The mysterious anelloviruses: investigating its role in human diseases.

Anelloviruses (AVs) that infect the human population are members of the Anelloviridae family. They are widely distributed in human populations worldwide. Torque teno virus (TTV) was the first virus of this family to be identified and is estimated to be found in the serum of 80-90% of the human population. Sometime after the identification of TTV, Torque teno mini virus (TTMV) and Torque teno midi virus (TTMDV) were also identified and classified in this family. Since identifying these viruses, have been detected in various types of biological fluids of the human body, including blood and urine, as well as vital organs such as the liver and kidney. They can be transmitted from person to person through blood transfusions, fecal-oral contact, and possibly sexual intercourse. Recent studies on these newly introduced viruses show that although they are not directly related to human disease, they may be indirectly involved in initiating or exacerbating some human population-related diseases and viral infections. Among these diseases, we can mention various types of cancers, immune system diseases, viral infections, hepatitis, and AIDS. Also, they likely use the microRNAs (miRNAs) they encode to fulfill this cooperative role. Also, in recent years, the role of proliferation and their viral load, especially TTV, has been highlighted to indicate the immune system status of immunocompromised people or people who undergo organ transplants. Here, we review the possible role of these viruses in diseases that target humans and highlight them as important viruses that require further study. This review can provide new insights to researchers.

Enhanced synergistic antiviral effects of thermally expanded graphite and copper oxide nanosheets in the form of a novel nanocomposite against herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) is responsible for a wide range of human infections, including skin and mucosal ulcers, encephalitis, and keratitis. The gold standard for treating HSV-1 infections is acyclovir. However, the use of this drug is associated with several limitations such as toxic reactions and the development of drug-resistant strains. So, there is an urgent need to discover and develop novel and effective agents against this virus. For the first time, this study aimed to investigate the antiviral effects of the Thermally Expanded Graphite (TEG)-copper oxide (CuO) nanocomposite against HSV-1 and compare results with its constituent components. After microwave (MW)-assisted synthesis of TEG and CuO nanosheets as well as MW-CuO/TEG nanocomposite and characterization of all these nanomaterials, an MTT assay was used to determine their cytotoxicity. The quantitative real-time PCR was then used to investigate the effects of these nanomaterials on viral load. Three-hour incubation of HSV-1 with TEG nanosheets (500 µg/mL), MW-CuO nanosheets (15 µg/mL), and MW-CuO/TEG nanocomposite (35 µg/mL) resulted in a decrease in viral load with an inhibition rate of 31.4 %, 49.2 %, and 74.4 %, respectively. The results from the post-treatment assay also showed that TEG nanosheets (600 µg/mL), MW-CuO nanosheets (15 µg/mL), and MW-CuO/TEG nanocomposite (10 µg/mL) led to a remarkable decrease in viral load with an inhibition rate of 56.9 %, 63 %, and 99.9 %, respectively. The combination of TEG and MW-CuO nanosheets together and the formation of a nanocomposite structure display strong synergy in their ability to inhibit HSV-1 infection. MW-CuO/TEG nanocomposites can be considered a suitable candidate for the treatment of HSV-1 infection.

Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency.

Viruses use various strategies and mechanisms to deal with cells and proteins of the immune system that form a barrier against infection. One of these mechanisms is the encoding and production of viral microRNAs (miRNAs), whose function is to regulate the gene expression of the host cell and the virus, thus creating a suitable environment for survival and spreading viral infection. miRNAs are short, single-stranded, non-coding RNA molecules that can regulate the expression of host and viral proteins, and due to their non-immunogenic nature, they are not eliminated by the cells of the immune system. More than half of the viral miRNAs are encoded and produced by Orthoherpesviridae family members. Human cytomegalovirus (HCMV) produces miRNAs that mediate various processes in infected cells to contribute to HCMV pathogenicity, including immune escape, viral latency, and cell apoptosis. Here, we discuss which cellular and viral proteins or cellular pathways and processes these mysterious molecules target to evade immunity and support viral latency in infected cells. We also discuss current evidence that their function of bypassing the host's innate and adaptive immune system is essential for the survival and multiplication of the virus and the spread of HCMV infection.

Human adenoviruses in children with gastroenteritis: a systematic review and meta-analysis.

PURPOSE: Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global epidemiology of these viruses in pediatric gastroenteritis is available. METHODS: A systematic search was conducted to obtain published papers from 2003 to 2023 in three main databases PubMed, Scopus, and Web of Science. RESULTS: The estimated global pooled prevalence of HAdV infection in children with gastroenteritis was 10% (95% CI: 9-11%), with a growing trend after 2010. The highest prevalence was observed in Africa (20%, 95% CI: 14-26%). The prevalence was higher in inpatients (11%; 95% CI: 8-13%) and patients aged 5 years old and younger (9%; 95% CI: 7-10%). However, no significant difference was observed between male and female patients (P = 0.63). The most prevalent species was found to be the species F (57%; 95% CI: 41-72%). The most common HAdVs observed in children with gastroenteritis were types 40/41, 38, and 2. Analysis of case-control studies showed an association between HAdV and gastroenteritis in children (OR: 2.28, 95% CI; 1.51-3.44). CONCLUSION: This study provided valuable insights into the importance of HAdVs in children with gastroenteritis, especially in hospitalized and younger children. The results can be used in future preventive measurements and the development of effective vaccines.

Worldwide prevalence and genotype distribution of human astrovirus in gastroenteritis patients: A systematic review and meta-analysis.

AIM: Human astrovirus (HAstV) is an important causative agent of gastroenteritis in humans, which mainly infects young children and the elderly. The goal of this study was to conduct a meta-analytic review of the prevalence of HAstV amongst patients with gastroenteritis, and to shed light on the connection between HAstV infection and gastroenteritis. METHODS: Systematic literature searches were conducted to identify all potentially relevant studies recorded up to April 8th, 2022. For study weighting, the inverse variance method was employed and the random-effects model was applied to evaluate data. For case-control studies, the pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to establish the relationship between HAstV infection and gastroenteritis. RESULTS: Among 302423 gastroenteritis patients from 69 different countries, the overall pooled prevalence of HAstV infection was 3.48% (95% CI: 3.11%-3.89%). Case-control approach was used in 39 investigations, and the overall prevalence of HAstV infection among the 11342 healthy controls was 2.01% (95% CI: 1.40%-2.89%). Gastroenteritis and HAstV infection were associated with a pooled OR of 2.16 (95% CI: 1.72-2.71; P < 0.0001; I2 = 33.7%). The most commonly found HAstV genotypes in gastroenteritis patients were HAstV1 (62.18%), HAstV7 (33.33%), and HAstV-MLB1 (17.43%). CONCLUSION: The frequency of HAstV infection was the highest in children under the age of five, and in developing countries. The prevalence rate of HAstV was not influenced by gender. Semi-nested and nested RT-PCR were highly sensitive assays for detecting HAstV infections.

Association between Epstein-Bar virus and colorectal cancer: A systematic review and meta-analysis.

AIM: This study aimed to investigate the prevalence and any potential association between Epstein-Barr virus (EBV) infection and colorectal cancer (CRC). METHODS: A systematic literature search was performed by finding relevant cross-sectional and case-control studies from main online databases. Heterogeneity, odds ratio (OR), and corresponding 95% confidence interval (CI) were applied to all studies through meta-analysis and forest plots. The analysis was performed using STATA Software v.14.1. RESULTS: Twenty-three articles were included in the meta-analysis, eight of them were case/control and 15 were cross-sectional. The pooled prevalence of EBV among 1954 CRC patients was 18% (95% CI: 12%-26%; I2 = 93.14%). Furthermore, in geographical regions, the highest and lowest prevalence of EBV was observed in South America 30% (95% CI: 18%-43%) and Africa 0% (95% CI: 0%-5%), respectively. An association was found between EBV infection and CRC [OR = 3.4 (95% CI (1.13-10.27); I2 = 72.3%)]. CONCLUSION: EBV infection is associated with CRC and can be considered a potential risk factor for the development of CRC. Although the exact molecular mechanism of EBV infection in the development of CRC is still unknown, it seems that latent infection by EBV, intestinal damage, and inflammation can be important factors in the induction of CRC.

Global prevalence and genotype distribution of norovirus infection in children with gastroenteritis: A meta-analysis on 6 years of research from 2015 to 2020.

In the post rotavirus vaccine era, norovirus (NoV) plays an increasingly important role in epidemic and sporadic gastroenteritis among children. This study was designed to provide an updated meta-analytic review of the prevalence of NoV among paediatric patients with gastroenteritis and to clarify the relationship between NoV infection and gastroenteritis. Systematic searches of the literature for potentially relevant studies were carried out from 1 January 2015 to 29 May 2020. The inverse variance method was chosen for weighting of the studies, and the random-effects model was used to analyse data. To determine the association between NoV infection and gastroenteritis in children, pooled odds ratio (OR) and its 95% confidence interval (CI) were computed for case-control studies. The pooled prevalence of NoV infection among 12,0531 children with gastroenteritis from 45 countries across the world was 17.7% (95% CI: 16.3%-19.2%). There were 28 studies with a case-control design, and the pooled prevalence of NoV infection among 11,954 control subjects was 6.7% (95% CI: 5.1%-8.8%). The pooled OR of the association of NoV infection and gastroenteritis was 2.7 (95% CI: 2.2-3.4). The most common NoV genotypes were GII.4 (59.3%) and GII.3 (14.9%). The highest frequency of NoV was found in the age group below 1 year. Our findings indicated a substantial burden of gastroenteritis caused by NoV globally, with GII.4 and GII.3 the major genotypes responsible for the majority of NoV-associated gastroenteritis cases among children. Younger age and male sex can be considered risk factors for NoV-associated gastroenteritis among children.

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.

Molecular Prevalence and Genotype Distribution of Human Adenovirus in Iranian Children with Gastroenteritis.

OBJECTIVE: We determined the molecular prevalence and genotype distribution of human adenovirus (HAdV) among children under five years of age with gastroenteritis in Iran. METHODS: One hundred stool samples from children hospitalized were tested by PCR for adenovirus, and some of the positive samples were sequenced to determine the specific genotype. RESULTS: HAdV DNA was found in 15 samples (15%). The highest and the lowest prevalence of HAdV was observed in the age groups 24-60 months (n = 6; 40%) and 7-12 months (n = 2; 13.3%), respectively (p = 0.01). Nine HAdV-positive samples were sequenced, of which four isolates were HAdV type 2 and five isolates were HAdV type 41. CONCLUSION: HAdV was most common in the 24-60-month-old children. Of the samples sequenced, we found only types 2 and 41. Our results show that in addition to HAdV types 40 and 41, HAdV type 2 may also play a role in causing gastroenteritis in children.

Prevalence and Clinical Relevance of cagA and oipA Genotypes of Helicobacter pylori in Children and Adults with Gastrointestinal Diseases in Tehran, Iran.

Background: Helicobacter pylori isa universal pathogen that causes gastric diseases and cancers in humans. In recent years, several virulence genes have been detected in this microorganism. Thus, we aimed to investigate the frequency of Helicobacterpylori strainswith cytotoxin-associated gene A(cagA) and outer membrane inflammatory protein A(oipA) genotypes among children and adult patients in Tehran, Iran, and evaluatetheir relation to themanifestations of different clinical symptoms. Methods: In this cross-sectional study, biopsy specimens were obtained from patients with gastrointestinal symptomsand evaluated for Helicobacter pylori infectionand its genotypes (cagA/oipA) througha polymerase chain reaction PCR assay. Clinical findings and demographic data of patients were documented and analyzed. Results: A total of 80 patients with Helicobacter pylori infectionwere included in the study (34 children and 46 adults). The cagA and oipA genotypes of Helicobacter pylori wereidentified in 22 (64.7%) and 24 (70.5%) children and in 31 (67.3%) and 34 (73.9%) adults, respectively. These differences were not statistically significant between the 2 studied groups. In addition, the frequency of cagA-positive strains of Helicobacterpylori wasfound more among patients with gastric ulcers rather than other clinical outcomes. Conclusion: Our findings demonstrate a highfrequency of Helicobacter pylori strains with oipA and cagA genotypes among children and adults in this region. Although we could not find a significant relationship between virulence genes and clinical outcomes in the patients, further studies are suggested to evaluate these factors in patients and assess their potential roles in the presence of antibiotic-resistant strains.

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 and genotype distribution of human papillomavirus infection in different anatomical sites among men who have sex with men: A systematic review and meta-analysis.

Men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviours. In this study, a meta-analytic approach was used to systematically analyse the literature to elucidate the prevalence and genotype distribution of anal, penile, oral and urethral HPV infection among MSM in the world. To carry out this systematic review, five electronic databases including Web of Science, PubMed, Scopus, Embase, and Google Scholar were searched for relevant studies published from January 2012 to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalence was calculated for each anatomical region using a random-effect model weighted by the inverse variance method. The meta-analysis was performed using the "Metaprop" function in the R package Meta. The overall pooled prevalence of anal, penile, oral and urethral HPV infection among MSM were 78.4% (95% confidence interval [CI]: 75.6%-81.0%), 36.2% (95% CI: 29.1%-44.0%), 17.3% (95% CI: 13.6%-21.7%) and 15.4% (95% CI: 7.8%-27.9%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis and oral cavity was HPV-16 (19.9%, 4.9% and 3.1%, respectively). HPV infection is rising in MSM because of high-risk sexual behaviours, suggesting an increased future risk of developing HPV-related diseases and malignancies in this population.

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.

Molecular Characterization of Streptococcus Pneumoniae from Patients Diagnosed with Pneumonia: Recommendation for Vaccination Program.

Background: Infections caused by Streptococcus pneumoniae (S. pneumoniae) have remained a significant public health concern worldwide. In developed countries, the highest prevalence of S. pneumonia has been reported among the elderly. The aim of this study was to evaluate the coverage of genotypes in the 13-valent pneumococcal conjugate vaccine (PCV-13) in the Iranian elderly population. Methods: A total of 41 isolates of S. pneumoniae were collected in the current retrospective cross-sectional study. The samples comprised 33 inpatients hospitalized for pneumococcal pneumonia and 8 outpatients. Multiplex polymerase chain reaction assay was performed to categorize the bacteria isolated into specific genotypes. Statistical analyses were performed using SPSS software, and the chi-square test was used to assess the statistical significance in percentages. Results: A total of 68 genotypes were identified in this study, in which 39 isolates (57.3%) were associated with invasive infections. The most common genotypes were 6A/B [8 (19.5%)], 1 [7 (17.5%)], 14 [5 (12.2%)], and 19A [4 (9.75%)], respectively. The coverage rates of PCV-7, PCV-10, and PCV-13 vaccines were 51.17%, 70.7%, and 99.9%, respectively. According to our results, the pneumococcal coverage rate of PCV-7, PCV-10, and PCV-13 vaccine types is estimated to be 51.2%, 70.7%, and 99.9%, respectively. Furthermore, the trend of pneumococcal serotypes included in the PCV-13 was steadily increasing during the study period. Conclusion: It can be concluded that the most circulating pneumococcal serotypes were in accordance with specific serotypes included in the PCV-13 vaccine types. Therefore, including PCV-13 vaccines in immunization programs against pneumococcus in the elderly can effectively reduce the rate of infections.

Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein-Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. METHODS: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs. RESULTS: The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77% (95% CI: 7.73-9.92%; I2 = 83.2%). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95% CI: 15.68-21.97; I2 = 55.4%) for studies with matched pairs design and 3.31 (95% CI: 0.95-11.54; I2 = 55.0%) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83%, vs. 5.72%) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95% CI: 15.55-29.63; I2 = 0%) than in males (14.07; 95% CI: 10.46-18.93; I2 = 49.0%) (P = 0.06). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) (P = 0.0002). CONCLUSIONS: EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer.

Prevalence and genotype distribution of genital human papillomavirus infection in female sex workers in the world: a systematic review and meta-analysis.

BACKGROUND: Female sex workers (FSWs) are amongst the most susceptible groups to acquire human papillomavirus (HPV) infection and consequently, to develop cervical intraepithelial neoplasia and cervical cancer. This is the first systematic review and meta-analysis to provide estimates of the pooled prevalence of HPV infection and the distribution of HPV types among FSWs across the world. METHODS: Five computerized databases were searched for relevant studies published since the inception date of databases to September 2019. The pooled HPV prevalence was calculated by the random effect model described by DerSimonian-Laird. Subgroup analysis was performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the "Metaprop" function in the R package Meta. RESULTS: Sixty-two studies involving 21,402 FSWs from 33 countries were included in this meta-analysis, and the pooled HPV prevalence was 42.6% (95% confidence interval (CI): 38.5-46.7%). HPV-16 (10.1, 95% CI: 8.2-12.5%), HPV-52 (7.9, 95% CI: 5.9-10.7%), and HPV-53 (6.0, 95% CI: 4.4-8.1%) were the most common high-risk HPV types identified among FSWs. The pooled estimated prevalence of HPV infection among FSWs before and after 2010 were slightly different, 43.6% (95% CI: 36.1-51.4%) and 41.9% (95% CI: 37.2-46.8%), respectively. CONCLUSION: Due to the high prevalence of HPV infection, particularly with high-risk types, FSWs have a great susceptibility to the development of cervical and vaginal cancers. Furthermore, they can transmit their infection to their clients, which may result in a high prevalence of HPV and the incidence of HPV-associated malignancies among the general population.

Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine.

BACKGROUND: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. METHODS: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. RESULTS: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control. CONCLUSIONS: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.

Epstein-Barr virus and risk of breast cancer: a systematic review and meta-analysis.

Despite the numerous publications regarding the role of Epstein-Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22-31%) from the 44 included studies. Meta-analysis of 30 case-control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92-7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.

Rotavirus Infection Enhances Levels of Autoantibodies Against Islet Cell Antigens GAD65 and IA-2 in Children with Type 1 Diabetes.

BACKGROUND: Some studies implicate rotavirus infection as a trigger for the development of type 1 diabetes mellitus (T1DM) in children, however findings are controversial. OBJECTIVES: We investigated the link between rotavirus infection and autoantibodies against islet antigens and T1DM in children. METHODS: Serum samples from 80 new-onset diabetic and 80 nondiabetic children were screened for anti-rotavirus IgG, anti-GAD65 and anti-IA-2 autoantibodies using ELISA kits. RESULTS: Positivity percentages of anti-rotavirus IgG detection in diabetic and nondiabetic children were 51.3% and 35.0%, respectively (p = 0.03). The mean anti-GAD65 and anti-IA-2 antibody titers in anti-rotavirus IgG positive samples were statistically higher than that the anti-rotavirus IgG negative samples. A positive correlation was found between anti-rotavirus IgG and anti-GAD65 antibody levels (p = 0.004; r = 0.22). CONCLUSIONS: Our findings support the hypothesis that rotovirus infection may induce T1DM in children.

Peg-interferon Plus Ribavirin Combination Therapy in HCV Mono-infected and HCV/HIV Co-infected Patients in Iran.

Background: Hepatitis C virus (HCV) infection is a cause of major liver complications, particularly in patients infected with human immunodeficiency virus (HIV). This study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) and a fixed dose of ribavirin treatment among Iranian HCV mono-infected and HCV/HIV-co-infected patients. Methods: A total of 214 HCV mono-infected and HCV/HIV co-infected patients attending Liver Disease Center in Tehran were assigned to receive treatment with Peg-IFN-α2a or -α2b plus ribavirin for 24-48 weeks. Sustained virologic response (SVR) was used as the primary efficacy endpoint of Peg-IFN and ribavirin therapy. Results: Treatment with Peg-IFN and ribavirin has been associated with a considerably higher rate of SVR (24 weeks for HCV genotype 3 and 48 weeks for HCV/HIV co-infected and HCV genotype 1 patients). Overall, the clearance of HCV-RNA at the end of therapy occurred in 48.6% of patients. Adverse events leading to treatment discontinuation were seen in 14% of patients. Conclusion: This retrospective study revealed a relatively well-tolerated response in both HCV mono-infected and HCV/HIV coinfected patients during treatment with Peg-IFN and ribavirin. However, the recent revolutionized interferon-free therapies for chronic HCV infection should be taken into account for achieving a greater response and minimal adverse events.