Combined in silico strategy for repurposing DrugBank entries towards introducing potential anti-SARS-CoV-2 drugs.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from China in December 2019 led to the coronavirus disorder 2019 pandemic, which has affected tens of millions of humans worldwide. Various in silico research via bio-cheminformatics methods were performed to examine the efficiency of a range of repurposed approved drugs with a new role as anti-SARS-CoV-2 drugs. The current study has been performed to screen the approved drugs in the DrugBank database based on a novel bioinformatics/cheminformatics strategy to repurpose available approved drugs towards introducing them as a possible anti-SARS-CoV-2 drug. As a result, 96 approved drugs with the best docking scores passed through several relevant filters were presented as the candidate drugs with potential novel antiviral activities against the SARS-CoV-2 virus.

CRISPR-interceded CHO cell line development approaches.

For industrial production of recombinant protein biopharmaceuticals, Chinese hamster ovary (CHO) cells represent the most widely adopted host cell system, owing to their capacity to produce high-quality biologics with human-like posttranslational modifications. As opposed to random integration, targeted genome editing in genomic safe harbor sites has offered CHO cell line engineering a new perspective, ensuring production consistency in long-term culture and high biotherapeutic expression levels. Corresponding the remarkable advancements in knowledge of CRISPR-Cas systems, the use of CRISPR-Cas technology along with the donor design strategies has been pushed into increasing novel scenarios in cell line engineering, allowing scientists to modify mammalian genomes such as CHO cell line quickly, readily, and efficiently. Depending on the strategies and production requirements, the gene of interest can also be incorporated at single or multiple loci. This review will give a gist of all the most fundamental recent advancements in CHO cell line development, such as different cell line engineering approaches along with donor design strategies for targeted integration of the desired construct into genomic hot spots, which could ultimately lead to the fast-track product development process with consistent, improved product yield and quality.

Nanoimmunoengineering strategies in cancer diagnosis and therapy

Cancer immunotherapy strategies in combination with engineered nanosystems have yielded beneficial results in the treatment of cancer and their application is increasing day by day. The pivotal role of stimuli-responsive nanosystems and nanomedicine-based cancer immunotherapy, as a subsidiary discipline in the field of immunology, cannot be ignored. Today, rapid advances in nanomedicine are used as a platform for exploring new therapeutic applications and modern smart healthcare management strategies. The progress of nanomedicine in cancer treatment has confirmed the findings of immunotherapy in the medical research phase. This study concentrates on approaches connected to the efficacy of nanoimmunoengineering strategies for cancer immunotherapies and their applications. By assessing improved approaches, different aspects of the nanoimmunoengineering strategies for cancer therapies are discussed in this study (AU)

The Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries.

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the mitogen-activated protein kinase (MAPK), plays a critical role in the severity of chronic inflammatory diseases such as diabetes mellitus (DM) and ARDS. The RAGE gene is most expressed in the alveolar epithelial cells (AECs) of the pulmonary system. Several clinical trials are now being conducted to determine the possible association between the levels of soluble isoforms of RAGE (sRAGE and esRAGE) and the severity of the disease in patients with ARDS and acute lung injury (ALI). In the current article, we reviewed the most recent studies on the RAGE/ligands axis and sRAGE/esRAGE levels in acute respiratory illness, with a focus on COVID-19-associated ARDS (CARDS) patients. According to the research conducted so far, sRAGE/esRAGE measurements in patients with CARDS can be used as a powerful chemical indicator among other biomarkers for assessment of early pulmonary involvement. Furthermore, inhibiting RAGE/MAPK and Angiotensin II receptor type 1 (ATR1) in CARDS patients can be a powerful strategy for diminishing cytokine storm and severe respiratory symptoms.

Nanoimmunoengineering strategies in cancer diagnosis and therapy.

Cancer immunotherapy strategies in combination with engineered nanosystems have yielded beneficial results in the treatment of cancer and their application is increasing day by day. The pivotal role of stimuli-responsive nanosystems and nanomedicine-based cancer immunotherapy, as a subsidiary discipline in the field of immunology, cannot be ignored. Today, rapid advances in nanomedicine are used as a platform for exploring new therapeutic applications and modern smart healthcare management strategies. The progress of nanomedicine in cancer treatment has confirmed the findings of immunotherapy in the medical research phase. This study concentrates on approaches connected to the efficacy of nanoimmunoengineering strategies for cancer immunotherapies and their applications. By assessing improved approaches, different aspects of the nanoimmunoengineering strategies for cancer therapies are discussed in this study.

Therapeutic approaches and vaccination in fighting COVID-19 infections: A review.

Coronavirus disease 2019 (COVID-19) is a remarkably contagious and pathogenic viral infection arising from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first appeared in Wuhan, China. For the time being, COVID-19 is not treated with a specific therapy. The Food and Drug Administration (FDA) has approved Remdesivir as the first drug to treat COVID-19. However, many other therapeutic approaches are being investigated as possible treatments for COVID-19. As part of this review, we discussed the development of various drugs, their mechanism of action, and how they might be applied to different cases of COVID-19 patients. Furthermore, this review highlights an update in the emergence of new prophylactic or therapeutic vaccines against COVID-19. In addition to FDA or The World Health Organization (WHO) approved vaccines, we intended to incorporate the latest published data from phase III trials about different COVID-19 vaccines and provide clinical data released on the networks or peer-review journals.

Iran COVID-19 Epidemiology Committee: A Review of Missions, Structures, Achievements, and Challenges.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic in Iran, the control and management of the epidemic were headed by the National Headquarter for the Control of COVID-19 Epidemic through setting up different scientific committees, including the COVID-19 National Epidemiology Committee. The present study reviews the missions, structures, achievements, and challenges of the Epidemiology Committee. STUDY DESIGN: A rapid review . METHODS: All relevant reports, documents, guidelines, published literature, and surveillance data related to the establishment, visions, missions, roles, activities, and outputs of the COVID-19 Epidemiology Committee were critically reviewed in this study. RESULTS: The efforts of the committee's working groups may have impacted improvements in data registration/usage, provincial data quality at provincial levels, and perception of the epidemic situation in the provinces. The committees have also played role in informing the policies in different stages of the epidemic through routine or problem-based data/evidence analyses, epidemic investigations, and mathematical modeling. CONCLUSION: The structure and experience gained by the committee can be used in similar situations within and outside the country. To further improve the impacts of our activities, it is essential to have effective interaction, collaboration, and data flow between the committee and a broad range of organizations within and outside the Ministry of Health and Medical Education.

The Inclusive Review on SARS-CoV-2 Biology, Epidemiology, Diagnosis, and Potential Management Options.

A novel coronavirus member was reported in Wuhan City, Hubei Province, China, at the end of the year 2019. Initially, the infection spread locally, affecting the Wuhan people, and then expanded rapidly throughout the world. On 11 March 2020, the World Health Organization (WHO) proclaimed it a global pandemic. The virus is a new strain most closely related to a bat coronavirus (RaTG13) which was not previously discovered in humans and is now formally known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) is the disease syndrome that the SARS-CoV-2 virus triggers. It is suggested that SARS-CoV-2 can be transmitted through aerosols, direct/indirect contact, and also during medical procedures and specimen handling. The infection is characterized by isolated flu-like symptoms, but there may be specific signs of fever, fatigue, cough, and shortness of breath, as well as the loss of smell and breathing difficulty. Within this report, we tried to review the most current scientific literature published by January 2021 on various aspects of the outbreak, including virus structure, pathogenesis, clinical presentation, epidemiology, diagnostic approaches, potential therapeutics and vaccines, and prospects. We hope this article makes a beneficial impact on public education to better deal with the SARS-CoV-2 crisis and push a step forward in the near term towards its prevention and control.

Upregulation of Pro-inflammatory Cytokine Genes by Parvovirus B19 in Human Bone Marrow Mesenchymal Stem Cells.

Chronic inflammation plays a prominent role in cancer initiation and development. On the other hand, the Inflammation can be established by a number of factors such as viral infections. Parvovirus B19 (B19V) is a pathogen with widespread infection, which infects bone marrow erythroid progenitor cells. It has been shown that B19V can also enter human bone marrow mesenchymal stem cells (BM-MSCs). In this study, we hypothesized that BM-MSCs as the main cellular component of bone marrow niche may be induced to secret pro-inflammatory cytokines after B19V infection. BM-MSCs were cultured up to passage 3. The cells were then subjected to nucleofection to transfer a plasmid containing B19V genome. After 36 h, total RNA was extracted and the expression levels of IL-1ß, IL-6, TNF-α and NF-κB genes were examined using qRT-PCR. Data analysis showed the significant increase in expression levels of all studied genes in the B19V-transfected cells (P < 0.05). Although further researches are required, our findings for the first time suggest the importance of B19V infection to establish an inflammatory microenvironment in the bone marrow and its involvement in inflammation-related diseases. Finally, based on our results, molecular assay to diagnose B19V infection of BM-MSCs prior to stem cell therapy is strongly recommended.

The effect of simultaneous administration of arsenic trioxide and microvesicles derived from human bone marrow mesenchymal stem cells on cell proliferation and apoptosis of acute myeloid leukemia cell line.

Acute Promyelocytic Leukemia is one of the most prevalent forms of leukemia which has been treated with arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Although, ATRA and ATO are broadly accessible and administrated, some adverse side effects have been reported recently. Nowadays, microvesicles (MVs) are considered as a potential therapeutic agent. Their capacity to alter the behavior of the cells is one of the most controversial issues. In this study, we investigated apoptotic effects of MVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) in combination with ATO on NB4 cell line. MVs were isolated by ultra-centrifugation. After 7 days, MTT assay, Annexin-V-fluorescein staining assay and RT-qPCR for BCL-2, KI67, BAX genes expression were performed. The results showed lower cell viability rate, higher apoptosis ratio, higher BAX gene, and lower KI67 and BCL-2 genes' expression in cells exposed to MVs in combination with ATO compared to cells treated with each agent alone and non-treated control. We showed that MVs in combination with ATO had more apoptotic effect on NB4 cell line than each agent alone. MVs in combination with ATO in APL treatment might play an effective therapeutic role with fewer adverse side effects compared to any other agents.

Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat's Hippocampus during Morphine Withdrawal.

INTRODUCTION: Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence. METHODS: In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats' brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile. RESULTS: Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKIIα at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKIIα gene expression on day 14. DISCUSSION: It can be concluded that CaMKIIα gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKIIα in the hippocampus over 14 days of morphine withdrawal.