Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. Previous studies have suggested that in the pathogenesis of this disease, regulatory pathways associated with de novo lipogenesis and ß-oxidation pathways genes are misregulated. Capparis spinosa (CS) belongs to the family of Capparidaceae and is a traditional plant used to treat various diseases, particularly dyslipidemia. The compounds and extracts of this plant in In vivo and in vitro studies resulted in a reduction in lipid profiles and glucose. However, the mechanism of these effects remains unknown. This study aimed to evaluate the effects of (CS) fruit extract on NASH compared to fenofibrate and explored the related molecular mechanism. RESULTS: In the rats (n = 40) model of NASH, biochemical and histopathological examinations showed that liver steatosis, inflammation, and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated sterol regulatory element-binding protein-1c (SREBP-1c) (p < 0.001), acetyl-CoA carboxylase (ACC) (p < 0.001), and up-regulated Carnitine palmitoyltransferase I (CPT1) expression (p < 0.001). In conclusion, CS has favorable therapeutic effects for NASH, which was associated with ameliorating steatosis and fibrosis via regulation of the DNL and ß-oxidation pathway genes.

Possible role of WNT10B in increased proliferation and tubule formation of human umbilical vein endothelial cell cultures treated with hypoxic conditioned medium from human adipocytes.

Regulation of angiogenesis plays an important role in adipose tissue expansion and function. The Wnt pathway and WNT10B, the main member of Wnt family, participate in angiogenesis in cancer tumors, but there is limited evidence to support the regulatory role of WNT10B in human adipose tissue angiogenesis. Subcutaneous white adipose tissue (scWAT) of 80 participants including obese and non-obese subjects was obtained and the expression of WNT10B and VEGFA genes were evaluated using qPCR. Human adipose-derived stem cells (hADSC) were differentiated to adipocytes and incubated under either hypoxic or normoxic conditions. The conditioned media of these adipocytes were collected and used as growth media for human umbilical vein endothelial cells (HUVEC) in Matrigel. We evaluated the proliferation, cell cycle phases, tubule formation and ß-catenin activation of these treated cells. We found a significant correlation between WNT10B and VEGFA expression in the scWAT of both obese and non-obese subjects. Proliferation and tubule formation of HUVEC treated with conditioned media of hypoxic adipocytes (hCM) in the S-phase were increased significantly compared to the HUVEC treated with the conditioned media of normoxic adipocytes (nCM). The expression of WNT10B and VEGFA was enhanced in hypoxic adipocytes compared to normoxic adipocytes; also, activation and nuclear translocation of ß-catenin was enhanced in the HUVEC treated with hCM compared to nCM. WNT10B acts as an angiogenic protein in scWAT under hypoxic conditions. Hypoxia induced WNT10B increases VEGFA expression and causes tube formation by HUVECs and angiogenesis in adipose tissue via the canonical Wnt/ß-catenin pathway.

Olive Leaf Extract Supplementation Combined with Calorie-Restricted Diet on Reducing Body Weight and Fat Mass in Obese Women: Result of a Randomized Control Trial.

The present trial aims to evaluate a supplementation of the olive leaf extract (OLE) in adjunct with a weight loss diet on anthropometric indices, glycemic indices, lipid profile, as well as the level of adipokines, and free fatty acid in obese women. We carried out an 8-week randomized, placebo-controlled, double-blind, parallel-group, clinical trial. The participants were randomly stratified according to age and they were assigned to one of the two study groups: Standard weight loss diet (estimated daily energy requirements minus 500 kcal) + OLE supplementation (n = 35) in intervention group or Standard weight loss diet (estimated daily energy requirements minus 500 kcal) + placebo (n = 35) in placebo group. The study groups were homogeneous regarding the baseline age, height, weight, body mass index (BMI), waist circumferences, married status, and physical activity levels (p > 0.05). The results of analysis of covariance presented significant decreases in BMI, fat mass, and body weight in the OLE group compared to those in the placebo group (p < 0.05). At the end of the study, the serum levels of fasting blood sugar, insulin, low-density lipoprotein cholesterol, total cholesterol, leptin, fatty free acid, and homeostasis model assessment-insulin resistance significantly decreased, and serum levels of high-density lipoprotein cholesterol and adiponectin elevated in the intervention group (p < 0.05). Based on results it seems that the addition of OLE to a hypocaloric diet for 8-week compared with a hypocaloric diet alone may be more effective in modifying obesity and metabolic risk factors. TRIAL REGISTRATION: Iranian Registry of Clinical Trials Identifier: IRCT20190129042552N2.

Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become significant global health concerns. In the present study, we aimed to investigate the effects of saroglitazar, a dual PPARα/γ agonist, fenofibrate, a PPAR-α agonist, and pioglitazone, a PPAR-γ agonist on an animal model of NASH. METHODS: Male Wistar rats were fed a high-fat (HF) emulsion via gavage for 7 weeks to induce NASH. The HF-treated rats were grouped into four groups to receive saroglitazar, pioglitazone, fenofibrate, or vehicle. We measured body and liver weight, liver enzymes, serum levels of adiponectin and leptin. We also performed histopathological examinations and gene expression analysis of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α), transforming growth factor-beta (TGF-ß), and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Body weight was markedly normalized by both saroglitazar and fenofibrate, while the liver index only decreased significantly with saroglitazar. Saroglitazar corrected ALT, AST, leptin, and adiponectin levels better than pioglitazone and fenofibrate. All PPAR agonists significantly attenuated the upregulation of the proinflammatory and TGF-ß genes, which correlated with the improved steatosis, inflammation of liver tissue, and fibrotic lesions. CONCLUSIONS: As documented by our results, the dual activation of PPARα/γ by saroglitazar could effectively improve steatosis, fibrosis, and aspects of necro-inflammation in the HF-induced NASH model more than fenofibrate and pioglitazone, and it can be more beneficial in the management of NASH.

Association between the rs615563 variant of PCSK9 gene and circulating lipids and Type 2 diabetes.

OBJECTIVE: Many different genetic variants of proprotein convertase subtilisin kexin 9 (PCSK9) are related to the serum levels of cholesterol and LDL cholesterol (LDL-C). The rs615563 variant of PCSK9 (a gain-of-function mutation) is associated with increased triglycerides and cholesterol levels, but its association with the incidence of diabetes is not well defined. This study aimed to investigate the relationship between the PCSK9 rs615563 variant with the incidence of type 2 diabetes. The data reported in this study are based on subsamples from a 5-year (2009-2014) cohort study of the adult population (590 subjects) aged 20 years and older. The rs615563 polymorphism was genotyped using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The distribution of PCSK9 rs615563 genotypes was not significantly different between the diabetic and non-diabetic individuals. The incidence of diabetes after five-years of follow-up was not different between the genotypes. Our findings also showed no significant relationship between this polymorphism and serum lipid parameters. The data extracted from our cohort study do not support the findings that the gain-of-function mutations of PCSK9 predispose to the incidence of type 2 diabetes.

Capparis spinosa improves the high fat diet-induced non-alcoholic steatohepatitis in rats: the possible role of FGF21.

OBJECTIVES: This study focused on the beneficial effects of Capparis spinosa (CS) treatment on the steatohepatitis induced by the administration of a high-fat emulsion in rats. Changes of hepatic expression and secretion of fibroblast growth factor 21 (FGF21) were also evaluated as a probable mechanism of the CS effects on fatty liver. Male Wistar rats were allocated in different groups to receive a normal diet (NC group), a high-fat diet (HF group), or the high-fat emulsion plus CS extract at a dose of 20 mg/kg (HF+CS group). Body and liver weight, liver index, serum biochemical factors, histopathological examination, and serum level and hepatic gene expression of FGF21 were determined. RESULTS: CS administration markedly reduced liver weight and index, serum levels of glucose, lipids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and improved histological features of nonalcoholic steatohepatitis (NASH) which were induced by HF feeding in this model. CS supplementation also restored the decreased hepatic and serum FGF21 levels in the fatty liver rats. We propose that the FGF21 up-regulation may partly account for the favorable effects of CS in this steatohepatitis model.

Assessing agreement between the three common clinical measurement methods of HbA1c.

Reliable measurement of hemoglobin A1c (HbA1c) has great importance in the diagnosis and monitoring of diabetes mellitus. The aim of the present study was to compare the performance parameters of the three common methods of HbA1c assay, including the Roche, Sebia and TOSOH G8 systems. We studied 120 patients referred to a clinical laboratory for HbA1c assay. The blood samples were analyzed with the Roche, Sebia and TOSOH G8 systems based on immunoassay, capillary electrophoresis, and ion-exchange chromatography techniques, respectively. The Spearman and the Passing-Bablok regression,as well as the Bland-Altman plots, were used to compare these methods. For each assay, the patients' classification was evaluated at the three cut-points of 6.5, 7, and 8% and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the methods were estimated. Our results showed that there were good correlations and agreement between the methods. We found a mean difference of 0.07% for the TOSOH G8 vs. Roche, 0.06% for the TOSOH G8 vs. Sebia and - 0.01% for the Roche vs. Sebia. The methods represented very low bias, indicating the good accuracy of the results. The sensitivity and specificity of the methods were comparable as well. The three methods also performed similarly in the classification of patients at the proposed cut-off points. Based on our results, the Roche, Sebia and TOSOH G8 systems showed a very high level of agreement with comparable performance parameters and yielded similar and accurate classification of diabetic patients. Therefore, these methods can be used interchangeably.

Investigation of JAK2V617F Mutation Prevalence in Patients with Beta Thalassemia Major.

BACKGROUND: Beta (ß)-thalassemia major is a genetic disorder with anemia and an increased level of erythropoietin by Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. JAK plays an important role in cell signaling, and the common mutation in the JAK2 gene in myeloid disorders is called JAK2V617F. METHODS: A total of 75 patients with beta (ß)-thalassemia major patients, including 34 males (45%) and 41 females (55%), were enrolled in this study. The presence of the JAK2V617F mutation was assessed using the amplification-refractory mutation-polymerase chain reaction (ARMS-PCR) technique. RESULTS: Among the 75 patients, 14 patients (19%) tested positive and 61 patients (81%) tested negative for JAK2V617F mutation. We observed no statistically significant difference in sex, age, genotype, and JAK2V617F mutation among patients (P> .05). However, a significant difference between blood-transfusion frequency and JAK2V617F mutation was observed (P <.05). CONCLUSION: Due to the low prevalence of JAK2V617F mutation in thalassemia, using a larger population of the patients to investigate this mutation in ineffective erythropoiesis can be useful.

HLA-B5, 7, 8, 27, and 51 Antigens and Immune Thrombocytopenic Purpura: Is There an Association?

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by low platelet counts in peripheral blood, impairment of thrombopoiesis in bone marrow, and risk of mild to severe bleedings. ITP can be seen among both sexes in different ages. Although definitive pathogenesis of this disorder is still ambiguous, some of risk factors for ITP are recognized, including human leukocyte antigens (HLAs). OBJECTIVE: Our goal was to evaluate the possible association between HLA-B5, 7, 8, 27, and 51 antigens with ITP for the first time. We were hoping to achieve new hypothetical diagnostic/prognostic biomarkers to introduce a new subject for further studies on HLA class I antigens as possible risk factors for ITP. MATERIALS AND METHODS: A total of 37 patients with ITP were included in this study. After confirmation of ITP diagnosis, peripheral blood samples were collected from them. The expression of each of HLA antigens was evaluated by standard lymphocytotoxicity technique. RESULTS: Compared with other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 22% of patients were positive for HLA-B5 and HLA-B51. Furthermore, no significant association was found between HLAs expressions with complete blood count parameters. CONCLUSIONS: We conclude that there is an association between HLA-B5 and HLA-B51 with ITP and that they are not likely to be used as diagnostic or prognostic biomarkers. We suggest studying the association between HLA-B antigens and ITP in large-scale studies to determine whether or not there is a significant association.

A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis.

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1ß, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.

HLAs in Autoimmune Diseases: Dependable Diagnostic Biomarkers?

BACKGROUND: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process. METHODS: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet's syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity". RESULTS: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet's syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively. CONCLUSION: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

The Association Between Human Leukocyte Antigens and ITP, TTP, and HIT.

BACKGROUND: Autoimmune thrombocytopenia in immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) is associated with immunologic degradation of platelets and reduced platelet counts in patients, leading to bleeding risk in patients. Considering the role of human leukocyte antigens (HLA) in the development of immune response, in this review, we examine the relationship between HLA and pathogenesis of the above-mentioned diseases. METHODS: Relevant English-language literature was searched and retrieved from Google Scholar search engine and PubMed database (1979 to 2018). The following keywords were used: "Immune Thrombocytopenic purpura," "Thrombotic Thrombocytopenic Purpura," Human Leukocyte Antigen," and "Heparin-induced thrombocytopenia." RESULTS: In autoimmune thrombocytopenia, HLA molecule presents self-antigens or foreign antigens similar to self-antigens, provoking an immune response against platelets that results in the degradation of platelets in peripheral blood and possible bleeding in the patient. For example, HLA-DRB1 *11 presents the self-antigen and induces an immune response against ADAMTS13, which is associated with thrombocytopenia in TTP patients. CONCLUSIONS: HLA alleles can be used as prognostic biomarkers for immunologic disorders of platelet such as ITP, TTP, and HIT. Different DRB1 alleles enable the assessment of resistance to common ITP treatments as well as disease prognosis. Due to the genetic association between HLA-DR1 and HLA-DQ1 alleles and the role of HLA-DRB1 *11 in TTP, the HLA-DQB1 *02: 02 allele may also play a role in TTP pathogenesis.

Dark Chocolate Effect on Serum Adiponectin, Biochemical and Inflammatory Parameters in Diabetic Patients: A Randomized Clinical Trial.

BACKGROUND: An appropriate snack for patients with diabetes mellitus should be considered to help them in their treatment due to their hard administrative diet. This study was conducted to evaluate the effect of dark chocolate on inflammatory markers, serum adiponectin, and certain biochemical factors in patients with type 2 diabetes (T2D). METHODS: This study was a randomized parallel clinical trial. Thirty grams of 84% dark chocolate, along with therapeutic lifestyle changes (TLCs) guidelines, were administrated to patients with T2D. Control group received only TLC guidelines. The intervention period was 8 weeks. Twenty-one subjects in dark chocolate and 23 subjects in control group completed the study. Fasting blood samples were collected before and after the intervention period and inflammatory markers, biochemical factors, and adiponectin levels were assessed. RESULTS: Fasting blood sugar, hemoglobin A1C, low-density lipoprotein and triglyceride levels declined significantly in the dark chocolate group and this decrease was significant between the intervention and control groups. Tumor necrosis factor-alpha, interleukin-6, and high sensitive C-reactive protein were significantly decreased in the dark chocolate group. Adiponectin levels were not significantly different between the two groups. CONCLUSIONS: In this study subjects who received dark chocolate along with TLC guidelines had lower levels of inflammatory markers such as hs-CRP, TNF-α, and IL-6, compared with the subjects who were devoid of dark chocolate and followed only the TLC guidelines. Other studies should be conducted to evaluate the most effective and administrative dosage of dark chocolate as a snack along with the common treatment of diabetes.

Adipose tissue miRNA level variation through conjugated linoleic acid supplementation in diet-induced obese rats.

BACKGROUND: Conjugated linoleic acid (CLA), which is an octadecadienoic acid isomer, is believed to play different positive physiological roles, such as lowering body fat. Due to some reported side effects of CLA, like lipodystrophy and impaired glucose metabolism, it is important to establish its safety by understanding detailed molecular mechanisms. One of these mechanisms may be the role of this dietary agent in modifying the function and activity of microRNAs (miRNAs). OBJECTIVES: The aim of the study was to investigate how adipocyte miR-27a and miR-143 expression may be influenced by CLA in obese rats. MATERIAL AND METHODS: In this study, 24 male Wistar rats were randomly divided into normal-fat diet (NFD) and high-fat diet (HFD) groups. After 8 weeks, the rats were weighed and half of the diet-induced obese rats were randomly selected to receive 500 mg CLA per 1 kg body weight for 4 weeks. At the end of this period, epididymal fat was isolated to investigate the expression level of miRNAs by real-time polymerase chain reaction (RT-PCR). RESULTS: After 12 weeks, the obese rats in the HFD group, compared with rats in the NFD group, demonstrated a significant decrease in the expression of miR-27a (p < 0.05) and a significant increase in the expression of miR-143 (p < 0.05). In the group which had received CLA for a 4-week period, these events were reversed. Moreover, the rats in this group gained less weight than other rats in HFD groups, although the difference was not statistically significant. CONCLUSIONS: In conclusion, this study demonstrated that CLA, as an anti-obesity agent, may minimize abnormal changes in miRNA expression in obesity. This suggests a new pathway for weight loss; however, further studies are needed.

What Genetics Tells us about Cardiovascular Disease in Diabetic Patients?

BACKGROUND: Long-term diabetes causes other disease development such as cardiovascular diseases (CVD). OBJECTIVE: Genetics can help us to predict cardiovascular diseases in diabetic patients. Method and Search Strategy: We searched PubMed and Google scholar for the terms: Cardiovascular disease, Diabetes, Polymorphism, Genetics from 2000 to 2017, and then included the relevant studies in our study. DISCUSSION: Essential role of inheritance in multifactorial disease is obviously clear, however, varies by disease and by other factors such as age of disease onset and subtype of disease. CVD is a multifactorial disease which can develop in diabetes patients as a result of increase in oxidative stress. It may also increase expression of pro-inflammatory factors and induce apoptosis in cardiomyocytes. CONCLUSION: Predictive polymorphisms are risk estimators for CVD incidence in diabetes patients. SNPs such as 894G>T in NOS3 gene, V16 in MnSOD gene, Rs3918188 in NOS3 gene and Rs11614913 in MiR-196a2 increase the risk of CVD in diabetic patients are precious polymorphisms for CVD prediction in diabetic population. CDKN2B, MTHFR and ACE genes have polymorphisms which increase the risk of diabetes and other polymorphisms on these genes increase the risk of CVD, we suggest these genes are valuable to study and find out if there are any polymorphisms that predict CVD susceptibility in diabetic patients.

Energy restriction combined with green coffee bean extract affects serum adipocytokines and the body composition in obese women.

BACKGROUND AND OBJECTIVES: Obesity has become a public health problem and is a cause of some preventable illnesses. Among several methods for treating obesity, the use of food supplements is highly common. A commonly used food supplement is green coffee bean extract. The objective of this study was to evaluate the efficacy of green coffee bean extract combined with an energy-restricted diet on the body composition and serum adipocytokines in obese women. METHODS AND STUDY DESIGN: In this randomised clinical trial, 64 obese women aged 20-45 years were selected and divided into two groups: an intervention group (receiving 400 mg green coffee bean extract for 8 weeks) and control group (receiving placebo). All participants were on an energy-restricted diet. The body composition, leptin, adiponectin, lipid profile, free fatty acids (FFAs), and fasting blood sugar were compared between the two groups. RESULTS: We observed significant reductions in the body weight, body mass and fat mass indices, and waist-to-hip circumference ratio in both groups; however, the decrease was higher in the intervention group. Moreover, serum total cholesterol, low-density lipoprotein, leptin, and plasma free fatty acids significantly decreased in the intervention group (p<0.05) after adjustment for energy and fibre intake. The serum adiponectin concentration significantly increased in the intervention group (p<0.05). CONCLUSIONS: Green coffee bean extract combined with an energy-restricted diet affects fat accumulation and lipid metabolism and is thus an inexpensive method for weight control in obese people.

Investigating the effects of Capparis Spinosa on hepatic gluconeogenesis and lipid content in streptozotocin-induced diabetic rats.

The present study aimed to investigate the effects of administration of Capparis spinosa (CS) fruit aqueous extract on liver metabolism in streptozotocin (STZ)-induced diabetic rats. The aqueous extract of CS was orally administered at a dose of 20mg/kg for 28 consecutive days and then its effects on blood glucose, lipid and insulin levels in normal and STZ diabetic rats were comparatively investigated. Furthermore, the effects of CS on the activity and expression of the key enzymes of gluconeogenesis and hepatic lipid content were investigated. The results showed that administration of CS extract in the STZ diabetic rats significantly decreased blood glucose level, while no significant influence on the insulin level. In addition, CS significantly decreased blood and liver triglyceride and cholesterol content in STZ diabetic rats. Furthermore, CS administration significantly reduced the mRNA expression and enzyme activities of glucose-6- phosphatase and phosphoenolpyruvate carboxykinase in liver tissues. Our findings demonstrated the beneficial effects of CS on blood glucose and lipid levels in an insulin- independent manner. This study also showed that CS improved the circulating levels of triglyceride and cholesterol. In addition, direct inhibition of gluconeogenesis in liver may be a probable mechanism of action of this plant. Since CS also decreased liver lipid content, we suggest that CS administration might be a beneficial therapeutic approach for metabolic syndrome and fatty liver.

Role of antioxidant property of carvedilol in mild to moderate hypertensive patients: A prospective open-label study.

OBJECTIVE: Carvedilol is a nonselective third generation ß-blocker that does not display the negative effects of traditional ß-blockers. Regarding the antioxidant, anti-inflammatory and distinct metabolic properties of carvedilol which are similar to that of high-density lipoprotein (HDL) and paraoxonase 1 (PON1), the present study intends to investigate the effects of carvedilol treatment on malondialdehyde (MDA) and soluble lectin-like ox-low-density lipoprotein (LDL) receptor (sLOX-1) as markers of oxidative stress in association to lipid profiles, apolipoproteins (apo), and PON1 activity in hypertensive patients. PATIENTS AND METHODS: This clinical trial study was performed on forty patients with mild to moderate essential hypertension. Subjects were studied before and after 2 months treatment with carvedilol, 25 mg daily. Lipids and lipoproteins were measured using a biochemistry analyzer. PON and arylesterase activity were assayed using paraoxon and phenyl acetate as substrates, respectively. MDA was quantified using a chemical colorimetric assay. ELISA was used to measure sLOX-1. RESULTS: Our results showed that carvedilol treatment decreased systolic and diastolic blood pressure as much as forty and 16 mmHg, respectively (P < 0.001). It also increased HDL, total cholesterol, and serum PON1 activity (P < 0.05), but the levels of triglyceride, LDL, apo A-I, and apo B did not significantly change. There was an inverse correlation between serum PON1 activity and serum MDA. CONCLUSION: This study confirmed the antihypertensive effect of the drug and its beneficial metabolic effects through augmenting HDL and PON1 activity. We propose that the antioxidant effects of carvedilol can be partially attributed to increased PON-1 activity.

Comparison of Serum Levels of Vitamin D and Inflammatory Markers Between Women With Gestational Diabetes Mellitus and Healthy Pregnant Control.

OBJECTIVE: Vitamin D appears to be involved in regulation of glycemic and inflammatory responses in gestational diabetes. The purpose of this study was to compare the serum levels of 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers and glycemic profile between gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women. MATERIALS AND METHODS: In this cross-sectional study, fasting serum levels of 25(OH)D, insulin, glucose, HOMA-IR, hs-CRP and TNF-α were measured in 45 GDM and 45 NGT women at week 20-30 gestation whom referred to Reference Medical Laboratory of Ahvaz, Iran in 1394. RESULTS: Serum 25(OH)D levels were significantly lower (p = 0.003 ) in the GDM group compared to the NGT group which remained even after controlling for confounders. Insulin and TNF-α levels were not statistically different between groups (p > 0.05). However, in unadjusted model, HOMA-IR and hs-CRP were significantly different between groups that disappeared in adjusted model. In the GDM group, there was a negative significant correlation between 25 (OH) D and fasting blood sugar (p = 0.009) and pre pregnancy BMI (p < 0.001). Levels of 25(OH)D were also negatively correlated with pre pregnancy BMI (p < 0.001) and hs-CRP levels (p = 0.003) in the NGT group. CONCLUSION: The lower level of vitamin D may be responsible for impairments of some glycemic and inflammatory markers in pregnant women. This is more important in overweight pregnant women. However, further studies with larger sample size are recommended in this regards.

The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is one of the commonest forms of musculoskeletal disorders that leads to joint degeneration and has a major impact on patients' quality of life. Experimental and in vitro studies have suggested the protective roles of pomegranate juice (PJ) as a rich antioxidant source for mitigating cartilage inflammation. In this interventional study, 38 patients with knee OA were randomly divided into two groups: PJ or control for 6 weeks to evaluate the effect of this intervention on clinical signs, inflammation and antioxidant status. RESULTS: Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention. The means of serum levels of matrix metalloproteinase (MMP)-13 was significantly decreased (P = 0.02) and glutathione peroxidase was increased in the intervention group compared with the control group after the study period (P = 0.02). CONCLUSIONS: According to the findings of this clinical trial, PJ consumption can improve physical function and stiffness, decrease breakdown cartilage enzymes and increase antioxidant status in patients with knee OA. © 2016 Society of Chemical Industry.