Enhancing the Antiviral Potential and Anti-inflammatory Properties of Astragalus membranaceus: A Comprehensive Review.

The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control and treatment of viral diseases are very important due to the evolution of viruses and the emergence of new viruses compared to other pathogens such as fungi and bacteria. Astragalus membranaceus (AM) is a significant medicinal plant. The potential use of this plant and its chemical components in the treatment of inflammatory illnesses and viral diseases has been vigorously researched recently. Astragalus polysaccharides (APS) make up the majority of AM's ingredients. The main mechanisms of the antiviral effect of APS have been investigated in some studies. The results of these studies show that APS can exert its antiviral effect by enhancing type I IFN signaling, inhibiting the expression of Bax and Caspase-3 proteins in the apoptosis pathway, and other antiviral mechanisms such as anti-inflammatory activities. The most well-known inflammatory products of APS's antiviral effects are B-cell proliferation, antibody products, nuclear factor-kappa B (NF-κB), and IL(s). Although it has a known effectiveness, there are some limitations to this substance's use as medicine. The use of nanotechnology is removing these limitations and its ability to be used as an anti-virus agent. The purpose of this review is to emphasize the role of AM, especially APS, in controlling inflammatory pathways in the treatment of viral infections. With the emergence of these herbal medications, a new path has been opened in the control and treatment of viral infections.

Evaluation of the prevalence of bovine leukemia virus DNA in peripheral blood mononuclear cells of multiple sclerosis patients.

Multiple sclerosis (MS) is an immune system-mediated neurodegenerative disease. Recent studies suggest that viral agents, especially the Epstein Barr virus (EBV), are etiological agents for MS. The roles of other viruses in MS have been investigated. Studies have shown an increase in the level of antibodies against bovine leukemia virus (BLV) in patients with MS. In this regard, our study aimed to examine the presence of BLV DNA in peripheral blood mononuclear cells (PBMCs) of MS patients in Iran. In this cross-sectional study, the presence of BLV in 109 Iranian MS patients and 60 healthy controls was evaluated. The isolated PBMCs were used for DNA extraction and PCR, using specific primers for two distinct genes. The mean age of the participants was 39 ± 9.5 years, and 27 (24.77%) of them were male. Clinical evaluation of these patients showed the most frequent MS type to be relapsing-remitting MS (RRMS) (71; 65.14%). BLV evaluation did not show any BLV DNA presence in the PBMCs of individuals in either the MS or healthy control groups. Therefore, our study showed no evidence of BLV infection in Iranian MS patients.

The effective factors in human-specific tropism and viral pathogenicity in orthopoxviruses.

The orthopoxvirus (OPV) genus includes several species that infect humans, including variola, monkeypox, vaccinia, and cowpox. Variola and monkeypox are often life-threatening diseases, while vaccinia and cowpox are usually associated with local lesions. The epidemic potential for OPVs may be lower than respiratory-borne viruses or RNA viruses. However, OPVs are notable for their spread and distribution in different environments and among different hosts. The emergence or re-emergence of OPVs in the human population can also occur in wild or domestic animals as intermediate hosts. More effective and safer vaccines for poxvirus can be developed by understanding how immunity is regulated in poxvirus and vaccines for DNA viruses. Downstream events in cells affected by the virus are regulated functionally by a series of characteristics that are affected by host cell interactions and responses of cells against viral infections, including the interferon pathway and apoptosis. Furthermore, infection outcome is greatly influenced by the distinct selection of host-range and immune-modulatory genes that confer the potential for pathogenesis and host-to-host transmission and the distinct host-range properties of each immune-modulatory gene. The present study reviewed the effective factors in human-restricted tropism and virus pathogenicity in OPVs.

Autophagy Modulation and Cancer Combination Therapy: A Smart Approach in Cancer Therapy.

The autophagy pathway is the process whereby cells keep cellular homeostasis and respond to stress via recycling their damaged cellular proteins, organelles, and other cellular components. In the context of cancer, autophagy is a dual-edge sword pro- and anti-tumorigenic role depending on the oncogenic context and stage of tumorigenesis. Cancer cells have a higher dependency on autophagy compared with normal cells because of cellular damages and high demands for energy. The carbon, nitrogen, and molecular oxygen are building blocks for highly proliferative cancer cells which extremely depend on glutaminolysis and aerobic glycolysis; when a cancer cell is restricted to glucose and glutamine, it initiates to activate a stress response pathway using autophagy. Oncogenic tyrosine kinases (OncTKs) and receptor tyrosine kinases (RTKs) activation result in autophagy modulation through activation of the PI3K/AKT/mTORC1 and RAS/MAPK signaling pathways. Targeted inhibition of tyrosine kinases (TKs) and RTKs have recently been considered as cancer therapy but drug resistance and cancer relapse continue to be a major limitation of tyrosine kinase inhibitors (TKIs). Manipulation of autophagy pathway along with TKIs may be a promising strategy to circumvent unknown existing drug-resistance mechanisms that may emerge in a treated patient. In this way, clinical trials are ongoing to modulate autophagy to treat cancer. This review aims to summarize the combination therapy of autophagy affecting compounds with anticancer drugs which target cell signaling pathways, metabolism mechanisms, and epigenetics modification to improve therapeutic efficacy against cancers.

Evaluation of molecular apoptosis signaling pathways and its correlation with EBV viral load in SLE patients using systems biology approach.

BACKGROUND: Considerable evidence supports that SLE could be related to apoptotic cells and EBV infection. OBJECTIVE: The aim of this study was to identify the transcriptional signature of EBV infection in SLE patients for survey of the molecular apoptosis signaling pathways. METHODS: The PBMCs gene expression profiles of healthy control and SLE patients were obtained from GEO. Functional annotation and signaling pathway enrichment were carried out using DAVID, KEGG. To validate bioinformatics analysis the changes in genes expression of some of obtained genes, Real time PCR was performed on PBMCs from 28 SLE patients and 18 controls. RESULTS: We found that mean viral load was 6013 ± 390.1 copy/µg DNA from PBMCs in all patients. QRT-PCR results showed that the expression of the DUSP1 and LAMP3 genes which had most changes in the logFC among 4 candidate genes, increased significantly in comparison with control. The consistent expression of LMP2 as viral latency gene involve in apoptosis signaling pathways was detected in SLE patients with EBV viral load and some controls. CONCLUSIONS: The study indicated that some cellular genes may have an important role in pathogenesis of SLE through apoptosis signaling pathways. Beside, EBV infection as an environmental risk factor for SLE may affect the dysfunction of apoptosis.

Molecular characterization of low pathogenic avian influenza H9N2 virus during co-circulation with newly-emerged highly pathogenic avian influenza H5N8 virus in Iran.

 Identification of molecular characteristics of low pathogenic avian influenza (LPAI) H9N2 virus provides insights into the evolution of this subtype due to the modulation of genomic characteristics in co-circulation with another subtype. The present study aimed to analyze the molecular and phylogenetic characteristics of the current LPAI H9N2 virus in characteristics of internal proteins are crucial for the adaptations of AIVs viruses to a new host. Since H9N2 is indigenous among poultry, continuous monitoring of viral genetic changes is needed for risk assessment of potential transmissibility to human population and emergence of new reassortant virus. domestic poultry during the emergence of new highly pathogenic avian influenza (HPAI) H5N8 virus in Iran. To this end, deep sequencing of LPAI H9N2 virus was performed on Illumina MiSeq sequencing platform and the complete sequences of avian influenza viruses were obtained from GISAID EpiFlu database. Phylogenetic analysis of the surface and internal gene segments showed that the H9N2 2018 virus was closely related to Pakistani H9N2 isolates. HA cleavage site motif sequence of the Iranian isolate was 317KSSR GLF323. The A/chicken/Iran/1/2018 H9N2 strain carried the amino acid substitution (Q216L), which is a mutation correlated with a shift in the affinity of the HA from avian type sialic receptors to human type. Besides surface glycoproteins, molecular. Keywords: A/H9N2; molecular characterization; A/H5N8; co-circulation; A/H5N1; Illumina MiSeq.

First Cases of SARS-CoV-2 in Iran, 2020: Case Series Report.

In Jan 2020, the outbreak of the 2019 novel coronavirus (SARS-CoV-2) in Wuhan, Hubei Province of China spread increasingly to other countries worldwide which WHO declared it as a public health emergency of international concern. Iran was included in the affected countries. Throat swab specimens were collected and tested by using real-time reverse transcription PCR (RT-PCR) kit targeting the E region for screening and RNA dependent RNA polymerase for confirmation. Conventional RT-PCR was conducted for the N region and the PCR products were sequenced by Sanger sequencing. The first seven cases of SARS-CoV-2 infections were identified in Qom, Iran. This report describes the clinical and epidemiological features of the first cases of SARS-CoV-2 confirmed in Iran. Future research should focus on finding the routes of transmission for this virus, including the possibility of transmission from foreign tourists to identify the possible origin of SARS-CoV-2 outbreak in Iran.

Molecular evaluation of HBV core gene mutations in asymptomatic HBV infected blood donors in Iran.

Mutations in the core promoter and precore regions of HBV cause down-regulation of HBeAg. These mutations are associated with chronic hepatitis, cirrhosis and Hepato Cellular Carcinoma (HCC). This study was carried out to sequence analysis of HBV core gene in HBsAg- positive blood donors in Iran. A total of 50 HBsAg- positive blood donor samples were examined in this study. Serological markers of hepatitis B including: HBsAg, HBeAg, HBeAb and HBcAb were measured by ELISA method. HBV-DNA was extracted from the sera, and then PCR was performed on extracted HBV-DNA  using specific primer of gene C. After direct sequencing, the nucleotide sequences from 50 blood donors were analyzed using a reference sequences and then phylogenetic analysis was performed. Also, the line probe assay was used to detect mutations. The majority of donors (62.5%) were in the age group of 29 - 40 years old. Among all the HBV DNA positive cases, 87.8% were HBeAg negative. The prevalence of PC and BCP mutants were 12% and 55% respectively, among asymptomatic HBV infected blood donors by direct sequencing method. The results of this study showed that some of HBV infected blood donors had mutation in core gene of HBV and amino acid changes in B cell, T helper and CTL epitopes that can cause reducing HBe and HBc antigenicity in asymptomatic HBV infected blood donors and the development of escape mutants from host immune.

Correlation between viral load of HBV in chronic hepatitis B patients and precore and Basal core promoter mutations.

BACKGROUND: More than two billion people have been exposed to hepatitis B virus (HBV) worldwide. Furthermore, four hundred million of them are infected with chronic HBV infection. The predominant mutation of the precore region involves a G to A change at nucleotide1896, which creates a premature stop codon at codon 28. Two mutations of A1762T and G1764A are reported as the most prevalent mutations in the basal core promoter (BCP). OBJECTIVES: The purpose of this study was to investigate the relationship between mutations in precore (PC) and basal core promoter regions, and the viral load. PATIENTS AND METHODS: Fifty serum samples from patients with hepatitis B were used. Levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the same time of serological markers of hepatitis B by ELISA. HBV-DNA was extracted from the sera, and then PCR performed on the HBV-DNA extracted with the use of specific primer of gene C. HBV viral load was determined by real-time PCR. The PC/ BCP mutations were determined by applying Line Probe Assay technique. The data were analyzed using SPSS software, version 20. RESULTS: Only 82% of the patients were HBeAb positive and 76% of the patients had basal core/ precore mutations and mean viral load was 3/7 × 106 ± 9/7 × 105 IU/ml. Prevalence of mutations in the precore and basal core promoter regions were 46% and 30%, respectively. CONCLUSIONS: Our data indicated that there is a statistically significant relationship between HBV viral load and mutations in precore region (P < 0.05).