Human Immunodeficiency Virus-1 Drug Resistance Mutations in Iranian Treatment-experienced Individuals.

BACKGROUND: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. OBJECTIVE: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. METHODS: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. RESULTS: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. CONCLUSION: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.

Multicenter Study of Rotavirus Infection, Diversity of Circulating Genotypes and Clinical Outcomes in Children ≤5 Years Old in Iran.

BACKGROUND: To determine the epidemiology of rotavirus group A (RVA) infection in symptomatic children, and analyze genotype diversity in association with clinical characteristics, geographical and seasonal changes. METHODS: The stool samples of symptomatic children 5≥ years old were collected from 5 different hospitals during December 2020 and March 2022. Rotavirus stool antigen test was done and G and P genotypes of the positive samples were determined. Associations of the infection and genotype diversity with demographical and clinical data were assessed by statistical methods. RESULTS: RVA infection was detected in 32.1% (300/934) of the patients (Ranges between 28.4% and 47.4%). An inverse association with age was detected, where the highest frequency was measured in children ≤12 months of age (175/482, 36.3%). The infection was more frequent during winter (124/284, 43.7%) and spring (64/187, 34.2%). Children who were exclusively fed with breast milk showed a lower rate of infection (72/251, 28.6%). Among the 46 characterized genotypes (17 single- and 29 mixed-genotype infections), G1P[8] and G9P[4] were more frequently detected in children <36 (67/234, 28.63%) and 36-60 (7/24, 29.16%) months of age children, respectively. A seasonal diversity in the circulating genotypes was detected in different cities. Children with G1P[8], G1P[6], and mixed-genotype infection experienced a shorter duration of hospitalization, and a higher frequency of nausea and severe diarrhea, respectively. CONCLUSIONS: In this study high frequency of RVA infection was detected in symptomatic children in Iran. Moreover, genotype diversity according to geographic area, seasons, age groups, and clinical features of disease was detected.

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.

Glioblastoma as a Novel Drug Repositioning Target: Updated State.

Glioblastoma multiforme (GBM) is an aggressive form of adult brain tumor that can arise from a low-grade astrocytoma. In recent decades, several new conventional therapies have been developed that have significantly improved the prognosis of patients with GBM. Nevertheless, most patients have a limited long-term response to these treatments and survive < 1 year. Therefore, innovative anti-cancer drugs that can be rapidly approved for patient use are urgently needed. One way to achieve accelerated approval is drug repositioning, extending the use of existing drugs for new therapeutic purposes, as it takes less time to validate their biological activity as well as their safety in preclinical models. In this review, a comprehensive analysis of the literature search was performed to list drugs with antiviral, antiparasitic, and antidepressant properties that may be effective in GBM and their putative anti-tumor mechanisms in GBM cells.

Amlodipine and Diltiazem Significantly Repress Human Rotavirus Infection In Vitro.

BACKGROUND: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication. OBJECTIVE: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection. METHODS: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID50, and real-time PCR assays. RESULTS: The highest inhibitory effect was obtained at concentrations of 0.5 µg/ml of amlodipine and 3 µg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the Ct values compared to the virus control, respectively (p-value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 µg/ml of amlodipine and above 25 µg/ml of diltiazem. CONCLUSION: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection.

Expression levels of miR-22, miR-30c, miR-145, and miR-519d and their possible associations with inflammatory markers among patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD. METHODS: The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-ß) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay. RESULTS: 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-ß were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-ß and IL-6, respectively. CONCLUSION: The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD.

Evaluation of the Expression Pattern of 4 microRNAs and their Correlation with Cellular/viral Factors in PBMCs of Long Term Non-progressors and HIV Infected Naïve Individuals.

BACKGROUND: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. OBJECTIVE: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. METHODS: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. RESULTS: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. CONCLUSION: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.

Molecular and serological markers of human parvovirus B19 infection in blood donors: A systematic review and meta-analysis.

BACKGROUND: Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not associated with significant disease in general population, while people with underlying problems such as immunodeficiency can cause anemia and arthritis. The current systematic review and meta-analysis aimed to estimate the overall prevalence of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies in blood donors worldwide. METHODS: A systematic search was carried out in online databases for relevant studies from inception until March 30, 2019. Study selection was performed based on predesigned eligibility criteria. The proportion of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies were pooled using the inverse variance method. All statistical analyses were performed using the R version 3.5.3, package "meta." RESULTS: According to the random-effects model, the pool prevalence of B19V DNA, anti-B19V IgM, and anti-B19V IgG among blood donors was calculated to be 0.4% (95% confidence interval [CI] =0.3%-0.6%), 2.2% (95% CI = 1.3%-3.7%), and 50.1% (95% CI = 43.1%-57.1%), respectively. CONCLUSION: For the transmission of B19V through blood, the presence of the virus genome is required, and the present study showed that the prevalence of the virus genome in blood donors is <1%. Therefore, there is no need to screen donated blood for B19V infection.

Molecular Investigation of Human Cytomegalovirus and Epstein-Barr virus in Glioblastoma Brain Tumor: A Case-Control Study in Iran

Background: Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM). Methods: This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively. Results: HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001). Conclusion: Our findings indicate that infection with EBV is associated with GBM.

Therapeutic effects, immunogenicity and cytotoxicity of a cell penetrating peptide-peptide nucleic acid conjugate against cagA of Helicobacter pylori in cell culture and animal model.

BACKGROUND AND OBJECTIVES: Helicobacter pylori causes several gastrointestinal diseases, including asymptomatic gastritis, chronic peptic ulcer, duodenal ulcer, lymphoma of the mucosa-associated lymphoid tissue (MALT), and gastric adenocarcinoma. In recent years, failure to eradicate H. pylori infections has become an alarming problem for physicians. It is now clear that the current treatment strategies may become ineffective, necessitating the development of innovative antimicrobial compounds as alternative treatments. MATERIALS AND METHODS: In this experimental study, a cell-penetrating peptide-conjugated peptide nucleic acid (CPP-PNA) was used to target the cagA expression. cagA expression was evaluated using RT-qPCR assay after treatment by the CPPPNA in cell culture and animal model. Additionally, immunogenicity and toxicity of the CPP-PNA were assessed in both cell culture and animal models. RESULTS: Our analysis showed that cagA mRNA levels reduced in H. pylori-infected HT29 cells after treatment with CPPPNA in a dose-dependent manner. Also, cagA expression in bacterial RNA extracted from stomach tissue of mice treated with PNA was reduced compared to that of untreated mice. The expression of inflammatory cytokines also decreased in cells and tissue of H. pylori-infected mice after PNA treatment. The tested CPP-PNA showed no significant adverse effects on cell proliferation of cultured cells and no detectable toxicity and immunogenicity were observed in mice. CONCLUSION: These results suggest the effectiveness of CPP-PNA in targeting CagA for various research and therapeutic purposes, offering a potential antisense therapy against H. pylori infections.

Human cytomegalovirus and Epstein-Barr virus infections in breast cancer: A molecular study on Iranian women.

BACKGROUND AND OBJECTIVES: The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in breast cancer pathology is not well understood. Our study aimed to investigate the association of HCMV and EBV infections with breast cancer and distinguish the types of positive EBV and LMP-1 samples in Iranian patients. METHODS: Seventy-two formalin-fixed paraffin-embedded (FFPE) breast cancer tissues were analyzed between December 2014 and April 2016. Samples were analyzed for HCMV and EBV using nested-PCR and conventional PCR assays, respectively. Statistical analysis was performed using SPSS software version 18. RESULTS: Overall, HCMV and EBV genomes were detected in 6.9% and 16.7% of FFPE breast cancer tissues, respectively. Clinical factors were not statistically associated with the presence of HCMV and EBV. CONCLUSION: In this study, we reported EBV and LMP-1 typing in breast carcinoma cases for the first time in Iran. Our findings indicate that HCMV and EBV infections are not associated with the development of breast cancer.

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.

MicroRNAs Profiling in HIV, HCV, and HIV/HCV Co-Infected Patients.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are important public health issues. OBJECTIVE: This study aimed to assess the association between microRNAs expression leveland immunological and viral markers in HIV, HCV, and HIV/HCV co-infected patients. METHODS: The expression level of miR-29, miR-149, miR-199, miR-let7, miR-223, miR-155, miR-122, and miR-150 was evaluated in 20 HIV, 20 HCV, 20 co-infected patients, and 20 healthy controls using real-time PCR assay. HIV and HCVviral loads were measuredby real-time PCR, and also, CD4+ T-lymphocyte count was measuredby the PIMA CD4 analyzer. RESULTS: The miRNA expression pattern in each mentioned group showed significantly different expression profiles, but some miRNA species were shared between the groups. MiR-122 and miR-155 were upregulated, while miR-29 and miR-223 were downregulated in three patients groups compared to healthy controls. A significant positive correlation was observed between the expression of miR-122 and HIV/HCV loads. But, miR-29 and let-7 were negatively correlated with HIV load, and miR-149 and let-7 were negatively correlated with HCV load. Also, miR-155 was positively correlated with HCV load. MiR-122 and miR-199 were negative while others were positively correlated with CD4+ T cell count. CONCLUSION: These miRNAs are probably involved in the clinical progression and pathogenesis of HIV and HCV infections. Therefore, determining and manipulating these miRNAs can lead to opening a new gate to control these important infections.

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.

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.

HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients.

The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.

Molecular evidence of human papillomaviruses in the retinoblastoma tumor.

Retinoblastoma tumor (RB) is one of the most prevalent ocular cancers among children. RB may be caused by inherited mutations in RB1 gene as well as some environmental risk factors. Human papillomaviruses (HPV) are suspected as a risk factor of RB due to their pRb inactivating protein. This study evaluated the molecular prevalence of HPV among the RB tumor specimens in Iran. The RB tumor samples were tested for detection of HPV-L1 gene using a nested-PCR approach, and then followed by sequencing and phylogenetic analysis to reveal HPV types. Overall, there were 61 RB tumor samples; 54/61 (88.5%) had unilateral and 7/61 (11.5%) bilateral RB; 55/61 cases (90.2%) had sporadic non-familial RB tumor. HPV-DNA was detected in 6/61 (9.8%) of patients' tumors; the HPV positive RB cases all had unilateral and unfamiliar sporadic RB tumor. HPV type 16 was the most prevalent type identified across the RB tumor samples (3/61, 4.9%). The rate of detected HPV among the RB specimens seems to be considerable. Further investigations are required to elucidate the exact association between HPV and progression to RB.

The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children.

BACKGROUND: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. OBJECTIVE: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. MATERIALS: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. RESULTS: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. CONCLUSION: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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.