Hyperglycemia results in decreased immune cell infiltration and increased viral load in the lung in a mouse model of RSV infection.

Respiratory Syncytial virus (RSV) infection is a feared disease in vulnerable populations with impaired immune responses. There is currently no vaccine against RSV and young children along with elderly people are at increased risk of severe or sometimes life-threatening RSV infection. Hyperglycemia with immunomodulatory patterns can impact on infectious disease outcomes and immune system responses in diabetic patients. Even though research continues to uncover the complex mechanisms underlying RSV immunopathogenesis and diabetes mellitus disease separately, limited information is available about interaction between these two phenomena. Here, we evaluated the influence of hyperglycemia as the hallmark of diabetes mellitus disease on the pathogenesis and immunopathogenesis of RSV in a mouse model. In this experiment, hyperglycemia was induced by intraperitoneal injection of Streptozotocin (STZ), and after diabetes confirmation, mice were infected with RSV-A2, and the immune responses were followed for 5 days until the mice were sacrificed. Analyses on airway immune cell influx, T-Lymphocyte subtypes, cytokines secretion, lung histopathology, and viral load were conducted. Our results showed that hyperglycemia resulted in reduced lung immune cells infiltration totally and it was associated with decreased pathological damage of the lung. Following RSV infection in hyperglycemic mice, the ratio of CD4/CD8 T-Lymphocytes due to CD8+ depletion, increased. Furthermore, the level of IFN-γ and IL-17A cytokines decreased, whereas IL-10 showed an upward trend and the viral load increased in hyperglycemic mice compared with normoglycemic mice. In conclusion, these findings indicate that hyperglycemia can ameliorate and downregulate RSV-induced inflammatory and antiviral responses, and result in increment of viral load.

Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking.

Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (CNR2) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the CNR2-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software. In silico molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the CNR2 gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.

Disease severity in respiratory syncytial virus infection: Role of host genetic variation.

Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis and pneumonia in the pediatric population worldwide. The immunopathology of RSV infection varies considerably and severe disease occurs only in a minority of the population. There are many factors (host, viral, and environmental) that contribute to the complicated disease phenotype. In this regard, host factors are decisive for pulmonary susceptibility to RSV infection. Host genetic diversity certainly affects the balance between control of viral replication and tissue damage during RSV infection, consequently impacting on diseases outcome. In this review, we discuss the role of host genetic variation in disease caused by RSV aiming to highlight genetic risk factors for one of the most common diseases in early childhood. Our findings clearly indicate that the response of each individual to infection is influenced by genetic diversity mainly linked to the regulation of host immune responses. Future genetic association and functional studies using more powerful and consistently reproducible approaches will likely be able to confirm, refine, and expand our developing concept of RSV disease pathogenesis.

Effects of microRNAs polymorphism in cancer progression.

MicroRNAs (miRNAs) are known as a new class of small RNAs (18-25 nucleotides) that regulate gene expression at multiple levels from transcription to translation. Considering the important role of miRNAs in cell proliferation, differentiation, and apoptosis, any variations in their expression can contribute to various anomalies, such as tumorigenesis. Single-nucleotide polymorphisms (SNPs) have received much attention as potential genetic markers for diseases due to their advantage of being present at a high frequency in the human genome. SNPs can occur in different parts of the miRNA genes (primary, precursor, and mature) which result in pathological conditions. In this study, recent findings related to the effects of SNPs in miRNAs on their biogenesis and functions and their role in cancer development and progression are discussed. This review was performed using PubMed to search for related reports. The identified effects may be useful for clinical decision-making and providing important new information about the pathophysiology of miRNAs.

Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Opioid system plays a significant role in pathophysiological processes, such as immune response and impacts on disease severity. Here, we investigated the effect of opioid system on the immunopathogenesis of respiratory syncytial virus (RSV) vaccine (FI-RSV)-mediated illness in a widely used mouse model. Female Balb/c mice were immunized at days 0 and 21 with FI-RSV (2 × 106 pfu, i.m.) and challenged with RSV-A2 (3 × 106 pfu, i.n.) at day 42. Nalmefene as a universal opioid receptors blocker administered at a dose of 1 mg/kg in combination with FI-RSV (FI-RSV + NL), and daily after live virus challenge (RSV + NL). Mice were sacrificed at day 5 after challenge and bronchoalveolar lavage (BAL) fluid and lungs were harvested to measure airway immune cells influx, T lymphocyte subtypes, cytokines/chemokines secretion, lung histopathology, and viral load. Administration of nalmefene in combination with FI-RSV (FI-RSV + NL-RSV) resulted in the reduction of the immune cells infiltration to the BAL fluid, the ratio of CD4/CD8 T lymphocyte, the level of IL-5, IL-10, MIP-1α, lung pathology, and restored weight loss after RSV infection. Blocking of opioid receptors during RSV infection in vaccinated mice (FI-RSV-RSV + NL) had no significant effects on RSV immunopathogenesis. Moreover, administration of nalmefene in combination with FI-RSV and blocking opioid receptors during RSV infection (FI-RSV + NL-RSV + NL) resulted in an increased influx of the immune cells to the BAL fluid, increases the level of IFN-γ, lung pathology, and weight loss in compared to control condition. Although nalmefene administration within FI-RSV vaccine decreases vaccine-enhanced infection during subsequent exposure to the virus, opioid receptor blocking during RSV infection aggravates the host inflammatory response to RSV infection. Thus, caution is required due to beneficial/harmful functions of opioid systems while targeting as potentially therapies.

Correction to: Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

In the original publication, seventh author's name was incorrectly published as 'Maryam Golaram'.

Evaluation of potential biomarkers of exposure to crystalline silica: A case study in an insulator manufacturer.

The purpose of this study was to examine the potential determinants of serum neopterin, malondialdehyde (MDA), and erythrocyte glutathione (GSH) as potential markers of oxidative stress, resulting in cellular immune response to inhaled silica particles. This descriptive analytical study was conducted on two groups of exposed workers ( n = 55) and unexposed office workers ( n = 38) of an insulator manufacturing plant. The sampling of airborne silica in the breathing zone of participants was done on the basis of the National Institute for Occupational Safety and Health Method 7601. The blood samples were analyzed by high performance liquid chromatography to determine the level of serum neopterin. A ZellBio GmbH assay kit was used for the quantitative assays of GSH and MDA on the basis of the colorimetric assay. The results of this study show that the measurements of serum neopterin, MDA, and GSH can be considered as potential biological markers of silica exposure for undertaking further comprehensive studies in this area.

Evaluation of the expression level of 12/15 lipoxygenase and the related inflammatory factors (CCL5, CCL3) in respiratory syncytial virus infection in mice model.

Human respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. Disease is thought to be caused, at least partially, by an excessive immune response. Pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. Lipoxygenases (LOXs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate inflammation and have been suggested to play an important role in the immune response in viral infection. To expand our understanding on the possible role of LOX in respiratory viral infection, we studied the 12/15- lipoxygenase expression in RSV-related airway inflammation, and the related inflammatory chemokines, Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (C-C motif) ligand 3(CC L3) in both lung tissue and Bronchoalveolar lavage (BAL) fluid during experimental RSV infection. RSV infection induced mRNA expression of CCL5 and CCL3 in both BAL and lung tissue cells. In addition RSV infection enhanced expression of 12/15-LOX in both BAL and lung cells. In conclusion, we confirm that RSV infection leads to the increased expression of 12/15 LOX and the related chemokines CCL5 and CCL3 in BAL fluid and lung tissue cells suggesting that the 12/15 LOX pathway could serve as a candidate target for prevention and treatment of RSV infection.

The role of microRNAs in respiratory viral infection: friend or foe?

MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host-pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral-encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of cannabinoids and their receptors on viral infections.

Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections.

Antitumor effect of therapeutic HPV DNA vaccines with chitosan-based nanodelivery systems.

BACKGROUND: Cervical cancer is the second-most-common cause of malignancies in women worldwide, and the oncogenic activity of the human papilloma virus types (HPV) E7 protein has a crucial role in anogenital tumors. In this study, we have designed a therapeutic vaccine based on chitosan nanodelivery systems to deliver HPV-16 E7 DNA vaccine, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer. We have developed a Nano-chitosan (NCS) as a carrier system for intramuscular administration using a recombinant DNA vaccine expressing HPV-16 E7 (NCS-DNA E7 vaccine). NCS were characterized in vitro for their gene transfection ability. RESULTS: The transfection of CS-pEGFP NPs was efficient in CHO cells and the expression of green fluorescent proteins was well observed. In addition, NCS-DNA E7 vaccine induced the strongest E7-specific CD8+ T cell and interferon γ responses in C57BL/6 mice. Mice vaccinated with NCS-DNA E7 vaccine were able to generate potent protective and therapeutic antitumor effects against challenge with E7-expressing tumor cell line, TC-1. CONCLUSIONS: The strong therapeutic effect induced by the Chitosan-based nanodelivery suggest that nanoparticles may be an efficient carrier to improve the immunogenicity of DNA vaccination upon intramuscular administration and the platform could be further exploited as a potential cancer vaccine candidate in humans.

Epidemiology and clinical features of respiratory syncytial virus (RSV) infection in hospitalized children during the COVID-19 pandemic in Gorgan, Iran.

Background and Aims: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection in infants and young children. Given the altered circulation patterns of respiratory viruses during the coronavirus disease pandemic-2019 (COVID-19), the study aimed to evaluate epidemiology and clinical features of RSV infections in hospitalized children during the COVID-19 pandemic in Gorgan, northeastern Iran. Molecular epidemiology studies on respiratory viral infections are necessary to monitor circulating viruses, disease severity, and clinical symptoms, in addition to early warning of new outbreaks. Methods: Overall, 411 respiratory swab samples from hospitalized children from October 2021 to March 2022 were collected at Taleghani Children's Hospital, Gorgan, Iran. The incidence of RSV, as well as the circulating subgroups and genotypes, were investigated and confirmed using PCR methods. Additionally, all samples tested for severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) and influenza, and demographic and clinical data were analyzed using SPSS software. Results: The share of RSV, SARS-CoV-2, and influenza among hospitalized children with acute lower respiratory infections (ALRI) were 27%, 16.5%, and 4.1%, respectively. The RSV subgroup A (genotype ON1) was dominant over subgroup B (genotype BA9), with more severe clinical symptoms. Compared with the prepandemic era there were high numbers of hospitalized SARS-CoV-2 positive children and low numbers of other respiratory viruses. Despite this, the prevalence of ALRI-related RSV-disease among hospitalized children in our specialized pediatric center was higher than COVID-19 disease in the same cohort. Conclusions: Studying the epidemiology of respiratory viruses and determining the circulating strains can contribute to effective infection control and treatment strategies.

Prevalence of CCR5 Delta 32 Genetic Variant in the Turkmen Population of Golestan Province, Northeast of Iran.

The 32 bp deletion in the chemokine receptor (C-C motif) 5 gene (CCR5Δ32) is a natural loss of function polymorphism that prevents the protein from locating on the cell surface. This genetic variation acts as a double-edge sword in the pathogenesis/defense mechanism of different health conditions, such as viral infections, autoimmune diseases, and cancers. Here, we evaluated the prevalence of the CCR5Δ32 polymorphism in the Turkmen population of Golestan province, northeast of Iran. Blood samples were collected from 400 randomly selected Turkmen populations (199 women and 201 men), and genomic DNA was extracted. Characterization of CCR5Δ32 genotypes was performed by PCR using primers flanking the 32-nucleotide deletion in the CCR5 gene. The amplified DNA fragments were visualized on 2% agarose gel electrophoresis with cybergreen staining under UV light. All individuals were of Turkmen ethnicity and lived in the Golestan province, northeast of Iran. The mean age of all participants was 35.46 years, with a 20-45 year range. All the studied subjects were healthy without any severe conditions such as autoimmune disease and viral infections. All individuals had no history of HIV infection. The PCR product visualization showed that all the samples are at the 330 bp size, which means the CCR5Δ32 allele was utterly absent from the study population. The presence of the CCR5Δ32 allele among Turkmens may be attributed to the admixture with European descent people. We conclude that the CCR5Δ32 polymorphism may be absent in the Iranian Turkmen population, and further studies with a large population are needed.

Cross-reactivity between Mycobacterium avium subspecies paratuberculosis 4027 peptide and Human IRF5 may contribute to Multiple Sclerosis in Iranian patients.

Background: The etiology of Multiple sclerosis (MS) is complicated and can be affected by several environmental factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) infection in genetically predisposed individuals. The link between MAP and MS depends on host genetic and epigenetic aspects and population-based features that require further investigation. We aimed to study the possible role of MAP in triggering MS using molecular and serological methods. Materials and methods: This case-control study examined 200 blood samples (100 MS patients and 100 HCs) to search for the MAP-specific IS900 gene. In addition, ELISA was conducted to determine the humoral response against MAP_402718-32 and its human IRF5424-434 peptide homolog. Results: The frequency of MAP detection based on the molecular method in MS patients and HCs was 48 % and 13 %, respectively (p < 0.0001). The presence of antibodies against MAP_402718-32 and IRF5424-434 was 55 % and 65 % in MS patients versus 9 % and 7 % in HCs, respectively (p < 0.0001). A good correlation was observed between MAP_4027 and IRF5 antibodies (r = 0.5782, p < 0.0001), indicating that the same antibodies recognized common peptide epitopes. Conclusion: Our research revealed a significant association between MAP and MS, highlighting the possible role of MAP as an important infection trigger factor of MS. It is hypothesized that cross-reactivity between MAP4027 and IRF5 may dysregulate immune homeostasis.

Hematological and Biochemical Laboratory Parameters in COVID-19 Patients: A Retrospective Modeling Study of Severity and Mortality Predictors.

Background: It is well known that laboratory markers could help in identifying risk factors of severe illness and predicting outcomes of diseases. Here, we performed a retrospective modeling study of severity and mortality predictors of hematological and biochemical laboratory parameters in Iranian COVID-19 patients. Methods: Data were obtained retrospectively from medical records of 564 confirmed Iranian COVID-19 cases. According to the disease severity, the patients were categorized into two groups (severe or nonsevere), and based on the outcome of the disease, patients were divided into two groups (recovered or deceased). Demographic and laboratory data were compared between groups, and statistical analyses were performed to define predictors of disease severity and mortality in the patients. Results: The study identified a panel of hematological and biochemical markers associated with the severe outcome of COVID-19 and constructed different predictive models for severity and mortality. The disease severity and mortality rate were significantly higher in elderly inpatients, whereas gender was not a determining factor of the clinical outcome. Age-adjusted white blood cells (WBC), platelet cells (PLT), neutrophil-to-lymphocyte ratio (NLR), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), erythrocyte sedimentation rate (ESR), mean corpuscular hemoglobin (MCHC), blood urea nitrogen (BUN), and creatinine (Cr) also showed high accuracy in predicting severe cases at the time of hospitalization, and logistic regression analysis suggested grouped hematological parameters (age, WBC, NLR, PLT, HGB, and international normalized ratio (INR)) and biochemical markers (age, BUN, and lactate dehydrogenase (LDH)) as the best models of combined laboratory predictors for severity and mortality. Conclusion: The findings suggest that a panel of several routine laboratory parameters recorded on admission could be helpful for clinicians to predict and evaluate the risk of disease severity and mortality in COVID-19 patients.

Detection of SARS-CoV-2 genome in the air, surfaces, and wastewater of the referral hospitals, Gorgan, north of Iran.

Background and Objectives: Coronavirus disease 2019 (COVID-19) is a pandemic caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowing the virus's behavior and its persistence in different environments are crucial and will lead to the proper management of the disease. In this study, air, surface, and sewage samples were taken from different parts of referral hospitals for COVID-19. Materials and Methods: Air samples were taken with impinger, surface samples with swabs, and sewage samples were taken from the hospital wastewater treatment plant. After viral genome extraction, a real-time RT-PCR test was applied to confirm the presence of SARS-CoV-2 RNA in the collected samples. Results: The virus genome could be traced in the wards and wastewater related to hospitalized COVID-19 patients. Overally, 29%, 16%, and 37.5% of air, surface, and sewage samples were positive for the SARS-CoV-2 genome, respectively. Conclusion: Findings of such studies provide valuable results regarding the degree of contamination of hospital environments and the risk of virus transmission in different environments and among hospital staff and patients.

Anti-inflammatory effects of curcumin-loaded niosomes on respiratory syncytial virus infection in a mice model.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in paediatrics. While antivirals are apparent candidates to treat RSV-induced diseases, they have not yet met expectations and have remained in infancy. There is growing evidence to suggest that modulating the exacerbated inflammation during RSV infection can improve disease outcome. Curcumin-loaded niosomes have anti-inflammatory effects against RSV-induced respiratory disease by reducing immune cells' infiltration and inflammatory cytokines' production. This study evaluated the effects of curcumin-loaded niosomes on RSV-induced immunopathology in a mice model. Curcumin-loaded niosomes were prepared using the thin-film hydration method and characterized in vitro. Female Balb/c mice were infected by RSV-A2 and treated daily with curcumin-loaded niosomes. The potential anti-inflammatory effects of curcumin-loaded niosomes were evaluated on day 5 after infection. Using curcumin-loaded niosomes decreased immune cell influx and the inflammatory mediators (MIP-1α, TNF-α and IFN-γ) production in the lung, resulting in alleviated lung pathology following RSV infection. These findings indicate that curcumin-loaded niosomes have anti-inflammatory potential and could be a promising candidate to alleviate RSV-associated immunopathology.

Evaluation of biochemical characteristics of 183 COVID-19 patients: A retrospective study.

INTRODUCTION AND AIM: Coronavirus disease 2019 (COVID-19), with a high mortality rate, has caught the eyes of researchers worldwide and placed a heavy burden on the health care system. Accordingly, this study aimed to evaluate the values of biochemical parameters on the outcomes of COVID-19 patients in Golestan, Iran. MATERIALS AND METHODS: This retrospective study was conducted on 183 COVID-19 patients (i.e., 94 males and 89 females) between March and September 2020. The biochemical parameters and demographic data of the patients (including age, sex, urea, creatinine [Cr], lactate dehydrogenase [LDH], and creatine kinase [CK]) were obtained from electrical medical records. According to the outcome of COVID-19, the patients were categorized into two groups (i.e., death [n = 63] and survival [n = 120] groups), and the biochemical parameters and outcomes of COVID-19 were analyzed. RESULTS: Of the 183 patients, 120 (65.5%) had a non-severe type and recovered from COVID-19, and 63 (34.4%) developed into a critically severe type and died. The mean age of all patients was 56.5 years old. The highest mortality was observed in patients with LDH ≥280. The data obtained by the one-sample t-test showed that there were significantly higher mean values of urea, Cr, CK, and LDH in COVID-19 patients when compared to their reference intervals (P˂0.0001 for all). CONCLUSIONS: Some biochemical parameters are effective in the evaluation of dynamic variations in COVID-19 patients. It can be concluded from the results that biochemical parameters and reinforce LDH may be useful for the evaluation of the COVID-19 outcome.

Recurrent viral RNA positivity and candidiasis findings in hospitalized patients with COVID-19.

Background: The aim of this study was to evaluate reinfection and fungal infections among 785 patients with COVID-19 disease admitted to Baqiyatallah Hospital in Northeastern Iran after the onset of the COVID-19 epidemic. Materials & Methods: In this descriptive-analytic study (20 February-21 July 2020), reinfection and fungal infections among 785 patients were investigated using epidemiological questionnaire, clinical trials, Real-time PCR and CT scan (chest computed tomography) from the hospital HIS (hospital's information system) and collected samples. Results: Reinfection and one oral candidiasis were diagnosed in one 68-year-old man and one 47-year-old man 63 and 42 days after the initial infection, respectively. Conclusion: The research results showed that exposure to COVID-19 may not establish long-term protective immunity to all patients.

COVID-19: Why does disease severity vary among individuals?

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current pandemic, coronavirus disease 2019 (COVID-19). While all people are susceptible to the SARS-CoV-2 infection, the nature and severity of the disease vary significantly among individuals and populations. Importantly, reported disease burdens and case fatality rates differ considerably from country to country. There are, however, still uncertainties about the severity of the disease among individuals or the reason behind a more severe disease in some cases. There is a strong possibility that the severity of this disease depends on a complicated interaction between the host, virus, and environment, which leads to different clinical outcomes. The objective of this article is to point out the essential influential factors related to the host, virus, and environment affecting the clinical outcome of COVID-19.