Mohammad Amin Manavi
Abstract
Coronavirus disease 2019 (COVID-19) has emerged in Wuhan, China, and because of fast transmission, it has led to its extensive prevalence in almost all countries, which has made it a global crisis. Drug repurposing is considered a fast way to discover new applications of the current drugs. This study ...
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Coronavirus disease 2019 (COVID-19) has emerged in Wuhan, China, and because of fast transmission, it has led to its extensive prevalence in almost all countries, which has made it a global crisis. Drug repurposing is considered a fast way to discover new applications of the current drugs. This study aims to recognize a possible small molecule as a primary protease inhibitor versus the main protease protein of SARS-CoV-2 by computational programs. Virtual screening procedures like using Molegro Virtual Docker, AutoDock Tool, and AutoDock Vina, were done for more than 1600 FDA-approved medicines downloaded from the ZINC database, were employed to characterize new implied molecule inhibitors for the recently published crystal structure of the main protease protein of SARS-CoV-2. Virtual screening results indicated, many drugs including ARBs, cephalosporins, some kinase inhibitors, HMG CoA reductase, and leukotriene receptor antagonist, may inhibit the main protease of SARS-COV-2. Velpatasvir, Molnupiravir, and Ivermectin were selected by virtual screening methods for further studies to find an efficient ligand for the treatment of COVID-19. Due to some other beneficial features, including anti-infectious, anti-inflammatory properties, and ADME profile, they could be a promising drug nominee for repurposing to the treatment of COVID-19. Velpatasvir was selected by some virtual screening methods for further studies to find a suitable ligand for the treatment of COVID-19. Furthermore, more studies need to approve this data and finally clinical trial needs to be done to examine the efficacy of Velpatasvir for the treatment of covid-19 as an anti-viral agent.
Akram Siavoshi; Mahdieh Taghizadeh; Elahe Dookhe; Mehran Piran; Mahsa Saliani; Shahla Mohammad Ganji
Abstract
Epithelial ovarian cancer (EOC), as a challenging disease among women with poor prognosis and unclear molecular pathogenesis, each year is responsible for 140000 deaths globally. Recent progress in the field revealed the importance of proteins as key players of different biological ...
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Epithelial ovarian cancer (EOC), as a challenging disease among women with poor prognosis and unclear molecular pathogenesis, each year is responsible for 140000 deaths globally. Recent progress in the field revealed the importance of proteins as key players of different biological events. Considering the complicated protein interactions, taking a deeper look at protein-protein interactions (PPIs) could be considered as a superior strategy to unravel complex mechanisms encountered with regulatory cell signaling pathways of ovarian cancer. Hence, PPI network analysis was performed on differentially expressed genes (DEGs) of ovarian cancer to discover hub genes which have the potential to be introduced as biomarkers with clinical utility. A PPI network with 600 DEGs was constructed. Network topology analysis determined UBC, FN1, SPP1, ACTB, GAPDH, JUN, and RPL13A, with the highest Degree (K) and betweenness centrality (BC), as shortcuts of the network. KEGG pathway analysis showed that these genes are commonly enriched in ribosome and ECM-receptor interaction pathways. These pivotal hub genes, mainly UBC, FN1, RPL13A, SPP1, and JUN have been reported previously as potential prognostic biomarkers of different types of cancer. However, further experimental molecular studies and computational processes are required to confirm the function and association of the identified hub genes with epithelial ovarian cancer prognosis.
Nima Dehdilani; Mohsen Fathi Najafi; Hesam Dehghani
Abstract
To achieve a reliable and persistent expression, the transgene should be precisely integrated into the genome safe harbor (GSH) loci. Little attention has been paid to find the safe harbor loci of the chicken (Gallus gallus domesticus) genome. Identification and characterization of GSH loci that allow ...
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To achieve a reliable and persistent expression, the transgene should be precisely integrated into the genome safe harbor (GSH) loci. Little attention has been paid to find the safe harbor loci of the chicken (Gallus gallus domesticus) genome. Identification and characterization of GSH loci that allow the persistent and reliable expression of knock-in genes could be a major area of interest within the field of transgenic technology and is central to the development of transgenic livestock. Randomly integrated transgenes might encounter position effects and epigenetic silencing, so unstable phenotypes, as well as unreliable and unpredictable expression of the knock-in transgene could occur. In contrast to random gene insertion, site-specific gene targeting provides a superior strategy that exploits homologous recombination to insert a transgene of interest into a pre-determined locus. In this study, based on bioinformatics, gene expression atlas, and Hi-C analyses, the GSH region was predicted in the chicken genome between DRG1 and EIF4ENIF1 genes. To do so, we introduce a fast and easy-to-use pipeline that allows the prediction of orthologue GSH loci in all organisms, especially chickens. In addition, the procedure to design targeting vectors for targeting these predicted GSH regions is described in detail.
Sepideh sadat Hosseini; Shadi Mehrzad; Halimeh Hassanzadeh; Hamid Reza Bidkhori; Mahdi Mirahmadi; Madjid Momeni-Moghaddam; Fatemeh Sadeghifar; Moein Farshchian
Abstract
Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, ...
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Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, some strategies were proposed to empower their beneficial effects during cell-therapeutic procedures to avoid confusing results. Licensing the cells with chemical compounds could be considered as one of the most applicable methods for induction of anti-inflammatory status in the cells. Human chorionic gonadotropin (hCG) is a pregnancy related hormone which has been shown to be essential for the establishment of a successful pregnancy. HCG supports the implantation of fetus in the maternal endometrium, due to its immunomodulatory effects. Moreover, the regulatory role of hCG has been previously mentioned in case of some autoimmune-based diseases. In the present study, the capacity of this hormone for induction of different immune-encountered genes expression was examined in primary cultures of human adipose tissue derived mesenchymal stem cells (Ad-MSCs). In this regard, Ad-MSCs were exposed to 10 IU of hCG for 72 hours. Molecular studies via quantitative Real-time PCR (qRT-PCR) experiments were performed to detect gene expression modifications based on the application of SYBR Green as the fluorescent dye and in comparison to the RPLP0 as the housekeeping gene. Results confirmed that hCG significantly upregulated TSG-6, TGF-β1, IL-1β and IL-6 expression levels comparing with the control group, while it downregulates COX-2 expression, and had no statistically significant effects on IL-10 andTDO2. In conclusion, priming Ad-MSCs with hCG may enhance the proliferation and immunoregulatory potential of these cells, although it needs further investigations to reveal involved molecular pathways.
Mohsen Mehrvarz; Mohsen Fathi Najafi; Taghi Zahraei Salehi; Behjat Majidi
Abstract
Clostridium perfringens and novyi species are two important toxin-producing pathogens which pose a risk to the livestock health. Epsilon and alpha toxins are major toxins of these two pathogens, respectively. Advances in current vaccine industrialization lead to the utilization ...
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Clostridium perfringens and novyi species are two important toxin-producing pathogens which pose a risk to the livestock health. Epsilon and alpha toxins are major toxins of these two pathogens, respectively. Advances in current vaccine industrialization lead to the utilization of toxin epitopes instead of the whole pathogen/toxoids to produce novel vaccines. In the present study, bioinformatics approaches were applied to design a fused protein containing both toxin fragments of interest with the highest antigenicity score for B-cells. To do so different specialized algorithms including I-TASSER, IEDB, ElliPro, PyDock and CLC Main Workbench were applied. The chimeric protein was successfully cloned, expressed, and purified using an immobilized-metal affinity chromatography for His-tagged proteins. During in vivo experiments on rabbits, the levels of immunization provided by the recombinant protein or native alpha and epsilon toxins were compared based on serological studies. Results indicated that the designed protein was able to stimulate effective immune responses against both alpha and epsilon toxins. This can be used as a proper strategy to design novel peptide-based subunit vaccines. Clostridium perfringens and novyi species are two important toxin-producing pathogens which pose a risk to the livestock health. Epsilon and alpha toxins are major toxins of these two pathogens, respectively. Advances in current vaccine industrialization lead to the utilization of toxin epitopes instead of the whole pathogen/toxoids to produce novel vaccines. In the present study, bioinformatics approaches were applied to design a fused protein containing both toxin fragments of interest with the highest antigenicity score for B-cells. To do so different specialized algorithms including I-TASSER, IEDB, ElliPro, PyDock and CLC Main Workbench were applied. The chimeric protein was successfully cloned, expressed, and purified using an immobilized-metal affinity chromatography for His-tagged proteins. During in vivo experiments on rabbits, the levels of immunization provided by the recombinant protein or native alpha and epsilon toxins were compared based on serological studies. Results indicated that the designed protein was able to stimulate effective immune responses against both alpha and epsilon toxins. This can be used as a proper strategy to design novel peptide-based subunit vaccines.
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