The Role of Innate and Adaptive Immune System in the Pathogenesis of Schizophrenia.

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia.

Immunoinformatics-based multi-epitope vaccine design for the re-emerging monkeypox virus.

BACKGROUND: On May 7, 2022, WHO reported a new monkeypox case. By May 2023 over 80,000 cases had been reported worldwide outside previously endemic nations. (This primarily affected the men who have sex with men (MSM) community in rich nations). The present research aims to develop a multi-epitope vaccine for the monkeypox virus (MPXV) using structural and cell surface proteins. METHODS: The first part of the research involved retrieving protein sequences. The Immune Epitope Database (IEDB) was then used to analyze the B and T lymphocyte epitopes. After analyzing the sensitizing properties, toxicity, antigenicity, and molecular binding, appropriate linkers were utilizedto connect selected epitopes to adjuvants, and the structure of the vaccine was formulated. Algorithms from the field of immunoinformatics predicted the secondary and tertiary structures of vaccines. The physical, chemical, and structural properties were refined and validated to achieve maximum stability. Molecular docking and molecular dynamic simulations were subsequently employed to assess the vaccine's efficacy. Afterward, the ability of the vaccine to interact with toll-like receptors 3 and 4 (TLR3 and TLR4) was evaluated. Finally, the optimized sequence was then introduced into the Escherichia coli (E. coli) PET30A + vector. RESULTS: An immunoinformatics evaluation suggested that such a vaccine might be safe revealed that this vaccine is safe, hydrophilic, temperature- and condition-stable, and can stimulate innate immunity by binding to TLR3 and TLR4. CONCLUSION: Our findings suggest that the first step in MPXV pathogenesis is structural and cell surface epitopes. In this study, the most effective and promising epitopes were selected and designed throughprecision servers. Furthermore,through the utilization of multi-epitope structures and a combination of two established adjuvants, this research has the potential to be a landmarkin developing an antiviralvaccine against MPXV. However, additional in vitro and in vivo tests are required to confirm these results.

The coumaric acid and syringic acid ameliorate acetic acid-induced ulcerative colitis in rats via modulator of Nrf2/HO-1 and pro-inflammatory cytokines.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes uncontrolled inflammation and ulcers in your digestive tract. The coumaric acid and syringic acid are phenolic derivative found in many fruits and vegetables and is widely recognized for the ability of anti-parasitic, anti-microbial, anti-viral, anti-inflammatory, and antioxidant. The purpose of this study was to investigate the anti-inflammatory and antioxidant properties of coumaric acid and syringic acid on acetic acid-induced colitis in rats. METHODS: A total of 64 male Wistar rats were divided into eight equal groups (n = 8). Colitis was induced by intrarectal administration of acetic acid, and rats orally received coumaric acid (100 and 150 mg/kg), syringic acid (10, 25, and 50 mg/kg), and dexamethasone (2 mg/kg) once per day for four days after colitis induction. Then, HO-1, Nrf2, and NQO1 mRNA expression were quantified by real time-PCR. Finally, the tissue levels of TNF-α and IL-1ß protein were measured by ELISA. RESULTS: Colitis led to a decrease in HO-1, Nrf2, and NQO1 mRNA expression and an increase in the tissue levels of TNF-α and IL-1ß protein in the colon tissue. Treatment with dexamethasone significantly increased HO-1, Nrf2, and NQO1 mRNA expression and decreased the tissue levels of TNF-α and IL-1ß protein compared to the UC group. Treatment with 150 mg/kg of coumaric acid and 50 mg/kg of syringic acid significantly increased HO-1, Nrf2, and NQO1 mRNA expression compared to the UC group. Also, treatment with 100 and 150 mg/kg of coumaric acid and 10, 25, and 50 mg/kg of syringic acid significantly decreased the tissue levels of TNF-α and IL-1ß protein compared to the UC group. CONCLUSION: The coumaric acid and syringic acid, especially at high doses, may be an alternative strategy for the treatment of UC by the reduction of TNF-α and IL-1ß levels and upregulation of the Nrf2/HO-1 pathway.

Current progress and challenges of immunotherapy in gastric cancer: A focus on CAR-T cells therapeutic approach.

Gastric cancer (GC) is a severe malignancy, accounting for the third most common cancer death worldwide. Despite the development of chemo-radiation therapy, there has not been sufficient survival advantage in patients with GC who were treated by these methods. GC immunogenicity is hampered by a highly immunosuppressive microenvironment; therefore, further understanding of the molecular biology of GC is the potential to achieve new therapeutic strategies in GC therapy, including specific immunotherapy. Current immunotherapies are mainly based on cytokines, immune checkpoints, monoclonal antibodies (mAb), bispecific antibodies (BisAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR). Immunotherapy has made significant progress in the treatment of GC, so that studies show that nivolumab as a programmed death 1 (PD1) inhibitor has proper safety and effectiveness as a third-line treatment for GC patients. Multiple monoclonal antibodies like ramucirumab and claudiximab were effective in treating GC patients, especially in combination with other treatments. Despite the challenges of CAR therapy in solid tumors, CAR therapy targets various GC cells targets; among them, intercellular adhesion molecule (ICAM)-1 CAR-T cell and CLDN18.2 CAR-T cell have shown promising results. Although responses to all these treatments are encouraging and in some cases, durable, these successes are not seen in all treated patients. The present review represents the development of various immunotherapies especially CAR-T cell therapy, its current use, clinical data in GC, and their limitations.

Correlation of miR-24-3p and miR-595 expression with CCL3, CCL4, IL1-beta, TNFalphaIP3, and NF-kappaBIalpha genes in PBMCs of patients with coronary artery disease.

Inflammation has been well recognized to play an important role in developing coronary artery disease (CAD). By regulating essential genes in this pathway post-transcriptionally, MicroRNAs (miRNAs) may help or hinder the development of atherosclerotic lesions. The aim of this study was to investigate the expression of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in the peripheral blood mononuclear cells (PBMCs) of CAD and control groups and to examine whether any correlation exists between the expression of miRs and genes in CAD group. A total of 168 subjects (84 CAD subjects and 84 control subjects) were examined in this research. Expression levels of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in PBMCs were measured using the real-time PCR technique. A comparison of the CAD group with the control group indicated significantly increased expression levels of CCL3, CCL4, and IL-1ß (Fold Change (FC)=4, P=0.009; FC=2.9, P=0.01; FC=1.8, P=0.019, respectively) and remarkably reduced expression levels of TNFαIP3 and NF-κBIα (FC=-1.4, P=0.03 and FC=-5.9, P=0.001, respectively). Moreover, the expression levels of miR-24-3p downregulated (FC=-2.5, P=0.005) and miR-595 upregulated (FC=1.9, P=0.009) in the CAD group. There was a statistical correlation between the number of clogged arteries with expression levels of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in the CAD group. Also, there was a statistical correlation between expression levels of miR-24-3p and miR-595 with CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα gene expression in the CAD group. In CAD patients, decreased expression of miR-24-3p and increased expression of miR-595 may aid the progression of atherosclerotic plaques by regulating CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα gene expression.

A Study of Autoantibodies against Some Central Nervous System Antigens and the IL-35 Serum Level in Schizophrenia.

Schizophrenia (SCZ) is a debilitating mental disorder with various causes involving complex interactions between genetic factors and environmental agents. The immune system plays a vital role in the pathology and function of the nervous system. Interleukin 35 (IL-35) is a regulatory and anti-inflammatory cytokine that can prevent autoimmune and inflammatory diseases. This study aimed to investigate the role of autoantibodies against some central nervous system (CNS) antigens and IL-35 serum levels in patients with Schizophrenia. This case-control study involved 80 participants. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the autoantibodies in the CNS by indirect immunofluorescence assay (IFA). The serum levels of IL-35 were decreased in patient groups compared to healthy subjects. Autoantibodies against N-methyl-D-aspartate receptor (NMDAR) and myelin-associated glycoprotein (MAG) were positive in 15% (6/40) and 7.5% (3/40), respectively; however, no antibodies against myelin, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), voltage-gated potassium channel (VGKC), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), γ-butyric acid receptor type B1 γ-butyric acid receptor type B1 (GABABR), antidipeptidyl peptidase-like protein-6 (DPPX), immunoglobulin-like cell adhesion molecule 5 (IgLON5), Glycine receptor (R) and acetylcholine receptor (Ach R) were detected (No statistics were computed).  We found that decreased serum IL-35 levels and the existence autoantibodies against NMDAR antigen may contribute to the pathogenesis of SCZ.

Relationship between mucosal TNF-α expression and Th1, Th17, Th22 and Treg responses in Helicobacter pylori infection.

Helicobacter pylori (H. pylori)-induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori-associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells. Fifty-five patients with H. pylori-associated gastritis, 47 patients with H. pylori-associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments. Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group. These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

Autoantibodies against Central Nervous System Antigens and the Serum Levels of IL-32 in Patients with Schizophrenia.

BACKGROUND: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. MATERIAL AND METHODS: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method. RESULTS: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens. CONCLUSION: Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

In silico design of a multi-epitope vaccine against HPV16/18.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. RESULTS: In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. CONCLUSIONS: According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

The Serum Levels of IL-36 in Patients with Coronary Artery Disease and Their Correlation with the Serum Levels of IL-32, IL-6, TNF-α, and Oxidative Stress.

INTRODUCTION: Atherosclerosis is a chronic inflammatory process maintained during all stages of the disease by several proinflammatory mediators, such as cytokines and chemokines. Interleukin (IL)-36 cytokines are proinflammatory and have an essential role in innate and adaptive immunity, but the role of IL-36 has not been determined in coronary artery disease (CAD). This study aimed to measure the serum levels of IL-36 in patients with CAD and their association with the serum levels of tumor necrosis factor (TNF)-α, IL-6, and IL-32 and also investigate their correlation with the serum levels of malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP). METHODS: A total of 168 subjects (84 CAD and 84 control subjects) were examined in this research. The total serum levels of IL-36 were measured using the enzyme-linked immunosorbent assay (ELISA). Also, some oxidative stress parameters were evaluated by FRAP and MDA assays in the serum. RESULTS: The serum levels of IL-36 and MDA were significantly higher, and FRAP was significantly lower in the CAD group compared to the controls. Furthermore, the serum levels of IL-36, MDA, and FRAP significantly correlated with the CAD group's cardiac arterial stenosis. Also, the serum levels of IL-36 had a positive and significant correlation with the serum levels of TNF-α, IL-6, IL-32, and biochemical parameters in the CAD group. CONCLUSION: Higher serum levels of IL-36 and its association with the serum levels of TNF-α, IL-32, and IL-6 may play a key role in the pathogenesis of CAD, leading to an increased risk of clogged arteries and oxidative stress.

Designing a novel multi­epitope vaccine against Ebola virus using reverse vaccinology approach.

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

Serum levels of IL-37 and correlation with inflammatory cytokines and clinical outcomes in patients with coronary artery disease.

Coronary artery disease (CAD) due to atherosclerosis is one of the important reasons for death worldwide. Recent evidence has suggested the essential role of inflammation in the progression of atherosclerosis. Interleukin (IL)-37 is a critical anti-inflammatory member of the IL-1 family which regulates the inflammatory processes. The aim of this study was to compare the serum levels of IL-37 in patients with CAD compared with the control group and its correlation with oxidative stress, cholesterol homeostasis, and inflammation in patients with CAD. A total of 42 patients with CAD and 42 sex-matched and age- matched controls who underwent coronary angiography were included in this study. The serum levels of IL-37 were evaluated via ELISA. Serum levels of biochemical risk factors were determined by enzymatic methods. Serum levels of IL-37 in the CAD group subjects were significantly lower than in the control group and IL-37 was significantly increased in men with CAD than in women with CAD. IL-37 significantly had an inverse correlation with IL-6, tumor necrosis factor-α, IL-32, high-sensitivity C reactive protein, oxidized low-density lipoprotein, and malondialdehyde. Also, IL-37 had a significantly positive correlation with ferric-reducing antioxidant power (FRAP) assay. In addition, IL-37 has positively correlated with ATP-binding cassette transporter A1 and G1 gene expression in peripheral blood mononuclear cells and serum levels of the FRAP. A receiver operating characteristic test displayed that IL-37 level ratios were a relatively significant CAD predictor. Our results indicated that decreased serum levels of IL-37 in patients with CAD and its relationship with inflammatory cytokines and reverse cholesterol transport genes are more likely to be associated in the inflammatory process with disease pathology.

The correlation of long non-coding RNAs IFNG-AS1 and ZEB2-AS1 with IFN-γ and ZEB-2 expression in PBMCs and clinical features of patients with coronary artery disease.

BACKGROUND: Aberrant expression of long non-coding RNAs (lncRNAs) can contribute to the pathogenesis of coronary artery disease (CAD). In this study, we aimed to evaluate the expression of lncRNA interferon γ-antisense 1 (IFNG-AS1), zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), and their direct target genes (IFN-γ and ZEB2, respectively) in peripheral blood mononuclear cell (PBMC) from CAD and healthy individuals. METHODS AND RESULTS: We recruited 40 CAD patients and 40 healthy individuals. After doing some bioinformatics analyses, the expressions of IFNG-AS1/ ZEB2-AS1 lncRNAs and IFN-γ/ ZEB2 in PBMCs were measured using quantitative real-time PCR. The possible correlation between the putative lncRNAs and disease severity was also assessed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive role of lncRNAs as diagnostic biomarkers in CAD patients. The expressions of IFNG-AS1 lncRNA as well as IFN-γ and ZEB2 genes were significantly reduced in CAD patients compared to healthy subjects. In contrast, the expression of ZEB2-AS1 was up-regulated in these patients. Linear regression analysis unveiled that there is a positive correlation between the expression of IFNG-AS1 and IFN-γ, also similarly, ZEB2-AS1 and ZEB2 in PBMCs of subjects. Moreover, the expression of IFNG-AS1 and ZEB2-AS1 correlated with the Gensini score. The area under the ROC curves ranged from 0.633-0.742 for ZEB2-AS1/ZEB2 and IFNG-AS1/IFN-γ, respectively. CONCLUSIONS: Our results indicated that the dysregulation of IFNG-AS1/IFN-γ and ZEB2-AS1/ZEB2 in PBMCs of CAD patients may be involved in CAD pathogenesis.

Frequency of virulence-associated genotypes of Helicobacter pylori and their correlation with clinical outcome and histological parameters in infected patients.

Helicobacter pylori (H. pylori) is a gram-negative which can cause several gastroduodenal diseases, including gastritis and peptic ulcer disease (PUD). H. pylori specific genotypes have been related to increased occurrence of gastritis and PUD. The aim of this study was to investigate the clinical relevance of the major virulence factors of H. pylori with clinical outcomes and histological parameters in Iranian patients. Totally, 200 subjects with PUD and gastritis disease who underwent gastroduodenal endoscopy were enrolled in this study. The presence of the cagA, vacA, oipA, babA2, and iceA genes in antral gastric biopsy specimens were determined by polymerase chain reaction (PCR) and the results were compared with clinical outcomes and histological parameters. The frequency of babA2 + , oipA + , vacA s1/m2, and vacA m2 genes was significantly higher in patients with peptic ulcer disease compared with patients with gastritis. In contrast, the frequency of vacA s1/m1 gene was significantly higher in gastritis subjects than PUD subjects. The high-density scores of H. pylori were strongly associated with iceA1 ¯ , babA2 + , and oipA + genes. Additionally, the high polymorphonuclear cell infiltration and high mononuclear cell infiltration scores were strongly associated with the cagA + , iceA1 ¯ , oipA + genes and cagA + , babA2 + , oipA + genes, respectively. Our study indicated that the vacA, babA2, and oipA virulence factors are related to a higher risk of PUD in subjects with H. pylori-infection. Infection with these strains was associated with a more severe gastropathy.

Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches.

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study.

In December 2019, a new virus called SARS-CoV-2 was reported in China and quickly spread to other parts of the world. The development of SARS-COV-2 vaccines has recently received much attention from numerous researchers. The present study aims to design an effective multi-epitope vaccine against SARS-COV-2 using the reverse vaccinology method. In this regard, structural proteins from SARS-COV-2, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, were selected as target antigens for epitope prediction. A total of five helper T lymphocytes (HTL) and five cytotoxic T lymphocytes (CTL) epitopes were selected after screening the predicted epitopes for antigenicity, allergenicity, and toxicity. Subsequently, the selected HTL and CTL epitopes were fused via flexible linkers. Next, the cholera toxin B-subunit (CTxB) as an adjuvant was linked to the N-terminal of the chimeric structure. The proposed vaccine was analyzed for the properties of physicochemical, antigenicity, and allergenicity. The 3D model of the vaccine construct was predicted and docked with the Toll-like receptor 4 (TLR4). The molecular dynamics (MD) simulation was performed to evaluate the stable interactions between the vaccine construct and TLR4. The immune simulation was also conducted to explore the immune responses induced by the vaccine. Finally, in silico cloning of the vaccine construct into the pET-28 (+) vector was conducted. The results obtained from all bioinformatics analysis stages were satisfactory; however, in vitro and in vivo tests are essential to validate these results.

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis.

BACKGROUND AND OBJECTIVE: Chronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-ß1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients. MATERIALS AND METHODS: Total RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-ß1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies. RESULTS: Results point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-ß1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don't find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05). CONCLUSION: These findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.

GJB2-related hearing loss in central Iran: Review of the spectrum and frequency of gene mutations.

Mutations in the GJB2 gene are a main cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be ∼16% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our two previous publications and data from searching other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in central Iran. In all, 332 unrelated families were included and analyzed for the prevalence and type of the GJB2 gene mutations. In total, the frequency of GJB2 mutations was found to be 16% in the central provinces, which is significantly higher than those identified in southern populations of Iran. Also, c.35delG was the most frequent mutation in the related population. The present study suggests that mutations in the GJB2 gene, especially c.35delG, are important causes of HL in central Iran and can be used as a basis of genetic counseling and clinical guidelines in this region.

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations.

BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL), one of the global public health concerns, is marked by a high degree of genetic heterogeneity. The role of GJB2, as the most common cause of ARNSHL, is only <20% in the Iranian population. Here, we aimed to determine the relative contribution of several apparently most common loci in a cohort of ARNSHL Iranian families that were negative for the GJB2 mutations. METHODS: Totally, 80 Iranian ARNSHL families with 3 or more affected individuals from Isfahan and Hamedan provinces, Iran were enrolled in 2017. After excluding mutations in the GJB2 gene via Sanger sequencing, 60 negative samples (30 families from each province) were analyzed using homozygosity mapping for 10 ARNSHL loci. RESULTS: Fourteen families were found to be linked to five different known loci, including DFNB4 (5 families), DFNB2 (3 families), DFNB7/11 (1 family), DFNB9 (2 families) and DFNB3 (3 families). CONCLUSION: Despite the high heterogeneity of ARNSHL, the genetic causes were determined in 23.5% of the studied families using homozygosity mapping. This data gives an overview of the ARNSHL etiology in the center and west of Iran, used to establish a diagnostic gene panel including most common loci for hearing loss diagnostics.

Genetics of Hearing Loss in North Iran Population: An Update of Spectrum and Frequency of GJB2 Mutations.

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.