Genetic predisposition to nonalcoholic fatty liver disease: insights from ANGPTL8 gene variants in Iranian adults.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease with a global prevalence, and modulation of ANGPTL8 expression has emerged as a promising predictor of NAFLD susceptibility. This research was conducted to scrutinize ANGPTL8 protein expression in NAFLD patients and elucidate the interplay between ANGPTL8 gene polymorphisms and their lipid profiles, thus shedding new light on the pathophysiology of this complex disease. The study comprised 423 unrelated participants, including 222 healthy controls and 201 individuals with NAFLD, screened using FibroScan/ultrasonography and laboratory tests. The main goal focused on the genotype and allele frequency distribution in the ANGPTL8 gene, specifically analyzing two genetic variations: rs737337 (T/C) and rs2278426 (C/T). The participants diagnosed with NAFLD were slightly younger (P ≥ 0.05) and had a higher body mass index (BMI) than the individuals in the control group. Notably, there was a significant difference in the occurrence of the rs737337 polymorphism between the NAFLD and control groups, with a lower frequency observed in the NAFLD group. Our results indicated that individuals with the TC + CC genotype and C allele of rs737337 (T/C) had a decreased risk of higher levels of ALT and AST. Conversely, those with the CT, CT + TT genotype, and T allele of rs2278426 (C/T) exhibited an increased risk of higher levels of ALT and AST. The results imply that the rs2278426 (C/T) variant of the ANGPTL8 gene is more strongly linked to an increased risk of NAFLD compared to the rs737337 polymorphism. However, additional research is needed to understand the specific molecular mechanisms responsible for the upregulation of ANGPTL8 in individuals with NAFLD.

Elevated angiopoietin-like protein 3 serum levels in diabetic nephropathy patients and its association with renal function and lipid profile.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a highly prevalent disease that has life-threatening consequences like micro and macrovascular complication. Diabetic nephropathy (DN) is one of the common consequences of T2DM which is related to secretory factors like hepatokines. Angiopoietin-Like Protein 3 (ANGPTL3) is a hepatokine that is perturbated in cardiometabolic diseases and experimental studies showed its effect on renal functions and lipid metabolism. For the first time, ANGPTL3 was measured in patients with T2DM and DN in the present study. METHODS: Serum levels of ANGPTL3, IL-6, and TNF-α were measured in 60 healthy control, 60 T2DM patients, and 61 DN patients. RESULTS: Serum levels of ANGPTL3 increased in T2DM (252.39 ± 66.01) and DN (284.59 ± 69.27) patients compared to controls (160.22 ± 48.96), and DN patients compared with T2DM patients. Urinary albumin excretion (UAE) was higher in the DN group compared to T2DM and control groups. Moreover, serum levels of IL-6 and TNF-α were elevated in both patient groups compared to controls. Moreover, ANGPTL3 represented a positive correlation with triglycerides, creatinine, and UAE in patients with both T2DM and DN groups and showed an inverse correlation with eGFR in patients with DN. Moreover, this hepatokine had a good potential to differentiate patients from controls, especially, DN patients. CONCLUSIONS: these findings provide invivo evidence for the relation of ANGPTL3 with renal dysfunction and hypertriglyceridemia in patients with DN which is in line with experimental findings and suggested a potential role for this hepatokine in DN pathogenesis.

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors.

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors' responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55-41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02-21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

Klotho, FOXO1 and cytokines associations in patients with coronary artery disease.

INTRODUCTION: Atherosclerosis is one of the main reasons for adult mortality in advanced populations and countries with high stress levels. Klotho family are single-pass trans-membrane proteins that involve in the genesis and progression of various diseases, including acardiovascular disease, apoptosis and stress oxidative imbalance. Present study, investigates the pattern of changes in Klotho and FOXO1 gene expressions and levels in atherosclerosis. METHODS: Present case control study consisted of 79 patients with atherosclerosis and 78 healthy controls. PBMC (peripheral mono-nuclear blood cells) expression levels of Klotho and FOXO1 were assayed, using qPCR method. Serum concentration of Klotho and FOXO1 were measured by ELISA method. RESULTS: A significant reduction was found in PBMC genes expression levels of Klotho (P < 0.01) of patients as comparison with controls. PBMC Gene expression of FOXO1 in patients was increased significantly (P < 0.01) when compared with controls. Pearson analysis showed a positive correlation between PBMC Klotho gene expression and Klotho levels of patients (P < 0.01). The correlation between serum concentrations of Klotho and FOXO1 of patients was also positive significantly (P < 0.01). AUC of ROC for gene expression and serum concentration of Klotho in patients were 0.701 and 0.737 respectively. CONCLUSION: Investigating the PBMC gene expression and serum concentration of Klotho in patients with atherosclerosis is suggested could be a convenient novel biomarker for predicting, prognosis, monitoring the disease progression and designing a suitable drug for patients with atherosclerosis.

Circulating levels of asprosin and its association with insulin resistance and renal function in patients with type 2 diabetes mellitus and diabetic nephropathy.

INTRODUCTION: Adipokines play an important role in the development of type 2 diabetes mellitus (T2DM) and its complications like nephropathy. Asprosin is a newly discovered adipokine involved in glucose metabolism and inflammation process. The present study aimed to evaluate asprosin levels in patients with T2DM and T2DM + nephropathy (NP) compared to control subjects as well as investigating its relationship with insulin resistance, inflammation, and renal function markers. METHODS: Serum levels of asprosin, adiponectin, IL-6, and TNF-α were measured in 55 control subjects, 54 T2DM, and 55 T2DM + NP patients using ELISA kits. RESULTS: Asprosin was found to be higher in the T2DM (6.73 ± 1.67) and T2DM + NP (7.11 ± 1.54) patients compared to the controls (4.81 ± 1.09) (p < 0.001), while adiponectin indicated a lower concentration in both patient groups compared to the control group. Moreover, IL-6 and TNF-α indicated higher levels in the two patients group compared to the control group. Asprosin was observed to have a positive correlation with HbA1c, FBG, TC, LDL-C, IL-6, and TNF-α in the T2DM group. In the patients with T2DM + NP, asprosin was found to be positively correlated with BMI, HbA1c, insulin, HOMA-IR, Cr, UAE, IL-6, and TNF-α, and it was inversely correlated with eGFR. CONCLUSION: Higher concentrations of asprosin in the T2DM and T2DM + NP groups and its relationship with glucose and lipid metabolism and markers of renal function and inflammation suggested a possible role for this adipokine in the pathogenesis of both T2DM and nephropathy.

Serum levels of Asprosin in patients diagnosed with coronary artery disease (CAD): a case-control study.

BACKGROUND: Coronary artery disease (CAD) is considered as a multi-faceted chronic inflammatory disease involving reduced blood supply to the myocardium as a result of accumulating lipids in the atrial walls. Visceral adiposity with disrupted release of adipokines play a key role in its pathogenesis. Asprosin is a newly identified fasting-induced glucogenic adipokine that has been related with metabolic disorders such as type II diabetes mellitus and polycystic ovary syndrome. The preset study sought to assess circulating asprosin in context of CAD. METHODS: In this study, serum levels of asprosin were determined in 88 CAD patients and 88 non-CAD healthy controls. Serum IL-6, TNF-α, asprosin and adiponectin were assessed using ELISA kits. RESULTS: Serum asprosin was found to be higher in CAD patients when compared to non-CAD subjects (7.84 ± 2.08 versus 5.02 ± 1.29 µg/mL, p <  0.001). Similarly, serum TNF-α, and IL-6 elevated in CAD group significantly (p <  0.001). However, circulating adiponectin diminished in CAD group when compared with non-CAD subjects (p < 0.001). Moreover, serum asprosin levels directly correlated with BMI, FBG, HOMA-IR, TG and TC. Logistic regression analyses showed that asprosin levels were associated with increased risk of developing CAD (odds ratio: 3.01, 95% CI: 2.16, 4.20 and p < 0.001), after adjusting for potential confounders (age, sex and BMI). CONCLUSIONS: The present study findings suggested a possible relation of serum asprosin with the pathogenesis of CAD, in particular through insulin resistance and dyslipidemia.

Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: A randomized, double-blind, placebo-controlled study.

Supplementation with saffron helps improve antioxidant status. Oxidative stress plays an important role in ulcerative colitis (UC). The present study aimed to investigate the effect of saffron supplementation on disease severity and Oxidative/Antioxidant factors in patients with UC. This randomized double-blinded study was conducted on 80 mild to moderate UC patients. Participants were randomly divided into intervention (100 mg saffron/daily) and placebo (100 mg maltodextrin/daily) groups. Of all the participants, 75 completed the study. After 8 weeks, there were significantly increased in the mean score of simple clinical colitis activity index questionnaire (3.83 ± 1.78 to 3 ± 1.60, p = .004), the serum levels of total antioxidant capacity (2.68 ± 0.90 to 2.79 ± 0.87, p = .016), superoxide dismutase (60.69 ± 9.59 to 66.30 ± 10.79, p = .009) and glutathione peroxidase (22.05 ± 14.27 to 29.67 ± 17.97, p = .011) in patients received saffron compared to the placebo group. Whereas, there was no significant difference in serum levels of malondialdehyde between the two groups. Finally, dietary saffron as an alternative therapy may effective in improving antioxidant factors and reducing the severity of disease in UC patients.

Serum levels of C1q/TNF-related protein-3 in inflammatory bowel disease patients and its inverse association with inflammatory cytokines and insulin resistance.

Ulcerative colitis (UC) and Crohn's disease (CD) are two major forms of inflammatory bowel disease (IBD), which is an inflammatory disease. Studies have shown that adipose tissue and inflammation play important roles in the pathogenesis of IBD. C1q/TNF-related protein-3 (CTRP3) is a newly discovered adipokine playing a substantial role during inflammatory process, and for the first time in the present study, serum levels of this adipokine were measured in the UC and CD patients. This case-control study included 70 control, 50 UC, and 50 CD patients who were diagnosed by standard criteria. Serum levels of adiponectin, IL-6, TNF-α, TGF-ß, and CTRP3 were evaluated using ELISA kits. Serum levels of IL-6, TNF-α, and TGF-ß elevated in the UC and CD patients compared with the controls while adiponectin and CTRP3 diminished in the patient's groups compared with the control. Furthermore, decrease in CTRP3 serum levels was associated with the risk of UC and CD diseases. Moreover, CTRP3 indicated negative correlation with BMI, FBS, insulin, homeostasis model assessment of insulin resistance, IL-6, TNF-α, and TGF-ß and also a positive correlation with adiponectin in both the UC and CD patients. For the first time, the present study demonstrated lower levels of CTRP3 in the UC and CD patients. Decreased serum levels of CTRP3 and its inverse relationship with inflammatory cytokines and TGF-ß levels suggested a possible role for CTRP3 in the pathogenesis of UC and CD diseases.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor-α-related protein-6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf-PCOS] and PCOS-RPL). This case-control study included 120 PCOS patients (60 inf-PCOS and 60 PCOS-RPL) and 60 healthy controls. Serum high-sensitivity C-reactive protein (hs-CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf-PCOS and PCOS-RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs-CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs-CRP in PCOS group and inf-PCOS subgroup, but not PCOS-RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

Serum levels of IL-32 in patients with type 2 diabetes mellitus and its relationship with TNF-α and IL-6.

Type 2 diabetes mellitus (T2DM) is an important public health worldwide. The main underlying mechanism of T2DM is insulin resistance which is associated with chronic inflammation. Interleukin-32 (IL-32) is a pro-inflammatory cytokine which has been implicated in pro-inflammatory responses of several human diseases. Previous studies have reported higher levels of IL-32 in inflammatory disease and obesity. The present study aimed to evaluate the serum concentrations of IL-32 in patients with T2DM and its association with cardio-metabolic parameters. This study was undertaken on 93 patients with TDM and 74 healthy controls. T2DM was diagnosed based on ADA criteria. Serum levels of IL-32, adiponectin, TNF-α, and IL-6 were measured by ELISA technique. Our findings revealed independent elevated levels of IL-32 in T2DM group (1061 (841.9-1601) pg/mL) compared to the control (630.4 (331.1-830.9) pg/mL). Furthermore, it was associated with increased risk of T2DM incidence. IL-32 indicated a positive correlation with body mass index, fasting blood glucose, TNF-α, and IL-6 in patients with T2DM. Furthermore, linear regression showed independent association between IL-32 and IL-6 plus TNF-α in patients' group. The results of the present study revealed higher levels of IL-32 in T2DM patients which have been associated with inflammatory markers. These results suggest the possible role of IL-32 in chronic inflammation in patients with T2DM.

Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease.

Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted adipokine that regulates lipid metabolism and is associated with cardiometabolic diseases, including type 2 diabetes and CAD. However, the association between circulating ANGPTL8 levels and CAD is inconsistent among studies and the mechanism by which ANGPTL8 contributes to CAD development remains poorly understood. Here we sought to evaluate the relationship between ANGPTL8 levels and endothelial dysfunction and adipose tissue inflammation in CAD patients. Concentrations of ANGPTL8, adiponectin, TNF-α, IL6, hsCRP, ICAM-1, and VCAM-1 were measured by ELISA in serum samples from 192 CAD patients diagnosed with stenosis > 50% in at least one coronary artery by angiography and 71 individuals with normal heart function. Serum ANGPTL8 levels were significantly higher in CAD patients compared to controls (83.84 ± 23.25 ng/mL vs. 50.45 ± 17.73; p < 0.001), independent of adjustment for age, sex, BMI, smoking and statin use. ANGPTL8 could also differentiate CAD patients from controls with 82.3% specificity and 81.4% sensitivity (p < 0.001). Adiponectin levels were lower in CAD patients, while ICAM-1, VCAM-1, TNF-α, IL6, and hsCRP levels were higher compared to non-CAD controls (all p < 0.001). ANGPTL8 levels were associated with BMI in controls and with BMI, TG, and ICAM-1 in CAD patients. The presence of elevated ANGPTL8 levels in CAD patients and independent association with TG and ICAM-1 suggest a possible role related to endothelial dysfunction in the pathogenesis of atherosclerosis.

Emerging Role of miR-372 and miR-101a in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: microRNAs (miRNAs) have an important role in cancer development and progression. It has been shown that miR-372 and miR-101 are involved in cancer progression. In the present study we evaluated expressions of these miRNAs and their serum levels in patients with head and neck squamous cell carcinoma (HNSCC) and controls. METHODS: We conducted this case-control study on 60 patients with HNSCC and 30 controls. Patients were diagnosed by histological assessments of their tissues. Expressions of EGFR, PTEN, PI3K/CA, miR-372, and miR-101a were evaluated in the tissues, along with serum levels of the miRNAs. RESULTS: Tissue expression of PTEN decreased in HNSCC, and expressions of EGFR and PI3K increased in HNSCC tissues compared to the controls. Tissue expressions of miR-372 increased and miR-101a decreased in HNSCC tissues compared to the controls. We observed significantly lower serum levels of miR-101a in patients; however, these findings for miR-372 were not significant. A strong correlation existed between serum levels and tissue expression of miR-101a. Notably, miR-101a serum levels showed good sensitivity and specificity for diagnosis of HNSCC. CONCLUSIONS: The results showed that HNSCC patients had higher tissue expression of miR-372 and lower expression of miR-101a. Also, serum levels of miR-101a were lower in HNSCC patients. We observed that miR-101a had good sensitivity and specificity for diagnosis of HNSCC. The present study suggested that miR-101a could be a potential biomarker for HNSCC.

Evaluation of lipid ratios and triglyceride-glucose index as risk markers of insulin resistance in Iranian polycystic ovary syndrome women.

BACKGROUND: Insulin resistance has a vital role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have shown that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. The present study was conducted to evaluate the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C), as well as fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR)) among the Iranian women diagnosed with PCOS. METHODS: In the current study, a total of 305 women with PCOS were evaluated. TG/HDL-C, TC/HDL-C, and TyG indices were calculated. Fasting insulin level was measured using ELISA technique. IR was defined as a HOMA-IR value of ≥2.63, FG-IR value of < 8.25, and QUICKI value of < 0.33. RESULTS: The insulin-resistant (IR) and insulin-sensitive (IS) groups, established by the HOMA-IR, FG-IR, and QUICKI values were different in terms of TG/HDL-C, TC/HDL-C, and TyG indices. These indices were associated with IR even after adjusting for age and BMI. ROC curve analyses showed that TyG, TG/HDL-C, and TC/HDL-C strongly predicted HOMA-IR with area under the curve (AUC) of 0.639, 0.619, and 0.623, respectively (P < 0.05). Further, TC/HDL-C was a good predictor of FG-IR with AUC of 0.614 (P = 0.04). CONCLUSION: TyG, TG/HDL-C, and TC/HDL-C indices might be good indicators of IR among Iranian women diagnosed with PCOS.

Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines.

BACKGROUND: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. METHODS: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn's disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. RESULTS: Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. CONCLUSIONS: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.

Circulating levels of oxidized low-density lipoprotein in patients with obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Patients with OSA have increased levels of oxidative stress and several studies have shown higher levels of oxidative stress markers. Oxidized-LDL (Ox-LDL) is an important risk factor for ASCVD and a number of studies have measured its levels in patients with OSA, though results from these studies are conflicting. This meta-analysis aimed to reassess circulating levels of Ox-LDL in patients with OSA in comparison with controls. METHODS: Studies evaluating Ox-LDL levels in patients with OSA and controls were explored in databases of PubMed, EMBASE, Scopus, and Web of Science. Two authors independently performed the search from January 1990 to February 2019. Two authors independently screened the studies according to title, abstract, and full text. In addition, the Newcastle-Ottawa Quality Assessment Scale was utilized to evaluate the quality of the studies. The impact of OSA on Ox-LDL levels was determined using the random effects model. RESULTS: Of 195 articles retrieved, 98 were duplicates, 49 were excluded by title, 20 excluded by abstract, and 22 by full texts. Six eligible studies were included in the meta-analysis. Pooled analysis demonstrated that Ox-LDL increased in patients with OSA compared with controls. In addition, subgroup analysis revealed that studies matching age or BMI between OSA patients and controls showed no significant difference between patients with OSA and healthy controls, while unmatched studies had higher levels of Ox-LDL in patients with OSA in comparison with controls. CONCLUSION: This study demonstrated higher circulating concentrations of Ox-LDL in patients with OSA. However, no significant difference was found in studies in which patients and controls were matched for age and BMI, suggesting the involvement of these two confounding factors as a cause for elevated concentrations of circulating Ox-LDL in patients with OSA.

The effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Our study aimed to determine the effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active RA. In this randomized, double-blind, placebo-controlled trial, 66 women older than 18 years old received 100 mg/day either saffron supplement in the intervention group (n = 33) or matched placebo in the placebo group (n = 33) for a period of 12 weeks. Sixty-one patients (30 in the control and 31 in the saffron group) remained for the final analysis. No adverse effects were reported by the patients. Saffron supplementation significantly decreased the number of tender (-1.38 ± 1.66 vs. 0.10 ± 0.40, p < .001) and swollen (-2.12 ± 2.34 vs. 0.63 ± 2.79, p < .001) joints, pain intensity based on visual analogue scale (-18.36 ± 15.07 vs. -2.33 ± 5.04), p < .001), and disease activity score (DAS28) (-0.75 ± 0.67 vs. 0.26 ± 0.77, p < .001) at the end of intervention between the two groups and in saffron group compared with baseline values. Physician Global Assessment (p = .002) and erythrocyte sedimentation rate were significantly improved after intervention (24.06 ± 12.66 vs. 32.00 ± 14.75, p = 0.028). High-sensitivity C-reactive protein reduced at the end of the intervention in the saffron group compared with baseline values (12.00 ± 7.40 vs. 8.82 ± 7.930, p = .004). Tumor necrosis factor alpha, interferon gamma, and malondialdehyde were decreased, and total antioxidant capacity were increased, but their differences between the two groups were not significant (p > .05). According to the results, saffron supplements could positively and significantly improve clinical outcomes in RA patients.

The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by oxidative stress and inflammation in the hepatocytes. Saffron and its constituents are reported to have several properties such as anti-inflammatory and anti-diabetic effects. MATERIALS AND METHODS: In a randomized double-blind placebo-controlled trial with two parallel groups including 76 eligible men and female patients with NAFLD aged 18-65, recruited from Hazrat Rasul Akram Hospital in Tehran, Iran. NAFLD was defined by a Gastroenterologist based on the American Gastrointestinal and Liver Association standards. Participants were randomly assigned to two groups receiving daily supplementation of either one tablet of 100 mg saffron (n = 38) or one placebo (n = 38) for 12 weeks. The primary outcome was high sensitive C-reactive protein (hs-CRP) and secondary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), total anti-oxidant capacity (TAC), leptin, adiponectin, anthropometric, and body composition Both groups were assigned similar diet and physical activity. RESULTS: In the treatment group, significant decreases in hs-CRP (-1.80 ng/ml, 95% CI = -2.97, -0.63, p = .032), leptin (-0.27 ng/ml, 95% CI = -0.65, -0.10, p = .040), MDA (-1.01 ng/ml, 95% CI = -1.89, -0.14, p = .023) and significant increase in TAC (0.34 µmol/L, 95% CI = 0.08, 0.61, p = .011) were observed compared to the placebo group. However, there were no significant changes in serum alanine aminotransferase, AST, TNF-α, body composition, and anthropometric indexes (p > .05). CONCLUSION: In the present study, 12 weeks of 100 mg of saffron supplementation indicated beneficial effects on serum levels of some inflammatory, oxidative stress, and adipokines biomarkers but it had no significant effect on serum concentrations of liver enzymes, anthropometric, and body composition measurements.

Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance.

Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis as the main underlying mechanism of CAD is associated with inflammation and adipose tissue dysfunction. C1q/TNF-related protein12 (CTRP12) is a newly discovered adipokine which is a paralog of adiponectin. CTRP12 has anti-inflammatory and insulin sensitizing effects. Circulating levels of this adipokine have been reported to be lower in patients with type 2 diabetes and women with polycystic ovarian syndrome. The present study was undertaken for the first time to evaluate serum levels of CTRP12 in CAD patients and its association with anthropometric and biochemical parameters. Serum levels of CTRP12 were measured using ELISA kit in 188 CAD patients (angiography confirmed) and 70 controls. The serum levels of adiponectin, TNF-α and IL-6 were measured using ELISA kits. Serum levels of CTRP12 were found to be lower in CAD patients (585.48 ±â€¯201.67 pg/mL) than in the controls (814.86 ±â€¯247.85 pg/mL; p < 0.001). CTRP12 also showed an independent association with the risk of CAD (OR [CI] = 0.998 [0.996-0.999]; p = 0.019). Moreover, it showed an inverse correlation with HOMA-IR (r = -0.298; p = 0.012) and TNF-α (r = -0.269; p = 0.023) and a positive correlation with adiponectin (r = 0.344; p = 0.003) in the controls. In CAD patients, CTRP12 was inversely correlated with BMI (r = -0.181, p = 0.013), HOMA-IR (r = -0.199; p = 0.006), TNF-α (r = -0.259; p < 0.001) and IL-6 (r = -320; p < 0.001) and a positive correlation with high density lipoprotein-cholesterol(r = 0.342; p < 0.001) and adiponectin (r = 0.398; p < 0.001). The present study showed for the first time that serum levels of CTRP12 are independently associated with CAD and that CTRP12 is associated with several CAD risk factors. The results suggest a possible link between CTRP12 and pathogenic mechanisms of atherosclerosis, such as inflammation and high density lipoprotein-cholesterol metabolism; however, more study is required in this regard.

Correction to: Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3.

Following publication of the original article [1], the authors reported that one of the co-authors has a mistake in the author name.

Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3.

OBJECTIVE: We investigated whether vitamin D receptor (VDR) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. METHODS: One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. RESULTS: One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI, the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [- 17.9(- 33.6, - 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI, ApaI, TaqI and FokI, BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. CONCLUSIONS: Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. TRIAL REGISTRATION: This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU).