Recent Advances in Immune Regulation by Targeting Dendritic Cells using Small Interfering RNAs.

Gene silencing through RNA interference (RNAi) technology has provided forceful therapeutic modalities to specific knockdown of the genes' expression related to diseases. Small interfering RNAs (siRNAs) can start a process that specifically degrades and silences the expression of cognate mRNAs. These RNA interference processes could effectively adjust many biological processes, including immune responses. Dendritic cells (DCs) are specialist antigen-presenting cells with potent functions in regulating innate and adaptive immunity. SiRNAs performed vital roles in coordinating immune processes mediated by DCs. This review describes the findings that shed light on the significance of siRNAs in DC immune regulation and highlight their potential applications for improving DC-based immunotherapies.

Kidney cancer in the Middle East and North Africa region: a 30-year analysis (1990-2019).

Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8-3.6), 1.4 (1.2-1.6), and 37.2 (32.0-42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75-79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5-19 age and males aged 5-14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region.

Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death.

AIMS: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α-tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD. METHODS AND RESULTS: The proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole-exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM_001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM. CONCLUSIONS: The identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at-risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM.

Pediatric asthma exacerbation and COVID-19 pandemic: Impacts, challenges, and future considerations.

OBJECTIVE: Asthma, a common disease among children and adolescents, poses a great health risk when ignored; therefore, a thorough follow-up to prevent exacerbations is emphasized. The aim of the present study is to investigate asthma exacerbation in children during the Coronavirus disease 2019 (COVID-19) era. DATA SOURCES: This narrative review has been done by searching the PubMed and Embase databases using Asthma, COVID-19, Pandemic, and Symptom flare up as keywords. STUDY SELECTIONS: Studies related to asthma exacerbation in COVID-19 pandemic were included. RESULTS: Based on studies, controlled or mild to moderate asthma has not been considered a risk factor for COVID-19 severity and has not affected hospitalization, intensive care unit (ICU) admission, and mortality. Surprisingly, emergent and non-emergent visits and asthmatic attacks decreased during the pandemic. The three main reasons for decreased incidence and exacerbation of asthma episodes in the COVID-19 era included reduced exposure to environmental allergens, increasing the acceptance of treatment by pediatrics and caregivers, and decreased risk of other respiratory viral infections. Based on the available studies, COVID-19 vaccination had no serious side effects, except in cases of uncontrolled severe asthma, and can be injected in these children. Also, there was no conclusive evidence of asthma exacerbation after the injection of COVID-19 vaccines. CONCLUSION: Further studies are recommended to follow the pattern of asthma in the post-pandemic situation and to become prepared for similar future conditions.

siRNA-Mediated B7H7 Knockdown in Gastric Cancer Lysate-Loaded Dendritic Cells Amplifies Expansion and Cytokine Secretion of Autologous T Cells.

BACKGROUND: Gastric cancer, ranked as the fifth most common cancer worldwide, presents multiple treatment challenges. These obstacles often arise due to cancer stem cells, which are associated with recurrence, metastasis, and drug resistance. While dendritic cell (DC)-based immunotherapy has shown promise as a therapeutic strategy, its efficacy can be limited by the tumor microenvironment and certain inhibitory immune checkpoint molecules, such as B7H7. SiRNA-medicated knockdown of B7H7 in tumor cell lysate-pulsed DCs can increase cytokine secretion and autologous T lymphocyte expansion. This study aimed to evaluate the impact of B7H7 suppression in gastric cancer cell lysate-pulsed DCs on the stimulatory potential of autologous CD3+ T lymphocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated and monocytes were obtained; then, they were differentiated to immature DCs (iDCs) by GM-CSF and IL-4. Tumor cell lysates from human gastric cancer cell lines were harvested, and iDCs were transformed into mature DCs (mDCs) by stimulating iDCs with tumor cell lysate and lipopolysaccharide. B7H7-siRNA was delivered into mDCs using electroporation, and gene silencing efficiency was assessed. The phenotypic characteristics of iDCs, mDCs, and B7H7-silenced mDCs were evaluated using specific surface markers, an inverted light microscope, and flow cytometry. CD3+ T cells were isolated via magnetically activated cell sorting. They were labeled with CFSE dye and co-cultured with mDCs and B7H7-silenced mDCs to evaluate their ability to induce T-cell proliferation. T-cell proliferation was assessed using flow cytometry. The concentration of TGF-ß, IL-4, and IFN-γ secreted from CD3+ T cells in the co-cultured supernatant was evaluated to investigate the cytokine secretory activity of the cells. RESULTS: Transfection of B7H7 siRNA into mDCs was performed in optimal conditions, and the siRNA transfection effectively reduced B7H7 mRNA expression in a dose-dependent manner. SiRNA-mediated B7H7 knockdown in mDCs enhanced maturation and activation of the DCs, as demonstrated by an increased surface expression of CD11c, CD86, and CD40. Co-culture experiments revealed that B7H7-silenced mDCs had more capacity to induce T cell proliferation compared to non-transfected mDCs. The cytokine production patterns of T cells were also altered. Upon examining the levels of TGF-ß, IL-4, and IFN-γ released by CD3+ T cells in the co-culture supernatant, we found that silencing B7H7 in mDCs resulted in a rise in IL-4 secretion and a reduction in TGF-ß levels compared to mDCs that were not transfected. CONCLUSIONS: The study found that suppressing B7H7 expression in DCs significantly enhances their maturation and stimulatory activity when exposed to gastric cancer cell lysate. These B7H7-silenced DCs can substantially increase cytokine production and promote co-cultured T-cell expansion. Consequently, inhibiting B7H7 in DCs may offer a practical strategy to enhance the ability of DCs to initiate T lymphocyte responses and improve the effectiveness of DC-based cell therapy for cancer patients.

The predictive value of cardiac MRI strain parameters in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction and a low fibrosis burden: a retrospective cohort study.

Background: Prompt interventions prevent adverse events (AE) in hypertrophic cardiomyopathy (HCM). We evaluated the pattern and the predictive role of feature tracking (FT)-cardiac magnetic resonance (CMR) imaging parameters in an HCM population with a normal left ventricular ejection fraction (LVEF) and a low fibrosis burden. Methods: The CMR and clinical data of 170 patients, consisting of 142 HCM (45 ± 15.7 years, 62.7% male) and 28 healthy (42.2 ± 11.26 years, 50% male) subjects, who were enrolled from 2015 to 2020, were evaluated. HCM patients had a normal LVEF with a late gadolinium enhancement (LGE) percentage below 15%. Between-group differences were described, and the potent predictors of AE were determined. A P-value below 0.05 was considered significant. Results: LV global longitudinal, circumferential, and radial strains (GLS, GCS, and GRS, respectively) and the LV myocardial mass index (MMI) were different between the healthy and HCM cases (all Ps < 0.05). Strains were significantly impaired in the HCM patients with a normal MMI. A progressive decrease in LVGLS and a distinct fall in LVGCS were noted with a rise in MMI. AE were predicted by LVGLS, LVGCS, and the LGE percentage, and LVGCS was the single robust predictor (HR, 1.144; 95% CI, 1.080-1.212; P = 0.001). An LVGCS below 16.2% predicted AE with 77% specificity and 58% sensitivity. Conclusions: LV strains were impaired in HCM patients with a normal EF and a low fibrosis burden, even in the presence of a normal MMI. CMR parameters, especially FT-CMR values, predicted AE in our HCM patients.

Non-spinal low back pain: Global epidemiology, trends, and risk factors.

Background and Aims: Low back pain (LBP) is one of the most debilitating and prevalent disorders. The prevalence of LBP ranges from 30% to 80%, depending on the population, and increases with age. Causes of LBP are typically classified as spinal and non-spinal. The main goal of this study was to investigate the non-spinal causes of LBP, since neglecting these factors leads to increases in the financial, psychological, and physical burden of LBP on individuals as well as on society. Methods: The data were extracted after searching the PubMed database and Google Scholar search engine up to October 27, 2021. We included all studies that were conducted on a human population and assessed the effects of epidemiological, biological, psychological, and sociodemographic factors on the incidence or progression of LBP. Results: The most common causes of non-spinal LBP were diseases such as nephrolithiasis, endometriosis, tumors, fibromyalgia, and conditions like psychological disorders and pregnancy. Nevertheless, the perceived intensity of the pain can be affected by factors such as socioeconomic level, genetics, age, habits, diet, and psychological status. Conclusion: The epidemiology, etiologies, and risk factors associated with LBP should be more clearly recognized to better prevent, diagnose, and treat the underlying disease and to reduce the burden of LBP.

The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis.

INTRODUCTION: Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients. METHODS: A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). RESULTS: Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.763; 95% CI: 0.602-0.966, I2: 0.0). FINDINGS: Most evidence supports that the use of antidepressant medications, mainly Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with SARS-CoV-2. Some studies showed contradictory findings regarding the effects of antidepressants on the severity of COVID-19. Further clinical trials should be conducted to clarify the effects of antidepressants on the severity of COVID-19.

A Systematic Literature Review and Bibliometric Analysis of Ophthalmology and COVID-19 Research.

This review is proposed to summarize the updates on COVID-19 and ophthalmology along with the bibliometric features of articles that have been published since the beginning of the COVID-19 outbreak. The databases, including PubMed, Scopus, and Web of Science, were searched using "Coronavirus," "COVID-19," "SARS-CoV-2," "pandemic," "ophthalmology," "ophthalmic," and "eye" keywords. All published articles except commentaries, errata, and corrigenda up to April 2021 were included. Titles and abstracts were screened, and ophthalmology-focused articles were collected. The bibliographic information of the articles, such as the name and country of the first author, type of study, date of publication, language, and journal name, were extracted. Included studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. After systematic searching, 2,669 distinct articles were screened by title/abstract, and 1,174 ophthalmology-focused articles were selected to be reviewed. Ophthalmology-focused publications accounted for less than 0.5 percent of the total COVID-19-related articles. Most of the articles were published in the Indian Journal of Ophthalmology, and the main publication type was "original article." Almost 88% of the publications were in English. There was a decline in the publication rate during the initial months of 2021 compared with the middle and last months of 2020. Most of the publications were affiliated with the United States of America. However, Singapore and the United Kingdom were the countries with the highest number of publications after population adjustment. Furthermore, a comprehensive review on major topics including SARS-CoV-2 ocular tropism, ophthalmic manifestations, ocular complications due to COVID-19 treatment strategies, the pandemic effect on ophthalmology care and operations, myopia progression during the pandemic, and telemedicine was conducted.

Contact Lens Associated Bacterial Keratitis: Common Organisms, Antibiotic Therapy, and Global Resistance Trends: A Systematic Review.

Introduction: Contact lens wearing has been increased globally during recent decades, which is one of the main risk factors for developing microbial keratitis. Microbial keratitis is a severe and dangerous condition that causes cornea inflammation. It can lead to corneal scarring and perforation or even endophthalmitis and visual loss if it remains untreated. Among bacterial, fungal, protozoal, and viral agents which can cause microbial keratitis, bacteria are the most common cause. Therefore, in this study, we aim to find common causative bacteria, sensitivity, and resistance to antibiotics and the outcome of antibiotic therapy in contact lens-related bacterial keratitis. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science for published studies and medRxiv for preprints up to February 30, 2021, and May 14, 2021, respectively. A combination of the following keywords was used: "Infection", "Corneal infection", "Keratitis", "Microbial keratitis", and "Contact lens", Also, we used the "Contact lenses" MeSH term. Lists of references for each selected article and relevant review articles were hand-searched to identify further studies. Results: Twenty-six articles were included. From 1991 to 2018, 2,916 episodes of contact lens-related microbial keratitis) CLMK(with 1,642 episodes of proven bacterial keratitis have been reviewed in these studies. Studies were conducted in 17 countries with different geographical regions, and four studies were conducted in Iran, which is the highest number of studies among these countries. According to 20 studies, the mean age of patients was 30.77 years. Females with 61.87% were more than males in 19 studies. A percentage of 92.3% of patients used soft contact lenses, and 7.7% of patients used hard contact lenses (including RGP), according to 16 studies. Pseudomonas aeruginosa, Staphylococcus spp., and Serratia marcescens were the three most common bacteria isolated from samples of patients with contact lens-related bacterial keratitis. Overall, isolated bacteria were most sensitive to fluoroquinolones and aminoglycosides, especially ciprofloxacin and gentamicin respectively, and most resistant against penicillin and cephalosporins especially cefazolin and chloramphenicol. Almost all patients responded well to antibiotic therapy, with some exceptions that needed further surgical interventions. Conclusion: Antibiotics are efficient for treating almost all patients with contact lens-related bacterial keratitis if they are appropriately chosen based on common germs in every geographical region and the sensitivity and resistance of these germs against them. In this regard, Pseudomonas aeruginosa is the most common causative germ of contact lens-associated bacterial keratitis all over the world and is almost fully sensitive to ciprofloxacin. Because of some different results about the sensitivity and resistance of germs against some antibiotics like gentamicin, vancomycin, and chloramphenicol in the Middle East region, especially Iran, more in vitro and clinical studies are suggested.