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.

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.

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.

Prevalence, molecular characterization, and clinical features of human bocavirus in children under 5 years of age with acute gastroenteritis admitted to a specialized children's hospital in Iran: A cross-sectional study.

Background and Aims: Although some reports have confirmed the role of human bocavirus (HBoV) in respiratory infections, the importance of this virus in causing acute gastroenteritis has not yet been proven. This study aimed to determine the molecular prevalence of HBoV in children under 5 years old with gastroenteritis and to compare the clinical symptoms of HBoV-positive and -negative gastroenteritis cases. Methods: A total of 100 stool samples were collected from children with gastroenteritis hospitalized in a pediatric hospital in Tehran, Iran. Demographic and clinical data were collected from patients' medical records. Viral genomic DNA was extracted from stool samples and amplified using the PCR assay. Finally, sequencing was used to determine the genotype of HBoV. Results: The HBoV genome was detected in 14 samples (14%). The highest prevalence of HBoV was observed in the age range of 24-60 months (n = 5; 35.7%); However, no statistically significant relationship was observed between the prevalence of HBoV and age groups (p = 0.09). Nine (64.3%) and 5 (35.7%) HBoV-positive cases were boys and girls, respectively (p = 0.45). Fever, vomiting, and heartache were seen in 5 (35.7%), 3 (21.4%), and 1 (7.1%) HBoV-positive patients, respectively. Overall, no significant difference was observed in any of the investigated clinical manifestations between patients positive or negative for HBoV. Five HBoV-positive samples were subjected to sequencing and all five sequenced samples were genotype 3. Conclusion: HBoV infections can be considered a risk factor for causing at least a portion of acute gastroenteritis cases in children under 5 years of age.

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.

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.

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.

Evaluation of Activity of Zinc Oxide Nanoparticles on Human Rotavirus and Multi-Drug Resistant Acinetobacter Baumannii.

BACKGROUND: Rotaviruses are the cause of acute gastroenteritis and severe diarrheal diseases in children worldwide. Children under the age of five are more susceptible to rotavirus infections. Due to such as the lack of effective drugs and supportive therapy only, the development of new antiviral agents against rotaviruses is required. Multi-drug-resistant Acinetobacter baumannii is also one of the most challenging Gram-negative bacteria to control and treat due to its antibiotic resistance, particularly in intensive care units. OBJECTIVE: This study aimed to investigate the activity of zinc oxide nanoparticles against human rotavirus and multi-drug resistant Acinetobacter baumannii. METHODS: The standard 50% tissue culture infectious dose method and the real-time polymerase chain reaction assay were used to investigate the effects of zinc oxide nanoparticles on rotaviruses. The well diffusion and the minimum inhibitory concentration method were used to assess the antibacterial activity of zinc oxide nanoparticles against Acinetobacter baumannii. RESULTS: 300 µg/ml of zinc oxide nanoparticles demonstrated the highest anti-rotavirus effects, resulting in a 3.16 logarithmic decrease in virus infectious titer, and a four-unit increase in the cycle threshold value of the real-time polymerase chain reaction assay compared to the untreated control (P value <0.001 and P value = 0.005, respectively). The diameter of the inhibition zone of zinc oxide nanoparticles solution against Acinetobacter baumannii was 17 mm. The minimum inhibitory concentration results of the zinc oxide nanoparticles solution against Acinetobacter baumannii was 1.56 mg/ml. CONCLUSION: Our findings showed that zinc oxide nanoparticles could be considered a promising antimicrobial compound.

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.

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 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.

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.

Identifying Potential New Gene Expression-Based Biomarkers in the Peripheral Blood Mononuclear Cells of Hepatitis B-Related Hepatocellular Carcinoma.

Objective: The analysis of the gene expression of peripheral blood mononuclear cells (PBMCs) is important to clarify the pathogenesis of hepatocellular carcinoma (HCC) and the detection of suitable biomarkers. The purpose of this investigation was to use RNA-sequencing to screen the appropriate differentially expressed genes (DEGs) in the PBMCs for the HCC. Methods: The comprehensive transcriptome of extracted RNA of PBMC (n = 20) from patients with chronic hepatitis B (CHB), liver cirrhosis, and early stage of HCC (5 samples per group) was carried out using RNA-sequencing. All raw RNA-sequencing data analyses were performed using conventional RNA-sequencing analysis tools. Next, gene ontology (GO) analyses were carried out to elucidate the biological processes of DEGs. Finally, relative transcript abundance of selected DEGs was verified using qRT-PCR on additional validation groups. Results: Specifically, 13, 1262, and 1450 DEGs were identified for CHB, liver cirrhosis, and HCC, when compared with the healthy controls. GO enrichment analysis indicated that HCC is closely related to the immune response. Seven DEGs (TYMP, TYROBP, CD14, TGFBI, LILRA2, GNLY, and GZMB) were common to HCC, cirrhosis, and CHB when compared to healthy controls. The data revealed that the expressions of these 7 DEGs were consistent with those from the RNA-sequencing results. Also, the expressions of 7 representative genes that had higher sensitivity were obtained by receiver operating characteristic analysis, which indicated their important diagnostic accuracy for HBV-HCC. Conclusion: This study provides us with new horizons into the biological process and potential prospective clinical diagnosis and prognosis of HCC in the near future.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

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.

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.