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Background: The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high‐risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. Methods: PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. Results: A total of seven saliva biomarkers were analyzed in this paper, including interleukin‐1alpha, interleukin‐6 (IL‐6), interleukin‐6‐8, tumor necrosis factor alpha (TNF‐α), copper, zinc, and lactate dehydrogenase. IL‐6 and TNF‐α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL‐6, TNF‐α, C‐reactive protein, total cholesterol, triglycerides, high‐density lipoproteins, low‐density lipoproteins, albumin, protein, β2‐microglobulin, fucose, lipid‐bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. Conclusion: IL‐6 and TNF‐α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration. [ABSTRACT FROM AUTHOR]

Introduction: Covid‐19 is linked with the development of cardio‐metabolic disorders, including dyslipidemia, dysregulation of high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL). Furthermore, SARS‐Co‐2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid‐19. Methods: This paper adopts the literature review method to obtain information about how Covid‐19 affects high‐risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented. Results: Reducing HDL in Covid‐19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid‐19. SARS‐CoV‐2 binds HDL, and this complex is attached to the co‐localized receptors, facilitating viral entry. Therefore, SARS‐CoV‐2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid‐19 severity. Conclusions: Covid‐19 is linked with the development of cardio‐metabolic disorders, including dyslipidemia in general and dysregulation of high‐density lipoprotein and low‐density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high‐density lipoprotein and Covid‐19. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate antidiarrheal potential of prickly pear cladode and its hepatoprotective role in different groups of diarrhea‐induced mice. Mice received cefixime (4 mg/kg of bw) and different concentrations of aqueous cladode extract (250 mg/kg of bw, 500 mg/kg of bw and 1000 mg/kg of bw). Feces Salmonella typhi ATCC 19430 was used to assess antidiarrheal potential and hematological, biochemical parameters, and histopathological analyses were carried out for 17 days. The results showed that administration of Salmonella typhi ATCC 19430 in mice produced liver injuries with histological damage, whereas 1000 mg/kg of bw cladode extract reduced the Salmonella typhi ATCC 19430 load of feces earlier as compared to the other groups during 17 days. Hematological parameters, like red blood cells (RBCs) (6.19 ± 1.85 × 106/mm3) and hemoglobin (Hb) (10.06 ± 2.03 g/dL), of negative control group decreased, while white blood cells (WBCs) (13.46 × 106/mm3) increased from reference values. In lipid profile, low‐density lipoprotein (LDL) (9.0 ± 2.41 mg/dL), high‐density lipoprotein (HDL) (6.07 ± 2.45 mg/dL) and total cholesterol (TC) (35.22 ± 8.29 mg/dL) of negative control group decreased, while triglycerides (TG) (168.35 ± 71.75 mg/dL) increased from reference values. Alanine transferase (ALT) (60.30 ± 20.33 IU/L), alkaline phosphatase (ALP) (359.9 ± 100.05 IU/L) and aspartate transferase (AST) (168.77 ± 66.61 IU/L) of negative control group increased from reference values. Urea (27.36 ± 10.54 mmol/L) and creatinine (35.29 ± 12.15 mmol/L) of the negative control group increased. Cefixime also ameliorated injuries due to the administration of Salmonella typhi ATCC 19430. Conclusively, these findings indicated that pure aqueous extract of cladode showed more promising results regarding antidiarrheal potential. Hence, cladode might be used in food and supplement formulations as a functional ingredient. [ABSTRACT FROM AUTHOR]

Background: Loss‐of‐function (LOF) variants of the angiopoietin‐like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high‐density lipoprotein cholesterol (HDL‐C) concentrations and thereby affect the risk of cardiovascular disease (CVD). Objective: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad‐Stroke and Heart‐Atherosclerotic‐Disorders (MASHAD) cohort. Methods: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow‐up. After a 12‐h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra‐ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. Results: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01–2.02, p = 0.041). There was a 1.3‐fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non‐carriers (OR = 1.32, 95%CI = 1.06–1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL‐C. Conclusion: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population. [ABSTRACT FROM AUTHOR]

Burn survivors experience profound physiological changes following injury, which may have lasting implications for cardiovascular health. This study aims to investigate the cardiovascular risk profile among burn survivors treated at a burn center in northern Iran. This observational study was conducted from 2022 to 2023 at the burn centre affiliated with Guilan University of Medical Sciences, Rasht, Iran. This study assessed a cohort study of 210 burn survivors, focusing on individuals with ≥20% TBSA burn injuries who had recovered and returned to their daily lives. This study assessed patients' lipid profiles, Framingham General Cardiovascular Risk Score (FGCRS) and risk factors, including demographics, clinical variables and physical activity. Statistical analysis employed descriptive and inferential statistics. The mean age was 49.23 years, and the mean TBSA burned was 37.06%. The risk of cardiovascular disease in 66% of the study population was less than 10%, and in 13%, it was more than 20%. Significant associations were identified between CVD risk and sex, diabetes, hypertension, BMI, TBSA burned, years after burn, physical activity level and LDL. Of the lipid profile measures, LDL, triglycerides and TC/HDL exceeded the desirable levels. This research highlights the heightened cardiovascular risk in burn survivors, emphasizing the necessity for targeted interventions and regular monitoring. Identifying modifiable risk factors enables healthcare practitioners to develop tailored strategies, enhancing cardiovascular health in this vulnerable population and improving overall outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Introduction: ANGPTLs (Angiopoietin‐like proteins) 3 and 4 play an important role in the development of type 2 diabetes. These glycoproteins affect the modulation of glucose and lipid metabolism. They inhibit lipoprotein lipase (LPL) activity and provoke lipolysis. This study was aimed to investigate the protein levels of ANGPTL3 and 4 in the serum of type 2 diabetic patients with metabolic syndrome in comparison to the type 2 diabetic patients without metabolic syndrome and the control group. Methods: Three groups of individuals were included in this study; Group I: 47 patients with type 2 diabetes and metabolic syndrome; Group II: 25 patients with type 2 diabetes without metabolic syndrome; Group III: 40 non‐diabetic healthy people without metabolic syndrome as a control group. After collection of 5 mL fasting blood samples, serum concentrations of fasting blood sugar (FBS), cholesterol (Chol), triglyceride (TG), HDL‐C (High‐density lipoprotein‐Cholesterol) and LDL‐C (Low‐density lipoprotein‐Cholesterol) were measured by the enzymatic method; blood pressure (BP), height and weight with stadiometers; and ANGPTL3 and 4 by the enzyme‐linked immunosorbent assay (ELISA). Results: The serum levels of ANGPTL3 was significantly different among our three groups (p =.000). In patients with type 2 diabetes and metabolic syndrome (Group I), ANGPTL3 and 4 levels were lower than the control group. The serum levels of the parameters evaluated in this study (except HDL‐C) was lower in the group II in comparison with the group I, and this difference was significant for TG, Chol, BP and BMI between these two groups. Also, our results revealed that there was a negative correlation between FBS, TG, Chol, LDL‐C and BMI with ANGPTL3 and 4. While, there was a significant positive correlation between ANGPTL4 and ANGPTL3. Conclusion: Altogether, our findings suggest that the decreased levels of ANGPTL3 and 4 may be a causative factor for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the association of serum uric acid to high‐density lipoprotein ratio (UHR) with the presence and severity of metabolic syndrome (MetS) among MASHAD cohort participants. Methods: In this cross‐sectional study, according to International Diabetes Federation criteria, the cohort participants were divided into MetS (+) and MetS (−) groups. MetS (+) were classified into Group 1 (those with 3 MetS criteria), Group 2 (those with 4 MetS criteria) and Group 3 (those with 5 MetS criteria). UHR was compared among the groups. Results: Data related to 9637 subjects including 3824 MetS (+) and 5813 MetS (−) were analysed. The mean UHR was significantly higher (p <.001) in the MetS (+) group compared with the MetS (−) group. UHR increased as the MetS severity increased (p <.001). ROC analysis revealed that UHR greater than 9.5% has 89.07% sensitivity and 77.03% specificity in differentiating MetS (−) from MetS (+) subjects. Conclusion: Among MASHAD cohort study participants, a significant association between UHR and MetS was found. Furthermore, there is an increase in UHR as the severity of MetS increases. Registration number of MASHAD cohort study: 85134. [ABSTRACT FROM AUTHOR]

Earlier investigations into the impact of purslane, Portulaca oleracea, on lipid profile and C‐reactive protein (CRP) produced contradictory findings. The effect of purslane consumption on lipid profiles and CRP was assessed in this comprehensive review and meta‐analysis. We conducted a thorough literature search in online databases, including PubMed, Scopus, the Cochrane library, and ISI Web of Science to find relevant randomized controlled trials up to June 2023. By incorporating 14 effect sizes from 13 RCTs, we were able to show that purslane consumption significantly decreases serum triglyceride (TG) (WMD: −16.72, 95% CI: −22.49, −10.96 mg/dL, p <.001), total cholesterol (TC) (WMD: −9.97, 95% CI: −19.86, −0.07 mg/dL, p =.048), and CRP (WMD: −1.22, 95% CI: −1.63, −0.80 mg/L, p <.001) levels in patients compared to the control group. In addition, purslane consumption significantly increases high‐density lipoprotein (HDL‐C) (WMD: 4.09, 95% CI: 1.77, 6.41 mg/dL, p =.001) levels. However, purslane consumption did not affect low‐density lipoprotein (LDL‐C) levels. According to a suggested optimal dosage, purslane consumption is considered to be safe up to 30 g/day. Purslane consumption can significantly improve cardiovascular health by improving lipid profile and inflammation status. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a group of chronic diseases caused by kidney damage from multiple causes. Metabolic syndrome (MS) manifests as dysfunction of endothelial cells and chronic functional inflammatory states, and may be involved in pathological changes related to renal impairment. Based on longitudinal data analysis of the association between estimated glomerular filtration rate (eGFR), proteinuria and MS in patients with CKD, this study aims to provide new ideas for the pathophysiological mechanism of CKD and a theoretical basis for the early prevention and effective intervention of MS‐related kidney damage. A total of 126 patients with CKD were divided into non‐MS group and MS group. According to the eGFR level, 126 patients with CKD were divided into G1 group, G2 group, G3a group, G3b group, G4 group and G5 group. Serum markers such as eGFR, urine protein, and triglycerides (TG) were collected. The correlation between eGFR, urine protein and MS‐related indexes was analysed, and the risk factors affecting CKD complicated by MS were analysed. In patients with CKD, the levels of urine protein, abdominal circumference, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose (FPG) were increased with the course of the disease, but the levels of eGFR and high density lipoprotein (HDL‐C) were decreased (p < 0.05). Abdominal circumference, TG, SBP, DBP, FP were significantly negatively correlated with eGFR, but HDL‐C was positively correlated with eGFR (p < 0.05). Diabetes, hyperlipidemia, UA, and SBP were independent risk factors affecting CKD complicated MS, and eGFR were independent protective factors (p < 0.05). The combination of diabetes, hyperlipidemia, UA, SBP, and eGFR exhibited higher prediction value for the CKD patients complicated by MS. There was a certain correlation between between MS components with eGFR and urinary protein in patients with CKD. The early intervention treatment of MS was helpful in delaying the development of CKD and reducing proteinuria. [ABSTRACT FROM AUTHOR]

High‐fat diets (HFD) adversely affect organ systems. Several studies have examined HFD‐related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time‐dependent HFD‐induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low‐density lipoprotein, high‐density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time‐dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention. [ABSTRACT FROM AUTHOR]

The detailed molecular structure of the complex formed by the apoprotein from porcine high density lipoprotein and dimyristoyl phosphatidylcholine (lecithin) has been investigated by a range of physical techniques. The complex, an oblate ellipsoid with major axis 11.0 nm and minor axis 5.5 nm (see the accompanying paper), is comprised of a section of lecithin bilayer with apoprotein at the surface. The main site of interaction between protein and lipid is in the lipid glycerophosphorytcholine group region; as with native high density lipoprotein the surface of the particle consists of a mosaic of lecithin polar groups and protein. The formation of this mosaic reduces the cooperativity of the lecithin chain motions and changes the curvature of the lipid-water interface, as compared to a bilayer. Otherwise, there are no major changes in lecithin motions indicating that no strong binding of lipid to protein occurs. The interaction involves the intercalation of amphipathic, 60 % α-helical, apoprotein molecules among the lecithin molecules so that the protein resides at the lipid-water interface. The apoprotein has a high affinity for the lipid-water interface but specific lipid-protein interactions are not involved. [ABSTRACT FROM AUTHOR]

Amphipathic helical repeals arc considered as the structural units of numerous apolipoproteins and have been described as being responsible for the interaction of apolipoproteins with phospholipids in high-density lipoproteins (HDL). Furthermore. apolipoproteins. and especially apolipoprotein Al (apoAl), are involved in various biological functions of these circulating particles in plasma. Studies with synthetic peptides corresponding to domains of the apoAl sequence have however shown that short 39-residue fragments do not interact strongly enough with phospholipids to generate particles that correctly mimic the physicochemical properties of HDL reconstituted with native apoAl [Vanloo, B., Demoor, L., Boutil- Ion. C.. Lins, L.. Baert, J,, Fruchart, J. C.. Tartar. A. & Rosseneu, M. (1995) Association of synthetic peptide fragments of human apolipoprotein A-I with phospholipids. i. Lipid Res. 36. 1686-1696.1. Here we show that synthetic branched multirneric peptides. often used as carriers for the design of synthetic vaccines (multiple-antigen peptides). can be used to mimic the physicochemical properties of apoAl in HDL. This type of molecule is obtained by using a small core matrix of Lys residues bearing radially branched synthetic peptides as dendritic arms. We compared the lipid-binding capacities and the structural properties of a linear peptide corresponding to residues 145--183 of apoAl [apoAl-(145-183)-peptide) with those of two multimeric peptides consisting respectively of three [trimeric apoAl-(145-183)j and four copies [tetrameric apoAl-( 145- 183)] of the selected sequence. branched on a covalent core matrix. This paper provides evidence for the increased abilities of the multimeric peptides to associate with phospholipids compared with the short linear peptides. Moreover, the trimeric apoAl-(145 - 183) peptide was most efficient in mimicking the physicochemical and structural properties of native apoAl in reconstituted HDL. As tools adequate to unravel the structure/function relationship of separate apolipoprotein domains are still missing. these multirneric peptides might constitute an alternative approach to linear peptides which are poor mimetics and to protein mutants which are difficult to produce and only provide information about the total sequence. [ABSTRACT FROM AUTHOR]

Adult bovine aortic endothelial (ABAE) cells, exposed to serum-free medium, specifically bind 125I-labeled human high-density lipoprotein (125I-HDL). Addition of human lipoprotein-deficient serum (LPDS) reduces the specific binding of 125I-HDL in a concentration-dependent manner, such that LPDS at a concentration of 6 mg protein/ml almost completely inhibits the specific binding of 125I-HDL. ABAE cultures exposed to 125I-labeled LPDS (125I-LPDS) specifically bind two peptides, which appear as minor iodinated components in 125I-LPDS. The binding of these two components is abolished in the presence of excess amounts of unlabeled LPDS or HDL. Preincubation of ABAE cells with 25-hydroxycholesterol (25-HC) results in an increase in the binding of the two 125I-LPDS components, similar to the increase observed in 125I-HDL binding in the presence of 25-HC. These two LPDS components comigrate on sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) with apolipoproteins A-I and A-IV of molecular masses 28 kDa and 43 kDa respectively. Furthermore, these two proteins were transfered from the SDS gel to nitrocellulose paper and interacted specifically with anti-(A-I) and anti-(A-IV) sera respectively. When ABAE cultures, pretreated with 25-HC in the presence of LPDS, are subjected to cell-surface iodination, the A-IV appears as one of the major proteins on the cell surface accessible to iodination. The interaction of A-IV with the cell surface of 25-HC-treated cells is not specific to ABAE cells and appears also in human skin fibroblasts. Analysis of the relative amounts of various apolipoproteins in the 125I-HDL bound to ABAE cells demonstrates a decrease in the relative amount of iodinated A-II concomitant with increase in the relative amounts of the other iodinated apolipoproteins, when compared to the composition of the native 125I-HDL. These changes are similar whether the binding is done in the presence or absence of LPDS. It indicates that the decrease in 125I-HDL binding in the presence of LPDS is not due to displacement of the iodinated apolipoproteins A-I and A-IV in the 125I-HDL by unlabeled A-I and A-IV present in LPDS. The results indicate that free apolipoproteins A-I and A-IV, present in LPDS, can displace HDL on the cell surface of ABAE cells. Thus, free A-I and A-IV, present in plasma, control the binding of HDL to endothelial cells and may regulate the process of cholesterol removal from the cells performed by HDL. [ABSTRACT FROM AUTHOR]

Acorn is a nutritious fruit with the reported potential of ameliorating diseases, including diabetes. This research aimed to assess the effects of acorn muffin consumption on glycemic, lipid indices, and appetite in patients with type 2 diabetes. Sixty‐six subjects were dichotomized to receive either one muffin containing 10 grams of acorn flour or a placebo muffin containing white wheat flour (no bran), per day, for 8 weeks. Acorn muffin consumption improved glycated hemoglobin (p =.06, mean difference [MD] = −0.65), triglyceride (p =.06, MD = −36.38), and high‐density lipoprotein (p =.05, MD = 1.30), albeit only marginally significantly. Among appetite parameters, hunger, desire to eat, and prospective to eat were significantly lower, and satiety and fullness were significantly higher, in the acorn muffin group. In conclusion, acorn muffins could be utilized as an adjuvant therapy to control appetite and ameliorate glycated hemoglobin in patients with type 2 diabetes. However, further investigations are required for a more comprehensive conclusion. [ABSTRACT FROM AUTHOR]

Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast orthologue of ACBP/DBI (ACB1) improves chronological aging, and this effect is reversed by knockout of essential autophagy genes (ATG5, ATG7) but less so by knockout of an essential mitophagy gene (ATG32). In humans, ACBP/DBI levels independently correlate with body mass index (BMI) as well as with chronological age. In still‐healthy individuals, we find that high ACBP/DBI levels correlate with future cardiovascular events (such as heart surgery, myocardial infarction, and stroke), an association that is independent of BMI and chronological age, suggesting that ACBP/DBI is indeed a biomarker of "biological" aging. Concurringly, ACBP/DBI plasma concentrations correlate with established cardiovascular risk factors (fasting glucose levels, systolic blood pressure, total free cholesterol, triglycerides), but are inversely correlated with atheroprotective high‐density lipoprotein (HDL). In mice, neutralization of ACBP/DBI through a monoclonal antibody attenuates anthracycline‐induced cardiotoxicity, which is a model of accelerated heart aging. In conclusion, plasma elevation of ACBP/DBI constitutes a novel biomarker of chronological aging and facets of biological aging with a prognostic value in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: Metabolic and vascular dysfunction are common features of obesity. Aryl hydrocarbon receptor (AhR) regulates lipid metabolism and vascular homeostasis, but whether vascular AhR are activated in obesity or have a protective and/or harmful effects on vascular function in obesity are unknown. Our study addresses whether AhR activation contributes to obesity‐associated vascular dysfunction and the mechanisms involved in these AhR effects. Experimental Approach Male AhR KO (Ahr−/−) and WT mice were fed either control or a HF (high‐fat) diet for 10 weeks. Metabolic and inflammatory parameters were measured in serum and adipose tissue. Vascular reactivity (isometric force) was evaluated using a myography. Endothelial NOS (eNOS) and AhR protein expression was determined by western blot, Cyp1A1 and Nos3 gene expression by RT‐PCR and.NO production was quantified by DAF fluorescence. Key Results: HF diet increased total serum HDL and LDL, as well as vascular AhR protein expression and proinflammatory cytokines in the adipose tissue. HF diet decreased endothelium‐dependent vasodilation. AhR deletion protected mice from HF diet‐induced dyslipidaemia, weight gain and inflammatory processes. HF diet‐induced endothelial dysfunction was attenuated in Ahr−/− mice. Vessels from Ahr−/− mice exhibited a greater NO reserve. In cultured endothelial cells, lysophosphatidylcholine (LPC) a major component of LDL and oxidized LDL [oxLDL]) reduced Nos3 gene expression and NO production. Antagonism of the AhR inhibited LPC effects on endothelial cells and induced decreased endothelium‐dependent vasodilation. Conclusion and Implications: AhR deletion attenuates HF diet‐induced dyslipidaemia and vascular dysfunction by improving eNOS/NO signalling. Targeting AhRs may prevent obesity‐associated vascular dysfunction. [ABSTRACT FROM AUTHOR]

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Okra (Abelmoschus esculentus) is a traditionally important vegetable herb used to treat numerous illnesses, including diabetes mellitus, in many rural parts of Bangladesh and the South Asian subcontinent. However, the scientific evidence for the aforementioned properties has not been adequately validated. Hence, the aim of this study was to explore the antidiabetic, antilipidemic activity of okra mucilage powder, and to compare its effectiveness with the isolated peel–seed of okra after mucilage extraction in Swiss albino mice. After extraction, both mucilage and peel–seed were made into powder. In addition, crude protein, mineral contents, and in vitro antioxidant activity of mucilage and peel–seed powder were assessed. After acute toxicity test, methanolic extracts of both powders were administered to alloxan‐induced diabetic mice for 3 weeks. Blood glucose levels were assessed weekly. Finally, blood samples were collected on day 21 to estimate blood glucose level, total protein (TP), and lipid profile levels. Okra mucilage powder showed less amount of protein, calcium, magnesium, phosphorus, potassium, sodium, and iron compared with peel–seed powder. In terms of antioxidant activity, the IC50 value and total phenolic content were found higher in okra mucilage powder in contrast to peel–seed powder. However, total flavonoid content was higher in peel–seed powder than mucilage powder. Three‐week administration of mucilage and peel–seed suspensions at a dose of 150 mg/kg and 200 mg/kg significantly (p <.05) reversed the abnormal changes of bodyweights, water consumption, feed consumption, and fasting blood glucose levels of diabetic subjects. Cholesterol, triglycerides, low‐density lipoproteins, high‐density lipoproteins, and total protein were found to be significantly (p <.05) improved after mucilage and peel–seed treatment. Thus, Okra can be recommended as a potential source of antidiabetic drug candidate for the effective management of diabetes mellitus and its complications. [ABSTRACT FROM AUTHOR]

Background and Purpose: Statins (HMG CoA reductase inhibitors) have beneficial effects independent of reducing cholesterol synthesis and this includes their ability to acutely activate endothelial nitric oxide synthase (eNOS). The mechanism by which this occurs is largely unknown and thus we characterized the pathways by which statins activate NOS, including involvement of scavenger receptor-B1 (SR-B1), which is expressed in endothelial cells and maintains cholesterol concentrations.Experimental Approach: Nitric oxide production was monitored in bovine aortic endothelial cells (BAECs) exposed to lovastatin (LOV) or pravastatin (PRA) for 10-20 min, alone or following pre-exposure to the end product of HMG-CoA reductase (mevalonate), G protein inhibitors (pertussis/cholera toxins), phospholipase C (PLC) inhibitor (U-73122), or intracellular and extracellular calcium chelators - BAPTA-AM and EGTA (respectively), or a function blocking antibody to SR-B1.Key Results: Both statins increased NO production in a rapid, dose-dependent and HMG-CoA reductase-independent manner. Inhibiting Gi protein or PLC almost completely blocked statin-induced NO generation. Additionally, removing extracellular calcium inhibited statin-induced NO production. COS-7 cells co-transfected with eNOS and SR-B1 increased NO production when exposed to LOV or high-density lipoprotein (HDL), an agonist of SR-B1. These effects were not observed in COS-7 cells with eNOS alone or co-transfected with bradykinin receptor 2, indicating specificity for SR-B1. Further, pretreatment of BAEC with blocking antibody for SR-B1 blocked NO responses to statins and HDL.Conclusions and Implications: LOV and PRA acutely activate eNOS through pathways that include the cell surface receptor SR-B1, Gi protein, phosholipase C and entry of extracellular calcium into endothelial cells. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hyperlipidaemia interferes with cardioprotective mechanisms, but the cause of this phenomenon is largely unknown, although hyperlipidaemia impairs the cardioprotective NO-cGMP system. However, it is not known if natriuretic peptide-cGMP-protein kinase G (PKG) signalling is affected by hyperlipidaemia. Therefore, we investigated the cardioprotective efficacy of cGMP-elevating agents in hearts from normal and hyperlipidaemic rats.Experimental Approach: Male Wistar rats were rendered hyperlipidaemic by feeding with 2% cholesterol-enriched chow for 12 weeks. Hearts isolated from normal and hyperlipidaemic rats were perfused (Langendorff mode) and subjected to 30 min occlusion of the left main coronary artery, followed by 120 min reperfusion. 8-Br-cGMP (CG, 10 nM), B-type natriuretic peptide-32 (BNP, 10 nM), S-nitroso-N-acetyl-penicillamine (SNAP, 1 microM) were perfused from 10 min prior to coronary occlusion until the 15th min of reperfusion. Infarct size (% of ischaemic risk zone) was determined by triphenyltetrazolium staining.Key Results: Treatment with CG, SNAP or BNP decreased infarct size significantly in normal hearts from its control value of 41.6 +/- 2.9% to 15.5 +/- 2.4%, 23.3 +/- 3.0% and 25.3 +/- 4.6%, respectively (P < 0.05). Protection by BNP was abolished by co-perfusion of PKG inhibitors KT5823 (600 nM) or Rp-8pCPT-PET-cGMPs (1 microM), confirming its PKG dependence. In hearts from hyperlipidaemic rats, CG, SNAP or BNP failed to decrease infarct size. Hyperlipidaemia did not alter basal myocardial PKG content, but decreased its activity as assessed by phosphorylation of cardiac troponin I.Conclusions and Implications: This is the first demonstration that defects in the cardioprotective cGMP-PKG system could be a critical biochemical anomaly in hyperlipidaemia. [ABSTRACT FROM AUTHOR]

Summary: Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high‐density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti‐inflammatory effects, despite some pro‐inflammatory actions having also been reported. The HDL role on the modulation of the immune response is further suggested by the detection of low levels together with a dysfunctional HDL in patients with autoimmune diseases. Here, we review the current knowledge of the immune mechanisms of atherosclerosis and the modulatory effects HDL may have on them. [ABSTRACT FROM AUTHOR]

Previous findings have highlighted the association between oxidized high‐density lipoprotein (ox‐HDL) and polycystic ovary syndrome (PCOS) development; however, the underlying mechanism remains unclear. Under such context, the present study aimed to investigate the mechanism underlying the involvement of ox‐HDL in PCOS in relation to the p65/micro‐RNA‐34a (miR‐34a)/FOS axis. PCOS rat models were established with the injection of dehydroepiandrosterone (6 mg/100 g body weight). Both PCOS‐modelled rats and granulosa cells (GCs) were received treatment with ox‐HDL in order to identify its role in PCOS. Next, apoptosis and viability of GCs were detected with the application of TdT‐mediated dUTP Nick‐End Labeling and flow cytometry and Cell counting kit‐8, respectively. A series of assays were performed to determine the interaction among ox‐HDL, p65, miR‐34a, FOS and nuclear factor‐κB (NF‐κB). The results revealed high expression of ox‐HDL in PCOS, and enhanced endocrine disorders and ovarian damage in rats. ox‐HDL promoted apoptosis of GCs and decreased its viability. ox‐HDL activated NF‐κB pathway and induced p65 phosphorylation to promote miR‐34a expression. miR‐34a targeted and inhibited FOS expression. In conclusion, our findings suggested that ox‐HDL promoted the activation of p65 and transcription of miR‐34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development. [ABSTRACT FROM AUTHOR]

Differential miRNA plasma profiles associated with the spontaneous loss of HIV-1 control: miR-199a-3p and its potential role as a biomarker for quick screening of elite controllers People living with HIV (PLWH) who are able to maintain suppressed viral load (VL) for years in the absence of antiretroviral therapy (ART) are known as elite controllers (ECs). From the 23 miRNAs, 22 miRNAs were positively correlated with viral load (VL), seven miRNAs were positively correlated with CD4 SP + sp T-cell counts, and 11 miRNAs were positively correlated with CD8 SP + sp T-cell counts (Table S3). Then, we also evaluated the plasma miRNA profile in TCs under the postloss condition and we found 38 miRNAs differentially expressed among groups, suggesting that viremia strongly influences the plasma miRNA profile of ECs (Figure 2A, Table S4). [Extracted from the article]

The Iowa (G26R) mutation in human apolipoprotein A‐I (apoA‐I), the major protein of plasma high‐density lipoprotein, is associated with systemic amyloidosis, and the N‐terminal 1–83 fragment of apoA‐I carrying this mutation has a strong propensity to form amyloid fibrils. Here, we generated and characterized novel monoclonal antibodies (mAbs) that display selective reactivity to apoA‐I amyloid fibrils. By immunizing BALB/c and A/J mice with apoA‐I 1‒83/G26R fibrils conjugated with hemocyanin and the hybridoma production, four IgM class mAbs were obtained. The generated mAbs exhibited strong reactivity to amyloid fibrils formed by the 1–83 fragment of apoA‐I, but not to the monomeric 1–83 fragment or full‐length apoA‐I. The apparent dissociation constant of the mAbs to apoA‐I fibrils was determined to be within the nM range. A time‐dependent aggregation assay demonstrated that the mAbs preferentially react with mature fibrils over non‐fibrillar aggregates formed by apoA‐I 1–83/G26R. In addition, dot blotting and ELISA using deletion or proline substituted variants of apoA‐I 1‒83/G26R suggest that the generated mAbs react to common structural features in apoA‐I amyloid fibrils. Indeed, the mAbs also recognized amyloid fibrils formed by α‐synuclein that has no sequence identity to apoA‐I. Thus, our newly generated anti‐apoA‐I fibril mAbs may be utilized for not only diagnosis of apoA‐I‐related amyloidosis but also structural analysis of amyloid fibrils as novel conformation‐selective antibodies. [ABSTRACT FROM AUTHOR]

Elaborates procedures for the isolation of two lipoprotein fractions from plasma high-density lipoproteins, characterized by apolipoprotein A-I and apolipoprotein A-I together with apolipoprotein A-II. Polyacrylamide gel electrophoresis; Immuno-double-diffusion; Amino acid compositions; Immunoelectrophoresis.

The morphology and structural organisation of the complexes formed from the apoprotein of porcine high-density lipoprotein and dimyristoyl phosphatidylcholine (lecithin) have been studied using the technique of small-angle X-ray scattering. Scattering measurements made in solvents of varying electron density were interpreted in terms of a scattering-equivalent model for the structure of the complex. This model is described by an oblate ellipsoidal morphology with dimensions at 20 °C: major axis 11.0 nm, minor axis 5.5 nm. Within this overall shape the lipid hydrocarbon chains are organised in an apolar core whilst the lipid polar head groups and protein are located in a outer shell 0.85 nm in thickness. The oblate morphology demonstrates that the structure of the complex is directed by the fundamental bilayer organisation of the lecithin. The dimension of the minor axis (5.5 nm) indicates that phospholipid hydrocarbon chains are orientated perpendicular to the interface. [ABSTRACT FROM AUTHOR]

Objective: The effects of anticonvulsants on lipids are the subject of considerable concern and investigation, but there are almost no data on this issue from randomized trials. We evaluated serum lipid profiles in adults with newly diagnosed epilepsy, following randomization to lacosamide (LCM) or carbamazepine (CBZ) monotherapy. Methods: We analyzed data from a Phase 3, international, randomized, double‐blind trial of LCM vs CBZ for the initial treatment of focal epilepsy. Serum lipid profiles in patients not taking lipid‐lowering agents and providing blood samples under fasting conditions before treatment, and following 3 or 12 months of treatment with LCM or CBZ at various doses were analyzed. Results: At 12 months, 271 patients satisfied the inclusion criteria for the analysis. No change was observed in LCM‐treated patients for total cholesterol, cholesterol fractions, or triglycerides. CBZ‐treated patients showed an increase of 21.1 mg/dL in total cholesterol, 12.6 mg/dL in low‐density lipoprotein (LDL) cholesterol, 12.5 mg/dL in non–high density lipoprotein (non‐HDL) cholesterol, and 8.5 mg/dL in HDL cholesterol; triglycerides remained unchanged. The proportion of patients with elevated total cholesterol levels (above the upper limit of the reference range) did not change in the LCM treatment group (37.0% at Baseline; 34.8% at 12 months), but increased from 30.8% (at Baseline) to 49.6% (at 12 months) in the CBZ treatment group. Significance: This study provides Class II evidence that CBZ elevates serum lipids, whereas LCM has no effect on lipids. It supports LCM as an appropriate choice for new‐onset focal epilepsy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the impact of weight gain prevention interventions on changes in cardiovascular risk factors over 6 years.Methods: The Study of Novel Approaches to Weight Gain Prevention (SNAP) randomized 599 participants (ages 18-35; 46% with BMI 21-25; 54% with BMI 25-30) to Large Changes (produce buffer by losing 5-10 pounds initially), Small Changes (daily small changes in intake and activity) or Control and followed 355 participants with ongoing intervention and assessments through 6 years.Results: There were no significant differences among interventions for changes in weight or cardiovascular disease (CVD) risk factors from baseline to 6 years. However, 44% of participants gained ≥5%, and only 14% lost ≥5% over 6 years. Weight changes, from baseline to year 6, were significantly associated with changes in risk factors, especially insulin and high-density lipoprotein cholesterol. Earlier weight changes (e.g., weight cycling) had no beneficial or adverse effect on changes in CVD risk factors at 6 years, independent of 6-year weight changes.Conclusions: Despite participation in a weight gain prevention trial, almost half of these young adults gained ≥5% or more over 6 years, with significant worsening in CVD risk factors. Greater attention to long-term weight gain prevention in young adults is needed. [ABSTRACT FROM AUTHOR]

The author reflects on the study by S. Holewijn and colleagues regarding the association of apolipoprotein B (apoB), non-high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol to atherosclerosis. He states that the authors did not report the values for apoA-I which is the major protein in HDL particles. He also notes that the combination of apoA-I and apoB can enhance the evaluation of cardiovascular (CV) risk.

Hyperlipidemia is closely related to oxidative stress, and it has been proved that the intake of legumes can protect the body from chronic diseases related to oxidative stress. In this study, we investigated the protective effects of mung beans and peas against high‐fat‐diet‐induced rats. It was found that, with 50% addition of mung beans or peas, the intake of mung beans and peas could significantly restore the levels of serum total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. Liver staining also showed that high‐fat diet (HFD) led to liver lesions, whereas whole‐grain intake could significantly relieve these symptoms. Compared with the HFD group, the antioxidant defense system and antioxidant gene expression in administered legume groups improved markedly. Furthermore, the antioxidant activities of the two legume extracts were determined. Characterization showed that the ethanol extracts of mung beans and peas possessed high antioxidant activities, for their ability to scavenge ABTS and DPPH, reduce Fe3+ and their antilipid peroxidation capacity. Treatments with ethanol extracts at different doses could restore the levels of intracellular lipid, malondialdehyde, and antioxidant enzyme activities in oleic acid‐induced HepG2 cells. All these results suggested that mung beans and peas or their extracts may be utilized as good candidates of natural antioxidant agents. [ABSTRACT FROM AUTHOR]

This study examined the relationship between the high‐fat, high‐sugar diet (HFHSD) and trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, the therapeutic effect of alpha‐linolenic acid (ALA) on mouse colitis, and the relationship between HFHSD and hyperlipidemia. We also examined the possible underlying mechanisms behind their interactions. Female BABL/c mice were fed with HFHSD for the 9 weeks. At the same time, ALA treatment (150 or 300 mg/kg) was administered on a daily basis. At the end of the 9 weeks, experimental colitis was induced by the intra‐colonic administration of TNBS. Body weight, spleen weight, disease activity index (DAI), histological changes, T‐cell‐related cytokine level, and lipid profiles were measured after treatment. TNBS induced severe clinical manifestations of colitis and histological damage. Low‐ALA (150 mg/kg) administration profoundly ameliorated TNBS‐induced clinical manifestations, body weight loss, spleen weight loss, and histological damage. On the contrary, the high‐ALA (300 mg/kg) administration did not ameliorate colitis and even exacerbated the symptoms. HFHSD consumption assisted TNBS in changing IL‐12, IFN‐γ, IL‐2, and IL‐17A in the liver. As expected, these changes were recovered through low‐ALA. In addition, HFHSD had a significant impact on the total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), and triglyceride (TG), which related to the increased risk of hyperlipidemia. In summation, HFHSD exacerbated the TNBS‐induced colitis via the Th1/Th17 pathway. The Low‐ALA (150 mg/kg) exhibited protective effects against the TNBS‐induced colitis via the Th1/Th2/Th17 pathway. [ABSTRACT FROM AUTHOR]

Hyperglycemia plays crucial roles in vascular disease development, including macrovascular and microvascular diseases from diabetes mellitus (DM). Our previous study demonstrated that Ruellia tuberosa L. (RTL) aqueous and ethanol extracts alleviate hyperglycemia and inhibit insulin resistance in diabetic rats. This study investigated the protective effect of RTL ethanol extract against aorta dysfunction in high‐fat diet (HFD) and streptozotocin (STZ)‐induced type 2 DM (T2DM) rats. Results showed that RTL ethanol extract (100 and 400 mg/kg BW/day) ameliorated serum lipid profiles, including triglyceride, free fatty acid, low‐density lipoprotein cholesterol, very low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol levels. It also significantly reduced the level of serum cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 in T2DM rats. Additionally, RTL extract decreased endothelin‐1 and endothelial nitric oxide contents, reduced the level of cell adhesion factors, including monocyte chemoattractant protein‐1 and cell adhesion factor vascular cell adhesion molecule‐1, while decreasing content of damage factors, namely tissue factor and von Willebrand factor in aortic tissues of diabetic rats. Equally noteworthy is that RTL extract enhanced the activity of aorta antioxidative enzymes, including superoxidase dismutase and catalase in diabetic rats, suggesting that RTL ethanol extract may ameliorate aorta dysfunction via enhancing aortic antioxidative enzyme activity, which subsequently suppresses aorta endothelial damage‐associated factors in HFD with STZ‐induced T2DM rats. [ABSTRACT FROM AUTHOR]

The use of herbal remedies is significantly considered in the atherosclerosis treatment, reduction of fatty elements, and prevention of activity of oxidative stress factors. The present study was conducted on 48 rats in 6 groups. The experimental and sham groups were fed with 2% cholesterol for 40 days; and experimental groups were separately treated by atorvastatin, quercetin, and hydroalcoholic extract for 4 weeks. After treatment procedure, some serum factors such as low‐density lipoprotein (LDL), total cholesterol (TC), malondialdehyde (MDA), and reactive oxygen species (ROS) were evaluated. Serum levels of LDL, TC, MDA, and ROS were significantly lower in experimental groups than sham group (p < .01). There was a significant decrease in serum MDA levels of these two groups in comparison with the atorvastatin‐treated group (p < .05). Blood pressure parameters were decreased in treated with quercetin and hydroalcoholic extract in comparison with the sham group (p < .05). Quercetin and hydroalcoholic extract similar to atorvastatin could decrease serum lipids [except high‐density lipoprotein (HDL)], oxidative stress factors, aorta contraction, weight gain, and blood pressure. These reagents improved the vascular structure and prevented the plaque formation. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity, and finally to cardiovascular disease. The authors aimed to investigate the role of increased HDL cholesterol (HDL-C) levels, which usually are considered protective against cardiovascular disease, in EG integrity in older hypertensive patients. The authors studied 120 treated hypertensive patients older than 50 years were divided regarding HDL-C tertiles in group HDLH (HDL-C ≥ 71 mg/dL, upper HDL-C tertile) and group HDLL (HDL-C < 71 mg/dL, two lower HDL-C tertiles). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranging from 5 to 9 µm) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. PBR 5-9 was significantly decreased in group HDLH (P = 0.04). In the whole population, HDL-C was inversely but moderately related to PBR 5-9 (r = -0.22, P = 0.01). In a multiple linear regression analysis model, using age, BMI, smoking habit, HDL-C, LDL-C, and office SBP, as independent variables, the authors found that BMI (β = 0.25, P = 0.006) independently predicted PBR 5-9 in the whole population. In older hypertensive patients, HDL-C ranging between 71 and 101 mg/dL might moderately protect EG and subsequently endothelial function. Future studies in several groups of low- or high-risk hypertensives are needed in order to evaluate the beneficial role of extremely elevated HDL-C regarding cardiovascular risk evaluation as well as endothelial glycocalyx as a novel index of target organ damage in essential hypertension. [ABSTRACT FROM AUTHOR]

Wnt signaling/LRP6 plays a critical role in metabolic syndrome and atherosclerosis, and variation in this pathway may lead to hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. In the present study, we investigated the effect of LRP6 rs2302685 (V1062I) on hyperlipidemia in Iranian children and adolescents. The population in this study consisted of 200 children (101 boys, 99 girls) aged 9–18 years old. Total cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), non‐HDL cholesterol, and triglyceride levels were measured. Body composition was evaluated by the Hologic DXA system. PCR/restriction fragment length polymorphism was performed for LRP6 rs2302685 (V1062I) genotyping. Logistic regression analysis was done to find the association between LRP6 rs2302685 (V1062I) and categorized lipid parameters in the adjusted model for confounding factors (age, sex, and puberty). Individuals with the CC genotype showed significantly higher levels of cholesterol, triglycerides, LDL, and non‐HDL compared to the CT and TT genotypes. In modeling analysis, for categorized lipid parameters, a significant association was found between CC versus CT, and CC versus TT in terms of cholesterol, LDL, and non‐HDL. It seems that LRP6 rs2302685 (V1062I) variant carriers are associated with an increased risk of hyperlipidemia in Iranian children and adolescents. [ABSTRACT FROM AUTHOR]

Objective To examine the effect on cardiovascular ( CVD) risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes. Search Strategy Electronic and manual citation searching to identify relevant randomized controlled trials ( RCTs). Inclusion Criteria RCTs that compared usual care to interventions to alter consultations between practitioners and patients. The population was adults aged over 18 years with type 2 diabetes. Trials were set in primary care. Data extraction and synthesis We recorded if explicit theory-based interventions were used, how consultations were measured to determine whether interventions had an effect on these and calculated weighted mean differences for CVD risk factors including glycated haemoglobin (HbA1c), systolic blood pressure ( SBP), diastolic blood pressure ( DBP), total cholesterol ( TC), LDL cholesterol ( LDL-C) and HDL cholesterol ( HDL-C). Results We included seven RCTs with a total of 2277 patients with type 2 diabetes. A range of measures of the consultation was reported, and underlying theory to explain intervention processes was generally undeveloped and poorly applied. There were no overall effects on CVD risk factors; however, trials were heterogeneous. Subgroup analysis suggested some benefit among studies in which interventions demonstrated impact on consultations; statistically significant reductions in HbA1c levels (weighted mean difference, −0.53%; 95% CI: [−0.77, −0.28]; P<.0001; I2=46%). Conclusions Evidence of effect on CVD risk factors from interventions to alter consultations between practitioners and patients with type 2 diabetes was heterogeneous and inconclusive. This could be explained by variable impact of interventions on consultations. More research is required that includes robust measures of the consultations and better development of theory to elucidate mechanisms. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic fatty liver disease ( NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Aim To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. Methods We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve ( AUROC) of models in validation group were compared. Results Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. Conclusions NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies. [ABSTRACT FROM AUTHOR]

Aims Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). Methods Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN ( n = 10) or placebo ( n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. Results The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1, 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1, 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1, 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1, 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1, 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. Conclusions The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]

It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with increased reactive oxygen and nitrogen species ( ROS/RNS) generation. ROS/RNS can modulate cardiac NO signalling and trigger various adaptive changes in NOS and antioxidant enzyme expressions/activities. While initially these changes may represent protective mechanisms in metabolic syndrome, later with more prolonged oxidative, nitrosative and nitrative stress, these are often exhausted, eventually favouring myocardial RNS generation and decreased NO bioavailability. The increased oxidative and nitrative stress also impairs the NO-soluble guanylate cyclase ( sGC) signalling pathway, limiting the ability of NO to exert its fundamental signalling roles in the heart. Enhanced ROS/RNS generation in the presence of risk factors also facilitates activation of redox-dependent transcriptional factors such as NF-κB, promoting myocardial expression of various pro-inflammatory mediators, and eventually the development of cardiac dysfunction and remodelling. While the dysregulation of NO signalling may interfere with the therapeutic efficacy of conventional drugs used in the management of metabolic syndrome, the modulation of NO signalling may also be responsible for the therapeutic benefits of already proven or recently developed treatment approaches, such as ACE inhibitors, certain β-blockers, and sGC activators. Better understanding of the above-mentioned pathological processes may ultimately lead to more successful therapeutic approaches to overcome metabolic syndrome and its pathological consequences in cardiac NO signalling. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit [ABSTRACT FROM AUTHOR]

Considerable studies have been carried out to investigate the relationship between the polymorphisms of PPARG (Pro12Ala, C161T and C1431T) and serum lipid levels, but the results were inconclusive. Hence, we conducted a meta-analysis to clarify the association. MEDLINE, EMBASE and the Cochrane Library databases were searched systematically. The subgroup analysis was performed based on ethnicity. Seventy-four studies with 54,953 subjects were included in this meta-analysis. In Pro12Ala, the group with the ' PP' (C/C genotype) genotype group had lower levels of total cholesterol ( TC) (mean difference, MD: −0.02, P < 0.00001; I 2 = 28%), low-density lipoprotein cholesterol ( LDL-C) ( MD: −0.02, P < 0.00001; I 2 = 30%) and higher levels of triglyceride ( TG) ( MD: 0.06, P < 0.00001; I 2 = 30%) than the combined ' PA+ AA' ( PA = C/G genotype, AA = G/G genotype) genotype group in Asian population, and the group with the ' PP' genotype had higher levels of TG ( MD: 0.07, P < 0.02; I 2 = 67%) than the combined ' PA+ AA' genotype group in non- Asian population. No statistically significant differences in the levels of TC, TG, high-density lipoprotein cholesterol, LDL-C were detected between different genotypes in C161T( Asian or non- Asian) and C1431T( Asian) polymorphisms. This meta-analysis was a renewed and confirmed study to assess the association between PPARG polymorphisms and serum lipid levels in Asian and non- Asian populations. There is a prominent association between Pro12Ala polymorphism and the levels of TC, LDL-C and TG in Asian population. No statistically significant differences in serum lipid levels were detected between different genotypes in C161T and C1431T polymorphisms. [ABSTRACT FROM AUTHOR]

Samples of virgin and refined organic grape seed oil were studied for their physicochemical quality, oxidative stability, and the bioactive compounds they contained. All of the samples were within the limits established by the Codex Alimentarius with regard to their quality parameters. Lutein, zeaxanthin, β-carotene, α-tocopherol, and catechin were the bioactive compounds analyzed, and the virgin oil afforded more significant results. No measurable amounts of zeaxanthin and β-carotene were observed in the refined oil, most likely due to the refining process that was carried out at high temperatures. The oxidative stability index decreased with increasing temperature, whereas the air flow had no effect on the stability index. The optimal parameters for the oxidative stability are 80 °C and a flow rate of 15 L h, and the virgin oil sample showed the best oxidative stability, possibly because it was not subjected to any treatment after extraction. The results from this study suggest that it would be preferable to consume virgin instead of refined grape oil because it is a better source of bioactive compounds and has a higher stability when heated. [ABSTRACT FROM AUTHOR]

Objective: In order to improve our understanding of high-density lipoprotein cholesterol (HDL-C) cardiovascular (CV) impact in obesity, the association of HDL-C plasma level with circulating early endothelial progenitor cell (early-EPC) number and endothelium-dependent vasodilatation (EDV) in obese women with normal or high low-density lipoprotein cholesterol (LDL-C) plasma levels was evaluated. Design and Methods: One hundred thirteen obese female subjects and a control group of 78 healthy female subjects were recruited. Circulating early-EPC were assessed by single- and two-color flow cytometric analyses with a fluorescence activated cell sorting (FACScan) flow cytometer. EDV was evaluated as response to ischemia by strain gauge plethysmography. Results: Both early-EPC number and EDV were significantly decreased in obese women compared with the control group. Obese women with low HDL-C showed a further decrease of early-EPC and EDV in the presence of both high or normal LDL-C plasmatic levels. In the normal HDL-C level subgroup, hypercholesterolemic and nonhypercholesterolemic subjects showed no difference in early-EPC number, whereas slight EDV impairment was present in hypercholesterolemic subjects. Conclusion: In obese women, low HDL-C is associated to decreased early-EPC number and impaired EDV, suggesting the need to assess whether evaluation of early-EPC and EDV may increase HDL-C prognostic value in the stratification of CV risk. [ABSTRACT FROM AUTHOR]

Aims/Introduction: It is important to identify individuals at risk of metabolic syndrome (MetS), namely those with insulin resistance. Therefore, the aim of the present study was to find anthropometric and metabolic parameters that can better predict insulin resistance. Subjects and Methods: We selected 3899 individuals (2058 men and 1841 women), excluding those with fasting plasma glucose (FPG) ≥126 mg/dL, on medication for hypertension, dyslipidemia or diabetes, and those with a history of advanced macrovascular disease. Using multivariate analyses, we selected components for obesity, lipids, and blood pressure based on the strength of their association with the homeostasis model assessment of insulin resistance (HOMA-IR). Results: In multiple linear regression analysis, body mass index (BMI), waist circumference (WC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and systolic blood pressure (SBP) were selected in men and women, and the effect of BMI on HOMA-IR outweighed that of WC. In multiple logistic regression analysis, BMI, TG, and SBP were significantly associated with HOMA-IR ≥2.5 in both genders, but WC and HDL-C were only selected in men. Combinations of BMI, TG, SBP, and FPG showed higher HOMA-IR values than those of the existing MetS components, considered useful for the identification of individual with higher insulin resistance. Conclusions: Body mass index, TG and SBP were selected as components significantly related to insulin resistance. The selected components were fundamentally adherent to the existing MetS criteria, the only difference being the measure of obesity, in which a stronger association with insulin resistance was observed for BMI than WC. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00162.x, 2011) [ABSTRACT FROM AUTHOR]

The burden of cardiovascular risk associated with obesity disproportionately affects African Americans and little is known about ethnic/racial differences in the relationship of obesity to cardiometabolic risk. This report assesses whether obesity is similarly associated with cardiometabolic risk factors in African Americans and whites of European ancestry. Cross-sectional observational data from the Jackson Heart Study (JHS) and the Framingham Heart Study (FHS) were compared. This analysis uses participants aged 35–74 years with BMI >18.5 kg/m2, and free of prevalent cardiovascular disease (CVD), from the initial JHS clinical examination (2000–2004) and the FHS Offspring (1998–2001) and Third Generation (2002–2005) cohorts. Participants were evaluated for the presence of lipid abnormalities, hypertension, and diabetes. Overall, 4,030 JHS (mean age 54 years, 64% women) and 5,245 FHS (mean age 51 years, 54% women) participants were available for analysis. The prevalence of all risk factors except high triglycerides and low high-density lipoprotein (HDL) was substantially higher in JHS (all P < 0.001) and BMI was associated with increasing prevalence of most CVD risk factors within each race. For diabetes mellitus, hypertension, and low HDL, steeper relationships to BMI were observed in FHS than in JHS (P values <0.001–0.016). There were larger proportional increases in risk factor prevalence with increasing BMI in whites than in African Americans. The higher prevalence rates of cardiometabolic risk factors at nearly all levels of BMI in African Americans, however, suggest that additional factors contribute to the burden of CVD risk in African Americans. [ABSTRACT FROM AUTHOR]

Higher levels of the adipocyte-specific hormone adiponectin have been linked to increased high-density lipoprotein (HDL) and lower insulin resistance. This study was conducted to determine the influence of macronutrient intake on adiponectin levels. One hundred and sixty-four pre- and stage-1 hypertensive adults participated in the Optimal Macro-Nutrient Intake Heart (OMNI-Heart) trial, a crossover feeding study originally testing the effects of macronutrients on blood pressure. Participants underwent three 6-week feeding periods: one rich in carbohydrates (CARB), one rich in monounsaturated fat (MUFA), and one rich in protein (PROT), while maintaining body weight. Their median plasma high molecular weight (HMW) and total adiponectin levels were 2.3 and 8.2 µg/ml, respectively, resulting in an average of 27% HMW adiponectin. Both HMW and total adiponectin levels decreased after baseline while the percent HMW adiponectin remained unchanged. Between diets, the MUFA diet maintained a higher level of both HMW and total adiponectin levels than either the CARB (HMW: +6.8%, P = 0.02; total: +4.5%, P = 0.001) or PROT (HMW: +8.4%, P = 0.003; total: +5.6%, P < 0.001) diets. Changes in total adiponectin levels were positively correlated to changes in HDL cholesterol irrespective of diets (Spearman r = 0.22–0.40). No correlation was found between changes in lipids, blood pressure, or insulin resistance by the homeostasis model assessment (HOMAIR). Macronutrient intake has effects on HMW and total adiponectin levels independent of weight loss. A diet rich in MUFA was associated with higher levels of total and HMW adiponectin in comparison to a carbohydrate- or protein-rich diet. Effects seen in adiponectin paralleled those found with HDL cholesterol. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of long-term exercise training on concentrations of five hormones related to appetite and insulin resistance in overweight adolescents. In addition, we were interested in the relationships of these hormones with each other and with anthropometric and/or cardiovascular disease marker changes. Participants were ≥ the 85th percentile for BMI for age and sex and participated in an 8-month supervised aerobic training program. Anthropometrics, cardiovascular fitness assessment, and fasting blood samples were taken pre- and post-training. Glucose, insulin, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, leptin, active ghrelin, total peptide YY (PYY), adiponectin, and resistin concentrations were measured. The participants increased their time to exhaustion on an incremental treadmill test and decreased both percent body fat and blood triglyceride concentrations. Total PYY concentration increased and resistin concentration decreased after long-term exercise training, which are favorable outcomes. Leptin concentrations were related to weight, percent body fat, waist circumference, and triglyceride concentrations pre- and post-training. The changes in resistin concentrations were related to the changes in triglyceride concentrations. We conclude that long-term exercise training has beneficial effects for overweight adolescents with respect to PYY and resistin, hormones related to appetite and insulin sensitivity.Obesity (2009) 17 6, 1189–1195. doi:10.1038/oby.2009.11 [ABSTRACT FROM AUTHOR]

Background and Purpose: Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib.Experimental Approach: Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models.Key Results: Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats.Conclusions and Implications: Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands. [ABSTRACT FROM AUTHOR]

This article presents a study that genotyped single-nucleotide polymorphisms (SNP) within ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) in Mexican American subjects and measured association with obesity and metabolic syndrome (MS)-related traits. An additive model was used in this study. Results showed that three traits were associated with at least four SNP. These traits include high-density lipoprotein (HDL) cholesterol, leptin and fasting plasma glucose (FPG). It also found a strong association between HDL-C and the four-SNP model.

Background and purpose:Sphingosine 1-phosphate (S1P) is a serum-borne naturally occurring sphingolipid, specifically enriched in high-density lipoprotein (HDL) fractions. S1P binds to G-protein-coupled S1P1 receptors to activate endothelial NO synthase (eNOS) in vascular endothelial cells. We explored whether and how statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, modulate expression of S1P1 receptors and endothelial responses for subsequent stimulation with S1P or with HDL.Experimental approach:Protein expression and phosphorylation and mRNA expression in cultured bovine aortic endothelial cells (BAEC) were determined using immunoblots and reverse transcription PCR analyses, respectively. NO synthesis was assessed as nitrite production.Key results:Stimulation of BAEC with pitavastatin or atorvastatin led to significant increases in S1P1-receptors, at levels of protein and mRNA, in a dose-dependent manner. When BAEC were treated with pitavastatin prior to stimulation with S1P or with normal human HDL, phosphorylation and activation of eNOS evoked by S1P or by HDL was enhanced. These effects of statins were counteracted by L-mevalonate and were mimicked by an inhibitor of geranylgeranyl transferase I, suggesting that inhibition of HMG-CoA reductase activity and subsequent decreases in protein geranylgeranylation may contribute to these actions of statins. Specific knock down of S1P1 receptors by small interfering RNA led to attenuation of eNOS responses to HDL.Conclusions and implications:Statins induce S1P1 receptors and potentiate responses of endothelial cells to HDL-associated sphingolipids, identifying a novel aspect of the pleiotropic actions of statins through which they may exert NO-dependent vascular protective effects.British Journal of Pharmacology (2007) 150, 470–479. doi:10.1038/sj.bjp.0707114; published online 15 January 2007 [ABSTRACT FROM AUTHOR]