Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.

Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.

Quantitative analysis of Epstein-Barr virus DNA in plasma and stomach biopsies of patients with gastric cancer.

Epstein-Barr virus (EBV) associated gastric carcinoma (EBVaGC) is a subtype of gastric cancer with distinct histological and molecular features. The study aimed to assess the EBV DNA copy number and the prevalence of EBVaGC in gastric cancer samples taken from Iranian patients. The next aim was to assess whether the DNA and microRNAs EBV are present in plasma. EBV load was analyzed in 68 gastric cancer biopsies and compared with the results of EBV-encoded small RNA in situ hybridization (EBER-ISH) test in these patients. After the detection of 6 EBV miRNAs in gastric tissue by stem-loop RT-PCR, plasma samples were evaluated for the viral load and EBV miRNAs. Four gastric cancer cases were EBER -ISH positive (5.8%), with a significantly higher viral load than the remaining cases, 47,781 vs. 1909 copies/µg of tissue DNA. Here, was also found a significant difference in plasma EBV load between EBER-positive and EBER-negative cases. Although EBV miRNAs were detectable in all the EBER-positive tumors, the test did not detect any of these miRNAs among the plasma samples tested. Our data indicate that the prevalence of EBVaGC among Iranian patients with gastric cancer is lower than the global prevalence and although none of the EBV miRNAs were detected in plasma, evaluation of EBV microRNAs in tumor tissue, especially miR-BART7-3p, may constitute useful biomarkers for diagnosis of EBVaGC.

Clinical and molecular aspects of human pegiviruses in the interaction host and infectious agent.

BACKGROUND: Human pegivirus 1 (HPgV-1) is a Positive-sense single-stranded RNA (+ ssRNA) virus, discovered in 1995 as a Flaviviridae member, and the closest human virus linked to HCV. In comparison to HCV, HPgV-1 seems to be lymphotropic and connected to the viral group that infects T and B lymphocytes. HPgV-1 infection is not persuasively correlated to any known human disease; nevertheless, multiple studies have reported a connection between chronic HPgV-1 infection and improved survival in HPgV-1/HIV co-infected patients with a delayed and favorable impact on HIV infection development. While the process has not been thoroughly clarified, different mechanisms for these observations have been proposed. HPgV-1 is categorized into seven genotypes and various subtypes. Infection with HPgV-1 is relatively common globally. It can be transferred parenterally, sexually, and through vertical ways, and thereby its co-infection with HIV and HCV is common. In most cases, the clearance of HPgV-1 from the body can be achieved by developing E2 antibodies after infection. MAIN BODY: In this review, we thoroughly discuss the current knowledge and recent advances in understanding distinct epidemiological, molecular, and clinical aspects of HPgV-1. CONCLUSION: Due to the unique characteristics of the HPgV-1, so advanced research on HPgV-1, particularly in light of HIV co-infection and other diseases, should be conducted to explore the essential mechanisms of HIV clearance and other viruses and thereby suggest novel strategies for viral therapy in the future.

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade.

BACKGROUND: MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. METHODS: For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. RESULTS: A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. CONCLUSION: The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines' low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

Detection and quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus-6 in stomach frozen tissue of chronic gastritis and gastric cancer patients.

Human herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the Epstein-Barr virus (EBV) and gastric cancer (GC) has been established, the role of the viruses in various stomach diseases remains unknown. The frequencies and viral copy number of EBV, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) among 50 gastric cancer tumors and 105 chronic gastritis tissues were measured by quantitative real-time PCR. In the tumor specimens and the adjacent normal tissues EBV was found in 60% and 30.9%, CMV in 14% and 4.7%, and HHV-6 in 18%, and 14.2%, respectively. The detection rate of EBV and CMV was found to be significantly higher in tumor tissues relative to the adjacent normal tissues. Also, in chronic gastritis, the frequency of EBV, CMV, and HHV-6 was 19%, 12.3%, and 15.2%, respectively, compared with 16.4%, 1.1%, and 8.2% in their corresponding normal tissues. Here, the CMV frequency was found to be significantly higher in gastritis tissues relative to the adjacent normal tissues. Furthermore, viral load in both gastric cancer and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between gastric cancer with both EBV and CMV. Meanwhile, analyses revealed a strong association between the EBV, CMV, and HHV-6 viral loads with gastritis (P = 0.0026, P < 0.0001, and P = 0.0405, respectively). Our results suggest that these three viruses might contribute to the induction and development the gastritis and gastric cancer.

A formulated poly (I:C)/CCL21 as an effective mucosal adjuvant for gamma-irradiated influenza vaccine.

BACKGROUND: Several studies on gamma-irradiated influenza A virus (γ-Flu) have revealed its superior efficacy for inducing homologous and heterologous virus-specific immunity. However, many inactivated vaccines, notably in nasal delivery, require adjuvants to increase the quality and magnitude of vaccine responses. METHODS: To illustrate the impacts of co-administration of the gamma-irradiated H1N1 vaccine with poly (I:C) and recombinant murine CCL21, either alone or in combination with each other, as adjuvants on the vaccine potency, mice were inoculated intranasally 3 times at one-week interval with γ-Flu alone or with any of the three adjuvant combinations and then challenged with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific humoral, mucosal, and cell-mediated immunity, as well as cytokine profiles in the spleen (IFN-γ, IL-12, and IL-4), and in the lung homogenates (IL-6 and IL-10) were measured by ELISA. The proliferative response of restimulated splenocytes was also determined by MTT assay. RESULTS: The findings showed that the co-delivery of the γ-Flu vaccine and CCL21 or Poly (I:C) significantly increased the vaccine immunogenicity compared to the non-adjuvanted vaccine, associated with more potent protection following challenge infection. However, the mice given a combination of CCL21 with poly (I:C) had strong antibody- and cell-mediated immunity, which were considerably higher than responses of mice receiving the γ-Flu vaccine with each adjuvant separately. This combination also reduced inflammatory mediator levels (notably IL-10) in lung homogenate samples. CONCLUSIONS: The results indicate that adjuvantation with the CCL21 and poly (I:C) can successfully induce vigorous vaccine-mediated protection, suggesting a robust propensity for CCL21 plus poly (I:C) as a potent mucosal adjuvant.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. METHODS: Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2-∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). RESULTS: While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). CONCLUSIONS: Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Evaluation of the antitumor immune responses of probiotic Bifidobacterium bifidum in human papillomavirus-induced tumor model.

As of present, a number of studies have shown anti-cancer effects of different strains of probiotics, but the precise host immunological mechanisms of these antitumor effects remain unclear. Thus, the aim of current study was to investigate the preventive-therapeutic effects of oral versus intravenous administration of probiotic Bifidobacterium bifidum on immune response and tumor growth of C57BL/6 mice bearing transplanted TC-1 cell of human papillomavirus (HPV)-related tumor, expressing HPV-16 E6/E7 oncogenes. Our major findings are that the intravenous or oral administration of Bifidobacterium bifidum effectively induces antitumor immune responses and inhibits tumor growth in mice. Compared to oral route only, intravenous administration of probiotic Bifidobacterium bifidum into tumor-bearing mice leads to the activation of tumor-specific IL-12 and IFN-γ, lymphocyte proliferation, CD8+ cytolytic responses that control and eradicate tumor growth. These observations meant intravenous administration of probiotics is an effective anticancer approach through modulation of the immune system. The potential of probiotic Bifidobacterium bifidum as an immunomodulator in the treatment of cervical cancer could be further explored.

Association of Interleukin-17 gene polymorphisms with susceptibility to chronic hepatitis B virus infection and clearance in Iranian population.

Hepatitis B virus (HBV) approximately infects 350 million people. Interleukin-17 (IL-17) as a pro-inflammatory cytokine, have been found to modulate the immune system in infectious and inflammatory diseases. Recently, the influence of genetic changes like single nucleotide polymorphisms (SNP) on expression rate and function of cytokine has been widely investigated. This study was performed to determine any possible association between four IL-17 SNPs (rs2397084, rs763780, rs2275913 and rs10484879) and chronic HBV infection. A total of 466 samples were recruited and studied including 199 chronic patients, 172 healthy controls and 95 spontaneous clearance individuals between genotype and allele frequencies. Genomic DNA was extracted from peripheral blood cells and Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) was used to determine the SNPs genotypes. Genotypes frequencies for rs10484879 were 63.8% CC, 31.7% AC, 4.5% AA in chronic group, 54.7% CC, 36.6% AC, 8.7% AA in control and 63.2% CC, 33.7% AC, 5.8% AA in cleared samples. The AC genotype for rs10484879 was significantly associated with a decreased risk of HBV chronicity (Pvalue = 0.031, OR = 2.699, 95%CI: 1.097-6.639). The genotype and allele frequencies of rs2397084, rs763780 and rs2275913 did not show significant difference between chronic HBV patients and healthy controls. Indeed, there is no significant difference between clearance and chronic patient's genotypes in four SNPs. Our results suggest that IL-17A rs10484879 single nucleotide polymorphism genotype is probably associated with susceptibility to HBV chronic infection, while no significant differences in IL-17 rs2397084, rs763780 and rs227591 distribution were found between HBV patients and spontaneous clearance individuals and control participants.

Correction to: Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment.

An amendment to this paper has been published and can be accessed via the original article.

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment.

BACKGROUND: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. METHODS: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). RESULTS: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. CONCLUSIONS: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.

Monitoring of rotavirus in treated wastewater in Tehran with a monthly interval, in 2017-2018.

Rotaviruses are among the major causes of viral acute gastroenteritis in newborns and children younger than 5 years worldwide. The ability of rotaviruses to remain infectious in harsh environments as well as in the wastewater treatment process makes them one of the most prevalent enteric viruses. The current study aimed to determine the presence of rotavirus genomes and to analyze them phylogenetically in secondary treated wastewater (TW) samples. In total, 13 TW samples were collected from September 2017 to August 2018. Viral concentration was carried out using the absorption-elution method, and after RNA extraction and cDNA synthesis, real-time and conventional polymerase chain reaction (PCR) were performed. A phylogenetic tree was drawn using Maximum Likelihood and Tamura 3-parameter using MEGA v.6 software. Rotavirus genomes were detected in 7/13 (53.8%) and 3/13 (23.07%) samples using reverse transcription (RT)-PCR and conventional PCR, respectively. Accordingly, phylogenetic analysis revealed G4P[8], G9P[4], and G9P[8] genotypes among the samples. The presence of rotavirus in secondary TW samples discharged into surface water emphasizes the importance of monitoring and assessing viral contamination in the water sources used for agricultural and recreational purposes.

Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population.

Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections. We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population. METHODS: In this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test. RESULTS: According to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups. Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006). DISCUSSION: Our results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.

Occurrence and molecular characterization of Torque teno virus (TTV) in a wastewater treatment plant in Tehran.

Torque teno virus (TTV) is a single-stranded DNA virus which is predominantly transmitted by the fecal-oral route and may be excreted in the absence of the clinical symptoms. TTV was previously considered a probable cause of hepatitis, but further studies could not strongly connect TTV to any serious health problem. TTV is highly resistant to water and wastewater treatment processes and can be a useful indicator for determining the fecal contamination of water. The purpose of the present study was to assess the prevalence and molecular characterization of TTV in treated wastewater in Tehran. Thirteen effluent samples were collected monthly from the biggest wastewater treatment plant in Tehran, Iran (from September 2017 to August 2018). The presence of the TTV was monitored in the samples by the nested polymerase chain reaction (PCR) method. The TTV genome was found in 76.9% of the samples, and TTV of groups 1 and 3 were determined using phylogenetic analysis. Therefore, treated wastewater can play a key role in the transmission of TTV and the usage of treated wastewater as a source of potable water needs to be carefully controlled.

Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice.

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.

Phylogenetic analysis of hepatitis C virus strains and risk factors associated with infection and viral subtypes among Iranian patients.

Hepatitis C virus (HCV) has infected approximately 170 million people worldwide. While the seroprevalence of anti-HCV antibody among Iranian blood donors is 0.13%, HCV infection is prevalent in 59-80% of Iranian injecting drug users. One hundred seventy-eight anti-HCV positive patients were referred to the Gastroenterology Department at the Taleghani Hospital (Tehran, Iran) between June 2007 and June 2012. Out of 178 samples, 142 were positive for HCV-RNA. HCV subtypes were determined using phylogenetic analysis of the NS5B or 5'UTR/core regions. Of 142 viremic patients, 71 (50%) were infected with HCV subtype 1a, 43 (30.3%) with subtype 3a, 20 (14.1%) with subtype 1b, 3 (2.1%) with subtype 4d, 2 (1.4%) with subtype 4a, 1 (0.7%) with subtype 2b, and 1 (0.7%) with subtype 6a. Interestingly, genetic analysis of a sub-genomic fragment from one patient identified a non-subtypeable HCV genotype-3 strain. There was a significant association between HCV subtype and a history of injecting drug use (P = 0.003). Subtype 3a was predominant among patients with such a history. Injecting drug use was associated with younger age (P < 0.001). HCV subtype was also significantly associated with a history of upper gastrointestinal endoscopy (P = 0.02). Subtype 1a was more frequent among patients with such a history. In addition, history of upper gastrointestinal endoscopy was significantly associated with older age (P = 0.002). In conclusion, while HCV subtype 1a is predominant among infected Iranian individuals, subtype 3a is predominant among Iranian injecting drug users.

Unravelling the diagnostic methodologies for SARS-CoV-2; the Indispensable need for developing point-of-care testing.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic that continues to be a global menace and since its emergence in the late 2019, SARS-CoV-2 has been vigorously spreading throughout the globe putting the whole world into a multidimensional calamity. The suitable diagnosis strategies are on the front line of the battle against preventing the spread of infections. Since the clinical manifestation of COVID-19 is shared between various diseases, detection of the unique impacts of the pathogen on the host along with the diagnosis of the virus itself should be addressed. Employing the most suitable approaches to specifically, sensitively and effectively recognize the infected cases may be a real game changer in controlling the outbreak and the crisis management. In that matter, point-of-care assays (POC) appears to be the potential option, due to sensitivity, specificity, affordable, and availability. Here we brief the most recent findings about the virus, its variants, and the conventional methods that have been used for its detection, along with the POC strategies that have been applied to the virus diagnosis and the developing technologies which can accelerate the diagnosis procedure yet maintain its efficiency.

Possible association between polyomaviruses and gastrointestinal complications: a narrative review.

Polyomaviruses are a group of small, double-stranded DNA viruses that are known to be associated with the development of certain human diseases, but there is evidence that these viruses might be associated with gastrointestinal (GI) cancers. Several polyomaviruses have been identified, such as JC polyomavirus (JCPyV), BK polyomavirus (BKPyV) and recently Merkel cell polyomavirus (MCPyV). Although the direct effects of polyomaviruses on transformation of human cells and cancer development are not clearly recognized, their association with certain human diseases including GI cancers has been proposed through several molecular and epidemiological studies. For example, JCPyV and BKPyV have been linked to colorectal cancer, as there is growing evidence of finding viral genomes in cancerous tissues. Nevertheless, the major role of JCPyV, BKPyV and MCPyV in colorectal cancer progression is still under extensive investigation, and further surveys is required to establish a conclusive cause-and-effect relationship. Understanding the role of these viruses in cancer development has significant implications for diagnosis, treatment, and prevention strategies. It seems that proving a causal link between polyomaviruses and GI cancers might provide a novel path for targeted therapies or design and development of specific therapeutic vaccines. In addition, performing research on the possible link can provide insights into the underlying molecular mechanisms of carcinogenesis, potentially leading to the identification of novel biomarkers. This review focuses on polyomaviruses, in particular a recently discovered polyomavirus, MCPyV, and their possible link with human gastrointestinal disorders.