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Background: Iran has been one of the most affected countries in the world by COVID-19. The aim of our study was to determine the outcome of COVID-19 in patients with inflammatory bowel disease (IBD). Furthermore, we analyzed the outcome of SARS-CoV-2 infection in patients with IBD treated with immunosuppressant. Materials and Methods: This is a cross-sectional, observational study. This study included all patients with IBD, regularly followed up in our IBD Clinic at a tertiary medical center from February 5th, 2020 to August 5th, 2022. We identified those patients with confirmed SARS-CoV-2 infection either by PCR test or chest computed tomography (CT) imaging. Results: A total of 401 patients were recruited (n=346 [86.28%] with ulcerative colitis, n=53 [13.22%] with Crohn’s disease, and 2 [0.5%] with indeterminate colitis). Of these patients, 273 (68.08%) developed no symptoms or signs during the follow-up period,128 patients developed symptoms similar to COVID-19, and 76 (18.9%) were diagnosed as confirmed COVID-19 cases. Men comprised 60.5% of the confirmed COVID-19 groups, which shows that men were statistically more likely to have symptoms of COVID-19 during the follow-up period (P=0.04). No significant differences were observed among confirmed and non-COVID-19 cases in terms of concomitant medications: steroids (P=0.6), thiopurines (P=0.23), anti-TNF (P=0.23), and aminosalicylate (P=0.61). Three patients required hospitalization, but there were no admissions to the intensive care unit or deaths related to COVID-19. Conclusion: The risk of COVID-19-related adverse outcomes and death in patients with IBD is low. Also, patients with IBD under immunosuppressive treatment are not at an increased risk of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population. Method: Saliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software. Results: The findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity. Conclusions: These findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease. [ABSTRACT FROM AUTHOR]

Objective Development of alloantibodies against coagulation factor VII (FVII) is the main therapeutic challenge in severe congenital FVII deficiency. About 7% of patients with severe congenital FVII deficiency develop an inhibitor against FVII. In this research, the relationship between interleukin (IL)-10 and tumor necrosis factor-alpha (TNF)-α gene variants and inhibitor development was evaluated for a group of Iranian patients with severe congenital factor VII deficiency. Methods Patients with FVII deficiency were divided into 2 groups: 6 cases and 15 controls. Genotyping was performed using the amplification-refractory mutation system polymerase chain reaction. Results We found that IL-10 rs1800896 A>G gene variant is associated with the risk of FVII inhibitor development (OR = 0.077, 95% CI = 0.016–0.380, P =.001), whereas the TNFα-rs1800629G>A variant has no relation with inhibitor development in severe FVII deficiency. Conclusion The results show that the IL-10 rs1800896 A>G variant increases the risk of developing an inhibitor in patients with severe congenital FVII deficiency. [ABSTRACT FROM AUTHOR]

Introduction: On average, patients suffering from non-alcoholic steatohepatitis after about seven years, their disease turns into fibrosis and reversibility at this stage becomes very difficult because this disease is an irreversible stage of the disease. Therefore, the effect of eight weeks of high-intensity interval training in water on inflammatory factors in patients with nonalcoholic steatohepatitis was investigated. Methods: In this study, eight-week-old male Sprague-Dawley rats were divided into healthy (n=20) and high-fat diet (HFD) (n=20) groups. After eight weeks and proof of disease induction, the HFD group was randomly divided into two groups: control-disease (n=9) and exercisedisease (n=9); Also, the healthy group was divided into two groups: control-healthy (n=9) and exercise-healthy (n=9). The rats in the training group performed HIIT swimming training, including 20 times of 30 seconds of swimming with 30 seconds of rest between each time, for eight weeks (three days a week). One-way ANOVA and Bonferroni's post hoc test (P<0.05) were used to determine the difference between groups. The proposal of this study has been approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REHAB.REC.1400.008). Results: As shown in diagram 1; Based on the results of the one-way analysis of variance test, it can be said that there was a significant difference between the mean TNF-α blood serum (P=0.001). According to the results of Bonferroni's post hoc test, there was a significant increase in the patient-control group compared to the healthy-control group (P=0.001) and also a significant decrease in the patient-exercise group compared to the patient-control group (P=0.012). Also, a significant decrease was observed in the exercise-healthy group compared to the control-patient group (P=0.001) and the exercise-patient group (P=0.002). Conclusions: The results of the present research showed that high-intensity intermittent swimming exercises reduce inflammatory and fibrotic factors, and in general, it can be concluded that eight weeks of high-intensity intermittent swimming exercises improve the inflammatory and fibrotic factors associated with non-alcoholic steatohepatitis. . However, to obtain a definitive result, this type of exercise should be studied in human studies in this patient community. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery disease (CAD) is the main cause of death and is characterized by atherosclerosis in coronary arteries. Inflammation plays a crucial role in the progression and development of atherosclerosis. Methods: The present study consisted of 132 Iranian individuals who underwent coronary angiography, 65 patients with CAD, and 67 controls. The matrix metalloproteinase-9 (MMP-9), TNF-α, IL-6, and vitamin D serum levels were measured by the ELISA technique. The gene expression of MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1) was estimated by realtime PCR assay. Results: A considerable increase in levels and PBMC gene expression of MMP-9 and serum levels of IL-6 and TNF-α were found in CAD patients compared with controls. A significant decrease was detected in vitamin D levels of CAD patients in comparison with controls. A considerable direct correlation was found between MMP-9 levels and MMP-9 and TIMP1 gene expression in CAD patients. MMP-9 levels positively correlated with LDL-C in CAD patients. The correlation between TIMP1 gene expression and IL-6 levels was also negatively significant. There were positive correlations between MMP-9 levels with IL-6 and TNF-α serum levels in CAD patients. Conclusion: This study showed that the interaction between MMPs, TIMP1, and cytokines could play a role in the pathogenesis of atherosclerosis. The present study suggested that high levels of TNF-α and IL-6 and vitamin D deficiency in our studied patients could disturb the MMP-9/TIMP-1 balance and lipid metabolism, leading to plaque formation/ rupture in predisposed CAD patients. [ABSTRACT FROM AUTHOR]

Objectives Febrile seizure is a neuroinflammatory disease involving feverinduced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (a genetic variant; G: Guanine, A: Adenine) (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Materials & Methods Sixty-eight FS patients and 136 controls were enrolled. The SSPPCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. Results The GG (a genetic sequence; G: Guanine) genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA (a genetic sequence; A: Adenine) genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) carriers were more susceptible to FS. Conclusion The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα. [ABSTRACT FROM AUTHOR]

Background: Middle molecules, including some cytokines such as IL-6 and TNF-α, parathyroid hormone, etc., are types of uremic toxins having roles in the development of inflammation in hemodialysis patients. Different studies evaluating effects of coenzyme Q10 (CoQ10) on different inflammation markers in hemodialysis patients have controversial results. Moreover, no study determined the effect of CoQ10 on plasma concentration of IL-6, the most powerful predictor of poor outcomes and mortality, in hemodialysis patients. Therefore, a study was designed to examine the effects of CoQ10 supplementation on IL-6, TNF-α, and intact parathyroid hormone (iPTH) in chronic hemodialysis patients. Methods: In this single-blind randomized controlled trial, patients undergoing hemodialysis were randomly assigned to CoQ10 (100 mg/day) or control group. The duration of the study was 12 weeks. The plasma concentrations of IL-6, as the primary outcome, and TNF-α and iPTH, as the secondary outcomes, were measured at baseline and week 12. Results: Of 73 enrolled patients, 68 completed the study. At the end of the study, there were no significant differences in the concentrations of IL-6 (p=0.570), TNF-α (p=0.301), and iPTH (p=0.642) between the two groups. The standardized mean difference (CoQ10 vs. control) was -0.13 (95% CI -0.60; 0.35) for IL-6, -0.25 (95% CI -0.73; 0.22) for TNF-α, and 0.11 (95% CI -0.36; 0.59) for iPTH. Conclusion: This study showed a trivial effect of CoQ10 supplementation on the concentrations of IL-6 and iPTH and a small effect on the level of TNF-α in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the most prevalent ones with high incidence and mortality worldwide. The aim of this study was to determine the serum levels of tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) as potential diagnostic biomarkers in the first-degree relatives of patients with gastric cancer. Method: The present work is a case-control study (case, n = 90; control, n = 90). The cases were selected from the first-degree relatives of the gastric cancer patients referred to Kosar Hospital of Semnan city, Iran, during 2019, consecutively. The controls were; however, a random sample from all the healthy people referred to Blood Transfusion Center of Semnan city in the same year. Demographic, laboratory, and pathological variables were collected from both groups. The levels of IL-6 and TNF-α were measured with ELISA method via platinum ELISA-8-11 kits. STATA 14 software was used for data analysis. Results: In the case and control groups, 74.44 and 78.79% were male, respectively. Their mean age (SD) was 39.17 (10.75) and 36.16 (10.19) in the case and control groups, respectively. Based on the multivariable logistic regression model, there was a statistically significant difference between the two groups in terms of TNF-α (OR = 1.15; 95% confidence interval (CI): 1.02 -- 1.30) and smoking (odds ratio (OR) = 3.57; 95% CI: 1.48 -- 8.64). However, no statistically significant difference was seen between them concerning the level of IL-6 (OR = 1.0004; 95% CI: 0.97 -- 1.03). Conclusion: Increased levels of TNF-α might be useful as diagnostic biomarkers in the first-degree relatives of patients with gastric cancer; nonetheless, studies with larger sample size are required. [ABSTRACT FROM AUTHOR]

Background and Aim: Adalimumab is a highly human monoclonal antibody that binds to tumor necrosis factor, a key proinflammatory cytokine pathogenic in psoriasis. It is considered as an influential factor in controlling moderate to severe psoriasis. This study aimed to evaluate the impact of Adalimumab on COVID-19 incidence in patients with psoriasis. Materials and Methods: This cross-sectional study was performed at Baqiyatallah Hospital in 2021. Eighty patients with psoriasis who referred to Baqiyatallah Hospital were included in the study. Patients were divided into two groups, one group was treated with Adalimumab, and the other group received the control treatment. The incidence of the disease was assessed by the history of COVID-19 signs and symptoms, positive RT- PCR testing and graphing, and physician diagnosis. Results: The mean age of patients was 39.5 (±7.9 S.D.). 36(45%) patients were infected with COVID-19, and 44 (55%) patients were not infected, and there was no significant difference between the two groups in the infection with COVID-19 (P value = 0.36). There was a significant relationship between infection with COVID-19 and the severity of psoriasis (P value=0.01). Although, in the severe psoriasis group, which was significantly more affected by COVID-19, there was no statistically significant relationship between Adalimumab consumption and COVID-19 affection (P value = 0.19). Conclusion: Psoriasis patients treated with Adalimumab are not more prone to COVID-19 infection. However, patients with severe psoriasis are more likely to develop COVID-19; this matter is not related to the use of Adalimumab, and it is not necessary to discontinue or change Adalimumab. [ABSTRACT FROM AUTHOR]

Background: The inflammation accelerates the progression of bipolar disorder. Supplementation of anti-inflammatory supplements in adjuvant with medications may alleviate disorder signs. This study aimed to investigate the effects of omega-3 fatty acid supplementation on the serum concentrations of pro-inflammatory cytokines and depression status in patients with bipolar disorder. Materials and Methods: This randomized clinical trial study was conducted in Zahedan city in 2021. Patients with bipolar disorder (n = 60) were grouped into two groups: omega-3 fatty acid supplement group (n = 30, 15 men and 15 women) and placebo one using a permuted block stratified randomization. The patients in the omega-3 group received 2 g of omega-3 fatty acids daily for 2 months while patients in the placebo group received 2 g soft gels daily in the same form. Depression score and the serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were assessed before and after the study. Results: Depression score and the serum concentrations of TNF-α, IL-6, and hs-CRP were decreased after intervention in the omega-3 fatty acid group also compared with the placebo group (P < 0.001). The results also show a positive correlation between the serum concentrations of TNF-α, IL-6, and hs-CRP with depression scores (P < 0.001). Conclusion: Prescription of omega-3 fatty acids can decrease inflammatory parameters and help to decrease depression in patients with bipolar disorder. This supplement can be used along with medications for decreasing the inflammatory markers in these patients. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease. Methods: This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The t test was used for the statistical analysis, with a significance level of P<0.05. Results: The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes. Conclusion: Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Previous studies have been reported that vitamin D deficiency increased the risk of metabolic syndrome (MetS). Nonetheless, the exact mechanisms underlying this association is unclear. Besides, inflammation and deregulation of adipokines secretion have been recognized as pivotal factors that contribute to the pathogenesis of these conditions. Therefore, we assessed whether serum vitamin D status is associated with serum levels of adipokines and inflammatory markers in these patients. Methods: This case-control study was carried out among 65 patients with MetS who had vitamin D insufficiency (cases) and 130 MetS patients who had vitamin D sufficiency (controls). Cases and controls were recruited from among those referred to health centers in Zabol County, Iran. Vitamin D insufficiency was regarded as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 30 ng/ml. Serum concentrations of leptin, adiponectin, visfatin, and resistin and also adiponectin/leptin ratio along with serum levels of interleukin 6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α), were evaluated. Results: Serum levels of leptin, resistin, and TNF-α were significantly higher, whereas, serum adiponectin and adiponectin/leptin ratio were significantly lower in cases than the controls. There was no significant difference in serum visfatin, IL-6, and IL-10 between the groups. Serum levels of 25(OH)D were inversely correlated with leptin, resistin, and TNF-α in both unadjusted models and after adjustment for potential confounders. Conclusion: Our findings indicated that vitamin D insufficiency in MetS patients is associated with increased inflammation and serum adipokine abnormalities which may be associated with developing metabolic complications in these patients. [ABSTRACT FROM AUTHOR]

Background and Aim: The COVID-19 disease is an emerging infectious disease that appeared in December 2019 in Wuhan, China. An uncontrolled systemic inflammatory response is one of the primary mechanisms causing death in this disease. In this study, the expression levels of some inflammatory cytokines, vitamin D, and some hematological and biochemical parameters were compared in patients with severe COVID-19 and mild types. Materials and Methods: In this cross-sectional study, 60 blood samples were taken from 30 severe coronavirus patients and 30 mild coronavirus patients. The expression levels of cytokines such as IL (interleukin)-6, interferon (IFN)-α, IL-12, transforming growth factor (TGF) β, IL-8 and tumor necrosis factor (TNF)-α were evaluated using Real-time PCR. A T-test was used for Statistical Analysis. Results: IL-6, IFN-α, IL-12, TGF-β, IL-8, and TNF-α cytokines in the peripheral blood of severe patients, were positive in 28/30 (93.33%), 27/30 (90%), 24/30 (80%), 25/30 (83.33%), 26/30 (86.66%), and 27/30 (90%) respectively. The positive rate of these cytokines in the mild patients were 20/30 (66.67%), 21/30 (70%), 18/30 (60%), 17/30 (56.67%), 19/30 (63.33%), 18/30 (60%), respectively. There was a statistically significant difference between these two groups in terms of cytokines biomarkers. A significant difference was found between both groups in terms of the serum level of lactate dehydrogenase (LDH), the mean number of lymphocytes and neutrophils as well as the mean percentage of neutrophils/ lymphocytes ratio (NLR). Conclusion: The expression of cytokine genes and their release into the peripheral blood was increased in both severe and mild patients with COVID-19. However, they were more intense in patients with severe symptoms than those with mild symptoms and can cause inflammatory and even destructive reactions. Vitamin D deficiency plays no role in causing severe COVID-19 in patients without risk factors. Severe COVID-19 is characterized by elevated serum levels of LDH and NLR≥3.45. [ABSTRACT FROM AUTHOR]

• The relationship between Toxoplasma gondii and gestational diabetes was investigated. • The role of the inflammatory biomarkers, leptin and TNF-α was simultaneously examined. • Leptin was significantly lower in healthy subjects compared to non-infected diabetics. • TNF-α was higher in healthy subjects compared to toxoplasma-infected diabetics. Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July–November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii , and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9–21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii , leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers. [ABSTRACT FROM AUTHOR]

Backgrounds: This randomized controlled trial aimed to investigate the effects of replacing red meat with legumes in the dietary approach to stop hypertension (DASH) diet on inflammatory markers over 16 weeks in overweight and obese individuals with type 2 diabetes. Also, the modulatory effects of TCF7L2 rs7903146 variant on this effect were assessed. Methods: In this trial, 300 participants with type 2 diabetes, aged 30–65 years with an identified TCF7L2 rs7903146 genotype, were studied. The participants were randomly assigned to the DASH diet or the legume-based DASH diet over 16 weeks. In the DASH diet group, the participants were instructed to follow the standard DASH diet. The legume-based DASH diet was similar to the standard DASH diet, with the exception that one serving of red meat was replaced with one serving of legumes at least five days a week. At the beginning of the study and 16-week follow-up, venous blood samples were collected from all participants who fasted for 12–14 h overnight. The serum concentration of High-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the serum malondialdehyde (MDA) concentration was assessed based on a colorimetric method using a commercial kit. The primary outcome was the difference in hs-CRP changes between the diets. A secondary outcomes was the difference in IL-6, TNF-α, and MDA between the groups among total population and based on TCF7L2 rs7903146 risk allele (CT + TT) and non-risk allele (CC) separately. Results: The hs-CRP level reduced in the legume-based DASH diet group as compared to the DASH diet group in the 16-week follow-up group. The levels of TNF-α, IL-6, and MDA reduced after the legume-based DASH diet relative to the DASH diet. Reduction of inflammatory markers was observed in both carriers of rs7903146 risk allele and non-risk allele. Conclusions: Substituting one serving of red meat with one serving of legumes in DASH diet, at least five days a week, could improve the hs-CRP, TNF-α, IL-6, and MDA in participants with type 2 diabetes regardless of having rs7903146 risk or non-risk allele. Trial registration IRCT, IRCT20090203001640N17. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of a 12 week exercise training on the immune system of kidney transplant recipients. 23 kidney transplant recipients were randomly divided into two groups including control (n = 10) and training (n =13) groups. The training groups participated in the training for 10 weeks (three days a week; each day 60-90 minutes). The control group performed no regular exercise during this time. The blood samples were taken before and after 12 weeks. ELISA and Real-time PCR were used to evaluate cytokine profiles, including TNF-a, IL-6, IL-4, IL-31 and IL-35 as well as T-bet, GATA-3, RORYt and FOXP3, respectively. Finally, the data were analyzed, using paired T-test. ELISA results showed decreased levels of TNF- α, increased levels of IL-6 and no significant differences in the IL-35, IL-31 and IL-4 levels in the training group in comparison to the control group. Gene expression profiles showed significantly increased expression of T-bet and no changes in the GATA-3, RORYt and FOXP3 levels. According to these results, a moderate exercise including aerobic and resistance training could inhibit inflammatory cytokines and have beneficial effects on the immune system, but this issue needs further research. [ABSTRACT FROM AUTHOR]

Background: Thalassemia syndromes are the most prevalent hereditary hemoglobinopathies in the world. Iran is located on the thalassemia belt. In this study, the effect of Xmn -1 polymorphism and coinheritance of alpha mutations on age at first transfusion and also transfusion interval in Iranian thalassemic patients with homozygous IVSI-5 mutation were assessed. Materials and Methods: In this retrospective cross-sectional study 154 transfusion dependent thalassemia (TDT) patients (140 patients with β-thalassemia major and 14 cases with β-thalassemia intermedia) who were homozygote of IVSI-5 mutation have been participated. Blood samples were collected from participants using EDTA containers for genomic DNA analysis. DNA extraction and amplification-refractory mutation to determine the Xmn -1 polymorphism were performed. Multiplex PCR was performed to identify alpha globin deletions. Results: The mean age of participants was 29±7, 58 of them were male and 96 were female. A significant relation between presence of Xmn -1 polymorphism and age at receiving first transfusion was detected. Coinheritance of alpha thalassemia mutation does not have significant effect on age at first transfusion or transfusion interval. Conclusion: Presence of Xmn -1 polymorphism can delay the onset of transfusion in patients with homozygote IVSI-5 mutation. [ABSTRACT FROM AUTHOR]

Background: Most data on the effect of inflammatory bowel disease (IBD) and its treatments on coronavirus disease 2019 (COVID-19) outcomes have not had non-IBD comparators. Hence, we aimed to describe COVID-19 outcomes in IBD compared to non-IBD patients. Methods: We conducted a prospective cohort study of registered IBD patients with confirmed COVID-19 from six provinces in Iran from February to April 2020. Proven COVID-19 patients were followed up at four weeks and the frequency of outcomes was assessed. Multivariable logistic regression was used to assess associations between demographics, clinical characteristics and COVID-19 outcomes. Results: Overall, 2159 IBD patients and 4721 household members were enrolled, with 84 (3.9%) and 49 (1.1%) participants having confirmed COVID-19, respectively. Household spread of COVID-19 was not common in this cohort (1.2%). While hospitalization was significantly more frequent in IBD patients compared with non-IBD household members (27.1% vs. 6.0%, P = 0.002), there was no significant difference in the frequency of severe cases. Age and presence of IBD were positively associated with hospitalization in IBD compared with non-IBD household members (OR: 1.06, 95% CI: 1.03-1.10; OR: 5.7, 95% CI: 2.0216.07, respectively). Age, presence of new gastrointestinal symptoms, and 5-aminosalicylic acid (5-ASA) use were associated with higher hospitalization rate in IBD patients (OR: 1.13, 95% CI: 1.05-1.23; OR: 6.49, 95% CI: 1.87-22.54; OR: 6.22, 95% CI: 1.90-20.36, respectively). Anti-tumor necrosis factor (TNF) was not associated with more severe outcomes. Conclusion: Age, presence of new gastrointestinal symptoms and use of 5-ASA were associated with increased hospitalization rate among IBD patients, while anti-TNF therapy had no statistical association. [ABSTRACT FROM AUTHOR]

Background: It is known that inflammatory responses occur in the airways of patients with non-cystic fibrosis bronchiectasis during respiratory exacerbations but the role of these cytokines is not clear in this condition. Herein we evaluated the levels of interleukin-1ß (IL-1ß), IL-8 and tumor necrosis factor a (TNF-a) in the serum and bronchoalveolar lavage among children with non-cystic fibrosis bronchiectasis. Materials and Methods: This cross-sectional study was performed on all children with non-cystic fibrosis bronchiectasis who were admitted with respiratory exacerbation in the pediatric pulmonology ward of Masih Daneshvari Hospital, Tehran-Iran. All patients underwent fiberoptic bronchoscopy and spirometry before and after the bronchoscopy. IL-1ß, IL-8, and TNF-a levels were measured in the serum and bronchoalveolar lavage. Results: Patients included 10 (59%) female and 7 (41%) male subjects with mean age of 13.8 years (range, 5-18). Mean values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were below the normal range before and after bronchoscopy. Mean value for FVC (from 55% to 63%, P= 0.01) and FEV1 (from 60% to 64%, P= 0.26) increased after bronchoscopy compared to before that. IL-1ß and IL-8 levels were increased and TNF-a level was decreased in the serum and bronchoalveolar lavage but no significant correlation was found between spirometry and these cytokines levels. Conclusion: Changes in inflammatory cytokines levels in serum and bronchoalveolar lavage during respiratory exacerbation in patients with noncystic fibrosis bronchiectasis have no significant correlation with spirometry and cannot be used in clinical practice. [ABSTRACT FROM AUTHOR]

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia that is the result of faulty ectodermal development leading to such ectodermal defects as hypotrichosis, anodontia or hypodontia, and hypohidrosis or anhidrosis. Xlinked HED is caused by mutations in ectodysplasin A (EDA) gene and accounts for 90% of all HED cases. Autosomal HED is caused by mutations in other involved genes, such as EDA-receptor (EDAR) gene. In this study, we included two distinct families with three HED patients. We collected 5 mL of peripheral blood from the probands, associated parents, and 120 matched unrelated controls (from related ethnicity) without any ectodermal disorder. DNA was extracted using the routine salting-out protocol from blood leukocytes. Polymerase chain reaction (PCR) purification and bidirectional Sanger sequencing of the PCR products were performed. We identified p.R156H (c.467 G > A) mutation in EDA gene in two affected brothers and their carrier mother (family 1) and a novel missense mutation c.1210G > A (p.A404T) in EDAR gene in a 4-year-old affected boy and his heterogeneous parents (family 2). Clinical evaluation, genetic findings, and bioinformatic analysis supported deleterious effects of both identified mutations on the EDA and EDAR gene products, which should be considered in genetic assessment of HED cases in Southwest of Iran. [ABSTRACT FROM AUTHOR]

Background: Exercise can reduce hepcidin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and improve the iron status, but the intensity of exercises is very important. This study will compare the effect of resistance training (RT) intensity on hepcidin levels, iron status, and inflammatory markers in overweight/obese girls with and without iron stores deficient. Materials and Methods: In this quasi-experimental study, 40 students of the University of Isfahan (18-22-year old, with 35 > body mass index [BMI] ≥25) voluntarily participated in the study. Participants were divided into two groups with 20 participants, based on serum ferritin (>30 ng/ml or ≤30 ng/ ml). Participants in each group were randomly and equally assigned to one of the moderate or high-intensity training groups. RT was performed 8 weeks, 4 days a week, and each session for 1 h, with an elastic band. The iron levels, hepcidin, total iron-binding capacity, ferritin, hemoglobin, TNF-α, and IL-6 before and after intervention were collected with the blood samples. Two-way analysis of variance was used to assess the impact of exercise and ferritin level and their interaction, and the paired test was utilized for test changes from baseline. Results: There are no significant interactions between ferritin levels and exercise intensity for the main outcomes (all P > 0.05). The significant impact of the mode of exercise was observed in TNF-α (P < 0.05), and a significant difference between low and high levels of ferritin was observed in hepcidin (P = 0.002). Besides, in all four groups, significant decreases were observed in BMI (28.00 ± 3.00 to 27.00 ± 3.00), hepcidin (1234.02 ± 467.00 to 962.06 ± 254.00), and TNF-α (223.00 ± 99.00 to 174.00 ± 77.00) compared to the baseline measurements (all P < 0.05). Conclusion: Basal ferritin levels appear to be effective on hepcidin levels, TNF-α, and IL-6 after the intervention. RT with two different intense can reduce BMI, hepcidin, ferritin, and TNF-α in all groups. It seems that performing RT reduces inflammation and hepcidin in obese/overweight participants with different iron stores. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the effects of hydro-alcoholic extract of spinach (HES) on hepatic and serum measurements of NAFLD in a rat model. Methods: In the prevention phase, 18 Sprague–Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, or a chow diet for seven weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, a chow diet, or a chow diet plus 400 mg/kg HES for four weeks (n = 6). Results: Administration of HES combined with high-fat diet in rats was associated with decreased food intake (P < 0.01), weight loss (P = 0.01), and increased superoxide dismutase (SOD) (P = 0.02) enzyme activity in the liver, at the end of the prevention phase. hs-CRP (P < 0.05), PTX-3 (P < 0.05), and TNF-α (P < 0.05) gene expression in the liver were decreased and PPAR-γ (P < 0.05) gene expression in the liver was increased by spinach intake, both in the prevention and treatment phases. Furthermore, administration of spinach in the treatment phase increased serum TAC (P = 0.03) and hepatic GPX (P = 0.01) enzyme activity. Conclusion: Taking into account the potential beneficial effects of HES on prevention and treatment of NAFLD in the present study, to confirm these findings, we propose that further clinical trials be conducted on human subjects with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) is a fatal clinical situation that rapidly leads to the loss of normal liver function. Esculetin is a natural herbal compound used for the management of various diseases such as cardiovascular and renal disorders. In this study, we evaluated the protective effects of esculetin in a mouse model of ALF. Methods: This article is a report on an experimental study that was conducted at Iran University of Medical Sciences in 2019. Forty- eight male C57BL/6 mice were randomly divided into control, LPS/D-Gal, and LPS/D-Gal+Esculetin (40 mg/kg) groups (n=16 per group). ALF was induced with an intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal).The LPS/D- Gal group received a mixture of LPS (50 μg/kg) and D-Gal (400 mg/ kg). The LPS/D-Gal+Esculetin group received esculetin by gavage 24 hours and one hour before receiving LPS/D-Gal. Six hours after LPS/D-Gal injection, the mice were sacrificed. Liver injury markers, including alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), were measured in the serum. Oxidative stress indices and inflammatory markers such as interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were measured in hepatic tissue. The histopathology of liver tissue was also assessed. The data were analyzed using one- way ANOVA, followed by the post hoc Tukey test. Results: Esculetin lowered oxidative stress and myeloperoxidase activity (P<0.001); reduced the serum levels of ALT (P=0.037), AST (P=0.032), and ALP (P=0.004); and decreased the hepatic levels of IL-1β (P=0.002), IL-6 (P=0.004), toll-like receptor 4 (P<0.001), TNF-α (P=0.003), and nuclear factor-kappa B (P<0.001) as compared with LPS/D-Gal. Additionally, esculetin ameliorated hepatic tissue injury following LPS/D-Gal challenge. Conclusion: Esculetin can reduce liver injury through the mitigation of oxidative burden, inflammation, and neutrophil infiltration and also exerts hepatoprotective effects against ALF. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints. Methods: The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF- α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees. Results: Levels of TNF-α (P=0.009), MDA (P0.001>), and IL-1β (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1β in the apigenin 0.3 µM with SMMSCs group reduced significantly (P>0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P>0.001). Conclusion: Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research have greatly supported the "Autoimmune theory." Vitiligo has two major forms: progressive and stable. As cytokines are important mediators of immunity, the most important of them are IL-2, IL-6, and tumor necrosis factor-α (TNF-α). Objectives: We aimed to study the serum level of IL-2, IL-6, and TNF-α in stable and progressive vitiligo and compared them to find a useful lab test to determine the form of vitiligo for diagnose and treatment. Materials and Methods: Serum IL-2, IL-6, and TNF-α were done by the indirect enzyme-linked immunosorbent assay (ELISA) in 40 cases of stable and progressive vitiligo. Results: Twenty patients had progressive vitiligo and 20 patients were stable vitiligo. In every group, there were seven male patients. Twenty-one patients had a positive family history of vitiligo and four patients had other autoimmune diseases. The average age and familial history between two groups and two genders were not meaningful. The mean serum TNF-α level was significantly higher in progressive than stable vitiligo. No significant difference was observed in the serum levels of IL-2, IL-6 between stable and progressive vitiligo. The mean serum IL-6 and TNF-α had higher levels in male patients. Conclusion: Analysis of TNF-α levels in every age or gender can show us the type of vitiligo, stable or progressive and we can choose the best form of treatment for patients. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate the anti-inflammatory effect of atorvastatin in patients with chronic bronchitis, exposed to sulfur mustard gas.Methods: In this randomized double-blinded clinical trial we recruited patients with chronic bronchitis after exposure to sulfur mustard gas. Ninety men 45-75 years old diagnosed with chronic bronchitis after exposure to mustard gas during the Iran-Iraq war, were randomly assigned to receive either atorvastatin (40 mg) or placebo once a day for 3 months. The interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), procalcitonin, highly sensitive CRP and COPD assessment test (CAT) score was compared at baseline and after 12 weeks.Results: After consuming atorvastatin for 12 weeks, IL-6 level (mean difference [95%CI]; 0.2 [- 0.05, 0.5]), TNF-α (mean difference [95%CI]; - 0.07 [- 0.2, 0.07]), high sensitive CRP (mean difference [95%CI] - 0.1 [- 1.2, 0.9]), and procalcitonin (mean difference [95%CI]; 0.003 [- 0.02, 0.03]) did not change significantly. However, in the placebo group, only IL-6 (mean difference [95%CI]; 0.6 [0.2, 1.05]) decreased significantly after 12 weeks, but levels of high sensitive CRP (mean difference [95%CI]; - 0.3 [- 1.4, 0.8]) TNF-α (mean difference [95%CI]; - 0.2 [- 0.34, - 0.06]) and procalcitonin (mean difference [95%CI]; 0.02 [- 0.001, 0.04]) did not change significantly. After 12 weeks, the mean differences in TNF- α, IL-6 level, high sensitive CRP, procalcitonin, and CAT score did not significantly differ between the two groups.Conclusions: The administration of 40 mg atorvastatin for 3 months did not significantly change the inflammatory markers or the quality of life of patients exposed to mustard gas with chronic bronchitis.Trial Registration: IRCT, IRCT138904144312N1. Registered 16 August 2014, https://en.irct.ir/trial/4577 . [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic Nephrotic Syndrome is a multifactorial disease that accompanying with immune system dysfunction. Cytokines as potent immunomodulators have a key role in pathogenesis of the disease. We aimed to evaluate the association between TNFα -308G > A polymorphism with Idiopathic Nephrotic Syndrome and its effect on the response to steroid therapy.Methods: This case-control study was performed on 168 patients with Nephrotic Syndrome and 153 healthy children. Genotyping of TNF-α rs1800629 (-308G > A) variant was detected by polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP).Results: The results revealed that there was no significant difference in allele (P > .05, OR = 0.92, 95% CI: 0.59 to 1.43) or genotype (P > .05, OR = 1.00; 95% CI: 0.62 to 1.65) frequency of TNF-α rs1800629 (-308G > A) between childhood cases of nephrotic syndrome and healthy controls. Also no association was found between genotype (P > .05, OR = 2.28; 95% CI: 1.03 to 5.04), and allele frequency (P > .05, OR = 1.93; 95% CI: 0.97 to 3.87) among the SSNS and SRNS groups.Conclusion: Our results did not support any association between the TNF polymorphism and the risk of nephrotic syndrome in a sample of southeast Iranian population. [ABSTRACT FROM AUTHOR]

In this study, we investigated the association between short-term exposure to different sources of fine particulate matter (PM2.5) and biomarkers of coagulation and inflammation in two different panels of elderly and healthy young individuals in central Tehran. Five biomarkers, including white blood cells (WBC), high sensitive C-reactive protein (hsCRP), tumor necrosis factor-soluble receptor-II (sTNF-RII), interleukin-6 (IL-6), and von Willebrand factor (vWF) were analyzed in the blood samples drawn every 8 weeks from the subjects between May 2012 and May 2013. The studied populations consisted of 44 elderly individuals at a retirement home as well as 40 young adults residing at a school dormitory. Positive Matrix Factorization (PMF)-resolved source-specific PM2.5 mass concentrations and biomarker levels were used as the input to the linear mixed-effects regression model to evaluate the impact of exposure to previously identified PM sources at retirement home and school dormitory in two time lag configurations: lag 1–3 (1–3 days before the blood sampling), and lag 4–6 (4–6 days before the blood sampling). Our analysis of the elderly revealed positive associations of all biomarkers (except hsCRP) with particles of secondary origin in both time lags, further corroborating the toxicity of secondary aerosols formed by photochemical processing in central Tehran. Moreover, industrial emissions, and road dust particles were positively associated with WBC, sTNF-RII, and IL-6 among seniors, while vehicular emissions exhibited positive associations with all biomarkers in either first- or second-time lag. In contrast, most of the PM2.5 sources showed insignificant associations with biomarkers of inflammation in the panel of healthy young subjects. Therefore, findings from this study indicated that various PM2.5 sources increase the levels of inflammation and coagulation biomarkers, although the strength and significance of these associations vary depending on the type of PM sources, demographic characteristics, and differ across the different time lags. Implications: Tehran, the capital of Iran with a population of more than 9 million people, has been facing serious air pollution challenges as a result of extensive vehicular, and industrial activities in the previous years. Among various air pollutants in Tehran, fine particulate matters (PM2.5, particles with aerodynamic diameters < 2.5 µm) are known as one of the most important critical pollutants, causing several adverse health impacts including lung cancer, respiratory, cardiovascular, and cardiopulmonary diseases. Therefore, a number of studies in the area have tried to investigate the adverse health impacts of exposure to PM2.5. However, no studies have ever been conducted in Tehran to examine the association between specific PM2.5 sources and biomarkers of coagulation and systemic inflammation as indicators of cardiovascular disorders. Indeed, this is the first study in the area investigating the association of source-specific PM2.5 with biomarkers of inflammation including white blood cells (WBC), high sensitive C-reactive protein (hsCRP), tumor necrosis factor-soluble receptor-II (sTNF-RII), interleukin-6 (IL-6), and von Willebrand factor (vWF). Our results have important implications for policy makers in identifying the most toxic sources of PM2.5, and in turn designing schemes for mitigating adverse health impacts of air pollution in Tehran. [ABSTRACT FROM AUTHOR]

Background and Aim Weight gain and vitamin D deficiency are associated with increased systemic inflammation and chronic diseases. The current study aimed to investigate the effects of regular Pilates training associated with Vitamin D intake on Tumor Necrosis Factor-α (TNF-α) and Interleukin-10 (IL-10) levels in overweight males. Methods & Materials This quasi-experimental study was conducted on 52 overweight men aged 45- 55 years. Volunteers were firstly selected through the convenience sampling method. Then, they were divided into Pilates training, Pilates training + vitamin D supplementation, vitamin D supplementation (combined), and control groups (n=13/group). The provided Pilates training program was performed for 8 weeks (with the intensity of 50%-75% of reserve heart rate, 3 sessions/week). The supplement and combined groups also received 50000 units of oral vitamin D weekly for 8 weeks. The serum levels of variables were determined using the ELISA method. The obtained data were analyzed by Paired Samples t-test, one-way Analysis of Variance (ANOVA), and Kruskal–Wallis test at the significant level of <0.05. Ethical Considerations This study was approved by the Research Ethics Committee at Islamic Azad University, Babol Branch, Iran (Code: IR.IAU.BABOL.REC.1398.088). Also, this study was approved by the Iranian Clinical Trial Registration Center (Code: IRCT20190831044650N2) Results The collected results indicated that 8 weeks of Pilates training, vitamin D intake, and the combined intervention were associated with a significant increase in IL-10 (P<0.001) and a decrease in TNF-α (P<0.001). Additionally, the presented combination intervention was associated with further alternations in the research variables, compared to the other two interventions; however, in the exercise group, the decrease in TNF-α level was more than that in the vitamin D intake group (P=0.012). Conclusion It seems that in overweight combined with vitamin D deficiency stats, the anti-inflammatory effects of Pilates training, vitamin D supplementation interventions, and a combination of the two methods can be attributed in part to up-regulation IL-10 and TNF-α reduction; however, the effectiveness of the combined intervention on the development of inflammation was greater than that of the other two interventions. Furthermore, the effect of Pilates training on reducing TNF-α was stronger than that of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Background and Aim: Weight gain and vitamin D deficiency are associated with increased systemic inflammation and chronic diseases. The aim of this study was to investigate the effects of regular Pilates training associated with VitaminD intake on Tumor necrosis factor-α (TNF-α) and Interleukin-10 (IL- 10) levels in men with overweight. Materials and Methods: This quasi-experimental study was conducted in 50 overweight men with 45- 55 years. Volunteers were firstly selected through convenience sampling and were divided into Pilates training, Pilates training +vitaminD supplementation, vitamin D supplementation (combined), and control groups (13 people in each group). The Pilates training program was performed for 8 weeks (with the intensity of 50-75% of reserve heart rate, 3 sessions/week). The supplement and combined groups also received 50000 units of oral vitamin D weekly for 8 weeks. Serum levels of variables were determined using ELISA method.The data were analyzed by paired t test, one wayANOVA and Kruskal Wallis tests at the significant level of less than 0.05. Ethical Considerations: This study with research ethics code IR.IAU.BABOL.REC.1398.088 has been approved by research ethics committee at Islamic Azad University, Babol Branch, Iran Findings: The results showed that 8 weeks of Pilates training, vitamin D intake and the combined intervention were associated with a significant increase in IL-10 (P<0.001) and decreased in TNF-α (P<0.001). In addition, combination intervention was associated with more changes in these variables compared to the other two interventions but in the exercise group, the decrease in TNF-α level was more than vitaminD group (p=0.012). Conclusion: It seems that in the overweight status with low levels of vitamin D, anti-inflammatory effects of each Pilates training, vitaminD supplementation interventions and a combination of the two methods can be attributed in part to up-regulation IL-10 and TNF-α reduction but the effectiveness of combined intervention on the development of inflammation was greater than on the other two interventions. Also, the effect of Pilates training on reducing TNF-α is stronger than vitaminD supplementation. [ABSTRACT FROM AUTHOR]

Liver fibrosis is an initial stage of cirrhosis being a result of the pathological deposition of the extracellular matrix. Plants, present a worthwhile source for new drug finding because of a remarkable chemical variety of compounds existing within. Vaccinium arctostaphylos (Va) fruit contains many bioactive anthocyanins that have powerful antioxidant, anti-inflammatory, and anti-tumor properties and traditionally are used to control hypertension and diabetes mellitus in Iran. The current study was established to evaluate the therapeutic effects of Va in chronic liver fibrosis. Liver fibrosis was induced by carbon tetrachloride in rats to evaluate the effect of the methanolic extract Vaccinium arctostaphylos. Total phenols, flavonoids, and antioxidant activity of the extract were measured. The anti-fibrotic properties of Va were evaluated on the inflammatory and fibrogenic parameters.Va significantly compensated CCl4-induced increase of liver function enzymes in serum and histopathological architectural, inflammatory, and fibrotic alterations. Moreover, overactivity of tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and an elevated level of nitric oxide (NO) were effectively blocked by Va, suggesting the suppression of liver inflammation. The expression of transforming growth factor-beta)TGF-β1(, transforming growth factor-beta receptor II)TGF-βRII(, matrix metalloproteinase-2)MMP-2(, matrix metalloproteinase 9(MMP-9), and alpha-smooth muscle actin (α-SMA_) was significantly downregulated, indicating regulated extracellular matrix content. These findings implicated that Va possessed a hepatoprotective effect by improving hepatic inflammation and fibrogenesis, and this potential was may be due to its antioxidant properties. [ABSTRACT FROM AUTHOR]

Background: Induction of septic shock by lipopolysaccharide (LPS) may lead to acute renal failure. The present study aimed to investigate the impact of sex differences on the effectiveness of low-dose LPS preconditioning (LPS-PC) on LPS-induced acute renal failure in rats. Methods: This study was conducted at Tehran University of Medical Sciences, in 2017. A total of 48 Wistar rats were equally divided into two groups of male and female rats. The rats in each group were then allocated to three groups (n=8 per group), namely control, septic shock, and LPS-PC group. A high dose of LPS was administered for septic shock induction. LPS-PC was induced by injecting LPS before sepsis induction. The effect of sex differences on renal functional indices, renal oxidative stress markers, plasma tumor necrosis factor-α level, and renal histological changes was evaluated. Data were analyzed using two-way ANOVA followed by Tukey's post hoc test. Results: In the septic shock groups, renal functional parameters (creatinine [Cr] and blood urea nitrogen [BUN]) were increased in both sexes. However, the increase was more significant in male rats (male rats: Cr=2.14±0.13, BUN=81±4.15; female rats: Cr=1.64±0.12, BUN=50±2.7). LPS-PC reduced these indices in both sexes (male rats: Cr=1.24±0.03, BUN=57±4.1; female rats: Cr=0.86±0.02, BUN=30.31±2.25). Renal superoxide dismutase (SOD) activity (male rats: 11.54±1.34, female rats: 24.4±2.04) and catalase (CAT) activity (male rats: 15±1.74, female rats: 25.75±1.97) were significantly higher in the female septic group. LPS-PC significantly increased SOD (male rats: 25.7±2.45, female rats: 42.6±3.31) and CAT (male rats: 37.25±2.34, female rats: 59.21±3.29) activities in renal tissue samples in the LPS-PC group in both sexes compared to the septic groups. In the LPS groups, plasma tumor necrosis factor-α (male rats: 375±25.65, female rats: 285.45±25.94) were significantly higher than in the LPS-PC groups (male rats: 250±21.35, female rats: 121±24.14). Conclusion: Male rats were more susceptible to sepsis-induced renal damage. LPS-PC had protective effects on the LPS-induced renal injury, and these effects were most prominent in female rats. [ABSTRACT FROM AUTHOR]

Background: Eating disorders (EDs) are widely known by abnormal eating behaviors associated with significant medical complications. Bulimia nervosa (BN) is an eating disorder characterized by uncontrolled episodes of overeating typically followed by some form of compensatory behaviors. We aimed to determine the relationships between socio-demographic characteristics, biochemical markers, and cytokine levels in BN candidates for laparoscopic sleeve gastrectomy (LSG). Methods: A case-control study was designed among 76 BN participants of Iranian descent who were candidates for LSG based on defined criteria for Bulimia by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The healthy control subjects (n = 42) were selected at random from academic staff in the college. Moreover, levels of biochemical parameters and serum cytokines were measured in serum samples. Results: Routine consumption of caffeine (odds ratio [OR] = 3.1, 95% CI: 1.23-6.41, P = 0.013), tobacco (OR = 1.8, 95% CI: 0.67--3.57, P = 0.03), and alcohol (OR = 3.6, 95% CI: 0.84-7.18, P = 0.048), and depression history (OR = 2.8, 95% CI: 0.76-5.79, P = 0.037) were substantially more common among patients with bulimia. Also, the serum levels of fasting blood sugar (P < 0.001), HbA1c (P = 0.04), cholesterol (P = 0.03), triglycerides (P = 0.01), blood urea nitrogen (P = 0.03), and pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α were significantly higher in BN candidates for LSG (P ≤ 0.001). Conclusion: Our findings reveal that lifestyle-related risk factors and a depression history were both related with a significantly increased risk of BN among the candidates for LSG. Furthermore, there is a relationship between clinical characteristics as well as levels of various biochemical and cytokines parameters in serum of BN patients. [ABSTRACT FROM AUTHOR]

Background and Aim Chronic Lymphocytic Leukemia (CLL) is the most commonly occurring leukemia in adults, accounting for about 30-25% of total leukemia. One of the important etiological causes of this leukemia is the disruption of the Nuclear Factor Kappa B (NF-kB) signaling pathway. The two proteins of Apoptosis-Inducing Ligand (APRIL) and B-Cell Activating Factor (BAFF) play a role in the pathogenesis of this leukemia by affecting the NF-kB signaling pathway. In this study, due to the effect of miRNAs in regulating many cellular processes, the prediction of the prominent miRNAs targeting APRIL and BAFF transcripts in B-cell CLL patients was evaluated using specific and different bioinformatics programs. Methods & Materials Afterwards retrieving the sequences of APRIL and BAFF proteins from the NCBI website, by using several programs including miRanda, TargetScan, miRWalk, DIANA and miRDB with different algorithms, the prediction of miRNAs targeting these genes was investigated. Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences. Results Based on the scoring system of bioinformatics programs, “hsa-miR-145-5p” and “hsa-miR-185-5p” were identified as miRNAs targeting APRIL gene, while “hsa-miR-424” and “hsa-miR-497”were miRNAs targeting BAFF gene. They were suggested for the practical studies in future. Conclusion Based on the important role of APRIL and BAFF genes in the normal process of cell death and B-cell evolution, it seems that the mi-RNAs predicted by bioinformatics programs using different algorithms can be used as a diagnostic molecular biomarker to identify B-cell CLL patients. [ABSTRACT FROM AUTHOR]

Introduction: Crocus sativus (saffron) is widely used in China, Iran, and India for dyeing and as a food additive and medicinal plant. Safranal, as one of the main constituents of saffron, is responsible for its aroma and has been reported to have anticancer, antioxidant, and anti-inflammation properties. Objective: In this study, we investigated the anti-inflammatory effects of Safranal in RAW264.7 cells, bone marrow-derived macrophages (BMDMs), and dextran sulfate sodium (DSS)-induced colitis mice. Methods: Safranal toxicity was determined using an MTT assay. We evaluated the inhibitory effect of nitric oxide (NO) and levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells and BMDMs. We assessed the inhibitory effect of pro-inflammatory cytokines, and the mRNA expressions of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), classical inflammatory pathways (MAPK and NF-κB), and the nuclear translocation factors AP-1 and NF-κB p65 were investigated. The in vivo anti-inflammatory effects of Safranal were assessed in a DSS-induced colitis model. DSS3.5% was used to induce colitis in mice with or without Safranal for 7 days; weight and disease activity index (DAI) were recorded daily. At the end of the experiment, the colon, mesenteric lymph nodes (MLNs), and spleen were collected for flow cytometry, ELISA, and Western blot analysis. Results: Safranal suppressed NO production, iNOS, and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BMDMs. Safranal decreased the production and mRNA expression of IL-6 and TNF-α in the RAW264.7 cell line and inhibited the phosphorylation and nuclear translocation of components of the MAPK and NF-κB pathways. Safranal alleviated clinical symptoms in the DSS-induced colitis model, and colon histology showed decreased severity of inflammation, depth of inflammatory involvement, and crypt damage. Immunohistochemical staining and flow cytometry showed reduced macrophage infiltration in colonic tissues and macrophage numbers in MLNs and the spleen. The levels of colonic IL-6 and TNF-α also decreased in Safranal-treated colitis mice. This study elucidates the anti-inflammation activity of Safranal, which may be a candidate for inflammatory bowel syndrome (IBD) therapy. [ABSTRACT FROM AUTHOR]

This study aimed to compare the hematologic variables and pro-inflammatory biomarkers in urban adults living in Tabriz, Iran, facing various levels of outdoor volatile organic compounds (VOCs). Of all 219 people (212 male and 7 female), 71 were from the low traffic area and 148 were from high traffic and industrial areas. To validate the exposure levels, 93 air samples were taken to determine the target VOCs (benzene, toluene, xylenes, and styrene collectively called BTXS) concentrations in the studied areas. ANOVA and Tukey's tests were used for statistical analysis. Based on the results, significant differences were observed between the mean concentrations of BTXS with the following order of abundance: industrial > high traffic > low traffic. The Considerable decrease was observed in red blood cells (RBCs), hemoglobin, hematocrit, and eosinophils of 0.324 (× 106/μL), 0.57 g/dL, 1.87%, and 0.17 (× 103/μL), respectively in industrial area participants as compared to the low traffic area. However, a significant increase was observed in white blood cell count (WBC), neutrophils number, neutrophils percent, TNF-α and INF-γ of 0.88 (× 103/μL), 0.80 (× 103/μL), 3.53%, 34.2 ng/mL, and 40.06 ng/mL, respectively in the same groups. The comparison of low and high traffic areas showed significant differences in RBC (p = 0.034), tumor necrosis factor alpha (TNF-α) (p < 0.001), and interferon gamma (INF-γ) (p < 0.001). On the contrary, no significant difference was observed in TNF-α and INF-γ among the high traffic and industrial areas. In conclusion, the results showed that the samples from high traffic and industrial areas were regularly exposed to higher values of BTXS due to traffic and industrial pollutants as compared to the samples residing in low traffic regions. Based on the results living in both high traffic and industrial regions can increase adverse effects on hematologic parameters and pro-inflammatory cytokines. • The mean concentration of outdoor benzene is higher than the recommended value in high traffic and industrial regions. • The residents of high traffic and industrial areas are regularly exposed to higher values of BTXS. • Living in high traffic and industrial regions may increase the risk of the adverse effects of pollutants on hematologic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Advances in the technology for percutaneous coronary angioplasty, such as coated stents, have reduced its complications, but restenosis remains an important clinical problem. The factors associated with an increased risk of restenosis include diabetes mellitus and multiple coronary artery disease. It is also possible that genetic factors play a role in restenosis although there are little data on this. We have investigated the association of three genetic markers of genes involved in inflammation leading to restenosis. Materials and Methods: In this case--control study, 306 unrelated Iranian patients who were thought to have restenosis on clinical grounds were investigated. Based on the results of angiography, 104 patients were found to have >50% stenosis within an implanted stent, and these were allocated to the in stent restenosis (ISR) group; 202 patients with no in stent stenosis or stenosis ≤50% were allocated to the non ISR (NISR) group. Demographic data were collected from medical records. Biochemical parameters were measured using routine methods. Genotypes of the interleukin 10 (IL 10), annexin A5 (AnxA5), and tumor necrosis factor alpha (TNFα) loci were determined using real time polymerase chain reaction and a high resolution melting assay. Results: Fasting blood glucose, serum triglycerides, and serum high sensitivity C reactive protein (hs CRP) concentrations were higher in the ISR group than in the NISR group (P < 0.05), and a history of diabetes mellitus was significantly related to the presence of restenosis (P < 0.001). There were no significant differences in the frequency of the genetic polymorphisms of IL 10, AnxA5, and TNFα genes and the presence of ISR. Conclusion: After adjustment for clinical variables, the genetic polymorphisms at the IL 10, TNFα, and ANXA5 gene loci do not appear to be risk factors for >50% ISR in our population. However, our data suggested a significant association between diabetes mellitus, serum hs CRP, stent type, and restenosis. [ABSTRACT FROM AUTHOR]

Saffron (Crocus sativus L.) is considered in the Iranian traditional medicine because of many therapeutic properties such as sedative agent, strengthen the stomach and liver, improving the uterus disorders and infectious wounds. The detoxification of alcohol was one of the most important of saffron effects in ancient medicine. In the current research, the protective effects of saffron aqueous extract (Aq. Ext.) versus oxidative stress, apoptosis, inflammation, histopathological and biochemical abnormalities induced by ethanol were evaluated. The male Wistar rats were divided into seven groups consisted of 6 rats in control (distilled water), ethanol (5 g/kg - 50% v/v), Aq. Ext. (40, 80 and 160 mg/kg) plus ethanol, Aq. Ext. 80 and 160 mg/kg. Animals were treated for four weeks and at the end of treatment period, histopathological damages, biochemical markers, apoptosis, levels of MDA and GSH, TNF-α and IL-6 were evaluated. Ethanol induced nephrotoxicity and hepatotoxicity as evidenced by histopathological damages and biochemical abnormalities. The level of MDA was significantly enhanced while GSH content was remarkably reduced in ethanol-treated rats, but protective groups restored them. Also, the levels of TNF-α and IL-6 were regulated by Aq. Ext. Furthermore, the effects of ethanol on histopathological and biochemical parameters were improved by Aq. Ext. The ethanol increased the expression of Bax/Bcl 2 ratio, caspase-3, -8, and -9. Real-time PCR and western blot analysis proved that Aq. Ext. treatment inhibited apoptosis induced by ethanol through decreasing the Bax/Bcl 2 ratio (mRNA and protein) and caspases-3, -8, and -9 levels in the kidney and liver. The results of this research demonstrated that Aq. Ext. could exert protective effects against ethanol toxicity in rat kidney and liver via antioxidant, anti-apoptosis, and anti-inflammatory effects. Image 1 [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor-alpha (TNF-α) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometriosis due to the presence of cytokines such as TNF-α. This study aimed to examine the association of four TNF-α polymorphisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population. Materials and Methods: We recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The allele frequency of TNF-α -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjusting for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028). Conclusion: For the first time the association of the four polymorphisms in the promoter region of the TNF-α gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science. [ABSTRACT FROM AUTHOR]

Objectives: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans. Methods: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus. Results: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue. Conclusion: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the association of MTHFR and TNF-α genes polymorphisms with Legg-Calvé-Perthes' disease (LCPD) risk in the Iranian children. Methods: A total of 45 children with LCPD and 55 healthy controls were recruited to the study. Genotyping was performed via the RFLP-PCR method and genetic risk was calculated by odds ratio (OR) with its corresponding 95% confidence interval (CI). Results & conclusion: Our case-control study failed to determine any association of MTHFR (677C > T and 1298A > C) and TNF-α (-308G > A and -238G > A) polymorphisms with LCPD risk. More studies with larger sample size are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Objective To evaluate the serum levels of interleukin (IL)–6, IL-8, tumor necrosis factor (TNF)–α, tumor growth factor (TGF)–β, endothelin, and immunoglobulin (Ig)E in patients with idiopathic epistaxis, compared with healthy control individuals. Methods Serum levels of IL-6, IL-8, TNF-α, TGF-β, endothelin, and IgE were evaluated in 110 patients with idiopathic epistaxis and 100 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-6 (P <.001) and TGF-β (P =.001) were significantly increased in patients with idiopathic epistaxis, compared with controls. TNF-α serum levels were significantly increased in male patients, compared with female patients (P =.053). We observed decreased antihistamine levels and increased expression of TGF-β (P =.02) and TNF-α (P =.02), respectively. Conclusions IL-6 and TGF-β appear to participate in the pathogenesis of idiopathic epistaxis. TNF-α may be considered a risk factor for male patients in developing epistaxis. Antihistamines may inhibit angiogenesis by decreasing expression of TGF-β and increasing expression of TNF-α. [ABSTRACT FROM AUTHOR]

Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-α (TNF-α), Interleukin (IL)-6 polymorphisms in patients with CHF was studied due to ischemic heart disease. Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms (SNPs) within the IL-6 (-174, nt565) and TNF-α (-308, -238) genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) assay. Results: The frequency of the TNF-α (-238) A/A genotype was significantly higher in patients comparing to controls (p=0.043), while TNF-α G/A genotype at the same position decreased significantly, in comparison with controls (p=0.018). The most frequent haplotype for TNF-α was A/A in the patient group in comparison with controls (p=0.003). There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-α at position -308. Conclusion: Certain alleles, genotypes, and haplotypes in TNF-α, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease. [ABSTRACT FROM AUTHOR]

Background: Infertility is defined as the inability to achieve pregnancy after one year of unprotected intercourse. A large proportion of infertile men fail to impregnate their female counterpart due to lack of sperm (azoospermia) or too little sperm (oligozoospermia). Infertility may also be due to estrogens, infections, heavy metals, cigarette smoking, reactive oxygen species (ROS) and sperm antibodies. Fas is a member of the TNFR (tumor necrosis factor receptor) family that is widely expressed on the surface of many different kinds of cells. Fas gene is involved in the apoptosis process. The purpose of this study was to evaluate the effect of Fas gene polymorphism in male infertility in a population in north of Iran. Methods: This study involved 132 patients with male infertility and 102 healthy controls. DNA samples were extracted from the peripheral blood and genotyped by RFLP-PCR method. Statistical analysis was performed using MedCalc. Results: The frequencies of AA, AG, GG in patients were 31.81%, 54.54% and 13.63%, respectively and in controls were 45.09%, 47.05%, 7.84%, respectively. Conclusion: It is concluded that there is no significant association between Fas-670A/G gene polymorphism and male infertility (p=0.07). Further studies with larger numbers of patients are required to elucidate the potential role of Fas gene polymorphism in male infertility. [ABSTRACT FROM AUTHOR]