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During the early days of the COVID-19 pandemic, low dose radiation therapy (LDRT) was proposed as a potentially effective treatment method. To minimize potential toxicity, the initial treatment approach involved a few mGy of adapting radiation followed by a single 250 mGy whole lung challenging dose. However, antiviral drugs were also introduced as a promising treatment option, which were thought to have the potential to revolutionize the management of the crisis. Despite early warnings, many physicians did not fully consider the key point that, in contrast with LDRT, antiviral drug treatments can result in strong selective pressure on the virus. This can lead to the emergence of new SARS-CoV-2 variants, a phenomenon that can have serious global consequences. After more than two years, the truth has been revealed: the WHO Guideline Development Group has advised against the use of remdesivir, a widely used antiviral medication, for COVID-19. Meanwhile, a growing body of evidence suggests that LDRT can be a promising, low-risk approach for avoiding or delaying invasive respiratory support in COVID-19 patients. Although there is substantial supporting documentation, more high-quality, controlled, and randomized double-blind clinical trials are needed to further investigate the efficacy and potential therapeutic mechanisms of LDRT for COVID-19.

Obsessive-compulsive disorder (OCD) is the fourth most common psychiatric disorder with a significant morbidity rate. Despite various treatment modalities and medications, some patients show no definitive response. The aim of this study is to classify the medications of OCD with machine learning (ML) methods and to compare the classification performances of the decision tree (DT), chi-square automatic interaction detection (CHAID) algorithm, and linear model in ML methods. This research is a descriptive analytical study based on co-word and artificial intelligence methods. The DT models were created with a target (total weight link strength). For hyperparameter optimization, the Gini index was used as the weight total link strength. The performance of the DT model was evaluated based on the prediction model. A total of 116 drugs were extracted from 6574 articles based on co-word analysis, and 56 drugs were classified as the DT's root. These drugs were categorized into six groups in the EWKM diagram. The DT was constructed using the weight.total.link index, with 7 items in Label 3 and 42 items in Label 5 serving as DT leaves. The ML analysis provided valuable insights into the efficacy of various medications such as clomipramine, duloxetine, and pindolol, as well as supplements such as folate, in the treatment of OCD. Treating concomitant diseases, namely hypothyroidism and streptococcal infection could improve the efficacy of treatment.

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P

Abstract Introduction Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case–control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history. Methods This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth’s bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups. Results The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06–0.20 and P

Background: Multiple sclerosis (MS) as a complex neurological abnormality is marked with loss of myelin and axons due to chronic inflammatory and autoimmune responses. The modulatory properties of the low dose radiation (LDR) on inflammatory and immune responses have well known.Objective: The current research aimed to assess the impacts of LDR on the disability in patients suffering from MS.Material and Methods: This experimental pilot study was done on 10 patients with secondary progressive multiple sclerosis (SPMS). After magnetic resonance imaging, the SPMS patients were treated by LDR at a daily dose of 2 Gray for 5 consecutive days (totally 10 Gray dose) using a linear accelerator. The extent of the disability was evaluated one week after the completion of radiotherapy using expanded disability status scale (EDSS).Results: After receiving radiotherapy, the patients had a feeling of wellbeing of some sort. The mean of EDSS was significantly reduced after radiotherapy compared with before irradiation (7.4±0.45 vs 6.35±1.18; P

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

ABSTRACT: Introduction: We assessed the potential relationship between COVID-19 and laboratory-confirmed cutaneous leishmaniasis (CL)-registered cases with a history of scarring, compared with volunteer participants without history of CL. Methods: This case-control retrospective study was conducted in southeastern Iran with a high anthroponotic cutaneous leishmaniasis (ACL) burden. Results: Overall, n=1010 CL cases (n=479 male, n=531 female) were evaluated for infection with SARS-CoV-2. In the CL case group, 2 men and 1 woman (0.3% in total) had a mild form of COVID-19 disease; none were hospitalized or died. In contrast, of n=2020 participants without history of CL, n=57 (2.9%) contracted laboratory-confirmed COVID-19, including mild (66.7%), hospitalized (26.3%), critical (3.5%) and fatal (3.5%). There was a strong negative association between CL infection and COVID-19. The burden of COVID-19 in CL-cured participants significantly reduced the morbidity (odds ratio: 0.12; CI: 0.03–0.30; P

At the beginning of the COVID-19 emergence, many scientists believed that, thanks to the proofreading enzyme of SARS-CoV-2, the virus would not have many mutations. Our team introduced the concept of radiation at extremely low doses in an attempt to establish selected pressure-free treatment approaches for COVID-19. The capacity of low-dose radiation to modulate excessive inflammatory responses, optimize the immune system, prevent the occurrence of dangerous cytokine storm, regulate lymphocyte counts, and control bacterial co-infections as well as different modalities were proposed as a treatment program for patients with severe COVID-19-associated pneumonia. There is now substantial evidence which indicates that it would be unwise not to further investigate low-dose radiation therapy (LDRT) as an effective remedy against COVID-19-associated pneumonia.

Objective: Following bone trauma, several factors participate in making a balance between the activity of osteoblasts and osteoclasts. The receptor activator of nuclear factor kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK), and osteoprotegerin (OPG) molecules play critical roles in the healing process via regulation of osteoclasts function. Turmeric is suggested to have an anti-osteogenic potential; however, its effect on accelerating bone healing has not been adequately studied. Here, we used a rat model of femur fracture to explore the effect of treatment with turmeric extract on the bone repair and the expression of RANK, RANKL, and OPG molecules.Materials and methods: Eight rats were subjected to surgery, randomly divided into two groups, and treated orally with turmeric (200 mg/kg), or olive oil. Four oil-treated rats without bone fracture were used as control group. After six weeks of treatment, the femurs of animals were examined for radiological, histological, and gene expression analysis.Results: X-ray radiography showed thicker callus and a more obscure fracture line in the turmeric group. Furthermore, higher osteoblast percentages but no osteoclasts were observed in turmeric-treated animals, representing better repair of bone in the fracture site. Also, real-time analyses showed that treatment with turmeric reduced RANK and RANKL expression (p

Background: Recent evidences revealed that some genetic factors strongly predict occurrence of lamotrigine (LTG)-related skin reactions. The present study aimed to assess the association between some human leukocyte antigen (HLA)-B alleles and risk of LTG-related skin reactions among a sample of epileptic patients.Methods: Totally, 36 epileptic patients expressing LTG-related skin reactions and 70 sex- and age-matched healthy individuals were enrolled into this case-control study. Blood samples were collected from all participants and genomic DNA was extracted by salting-out method. HLA-B alleles were determined using standard sequence specific primer-PCR (SSP-PCR) technique.Results: Of the 31 HLA alleles assessed in our survey, the frequencies of HLA-B*38 and HLA-B*40 were significantly higher in epileptic patients with LTG-related skin reactions when compared to the control group. In term of gender, the frequency of HLA-B*40 allele was significantly higher in the epileptic men with LTG-related skin reactions, whereas the frequency of HLA-B*38 allele was significantly higher in the epileptic women with LTG-related skin reactions than controls with the same gender. Moreover, the frequency of HLA-B*38 allele in patients with high grade of LTG-related skin side effects was significantly higher than patients with low grade of LTG-related skin side effects.Conclusion: These results indicated possible association between HLA-B*40 and HLA-B*38 alleles and LTG-induced skin lesions in Iranian epileptic patients. HLA-B*40 and HLA-B*38 alleles might be differentially expressed in male and female epileptic patients with LTG-induced skin lesions.

Mutations and the glycosylation of epitopes can convert immunogenic epitopes into non-immunogenic ones via natural selection or evolutionary pressure, thereby decreasing their sensitivity to neutralizing antibodies. Based on Thomas Francis’s theory, memory B and T cells induced during primary infections or vaccination will freeze the new mutated epitopes specific to naïve B and T cells from the repertoire. On this basis, some researchers argue that the current vaccines derived from the previous strains of the SARS-CoV-2 virus do not increase immunity and may also prevent the immune response against new epitopes. However, evidence shows that even if the binding affinity is reduced, the previous antibodies or T cell receptors (TCRs) can still bind to this new epitope of the Beta, Gamma, and Delta variant if their concentration is high enough (from a booster injection) and neutralize the virus. This paper presents some convincing immunological reasons that may challenge this theory and argue for the continuation of universal vaccination to prevent further mutations of the SARS-CoV-2 virus. Simultaneously, the information presented can be used to develop vaccines that target novel epitopes or create new recombinant drugs that do not lose their effectiveness when the virus mutates.

In addition to the respiratory system, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strikes other systems, including the digestive, circulatory, urogenital, and even the central nervous system, as its receptor angiotensin-converting enzyme 2 (ACE2) is expressed in various organs, such as lungs, intestine, heart, esophagus, kidneys, bladder, testis, liver, and brain. Different mechanisms, in particular, massive virus replication, extensive apoptosis and necrosis of the lung-related epithelial and endothelial cells, vascular leakage, hyper-inflammatory responses, overproduction of pro-inflammatory mediators, cytokine storm, oxidative stress, downregulation of ACE2, and impairment of the renin-angiotensin system contribute to the COVID-19 pathogenesis. Currently, COVID-19 is a global pandemic with no specific anti-viral treatment. The favorable capabilities of the ginger were indicated in patients suffering from osteoarthritis, neurodegenerative disorders, rheumatoid arthritis, type 2 diabetes, respiratory distress, liver diseases and primary dysmenorrheal. Ginger or its compounds exhibited strong anti-inflammatory and anti-oxidative influences in numerous animal models. This review provides evidence regarding the potential effects of ginger against SARS-CoV-2 infection and highlights its antiviral, anti-inflammatory, antioxidative, and immunomodulatory impacts in an attempt to consider this plant as an alternative therapeutic agent for COVID-19 treatment.

Downregulated expression of anti-tumor miR-383 has been found in many kinds of cancer. MiR-383 family members can directly target the 3′-untranslated region (3′-UTR) of the mRNA of some pro-tumor genes to attenuate several cancer-related processes, including cell proliferation, invasion, migration, angiogenesis, immunosuppression, epithelial-mesenchymal transition, glycolysis, chemoresistance, and the development of cancer stem cells, whilst promoting apoptosis. Functionally, miR-383 operates as a tumor inhibitor miRNA in many types of cancer, including breast cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, colorectal cancer, esophageal cancer, lung cancer, head and neck cancer, glioma, medulloblastoma, melanoma, prostate cancer, cervical cancer, oral squamous cell carcinoma, thyroid cancer, and B-cell lymphoma. Both pro-tumor and anti-tumor effects have been attributed to miR-383 in ovarian cancer. However, only the pro-tumor effects of miR-383 were reported in cholangiocarcinoma. The restoration of miR-383 expression could be considered a possible treatment for cancer. This review discusses the anti-tumor effects of miR-383 in human cancers, emphasizing their downstream target genes and potential treatment approaches.

Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions.

As effector innate immune cells and as a host to the protozoan parasite Leishmania, macrophages play a dual role in antileishmanial immunoregulation. The 2 key players in this immunoregulation are the macrophage-expressed microRNAs (miRNAs) and the macrophage-secreted cytokines. miRNAs, as small noncoding RNAs, play vital roles in macrophage functions including cytokines and chemokines production. In the reverse direction, Leishmania-regulated cytokines alter miRNAs expression to regulate the antileishmanial functions of macrophages. The miRNA patterns vary with the time and stage of infection. The cytokine-regulated macrophage miRNAs not only help parasite elimination or persistence but also regulate cytokine production from macrophages. Based on these observations, we propose a novel immunoregulatory framework as a scientific rationale for antileishmanial therapy.

Abstract Background Epidemics of cutaneous leishmaniasis (CL) are occurring more frequently and spreading faster and farther than before in many areas of the world. The present study aimed to assess a long-lasting emerging epidemic (2005–2019) of 5532 cases with anthroponotic CL (ACL) in peri-urban areas of Kerman city in southeastern Iran. Methods This descriptive-analytical study was carried out for 15 years in Kerman province, southeastern Iran. The data were passively obtained through the health surveillance system and the Kerman Leishmaniasis Research Center. Every subject was diagnosed using direct smear microscopy. The representative causative agent was further examined by ITS1-PCR, PCR-RFLP, 7SL RNA gene sequencing and phylogenetic analyses. For each subject, a case report form designating demographic and clinical data was recorded. Results A different pattern of ACL incidence was found in peri-urban areas compared to that in the city of Kerman. The incidence rate of ACL cases has significantly increased (P

ABSTRACT BACKGROUND: During the Helicobacter pylori (HP) infection, the infiltration of the leukocytes into stomach mucosa is directed by locally produced chemokines that play a decisive role in infection outcome. The CagA is the most potent virulence factor of HP, so that the infection with CagA + strains is associated with more severe complications than infection with CagA - HP. OBJECTIVE: The aim was to determine the expression of chemokines CXCL10, CCL17, CCL20 and CCL22, and their receptors by CagA + HP- and CagA - HP-derived crude extract (HP-CE)-stimulated peripheral blood mononuclear cells (PBMCs) from peptic ulcer (PU) patients. METHODS: The serum and the PBMCs were collected from 20 HP-infected PU patients, 20 HP-infected asymptomatic subjects (HIA) and 20 non-infected healthy subjects (NHS). The PBMCs were cultured in absence of stimulator or with 10 µg CagA + HP crude extract (CagA + CE), 10 µg CagA - HP crude extract (CagA - CE). Chemokines and receptors were measured by ELISA and real time-PCR respectively. RESULTS: In PU patients, the production of chemokines CXCL10, CCL17, CCL20 and CCL22, and the expression of chemokine receptors CXCR3, CCR4 and CCR6 by CagA + CE-induced PBMCs were significantly higher than non-stimulated and CagA - CE stimulated cultures. The CXCL10 production by CagA + CE stimulated PBMCs from HIA subjects was significantly higher than the equal cultures from PU and NHS groups. The CCL17 and the CCL20 production by non-stimulated, CagA + CE stimulated, and CagA - CE stimulated PBMCs from PU subjects were significantly higher than the equal cultures from NHS and HIA groups. The CCL22 production by non-stimulated, CagA + CE stimulated and CagA - CE stimulated PBMCs from NHS group were significantly higher than the equal cultures from HIA and PU groups. The CagA + CE stimulated PBMCs from HIA subjects expressed lower amounts of CCR6 in comparison with CagA + CE stimulated PBMCs from NHS and PU groups. The serum levels CXCL10 and CCL20 in PU and HIA groups were significantly higher than NHS subjects. NHS and HIA groups displayed higher serum levels of CCL22 in comparison with PU patients. CONCLUSION: Results indicated that the CagA status of bacterium influence the expression of chemokines and receptors by HP-CE stimulated PBMCs from PU patients.

COVID-19 and malignancy can affect the susceptibility of one another. Clinically recovered COVID-19 individuals display immune abnormalities that persist several months after discharge. The lymphopenia-related immunosuppression, functional exhaustion of cytotoxic lymphocytes (such as CD8+ cytotoxic T-cells and natural killer cells), hyperinflammatory responses, oxidative stress, downregulation of interferon response, development of the myeloid-derived suppressor cells, downregulation of tumor suppressor proteins and perhaps reactivation of the latent oncogenic viruses may directly and/or indirectly play a role in the cancer development and recurrence in severe COVID-19 patients. SARS-CoV-2-infected malignant patients may be at higher risk of death of their cancer than SARS-CoV-2-uninfected patients with the same cancers. On the other side, the patients with some types of cancers may be more vulnerable to SARS-CoV-2 infection compared with the non-cancerous individuals, due to their immunocompromised state resulted from malignancy, chemotherapy, and other concomitant abnormalities as well as perhaps greater expression of angiotensin-converting enzyme 2. SARS-CoV-2-infected cancerous patients are unable to produce an effective anti-virus immune response and may exhibit more severe forms of COVID-19. This review described the possible impacts of SARS-CoV-2 infection on cancer development and recurrence, and the potential cancer impacts on COVID-19 development, while the possible interventions are highlighted.

Metformin, cimetidine, and ibuprofen separately exhibit immunomodulatory and anti-tumorigenic effects. Herein, the impacts of metformin alone and in combination with cimetidine/ibuprofen on some Th1- and regulatory T (Treg) cell-related parameters were evaluated using a breast cancer (BC) model. For establishing the BC model, four groups of Balb/c mice were challenged with the carcinoma cell line. After 11-30 days post-induction, they were treated intraperitoneally (with metformin (200 mg/kg), "metformin plus cimetidine (20 mg/kg)"; "metformin plus ibuprofen (20 mg/kg)", or with all three drugs in mentioned doses. Untreated BC and without tumor mice were enrolled as control groups. On day 31, splenic Th1 and Treg cell frequencies, serum interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) concentration, and intra-tumoral T-bet, TGF-β, and forkhead box protein P3 (FOXP3) expression were measured; using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time-PCR, respectively. Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-γ concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-β concentration, and the expression of FOXP3 and TGF-β compared with un-treated BC mice. FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy. Survival rate and body weight were increased, while tumor size and spleen index were reduced in mice treated with metformin alone and its combination with cimetidine and/or ibuprofen. No remarkable differences were found between metformin-treated mice and those who received combination therapies regarding Th1 and Treg cell percentages, TGF-β expression, body weight, tumor size, and spleen index. The benefits of combinational therapy may be largely attributed to metformin. Immunotherapeutic potentials of metformin in cancers need further considerations.

Cutaneous leishmaniasis (CL) is a curable disease; however, due to various risk factors, unresponsiveness to CL treatments is inevitable. The treatment of CL has been firmly correlated with multiple determinants, such as demographical, clinical, and environmental factors, the host’s immune response, poor treatment adherence, the parasite’s genetic make-up, and Leishmania RNA virus. This study primarily focuses on the risk factors associated with different therapeutic outcomes following meglumine antimoniate (MA; Glucantime®) treatment and policy approaches to prevent unresponsiveness in CL patients with a focus on anthroponotic form (ACL). Findings suggest that effective preventive and therapeutic measures should be more vigorously implemented, particularly in endemic areas. Accordingly, extensive training is essential to monitor drug unresponsiveness regularly, especially in tropical regions where the disease is prevalent. Since humans are the fundamental reservoir host of ACL due to L. tropica, prompt detection, early diagnosis, and timely and effective treatment could help control this disease. Furthermore, major challenges and gaps remain: efficacious vaccine, new tools, and expert staff are crucial before CL can be definitively controlled.

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel anti-inflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores >5 werehigher than those with WOMAC scores25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner.The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

Cesarean section (CS) is an important challenge for a pregnant woman and her newborn. The most common anesthesia techniques used for CS are general anesthesia (GA) and spinal anesthesia (SA). This study was designed to compare the modulation of genes whose expression level is indicative of the immune system following exposure to GA and SA. The present study was performed on 40 women who were scheduled for elective CS receiving GA or SA. The expression levels of the relative mRNA of Interleukin (IL)-4, IL-6, IL-10, IL-17, Interferon (IFN)-γ, and tumor growth factor (TGF)-β before anesthesia (T0) and 24 hours post-anesthesia (T1) were analyzed by real-time polymerase chain reaction (RT-PCR) technique. Twenty-four hours post-anesthesia, the expression levels of IL-10, IL-17, and IFN-γ genes were decreased while the expressions of IL-4, IL-6, and TGF-β genes were upregulated in two groups, however, the differences were not significant. The mRNA level of IL-4 was increased in the SA group significantly. The post-CS mRNA levels of IL-4 in the SA group may indicate that SA is more appropriate than GA for the initiation of tissue repair pathways.

IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy.

COVID-19, a respiratory infection caused by the virus SARS-CoV-2, causes a variety of symptoms in infected people. We have recently addressed our concerns over unintentional “Directed Accelerated Evolution” of the SARS-CoV-2 and introduced a modified treatment method for ARDS associated with COVID-19. COVID-19 outbreak could last for a long time in communities. Due to growing requests for medical equipment such as ventilators and ICU beds, “flattening the epidemic curve” has been considered as an effective strategy to adjust the level of health care demand to potential capacity of the system. In this paper, we compare possible outcomes of “Without Precaution” and “With Precaution” epidemic models. When there are no precautions, a higher number of people would be infected. RNA viruses such as SARS-CoV-2 have extremely high mutation rates. Accordingly, the combination of a higher number of infected people and any effort for inactivation of the viruses is expected to exert a strong selective pressure on SARS-CoV-2 that can lead to more mutations. These mutations can be either pathogenicity attenuating mutations (PAMs) or pathogenicity promoting mutations (PPMs). On the other hand, when flattening strategy is used, the number of infected people will be lower than the previous model, but both type of mutations may occur, although with lower frequency. Although the occurrence of PAMs helps the development of herd immunity, possible occurrence of PPMs needs serious tracking, especially in patients with severe COVID-19, to prevent new endemic with more virulent mutant viruses.

Introduction: Multiple Sclerosis (MS) is an inflammatory disorder caused by self-reactive Th1 lymphocytes, while Th2 cells may confer protection. The Th1 and Th2 cell differentiation are regulated by specific transcription factors, especially T-bet and GATA-3, respectively. This investigation aimed to measure the T-bet and GATA-3 expression by Peripheral Blood Mononuclear Cells (PBMCs) obtained from MS patients after specific and non-specific in vitro stimulation. Methods: The PBMCs were separated from 22 patients with MS and 20 healthy individuals. They were cultured at 37°C for 24 h in the absence of a stimulator or in the presence of Myelin oligodendrocyte Glycoprotein (MOG) or Phytohemagglutinin (PHA) at a concentration of 10 μg/mL. Then the T-bet and GATA-3 expression was measured by real time-PCR. Results: The T-bet expression was enhanced, while the GATA-3 expression diminished. Therefore the expression of T-bet/GATA-3 ratio diminished in not-stimulated, MOG-stimulated and PHA-stimulated PBMCs from MS patients compared with equal cultures from the healthy individuals (P

Background & objective The immunoregulatory effects of transforming growth factor (TGF)-βand interleukin-12 (IL-12) and immunomodulatory actions of vitamin D (VD) were reported in several studies. This study aims to evaluate VD effects on IL-12 and TGF-β expression in experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in three groups of C57BL/6 mice by immunization with MOG and administered intra-peritoneally 200 ngVD, PBS or olive oil (OO) from day +3 to +30. One group was also considered as healthy control group. At day 31, cytokines expression in the spinal cord and their serum levels were determined using real time-PCR and ELISA, respectively. Results: IL-12 gene expression and its serum levels in PBS-injected- or OO-administrated EAE groups were significantly higher than healthy group. IL-12 gene expression in EAE group treated with VD was significantly decreased compared to PBS-injected- or OO-administrated EAE groups (P Conclusion: VD modulates the expression of IL-12 and TGF-β in spinal cord and serum of EAE mice.

Objectives: Imbalances in effector T cell functioning have been associated with a number of autoimmune diseases, including Hashimoto’s thyroiditis (HT). Differentiation of effector T helper (Th) 1, Th2, Th17 and regulatory T cell (Treg) lymphocytes is regulated by transcription factors, including Th1-specific T box (T-bet), GATA binding protein-3 (GATA3), retinoid-related orphan receptor (ROR)-α and forkhead box P3 (FOXP3). This study aimed to investigate Th1/Th2, Th1/Treg, Th2/Treg and Th17/Treg balances at the level of these transcription factors. Methods: This study took place between October 2015 and August 2016. Peripheral blood mononuclear cells were collected from a control group of 40 healthy women recruited from the Zahedan University of Medical Sciences, Zahedan, Iran, and a patient group of 40 women with HT referred to the Hazrat Ali Asghar Hospital, Zahedan. Total ribonucleic acid extraction was performed and the gene expression of transcription factors was quantitated using a real-time polymerase chain reaction technique. Results: Expression of T-bet and GATA3 was significantly elevated, while FOXP3 expression was significantly diminished among HT patients in comparison with the controls (P = 0.03, 0.01 and 0.05, respectively). Expression of RORα was higher among HT patients, although this difference was not significant (P = 0.15). Expression of T-bet/FOXP3, GATA3/FOXP3 and RORα/FOXP3 ratios were increased among HT patients in comparison with the controls (P

The severity of postoperative pain and hemodynamic changes during and post-cesarean section have a direct effect on the neonatal and maternal condition. This study aimed to compare pain severity, hemodynamic changes, and patient satisfaction following two anesthesia techniques in elective cesarean section. In this blinded study, 60 women who were candidate for cesarean section were allocated into two equal groups of general anesthesia (GA) and spinal anesthesia (SA). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and O2 Saturation at pre cesarean (T0), the uterine incision time (T1), end of surgery (T2), 6h (T3), 12h (T4), and 24 hours post-cesarean (T5) were measured. A Visual Analog Scale assessed post-cesarean pain, 6, 12, and 24 hours post-cesarean. Gender, birth weight, first- and fifth- minutes’ apgar score was recorded in the checklists. The VAS score was significantly higher in the GA group at 6h, 12h, and 24 hours post-cesarean (P=0.014, P=0.002, P=0.017, respectively). SBP and DBP at T1 in the GA group were significantly higher than in the S.A group (P

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys­tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review.

Objective: The main function of IL-12 is differentiation of naive T cells intoTh1 cells and TGF-β is a powerful immunoregulatory cytokine. The immunomodulatory and anti-inflammatory properties of ginger have also been reported in some studies. The aim of this study was to evaluate the effects of ginger extract on the expression of IL-12 and TGF-β in a model of experimental autoimmune encephalomyelitis (EAE).Materials and Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein emulsified in complete Freund's adjuvant. The mice were administered intra-peritoneally with ginger extracts or PBS, from day +3 to +30. On day 31, mice were scarified and the expression of IL-12 and TGF-β mRNA in the spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA.Results: In PBS-treated EAE mice, the expression of IL-12 P35 and IL-12 P40 mRNA in the CNS and the mean serum levels of IL-12 were significantly higher than those of healthy group (p

Background: Multiple sclerosis (MS) is a chronic inflammatory disorder of the CNS characterized by destruction of the myelin sheath, gliosis and progressive neurological dysfunction. The regulatory T (Treg) cells play a major role in the control of the autoimmunity and inflammation. The forkhead box p3 (FOXP3) is a central molecule in the function of Treg cells that play an important role in the immunoregulation. The aim of this study was to investigation single nucleotide polymorphism (SNP), rs2232365, in FOXP3 gene in patients with multiple sclerosis. Methods: In a case-control study, peripheral blood samples were collected from 90 patients with MS (46 men and 94 women with different patterns of disease) from January 2014 to April 2015 in the Afzalipoor Hospital, Kerman (a city located in the southeast of Iran). In a total, 90 healthy subjects were also enrolled into the investigation as a control group. The healthy subjects were recruited among blood donations of the Kerman Transfusion Organization and interviewed regarding CNS disease, and none of them had any history of CNS diseases or other relevant disorders. The SNP rs2232365 in FOXP3 gene was assessed by single specific primer-polymerase chain reaction (SSP-PCR) method. Finally, statistical analysis was performed using SPSS version 22 (Chicago, IL, USA). Results: In both patients and healthy control groups, there was significant difference among subjects with GG, AG, and AA genotypes at rs2232365 in FOXP3 gene. The frequencies of AA and AG genotypes at rs2232365 in the FOXP3 gene were significantly higher in MS group as compared with healthy subjects (P

Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce permanent activation of the immune system and may be considered the most promising method for cancer treatment, especially in combination with other agents of passive immunotherapy. Among various approaches to cancer vaccines, whole tumor cell vaccines have been attracting attention for several years. Despite their low to moderate clinical effects, these vaccines have numerous advantages. Their ability to generate immune responses against tumor-associated antigens reduces the possibility for tumor cells to escape and facilitates the development of “off-the-shelf” allogeneic tumor vaccines. Understanding the reciprocal interactions between tumor cells and leukocytes is a key to harness the full potential of whole cell vaccination. Cytokines are considered as potent immunomodulatory molecules which behave as adjuvants in whole tumor cell vaccines. Improved mechanistic understanding of key cytokines in tumor immunity will serve as a resource for rational design of whole cell cancer vaccines. Although there are several reports about the use of different immunostimulatory cytokines as adjuvants, interleukin (IL)-12 appears to have superior effects compared to other cytokines. This review describes the effects of IL-12 compared to other immunomodulatory cytokines, such as IL-2 and IL-15, and highlights its application in whole cell tumor vaccination.

Background: Anesthesiologists should obtain the best technique for cesarean section (CS). This study designed to compare the effect of general anesthesia (GA) and spinal anesthesia (SA) on immune system function in elective CS. Materials and Methods: This descriptive study was performed on forty candidates for elective CS. They were randomly divided into GA and SA groups. The serum concentrations of interleukin (IL)-4, IL-6, IL-10, and IL-17 and interferon-gamma (IFN-γ) were measured using ELISA method prior to anesthesia (T0), immediately after the uterine incision (T1), 2 h post CS (T2), and 24 h post CS (T3). Data were analyzed using descriptive statistics and Chi-square, independent t-test, and repeated measures. Results: No significant differences were observed between the GA and SA groups regarding the serum levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ. The serum levels of transforming growth factor beta (TGF-β) in the SA group were significantly (P = 0.003) more than that of the GA group at T3. Conclusion: According to the angiogenesis properties of TGF-β, it seems that SA probably affects the rate of recovery more than that of the GA.

Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain. The CARs provide the recognition of target antigen in a MHC-independent manner. CAR-armed T cells may be unable to kill their targets in the absence of co-stimulators like NK cells. On the other hand, CAR-armed NK cells may also be unable to destroy their targets without receiving help signals from Th cells. Thus, if CAR-armed NK cells use together with CAR-armed T cells, NK cells will be aggregated to the tumor site. Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from NK cells, but also other tumor specific T cells will be primed by recognition of tumor specific antigen (TSA) associated with MHC class I. These new specific primed T cells probably combat against tumor cells which have lost their TAAs that CAR-T cells are redirected to them.

Background: Semaphorins play prominent roles in physiological and pathological processes such as vascular development, tumor growth and immune responses. Semaphorins have different roles in various kinds of cancers, but there is no study concerning their expression in the chronic lymphocytic leukemia (CLL). This study aimed to assess the SEMA3A, SEMA4A and SEMA4D expression in patients with CLL. Materials and Methods: Peripheral blood specimens were collected from 30 newly-diagnosed untreated patients with CLL and 30 healthy subjects as a control group. The SEMA3A, SEMA4A and SEMA4D expression was determined by real-time PCR method. Results: The fold change expression of SEMA3A and SEMA4D was 7.58 ± 2.66 and 3.20 ± 0.99 in patients with CLL, and was 1.01 ± 0.31 and 1.00 ± 0.27 in healthy subjects, respectively. The CLL patients expressed higher amounts of SEMA3A and SEMA4D in comparison with healthy subjects (P

Objectives: Interleukin (IL)-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF) IL-33 concentrations in patients with multiple sclerosis (MS). Methods: Blood specimens were obtained from 140 patients with MS (46 males and 94 females) with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females), who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. Results: The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p

Objective(s):IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. Materials and Methods:Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP. Results:The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P

Background: The risk of infectious, autoimmune and immunodeficiency diseases and cancers rise in opioid addicts due to changes in innate and acquired immune responses. Three types of opioid receptors (К،δ،μ) are expressed on the surface of lymphocytes and mononuclear phagocytes. The present study was designed to examine the effects of different concentrations of opium on the secretion of some cytokines produced by lymphocyte cells. Methods: Jurkat cells were exposed to different concentrations of opium for periods of 6, 24 and 72 h in cell culture medium. The amount of interleukin-6 (IL-6), interferon-γ (IFN-γ) and transforming growth factor-b (TGF-β) were then measured using enzyme-linked immunosorbent assay (ELISA) method. Findings: The results showed that opium increases the secretion of IL-6 in different concentration of opium in 6 h. The amount of IFN-γ decreased in 6 h and increased in 24 h significantly compared with control. On the other hand, opium had an inhibitory effect on the TGF-β secretion in 6, 24 and 72 h. Conclusion: Overall, the study showed that opium stimulates pro-inflammatory and suppressed anti-inflammatory cytokine secretion in Jurkat cells. This may account for the negative effect of opium on the immune system leading to chronic inflammation and a base for many disorders in opium addicts.

Objectives: H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group.Methods: A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA.Results: The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p

Background/Aim: Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI. Materials and Methods: In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg - /anti-HBc + samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA. Results: Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg - /anti-HBc + and HBV-DNA was detected in 57/352 (16.1%) of HBsAg - /anti-HBc + samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines. Conclusion: According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.

It has been reported that the immune system undergoes age and gender changes. The aim of this study was to investigate the age- and gender-dependent changes of salivary IgA and IgE levels among healthy subjects. A total of 203 healthy individuals (aged 1-70 years) were enrolled in the study. Two milliliters of saliva were collected from all participants, and salivary IgA and IgE levels were measured by the ELISA technique. Mean salivary IgA levels were significantly higher in subjects aged 11-20 years as compared to subjects aged 1-10 years (P < 0.01). Mean salivary IgA levels increased with age up to the age of 60 years, and then slightly decreased in subjects aged 61-70 years. The frequency of subjects with detectable levels of salivary IgE and mean salivary IgE levels gradually increased with age, with maximum levels being observed in the 31-40 years age group and not changing significantly thereafter. The mean levels of salivary IgA and IgE in adults were significantly higher than those observed in children (P < 0.00001 and P < 0.05, respectively). No significant differences were observed between men and women regarding both salivary immunoglobulins. These results showed age-dependent changes of the salivary IgA and IgE levels. Gender had no effect on the salivary levels of IgA and IgE.

(Received 5 Oct, 2008; Accepted 14 Feb, 2009)AbstractBackground and purpose: Occult hepatitis B infection (OBI) is defined as a form of hepatitis B that despite absence of detectable HBsAg, HBV-DNA is present in patient’s peripheral blood. Genetic and immunological differences appear to play important roles in producing OBI. Therefore, this project was aimed to examine the expression of a chemokine receptor (CCR5) on CD8 T cells of OBI patients.Materials and methods: In this experimental study, 3,700 HBsAg- plasma samples were collected. Samples were tested for anti-HBc antibody and all of HBsAg-/anti-HBc+ samples were screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases. Also, flow cytometry analysis was performed to examine the expression of CCR5 on CD8 T cells of OBI patients.Results: Results of current study showed that 352 (9.5%) cases of samples were positive for anti-HBc. Examination of HBsAg-/anti-HBc+ samples for HBV-DNA by PCR showed that 57 (16.1%) cases had HBV-DNA. Flow cytometric studies indicated lymphocytosis in these patients; however, the number of cells which expressed CD8 and CCR5 is decreased significantly in patients, compared to healthy control. In addition to CD8 T cells, the expression of CCR5 is also decreased on all immune cells.Conclusion: One of the chemokine receptors which are expressed by CD8+ T cells is CCR5 and these cells are recruited to infected tissues, including liver by CCR5. Therefore, based on results of this investigation, one may conclude that due to the decreased expression of CCR5, the CD8+ T cells are unable to respond to the chemokines (CCR5 ligands) and, hence, can not immigrate to the infected liver and incorporate in clearance of hepatitis B virus.J Mazand Univ Med Sci 2009; 19(68): 11-18 (Persian)

Hepatitis B virus (HBV) infection and its sequelae such as cirrhosis and hepatocellular carcinoma has remained a serious public health problem throughout the world. The WHO strategy for effective control of HBV infection and its complications is mass vaccination of neonates and children within the framework of Expanded Programme on Immunization (EPI). Vaccination with hepatitis B surface antigen (HBsAg) induces protective antibody response (anti-HBs ≥ 10 IU/L) in 90-99% of vaccinees.The lack of response to HBsAg has been attributed to a variety of immunological mechanisms, including defect in antigen presentation, defect in HBsAg-specific T and/or B cell repertoires, T-cell suppression, increase in the regulatory T cell count, lack of necessary help of T-cells for production of anti-HBs by B cells, defect in Th1 and/or Th2 cytokine production and selective killing of HBsAg-specific B-cells by human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes. The HLA complex plays an important role in many of these immunological processes.A variety of HLA class I, II, and III alleles and antigens have been reported to beassociated with antibody response to HBsAg vaccination in different ethnic populations. Moreover, some HLA haplotypes were also associated with responsiveness to HBsAg.In this review the association of the HLA specificities with antibody response to hepatitis B (HB) vaccine is discussed.

BACKGROUND: Helicobacter pylori (H. pylori) infection is thought to play an etiologic role in several gastroduodenal diseases including gastric ulcer, duodenal ulcer, gastric MALT lymphoma, and distal gastric cancer. Several studies have suggested that H. pylori which express cytotoxin-associated gene A (CagA) may be more virulent than those that do not, but limited populations have been studied to date. The aims of the present study were to evaluate the seroprevalence of anti-H. pylori IgG, IgA and anti-CagA antibodies in peptic ulcer (PU) patients and healthy individuals in the city of Rafsanjan. METHODS: A total of 60 PU patients (30 males and 30 females, aged 17 to 60 years) and 138 age-matched healthy individuals (65 males, 73 females) were enrolled in this study. Diagnosis of PU disease was established on the basis of findings by gastrointestinal endoscopy. The control group was recruited from among healthy blood donors referred to Blood Transfusion Center of Rafsanjan. A blood sample was collected from each participant and the sera were tested for the presence of anti- H. pylori IgG and IgA antibodies and antibody to bacterial virulence factor (CagA) by use of enzyme-linked immunosorbent assay. The serum concentrations of anti-H. pylori IgA and anti-CagA antibody were expressed as mean ± SD in each group. RESULTS: In PU patients the overall seroprevalence of anti-H. pylori IgG (95.8%), IgA (96.6%) and anti-CagA (91.6%) were higher than those observed in the control group (73.2%, P

It has been also reported that that H. pylori infection may be responsible for some endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus and primary hyperparathyroidism. H. pylori which express cytotoxin-associated gene A (CagA) may be more virulent than those that do not. The aim was to evaluate the seroprevalence of anti-H. pylori IgG and anti-CagA antibodies in patients with type 2 diabetes mellitus (type 2 DM) and healthy individuals from Rafsanjan city (Iran). A total of 100 patients with type 2 diabetes and 100 age-matched healthy individuals were enrolled to study. A blood sample was collected from each participant. The type 2 DM established according to the fasting blood glucose level of 126 mg/dl. The sera were tested for the presence of anti-H. pylori IgG antibodies and antibody to CagA by use of enzyme linked immunosorbent assay. The seroprevalence of anti-H. pylori antibodies in diabetic patients (76%) was similar to that observed in healthy subjects (75%). The mean titer of anti-H. pylori IgG in healthy control group (131.63±11.68 U/ml) was significantly higher than diabetic group (54.43±4.50 U/ml; P

Background and Objectives: Alterations in CXCL10 (a Th1 chemokine) expression have been associated with various diseases. The aim of this study was to evaluate the serum CXCL10 levels in H. pylori-infected patients with peptic ulcer (PU), H. pylori-infected asymptomatic (AS) subjects and healthy H. pylori-negative subjects, and also to determine its association with bacterial virulence factor cytotoxin-associated gene A (CagA). Materials and Methods: Serum samples from 90 H. pylori infected patients with PU (70 were anti-CagA+, 20 were anti- CagA-), 65 AS carriers (40 were anti-CagA+, 25 were anti-CagA-) and 30 healthy H. pylori-negative subjects (as a control group) were tested for concentrations of CXCL10 by using the ELISA method. Results: The mean serum levels of CXCL10 in PU patients (96.64 ± 20.85 pg/mL) were significantly lower than those observed in AS subjects (162.16 ± 53.31 pg/mL, P < 0.01) and the control group (193.93 ± 42.14 pg/mL, P < 0.02). In the PU group, the serum levels of CXCL10 in anti-CagA+ subjects was significantly higher in comparison to anti-CagA- patients (P < 0.04). Conclusion: These results showed that the mean concentrations of CXCL10 in H. pylori-infected-PU patients was lower than AS carriers and control group. In the PU group, the serum levels of CXCL10 were associated with bacterial factor CagA.

The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg. PBMCs were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stimulated in vitro with rHBsAg and the concentration of IL-4, IL-10, IL-12 and IFN-γ were quantitated in culture supernatant by sandwich ELISA. HLA typing was performed by microlymphocytotoxicity method. Significant diminished secretion of both Th1 (IFN-γ) and Th2 (IL-4, IL-10) cytokines was observed in HBsAg-stimulated PBMC from vaccinees expressing the HLA-DR7 compared to DR7 negative vaccinees. Similarly, lower production of these cytokines was also observed in vaccinees with DR7-DR53-DQ2, B7-DR7-DR53-DQ2 and A2-DR7-DR53-DQ2 haplotypes (p

H. pylori is a human pathogen that colonizes the epithelium of the stomach. The host immune response may influence the disease process, where cytokines play important roles in the development of disease. In this study, the concentrations of selected cytokines in the gastric antrum and stomach body mucosa and also in the serum were evaluated. Eighty patients according to their rapid urease test were divided into two groups: H. pylori positive (n=39) and H. pylori-negative (n=41). The concentrations of cytokines in biopsies and serum were determined by ELISA method. The mean TNF-α and IFN-γ levels in the infected group were significantly higher than that of uninfected patients. In contrast, IL-10 level in most patients was undetectable. The mean antral of stomach TNF-α and IFN-γ levels were significantly higher than that of the stomach body. IFN-γ serum level showed positive correlation with antrum and stomach body levels, whereas no correlation was found in TNF-α in different samples. Higher levels of TNF-α and IFN-γ in antral indicate that the colonization of bacteria in the antrum may be higher than stomach body (culture results from two sites support this statement). Increased serum level of IFN-γ indicates the activation of circulating-T cells against infection. Induced H. pylori-related TNF-α is concentrated is gastric mucosa and this pathogen does not cause any significant change in the serum level of this cytokine. Therefore H. pylori by inducing certain inflammatory cytokines but not IL-10 may contribute the process of disease development.

Stromal derived factor-a (SDF-1-a) is a CXC chemokine which has been demonstrated as a recruitment factor for leukocytes to the site of inflammation, infection, injury and following stress. This chemokine has been shown to be expressed by liver cells and in liver diseases. Hence, the aim of this study was to examine the expression of SDF-1 by hepatocytes in responses to the stress imposed during isolation by collagenase perfusion and under heat shock stimulation. In this study hepatocytes (2-5 x 106) were isolated from male Sprague Dawley rat liver and cultured in plates that were pre-coated with collagen Type-I matrix. The western and northern blotting analysis were employed to detect SDF-1 at protein and mRNA levels in isolated and cultured hepatocytes in response to isolation and heat shock stresses. The SDF-1 is expressed by isolated rat hepatocytes immediately after isolation and early culture and decreased with time. SDF-1 protein was highly expressed in freshly isolated cells and decreased by time (27h) (P

Chemokines are classified in four distinct groups as CXC, CC, CX3C and C, depending on the presence or absence of a motif called ELR (Arg-Leu-Glu) before the first cysteine residue in their structure. CXC chemokines are also subdivided into ELR+ and ELR-. Increasing evidence has indicated the existence of a chemokine network in the liver which is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury. The CXC chemokines play a major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. The aim of this study was to examine the response of cultured hepatocytes to exogenous inflammatory cytokines (TNF-a and IFN-g) regarding expression of IP-10 and growth regulatory oncogen (Gro) chemokines. In this study we employed western and northern analysis to measure chemokines at the level of protein and mRNA by hepatocytes in response to pro-inflammatory cytokines. We found that, the pro-inflammatory cytokines, TNF-a and IFN-g, selectively stimulated expression of IP-10 but were without effect on Gro. This confirms a potential direct involvement of these cytokines in chemokine production by hepatocytes. Thus, IFN-g and TNF-a may play a role in hepatic injury and inflammation and produce some of their biological effects by localized induction of chemokines by hepatocytes. Given the similarity to an acute phase response, we were able to show that IFN-g and TNF-a mimicked the effects of cell isolation and culture on induction of IP-10 expression. Further, evidence for linkages between IFN-g and TNF-a and liver injuries is seen in hepatitis C and hepatitis B in which increased levels of TNF-a and its soluble receptor were reported.