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.

The effect of continuous positive airway pressure on total antioxidant capacity in obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA), a sleep-related disorder with high prevalence, is associated with an imbalance in oxidative stress and is linked to cardiovascular disease. There are conflicting reports regarding the effectiveness of continuous positive airway pressure (CPAP) therapy on oxidative stress/antioxidant markers in patients with OSA. This review was performed to evaluate the influence of therapy with CPAP on serum/plasma total antioxidant capacity (TAC) in patients with OSA. METHODS: The Cochrane Library, Web of Science, Scopus, Embase, and PubMed were searched through June 2022 to obtain studies evaluating CPAP treatment on TAC in patients with OSA. Overall results were tested using standardized mean difference (SMD) with a 95% confidence interval (CI). Comprehensive Meta-Analysis V2 software was employed to perform analyses. RESULTS: Ten studies with 12 effect sizes were eligible for inclusion in this analysis. The overall SMD revealed that CPAP therapy significantly increased TAC [SMD 0.497; 95% CI: 0.21 to 0.77; p: 0.00] in OSA. Analyses based on subgroups showed that the effect of CPAP therapy was significant in all subgroups according to therapy duration, age, BMI, and AHI. Whereas the meta-regression results indicated that the impact of therapy with CPAP on TAC is associated with AHI, BMI, and age in patients with OSA. CONCLUSIONS: The finding of this meta-analysis demonstrated a favorable impact of CPAP therapy on TAC levels in patients suffering from OSA.

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.

Oxidative modification of HDL by lipid aldehydes impacts HDL function.

Reduced levels of high-density lipoprotein (HDL) cholesterol correlate with increased risk for atherosclerotic cardiovascular diseases and HDL performs functions including reverse cholesterol transport, inhibition of lipid peroxidation, and suppression of inflammation, that would appear critical for cardioprotection. However, several large clinical trials utilizing pharmacologic interventions that elevated HDL cholesterol levels failed to provide cardioprotection to at-risk individuals. The reasons for these unexpected results have only recently begun to be elucidated. HDL cholesterol levels and HDL function can be significantly discordant, so that elevating HDL cholesterol levels may not necessarily lead to increased functional capacity, particularly under conditions that cause HDL to become oxidatively modified, resulting in HDL dysfunction. Here we review evidence that oxidative modifications of HDL, including by reactive lipid aldehydes generated by lipid peroxidation, reduce HDL functionality and that dicarbonyl scavengers that protect HDL against lipid aldehyde modification are beneficial in pre-clinical models of atherosclerotic cardiovascular disease.

High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to an accelerated risk of cardiovascular disease (CVD). Some key CVD risk factors are present in patients suffering from OSA such as hypertension, inflammation, oxidative stress, and dyslipidemia. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is proposed as a reliable biomarker of HDL function and the present study aimed to quantify this biomarker in patients with OSA. METHODS: ATP binding cassette subfamily A member 1 (ABCA1), non-ABCA1, and total CEC were determined in 69 polysomnographic-confirmed OSA patients and 23 controls. Moreover, paraoxonase (PON) activities, high-sensitivity C-reactive protein (hsCRP), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) circulating levels were quantified in the studied population. RESULTS: All CEC measures were reduced in the OSA group compared to the control group. Strikingly, ABCA1 CEC was diminished in severe OSA in comparison with mild OSA. Furthermore, PON activities and apo A-I showed lower levels, while hsCRP and apo B were elevated in OSA patients compared to controls. Moreover, ABCA1 CEC showed an inverse association with hsCRP and a positive association with apo A-I, while non-ABCA1 CEC presented an association with HDL-C. CONCLUSION: These results suggest the presence of an impaired HDL function in OSA. In particular, ABCA1 CEC was associated with disease severity and inflammation which could be a factor increasing the risk of CVD.

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.

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.

Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF-κB ligand in nonalcoholic fatty liver disease.

Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies.

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.

Increased the circulating levels of malondialdehyde in patients with obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with increased risk of cardiovascular disease. Several studies have demonstrated elevated oxidative stress in patients with OSA. This oxidative stress is a direct inducer of lipid peroxidation. Malondialdehyde (MDA), a robust marker of lipid peroxidation, has been evaluated in patients with OSA but results have been inconsistent. The present systematic review and meta-analysis was performed to quantify the circulating levels of MDA in patients with OSA compared to controls. METHODS: Search was performed in data bases of PubMed, Scopus, EMBASE, Web of Science, and Cochrane library, to find out those studies that measured MDA in patients with OSA compared to controls. RESULTS: The search produced 563 records and after removing duplicates, 383 records remained. Screening by title and abstract and the evaluation of the full text resulted in the selection of 14 articles, which were included in the meta-analysis. Pooled analysis demonstrated higher levels of MDA in the patients compared to the controls (SMD (95% CI): 1.18 (0.68, 1.68), p < 0.0001). CONCLUSION: The results of this meta-analysis demonstrated considerable elevation of MDA in patients with OSA compared to controls. The meta-analysis also indicated a positive association of MDA levels with the degree of severity of OSA. These results suggest a state of increased lipid peroxidation in patients with OSA.

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.

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.

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.

Lower Expression of miR-10a in Coronary Artery Disease and its Association with Pro/Anti-Inflammatory Cytokines.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis, the main underlying cause of CAD, is a progressive inflammatory disease. microRNAs play a substantial role in the inflammatory process and pathogenesis of atherosclerosis. miR-155, a widely studied microRNA, is associated with inflammation but there are conflicting data regarding expression of miR-155 in CAD. miR-10a is also one of the key regulators of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway which have not been evaluated in peripheral blood mononuclear cells (PBMCs) of CAD patients. METHODS: This is a case-control study conducted on 69 angiography confirmed CAD patients and 65 controls. PBMC expressions of miR-155, miR-10a, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were evaluated by real-time PCR in the study population. Also, serum levels of IL-6, TNF-α, interleukin-10 (IL10), and adiponectin were measured by ELISA. RESULTS: No significant differences in miR-155 expression was found between CAD and control group (p = 0.059), while lower expression of miR-10a was observed in CAD individuals compared to controls (p < 0.001). An independent association of miR-10a expression with risk of CAD was also demonstrated. Higher serum levels and PBMC expressions of IL-6 and TNF-α were observed in the CAD group compared to controls (p = 0.002 and p = 0.001). However, serum concentrations of IL-10 and adiponectin were lower in CAD individuals compared to controls (p < 0.001 and p = 0.005, respectively). We found a negative association of miR-10a expression with miR155, TNF-α and IL-6 gene expression as well as serum TNF-α and IL-6 levels. A positive correlation between miR10a and serum IL-10 concentrations was also shown. CONCLUSIONS: Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding.