The role of S477N mutation in the molecular behavior of SARS-CoV-2 spike protein: An in-silico perspective.

The attachment of SARA-CoV-2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD. Today's computational approaches in biology, especially during the SARS-CoV-2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N-hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein-protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD-ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC-II.

Association between human herpesviruses and multiple sclerosis: A systematic review and meta-analysis.

AIM: The aim of this study was to investigate the prevalence and potential association between infection with different herpes viruses and multiple sclerosis (MS). METHODS: A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, Odds ratio (OR), and corresponding 95% Confidence interval (CI) were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14. RESULTS: One hundred and thirty-four articles (289 datasets) were included in the meta-analysis, 128 (245 datasets) of which were case/control and the rest were cross-sectional. The pooled prevalence of all human herpes viruses among MS patients was 50% (95% CI: 45-55%; I2 = 96.91%). In subgroup analysis, the pooled prevalence of Herpes simplex virus (HSV), Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpes virus 8 (HHV-8) was 32%, 52%, 74%, 41%, 39% 28%, and 28%, respectively. An association was found between infection with human herpes viruses and MS [summary OR 2.07 (95% CI (1.80-2.37); I2 = 80%)]. CONCLUSION: The results of the present study showed that EBV, VZV, and HHV-6 infection are associated with multiple sclerosis and can be considered as potential risk factors for MS. Although the exact molecular mechanism of the role of herpes viruses in the development of MS is still unknown, it seems that molecular mimicry, the release of autoreactive antibodies, and inflammation in the CNS following viral infection can be important factors in the induction of MS.

Global epidemiology of HBV infection among hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Hemodialysis (HD) is a life-saving procedure that purifies the blood in patients with end-stage renal disease (ESRD). Among all major complications, blood-borne diseases like hepatitis B virus (HBV) may be exposed as serious side effects of hemodialysis. A comprehensive review of the global burden of HBV among HD patients has not been written so far. The aim of the current systematic review and meta-analysis was to determine the globally epidemiology of HBV infection among HD patients. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles that investigated the prevalence of HBV among HD patients were searched from the major databases such as EMBASE, PubMed, Web of Science collection, and Scopus. Pooled prevalence with 95% CI and identification of heterogeneity were obtained using the random effects model and Cochran's Q-test, respectively, and quantification was evaluated using the I2 statistics. All statistical analyses were performed by STATA 14.1 statistical software. RESULTS: among 322 datasets (795,623 cases) that included in this study, the pooled prevalence of HBV infection among HD patients was 7.32% (95% CI: 6.53-8.15%; I2 = 97.91%), including 7.57% (95% CI: 6.69-8.48%) for HBsAg and 6.09% (95% CI: 4.05-8.49%) for DNA, respectively. In addition, based on geographic area, the prevalence was 7.44% (95% CI: 6.35-8.61%) in Asia, 4.32% (95% CI: 2.21-7.04%) in North America, 7.07% (95% CI: 6.35-8.61%) in Europe, 5.52% (95% CI: 3.60-7.78%) in Africa, 8.45% (95% CI: 5.81-11.78%) in Oceania, and 9.73% (95% CI: 7.11-12.70%) in South America. CONCLUSIONS: Our analysis indicates a relatively high prevalence of HBV infection in HD patients, even in some developed countries. Considering that ESRD patients are not able to properly respond to the vaccination strategies in order to develop an acceptable immunity, vaccination of healthy individuals is highly recommended to arm their bodies for possible immunocompromise conditions in the future. Moreover, donated blood in blood transfusion centers should be checked for possible hepatitis B virus infection using sensitive molecular tests.

Molecular Detection of Pathogens Causing Sexually Transmissible Infections in Patients with Prostate Cancer and Hyperplasia by Quantitative TaqMan Real-Time PCR Assay.

BACKGROUND: Prostate cancer is considered the most prevalent cancer among men. Recent studies suggest that sex-ually transmissible infections (STIs) may be related to prostate carcinogenesis. Therefore, the aim of this study was to investigate whether STI pathogens (Atopobium vaginae (ATO), Neisseria gonorrhoeae (NG), Chlamydia tra-chomatis (CT), Treponema pallidum (TP), Ureaplasma urealyticum (UU), Gardnerella vaginalis (GV), Herpes Sim-plex Virus (HSV), Cytomegalovirus (CMV), Human herpesvirus (HHV), Human papillomavirus (HPV), and Tricho-monas vaginalis (TV)) presence in prostate tissues are associated with the risk of prostate cancer. METHODS: Paraffin-embedded prostate tissues obtained from patients with hyperplasia and prostate cancer were extracted. Determination of infectious microorganisms of interest was done by quantitative TaqMan real-time PCR assay. RESULTS: STI DNA was detected in 53/243 (21.8%) of the prostate tissues samples (ATO 3.7%, UU 2.88%, GV 2.46%, HSV-2 2.05%, CT 2.05%, CMV 1.64%, NG 1.64%, TP 1.64%, HHV-8 1.23%, HPV 1.23%, and TV 1.23%.) The statistical analysis revealed significant correlation between prevalence of Gardnerella vaginalis (GV) and Herpes Simplex Virus (HSV-2) between hyperplasia and cancerous groups (p = 0.02), respectively. CONCLUSIONS: No statistically significant difference was observed in the prevalence of most candidate infectious or-ganisms between hyperplasia and cancerous groups except for GV and HSV-2. It appears that inflammation in the prostate gland is more associated with prostate hyperplasia than prostate cancer. According to the role of in-fectious microorganisms in induction of chronic inflammation, we cannot exclude the importance of these patho-gens in progression of cancer. More studies are required to explore the associations of cancer with different infec-tious organisms.

Human T-cell lymphotropic virus type 1 (HTLV-1) grip on T-cells: investigating the viral tapestry of activation.

INTRODUCTION: Human T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL). This study aims to investigate the mRNA expressions of key proteins correlated to T-cell activation in asymptomatic carriers (ACs) HTLV-1 infected patients, shedding light on early molecular events and T-cell activation following HTLV-1 infection. MATERIAL AND METHODS: The study involved 40 participants, including 20 ACs and 20 healthy subjects. Blood samples were collected, ELISA assessment for screening and confirmation with PCR for Trans-activating transcriptional regulatory protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) of the HTLV-1 were done. mRNA expressions of C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3ß), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1), Protein Tyrosine Phosphatase non-Receptor Type 6 (PTPN6) and Mitogen-Activated Protein Kinase Kinase Kinase-7 (SLP-76) and Mitogen-Activated Protein Kinase14 (MAP3K7 or TAK1) were assayed using RT-qPCR. Statistical analyses were performed using PRISM and SPSS software. RESULTS: While there were no significant upregulation in CSK and PTPN6 in ACs compared to healthy individuals, expression levels of GSK3ß, MAP3K14, PLCG1, SLP-76, and TAK1 were significantly higher in ACs compared to healthy subjects which directly contributes to T-cell activation in the HTLV-1 ACs. CONCLUSION: HTLV-1 infection induces differential mRNA expressions in key proteins associated with T-cell activation. mRNAs related to T-cell activation showed significant upregulation compared to PTPN6 and CSK which contributed to T-cell regulation. Understanding these early molecular events in ACs may provide potential markers for disease progression and identify therapeutic targets for controlling viral replication and mitigating associated diseases. The study contributes novel insights to the limited literature on T-cell activation and HTLV-1 pathogenesis.

Effects of HTLV-1 on leukocyte trafficking and migration in ACs compared to healthy individuals.

Human T-lymphotropic virus type 1 (HTLV-1) is a RNA virus belonging to Retroviridae family and is associated with the development of various diseases, including adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Aside from HAM/TSP, HTLV-1 has been implicated in the development of several disorders that mimic auto-inflammation. T-cell migration is important topic in the context of HTLV-1 associated diseases progression. The primary objective of this case-control study was to assess the relationship between increased mRNA expression in virus migration following HTLV-1 infection. PBMCs from 20 asymptomatic patients and 20 healthy subjects were analyzed using real-time PCR to measure mRNA expression of LFA1, MLCK, RAC1, RAPL, ROCK1, VAV1 and CXCR4. Also, mRNA expression of Tax and HBZ were evaluated. Mean expression of Tax and HBZ in ACs (asymptomatic carriers) was 0.7218 and 0.6517 respectively. The results revealed a noteworthy upregulation of these genes involved in T-cell migration among ACs patients in comparison to healthy individuals. Considering the pivotal role of gene expression alterations associated with the progression into two major diseases (ATLL or HAM/TSP), analyzing the expression of these genes in the ACs group can offer probable potential diagnostic markers and aid in monitoring the condition of ACs.

Poor Sleep Quality and Its Influencing Factors Among Iranian Patients with Esophageal and Gastric Cancer.

Background: Sleep quality is a notable factor of well-being. It also may play a role in the development and progression of chronic diseases and cancers. Therefore, this study was performed to investigate poor sleep quality and its influencing factors among Iranian patients with esophageal and gastric cancer. Methods: In this cross-sectional study, a total of 312 Iranian adult patients who suffered from esophageal and gastric cancers were employed from a gastrointestinal cancer-based cohort study conducted in a referral hospital in Tehran between 2015 and 2018. Persian version of the Pittsburg Sleep Quality Index (PSQI) was used to measure poor sleep quality. Univariate and multiple logistic regression models were applied to determine the related factors to poor sleep quality. Results: Of the participants, 203 (65.06%) were men, and 75.96% had gastric cancer. The mean age was 63.13±12.10 years. The results demonstrated that more than 62% of the patients had poor sleep quality. 148 (62.44%) patients out of 237 patients with gastric cancer had poor-quality sleep. Also, 46 (64.38%) patients out of 237 patients with esophageal cancer had poor-quality sleep. Based on the results of multiple logistic regression models, marital status has a negative association with poor sleep quality (odds ratio [OR]=0.32, P=0.015). In addition, having chronic disease (OR=2.16; P=0.028) and wealth index (OR=3.11, P=0.013; OR=3.81, P=0.003; OR=3.29, P=0.009; OR=3.85, P=0.003 for rich, moderate, poor, and poorest subgroups, respectively) had a positive association with poor sleep quality. Conclusion: The findings showed that about two-thirds of the patients studied were poor sleepers. Also, it was observed that marital status, chronic disease, and wealth index were important factors associated with poor sleep quality.

Illuminating (HTLV-1)-induced adult T-cell leukemia/lymphoma transcriptomic signature: A systems virology approach.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis malignancy of peripheral T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The low survival rates observed in the patients are the result of the lack of sufficient knowledge about the disease pathogenesis. METHODS: In the present study, we first identified differentially expressed genes in ATLL patients and the cellular signaling pathways affected by them. Then, genes of these pathways were subjected to more comprehensive evaluations, including WGCNA and module validation studies on five external datasets. Finally, potential biomarkers were selected for qRT-PCR validation. RESULTS: Thirteen signaling pathways, including Apoptosis, Human T-cell leukemia virus 1 infection, IL-17 signaling pathway, pathways in cancer, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, and seven others were selected for deeper investigations. Results of our in-depth bioinformatics evaluations, highlighted pathways related to regulation of immune responses, T-cell receptor and activation, regulation of cell signaling receptors and messengers, Wnt signaling pathway, and apoptosis as key players in ATLL pathogenesis. MAPK3, PIK3CD, KRAS, NFKB1, TNF, PLCB3, PLCB2, PLCB1, MAPK11, JUN, ITPR1, ADCY1, GNAQ, ADCY3, ADCY4, CHEK1, CCND1, SOS2, BAX, FOS and GNA12 were identified as possible biomarkers. Upregulation of ADCY1 and ADCY3 genes was confirmed via qRT-PCR. CONCLUSIONS: In this study, we performed a deep bioinformatic examination on a limited set of genes with high probabilities of involvement in the pathogenesis of ATLL. Our results highlighted signaling pathways and genes with potential key roles in disease formation and resistance against current treatment strategies. Further studies are required to test the possible benefits of highlighted genes as biomarkers and targets of treatment.

Household Food Insecurity and Associated Factors among Iranian Patients with Esophageal and Gastric Cancers.

Background: Household food insecurity (HFI) which has still been one of the major global public health issues is related to adverse health outcomes in individuals. Therefore, this study aimed to determine the prevalence of HFI and its associated factors in Iranian patients with esophageal and gastric cancers. Methods: The data of this cross-sectional study was obtained from 315 patients with esophageal and gastric cancers who were selected from a gastrointestinal cancer-based cohort study conducted in Firoozgar hospital, in Tehran. Food insecurity (FI) was measured using the Iranian version of the HFI questionnaire that was completed by a trained interviewer. The multivariable logistic regression model was used to determine the independent association of each factor with HFI. A P value lower than 0.05 was considered statistically significant. Results: The mean±SD of participants' age was 63.2±12.6 years and 65.4% were men. Most of the patients (75.8%) suffered from gastric cancer and 24.2% from esophageal cancer. The overall prevalence of FI among participants' households was 35.2%. There was an independent significant association between wealth index (WI) and HFI after the use of the multivariable logistic regression model, in such a way that the odds of FI in the poorest, poor, moderate, and rich patients' households were respectively, 6.41, 5.05, 2.74 and 2.04 times higher compared with the richest households. Conclusion: More than a third of participants' households struggled with FI, which was found to have a higher prevalence in loweconomic households. Therefore, health policymakers should intervene in food-insecure households by developing, establishing, and implementing strategies and control programs to improve affordable food access.

Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL).

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.