A negative correlation between hsa-miR29a-3p level and HIV-1 viral load in human serum; potentiate criteria for patients screening.

Human Immunodeficiency Virus type-1 (HIV-1) causes persistent and life-threatening infection, leading to progressive disease. MicroRNAs (miRNAs) are regulators of gene expression which can be found in circulating human blood samples. hsa-miR-29a-3p has been identified as a potential regulator of the Negative Regulatory Factor (Nef) gene from the HIV-1 viral genome. In this study, we aimed to compare the serum levels of hsa-miR-29a-3p with HIV-1 viral load in a substantial number of infected individuals. We collected serum samples from a total of 48 participants, including 36 untreated HIV-positive patients, and 12 HIV-negative individuals as a control group, matched for age and sex. The HIV-1 viral load in both the case and control groups was confirmed using qRT-PCR. Subsequent qRT-PCR analysis of circulating hsa-miR-29a-3p levels revealed lower miRNA expression in the groups with higher viral loads. A negative correlation (r = -0.58) was calculated between hsa-miR-29a-3p levels and HIV-1 viral load. These findings suggest that the expression level of hsa-miR-29a-3p may serve as an indicator of HIV-1 viral load in human serum samples. Additionally, this miR may hold promise as a potential tool for enhancing HIV-1 treatment strategies.

Exploring the correlation between progression of human papillomavirus infection towards carcinogenesis and nutrition.

Human papillomavirus (HPV) is a common sexually transmitted virus that can lead to the development of various types of cancer. While there are vaccines available to prevent HPV infection, there is also growing interest in the role of nutrition in reducing the risk of HPV-related cancers in HPV positive patients. Diet and nutrition play a critical role in maintaining overall health and preventing various diseases. A healthy diet can strengthen the immune system, which is essential for fighting off infections, including HPV infections, and preventing the growth and spread of cancer cells. Therefore, following a healthy diet and maintaining a healthy weight are important components of HPV and cancer prevention. This article explores the current scientific evidence on the relationship between nutrition and HPV, including the impact of specific nutrients, dietary patterns, and supplements on HPV infection toward cancer progression.

Relationship of serum homocysteine and vitamin D with positive, negative, and extrapyramidal symptoms in schizophrenia: a case-control study in Iran.

BACKGROUND: Schizophrenia is a devastating condition characterized by frequent recurrences, cognitive decline, and emotional and functional disabilities. This condition includes positive and negative symptoms and cognitive impairments resistant to drug treatment. According to studies, many biomarkers can affect this disorder. However, there is little information about vitamin D and homocysteine levels in patients with disease complications. We aimed to investigate this relationship in schizophrenia. METHOD: In this case-control study, 33 patients with schizophrenia and 33 healthy individuals were enrolled from Golestan, the north of Iran, in 2021. Blood samples were taken from all participants to assess vitamin D and homocysteine serum levels. In addition, schizophrenic patients completed the Positive And Negative Syndrome Scale (PANSS) and Simpson-Angus Extrapyramidal Side Effects Scale (SAS). Data analysis was performed at a significance level of 0.05 using SPSS 16 software. RESULTS: Of the 66 participants, 66.7% had vitamin D deficiency, and 71.2% had normal homocysteine levels. However, the serum level of vitamin D was lower in schizophrenic patients than in controls (p = 0.035), and serum homocysteine levels were higher in the schizophrenic group than in controls (p < 0.001). Vitamin D levels in patients with schizophrenia were significantly correlated with the overall assessment of extrapyramidal symptoms (r = 0.35, p = 0.04). However, no significant relationship existed between vitamin D and homocysteine levels and PANSS results (p > 0.05). CONCLUSION: Serum levels of vitamin D and homocysteine were significantly lower and higher in schizophrenic patients than in the control group. Improvement of extrapyramidal symptoms in schizophrenic patients had a direct and significant relationship with serum vitamin D.

VDR gene polymorphisms are associated with the increased susceptibility to COVID-19 among iranian population: A case-control study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID-19 in a sample of the Iranian population. This case-control study enrolled 188 hospitalized COVID-19 patients as the case group and 218 suspected COVID-19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction - Fragment Length Polymorphism (PCR-RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID-19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C > T polymorphism showed significant association with a 3.088 fold increased odds of COVID-19 (p < .0001; adjusted OR: 3.088; 95% CI: 1.902-5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID-19 in male and female groups (p = .001; adjusted OR: 3.125; 95% CI: 1.630-5.991 and p = .002; adjusted OR: 3.071; 95% CI: 1.485-6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS-CoV-2-infected patients and controls (p > .05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID-19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS-CoV-2 infection susceptibility.

Characterization of occult hepatitis B infection among Iranian liver transplant recipients.

BACKGROUND: The prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients. METHODS: This study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes. RESULTS: At the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti-HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti-HBc and negative for anti-HBs, anti-HCV, and anti-HDV. HBV-related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution. CONCLUSIONS: The prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.

Socio-demographical Profile of 7285 SARS-Cov-2 Positive Early Cases; Comparison with National Four Epidemic Waves.

Background: Objectives were to investigate aspects of the COVID-19 epidemics via testing the individuals who were referred to Aramesh Medical Laboratory in Tehran and to integrate the molecular results with epidemiological data since the beginning of the epidemic. Methods: In this cross-sectional Study 77528 outpatients were referred to Aramesh Medical laboratory by physicians for the diagnosis of SARS-CoV-2 infection between March 2019 and May 2021. Viral acid nucleic extracted from nasal and throat specimens and subsequently amplified using Reverse Transcriptase Real-Time PCR. Laboratory data including Ct values compared with epidemic peaks of COVID-19 countrywide. Statistical Analysis was done by SPSS 21 Software. Results: 14312 (18.46%) tested positive.36.5% of the positive cases were in the 30 to 39 years old age group. The positive result rate was significantly different based on months, ranging from 6% to 28%, compatible with four recognized epidemic peaks encompassing the end of March through the first week of April (first epidemic peak), from June to July 2020 (second epidemic peak), October until mid of November 2020 (third epidemic wave) followed by the end of April to May 2021 (until the end period of study, in the middle of 4th peak). In 37.8% of cases, the Ct value was between 21 and 28. Two separate trends were seen for Ct ≤ 25 and Ct ≤ 20 for the first and fourth epidemic peaks, respectively. There was an association between the number of total monthly positive results and total deaths in the country, especially with the second to third peaks (in the course of summer 2020) and fourth epidemic peak. Conclusion: It might be useful to consider laboratory admission rates as an indicator for changes in the epidemic level in the country to continue the SARS-CoV-2 surveillance in accordance with public decision-makers.

High prevalence of occult hepatitis B infection (OBI) among healthy children and their parents in Alborz province, Iran; Vertical OBI, myth or truth?

BACKGROUND: Occult hepatitis B infection (OBI) has been described in various clinical settings including after hepatitis B virus (HBV) immunization. The purpose of study was to characterize the prevalence of OBI among immunized children from a subset of general population and the parents of OBI-positive cases. METHODS: Sera of 1200 children from general population who have been previously immunized by HBV vaccine were assayed for anti-HBs. 660 were randomly selected for HBV DNA testing by different polymerase chain reaction (PCR) methods and were analysed by direct sequencing on surface genes. RESULTS: None of participants were positive for HBsAg and anti-HBc. 549 (45.7%) and 651 (54.3%) cases had anti-HBs > 10 mIU/mL (responders) and < 10 mIU/mL (nonresponders) respectively. Of 660 selected specimens, 91 (16%) of children were positive for OBI. 23 (25.2%) and 68 (74.8%) of HBV DNA positive cases were belonged to responders and nonresponders, respectively, showing significant difference (P < .001). The mean levels of anti-HBs in OBI-positive and OBI-negative groups, showed no considerable variations. The mean viral load for OBI-positive cases showed substantial differences between responders and nonresponders (P = .007). Of 49 parents (98 individuals) of OBI-positive children 11 (22%) and 18 (36%) were positive for anti-HBc and anti-HBs respectively. Molecular testing was positive in 32 subjects (16 couples, 32.6%). In total, 6 mothers and 11 fathers were positive for OBI. CONCLUSION: A proportion of OBI-positive vaccinated children could be existed in different populations. This finding could be arisen from vertical HBV transmission or vertical OBI possibly from their parents.

Techniques, perspectives, and challenges of bioactive peptide generation: A comprehensive systematic review.

Due to the digestible refractory and absorbable structures of bioactive peptides (BPs), they could induce notable biological impacts on the living organism. In this regard, the current study was devoted to providing an overview regarding the available methods for BPs generation by the aid of a systematic review conducted on the published articles up to April 2019. In this context, the PubMed and Scopus databases were screened to retrieve the related publications. According to the results, although the characterization of BPs mainly has been performed using enzymatic and microbial in-vitro methods, they cannot be considered as suitable techniques for further stimulation of digestion in the gastrointestinal tract. Therefore, new approaches for both in-vivo and in-silico methods for BPs identification should be developed to overcome the obstacles that belonged to the current methods. The purpose of this review was to compile the recent analytical methods applied for studying various aspects of food-derived biopeptides, and emphasizing generation at in vitro, in vivo, and in silico.

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis.

BACKGROUND: Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. RESULTS: High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). CONCLUSIONS: High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.

Measurement of serum hepatitis B surface antibody levels in Iranian autistic children and evaluation of immunological memory after booster dose injection in comparison with controls.

BACKGROUND: Responsiveness to hepatitis B vaccine among patients with autism spectrum disorders (ASD) has not been evaluated worldwide. We aimed to determine the anti-HBs antibody duration in autistic and healthy children few years after primary vaccination and evaluate their immunological memory against hepatitis B virus (HBV) vaccine with booster dose administration. METHODS: One hundred seven and 147 HBsAg-negative children from ASD and normal population were recruited, respectively. HBV seromarkers (HBc-Ab, HBsAg, and HBs-Ab) were assessed and subsequently, molecular tests were used on all the subjects. A booster dose of vaccine was injected for those who showed low levels (<10 mIU/mL) of anti-HBs and their antibody levels was measured 4 weeks later. RESULTS: The mean ages of ASD and control groups were 7.14 ± 2.42 and 8.68 ± 1.96, respectively. Seven (6.5%) of the ASD group were positive for anti-HBc and one child was positive for occult hepatitis B infection (HBsAg negative, HBV DNA positive). In ASD, 54 (50.4%) and 53 (49.6%) had adequate (>10 mIU/mL) and low anti-HBs levels, respectively. Among control group, 74 (50.4%) and 73 (49.6%) had sufficient and low antibody levels, respectively. After injection of a booster dose for all children with low antibody, 100% of ASD and 92% (59 of 64) of control pupils contained >10 mIU/mL of antibody, respectively. In both the groups, the HBs-Ab titer increased similarly in response to the booster injection (P < 0.05). CONCLUSION: Despite previous investigations regarding immune impairment in individuals with autism, the immune system of these individuals was able to manage the hepatitis B vaccine challenge.

Effect of inulin-type fructans in patients undergoing cancer treatments: A systematic review.

BACKGROUND AND OBJECTIVE: Current studies give us inconsistent results regarding the inulin consumption in cancer patients. The results of to-date studies are summarized in this systematic review. METHODS: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL Science direct, Google scholar, Scopus and Cochrane were searched. Cochrane Collaboration's 'Risk of Bias' tool was used to assess the quality of included articles. RESULTS: Our search yielded 2652 studies after the elimination of duplicates. Three randomized controlled trials (RCTs), reporting results from 197 patients, were eligible for inclusion in the present systematic review. Risk of bias in these studies was assessed as high and moderate. CONCLUSION: The available evidence is inconclusive regarding the effect of inulin and oligofructose on cancer outcomes. Nonetheless, possible inulin positive effects including improved stool consistency after abdomen radiotherapy and increased stool butyrate content which is involved in controlling tumor cells proliferation and apoptosis should not be denied. Further research is needed in this area before strong conclusions can be drawn.

Human T-lymphotropic virus 1 (HTLV-1) pathogenesis: A systems virology study.

The main mechanisms of interaction between Human T-lymphotropic virus type 1 (HTLV-1) and its hosts in the manifestation of the related disease including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the changes in the genes expression toward an asymptomatic or symptomatic states. To this end, the systems virology analysis was performed. Firstly, the differentially expressed genes (DEGs) were taken pairwise among the four sample sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the protein-protein interaction networks were reconstructed utilizing the hub genes. In conclusion, the pathways of cells proliferation and transformation were identified in the ACs state. In addition to immune pathways in ATLL, the inflammation and cancer pathways were discened in both diseases of ATLL and HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help to design the drugs in the future.

Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran.

Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95% credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs.

Evaluation of HTLV-1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP.

Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014-2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN λ3 expression, and PVL using real-time PCR (TaqMan method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN λ3 expression in the HAM/TSP group was significantly higher than in the ACs (P = 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN λ3 in HTLV-1 positive patients. The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN λ3 can be used as pathogenic factors of HTLV-1 infected patients at risk of HAM/TSP manifestation. J. Med. Virol. 89:1102-1107, 2017. © 2016 Wiley Periodicals, Inc.

HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of HBsAg.

BACKGROUND: Occult hepatitis B infection (OBI) is a frequent finding in human immunodeficiency virus (HIV)-infected patients. While several related mutations in the hepatitis B virus (HBV) genome have been reported, their distinct impact on HBsAg synthesis is largely obscure. METHODS: Thirty-one (18%) out of 172 HIV-infected patients, who were selected from HBsAg-negative patients, were positive for HBV-DNA assigned as being OBI-positive. We generated a series of expression constructs of variant HBsAg with "a" determinant amino acid substitutions including P127L, P127T, S136Y, and P127T + S136Y using site-directed mutagenesis. The expression of variant HBsAg was examined by transient transfection in hepatoma cells, followed by HBsAg immunoassay and immunofluorescence stained with specific anti-HBs antibodies. The potential impact of amino acid substitutions at different positions for conformational changes in the HBsAg was investigated using bioinformatics. RESULTS: All variants comprising either single or combined mutations resulted in significantly reduced HBsAg detection in supernatants and in cell lysates of hepatoma cells transfected with the constructs. Moreover, intracellular immunofluorescence staining of cytoblocks showed perinuclear and cytoplasmic fluorescence of HBsAg constructs with significantly diminished fluorescent intensity in comparison to the wild type. Altered protein conformations by predictive models, indicating an impaired detection by the host's immune response as well as by commercial antibody-based test assays. CONCLUSION: Mutations in the "a" determinant region of HBV as often found in OBI remarkably impair the detection of HBsAg from serum and infected cells, emphasizing the relevance of alternative methods such as HBV-DNA quantification for high-risk groups like HIV-infected individuals. J. Med. Virol. 89:246-256, 2017. © 2016 Wiley Periodicals, Inc.

CRF35-AD as the Main Circulating Genotype of Human Immunodeficiency Virus Type 1 Infection in Iran: A Phylogenetic and Demographic-Based Study.

Finding the predominant circulating subtype of human immunodeficiency virus type 1 (HIV-1) and surveying co-infection with other infectious viruses are crucial to making preventive decisions. To this end, 50 Iranian HIV-positive patients made up of 37 men and 13 women were selected. Most of the HIV-positive patients (70%) were intravenous drug users (IDUs), and 48 and 32% of patients were co-infected with HCV and HBV, respectively. The rate of simultaneous infection with HIV, HCV, and HBV was found to be 6%. The p17 region of the gag and the c2-v5 region of the env genes were sequenced and then clustered by phylogenetic analyses. CRF35-AD was specified as the predominant circulating subtype among different high-risk groups. In our survey, most of the patients in the IDU group had co-infections with HCV and HBV. Some possible reasons for the increased transmission risk of HIV in IDUs could be low levels of education, poor hygiene and housing conditions, and limited access to health services.

Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.

Characterization of overt and occult hepatitis B virus infection among HTLV-1 positive healthy carriers in the Northeast of Iran; AN HTLV-I endemic area.

To date, no studies have provided data on hepatitis B virus (HBV) prevalence among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive carriers. This sero- and molecular epidemiology study was performed on patients in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total of 109 sera were collected from HTLV-I positive healthy carriers who were admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and subsequently, real time PCR was carried out on the samples, regardless of the results of the serology. Standard PCR and direct sequencing were applied on positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19 (17.4%) cases that were positive only for anti-HBs, and they had already received HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%) were negative for all HBV serological markers. Only one subject (0.9%) had detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection. The low prevalence of HBsAg, despite the high percentage of anti-HBc positive cases, might be related to the suppression effect of HTLV-I on surface protein expression. The low prevalence of HBV infection among HTLV-I positive healthy carriers from an endemic region, indicates that the epidemiology of HTLV-I and HBV coinfection is related to the endemicity of HBV in that region, rather than HTLV-I endemicity.

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis.

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.

Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study.

Background and Objectives: Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main factors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibility to COVID-19 in a sample of the Iranian population. Materials and Methods: This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was genotyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a significant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P<0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167). Conclusion: SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.