Immunomodulatory Therapeutic Effects of Curcumin on M1/M2 Macrophage Polarization in Inflammatory Diseases.

BACKGROUND: Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties. OBJECTIVE: Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis. RESULTS: The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation. CONCLUSION: Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Evaluation of the Effects of 1,25VitD3 on Inflammatory Responses and IL-25 Expression.

VitD3 may contribute to a successful pregnancy through modulation of immune responses, so VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well. Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on IL-25 and related cytokines of Th17 cells including IL-17A, IL-6, and IL-23 in peripheral blood mononuclear cells of healthy women as a control group and women with unexplained recurrent spontaneous abortion. Method: Isolation of peripheral blood mononuclear cells (PBMCs) was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 h) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, real-time PCR and ELISA were carried out. Results: The proportion of Th17 cells in women with URSA was considerably higher than in the control group. IL-25 mRNA and protein levels in cultured PBMCs from women with URSA were lower than the controls. 1,25VitD3 increased IL-25 expressions at both the protein and mRNA levels in PBMCs from women with URSA relative to the control group. Additionally, 1,25VitD3 treatment not only significantly decreased the percentage of Th17 cells frequency but also reduced expressions of IL-6, IL-17A, and IL-23 in PBMCs from women with URSA. Conclusion: 1,25VitD3 may diminish inflammatory responses cells via downregulation of IL-25 expression. It could be an interesting subject for future researches in the field of the immunopathology of URSA to identify molecular pathways in URSA treatment.

Evaluation of nutritional adjustment program on quality of life in children with chronic liver disease.

BACKGROUND: Chronic liver disease is associated with decreased quality of life. The quality of life of children with chronic liver disease is related to their quality of life. Malnutrition is associated with death from cirrhosis, development of complications, and health-related quality of life in people with liver disease. Therefore, this study was conducted to determine the effect of nutritional adjustment program on quality of life in children with chronic liver disease. MATERIALS AND METHODS: This clinical trial study was performed on children with chronic liver disease referred to the nutrition clinic of Ghaem Educational-Research Center in Mashhad in 2015. In this study, 77 children with chronic liver disease were randomly divided into two groups. Before and after the intervention, patients' quality of life was assessed with the PedsQL™ 4.0 generic core scale questionnaire. Data analysis was performed using SPSS16 software. RESULTS: In the postintervention stage, the mean total score of quality of life in the experimental group was 1965.0 ± 270.9 and in the control group was 1522.5 ± 321.3 (P < 0.001). The difference in quality of life score of physical, social, and school performance in the two groups was significant. CONCLUSION: According to the results of this study, it seems that interventions that can improve the quality of life of children with chronic liver disease can be an important step in advancing these people toward a healthy and quality life. As a result, it is possible to take steps to improve the quality of life of patients by encouraging children with liver disease and providing information about diet.

The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine.

Pregnancy complications including preeclampsia, preterm birth, intrauterine growth restriction, and gestational diabetes are the main adverse reproductive outcomes. Excessive inflammation and oxidative stress play crucial roles in the pathogenesis of pregnancy disorders. Curcumin, the main polyphenolic compound derived from Curcuma longa, is mainly known by its anti-inflammatory and antioxidant properties. There are in vitro and in vivo reports revealing the preventive and ameliorating effects of curcumin against pregnancy complications. Here, we aimed to seek mechanisms underlying the modulatory effects of curcumin on dysregulated inflammatory and oxidative responses in various pregnancy complications.

The Risk of Developing Obesity, Insulin Resistance, and Metabolic Syndrome in Former Power-sports Athletes - Does Sports Career Termination Increase the Risk.

INTRODUCTION: Obesity is associated with several complications like metabolic syndrome. Many professional athletes adopt a sedentary lifestyle after retirement. This study was aimed at assessing the risk of developing obesity, insulin resistance (IR), and metabolic syndrome among former power-sports athletes, compared with age-matched active athletes and nonathletes. MATERIALS AND METHODS: The study was conducted in Mashhad during 2012-2014. The individuals were recruited through announcements and were divided into three groups of active athletes (n = 34), ex-athletes (n = 30), and nonathletes (n = 30). Demographic and anthropometric data were collected and biochemical factors including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides (TG), fasting plasma glucose, insulin, and high-sensitive C-reactive protein were measured. RESULTS: Ex-athletes had significantly higher mean values of weight, body mass index, diastolic blood pressure, LDL-C, insulin, homeostatic model assessment (HOMA) IR, and HOMA ß-cell function (HOMA-%ß-cell) compared with active athletes and nonathletes (P < 0.001, P < 0.001, P < 0.001, P = 0.03, P = 0.01, P = 0.02, and P = 0.01, respectively). However, mean values of HDL-C was significantly lower in ex-athletes compared with nonathletes (P < 0.001). The prevalence of metabolic syndrome showed no significant difference among three groups, although its mean was higher among ex-athletes. CONCLUSIONS: The results showed that abandoning regular athletic exercise and weight cycling in power sports athletes leads to adverse outcomes such as obesity and IR. Although higher IR might not necessarily result in metabolic syndrome in short term, it could cause metabolic syndrome in the long run.

Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study.

BACKGROUND: Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. OBJECTIVE: The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. METHODS: Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. RESULTS: The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. CONCLUSION: Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders.

Depression and anxiety both associate with serum level of hs-CRP: A gender-stratified analysis in a population-based study.

BACKGROUND: Depression and anxiety are two important mood disorders that are frequently associated with chronic diseases such as cardiovascular diseases (CVDs). Hyper-inflammation is related to both CVDs and psychological conditions such as depression and anxiety. Therefore, inflammation may partially explain the relationship between depression and cardiovascular disease. OBJECTIVE: The objective of this study was to perform a gender-stratified examination of the association between symptoms of depression/anxiety disorders and serum hs-CRP and inflammation linked conditions in a large Iranian population. METHODS: Symptoms of depression and anxiety disorders and serum hs-CRP levels were measured in 9759 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated with Beck Depression and Anxiety Inventories. According to the scores of depression and anxiety, individuals were categorized into four groups of no or minimal, low, moderate and severe categories. RESULTS: The median serum hs-CRP concentration increased with increasing severity of depression and anxiety disorders. Male participants with severe depression had significantly higher levels of hs-CRP (p<0.001); however, this relationship was less marked among women (p=0.04). Subjects with severe anxiety also had significantly higher levels of hs-CRP (p<0.001). Moreover, women with severe depression and anxiety had higher BMI. There was also a positive association between current smoking habit and depression/anxiety disorders. CONCLUSION: Depression and anxiety disorders are associated with elevated levels of hs-CRP, particularly among men. Also, there is a significant positive association between depression/anxiety disorders and inflammation linked conditions such as smoking and obesity; however, in the case of obesity this association is only present in women.