Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction.

BACKGROUND: obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA. METHOD: This case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits. RESULTS: miR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls. CONCLUSIONS: Circulating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.

Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study.

OBJECTIVE: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantation failure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluate the endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrial expressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) in patients with RIF compared to control subjects. MATERIALS AND METHODS: This case-control study was carried out between June 2021-July 2022. Subjects included 17 patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referred to the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopy and Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulation in all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The student's t test, chi-square, Mann-Whitney U, and analysis of covariance (ANCOVA) were used for data analyses. RESULTS: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions of miR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased in patients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrial miR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF. CONCLUSION: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can be reliable, novel biomarkers for diagnosis of RIF.

Therapeutic Potential of Resveratrol and Atorvastatin Following High-Fat Diet Uptake-Induced Nonalcoholic Fatty Liver Disease by Targeting Genes Involved in Cholesterol Metabolism and miR33.

The present study was designed to evaluate the effects of resveratrol, atorvastatin, and a combination of resveratrol and atorvastatin on expression levels of genes involved in the cholesterol metabolic pathway in the fatty liver of C57/BL6 mice. A high-fat diet was used to induce fatty liver in C57/BL6 mice treated with resveratrol, atorvastatin, or a combination of resveratrol and atorvastatin. Pathological and biochemical studies were performed. In addition, hepatic gene expressions of ATP-binding cassette transporter A1 (ABCA1), ABCG1, liver X receptor (LXR)α, scavenger receptor B1 (SR-B1), low-density lipoprotein receptor (LDLR), and miR33 were evaluated by the real-time PCR method, and the Western blot method was used to measure the ABCA1, ABCG1, and LXRα protein levels. Resveratrol and atorvastatin reduced fat accumulation in the liver of mice with fatty liver, and this effect was correlated with decreased blood glucose levels, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol blood levels compared with the positive control (PC) group. In contrast to the animals of the PC group, fatty liver groups that received resveratrol and atorvastatin had a significant effect on the mRNA levels of the ABCA1, ABCG1, LXRα, SR-B1, LDLR, and miR33 genes. Moreover, resveratrol and atorvastatin administration elevated ABCA1 and ABCG1 and reduced LXRα protein expression. Obtained results showed that resveratrol and atorvastatin combination therapy can improve nonalcoholic fatty liver disease by targeting genes involved in cholesterol metabolism and miR33.

Circulating Levels of C1q/TNF-Related Protein 3 (CTRP3) and CTRP9 in Gestational Diabetes and Their Association with Insulin Resistance and Inflammatory Cytokines.

OBJECTIVE: Gestational diabetes mellitus (GDM) is closely related to obesity, adipose tissue, and adipokines. Adiponectin-homologous adipokines with anti-inflammatory properties, including C1q/TNF-related protein 3 (CTRP3) and CTRP9, regulate glucose and lipid metabolism, which was measured in pregnant women with GDM with the aim to assess their circulating levels and their relation with inflammatory cytokines and other biochemical data. METHODS: Serum levels of CTRP3, CTRP9, adiponectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured in 43 subjects with GDM and 42 healthy controls by enzyme-linked immunosorbent assay. RESULTS: Serum levels of adiponectin and CTRP3 were lower in GDM subjects than in controls, whereas CTRP9, TNF-α, and IL-6 showed higher concentrations in subjects with GDM than in controls. In the subjects with GDM, there was a significant association of CTRP3 with homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, and triglycerides, whereas CTRP9 is associated with TNF-α and HOMA-IR. CONCLUSION: The differences in the assessed levels of CTRP3 and CTRP9 suggest a possible relation with the pathogenesis of GDM, in particular insulin resistance, which showed significant association with both adipokines.

Evaluation of MMP-9, IL-6, TNF-α levels and peripheral blood mononuclear cells genes expression of MMP-9 and TIMP-1 in Iranian patients with coronary artery disease.

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 real-time 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.

Captopril and Spironolactone can Attenuate Diabetic Nephropathy in Wistar Rats by Targeting ABCA1 and microRNA-33.

BACKGROUND: Nephropathy diabetes is one of the important causes of death and a more prevalent cause of end-stage renal disease. OBJECTIVE: The present study investigated the effect of applying spironolactone and captopril and their combination on some renal performance indices and cholesterol-efflux-related gene expression in nephropathy diabetic rats. METHODS: Intraperitoneal injection of streptozotocin was used to induce diabetes in rats. FBS, creatinine, and BUN were assayed using the calorimetry technique; also, urine microalbumin was assayed by ELISA. Hepatic gene expressions of ABCA1, ABCG1, and miR-33 were evaluated by the real-time PCR method. RESULTS: FBS levels in the captopril-treated group were significantly decreased compared with the untreated diabetic group. BUN levels of treated groups with captopril and a combination of captopril + spironolactone were significantly increased. GFR of both treated diabetic groups with captopril and spironolactone was significantly lower than an untreated diabetic group. ABCA1 gene expression in hepatic cells of the combination of spironolactone + captopril treated group was significantly increased compared to other treated and untreated diabetic groups. The hepatic expression of the ABCG1 gene in the treated and untreated diabetic groups was significantly lower than in the control group. Treatment of the diabetic group with only combination therapy decreased the hepatic gene expression of miR-33 significantly. CONCLUSION: Obtained results suggest that S+C combination therapy can improve nephropathy and diabetes disorders by targeting the ABCA1 and miR-33 gene expression. It is suggested that miR-33 and ABCA1 genes evaluation could be a new therapeutic strategy for nephropathy diabetes remediation.

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2.

Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.

Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

Evaluation of changing the pattern of CTRP5 and inflammatory markers levels in patients with coronary artery disease and type 2 diabetes mellitus.

PURPOSE: It has recently found that adipokines, play a numerous functional roles in inflammation, lipids and glucose metabolism and in the pathogenically conditions such as atherosclerosis and insulin resistance. Therefore, for the first time we aimed the present study to evaluating serum levels of CTRP5 and inflammatory cytokines patients with CAD and T2DM in comparison with controls. METHODS: This study was done on 44 patients with CAD, 45 type 2 diabetes mellitus (T2DM), 41 CAD + T2DM and 41 controls. Serum levels of TNF-α, IL-6, MCP-1 and CTRP5 were investigated by ELISA method. RESULTS: The CTRP5 levels of all patients groups were lower in comparison with control group. There was a significant negative relationship between CTRP5 levels and cytokines concentration in the studied patients. CONCLUSIONS: Our findings suggested a potential role of CTRP5 in inflammatory process of underlying atherosclerosis and diabetes; however, more studies are needed to support these finding.

Higher serum level of CTRP15 in patients with coronary artery disease is associated with disease severity, body mass index and insulin resistance.

BACKGROUND: CTRP15 is a prologue of adiponectin which has shown to have favourable effects on glucose and lipid metabolism. Studies have reported lower levels of CTRP15 in T2DM and metabolic syndrome; however, its circulating levels have not been evaluated in CAD patients. METHODS: This case-control study was conducted on 190 angiographically confirmed coronary artery disease (CAD) patients and 70 controls. Serum levels of CTRP15, adiponectin, TNF-α, and IL-6 were measured using the ELISA technique. RESULTS: CTRP15 was shown to occur in higher levels in CAD patients compared with controls. In CAD patients, CTRP15 showed a positive correlation with BMI, FBS, insulin, HOMA-IR, IL-6, and TNF-α and a negative correlation with HDL-C and adiponectin. CONCLUSION: Elevated levels of CTRP15 in CAD patients and the relation of CTRP15 with pathogenic conditions such as insulin resistance, inflammation, and decreased adiponectin and HDL-C suggest a possible compensatory response to these conditions in CAD patients.

Alteration of miR-21, miR-433 and miR-590 tissue expression related to the TGF-ß signaling pathway in ulcerative colitis patients.

Ulcerative colitis (UC) is an inflammatory disease, and studies have suggested a role for TGF-ß signalling pathway in the pathogenesis of UC. In the present study, we evaluated expression of TGF-ß signalling genes and their regulatory microRNAs in patients with UC and control subjects. The expression of TGF-ß1, SMAD2, SMAD3, miR-21, miR-101, miR-433, and miR-590 were evaluated using real-time PCR in biopsy samples of the patients and controls. Results showed increased expression of TGF-ß1 and SMAD3 in the patients compared to controls. In addition, miR-21 and miR-433 were found to be higher in the patients compared to controls; however, miR-590 was found to be lower. Moreover, miR-433 was demonstrated to have positive correlation with SMAD3 and TGF-ß while miR-21 was positively correlated with TGF-ß1. MiR-590 was negatively correlated with SMAD2 and SMAD3. Results of the present study suggested a role for TGF-ß signalling pathway related microRNAs in pathogenesis of UC.

Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial.

BACKGROUND: Both human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors. METHODS: This is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories. DISCUSSION: Genetic variation is a fundamental factor influencing individuals' divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals' dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes. Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153.

Epigenetic Modification of MicroRNA-219-1 and Its Association with Glioblastoma Multiforme.

MicroRNA-219-1 (miR-219-1) acts as a tumor suppressor in a variety of cancers but, the regulatory epigenetic mechanism involved in its gene expression level has not been studied. Using real-time polymerase chain reaction (real-time PCR) and bisulfite genomic sequencing technology, promoter methylation level of miR-219-1 and gene expression levels of miR-219-5p and miR-219-1-3p were determined respectively, in glioblastoma multiforme (GBM) (n = 31), their adjacent normal tissues (n = 31), and GBM U87 cell line. Following treatment of GBM U87 cells with 5-aza-2'-deoxycitidine (5-aza-dC), miR-219-1 promoter methylation, their target mRNA, and protein levels were determined by genomic bisulfite modification, real-time-PCR, and ELISA techniques, respectively. Our results showed that gene expression levels of miR-219-5p and miR-219-1-3p were significantly lower in GBM patients relative to their adjacent normal tissues (p < 0.01). MiR-219-1 promoter had a high level of methylation in GBM tissues (p < 0.01) and a negative correlation was observed between the miRNAs gene expression and methylation levels in GBM tissues (p < 0.01). Treatment of GBM U87 cells by 5-aza-dC decreased the level of miR-219-1 methylation, amount of target mRNA, and levels of cyclin A2 and mucin 4 (MUC4) proteins, and increased the expression levels of miR-219-5p and miR-219-1-3p (p < 0.01). Using external miR-219-5p and miR-219-1-3p, the expression of cyclin A2 and MUC4 were suppressed and proliferative activity of the U87MG cell line was reduced (p < 0.01). These findings suggested that DNA methylation has a crucial role in the regulation of miR-219-1 gene expression and that hypermethylated miR-219-1 may be involved in GBM pathogenesis.

The impacts of C1q/TNF-related protein-15 and adiponectin on Interleukin-6 and tumor necrosis factor-α in primary macrophages of patients with coronary artery diseases.

Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays a key role in the pathogenesis of atherosclerosis and some previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages. METHODS: THP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15. RESULTS: Adiponectin and CTRP15 have reduced IL-6 and TNF-α secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines' expressions and secretions in primary macrophages of both patient and control groups. However, CTRP15 has only reduced cytokines' expressions and secretions in controls and it was not able to ameliorate inflammation in macrophages of CAD patients. CONCLUSION: The results of the present study indicate anti-inflammatory impact of adiponectin and CTRP15, while this property was stronger for CTRP15. In addition, it seems likely that anti-inflammatory CTRP15's impact on macrophages in the CAD patients was weaker than macrophages from the controls.

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.

Randomized Study of the Effects of Zinc, Vitamin A, and Magnesium Co-supplementation on Thyroid Function, Oxidative Stress, and hs-CRP in Patients with Hypothyroidism.

Hypothyroidism can occur due to deficiencies in micronutrients such as zinc, magnesium, and vitamin A. The aim of this study was to determine the effects of supplementation with these micronutrients on thyroid function, oxidative stress, and hs-CRP levels in patients with hypothyroidism. In a randomized double-blind, placebo-controlled trial with two parallel groups, 86 hypothyroid patients aged 20-65 were allocated to receive daily supplementation with either: (intervention group, n = 43) one 30 mg zinc gluconate capsule per day, one 250 mg magnesium oxide tablet per day, and one 25,000 IU vitamin A capsule twice/week for 10 weeks or (placebo group, n = 43) placebo capsules and tablets as above for 10 weeks. Neither of the groups changed their diet or physical activity. Thyroid hormones (free and total thyroxine (FT4 and TT4), free tri-iodothyronine (FT3), and thyroid-stimulating hormone (TSH)), oxidative markers (malondialdehyde (MDA) and total antioxidant capacity (TAC)), serum hs-CRP, and anthropometric indices (height and weight) were assessed at the baseline and at the end of the study. In the intervention group, we found a significant increase in serum FT4, decreased anthropometric indices, and lower levels of serum hs-CRP by the end of the 10 week protocol (P < 0.05). In the placebo group, serum TAC was decreased and hs-CRP increased (P < 0.05), with no significant changes in serum TSH, FT3, TT4, and MDA after the intervention. Zinc, vitamin A, and magnesium supplementation may have beneficial effects in patients with hypothyroidism and in diseases associated with hyperthyroidism.

Impaired cholesterol efflux capacity in patients with Helicobacter pylori infection and its relation with inflammation.

BACKGROUND: Gut microorganisms are associated with atherosclerosis and related cardiovascular disease. Helicobacter pylori (H. pylori) infection is associated with dyslipidemia and inflammation contributing to the progression of atherosclerosis. OBJECTIVE: Several studies have reported reduced HDL-C levels in H. pylori infected patients, but HDL cholesterol efflux capacity (CEC) as the most important function of HDL has not been evaluated yet. METHODS: This cross-sectional study was conducted with 44 biopsy confirmed H. pylori patients and 43 controls. ABCA1-mediated, non-ABCA1 and total CEC were measured in ApoB-depleted serum and levels of ApoA-I, ApoB and hsCRP were estimated using ELISA technique. RESULTS: Total and ABCA1 mediated-CEC were reduced in patients compared to controls, independent of age, sex, body mass index and HDL-C (p < 0.001), while non-ABCA1 CEC indicated no significant change between the groups. In addition, patients showed lower serum levels of ApoA-I but increased levels of hsCRP when compared to controls. Total CEC and ABCA1-mediated CEC positively correlated with ApoA-I and HDL-C, furthermore, ABCA1-mediated CEC as well as ApoA-I inversely correlated with hsCRP. CONCLUSION: The results of the present study indicate reduced CECs in H. pylori infected patients, especially ABCA1-mediated CEC which is associated with decreased ApoA-I and increased inflammation.

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.

The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease.

INTRODUCTION: Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer Disease (AD). METHODS: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction. RESULTS: There was a significant increase in TNF-α (p=0.006), IL-1ß (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1ß (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02). CONCLUSION: TNF-α, IL-1ß, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR-195 indicated the role of miRNAs in the AD process.

Circulating levels of CTRP3 in patients with type 2 diabetes mellitus compared to controls: A systematic review and meta-analysis.

Growing evidence suggests that adipokines may be therapeutic targets for cardiometabolic diseases such as type 2 diabetes mellitus (T2DM). C1q TNF Related Protein 3 (CTRP3) is a newly discovered adipokine which shares properties with adiponectin. The literature about the association between circulating levels of CTRP3 and T2DM has been conflicting. The present study reassessed the data on circulating CTRP3 levels in T2DM patients compared to controls through a systematic review and meta-analysis. A literature search was performed in Medline, Embase, Scopus, and Web of science to identify studies that measured circulating CTRP3 levels in T2DM patients and controls. The search identified 124 studies of which 59 were screened for title and abstract and 13 were subsequently screened at the full text stage and 12 studies included into the meta-analysis. Subgroup analyses, depending on the presence of T2DM complications, matching for BMI, age, and cut off value of fasting blood sugar and HOMA-IR, were performed. The results show that circulating CTRP3 levels are negatively associated with T2DM status (SMD: -0.837; 95% CI: (-1.656 to -0.017); p = 0.045). No publication bias was identified using the Begg's rank correlation and Egger's linear regression tests (P = 1 and P = 0.44, respectively). Meta-regression demonstrated significant association between CRTP3 levels with BMI (slope: 0.11; 95% CI: 0.04-0.19; p = 0.001) and sex (slope: -0.07; 95% CI: -0.12 to -0.01; p = 0.008). The present systematic review and meta-analysis evidences a negative association between circulating level of CTRP3 and T2DM status. BMI and sex may modify this association.