Increase In High-density Lipoprotein Cholesterol Levels Research Articles

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated.Materials and methods226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance.ResultsThe prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58–163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16–268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs.ConclusionsHDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.

Etlingera elatior (Jack) R.M, Sm Containing Diet Normalizes Some Metabolic Syndrome Markers due to High-fat High-fructose Diet in Wistar Rats

Background: Etlingera elatior (Ee) contains phytochemical compounds that are rich in antioxidants, which may reduce several biochemical markers of metabolic syndrome (MetS). Objective: We aimed to study the effect of fresh Etlingera elatior (FEe) and steamed Etlingera elatior (SEe) as a part of rat diet on body weight, serum lipid, and malondialdehyde (MDA) level in Wistar rats with MetS induced by a high-fat, high-fructose diet. Methods: Our research was a true experimental randomized control group design with pre- and post-test. A total of 24 male Wistar rats were divided randomly into the following four groups: 1) Control, fed standard rat diet during the whole duration of the study, 2) HFFr-Sd, fed high-fat high- -fructose (HFFr) diet for 29 days, followed by 29 days of the standard diet, 3) HFFr-FEe, fed HFFr diet for 29 days, followed by 29 days of a standard diet containing 33.3% FEe, and 4) HFFr-SEe, fed HFFr diet for 29 days, followed by 29 days of a standard diet containing 33.3% SEe. The HFFr diet was given at 15 g/day along with fructose drink (20% pure fructose) at 100 ml/day. The diets in each group after the MetS induction period are referred to as intervention diets. Data at the end of HFFr (pre) and intervention diets (post) were analyzed by paired t-test. The data among groups were analyzed by one-way analysis of variance followed by post hoc test. Results: HFFr diet for 29 days induced MetS in Wistar rats fulfilling the criteria of obesity (Lee Index), hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-C). Also, there was a significant increase in serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and MDA level (p &lt; 0.05). Feeding a diet containing FEe or SEe can significantly reduce body weight, serum triglyceride, total cholesterol, LDL-C, and MDA, and increase HDL-C levels (p &lt; 0.05). The effect of FEe was more pronounced in ameliorating body weight and lipid profile than SEe. Conclusion: Fresh Ee and Steamed Ee can ameliorate obesity, dyslipidemia, and oxidative stress in MetS Wistar rats induced by a high-fat, high-fructose diet. It suggests that dietary Ee accounting for one-third of daily standard diet can assist in normalizing some MetS markers in rats.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus among Chinese: the Beijing longitudinal study of aging

BackgroundSome previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration.MethodsIn total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables.ResultsOver the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes).ConclusionsLevels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among middle-aged and elderly Chinese.

Black Chokeberry (Aronia melanocarpa) Functional Beverages Increase HDL-Cholesterol Levels in Aging Rats.

Plant-based foods rich in phenolic phytochemicals are among the promising strategies to counteract age-related changes in lipid profile. Aronia melanocarpa (AM) fruits are a rich source of phenolic compounds possessing lipid-modulating effects. The present study investigated the effect of 3-month supplementation of AM-based functional beverages on the lipid profile of healthy aging rats. Male Wistar rats (n = 40) were separated into five groups: (YC) young controls (2-month-old); (AC) adult controls (13-month-old); (A) adult animals supplemented with pure AM extract; (A + P) adult animals supplemented with pectin-enriched (1%) AM extract; (A + H) adult animals supplemented with AM extract enriched with a herbal mixture. Total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and atherogenic indices were investigated at the end of the study. Adult controls demonstrated age-related dyslipidemia resulting in decreased HDL-C, and increased TG and TC/HDL index. The supplemented groups showed a significant increase in HDL-C levels: A + P (1.49 mmol/L) and A + H (1.61 mmol/L), respectively, vs. AC (1.09 mmol/L), p < 0.05. The TC/HDL-C and LDL-C/HDL-C indices were decreased in the A + P and A + H groups in comparison to the AC group (p < 0.05). These results indicate that supplementation with polyphenol-rich AM beverages can successfully alter HDL-C levels and this effect is further potentiated by pectin and herbs.

Dapagliflozin reduces thrombin generation and platelet activation: implications for cardiovascular risk reduction in type 2 diabetes mellitus

Aims/hypothesisPeople with diabetes have an increased cardiovascular risk with an accelerated development of atherosclerosis and an elevated mortality rate after myocardial infarction. Therefore, cardioprotective effects of glucose-lowering therapies are of major importance for the pharmacotherapy of individuals with type 2 diabetes. For sodium–glucose cotransporter 2 inhibitors (SGLT2is), in addition to a reduction in blood glucose, beneficial effects on atherosclerosis, obesity, renal function and blood pressure have been observed. Recent results showed a reduced risk of worsening heart failure and cardiovascular deaths under dapagliflozin treatment irrespective of the diabetic state. However, the underlying mechanisms are yet unknown. Platelets are known drivers of atherosclerosis and atherothrombosis and disturbed platelet activation has also been suggested to occur in type 2 diabetes. Therefore, the present study investigates the impact of the SGLT2i dapagliflozin on the interplay between platelets and inflammation in atherogenesis.MethodsMale, 8-week-old LDL-receptor-deficient (Ldlr−/−) mice received a high-fat, high-sucrose diabetogenic diet supplemented without (control) or with dapagliflozin (5 mg/kg body weight per day) for two time periods: 8 and 25 weeks. In a first translational approach, eight healthy volunteers received 10 mg dapagliflozin/day for 4 weeks.ResultsDapagliflozin treatment ameliorated atherosclerotic lesion development, reduced circulating platelet–leucocyte aggregates (glycoprotein [GP]Ib+CD45+: 29.40 ± 5.94 vs 17.00 ± 5.69 cells, p < 0.01; GPIb+lymphocyte antigen 6 complex, locus G+ (Ly6G): 8.00 ± 2.45 vs 4.33 ± 1.75 cells, p < 0.05) and decreased aortic macrophage infiltration (1.31 ± 0.62 vs 0.70 ± 0.58 ×103 cells/aorta, p < 0.01). Deeper analysis revealed that dapagliflozin decreased activated CD62P-positive platelets in Ldlr−/− mice fed a diabetogenic diet (3.78 ± 1.20% vs 2.83 ± 1.06%, p < 0.01) without affecting bleeding time (85.29 ± 37.27 vs 89.25 ± 16.26 s, p = 0.78). While blood glucose was only moderately affected, dapagliflozin further reduced endogenous thrombin generation (581.4 ± 194.6 nmol/l × min) × 10−9 thrombin vs 254.1 ± 106.4 (nmol/l × min) × 10−9 thrombin), thereby decreasing one of the most important platelet activators. We observed a direct inhibitory effect of dapagliflozin on isolated platelets. In addition, dapagliflozin increased HDL-cholesterol levels. Importantly, higher HDL-cholesterol levels (1.70 ± 0.58 vs 3.15 ± 1.67 mmol/l, p < 0.01) likely contribute to dapagliflozin-mediated inhibition of platelet activation and thrombin generation. Accordingly, in line with the results in mice, treatment with dapagliflozin lowered CD62P-positive platelet counts in humans after stimulation by collagen-related peptide (CRP; 88.13 ± 5.37% of platelets vs 77.59 ± 10.70%, p < 0.05) or thrombin receptor activator peptide-6 (TRAP-6; 44.23 ± 15.54% vs 28.96 ± 11.41%, p < 0.01) without affecting haemostasis.Conclusions/interpretationWe demonstrate that dapagliflozin-mediated atheroprotection in mice is driven by elevated HDL-cholesterol and ameliorated thrombin–platelet-mediated inflammation without interfering with haemostasis. This glucose-independent mechanism likely contributes to dapagliflozin’s beneficial cardiovascular risk profile.Graphical abstract

HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research.

Low high-density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect high-density lipoprotein (HDL) function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target. HDLs comprise distinct subpopulations of particles of varying size, charge, and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties. HDLs can be anti-inflammatory (which may protect against atherosclerosis and diabetes) and proinflammatory (which may help clear pathogens in sepsis). The molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and noncoding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A through I) have revealed nonlinear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus noncoronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers (namely, cholesterol efflux capacity) are associated with coronary disease, but they remain research tools. Therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None has proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs.

Antioxidant activities and glycemic indices of ice creams enriched with orange ( Citrus sinensis ) and shaddock ( Citrus maxima ) peels and effects on rat lipid profiles

This study evaluated the effects of ice creams produced from blends of orange (Citrus sinensis) and shaddock (Citrus maxima) peels on the blood lipid profile, glycemic index, and antioxidant indices in the liver and heart of rats. Formulated ice cream was produced at a different proportion of citrus (orange and shaddock) blends and fed to rats for 28days. The result showed that the formulated ice cream enriched with citrus peels blends caused a significant increase in high-density lipoprotein-cholesterol level in the plasma and antioxidant status in the liver and heart homogenates, decreased the glycemic index, concentration of total cholesterol, triglycerides, and low-density lipoprotein in the plasma as against rats fed on plain and commercial ice creams. To conclude, the use of ice creams from blends of orange and shaddock peels could serve as a functional food for weight reduction, glycemic index, management of lipid-related diseases, and prevention of oxidative stress-related complications in the liver and heart. PRACTICAL APPLICATIONS: The consumption of ice creams has increased in many parts of the world. However, there have been limited efforts aimed at improving the medicinal properties of frozen dairy products. Hence, these ice creams could be produced on a large scale under regulated condition since they have improved medicinal properties which would be a good option for preventing/combating degenerative conditions and their related complications.

High-Density Lipoprotein Cholesterol: A Component of the Metabolic Syndrome with a New Role in Lung Function.

Background A considerable uncertainty exists about the relationship between adult metabolic syndrome (MS) and obstructive lung disease (OLD), perhaps owing to systemic inflammation. Therefore, this study aimed to investigate the relationship between MS (with its components) and the patterns of lung function impairment. Methods The participants in this study were 3978 adults aged 30-78 years from the baseline cohort of the Ningxia Cohort Study. The participants underwent pulmonary function tests, questionnaire surveys, physical examinations, and analysis of blood specimens. Results No significant difference in the prevalence of OLD was observed between male (15.9%) and female (14.2%) participants. After adjusting for possible confounding factors (e.g., age and family income), impaired lung function was found to be related to some MS components, such as abdominal obesity, high blood pressure, and low levels of high-density lipoprotein cholesterol (HDL-C) (all P < 0.05). Conclusions As an important component of MS, abdominal obesity is related to impaired lung function. Surprisingly, this study found that increased HDL-C levels could accelerate the decline of lung function; it also suggests that in the presence of different metabolic health conditions, especially abdominal obesity and low levels of HDL-C, various metabolic indicators should be comprehensively considered to prevent the decline of lung function. This partly explains the increase in the incidence of two or more chronic diseases. Therefore, the prevention of chronic diseases should shift from single-disease prevention to a comprehensive consideration of multi-disease prevention in the future. Therefore, a more sensitive evaluation of the role of HDL-C in lung function is warranted.

Transition Patterns of Weight Status and Their Predictive Lipid Markers Among Chinese Adults: A Longitudinal Cohort Study Using the Multistate Markov Model.

BackgroundObesity is well recognized as a risk factor for cardiometabolic diseases. The development of obesity is a dynamic process that can be described as a multistate process with an emphasis on transitions between weight states. However, it is still unclear what convenient biomarkers predict transitions between weight states. The aim of this study was to show the dynamic nature of weight status in adults stratified by age and sex and to explore blood markers of metabolic syndrome (MetS) that predict transitions between weight states.MethodsThis study involved 9795 individuals aged 18 to 56 at study entry who underwent at least two health check-ups in the eight-year period of study in the health check-up centre of our institution. Weight, height and biochemical indices were measured at each check-up. The participants were divided into four groups based on age and sex (young male, middle-aged male, young female and middle-aged female groups). A multistate Markov model containing 3 states (healthy weight, overweight and obesity) was adopted to study the longitudinal weight data.ResultsYoung people were more likely to transit between weight states than middle-aged people, and middle-aged people were more resistant to recover from worse states. The mean sojourn time in obesity was greatest in the middle-aged male group (6.23 years), and the predicted rate of obesity beginning with healthy weight was greatest in the young male group (13.7%). In multivariate models, age group and triglyceride (TG) and high-density lipoprotein cholesterol (HDL) levels were significant for specific transitions in females, whereas age group and HDL levels were significant in males. In females, if HDL levels increased 1 mmol/L, the probability of progression from healthy weight to overweight decreased by 37.0% (HR= 0.63), and the probabilities of recovery (overweight to healthy weight and obesity to overweight) increased by 62.0% (HR= 1.62) and 1.23-fold (HR= 2.23), respectively. In males, if TG levels increased 1 mmol/L, the risk of progression from healthy weight to overweight increased by 24.0% (HR= 1.24). Each unit increase in HDL levels was associated with a 0.99-fold (HR= 1.99) increase in the chance of recovery from overweight to healthy weight and with a 0.37-fold (HR= 0.63) decrease in the risk of progression from healthy weight to overweight.ConclusionThe weight status of young people was less stable than that of middle-aged people. Males were more likely to become overweight and more resistant to recover from worse states than females. Young males with healthy weight were more likely to develop obesity than other healthy weight groups. Blood lipid levels, especially HDL, were predictors of weight transitions in adults. Prevention and intervention measures should be applied early.

Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

IntroductionStudies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose–response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis.MethodsWe performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C–stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose–response associations.ResultsWe included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76–0.89; I 2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69–0.82; I 2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04–1.42; I 2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96–1.00; I 2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg’s test and Egger’s test for the association of HDL-C level with risk of total stroke, IS, and ICH.ConclusionA high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

Effectiveness of boiled Chrysicthys nigrodigitatus against rats-induced Salmonella Typhi infection

The decline in efficiency and the frequent toxicity effects observed with antibiotics has urge researchers to turn to food as alternative. The present work aimed at valorizing boiled Chrysicthys nigrodigitatus against Salmonella Typhi infections. Flesh of C. nigrodigitatus was boiled in 4.7 L with a ratio of 1/1.5 (Kg/V) for 17 min at approximately 100 °C. Oil extraction was done using Bligh and Dyer method. In vivo activity of different diets formulated with boiled fish oil, oil + amoxicillin and boiled fish was evaluated on rat-induced Salmonella Typhi infection. The bacterial load in blood, dietary intake and weight gain of treated rats were used to monitor the disease progression. The hematological and lipid parameters were evaluated after treatment. Diets formulated with oil and flesh of C. nigrodigitatus healed the infected rats between the 16th and 18th day. Moreover, the fish-based diet corrected the anorexia involved in the infection, increased the body weight of infected rats and normalizing the levels of red blood (6.01 ± 0.58 × 106 cells/μL) and white blood cells (22.85 ± 1.20 × 103 cells/μL). This diet also lowered total cholesterol (76.44 ± 3.57 mg/dL), LDL-cholesterol (24.32 ± 4.60 mg/dL), atherogenic index (0.850 ± 0.367 mg/dL) and increased HDL-cholesterol level (41.62 ± 3.41 mg/dL). The overall results indicated that boiled C. nigrodigitatus can be used alone or associated to amoxicillin to overcome typhoid fever and regulate the levels of red blood cells, white blood cells, total cholesterol, LDL-cholesterol, atherogenic index and HDL-cholesterol associated in S. Typhi infection.

High Density Lipoproteins and Diabetes

Epidemiological studies have established that a high plasma high density lipoprotein cholesterol (HDL-C) level is associated with reduced cardiovascular risk. However, recent randomised clinical trials of interventions that increase HDL-C levels have failed to establish a causal basis for this relationship. This has led to a shift in HDL research efforts towards developing strategies that improve the cardioprotective functions of HDLs, rather than simply increasing HDL-C levels. These efforts are also leading to the discovery of novel HDL functions that are unrelated to cardiovascular disease. One of the most recently identified functions of HDLs is their potent antidiabetic properties. The antidiabetic functions of HDLs, and recent key advances in this area are the subject of this review. Given that all forms of diabetes are increasing at an alarming rate globally, there is a clear unmet need to identify and develop new approaches that will complement existing therapies and reduce disease progression as well as reverse established disease. Exploration of a potential role for HDLs and their constituent lipids and apolipoproteins in this area is clearly warranted. This review highlights focus areas that have yet to be investigated and potential strategies for exploiting the antidiabetic functions of HDLs.

Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

HDL CHOLESTEROL LEVELS AND ENDOTHELIAL GLYCOCALYX INTEGRITY IN TREATED HYPERTENSIVE PATIENTS OVER 40 YEARS OLD

Abstract Objective: 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. We aimed to investigate the role of increased HDL cholesterol levels (HDL-C), which usually are considered protective against cardiovascular disease, in EG integrity in middle aged hypertensive patients. Design and method: We studied 186 treated hypertensive patients, apparently healthy and older than 40 years. They were divided regarding sex distribution in two groups. In males’ group, HDL-C was 48 + 19 mg/dl (n = 77, mean age 51 + 11 years) while in females’ group, HDL-C was 67 + 16 mg/dl (n = 109, mean age 63 + 12 years). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–9 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. Results: Females were older (p = 0.04) with fewer smokers (p = 0.04), higher levels of office SBP (148 + 19 mmHg vs. 139 + 15 mmHg, p &lt; 0.001) as well as higher HDL levels (p &lt; 0.001). No differences were found within groups regarding BMI, DBP, total Cholestelol and PBR 5–9. In males, HDL-C was inversely related with PBR 5–9 (r = -0.29, p = 0.01). In a multiple linear regression analysis model, using smoking habit and office SBP levels, as independent variables, we found that HDL-C independently predicted PBR 5–9 (Beta = 0.25, p = 0.006) in male hypertensives. Conclusions: In middle-aged, apparently healthy, hypertensive patients, higher HDL-C levels protect EG and subsequently endothelial function. However, the role of EG as a novel index regarding cardiovascular risk in essential hypertension needs to be extensively investigated in future studies.

The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials.

Background:Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis.Methods:Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed.Results:Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels.Conclusions:Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.

Phoenix dactylifera polyphenols improve plasma lipid profile in hyperlipidemic rats and oxidative stress on HepG2 cells

ABSTRACT The anti-hyperlipidemic potential of Algerian date palm fruits of three varieties [Deglet nour (DN), Ghars (GH), Degla baida (DB)] and its influence on oxidative stress were explored in rat models using human hepatocellular carcinoma cells (HepG2). Phenolic profile and total phenolic content of the extracts revealed in vitro antioxidant potential, which was confirmed using HepG2 cells. Reduction of TBARS level and increase in NO levels were observed in cell medium. In vivo assays showed that administration of date extracts influenced the hypolipidemic effect in rats by decreasing total cholesterol (−51% for DB, −31% for GH and −30% for DN), triacylglycerol (−61% for DN, −54% for DB and −32% for GH) and LDL-Cholesterol, while increasing HDL-Cholesterol level, indicating strong cardioprotective properties of date fruit.

Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naïve or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions. ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naïve patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study. The study included a total of 614 switched and treatment-naïve patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 ± 12years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 ± 29months. The median duration of E/C/F/TAF use was 20 ± 36 months and that of previous treatment was 23 ± 18months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively (p > 0.05). Mean CD4 counts were 708 ± 287cells/µL and 802 ± 305 cells/µL at baseline and month 12, respectively (p < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211mg/dL (p < 0.01), LDL-cholesterol 104 and 138mg/dL (p < 0.01), HDL-cholesterol 39 and 49mg/dL (p < 0.01) and triglycerides 134 and 174mg/dL (p < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient's decision: 1). Of 184 treatment-naïve patients, 88% (162) were men, and the mean age was 36.5±12years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 ± 17.1months. The mean duration of E/C/F/TAF use was 16 ± 4months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 ± 223 cells/µL and 740 ± 298 cells/µL, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211mg/dL (p < 0.01), LDL-cholesterol 108 and 143mg/dL (p < 0.01), HDL-cholesterol 41 and 47mg/dL (p < 0.01) and triglycerides 136 and 172mg/dL, respectively (p < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient's decision: 1). Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment. E/C/F/TAF use was associated with an increase in LDL-cholesterol and triglyceride levels along with an increase in HDL-cholesterol levels.

Hepatic Scavenger Receptor Class B Type 1 Knockdown Reduces Atherosclerosis and Enhances the Antiatherosclerotic Effect of Brown Fat Activation in APOE*3-Leiden.CETP Mice.

[Figure: see text].

Beneficial Effect of Taraxacum coreanum Nakai via the Activation of LKB1-AMPK Signaling Pathway on Obesity.

Objective Liver kinase B (LKB) 1 and AMP-activated protein kinase (AMPK) are master regulators and sensors for energy homeostasis. AMPK is mainly activated via phosphorylation of LKB1 under energy stress. Here, we highlighted the antiobesity effect and underlying mechanism of Taraxacum coreanum Nakai (TCN) in connection with LKB1-AMPK signaling pathway. Methods Male C57BL/6 mice were fed on a high-fat diet (60% kcal fat; HFD) to induce obesity. Simultaneously, they received 100 or 200 mg/kg TCN orally for 5 weeks. We measured the body weight gain and liver weight along with liver histology. Moreover, the changes of factors related to lipid metabolism and β-oxidation were analyzed in the liver, together with blood parameters. Results The body weights were decreased in mice of the TCN200 group more than those of the HFD control group. Moreover, TCN supplementation lowered serum triglyceride (TG) and total cholesterol (TC) levels, whereas TCN increased HDL-cholesterol level. Liver pathological damage induced by HFD was alleviated with TCN treatment and accompanied with significant reduction in serum AST and ALT activities. In addition, TCN significantly increased the expression of p-AMPK compared with the HFD control group via the activation of LKB1/AMPK signaling pathway. Lipid synthesis gene like ACC was downregulated and factors related to β-oxidation such as carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP-2) were upregulated through peroxisome proliferator-activated receptor (PPAR) α activation. Conclusion Taken together, these data suggest that TCN treatment regulates lipid metabolism via LKB1-AMPK signaling pathway and promotes β-oxidation by PPARα; hence, TCN may have potential remedy in the prevention and treatment of obesity.

The minor C-allele of the rs2014355 variant in ACADS gene is associated with exercise-induced increase in HDL cholesterol levels in Taiwanese adults.

We investigated the association between high-density lipoprotein cholesterol (HDL-C) and rs2014355 variant in the gene, short-chain acyl-coenzyme A dehydrogenase (ACADS) based on exercise habits.Data collected between 2008 and 2015 for individuals aged 30 to 70 years were available in the Taiwan Biobank (TWB) database. Backward stepwise linear regression was used to evaluate the associations of rs2014355 and exercise with HDL-C levels.We analyzed data of 5515 physically active and 4169 inactive biobank participants. The HDL-C concentrations were higher in the exercise compared to no exercise group (beta value, β = 1.79856; P < .0001). We observed that the test for interaction was significant for the ACADS rs2014355 variant and exercise (P for interaction =.0412). Multivariate analyses showed significant association between TC+CC genotype and HDL-C in the exercise (β = 1.09785; P value = .0146) compared to the no-exercise group (β = −0.03754, P = .9154).In summary, the association between HDL-C and exercise differed significantly with respect to ACADS rs2014355 genotypes. Compared to the TT genotype, the TC+CC genotype together with exercise was associated with higher levels of HDL-C.