mine & trade organization of West Azerbaijan Province

The decision-making is so important in administration of organization affairs that some authors defined the organization as “decision network” and management as “decision-making action”. In this study that with respect to the objective is an applied and with respect to the method is a survey study, considers the dilemmas and problems of decision-making in Industry, Mine and Trade Organization of West Azerbaijan Province. In order to identify the problems and dilemmas of decision-making, in addition to theoretical studies, the opinions of professors particularly advisors and counseling professors were used, and after identification thereof, a questionnaire including 10 main factors and 39 subfactors were designed as paired comparisons. After approval of questionnaire validity of questionnaire, upon obtaining the comments of professors and experts, 21 questionnaires distributed among skilled deputies and experts of organization. The collected data were analyzed by means of hierarchic analysis technique and prioritized. According to the research results, the elements including applying the personal opinion in decision-making and excessive rely on individual experiences, unwillingness to the future and tendency to early results and unwillingness to making decision are more significant and in fact there factors form the major problems of decision makers in the organization

Problems and dilemmas in decision-making in industry, mine & trade organization of West Azerbaijan Province

The decision-making is so important in administration of organization affairs that some authors defined the organization as “decision network” and management as “decision-making action”. In this study that with respect to the objective is an applied and with respect to the method is a survey study, considers the dilemmas and problems of decision-making in Industry, Mine and Trade Organization of West Azerbaijan Province. In order to identify the problems and dilemmas of decision-making, in addition to theoretical studies, the opinions of professors particularly advisors and counseling professors were used, and after identification thereof, a questionnaire including 10 main factors and 39 subfactors were designed as paired comparisons. After approval of questionnaire validity of questionnaire, upon obtaining the comments of professors and experts, 21 questionnaires distributed among skilled deputies and experts of organization. The collected data were analyzed by means of hierarchic analysis technique and prioritized. According to the research results, the elements including applying the personal opinion in decision-making and excessive rely on individual experiences, unwillingness to the future and tendency to early results and unwillingness to making decision are more significant and in fact there factors form the major problems of decision makers in the organization

Gene-enhanced personalized regenerative medicine for bone

Regenerative medicine (RM) is a developing multidisciplinary science that uses different principles and methods of other fields or sciences for tissue regeneration, repair or replacement. Gene therapy refers to transferring genes or gene expression regulator factors for the desired purposes. In some cases, gene therapy plays an important role in regenerative medicine by modulating stem cells from different sources. Genetic heterogeneity of individuals can affect the results of gene therapy or other therapies in RM. This is why personal genomics should be considered in RM and is called personalized regenerative medicine (PRM). The purpose of PRM is to employ strategies and methods tailored to the individual’s genetics in order to efficiently reconstruct or substitute various parts of the body. In this study, the strategies and recent advances in bone regeneration such as gene therapy, epigenetic-based therapies, RNA-based therapy and CRISPR/Cas9 system with an attitude to personalized medicine are introduced

Plasma Level Of miR-21 And miR-451 In Primary And Recurrent Breast Cancer Patients.

PURPOSE: MiR-21 and miR-451 are closely associated with tumor initiation, drug resistance, and recurrence of breast cancer (BC). This study was conducted to evaluate the possible value of the plasma level of miR-21 and miR-451 as potential biomarkers for the detection of primary and recurrent BC. PATIENTS AND METHODS: In this descriptive-analytical study, the plasma level of miR-21 and miR-451 was measured in 23 primary BC patients, 24 recurrent (local/distant metastasis) BC patients, and 24 aged-match women as healthy controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, data were analyzed using SPSS software, and the area under the receiver operating characteristic (ROC) curve of miRNAs was measured. RESULTS: The plasma level of miR-21 was significantly increased in both groups of primary (P<0.001) and recurrent (P<0.001) BC patients in comparison with healthy women. However, the plasma level of miR-451 was not significantly changed in primary (P=0.065) and recurrent (P=0.06) BC patients than healthy controls. The elevation of both miR-21 and miR-451 plasma level was not significantly changed in recurrent patients compared with non-recurrent (primary) patients (P=0.481, and P=1, respectively). Based on the ROC analyses, the areas under the curves (AUC) for miR-21 in discriminating primary BC and recurrent BC patients from healthy controls were 0.828 (95% CI: 0.712 to 0.944) and 0.865 (95% CI: 0.756 to 0.974), respectively. CONCLUSION: These data indicating that plasma miR-21 may be useful as a biomarker for the detection of both primary and recurrent BC. However, plasma miR-451 lacks enough sensitivity in the detection of primary and recurrent BC, and more studies are needed in this area

MicroRNA-21 over expression in umbilical cord blood hematopoietic stem progenitor cells by leukemia microvesicles

Microvesicles are able to induce the cell of origin's phenotype in a target cell. MicroRNA-21, as an oncomir, is up-regulated in almost all cancer types such as leukemia which results in cell proliferation. In this study, we examine the ability of leukemia microvesicles to induce proliferation in hematopoietic stem progenitor cells (HSPCs) via microRNA-21 dysregulation. Herein, leukemia microvesicles were isolated from HL-60 and NB-4 cell lines by ultracentrifugation, and then their protein content was measured. Normal HSPCs were isolated from umbilical cord blood samples by a CD-34 antibody. These cells were treated with 20 and 40 μg/mL leukemia microvesicles for 5 and 10 days, respectively. Cell count, CD-34 analysis, and a microRNA-21 gene expression assay were done at days 5 and 10. HSPCs showed a significant increase in both microRNA-21 gene expression and cell count after treating with leukemia microvesicles compared with the control group. CD-34 analysis as stemness proof did not show any difference among the studied groups. This data suggests that HSPC proliferation followed by microRNA-21 gene over expression can be another evidence of a leukemia-like phenotype induction in a healthy target cell by leukemia microvesicles

Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy

Rutin is a unique antioxidant flavonoid that is mainly found in fruit, vegetables, cereals, and many other plant-based human diets. This review aims to highlight the in vitro anticancer properties of rutin including combination therapeutic strategies. Literature resources were gathered through PubMed, Scopus, Web of Science, and Google Scholar databases that cover the period of 1995-2021. Rutin is demonstrated to inhibit the proliferation of breast, colon, lung, and prostate cancers and other tumors. Furthermore, rutin alone or in combination with other therapeutic agents has been shown to regulate several signalling pathways involving the Ras/Raf and PI3K/Akt, MAPK, and TGF-beta 2/Smad2/3Akt/PTEN, etc., which are related to the processes of carcinogenesis and induction of apoptosis. The combination of rutin with other chemotherapy drugs may benefit on prevention of tumor cells by decreasing drug resistance and chemotherapy side effects. Moreover, rutin induces apoptosis synergistically with the therapeutic agent. More in vivo and clinical data are however needed to evaluate the true potential of rutin as an anticancer agent as an adjuvant. The present review highlights the effects of rutin which can be a promising candidate in combination with other antitumor drugs or alone for cancer treatment in vitro. Also, rutin can lead to decrease in drug resistance and chemotherapeutic side effects

LY86, LRG1 and PDE9A genes overexpression in umbilical cord blood hematopoietic stem progenitor cells by acute myeloid leukemia (M3) microvesicles

Background Microvesicles as a new device of cell–cell communication are potentially able to induce some phenotypes and genotypes of an origin cell in a target cell. We evaluate the role of leukemia microvesicles on the leukemia stem cells (LSCs)-specific genes expression in healthy hematopoietic stem progenitor cells (HSPCs). Methods HL-60 and NB-4 cell lines were selected for microvesicles isolation by ultracentrifugation. Healthy HSPCs were obtained by magnetic association cell sorting (MACS) and CD-34 micro-beads from umbilical cord blood samples and then, were treated with 20 and 40 μg/ml leukemia microvesicles for 10 days, respectively. LY86, LRG1 and PDE9A genes expression as LSC specific genes were analyzed by QRT-PCR. Surface CD-34 antigen as stemness marker was measured by flow cytometry technique. Results Healthy HSPCs showed a significant increase in LSC specific genes expression after treatment with both 20 and 40 μg/ml leukemia microvesicles at day 10. All studied groups showed more than 70% surface CD-34 antigen at the last day of experiment which proved HSPCs stemness. Conclusion Our results suggest that healthy HSPCs can be transformed genetically by leukemia microvesicles to over express LSC specific genes. This may be further evidence of leukemia-like transformation by leukemia microvesicles. Keywords: Microvesicles, Hematopoietic stem progenitor cells, Leukemia, Cell communicatio

Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation

Resistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium-chitosan nanoparticles loaded with TMZ on the efficacy of TMZ on the expression of MGMT, E2F6, and RELA genes and the rate of apoptosis in the C6 cell line. Selenium nanoparticles (SNPs) were loaded with TMZ and then they were coated by Eudragit(R) RS100 (Eud) and chitosan (C-S) to prepare Se@TMZ/Eud-Cs. Physicochemical properties were determined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDAX), thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) methods. Se@TMZ/Eud-Cs was evaluated for loading and release of TMZ by spectrophotometric method. Subsequently, SNPs loaded with curcumin (as a fluorophore) were analyzed for in vitro uptake by C6 cells. Cytotoxicity and apoptosis assay were measured by MTT assay and Annexin-PI methods. Finally, real-time PCR was utilized to determine the expression of MGMT, E2F6, and RELA genes. Se@TMZ/Eud-Cs was prepared with an average size of 200 nm as confirmed by the DLS and microscopical methods. Se@TMZ/Eud-Cs presented 82.77 +/- 5.30 loading efficiency with slow and pH-sensitive release kinetics. SNPs loaded with curcumin showed a better uptake performance by C6 cells compared with free curcumin (p-value < 0.01). Coated nanoparticles loaded with TMZ showed higher cytotoxicity, apoptosis (p-value < 0.0001), and down-regulation of MGMT, E2F6, and RELA and lower IC50 value (p-value < 0.0001) than free TMZ and control (p-value < 0.0001) groups. Using Cs as a targeting agent in Se@TMZ/Eud-Cs system improved the possibility for targeted drug delivery to C6 cells. This drug delivery system enhanced the apoptosis rate and decreased the expression of genes related to TMZ resistance. In conclusion, Se@TMZ/Eud-Cs may be an option for the enhancement of TMZ efficiency in GBM treatment