Serum Interleukin-38 and Tumor-Infiltrating Lymphocytes in Primary Brain Tumors.

Background: Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. However, its biological roles in brain tumors are not well defined. Objective: To assess the serum levels of IL-38 and the percentages of TILs in the tumor tissues of patients with primary brain tumors and to determine their associations with the pathological features of the disease. Methods: IL-38 was evaluated in sera using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E)-stained sections were scored to determine the percentages of TILs in four different areas: the invasive margin, central tumor, perivascular and perinecrotic areas. Results: IL-38 serum levels were significantly higher in low- and high-grade tumors than in healthy individuals, meanwhile, its levels remained consistent between these two grades. Although no significant difference was found in IL-38 serum levels between different histological subtypes of brain tumors, its levels were significantly higher in intra-axial brain tumors than in extra-axial ones. Additionally, a significant positive correlation was observed between serum levels of IL-38 and tumor size in patients with low-grade tumors. TILs were detected in at least one of the four examined areas; however, no statistically significant correlation was found between IL-38 levels and TILs. Conclusion: Our data may suggest a connection between IL-38 and immune suppression and tumor progression in primary brain tumors. Further investigation is needed to uncover the role of IL-38 in the brain tumor microenvironment.

Systematic review and meta-analysis of knowledge, attitudes, and practices regarding COVID-19 among chronic disease patients: A global perspective.

Background: Chronic health conditions were significantly correlated with an increased clinical severity of coronavirus 2019 (COVID-19) and a heightened risk of COVID-19 mortality. This study aims to determine global knowledge, attitudes, and practices (Knowledge Abuse Profile) of the patients with chronic diseases toward COVID-19. Methods: The study was initiated in December 2019 and extended until April 2023, during which an extensive search for relevant English-language literature was conducted as part of this systematic review and meta-analysis. Google Scholar, Scopus, PubMed/MEDLINE, Science Direct, Web of Science, EMBASE, Springer, and ProQuest were utilized for the search. The quality of included studies was assessed using a quality rating checklist created by Joanna Briggs Institute for cross-sectional research. In the STATA software version 14, inverse variance and Cochran Q statistics were used for statistical analysis to assess heterogeneity among the studies. The Dersimonian and Liard random-effects models were applied in cases where heterogeneity existed. Results: A total of 23 studies involving 14,587 patients contributed to this meta-analysis. These studies comprised 21 studies focused on knowledge, with 6864 participants, 12 studies on attitudes involving 3597 patients, and 12 on practices, encompassing 4126 patients. The pooled estimates for sufficient knowledge, positive attitudes, and COVID-19 preventive behaviors among chronic disease patients were determined as 48.2% (95% confidence interval [95% CI]: 33.9%-62.5%), 60.8% (95% CI: 46.8%-74.8%), and 58.3% (95% CI: 39.5%-77.0%), respectively. Over the years, there was a consistent decrease in adequate knowledge, positive attitudes, and COVID-19 preventive behaviors among the population. Specifically, regarding knowledge, the rates declined from 50.2% in 2020 to 49.7% in 2021 and dropped to 45.1%. Similarly, the percentage of individuals with a positive attitude fell, decreasing from 64.1% in 2020 to 60.3% in 2021 and dropping to 57.9% in 2022. Furthermore, COVID-19 preventive behaviors showed fluctuations, with the rates recorded at 63.7% in 2020, increasing to 75.4% in 2021, and then decreasing to 47% in 2022, in line with the publication dates of included studies. Conclusion: The findings of meta-analysis show a significant decrease in the levels of knowledge, attitudes, and adherence to preventative interventions for COVID-19 among individuals with chronic diseases. The findings emphasize the need for targeted interventions, and ongoing education to address this trend.

Comparison of Interleukin-33 Serum Levels in Patients with Breast Cancer and Idiopathic Granulomatous Mastitis.

BACKGROUND: Breast cancer (BC) is the main cause of cancer death in women. Idiopathic granulomatous mastitis (IGM), a rare chronic disease that clinically mimics breast carcinoma, and is associated with high mortality and morbidity, but an immediate and accurate diagnosis can substantially decrease these rates. Expressed by numerous human tissues, interleukin-33 (IL-33) has an inductive role in the network of pro-inflammatory cytokines. The aim of this study was to investigate the serum levels of IL-33 in BC and IGM patients in comparison with healthy women. MATERIALS AND METHODS: This descriptive-analytical study was carried out on 28 patients with BC and 25 patients with IGM as the patient groups and 25 healthy volunteers with normal screening reports as the control group. Histopathological pattern of BC and IGM were confirmed by specialized pathologists. The serum concentration of IL-33 was measured using enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. RESULTS: The mean age of the patients with BC and IGM and the control group was 49.1, 37.1, and 36.8 years, respectively. There was no significant difference in IL-33 expression among the participants with regard to age, marital status, body mass index (BMI), and menopausal status. IL-33 assay indicated a significant difference between the BC (P=0.011) and IGM (P=0.031) groups compared to the controls, although no substantial differences were observed between the IGM and BC groups. CONCLUSION: IL-33 can be considered a significant factor distinguishing IGM and BC patients from controls, although it cannot be applied to diagnose and differentiate BC from IGM patients.
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Simultaneous Increase in Serum Levels of IL-37 and IL-18 Binding Protein In Low-Grade and High-Grade Brain Tumors.

BACKGROUND: IL-18binding protein (IL-18BP) might play a role in tumor escape from immune surveillance through interacting with IL-37. Such interactions modulate the antitumor activity of IL-18 and affect regulatory T cell (Treg) function. However, the biological roles of IL-37 and IL-18BP have not yet been explored in brain tumors. This study aimed to investigate serum levels of IL-37 and IL-18BP in high-grade and low-grade brain tumors and determine their associations with pathological characteristics of the patients. SUBJECTS AND METHODS: This case-control study consisted of 60 patients with brain tumors (40 low-grade and 20 high-grade) and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the levels of IL-37 and IL-18BP in serum. RESULTS: Our results indicated that serum levels of IL-37 and IL-18BP were significantly higher in patients with brain tumors (109.02, 426.37 pg/mL), high-grade (104.44, 428.87 pg/mL), and low-grade (113.88, 426.37 pg/mL) tumors in compared to healthy controls (35.03, 362.00 pg/mL), (P<0.05). Interestingly, our results revealed a significant positive correlation between IL-37 and IL-18BP serum levels in brain tumors (n=60, R=0.42, P=0.001). Our study also showed that serum levels of IL-37 and IL-18BP in glioblastoma grade IV were approximately similar to those in astrocytoma grade II, meningioma type I, and pituitary adenoma. Furthermore, no significant differences were found in serum levels of IL-37 and IL-18BP between patients with low-grade and high-grade tumors (P=0.24 and P=0.61, respectively). CONCLUSION: The simultaneous increase in IL-37 and IL-18BP serum levels and their positive correlation may facilitate disease progression in low-grade and high-grade brain tumors by inhibiting antitumor immune responses.

The effect of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells in allergic asthma.

INTRODUCTION: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. RESULTS: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10⁻7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. CONCLUSION: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.

Platelet-Derived Procoagulant Microparticles as Blood-based Biomarker of Breast Cancer.

OBJECTIVE: Breast cancer is the main cause of cancer death in women worldwide. Elevated plasma levels of circulating cell-derived microparticles (MPs) have been reported in various types of cancer, including breast cancer, with the ability to mediate inflammation and thrombosis. Microparticles are bioactive agents, and it has been suggested that MPs can be used as a diagnostic, prognostic, or therapeutic biomarker in various diseases. The aim of this study was to investigate the levels of platelet-derived MPs (PMPs) in breast cancer patients. MATERIALS AND METHODS: In this case-control study, 30 patients with breast cancer and 20 normal subjects were sampled after obtaining written consent. MPs were isolated from blood samples by centrifugation technique. CD42b and annexin V markers were used respectively for counting PMPs and procoagulant MPs with flow cytometry. RESULTS: Flow cytometry results showed that the number of PMPs and procoagulant annexin V positive MPs was significantly higher in the breast cancer patients than normal subjects (p <0.001). The number of the annexin V MPs differed significantly in patients with high tumor size (T2) compared to the patients with low tumor size (T1) and controls (p <0.001). Significant and positive correlations were found between PMP levels and tissue-based biomarkers, tumor grading, and distant metastasis (p <0.05). Tumor histological type did not correlate with the numbers of PMPs (p=0.065). CONCLUSION: Increased levels of PMPs and activity in terms of hemostasis and having a positive and significant relationship with tumor grading and metastasis may indicate the effective role of PMPs in the pathogenesis and prognosis of breast cancer.

Toxicity of Saffron Extracts on Cancer and Normal Cells: A Review Article.

BACKGROUND AND AIM: Medicinal plants have played an important role in human health since the Stone Age. According to WHO, 80% of Asian and African people rely on traditional medicine and medicinal plants to conserve their health. Saffron has received much attention among the herbal compounds related to cancer treatment. METHODS: This review aims to provide an overview of in-vitro and in-vivo evaluation molecule mechanism for anti-tumor activity, cancer preventing and protective effects of saffron extract. The review is based on the available data accessible in PubMed, Science Direct, Google Scholar, Magiran.ir, and SID.ir databases. RESULTS: Saffron has selective toxic and preventive effects on cancerous cells and without adverse effects on normal cells and prevents tumor formation. Saffron appears to reduce the toxic effects of anticancer drugs. Saffron has toxicity effects when used in high amounts, which are far greater than those  are used in human food culture. CONCLUSIONS: Considering the observed effects of saffron on the removal of cancer cells, saffron extract can be used in the treatment and prevention of cancer after confirmation in human clinical trials. According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the  more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers.

Prevalence and clinical characteristics of metabolically unhealthy obesity in an Iranian adult population.

PURPOSE: The incidence of obesity is globally increasing and it is a predisposing factor for morbidity and mortality. This study assessed the prevalence of metabolically unhealthy (MU) individuals and its determinants according to body mass index (BMI). MATERIALS AND METHOD: In our cross-sectional study, 891 persons aged 30 years or older participated. Participants were classified as obese (BMI ≥30 kg/m2), overweight (BMI 25-<30 kg/m2 and normal weight (BMI <25 kg/m2). Metabolic health status was defined using four existing cardio-metabolic abnormalities (elevated blood pressure, elevated serum concentrations of triglyceride and fasting glucose and a low serum concentration of high density lipoprotein cholesterol). Then, two phenotypes were defined: healthy (existence of 0-1 cardio-metabolic abnormalities) and unhealthy (presence of 2 or more cardio-metabolic abnormalities). RESULT: Overall, 10.9% (95% confidence interval (CI): 8.8-13.0) and 7.2% (95% CI: 5.5-8.9) of participants were MU obese and metabolically healthy obese, respectively. The prevalence of MU was higher in overweight (55.6%; 95% CI: 50.6-60.6, p<0.001) and obese (60.2%; 95% CI: 52.8-67.6, p=0.001) subjects than in individuals with a normal weight (37.5%; 95% CI: 29.4-42.6). Multiple logistic regression analysis showed an association of a MU state with age and dyslipidaemia in the BMI subgroups and with female sex in the normal weight individuals. CONCLUSION: The prevalence of a MU state increased with increasing BMI. Ageing and dyslipidaemia were associated with an unhealthy metabolic state in normal weight, overweight and obese subjects and with the female sex in normal weight subjects.

Sero-Epidemiological Study of Hepatitis E Virus among Thalassemia as High Risk Patients: A Cross-Sectional Survey in Jahrom, Southern, Iran.

Hepatitis E virus (HEV) could be cause of viral hepatitis in the developing countries and cause severe epidemics. According to other studies, blood transfusion as a probable route of HEV infection has been suggested. An infection with hepatitis agents such as HEV causes active liver failure in multi-transfusion patients in particular thalassemia. The purpose of this study determines the seropositivity of anti-HEV antibodies in thalassemia individuals in Jahrom. In a cross-sectional study, sera from 110 thalassemia were collected between 2013 and 2014. Enzyme-linked immunosorbent assay (ELISA) method was performed to detection of anti-HEV antibodies. Individuals' data were collected such as, demographic and clinical, for statistical analysis. Our results show that 10% and 1.8% of the enrolled patients were HEV Ig-G and Ig-M positive antibodies respectively. In addition, there was statiscally significant difference in age groups for prevalence of anti-HEV Ig-G (P = 0.01). Also the serum levels of liver enzymes such as ALT and AST in the HEV Ig-G and Ig-M positive samples were significantly higher than anti-HEV negative samples. But there were no significant difference between sex and splenectomy with anti-HEV positive samples. The results indicate more study are needed to assess HEV screening of blood products to these patients that those have a probably risk of exposure to HEV especially in higher years old.

Ibrutinib-A double-edge sword in cancer and autoimmune disorders.

Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk.

The Association Between Pre-Diabetes With Body Mass Index and Marital Status in an Iranian Urban Population.

Pre-diabetes increased the development of diabetes mellitus (type 2). The aim of study was to determine the association of body weight, education and marital status with pre-diabetes in an Iranian urban population.A sample of 788 subjects (360 men and 428 women) between the ages 30-85 years participated in our study and anthropometric measurements, educational level and fasting blood sugar of participants were recorded. The t and Chi square tests were used for continuous and categorical variables. The association of age, BMI categories, educational level and marital status to pre-diabetes was assessed by estimating the odds ratio. A p-value ≤ 0.05 were considered significant. The analysis was done using SPSS version 11.5. Our study showed that pre-diabetic subjects were older and low educated than normoglycemic subjects. Mean BMI and educational level were associated to pre-diabetes only in women. The odds of being pre-diabetes also were higher in obese women than in normal BMI women. No relationship was found between education and marital status with pre-diabetes in both men and women. Based on our finding, it is possible that advancing age and obesity has increased in pre-diabetes. This highlights the importance of population based survey to monitor blood glucose for effective prevention and control.

Association of Tumor Growth Factor-ß and Interferon-γ Serum Levels With Insulin Resistance in Normal Pregnancy.

Pregnancy is related to change in glucose metabolism and insulin production. The aim of our study was to determine the association of serum IFN-γ and TGF- ß levels with insulin resistance during normal pregnancy. This cross sectional study was carried out on 97 healthy pregnant (in different trimesters) and 28 healthy non-pregnant women. Serum TGF-ß and IFN- γ level were measured by ELISA method. Pregnant women had high level TGF-ß and low level IFN-γ as compared non-pregnant women. Maternal serum TGF-ß concentration significantly increased in third trimester as compared first and second trimester of pregnancy. Maternal serum IFN-γ concentration significantly decreased in third trimester as compared first and second trimester of pregnancy. Pregnant women exhibited higher score of HOMA IR as compared non-pregnant women. There were association between gestational age with body mass index (r=0.28, P=0.005), TGF-ß (r=0.45, P<0.001) and IFN-γ (r=-0.50, P<0.001). There was significant association between Insulin resistance and TGF-ß (r=0.17, p=0.05). Our findings suggest that changes in maternal cytokine level in healthy pregnant women were anti-inflammatory. Furthermore, Tumor Growth Factor-ß appears has a role in induction insulin resistance in healthy pregnant women. However, further studies needed to evaluate role of different cytokines on insulin resistance in normal pregnancy.

Lack of Association Between rs17568 Polymorphism in OX40 Gene and Myocardial Infarction, Southern of Iran.

Tumor necrosis factor (TNF) is one of the inflammatory cytokines which has an important role in inflammation and migration of other inflammatory cells to the atherosclerotic plaques. OX40 is a member of the TNF super family receptor protein. OX40 and OX40 ligand are co-stimulators for T-cells and can increase inflammatory response in atherosclerotic plaques. The aim of this study was to determine the association of rs17568 polymorphism in OX40 gene with premature myocardial infarction. This case control study was done on 100 patients with premature acute myocardial infarction (AMI) and a similar number of sex, age and some other cardiovascular risk factor matched healthy people. The OX40 rs17568 polymorphism was genotyped, using PCR-RFLP method. A-allele frequency of rs17568 SNP was lower non-significantly in Premature AMI, compared to healthy subjects (49% vs. 51%). The analysis of rs17568 (A/G) polymorphism showed an odds ratio of 1.127 (95% CI: 0.635-1.999; P= 0.686) for the GG genotype and 5.761 (95% CI: 1.200-27.655; P= 0.029) for the AG genotype, compared to the AA genotype. The results of this study indicate that the rs17568 SNP of OX40 gene is not associated with premature AMI in the evaluated population.

Molecular Survey on Detection of Leishmania Infection in Rodent Reservoirs in Jahrom District, Southern Iran.

BACKGROUND: Zoonotic Cutaneous Leishmaniasis (ZCL) is endemic in many parts of Iran. Recently its incidence is considerable in different parts of Jahrom district, in Fars Province, southern Iran. The aims of our study were to investigate the prevalence of leishmania infection, and identify and characterize the Leishmania species present, among the rodents by molecular methods in a new endemic focus of ZCL, in an urban and rural area of the Jahrom district, Fars Province, southern Iran. METHODS: From May to November 2010), 55 rodents in four regions of Jahrom focus were caught and checked for leishmania infection by the microscopical examination of liver, spleen, ears, and footpads' smears. RESULTS: Overall 18 Meriones persicus, 15 Tatera indica, 14 Mus musculus, and 8 Rattus rattus were caught. Totally, four (16.5%) and two (13.3%) of the Me. persicus and Ta. indica, but only one of Mu. musculus and Ra. rattus were found smear-positive for leishmania amastigotes, respectively. In the nested-PCR assay 8 (14.6%) smears were found positive for Leishmania major, none was found positive for any other Leishmania species. Sequencing based detection of Leishmania confirmed the microscopic and PCR findings. All positive specimens were shown 95-96% similarity with L. major Friedlin. CONCLUSION: Tatera indica and Me. persicus are incriminated as the main 'reservoir' hosts of L. major in the rural area of Jahrom, moreover, Mu. musculus and Ra. rattus have the minor but remarkable role in the maintenance of the disease in the urban regions of Jahrom focus.

Relation of type 2 diabetes mellitus with gender, education, and marital status in an Iranian urban population.

BACKGROUND: Type 2 diabetes mellitus is one of the most important cardiovascular risk factors. OBJECTIVES: This study was performed to assess the relationship of diabetes with gender, education, and marital status in an Iranian urban population. METHODS: A total of 892 men and women aged 30-85 were recruited using a cluster-stratified sampling method from an urban population. Using a questionnaire, demographical data including gender, education, and marital status were collected. A blood sample after fasting for at least eight hours was collected from each subject. Associations of type 2 diabetes mellitus and studied variables were tested for significance. RESULTS: The prevalence of diabetes mellitus was 11.6%; 11.1% in men and 12.1% in women with no significant difference between them. Diabetes mellitus was most prevalent in the oldest age (age more than 60 years, 22.9%) and low education groups (17.9%, P < 0.001). Marital status was not significantly related to diabetes mellitus (P= 0.37). CONCLUSION: The prevalence of diabetes mellitus is related to education within the Iranian population. Thus preventive strategies should be based on the affective factors.

Hepatitis E virus and serum level aminotransferases in blood donors.

BACKGROUND: Hepatitis E virus (HEV) infection is a self-limiting viral infection that can lead to severe complications and death. In different regions the epidemiology of this infection varies. In this study we evaluated the seroepidemiology of hepatitis E infection in Jahrom, a city in southern Iran. METHODS: This was a cross-sectional descriptive study of serum samples from 477 subjects, including 30 females and 447 males. HEV immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-linked immunosorbent assays (ELISA). Alanine transaminase (ALT) and aspartate transaminase (AST) levels were also determined. Four hundred forty-seven subjects were male and 30 were female. Subjects were classified by age and sex. RESULTS: One woman (3.3%) and 25 men (5.5%) were positive for HEV antibodies (IgG and/or IgM). There was found an association between serum level of aminotransferases and seropositivity for HEV. CONCLUSION: The result of this study indicates that HEV is an etiological factor for hepatitis in this area of IRAN. The cost benefit of active immunization in endemic regions should be evaluated because an outbreak could have tragic consequences.