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Infection with hepatitis A virus (HAV) in patient with chronic liver disease (CLD; due to hepatitis B or hepatitis C) may cause severe disease and fulminant liver failure. This study aimed to determine the seroprevalence of HAV antibodies in patients infected with HCV or HBV in Iran (Jahrom city). A total of 159 patients with underlying CLD were recruited between September 2012 and February 2013. Serum samples were collected from each patient and tested for anti-HAV using enzyme-linked immunosorbent assay (ELISA). The overall seroprevalence of total anti-HAV was 79·2%. Patients aged 20–30 years had the lowest (28·3%) anti-HAV seropositivity and those aged >50 years had the highest (95%) seropositivity. The overall prevalence of anti-HAV in patients with chronic HCV and HBV infection was 93·7% and 77·1%, respectively. The anti-HAV seropositivity in liver cirrhosis patients was 100% compared to CLD patients. Because of low HAV immunity in younger CLD patients, vaccination against HAV should be considered. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia (PE) is a medical condition characterized by high blood pressure and significant amounts of protein in a pregnant woman‘s urine. If left untreated, it can develop into eclampsia and life-threatening occurrence of seizures during pregnancy that may lead to fetal and maternal deaths. Although the etiology of preeclampsia remains unknown, there are many proposed theories regarding the pathogenesis of the preeclamptic disease processes: oxidative stress, abnormal trophoblast invasion, vascular endothelial dysfunction, genetic predisposition, dietary deficiencies, and defective immunological adaptation to pregnancy. Several lines of evidence also support the concept that preeclampsia is an excessive maternal inflammatory response to normal pregnancy. We, therefore, examined IL-17 expression in the peripheral blood of patients with PE. Materials and Methods: The peripheral blood was collected from patients with PE (30 patients), normal pregnant control group (30 volunteers) and non-pregnant normal control group (30 healthy people) as control groups in hospitals affiliated to Jahrom University of Medical Sciences. Serums were then, isolated and assessed for IL-17 using by ELISA (ebiosciences kit). Results: The cytokine profile in preeclampsia shows that the production of Th17 cytokines, which induce inflammation. Maternal cytokine levels IL-17 and TGF-β are increased during preeclampsia as compared to normal pregnancy and non-pregnancy. Conclusion: Cytokines have major roles in the pathogenesis of preeclampsia. It seems that circulating placental microvesicles which are shed by placenta influence on immune cells increase inflammatory cytokines such as IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TGF-β, G-CSF, IFN-γ, MCP-1, MIP-1, RANTES and TNF-α. Consistent with elevated innate cytokine levels including TGF-β and IL-6 in the maternal circulation, placental tissue and blood cytokine levels from Th17 are also altered, that implies that Th17 inflammatory responses which may occur both in maternal and placental compartments. Therefore, increased inflammatory factors may lead to abortion. On the other hand, we can use inflammatory biomarkers as noninvasive predictors at the outset of diseases. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis and cancer metastasis depend on the DLL4/Notch signaling pathway. A new approach to treating angiogenesis could inhibit or block this pathway. In the present study, we investigated DLL4 expression as a biomarker capable of predicting survival outcomes in gastric cancer patients using a novel anti-DLL4 Nanobody., Patients and Methods: By using a recently developed anti-DLL4 Nanobody, the expression of DLL4 was evaluated in tissue samples from 135 gastric cancer patients. It was evaluated whether DLL4 expression is related to clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS)., Results: Sixty-five (48%) gastric cancer patients had a positive expression of DLL4 within the tumor tissue. Based on both the univariate and multivariate regression analyses, the expression of DLL4 was strongly associated with RFS (HR, 1.94; p = 0.008) and OS (HR, 2.06; p = 0.004). Moreover, the survival analysis demonstrated that DLL4 expression was a significant independent factor of unfavorable OS (HR, 2.7; p = 0.01) and RFS (HR, 2.3; p = 0.02) in gastric cancer patients., Conclusion: DLL4 expression in gastric cancer patients may predict poor prognosis and survival. Furthermore, the current data demonstrate the potential of Nanobody for detecting DLL4, and it may lead to develop novel therapies and diagnostics for tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: The consumption of contaminated poultry meat is considered as a significant route of campylobacteriosis transmission. Lactic acid is a disinfectant agent with bactericidal effects on Campylobacter spp. The purpose of this study was to assess the low concentrations of lactic acid effect and different temperatures on the transcriptomic responses of Campylobacter jejuni (C. jejuni) adhesion and virulence-associated genes including peb4, ciaB, cdtA, cdtB, and cdtC ., Materials and Methods: The samples were incubated at 10°C and 22°C for 48 h upon exposure to 30% and 60% lactic acid. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of lactic acid was also determined. Then, gene expression was assessed using real-time polymerase chain reaction (RT-PCR)., Results: Lactic acid had lower MIC and MBC levels at lower temperature. The utilization of both levels of lactic acid significantly reduced the expression of peb4, ciaB, cdtB, and cdtC genes over 48 h of incubation at 22°C. However, no significant difference was found in the expression of the cdtA gene between 10 and 22°C at 30% lactic acid., Conclusion: These results highlight the potential of low-concentration lactic acid in the downregulation of adhesion and virulence-associated genes as well as reduction of C. jejuni pathogenicity., (Copyright© 2024 The Authors. Published by Tehran University of Medical Sciences.)

The most common central nervous system (CNS) inflammatory disease is multiple sclerosis (MS), modeled using experimental autoimmune encephalomyelitis (EAE). Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory capabilities, including the suppression of immune cell functions and anti-inflammatory cytokine production. Female C57BL/6 mice (8-10 weeks old) were divided into three groups: 1. Control, 2. Allogeneic MSCs (ALO) treatment, and 3. Syngeneic MSCs (SYN) treatment. To induce EAE, myelin oligodendrocyte glycoprotein was injected subcutaneously with complete Freund's adjuvant, followed by intraperitoneal pertussis toxin. On Days 6 and 12 postimmunization, the treatment groups received intraperitoneal injections of 2 × 10 6 MSCs. Daily clinical and weight assessments were performed, and on Day 25, the mice were euthanized. At the end of the period, brain histological analysis was conducted to quantify lymphocyte infiltration. T-cell characteristics were determined using enzyme-linked immunosorbent assay and Real-time polymerase chain reaction (RT-PCR). The assessment of transcription factor expression levels in the CNS was also performed using RT-PCR. Compared to the control group, both the allogeneic (ALO) and syngeneic (SYN) groups demonstrated significantly reduced disease progression. The maximum clinical scores for the control, ALO, and SYN groups were 4.4 ± 0.1, 2.4 ± 0.2, and 2.1 ± 0.2, respectively (ALO and SYN vs. Control: p < .001). In comparison to the control group, histological studies demonstrated that the allogeneic and syngeneic groups had less lymphocytic infiltration (ALO: 1.4 ± 0.1, SYN: 1.2 ± 0.2, and control: 2.8 ± 0.15; p < .001) and demyelination (ALO: 1.2 ± 0.15, SYN: 1.1 ± 0.1 and control: 2.9 ± 0.1, p < .001). ALO and SYN groups had lower expression of Th1 and Th17 cytokines and transcription factors (IFN-γ: 0.067, 0.051; STAT4: 0.189, 0.162; T-bet: 0.175, 0.163; IL-17: 0.074, 0.061; STAT3: 0.271, 0.253; ROR-γt: 0.163, 0.149, respectively) compared to the control group on Day 25 following EAE induction. Additionally, ALO and SYN groups compared to the control group, expressed more Th2 and Treg cytokines and transcription factors (IL-4: 4.25, 4.63; STAT6: 2.78, 2.96; GATA3: 2.91, 3.08; IL-27: 2.32, 2.46, IL-33: 2.71, 2.85; TGF-β: 4.8, 5.05; IL-10: 4.71, 4.93; CTLA-4: 7.72, 7.95; PD1: 4.12,4.35; Foxp3: 3.82,4.08, respectively). This research demonstrated that MSCs possess the potential to be a therapeutic option for MS and related CNS inflammatory disorders. Their immunomodulatory properties, coupled with the observed reductions in disease severity, lymphocytic infiltration, and demyelination, indicate that MSCs could play a crucial role in altering the course of MS by mitigating inflammatory immune responses and promoting regulatory immune processes. These findings open up new possibilities for the development of MSC-based therapies for MS, and further investigation and clinical trials may be warranted to explore their efficacy and safety in human patients., (© 2024 International Federation of Cell Biology.)

Multiple sclerosis is a demyelinating neurodegenerative disease, and its animal model, experimental autoimmune encephalomyelitis (EAE), exhibits immunological and clinical similarities. The study aimed to examine mechanisms underlying therapeutic effects of mesenchymal stem cell administration in EAE. C57BL/6 mice were separated into control and treatment groups (T1, T2, and T3); EAE was induced in all animals. Clinical examinations were conducted daily, and on 25th day, animals were sacrificed, and spinal cord was stained for histological analysis. Additionally, spleen cell proliferation assay, assessments of cytokine, and gene expression in both spinal cord and spleen cells were performed. The results indicated a significant reduction in clinical symptoms among treatment groups compared to control group. Histological analyses revealed decreased infiltration of lymphocytes into the spinal cord and reduced demyelinated areas in treatment groups compared to control group. Cytokine production of IL-10, TGF-β, and IL-4 were significantly enhanced and IFN-γ and TNF-α in treatment groups were decreased relative to control group. Also, gene expression of CTLA-4, PD-1, IL-27, and IL-33 indicated a significant increase in treatment groups. The administration of MSCs significantly improved clinical symptoms, attenuated inflammation, and reduced spinal cord demyelination in EAE, suggesting a potential protective effect on disease progression., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Multiple sclerosis (MS) is a condition where the central nervous system loses its myelin coating due to autoimmune inflammation. The experimental autoimmune encephalomyelitis (EAE) simulates some aspects of human MS. Boswellic acids are natural compounds derived from frankincense extract, known for their anti-inflammatory properties. The purpose of this research was to investigate therapeutic potential of boswellic acids. Mice were divided into three groups: low-dose (LD), high-dose (HD), and control groups (CTRL). Following EAE induction, the mice received daily doses of boswellic acid for 25 days. Brain tissue damage, clinical symptoms, and levels of TGF-β, IFN-γ, and IL-17 cytokines in cell cultured supernatant of lymphocytes were assessed. Gene expression of transcription factors in brain was measured using real-time PCR. The levels of brain demyelination were significantly lower in the treatment groups compared to the CTRL group. Boswellic acid reduced the severity and duration of EAE symptoms. Furthermore, boswellic acid decreased the amounts of IFN-γ and IL-17, also the expression of T-bet and ROR-γt in brain. On the contrary, it increased the levels of TGF-β and the expression FoxP3 and GATA3. Our findings suggest that boswellic acids possess therapeutic potential for EAE by modulating the immune response and reducing inflammation., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-β (TGF-β) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD., Methods: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed., Results: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores., Conclusions: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-β. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Berberine is a benzylisoquinoline alkaloid found in such plants as Berberis vulgaris, Berberis aristata, and others, revealing a variety of pharmacological properties as a result of interacting with different cellular and molecular targets. Recent studies have shown the immunomodulatory effects of Berberine which result from its impacts on immune cells and immune response mediators such as diverse T lymphocyte subsets, dendritic cells (DCs), and different inflammatory cytokines. Multiple sclerosis (MS) is a chronic disabling and neurodegenerative disease of the central nervous system (CNS) characterized by the recruitment of autoreactive T cells into the CNS causing demyelination, axonal damage, and oligodendrocyte loss. There have been considerable changes discovered in MS regards to the function and frequency of T cell subsets such as Th1 cells, Th17 cells, Th2 cells, Treg cells, and DCs. In the current research, we reviewed the outcomes of in vitro, experimental, and clinical investigations concerning the modulatory effects that Berberine provides on the function and numbers of T cell subsets and DCs, as well as important cytokines that are involved in MS., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction Multiple sclerosis (MS) is an autoimmune condition marked by inflammation and the loss of myelin in the central nervous system (CNS). The aim of this research was to understand how Thymoquinone regulate the molecular and cellular processes involved in controlling experimental autoimmune encephalomyelitis (EAE), which is an animal model often used to study MS. Methods Female C57BL/6 mice were split into different groups receiving different doses (low, medium, and high) of Thymoquinone simultaneously with EAE induction. Clinical scores and other measurements were observed daily throughout the 25-day post immunization. We assessed lymphocyte infiltration and demyelination in the spinal cord through histological staining, analyzed T-cell profiles using ELISA, and quantified the expression levels of transcription factors in the CNS using Real-time PCR. Results Thymoquinone prevented the development of EAE. Histological experiments revealed only a small degree of leukocyte infiltration into the CNS. Thymoquinone resulted in a notable reduction in the generation of IFN-γ, IL-17, and IL-6, while simultaneously increasing the production of IL-4, IL-10, and TGF-β in Th2 and Treg cells. Results from Real-time PCR suggested Treatment with Thymoquinone decreased the expression of T-bet and ROR-γt while increasing the expression of Foxp3 and GATA3. Conclusion These findings showed that Thymoquinone could decrease both disease incidence and severity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions., Methods: In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease., Results: Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors., Discussion/conclusion: Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients.

Background: Multiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder indicated by demyelination, chronic inflammation, and neuronal destruction. Regional demyelination, inflammation responses, scar development, and various axonal damage are pathological characteristics of MS. Curcumin is a hydrophobic polyphenol extracted from the rhizome of the turmeric plant. In addition to anti-inflammatory effects, beneficial therapeutic effects such as antioxidant, anti-cancer and nerve protection have also been seen from this compound. The purpose of the current investigation was to provide light on the potential benefits of Curcumin in treating experimental autoimmune encephalomyelitis (EAE), the animal model of MS., Methods and Results: in Female C57BL/6 mice were used to induce EAE through myelin oligodendroglial glycoprotein (MOG). Curcumin doses of 100 and 200 mg/kg were administered orally in the treatment groups starting on the first day of EAE induction. Brains and splenocytes were extracted from euthanized animals on day 25 following EAE induction. Demyelination and leukocyte infiltration, proliferation, cytokine, and gene expression profiles were assessed. Our findings demonstrate that both low and high doses of Curcumin decreased the progression of EAE. Histological analyses revealed low infiltration of leukocytes into the CNS. Curcumin therapy enhanced Th2 and Treg cell secretion of IL-4, IL-10, and TGF-β although considerably decreasing IFN-γ and TNF-α. Curcumin-induced Th2 and Treg cell cytokine production and transcription factor gene expression (IL-13, GATA3, STAT6 and IL-35, CTLA4, Foxp3) and anti-inflammatory cytokines (IL-27, IL-33)., Conclusion: Overall, these findings provide additional evidence that Curcumin can slow disease development and alleviate symptoms in EAE through stimulating Treg and Th2 cell polarization. They support Curcumin's potential therapeutic role in MS., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Asthma is known as one of the most common chronic inflammatory diseases characterized by recurrent obstruction and inflammation of the airways. Probiotics are defined as a group of beneficial living microorganisms that are beneficial in many disorders, including allergies. The aim of this study was to investigate the probiotic supplement effects on improvement of clinical asthma symptom and changes in the pattern of Th17-related inflammatory cytokines in asthmatic patients., Methods: This was a randomized controlled clinical trial with parallel, double-blind groups. Forty patients with asthma were enrolled and received 1 capsule/day of a probiotic supplement for 8 weeks. Respiratory function tests; and the level of IL-6, IL-17, IL-21 and TGF-β were evaluated at the baseline and end of intervention., Results: The results showed that the level of IL-6 and IL-17 in patients after receiving probiotics was reduced and expression of TGF-β was increased as compared to the baseline. Also, the expression of IL-17 and IL-21 in the probiotic group was significantly lower than the placebo group at the end of the intervention. In addition, an improvement in pulmonary function tests and clinical symptoms was observed after receiving probiotics., Conclusions: Eight-weeks treatment with a probiotic supplementation suggests that it may effect on Th17 cells-associated IL-6, IL-17 and TGF-β; and Forced Expiratory Volume in 1 s and Forced Vital Capacity. Taken together, these results suggest that probiotics may have the ability to affect neutrophilic asthma and they can possibly be used besides common treatments for patients with neutrophilic asthma.

Evidence demonstrated that metabolic-associated T cell abnormalities could be detected in the early stage of RA development. In this context, molecular evaluations have revealed changes in metabolic pathways, leading to the aggressive phenotype of RA T cells. A growing list of genes is downregulated or upregulated in RA T cells, and most of these genes with abnormal expression fall into the category of metabolic pathways. It has been shown that RA T cells shunt glucose towards the pentose phosphate pathway (PPP), which is associated with a high level of nicotinamide adenine dinucleotide phosphate (NADPH) and intermediate molecules. An increased level of NADPH inhibits ATM activation and thereby increases the proliferation capabilities of the RA T cells. Defects in the DNA repair nuclease MRE11A cause failures in repairing mitochondrial DNA, resulting in inhibiting the fatty acid oxidation pathway and further elevated cytoplasmic lipid droplets. Accumulated lipid droplets employ to generate lipid membranes for the cell building program and are also used to form the front-end membrane ruffles that are accomplices with invasive phenotypes of RA T cells. Metabolic pathway involvement in RA pathogenesis expands the pathogenic concept of the disease beyond the common view of autoimmunity triggered by autoantigen recognition. Increased knowledge about metabolic pathways' implications in RA pathogenesis paves the way to understand better the environment/gene interactions and host/microbiota interactions and introduce potential therapeutic approaches. This review summarized emerging data about the roles of T cells in RA pathogenesis with a focus on immunometabolism dysfunctions and how these metabolic alterations can affect the disease process., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Asthma is considered to be a chronic inflammatory disorder of the airways. Probiotics are living microorganisms that are found in the human gut and have protective effects against a wide range of diseases such as allergies. The aim of this study was to investigate the improvement of clinical asthma symptoms and changes in the expression pattern of selective microRNAs in patients with asthma and the changes in IL-4 and IFN-γ plasma levels after receiving probiotics., Materials and Methods: The present study was a randomized, double-blind, placebo-controlled trial that enrolled 40 asthmatic patients. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function tests, IL-4 and IFN-γ levels, and expression of microRNAs were assessed at baseline and after treatment., Results: The results showed that the expression of miR-16, miR146-a and IL-4 levels in patients with asthma after receiving probiotic supplementation was significantly reduced and miR-133b expression was increased. In addition, pulmonary function tests showed a significant improvement in Forced Expiratory Volume in 1 s and Forced Vital Capacity after receiving probiotics., Conclusion: In our study, 8-week treatment with probiotic supplementation led to reduced Th2 cells-associated IL-4 and improved Forced Expiratory Volume and Forced Vital Capacity. It appears probiotics can be used in addition to common asthma treatments., (© 2022. The Author(s).)

Introduction: The favorable effects of probiotics have been demonstrated in allergic disorders. However, the underlying immunological mechanisms are poorly understood. In the present study, we investigated the improvement of clinical symptoms and immunological balance after receiving probiotics in patients with asthma., Methods: The present study was a randomized, double-blind, placebo-controlled trial in which 40 patients with asthma were enrolled. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function test, percentage of CD4+ CD25+ FoxP3+ Tregs, and gene expression of T-bet, GATA-3, RORγt, and Foxp3 in PBMCs were assessed at baseline and after treatment., Results: Our results showed a significant increase in the expression of FoxP3 and CD4+ CD25+ FoxP3+ Tregs population, while RORγt and GATA3 expression were reduced. In addition, pulmonary function tests showed a significant improvement in forced expiratory volume and forced vital capacity after receiving probiotics., Discussion/conclusion: Our findings demonstrate that 8-week treatment with probiotic supplementation can control T-helper 2-predominant and Th17 pro-inflammatory responses and improve forced vital and forced expiratory volume in asthmatic patients. It seems probiotics can be used besides common treatments for patients with asthma., (© 2022 S. Karger AG, Basel.)

Introduction: The prevalence of coronavirus disease 2019 (COVID-19) has rapidly increased worldwide. More investigation is needed to progress toward understanding the exact role of immune responses in the pathology of the disease, leading to improved anticipation and treatment options., Methods: In the present study, we examined the relative expression of T-bet, GATA3, RORγt, and FoxP3 transcription factors as well as laboratory indicators in 79 hospitalized patients along with 20 healthy subjects as a control group. In order to make an exact comparison between various degrees of severity of disease, patients were divided into critical (n = 12) and severe (n = 67) groups. To evaluate the expression of genes of interest by performing real-time PCR, blood samples were obtained from each participant., Results: We found a significant increase in the expression of T-bet, GATA3, and RORγt and a reduction in the expression of FoxP3 in the critically ill patients compared to the severe and control groups. Also, we noticed that the GATA3 and RORγt expressions were elevated in the severe group in comparison with healthy subjects. Additionally, the GATA3 and RORγt expressions showed a positive correlation with elevation in CRP and hepatic enzyme concentration. Moreover, we observed that the GATA3 and RORγt expressions were the independent risk factors for the severity and outcome of COVID-19., Discussion: The present study showed that the overexpression of T-bet, GATA3, and RORγt, as well as a decrease in the FoxP3 expression was associated with the severity and fatal outcome of COVID-19., (© 2023 S. Karger AG, Basel.)

The aim of this study was to evaluate antibody response against influenza vaccine in beta thalassemia major patients from Iran. Thirty beta thalassemia major patients were enrolled and divided into three groups: single dose (group 1), double dose (group 2), and control (group 3). Seroconversion, seroprotection, and geometric mean titer (GMT) assays were performed through hemagglutination inhibition (HI) on days 0, 14, and 60. Based on the results, the level of antibody titer was increased in group 2. Two weeks after vaccination, seroconversion rate was about 20% and 30% in groups 1 and 2. Sixty days after vaccination, the seroconversion rate was around 70% and GMT showed a more than 2-fold increase in group 2. Based on the results, the immunogenicity of double dose vaccination against influenza infection appears to be higher than the single dose vaccine in beta thalassemia major patients, and thus it is recommended to use two doses of vaccine, especially in splenectomized patients who are more sensitive than others., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic lymphocytic leukemia (CLL) is a blood malignancy that is characterized by remarkable expression of CD69 and Ki67 in CLL cells. Elevated levels of Cleaved-Poly (ADP-ribose) polymerase-1 (PARP1) and microRNA-155 (MiR-155) are related to poor prognosis of disease. Berberine as a natural isoquinoline alkaloid, has shown an anti-tumor potential in tumor cells. The objective of present study was to explore some aspects of molecular mechanisms of berberine effect in CLL cells. To analyze the expression of CD69 and Ki67 using flow cytometry, 16 peripheral blood samples and seven bone marrow aspirates were collected from CLL patients. Isolated peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) were treated with 25 µM of berberine for 24 h. The level of miR-155 expression was subsequently evaluated by real-time PCR. Furthermore, western blot was used for assessment of cleaved PARP1. Our results demonstrated a significant reduction in CD69 and Ki67 expression on CD19 + cells when the cells were treated by berberine. Interestingly, the expression level of miR-155 was reduced after berberine treatment in compare to the control group. Furthermore, western blotting revealed an increased level of cleaved PARP1 in dose-dependently manner in CLL cells. The results confirmed the anti-tumor impact of berberine on CLL cells through reducing CD69, Ki67, and miR-155 expression and increasing cleaved PARP1 may be considered as an option for future clinical studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Targeted tumor therapy is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) is overexpressed in tumor vasculature and plays a pivotal role in tumor neovascular development and angiogenesis during tumor progression. Immunotoxins due to their superior cell-killing ability and the relative simplicity of their preparation, have great potential in the clinical treatment of cancer. The aim of this study was to develop a novel immunotoxin against DLL4 as a cell cytotoxic agent and angiogenesis maturation inhibitor. In present study, an immunotoxin, named DLL4Nb-PE, in which a Nanobody as targeting moiety fused to the Pseudomonas exotoxin A (PE) was constructed, expressed and assessed by SDS-PAGE, western blotting, ELISA and flowcytometry. The functional assessment was carried out via MTT, apoptosis and chicken chorioallantoic membrane (CAM) assays. It was demonstrated DLL4Nb-PE specifically binds to DLL4 and recognizes DLL4-expressing MKN cells. The cytotoxicity assays showed that this molecule could induce apoptosis and kill DLL4 positive MKN cells. In addition, it inhibited neovascularization in the chicken chorioallantoic membrane. Our findings indicate designed anti-DLL4 immunotoxin has valuable potential for application to the treatment of tumors with high DLL4 expression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Angiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients., Patients and Methods: Three hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF, and DLL4 in the patients using ELISA., Results: Our results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-β and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group., Conclusions: In summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients., (© 2022. The Author(s).)

Berberine is a natural isoquinoline alkaloid that has been shown to inhibit the proliferation and induce apoptosis in a wide variety of tumor cells. However, the action mechanism of berberine in CLL cells is unknown. The previous study has shown that berberine leads to reduced viability and elevated levels of apoptosis in PBMCs of CLL patients. CLL cells are characterized by remarkable expression of Bcl-2 and ROR1 which leads to activation and survival and increases disease progression in patients. High-level expression of miR-21 in patients with CLL is associated with a higher risk of death. Here we investigated the anticancer effects of berberine upon peripheral blood mononuclear cells (PBMCs) of CLL patients. To evaluate the expression of anti-apoptotic proteins and ROR1 using flow cytometry and western blot, PBMCs were treated with 25 μM of berberine for 24 hr. The expression levels of mir-21 were evaluated by real-time PCR. Examination of treated cells demonstrated that berberine decreased Bcl-2 and ROR1 levels. Although western blot results did not show any change in Bax as a pro-apoptotic protein, an increased Bax/Bcl-2 ratio indicated that mitochondrial pathway is involved in berberine-induced apoptosis of CLL cells. Interestingly, berberine could reduce the expression of miR-21 in comparison to the untreated group. Our findings describe some of the molecular mechanisms of berberine by decreasing Bcl-2, ROR1, and mir-21 which may be considered as a novel apoptosis inducer in CLL cells., (© 2020 John Wiley & Sons, Ltd.)

Coronaviruses (CoVs) were first discovered in the 1960s. Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has been identified as the cause of COVID-19, which spread throughout China and subsequently, across the world. As COVID-19 causes serious public health concerns across the world, investigating the characteristics of SARS-CoV-2 and its interaction with the host immune responses may provide a clearer picture of how the pathogen causes disease in some individuals. Interestingly, SARS-CoV-2 has 80% sequence homology with SARS-CoV-1 and 96-98% homology with CoVs isolated from bats. Therefore, the experience acquired in SARS and Middle East Respiratory Syndrome (MERS) epidemics may improve our understanding of the immune response and immunopathological changes in COVID-19 patients. In the present paper, we have reviewed the immune responses (including the innate and adaptive immunities) to SARS-CoV, MERS-CoV, and SARS-CoV-2, so as to improve our understanding of the concept of the COVID-19 disease, which will be helpful in developing vaccines and medications for treating the COVID-19 patients., (© 2021 S. Karger AG, Basel.)

There is a significant fluctuation in clinical symptoms of asthmatic females during their life course, suggesting that the reproductive status and the level of sex hormones may affect the development of asthma and its exacerbation. In this study, we aimed to assess the biological effects of 17β-estradiol (E2) and progesterone (P4), alone or in combination form, on the transcription factors and production of cytokines in peripheral blood mononuclear cells (PBMCs). PBMCs of the mild-to-moderate asthmatic patients and healthy controls (HCs) were treated with equivalent serum levels of E2 or P4 maintained during hormone replacement therapy (HRT). The expression levels of T-bet, GATA-3, RORγt, PU.1, and Foxp3 were assessed by quantitative PCR. We also measured the concentration of IL-4, IL-9, IL-10, IFN-γ, and TGF-β in cell culture supernatants using ELISA. IL-4 production and GATA-3 expression levels slightly increased when asthmatic PBMCs were treated with E2 (p < 0.01), P4 (p < 0.01), or E2 + P4 (p < 0.001) compared to the untreated cells. IL-9 secretion (p < 0.001) and PU.1 gene expression levels (p < 0.05) were slightly higher in asthmatic patients' PBMCs before treatment but hormone therapy did not affect the level of them. Although the untreated asthmatic PBMCs produced a lower amount of IFN-γ compared to HCs (p < 0.01), hormone treatment did not affect the levels of IFN-γ secretion in patient groups. Moreover, we did not observe any significant changes in IL-10 and TGF-β secretion in the supernatant of hormone treated cells. We found that the common applied HRT may faintly increase GATA-3 expression and IL-4 production levels in PBMCs of asthmatic patients and can slightly increase asthma severity.

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment., (© 2019 Wiley Periodicals, Inc.)

Introduction: The interleukin 28B (IL28B) genotype is associated with changes of lipid metabolism in patients infected with hepatitis C virus (HCV). The association of steatosis with serum levels of adiponectin in chronic hepatitis C (CHC) patients has also been documented. This study aimed for the evaluation of serum levels of IL28B and adiponectin as well as the association of IL28B SNPs with different clinicopathological parameters in HCV-infected patients., Methodology: All 142 HCV-infected patients received peg-interferon plus ribavirin. Detection of rs8099917 and rs12979860 IL-28B genotypes was done with specific primers. Serum IL28 and adiponectin levels were measured using commercial ELISA kits., Results: Higher levels of both IL28 and adiponectin were found in patients. In Genotype 3a (G3a) -infected patients, IL28 and adiponectin serum levels were significantly higher than those infected with G1a. A correlation was found between increasing levels of AST and ALT in G3a-infected patients and the decrease in IL28 and adiponectin serum levels, respectively, in contrast to G1a-infected patients. Higher levels of both IL28 and adiponectin were associated with both CT allele of rs12979860 and TT allele of rs8099917 in patients in comparison with corresponding alleles in controls., Conclusions: In contrast to other studies, this study showed higher serum adiponectin levels in HCV-infected patients compared to that in healthy controls. This finding is possibly due to adiponectin resistance caused by down-regulation of adiponectin receptors or tumorigenic effects of adiponectin. Our genotype-based analyses revealed, at least in part, the involvement of the viral factors in the outcome of HCV infection., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Kaveh Sadeghi, Abbas Ahmadi Vasmehjani, Rasoul Baharlou, Zamaneh Hajikhezri, Seyed Jalal Kiani.)

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA.

Objectives: Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor., Materials and Methods: In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays., Results: Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM., Conclusions: These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.

Antibody-based targeting of angiogenesis is a key approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in tumor neovascular development and angiogenesis during tumor progression. It forecasts the prognosis of human malignancies and blocking its signaling can help to inhibit neovascularization and tumor metastasis. Nanobodies are the smallest antigen-binding domains of heavy chain antibodies in camelidae. The aim of this study was to develop a Nanobody against DLL4 and apply binding and functional approaches to target it. In this work, a Nanobody library against human recombinant DLL4 was developed. After panning, the periplasmic-extract (PE) of individual colonies were screened through ELISA. The interactions between Nanobody and DLL4 were assessed using immunohistochemistry and FACS. The functional assessment was carried out via tube formation assay. We selected a Nanobody (3Nb3) with a high binding signal to DLL4, associated with a binding affinity of 3.6 nM. It was demonstrated that 3Nb3 binds to native DLL4 on the surface of MKN cells and gastric carcinoma tissue, and also inhibits the maturation of capillary-like structures in HUVECs. The results were indicative of the potential of Nanobody for DLL4 identification and can broaden the scope for development of cancer diagnosis and treatment techniques., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV) modulates immune-related inflammatory responses to induce milder reactions leading to virus persistence. In this regard, the present study aimed to investigate the link between the HCV genotypes and the proinflammatory and regulatory cytokine levels. Ninety patients with hepatitis C infection (68 treatment-naive and 22 treated patients) and 76 healthy blood donors were studied. The serum levels of IFN-γ, IL-10, IL-17A, and IL-21 were measured by ELISA in the patients and healthy controls. IL-10, IL-17A, and IL-21 levels were significantly higher in HCV patients than in the healthy controls. The same cytokines were also higher in genotype 3a-infected patients compared with genotype 1a-infected patients. Interestingly, in treated patients, lower serum levels of IL-17A and IL-21 were detected in G3a-infected individuals, but not in those infected with G1a. G3a viral load displayed a significant correlation with IL-21 and IL-17A levels. In addition, G1a viral load correlated with IL-10 levels. In G3a-infected patients, a significant association was found between IL-17A serum levels and ALT. We found differences in IL-21 and IL-17A serum levels among HCV-infected patients which were genotype dependent. Since Th17-associated cytokines are associated with the progression of liver disease in HCV patients, IL-17A and IL-21 can be used as important biological markers for evaluating the immunopathogenesis of chronic hepatitis. Our results suggest that HCV G3a along with immune responses such as cytokines in HCV patients should be taken into account when interpreting clinical data and IFN-based therapeutic response.

Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-β estradiol (E2) and phytohemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IL-6, IL-17, IL-23 and TGF-β. We observed a significant increased IL-17, IL-23 and TGF-β expression in PBMCs of patients compared to the healthy individuals. In addition, our findings indicated that IL-6 and IL-17 expressions in PBMCs were induced, following E2 treatment. Our results identified an impact of E2 in stimulation of Th17 phenotype, and upon hormonal oscillations and hormone replacement therapy (HRT), asthma inflammation may be mediated by Th17-associated cytokines.

Background and Objectives: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines., Materials and Methods: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively., Results: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs., Conclusions: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA., (Copyright © 2017. Published by Elsevier B.V.)

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection has become a serious public health problem. The influence of HIV/HCV coinfection on plasma HCV RNA loads and clinical criteria which are usually regarded as a predictor of the progress of liver disease have not been reliably evaluated., Objectives: This study investigated the impact of HIV infection on HCV RNA load and clinical indexes in Yazd and Tehran., Materials and Methods: HCV/HIV-coinfected patients and HCV-monoinfected controls were examined and compared for plasma HCV RNA and related risk factors such as HCV genotypes, liver enzymes, and transmission routes., Results: A total of 54 HCV/HIV-coinfected patients and 88 HCV-monoinfected controls were studied. The HCV RNA load mean was significantly higher in HCV/HIV-coinfected patients than in HCV-monoinfected patients (p < 0.001). HCV RNA load mean in patients infected with HCV without anti-HCV therapy was lower than HIV/HCV patients with and without highly active antiretroviral therapy that this difference was significant (p < 0.001). The HCV RNA levels were significantly higher in HIV/HCV genotype 3a coinfected patients than in genotype 3a monoinfected patients (p < 0.001). HIV RNA levels were lower in genotype 1a infected patients than in genotype 3a infected patients, but this difference was not significant statistically. The ALT mean levels were significantly higher in genotype 3a HIV/HCV-coinfected patients than in genotype 3a HCV-monoinfected patients (p < 0.001)., Conclusions: HIV/HCV coinfection leads to a significant increase in plasma HCV RNA. Further evaluations of the effects of ART and HIV infection on the course of HCV infection and the response to treatment against HCV infection in other and different genotypes are also needed. Moreover, HIV-infected patients should be screened regularly for HCV coinfection, particularly if they are in high-risk groups such as IDUs and recipients of blood transfusions.

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans., Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients., Patients and Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA)., Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group., Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages.

Background/aim: Recent studies have shown that IL-17-producing CD4+ T helper (Th17) cells play an important role in proinflammatory processes. In this report we analyzed IL-17, IL-21, and TGF-β serum levels in the peripheral blood of Iranian beta-thalassemia major patients that clinically exhibited splenectomy and iron overload., Materials and Methods: Blood samples were collected from 43 beta-thalassemia patients and 43 healthy individuals with no history of malignancies or autoimmune disorders. Then serum levels of IL-17, IL-21, and TGF-β were measured by enzyme linked immunosorbent assay (ELISA)., Results: The levels of IL-17 (P = 0.005) and TGF-β (P < 0.001) were significantly higher in the thalassemia patients compared to the healthy control. No significant differences in the level of serum IL-21 was observed between the patients and controls. There were no significant differences in serum levels of IL-17, IL-21, and TGF-β between patients with high or low serum levels of ferritin., Conclusion: Multiple blood transfusions cause constant immune stimulation, as a result of repeated exposure to new alloantigens. This might have significant effects on the stimulation of cytokine producing cells in those patients and cytokine profile can be used as a related marker for assessing disease severity and consequently therapeutic intervention.

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. The aim of this study was to determine the frequency of HLA-DRB1 alleles in Iranian patients with AIH and investigate the association between HLA alleles and the different types of the disease. Fifty-four AIH patients and 100 age- and sex-matched healthy controls were subjected to low resolution HLA-DRB typing performed by polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. The results revealed higher frequencies of HLA-DRB1(∗)03, and DRB1(∗)13 alleles in patients with AIH compared to controls. However, DRB1(∗)11 was less frequent in AIH patients. In type I AIH patients HLA-DRB1(∗)03, HLA-DRB1(∗)04, HLA-DRB1(∗)08, and HLA-DRB1(∗)13 were the most frequent alleles. While in type II, the most frequent alleles were HLA-DRB1(∗)07 and HLA-DRB1(∗)13. The seronegative patients showed more frequency of HLA-DRB1(∗)03 and HLA-DRB3. In contrary, the frequency of HLA-DRB1(∗)11, HLA-DRB1(∗)15 and HLA-DRB5 in type 1 was less than healthy individuals. These findings indicate the role of HLA-DRB haplotypes in AIH susceptibility and protection, in the Iranian population., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Interleukin (IL)-17-producing CD4(+) T helper (Th17) cells that are known to produce IL-17 have recently been defined as a unique subset of proinflammatory helper cells. Interleukin 17 is an inflammatory cytokine with robust effects on many cells. It can play important roles in the pathogenesis of diverse groups of immune-mediated diseases. In this regard, the present case-control study aimed at determining serum levels of IL-17, IL-6, and transforming growth factor β (TGF-β) in Iranian breast cancer patients. Blood samples were collected from 55 patients with breast cancer and 34 healthy individuals with no history of malignancies or autoimmune disorders, based on simple sampling. The serum levels of IL-17, IL-6 and TGF-β were measured by enzyme-linked immunosorbent assay (ELISA). The serum level of IL-6 was significantly lower in patients with breast cancer compared with healthy individuals (p = 0.0003), and also the IL-17 was lower in the patient group than in controls (p = 0.01). Interestingly, the TGF-β serum level in patients was less than in controls (p < 0.0001). As most of the cases investigated in this study were in their early stages, it can be concluded that reduced IL-17, IL-6, and TGF-β can be used as predictors for clinical stage and prognosis of cancers such as breast carcinoma.

Aim: The purpose of this study was to compare the distribution of interleukin (IL)-28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C based on the genotype., Background: Polymorphisms in the region of IL-28B gene have been identified as the strongest genetic pretreatment predictor of sustained virological response (SVR) in hepatitis C infection., Patients and Methods: In this study, 147 patients with chronic hepatitis C and 80 healthy individuals were included. The IL-28B rs12979860 and rs8099917 polymorphisms were genotyped by PCR-RFLP method and the frequency of IL-28B polymorphisms with respect to HCV genotypes was also determined., Results: The frequencies of rs12979860 TT, CC and CT genotypes in the chronic hepatitis C patients and healthy individuals were as follows: 10.8% vs. 11.3%, 38.7% vs. 46.2% and 50.3% vs. 42.5%. Also, the frequencies of rs8099917 TT, GG and GT genotypes in the chronic hepatitis C patients was 61.9%, 6.1% and 32% and in controls was 47.5%, 11.2% and 41.3%. The differences in the distribution of rs12979860 genotypes and alleles between HCV genotype 1 and HCV genotype 3a infected patients were statistically significant., Conclusion: The rs12979860 C allele is the favorable allele for the spontaneous clearance of HCV. It seems that the impact of IL-28B polymorphism on the spontaneous clearance of HCV genotype 3 is more prominent than HCV genotype 1, which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

Background: Interleukin (IL)-17-producing CD4+ T helper (Th17) cells thatare known by producing IL-17 have recently been defined as a unique subset of proinflammatory helper cells. IL-17 is an inflammatory cytokine with robust effect on many cells and it can play important roles in pathogenesis of diverse groups of immune-mediated diseases., Objectives: The aim of this case-control study was to determine the gene expression of IL-6, IL-17, and transforming growth factor beta (TGF-β) in Iranian patients with bladder cancer., Patients and Methods: Blood samples were collected from 37 patients with bladder cancer and 37 healthy individuals with no history of malignancies or autoimmune disorders, based of simple sampling. The expression of IL-6, IL-17, and TGF-β were measured by quantitative real-time polymerase chain reaction (qRT-PCR)., Results: The mean of IL-17 transcripts was significantly higher in patients with bladder cancer compared with healthy individuals (0.33 ± 0.06 vs. 0.42 ± 0.14, ) (P = 0.04), but their TGF-β was lower (12.53 ± 8.41 vs. 54.94 ± 17.95, ) (P = 0.04). However, the IL-6 transcripts level was similar in both groups (5.34 ± 2.40 vs. 8.07 ± 3.28, ) (P > 0.05) and there was not any significant difference between the noted cytokines expressions among patients with different stages and grades., Conclusions: As most of the cases studied in this investigation were in stages I and II, IL-17 as a prominent proinflammatory cytokine may play an important role in recruiting and infiltrating of antitumor immune responses in early stages of bladder cancer. Furthermore, it can be used as predictor for the clinical stage and prognosis of cancers such as bladder carcinoma.

Background: The immune system plays important roles in determining the outcomes of hepatitis C virus (HCV) infection. Interleukin-23 and -27 (IL-23 and IL-27) are two novel IL-12 cytokine family members known to enhance the T-lymphocyte response, but their precise involvement in HCV infection is not well known., Objectives: We investigated the serum IL-27 and IL-23 levels in patients with HCV infection and in healthy individuals., Patients and Methods: In this case-control study, we assessed IL-23 and IL-27 levels in serum of 37 healthy individuals and 64 patients with chronic HCV using Enzyme-linked immunosorbent assay (ELISA). The relationship of cytokines level with liver enzymes (ALT, AST, and ALP), HCV genotype and viral load were analyzed. The differences of these cytokine levels in the groups of treatment and no treatment was compared. HCV genotypes were classified by HCV-specific primers methods. HCV RNA loads were determined by fluorescence quantitative PCR., Results: Serum level of IL-23 was higher in HCV infected patients compared to control group (P = 0.005). However, no significant difference was seen in IL-27 serum level between patients compared to the control group (P = 0.65). There was no significant difference in IL-23 and IL-27 level between genotype 1 HCV-infected- and 3a HCV-infected- patients. Positive moderate correlation between IL-23 and IL-27 with viral load was found in type 3a and 1 HCV-infected patient. Positive relative correlation was seen between ALT and IL-23 in 1a HCV-infected patients, which was higher than 3a HCV-infected patients; but there were no significant difference between serums liver enzymes with IL-23 and IL-27 in respect to genotype 3a and 1a HCV-infected patients., Conclusions: These findings may reflect a vigorous pro-inflammatory reaction orchestrated by the host immune system against chronic HCV. Also, a better understanding of the involvement mechanism considering the correlation between other genotypes with inflammatory cytokines in various stages of disease can be obtained.

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-β) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-β were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-β (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

Background: The Hepatitis C Virus (HCV) is considered essentially hepatotropic, yet the virus compartments have also been found in important extra hepatic sites. Detection of HCV RNA in extra hepatic reservoirs such as peripheral blood mononuclear cells (PBMCs) is important for determining disease progression and treatment effectiveness., Objectives: The present study aimed to determine different HCV genotypes in patients' plasma and PBMC specimens, in Jahrom city of Iran., Patients and Methods: Blood samples of 137 patients with established HCV were collected at the Honari clinic. These patients were anti-HCV and plasma HCV RNA positive. After plasma RNA extraction and obtaining a pellet of approximately 3-5 × 10(6) PBMCs, Real-time PCR was performed, using specific-genotype primers. Finally, data analysis was done by the Statistical Package for Social Sciences (SPSS) software., Results: Subtype 3 was the most common genotype in plasma (57.7%) and PBMCs (51.1%). Subtype 1a was detected in 36.5% and 30.7% of plasma samples and PBMCs, respectively whereas subtype 4 was not detected in any of the cases. There was a genotype difference between plasma and PBMCs of 12.4% of patients. In four patients no genotype was detected in their plasma but genotype 3 was detected in the PBMCs., Conclusions: It is suggested that determination of the target genotype by plasma subtyping for choosing the proper antiviral therapy is essential but may result in therapy failure. HCV genotyping in PBMC samples, along with plasma specimens, might be more beneficial. Therefore determining the HCV genotype in PBMCs, before beginning the therapy is useful due to the possibility of occult infection detection.