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.

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.

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.

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.

Update of spectrum c.35delG and c.-23+1G>A mutations on the GJB2 gene in individuals with autosomal recessive nonsyndromic hearing loss.

Hearing loss (HL) is the most common birth defect and the most prevalent sensorineural condition worldwide. It is associated with more than 1,000 mutations in at least 90 genes. Mutations of the gap junction beta-2 protein (GJB2) gene located in the nonsyndromic hearing loss and deafness (DFNB1) locus (chromosome 13q11-12) are the main causes of autosomal recessive nonsyndromic hearing loss worldwide, but important differences exist between various populations. In the present article, two common mutations of the GJB2 gene are compared for ethnic-specific allele frequency, their function, and their contribution to genetic HL in different populations. The results indicated that mutations of the GJB2 gene could have arisen during human migration. Updates on the spectrum of mutations clearly show that frequent mutations in the GJB2 gene are consistent with the founder mutation hypothesis.

A novel variant of SLC26A4 and first report of the c.716T>A variant in Iranian pedigrees with non-syndromic sensorineural hearing loss.

The autosomal recessive non-syndromic hearing loss (ARNSHL) can be associated with variants in solute carrier family 26, member 4 (SLC26A4) gene and is the second most common cause of ARNSHL worldwide. Therefore, this study aims to determine the contribution of the SLC26A4 genotype in the hearing loss (HL) of 40 ARNSHL pedigrees in Iran. A cohort of the 40 Iranian pedigrees with ARNSHL, having no mutation in the GJB2 gene, was selected. The linkage analysis with five short tandem repeat (STR) markers linked to SLC26A4 was performed for the 40 ARNSHL pedigrees. Then, two out of the 40 pedigrees with ARNSHL that linked to DFNB4 locus were further screened to determine the variants in all exons of SLC26A4 gene by direct DNA sequencing. The 21 exons of SCL26A4 were analyzed for the two pedigrees. A known variant (c.716T>A homozygote), it is the first reported incidence in Iran, a novel variant (c.493A>C homozygote) were detected in the two pedigrees and pathogenesis of c.493A>C confirmed in this study with review 100 hearing ethnically matched controls by PCR-RFLP analysis. The present study suggests that the SLC26A4 gene plays a crucial role in the HL occurring in Iranian pedigrees. Also, the results probably support the specificity and unique spectrum of SLC26A4 variants among Iranian HL patients. Molecular study of SLC26A4 gene may lead to elucidation of the profile of the population-specific variants which has importance in diagnostics of HL.

Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection.

BACKGROUND: Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-ß1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-ß1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.

Clinical relevance of Helicobacter pylori virulence factors in Iranian patients with gastrointestinal diseases.

Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H. pylori virulence factors might be useful in identifying the strains with different degrees of pathogenicity. The geographic distribution of distinct H. pylori genotypes is largely unknown and should be established. The prevalence of more pathogenic genotypes in certain areas may have important epidemiological consequences. It also might be associated with the severity of H. pylori related diseases in such regions. Given that Iran is located in the Middle East and Asian populations have revealed high levels of gastric cancer, it is of clinical interest to clarify the potential of H. pylori virulence markers in predicting the associated clinical outcomes. In this review, clinical relevance of adhesion molecules and significant virulence factors of H. pylori in Iranian patients with gastrointestinal diseases are discussed in comparison to other countries.

Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism.

Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-ß1 was significantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not significant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer.

The biological functions of IL-17 in different clinical expressions of Helicobacter pylori-infection.

Helicobacter pylori (H. pylori) infection is regarded as the major cause of various gastric diseases (gastritis, peptic ulcers and gastric cancer) and induces the production of several cytokines. Interleukin-17 (IL-17) is recently recognized as an important player in the pathophysiology of infectious and immune-mediated gastrointestinal diseases. H. pylori infection increases IL-17 in the gastric mucosa of humans. IL-17 usually causes secretion of IL-8 through activation of ERK 1/2 MAP kinase pathway. The released IL-8 attracts neutrophils promoting inflammation. T regulatory cells (Tregs) suppress the inflammatory reaction driven by IL-17, there by favoring bacterial persistence in H. pylori-infection. The pathogenesis of H. pylori-induced inflammation is not well understood. Inflammation is promoted by both host factors and H. pylori factors, such as the proteins cytotoxin associated gene A (cagA) and vacuolating cytotoxin A (vacA). IL-1ß, IL-6, tumor necrosis factor (TNF)-α, TGF-ß1, IL-17, IL-18, IL-21 and IL-22 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relation to different patterns of inflammation remain unclear. Numerous studies have demonstrated important functions of IL-17 in acute and chronic inflammatory processes. This paper reviews the role of IL-17 in gastritis, peptic ulcers and gastric cancer related to H. pylori.

Frequency of virulence factors in Helicobacter pylori-infected patients with gastritis.

UNLABELLED: The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The vacuolating cytotoxin (vacA), cagA gene, oipA and babA2 gene are important virulence factor involving gastric diseases. The objective of this study was to assess the relationship between virulence factors of H. pylori and histopathological findings. MATERIAL AND METHODS: Gastroduodenoscopy was performed in 436 dyspeptic patients. Antrum biopsy was obtained for detection of H. pylori, virulence factors and for histopathological assessment. The polymerase chain reaction was used to detect virulence factors of H. pylori using specific primers. RESULTS: vacA genotypes in patients infected with H. pylori were associated with cagA, iceA1 and iceA2. In the patients with H. pylori infection there was a significant relationship between cagA positivity and neutrophil activity (P = 0.004) and chronic inflammation (P = 0.013) and with H. pylori density (P = 0.034). Neutrophil infiltration was found to be more severe in the s1 group than in the s2 group (P = 0.042). Also was a significant relationship between oipA positivity and neutrophil activity (P = 0.004) and with H. pylori density (P = 0.018). No significant relationships were observed between other vacA genotypes and histopathological parameters. CONCLUSION: H. pylori strains showing cagA, vacA s1 and oipA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

The role and spectrum of SLC26A4 mutations in Iranian patients with autosomal recessive hereditary deafness.

OBJECTIVE: To determine the prevalence and types of SLC26A4 mutations and the relevant phenotypes in a series of Iranian deaf patients. DESIGN: A descriptive laboratory study. STUDY SAMPLE: One hundred and twenty-one families including 60 unrelated patients and 61 unrelated multiplex families with autosomal recessive deafness were included. In the 61 multiplex families, linkage was conducted for short tandem repeats (STRs) of the DFNB4. Selected individuals from the linked families and all of the 60 deaf individuals were subjected to sequencing of SLC26A4. RESULTS: Seven out of the 61 (11.5%) families were linked to the locus which upon further inquiry led to identification of eight different mutations. Also, five out of the 60 (8.3%) patients were positive for the mutations. The SLC26A4 mutations clarified in 9.1% (12 families) of total investigated alleles included: c.2106delG, c.65-66insT, c.881-882delAC, c.863-864insT, c.1226G> A, c.1238A> G, c.1334T> G, c.1790T> C, c.1489G> A, c.919-2A> G (IVS7-2A> G), c.1412delT, and c.1197delT. Six out of 12 (50%) families with mutations were confirmed to be Pendred syndrome (PS). CONCLUSIONS: The results probably suggest a high prevalence and specificity of SLC26A4 mutations among Iranian deaf patients. Molecular study of SLC26A4 may lead to elucidation of the population-specific mutation profile which is of importance in diagnostics of deafness.

Mucosal interleukin-21 mRNA expression level is high in patients with Helicobacter pylori and is associated with the severity of gastritis.

Helicobacter pylori (H. pylori) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells. Different clinical forms of the infection may reflect distinctive patterns of cytokine expression. Interleukin (IL)-17, IL-21, IL-22, and IL-23 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relationship to different patterns of inflammation and virulence factors remain unclear. The present study was launched to analyse IL-6 expression in H. pylori-infected and uninfected gastric patients and to investigate its correlation with chronic gastritis among H. pylori-infected patients. Total RNA was extracted from the gastric antrum biopsies of 48 H. pylori-infected patients and 38 H. pylori uninfected patients. Mucosal IL-21 mRNA expression level in H. pylori-infected and uninfected gastric biopsy was determined by real-time PCR. The presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR. Interleukin-21 mRNA expression was significantly high in biopsies of H. pylori-infected patients compared to H. pylori uninfected patients, and the mucosal IL-21 mRNA level was positively correlated with the grade of chronic inflammation. There was no association between virulence factors and IL-21 mRNA expression. We believe that IL-21 might be involved in the pathogenesis of H. pylori and might be an index of the severity of chronic gastritis.

Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-ß1 mRNA expression in gastritis patients.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-ß1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-ß1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors. PATIENTS AND METHODS: Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-ß1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR. RESULTS: TGF-ß1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-ß1 mRNA expression. TGF-ß1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1. CONCLUSIONS: TGF-ß1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-ß1 mRNA.

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.

Association between virulence factors of helicobacter pylori and gastric mucosal interleukin-18 mRNA expression in dyspeptic patients.

BACKGROUND: Helicobacter pylori (Hp) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustain and expand the local inflammation. Different clinical expressions of the infection may reflect distinctive patterns of cytokine expression. IL-1ß, TNF-α, IL-17 and IL-23 have been reported to be involved in Hp-induced gastric mucosal inflammation, but the details and association to different patterns of inflammation and virulence factors remain unclear. METHODS: Total RNA was extracted from gastric biopsies of 51 Hp-infected patients and 44 Hp-negative patients. Mucosal IL-18 mRNA expression in gastric biopsies was determined by Real-Time PCR. Presence of virulence factors was evaluated using PCR. RESULTS: IL-18 mRNA expression was significantly increased in biopsies of Hp-infected patients compared to Hp-uninfected individuals. There was no association between virulence factors and IL-18 mRNA expression. Also severity of mononuclear infiltration was significantly higher in gastritis patients with vacA (m1)-positive compare patients with vacA (m2)-positive. CONCLUSIONS: IL-18 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the stomach. This may ultimately influence the outcome of Hp-associated diseases that arise within the context of gastritis.

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.