Dental complications as a potential indicator of Redondovirus infection: a cross-sectional study.

BACKGROUND: Redondoviridae is a newly discovered virus family linked to oral and respiratory conditions in people, while there is still debate about whether it is also coinfected with other respiratory viruses. This study aimed to determine the frequency of Redondovirus (ReDoV) in nasopharyngeal samples and to investigate any possible links to SARS-CoV-2 infections. METHODS: A polymerase chain reaction (PCR) test was conducted on 731 nasopharyngeal samples from individuals referred to medical centers in Tehran, Iran, for SARS-CoV-2 testing to investigate the prevalence of ReDoV. An oral interview was performed to complete information on dental issues and the individuals' demographics, symptoms, and vaccination history. RESULTS: The prevalence of ReDoV was 25.99%, and 15.26% had a coinfection with SARS-CoV-2. No notable correlation was found regarding ReDoVs and SARS-CoV-2 infections (p > 0.05). Women had a higher ReDoV positivity rate of 18.47% compared to men at 7.52% (p = 0.12), and there was no significant correlation between age groups and ReDoV presence. Nonetheless, a significant association was noted between ReDoVs and dental/gum issues (p < 0.0001, OR: 13.0326). A phylogenetic analysis showed that ReDoVs originated from various human-related clusters. CONCLUSIONS: These results highlight the potential for detecting ReDoVs in nasopharyngeal samples of people with gum or dental issues. Additionally, conducting more ReDoV epidemiological research and proposing oral health as a possible marker for ReDoV infections is important.

Epidemiological surveillance of respiratory viral infections in SARS-CoV-2-negative samples during COVID-19 pandemic in Iran.

BACKGROUND: To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran. METHODS: In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records. RESULTS: In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years. CONCLUSION: Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus.

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.

High resolution melting curve analysis for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

Since the emergence of the original Wuhan SARS-CoV-2 strain, several new variants of the virus have emerged. Alpha, Beta, Gamma, Delta and the most recent Omicron variants have been introduced during this pandemic. Several methods including, but not restricted to, allele-specific PCR, ligation with rolling circle amplification and real-time PCR with allele-specific probes are able to detect mutations as low as a single nucleotide polymorphism. High-resolution melting curve analysis is ano-ther technique to assess any mutations in a nucleic acid chain. Confirmed samples with SARS-CoV-2 infection were subjected to variant identification using a de novo-designed HRM assay. In order to select for mutations with the highest effect on Tm of the amplicon, deletion mutations of NSP6 (Del 3675-3677), and S1 (Del 144) were chosen for HRM analysis. HRM analysis for the amplicon of the primer set-1 (NSP6) resulted in Tm differences of -0.39°C, +0.4°C, and -0.6°C between Alpha, Delta, and Omicron variants, respectively, in comparison to the original Wuhan strain. Moreover, HRM analysis of the amplification performed by primer set-2 (S1) led to Tm differences of +0.32°C, -0.26°C, and +0.24°C between Alpha, Delta, and Omicron variants, respectively, in comparison to original Wuhan strain. The test was able to specify each sample to its variant group with more than 90 percent of confidence. The results obtained in this study demonstrate that using a single closed-tube strategy with a HRM-equipped machine, screening new variants of the virus is possible in a fast and reliable way. Keywords: high resolution melting; SARS coronavirus 2; mutation; variant; genotyping.

Human papilloma virus (HPV) and prostate cancer (PCa): The potential role of HPV gene expression and selected cellular MiRNAs in PCa development.

BACKGROUND: Prostate cancer (PCa) is one of the most common and health-threatening cancers in men worldwide. The human papillomavirus (HPV) is considered one of the organisms with the potential to be involved in the progression of this cancer. In the present study, we evaluated the association between the expression levels of HPV genes with the expression of selected cellular miRNAs (miR-19a, miR-21, miR-23b, miR-34a, miR-150-5p, and miR-155) and their targets genes (P53, Rb, c-Myc, TIMP-1, MMP-2, MMP-9, PDCD4, Bcl-2, and Survivin) in PCa tissue samples. METHODS: HPV detection and genotyping were performed on the tissues of 112 PCa patients and 39 healthy individuals. The expression profile of miRNA was evaluated by SYBR Green-based real-time PCR. As well Human Survivin ELISA Kit was utilized to determine the concentrations of Retinoblastoma, P53, survivin, Bcl-2, c-Myc, TIMP-1, MMP-2, MMP-9, and PDCD4 in the prostate tissues. RESULTS: According to our findings, HPV genome was detected in 28.7% (21/73) of PCa tissue specimens and 17.94% (7/39) control samples. There was no significant association between the presence of HPV infection with PCa (OR = 2.01, 95%CI = 0.8-5.68, P = 0.102). We found that mean expression level of miR-19a (3.7 ± 4.3, p-value: 0.0007), and -21 (2.5 ± 2.8, p-value<0.0001) were significantly higher and miR-23b (-2.14 ± 3.08, p-value: 0.003) and -34a (-3.12 ± 3.28, p-value: 0.0001) levels were significantly lower in PCa tissue samples than in control tissue samples. CONCLUSION: Present research indicated that HPV positive PCa has a distinct miRNA profile compared with HPV negative PCa.

Prevalence of SARS-CoV-2 infection in neonates born to mothers or relatives with COVID-19.

BACKGROUND: In December 2019, in Wuhan, China, coronavirus disease 2019 (COVID-19) was emerged due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It seems that children and neonates, similar to adult and elderly individuals, are at risk of SARS-CoV-2 infection. However, adequate data are not available about neonates infected with SARS-CoV-2. METHODS: This study evaluated the presence of SARS-CoV-2 infection in neonates born to mothers or relatives with COVID-19. This cross-sectional study was performed on 25,044 consecutive Iranian participants in Tehran, Iran, from January 2020 to August 2020. Viral ribonucleic acid (RNA) was extracted from 500 µl of the oropharyngeal and nasopharyngeal specimens of the participants. The genomic RNA of SARS-CoV-2 was detected by real-time polymerase chain reaction (PCR) assay. RESULTS: Out of all participants, 98 (0.40%) cases were neonates born to mothers or relatives with SARS-CoV-2 infection. Therefore, the current study was performed on these neonates. Out of 98 studied neonates, 6 (6.1%) cases had positive PCR results for SARS-CoV-2 infection. Moreover, among 98 studied neonates' mothers, 25 (25.5%) cases had positive PCR results for SARS-CoV-2 infection. CONCLUSION: The findings of this study demonstrated that the rate of COVID-19 in neonates born to mothers or relatives with SARS-CoV-2 infection in the Iranian population is about 6.1%.

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.

Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients.

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant higher CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.

High non-adherence rates to secondary prevention by chemical adherence testing in patients with TIA.

INTRODUCTION: Transient ischaemic attack (TIA) clinics are important for secondary prevention of fatal or disabling stroke. Non-adherence to prescribed medications is an important reason for treatment failure but difficult to diagnose. This study ascertained the utility of a novel biochemical tool in the objective biochemical diagnosis of non-adherence. METHODS: One-hundred consecutive urine samples collected from patients attending the TIA clinic, at a tertiary centre, were analysed for presence or absence of prescribed cardiovascular medications using liquid chromatography-mass spectrometry (LC-MS/MS). Patients were classified as adherent or non-adherent, respectively. Demographic and clinical characteristics were compared between the two cohorts. Univariate regression analyses were performed for individual variables and model fitting was undertaken for significant variables. RESULTS: The mean duration of follow-up from the index event was 31 days [standard deviation (SD): 18.9]. The overall rate of non-adherence for at least one medication was 24%. In univariate analysis, the number of comorbidities [3.4 (SD: 1.9) vs. 2.5 (1.9), P = 0.032] and total number of all prescribed medications [6.0 (3.3) vs 4.4 (2.1), P = 0.032] were higher in the non-adherent group. On multivariate analysis, the total number of medications prescribed correlated with increased non-adherence (odds ratio: 1.27, 95% Confidence Intervals: 1.1-1.5, P = 0.01). CONCLUSIONS: LC-MS/MS is a clinically useful tool for the diagnosis of non-adherence. Nearly a quarter of TIA patients were non-adherent to their cardiovascular medications Addressing non-adherence early may reduce the risk of future disabling cardiovascular events.

A systematic review and meta-analysis on the global status of Trichomonas vaginalis virus in Trichomonas vaginalis.

BACKGROUND: The small (4.5-5kbp), double-stranded Trichomonas vaginalis virus (TVV) that inhabits in the T. vaginalis parasite has been potentially associated to parasite virulence or its drug resistance. The aim of present study was to estimate the global and regional status of TVV in T. vaginalis. METHODS: A systematic search was conducted for published articles between January 1990 and December 2020 by using five major databases include PubMed, Embase, Scopus, and Web of Science as well as Google scholar search engine. The random-effect model was applied for pooled prevalence of TVV, geographical distribution, and heterogeneity by comprehensive meta-analysis (V2.2, Bio stat) software. FINDINGS: A total of 28 studies were included for final meta-analysis. The pooled prevalence of TVV was estimated at 47% (95% CI, 39.3-54.8%). With respect to WHO regions, the lowest and highest prevalence rates were reported from South-East Asia 23% (95% CI, 12-41%) and African 66% (95% CI, 25-92%), respectively. Considering the countries, the prevalence was highest in the Brazil 90% (95% CI, 73-97%) and lowest in the South Korea 14% (95% CI, 4-35%). CONCLUSION: The high prevalence of the parasitic virus emphasizes the need to pay attention to the behavior of the parasite, both in terms of clinical symptoms and drug resistance. Moreover, it is suggested that more studies (i.e. in vitro, in vivo, and case-control studies) should be conducted for deep understanding of this coexistence.

Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.

BACKGROUND: The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis. METHODS: In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated. RESULTS: HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens. CONCLUSION: Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.

Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer.

BACKGROUND: This study aimed to evaluate the possible role of human papillomavirus (HPV) and Epstein-Barr virus (EBV) coinfection as an etiological factor for prostate cancer (PCa) development. METHODS: This case-control study was conducted on 67 patients with PCa and 40 control subjects. The expression levels of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantified, using the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assay. RESULTS: The EBV/HPV coinfection was reported in 14.9% of patients in the case group and 7.5% of the control subjects. The high-risk types of HPV, that is, HPV 16 and HPV 18, were responsible for 50 and 30% of HPV/EBV-coinfected PCa cases (n = 10), respectively. No significant relationship was observed between PCa and HPV/EBV coinfection (OR = 2.9, 95% CI: 0.18-45.2, P = 0.31). However, the highest percentage of HPV genome integration was found in the HPV/EBV-coinfected PCa group (8/10; 80%). Also, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS, and RNS), anti-apoptotic mediators (Bcl-2 and survivin), and anti-anoikis factors (Twist and N-cadherin) were significantly higher in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Nevertheless, the tumor-suppressor proteins (p53 and pRb) and E-cadherin (inhibitor of anoikis resistance) showed significant downregulations in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. CONCLUSION: The HPV/EBV coinfection may be an etiological factor for PCa through modulation of cellular behaviors.

Comparison of real-time PCR and nested PCR for toxoplasmosis diagnosis in toxoplasmic retinochoroiditis patients.

BACKGROUNDS: PCR is a proper technique that significantly improves toxoplasmosis diagnosis. However, a more sensitive technique is required. This study compared real-time PCR with nested PCR using B1, SAG-4, and MAG-1 bradyzoite genes to diagnose toxoplasmosis in toxoplasmic retinochoroiditis patients. METHODS: Blood samples were collected from 10 patients with active toxoplasmic chorioretinal lesions and 10 healthy individuals. Blood samples including peripheral blood mononuclear cells (PBMCs), serum and whole blood samples were used for DNA extraction. Serum was also used to detect anti-toxoplasma IgG and IgM antibodies. Nested PCR and real-time PCR were performed using B1, SAG-4, and MAG-1 target genes. RESULTS: Five (50%) out of the 10 patients were tested positive for toxoplasmosis with nested PCR using the PBMC samples. All the five patients tested positive with nested PCR were also tested positive for toxoplasmosis with real-time PCR using the PBMC samples. The real-time PCR results demonstrated that 9(90%) out of the 10 patients were positive based on B1 and the remaining one (10%) was positive only based on MAG-1. In general, of the patients, five (50%) were positive using SAG-4 and three (30%) were positive in term of MAG-1 using PBMCs with real-time PCR. CONCLUSION: It appears that PBMC samples have the best performance as the PCR extraction method and are a good source for toxoplasmosis diagnosis. The use of B22 and B23 target genes due to their high sensitivity and specificity along with bradyzoite genes are recommended for toxoplasmosis diagnosis using PBMC samples with real-time PCR.

The effect of influenza vaccine on severity of COVID-19 infection: An original study from Iran.

Background: The COVID-19 infection is a novel virus that mainly targets the respiratory system via specific receptors without any coronavirus-targeted therapies. Many efforts have been made to prepare specific vaccines for COVID-19 or use of prefabricated vaccines of other similar viruses, especially severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza (flu). We aimed to evaluate the effects of previous flu vaccine injection on severity of incoming COVID-19 infection. Methods: We conducted a large cross-sectional study of 529 hospitalized Iranian COVID patients to evaluate the severity of disease courses in patients with or without previous flu vaccination history using some main factors like length of hospitalization, need for the intensive care unit (ICU) admission and length of stay in the ICU for comparison between COVID-19 infected patients with or without flu vaccination history. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using the Fisher exact and chi-square tests in IBM SPSS Statistics version 22 (SPSS Inc) and P value <0.05 was considered statistically significant. Results: There were no significant differences in the demographic data of patients, disease, and severity-related parameters between the 2 groups. It means that there were not any significant differences between patients with and without history of flu vaccination regarding mean days of hospitalization, percentage of needing to be admitted to the ICU, days being admitted to the ICU (8.44±6.36 vs 7.94±8.57; 17% vs 11.5%; and 1.17±3.09 vs 0.92±3.04, retrospectively) (p=0.883, 0.235, and 0.809, respectively). In the laboratory tests, in comparison between patients with and without history of previous flu vaccination, only lymphocytes count in the vaccine positive group was higher than the vaccine negative group (20.82±11.23 vs 18.04±9.71) (p=0.067) and creatine phosphokinase (CPK) levels were higher in the vaccine negative group (146.57±109.72 vs 214.15±332.06) (p=0.006). Conclusion: We did not find any association between flu vaccination and decrease in disease severity in our patients. It seems that patients with previous history of flu vaccination may experience less laboratory abnormalities in some parameters that could be interpreted in favor of lower overall inflammation; however, this study cannot answer this definitely because of its design. As we collected retrospective data from only alive discharged patients and had no healthy control group, we could not discuss the probable effect of the vaccine on the mortality rate or its probable protective role against the infection. We need more well-designed controlled studies with different populations in different geographic areas to address the controversies.

Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review.

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.

The role of miR-146a in viral infection.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.

Occult HCV and occult HBV coinfection in Iranian human immunodeficiency virus-infected individuals.

The presence of hepatitis C virus (HCV) genome in liver biopsy or peripheral blood mononuclear cell (PBMC) specimens in the absence of detectable HCV-RNA in plasma of the people with or without anti-HCV antibodies has defined as occult HCV infection (OCI), whereas occult hepatitis B virus infection (OBI) is detection of hepatitis B virus (HBV) genome in the absence of traceable hepatitis B surface antigen in the plasma samples of patients. The purpose of this study is to determine the presence of OBI and OCI in human immunodeficiency virus (HIV)-infected individuals. In this cross-sectional research, 190 Iranian HIV-infected individuals were enrolled from September 2015 to February 2019. All participants were tested regarding various serological markers for HCV and HBV infections. Viral RNA and DNA were extracted from plasma and PBMC specimens, and the presence of HCV-RNA in plasma and PBMC samples was tested using reverse transcriptase-nested polymerase chain reaction (PCR), HBV viral load was determined in plasma samples using COBAS TaqMan 48 Kit, and also the presence of the HBV-DNA in PBMC samples was tested by real-time PCR. In this study, the prevalence of OBI and OCI in HIV-infected individuals was 3.1% and 11.4%, respectively. The genotypes of HCV in the patients with OCI were as follows: 57.1% were infected with subtype 3a, 35.7% were infected with subtype 1a, and 7.1% was infected with subtype 1b. It is noteworthy that in this study, two patients (1.1%) had OCI/OBI coinfections. The present study revealed that 1.1% of Iranian HIV-infected individuals had OBI and OCI at the same time. Therefore, it seems that designing prospective surveys to determine the presence of this coinfection in HIV-infected individuals is informative.

Evaluation of CCR5-Δ32 mutation among individuals with high risk behaviors, neonates born to HIV-1 infected mothers, HIV-1 infected individuals, and healthy people in an Iranian population.

One of the important genetic factors related to resistance to HIV-1 infection is the presence of the C-C chemokine receptor type 5 delta 32 (CCR5-Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5-Δ32 mutation among individuals with high-risk behaviors, neonates born to HIV-1-infected mothers in the prevention of mother-to-child transmission (PMTCT) project, HIV-1-infected individuals, and healthy people. The frequency of the CCR5-Δ32 genotype was assessed in a cross-sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV-1-infected mothers in the PMTCT project, 71 people with high-risk behaviors, and 76 HIV-1-infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5-Δ32 heterozygous deletion was detected in five (6.6%) HIV-1-infected individuals, four (4.7%) neonates born to HIV-1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high-risk behaviors whereas the CCR5-Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5-Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV-1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.

The assessment of selected MiRNAs profile in HIV, HBV, HCV, HIV/HCV, HIV/HBV Co-infection and elite controllers for determination of biomarker.

BACKGROUND: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. MATERIALS AND METHODS: The expression level of miRNAs was evaluated in 6 group patients, Elite Controller (EC), HIV, HBV, HCV, HIV-HBV-HIV-HCV, and healthy controls using real-time PCR assays. Also, liver enzymes (ALT and AST) and CD4 T cell count was assessed. RESULTS: After adequate normalization, expression level of miRNAs was determined. The expression level of miR-146 in HIV/HCV co-infected patients was the highest in all groups. The miRNAs expression profile was significantly different in patient groups compared to control and EC. Some miRNA was significantly correlated with viral load and CD4 T cell count. CONCLUSIONS: The involvement of the mentioned miRNAs and correlation of these with viral and cellular parameters can justify the clinical outcome of all patient groups. The differentially expressed miRNA profile in patients suggests that miRNAs can be serve as biomarkers for risk of disease progression and differentiation of infections. Moreover, determining the profiles of miRNAs due to involvement of these in the pathogenesis of infection and manipulating these miRNAs could lead to opening a new gate to infection control.