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Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100’s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants. [ABSTRACT FROM AUTHOR]

The ability of the Torpedo nicotinic acetylcholine receptor (nAChR) to undergo agonist-induced conformational transitions requires the presence of cholesterol and/or anionic lipids. Here we use recently solved structures along with multiscale molecular dynamics simulations to examine lipid binding to the nAChR in bilayers that have defined effects on nAChR function. We examine how phosphatidic acid and cholesterol, lipids that support conformational transitions, individually compete for binding with phosphatidylcholine, a lipid that does not. We also examine how the two lipids work synergistically to stabilize an agonist-responsive nAChR. We identify rapidly exchanging lipid binding sites, including both phospholipid sites with a high affinity for phosphatidic acid and promiscuous cholesterol binding sites in the grooves between adjacent transmembrane α-helices. A high affinity cholesterol site is confirmed in the inner leaflet framed by a key tryptophan residue on the MX α-helix. Our data provide insight into the dynamic nature of lipid-nAChR interactions and set the stage for a detailed understanding of the mechanisms by which lipids facilitate nAChR function at the neuromuscular junction. Multiscale molecular dynamics simulations reveal rapidly exchanging lipid binding sites on the nicotinic acetylcholine receptor, including sites with high affinity for phosphatidic acid and promiscuous cholesterol sites in inter-α-helix grooves. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of timing of statin administration on lipid-lowering efficacy. Methods: Computer searches of Pubmed, Embase, Cochrane Library, and Web of Science databases from 1986 to 2023. The impact of administration time on the lipid-lowering efficacy of statin drugs was investigated. Following a series of screenings, a funnel plot was constructed to assess its symmetry, and Egger and Beggar tests were conducted using StataMP-64 to evaluate publication bias. Meta-analysis was performed using RevMan 5.3 to combine MD values. Results: Fifteen papers (1352 participants) met and included the criteria. The results of the meta-analysis showed that the effect of morning and evening administration time on plasma triglycerides (TG) (P > 0.05) and plasma high-density lipoprotein cholesterol (HDL-C) (P > 0.05) was not statistically significant. There were significant reductions in total cholesterol (TC) (MD: 0.15 mmol/L, 95% CI: 0.06–0.23, P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (MD: 0.10 mmol/L, 95% CI: − 0.00–0.20, P < 0.01) in the night group. According to the analysis results of the half-life of statins, only short half-life statins showed that nocturnal administration reduced LDL-C (MD: 0.21 mmol/L, 95% CI: 0.09–0.33, P < 0.01) and TC (MD: 0.32 mmol/L, 95% CI: 0.18–0.46, P < 0.01) levels and was better than morning administration. Long half-life statins did not show significant differences. In addition, the administration time of short half-life statins also showed that night administration tended to reduce TG (MD: 0.16 mmol/L, 95% CI: 0.02–0.30, P < 0.05) levels. In subgroup analysis according to clinical factors in patients aged < 55 years, there was no significant difference in the timing of administration between the two groups; the efficacy of statins in lowering lipids in patients aged ≥ 55 years was significantly different in the TC group (P < 0.01) and LDL-C group (P < 0.01). The administration time of the TC group (P < 0.05) and LDL-C group (P < 0.05) in the Americas, Europe, and Asian groups was significantly different for statins. In addition, the American group also showed that the administration time of the two groups was significantly different from the TG group (P < 0.05). Conclusion: The efficacy of administering short half-life statin drugs at night in reducing plasma levels of TC, LDL-C, and TG surpasses that of morning administration. However, this study did not determine the impact of timing of statin administration in patients taking long half-life statins on the efficacy of the medication. Therefore, it is recommended to consider patient adherence when. The study was registered on PROSPERO (International Prospective Register of Systematic Reviews) as CRD42022372105 (available at https://www.crd.york.ac.uk/prospero/). [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematological malignancy worldwide, characterized by abnormal proliferation of malignant plasma cells within a tumor-permissive bone marrow microenvironment. Metabolic dysfunctions are emerging as key determinants in the pathobiology of MM. In this review, we highlight the metabolic features of MM, showing how alterations in various lipid pathways, mainly involving fatty acids, cholesterol and sphingolipids, affect the growth, survival and drug responsiveness of MM cells, as well as their cross-talk with other cellular components of the tumor microenvironment. These findings will provide a new path to understanding the mechanisms underlying how lipid vulnerabilities may arise and affect the phenotype of malignant plasma cells, highlighting novel druggable pathways with a significant impact on the management of MM. [ABSTRACT FROM AUTHOR]

Background: Some physiological responses such as circulating glucose as well as muscle performance show a circadian rhythmicity. In the present study we aimed to quantitatively synthesize the data comparing the metabolic adaptations induced by morning and afternoon training. Methods: PubMed, SCOPUS, and Web of Science databases were systematically searched for studies comparing the metabolic adaptations (> 2 weeks) between morning and afternoon training. A meta-analysis was performed using random-effects models with DerSimonian–Laird methods for fasting blood glucose, hemoglobin A1c (HbAc1), homeostatic model assessment (HOMA), insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Results: We identified 9 studies with 11 different populations (n = 450 participants). We found that afternoon exercise was more effective at reducing circulating triglycerides [standardized mean difference (SMD) − 0.32; 95% confidence interval (CI) − 0.616 to − 0.025] than morning training. Moreover, afternoon tended to decrease fasting blood glucose (SMD − 0.24; 95% CI − 0.478 to 0.004) to a greater extent than morning training. Conclusion: Metabolic adaptations to exercise may be dependent on the time of day. Morning training does not show superior effects to afternoon exercise in any of the analyzed outcomes. However, afternoon training is more effective at reducing circulating triglyceride levels and perhaps at reducing fasting blood glucose than morning training. The study was preregistered at PROSPERO (CRD42021287860). [ABSTRACT FROM AUTHOR]

The cell membrane undergoes various changes to modify its composition and mechanical properties to control the functioning of cellular mechanisms, in which cholesterol is highly involved. We have investigated the formation of cholesterol-rich nano-domains in pure 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) solid-supported lipid bilayer (SLB) at room temperature. The mechanical properties of the lipid bilayer in the presence of 0 to 40 mol% of cholesterol have been explored by using Peak-Force Quantitative Nano-Mechanical Atomic Force Microscopy. Cholesterol-rich domains with different mechanical strengths are distinctly observed at 5% cholesterol in SLB of DOPC-cholesterol. The cholesterol-rich domains with increased height are observed up to 25% cholesterol insertion within the bilayer. Further increase of cholesterol concentration leads to shrinkage of bilayer height and moderate rise of rigidity modulus. We believe that the reduction of bilayer height is due to the decoupling of the two leaflets within the membrane at high cholesterol concentration. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. Methods: In a randomized, placebo-controlled trial, 34 women, aged 30–60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. Results: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. Conclusion: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. Clinical trial registration: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to assess the impact of the daily consumption of bread enriched with hydroxytyrosol on HbA1c and blood lipid levels, inflammatory markers and weight loss. Methods: Sixty adults with overweight/obesity and type 2 diabetes mellitus (29 male, 31 female) participated in a 12-week dietary intervention based on the Mediterranean diet and consumed daily 60 g of conventional whole wheat bread (WWB) or whole wheat bread enriched with hydroxytyrosol (HTB). Anthropometric characteristics were measured and venous blood samples were collected at baseline and at the end of the intervention. Results: Both groups experienced significant weight loss, body fat and waist circumference decrease (p < 0.001). Nonetheless, a greater body fat mass decrease was observed in the HTB group compared to the WWB group (14.4 ± 1.6 vs 10.2 ± 1.1%, p = 0.038). Significant reductions were also reported in fasting glucose, HbA1c and blood pressure in both groups (p < 0.05). Regarding glucose and HbA1c, greater decreases were observed in the intervention group (101.4 ± 19.9 vs. 123.2 ± 43.4 mg/dL, p = 0.015 and 6.0 ± 0.6 vs. 6.4 ± 0.9%, p = 0.093, respectively). At HTB group, significant reductions in blood lipid, insulin, TNF-αand adiponectin levels (p < 0.05) and a marginally significant reduction in leptin levels (p = 0.081) were also reported. Conclusion: Enrichment of bread with HT resulted in significant body fat mass reduction and positive effects on fasting glucose, insulin and HbA1c levels. It also contributed to reductions in inflammatory markers and blood lipid levels. Incorporation of HT in staple foods, like bread, may improve their nutritional profile and, in terms of a balanced diet, may contribute to the management of chronic diseases. Trial registration: The study was prospectively registered in clinicaltrials.gov (24th May 2021). ClinicalTrials.gov Identifier: NCT04899791. [ABSTRACT FROM AUTHOR]

Boron-containing conjugates of cholesterol were synthesized by the copper(i)-catalyzed 1,3-dipolar [3+2] cycloaddition reactions of cobalt and iron bis(dicarbollide) azide derivatives with alkynyl cholesterol. The antiproliferative activity (IC50) of the conjugates was evaluated against a series of human cell lines by the MTT assay. All conjugates were shown to be nontoxic (IC50 >200 µmol L−1) and to be applicable for the preparation of boron-containing liposomes as potential drugs for boron-neutron capture therapy (BNCT) of cancer. [ABSTRACT FROM AUTHOR]

Aim: To determine the association of fasting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) with dyslipidemia in newly diagnosed diabetes (NDD). Method: This collaborative prospective interventional clinical study was carried out by the Biochemistry Department, at the University of Karachi-Pakistan, Baqai Institute of Diabetology and Endocrinology, Karachi-Pakistan and Kansai Electric Power Medical Research Institute, Osaka, Japan. The study duration was from March 2019 to May 2020. Participants were identified on the basis of oral glucose tolerance test (OGTT) results. Of 34 participants, 17 were NDD and 17 were healthy. Demographics and anthropometric details were noted on a predesigned questionnaire. Blood samples were collected at fasting state for plasma glucose, lipid profile, HbA1c, and hormones (GIP and GLP-1). Results: The healthy participants included nine males and eight females, and the NDD participants included ten males and seven females. Mean age was 50.78±2.44 years and BMI was 28.41±0.76 kg/m2. Among healthy participants, both GIP and GLP-1 showed non-significant weak correlation for biochemical parameters. In NDD participants, GIP showed significantly negative moderate correlation with age and non-HDL and positive moderate correlation with LDL only. However, GLP-1 showed significantly positive moderate correlation with total cholesterol (r = 0.564, p = 0.018), LDL (r = 0.498, p = 0.042), HDL (r = 0.50, p = 0.041) and non-HDL (r = 0.503, p = 0.047) in NDD participants. Conclusion: The effect of GIP and GLP-1 measures on dyslipidemia were substantially different among NDD participants in our population. In the NDD group, GLP-1 is significantly moderately associated with dyslipidemia compared to GIP. [ABSTRACT FROM AUTHOR]

Summary: It has been hypothesized that lipid profiles are associated with bone mineral density (BMD), but previous results have been controversial. In this study, serum triglycerides showed a significant inverse association with BMD, and the relationship is thought to correlate with vitamin D status among older adults. Introduction: The purpose of this study was to investigate the relationship between lipid profiles and bone mineral density (BMD) in older adults using data from the Korean National Health and Nutrition Examination Survey (KNHANES). Methods: We enrolled men older than 50 years and postmenopausal women who participated in the KNHANES 2008–2011. Subjects with liver cirrhosis, thyroid disease, or renal dysfunction and those receiving treatment for hyperlipidemia or osteoporosis were excluded. Results: A total of 4323 subjects (2286 men and 2037 women) was analyzed. The prevalence of osteoporosis was 8.7% in men older than 50 years and 38.4% in postmenopausal women. Osteopenia and osteoporosis groups were generally older and tended to have a lower body mass index compared to the normal group (p for trend < 0.001). The correlation between each lipid profile and BMD was analyzed in the linear model adjusted for age and body mass index. Total cholesterol and high-density lipoprotein cholesterol showed a negative correlation with BMD in the total population, but there was no significant correlation when analyzed separately for men and women. Triglycerides had a negative association with whole-body BMD in both men and women (p < 0.05). The adjusted odds ratio of logarithmic triglyceride level for osteoporosis was 2.50 (95% confidence interval 1.13–5.51) in women older than 65 years. Conclusion: Serum triglycerides showed a significant inverse association with BMD, and the relationship is thought to correlate with vitamin D status among older adults. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the association between coffee consumption and serum lipid profile in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This is a cross-sectional study on baseline data from participants of the cohort ELSA-Brasil. Only participants of São Paulo Research Center who underwent a nuclear magnetic resonance (NMR) spectroscopy examination of lipid profile were included (N = 4736). Coffee intake was categorized into four categories (cups/day, in reference cup size of 50 mL, which is the household measure adopted in Brazil): never/almost never, ≤ 1, 1–3, and > 3. Serum lipid profile [i.e., Total Cholesterol (TC), Total Triglycerides (TG), Very Low-Density Lipoprotein-cholesterol (VLDL-c), Low-Density Lipoprotein-cholesterol (LDL-c), High-Density Lipoprotein-cholesterol (HDL-c), Triglyceride-rich Lipoprotein Particles (TRLP) and subfractions particles] was analyzed. To estimate the effect of coffee consumption on serum lipid profile, multivariate Generalized Linear Models were performed. Results: Compared to participants who never or almost never drink coffee, individuals who consumed more than 3 cups/day showed an increase in concentrations of TC (β: 4.13; 95% CI 0.81, 7.45), TG (β: 9.53; 95% CI 1.65, 17.42), VLDL-c (β: 1.90; 95% CI 0.38, 3.42), TRLP (β: 8.42; 95% CI 1.24, 15.60), and Very Small-TRLP and Medium-TRLP subfractions (β: 7.36; 95% CI 0.21, 14.51; β: 2.53; 95% CI 0.89, 4.16, respectively), but not with HDL-c and LDL-c. Among individuals with low (≤ 1 cup/day) and moderate (1–3 cups/day) coffee consumption, no significant associations with lipids was observed. Conclusion: High coffee consumption (more than 3 cups per day) was associated with an increase in serum lipids, namely TC, TG, VLDL-c, and TRL particles, highlighting the importance of a moderate consumption of this beverage. [ABSTRACT FROM AUTHOR]

Background: No previous systematic review has examined the physical health benefits of playing golf or caddying. Objective: To establish the influence of golf participation and physical health in golfers and caddies. More specifically, the review intended to explore the domains of cardiovascular, metabolic and musculoskeletal health, in addition to body composition. Design: Systematic review. Data Sources: Electronic literature searches were conducted using PubMed, SPORTDiscus and CINAHL databases in July 2021. Eligibility Criteria: Experimental (randomised controlled trials, quasi-experiment, pre-post) and non-experimental (case–control, cross-sectional, cohort) articles relating to health and golf, written in English and published in peer-reviewed journals. Results: Of the 572 articles initially identified, 109 full-text articles were assessed for eligibility with 23 meeting the inclusion criteria. Sixteen articles were rated 'good 'and seven 'fair'. The influence of golf on physical health was mixed, although various articles displayed improvements in balance, systolic blood pressure (SBP) and diastolic blood pressure (DBP), high density lipoprotein-cholesterol (HDL-C) and the ratio of HDL to total cholesterol within golfers. Caddies observed improvements in bone mineral density (BMD), stiffness index and strength. Most of the findings indicate that playing golf or caddying does not influence body mass index (BMI); however, playing golf can positively change other body composition markers such as lean and fat mass. Conclusion: This review demonstrated that golf participation may be an effective method for improving musculoskeletal and cardiovascular health, although mixed findings were observed. Moreover, limited longitudinal evidence suggests that playing golf can positively impact metabolic health and the influence on body composition may be parameter dependent. Additionally, the initial evidence suggests that caddying may improve musculoskeletal health. However, the studies included were limited by their methodological inconsistencies such as: study design, participant demographics and intervention prescription. PROSPERO Registration: CRD42021267664. [ABSTRACT FROM AUTHOR]

Background: Ash-Kardeh is one of the few fermented foods without a dairy base in Iran, which is traditionally prepared from cereals and plants in the presence of microorganisms (mainly lactic acid bacteria). Purpose: This study aimed to assess the effects of Ash-Kardeh consumption on blood glucose, lipid profile, and blood pressure in type 2 diabetic patients. Methods: Forty-six patients with type 2 diabetes were studied in this randomized controlled clinical trial. Subjects were randomly allocated into intervention (n = 23) and control (n = 23) groups. Individuals of both groups received the usual treatment of diabetic patients, while those in the intervention group, in addition to the usual treatment, received 250 g of Ash-Kardeh daily for 6 weeks. Fasting blood glucose, blood pressure, and lipid profiles were measured before and after the intervention. Results: Compared to the control group, Ash-Kardeh consumption led to a significant decrease in fasting blood glucose (P = 0.003), total cholesterol (P = 0.025), triglyceride (P = 0.003), systolic (P < 0.001), and diastolic blood pressure (P = 0.014) in the intervention group. Also, a significant increase in the concentrations of high-density lipoprotein cholesterol (P = 0.048) was observed after Ash-Kardeh consumption. Conclusion: It seems that Ash-Kardeh consumption could improve high blood glucose, lipid profile, and hypertension in type 2 diabetic patients but does not affect low-density lipoprotein cholesterol concentrations. This study was registered on 2019-09-15 in the Iranian Registry of Clinical Trials (www.irct.ir) with the code number IRCT20170202032367N3. [ABSTRACT FROM AUTHOR]

Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

Purpose: The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16 weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. Methods: This study was a randomized controlled trial. Three-hundred participants, aged 30–65 years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. Results: A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. Conclusion: The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. Registration number of Clinical Trial: Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17). [ABSTRACT FROM AUTHOR]

Introduction: Different strategies were proposed to stratify cardiovascular risk and assess the appropriate use of statins in patients with chronic kidney disease (CKD). Aim: (1) To apply two strategies on the management of lipids in patients with CKD, analyzing what proportion of patients received lipid-lowering treatment and how many patients without statin therapy would be candidates for receiving them; (2) to identify how many patients achieve the lipid goals. Methods: A cross-sectional study was performed. Patients aged between 18 to 70 years and CKD with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 (without hemodialysis) were included. The indications for statin therapy according to 2019 ESC/EAS and 2013 KDIGO guidelines were analyzed as well as the achievement of LDL-C goals. Results: A total of 300 patients were included. According to ESC/EAS guidelines, 62.3 and 37.7% of the population was classified at high or very high cardiovascular risk. In total, 52% of patients received statins. Applying the 2013 KDIGO and the 2019 ESC/EAS guidelines, 92.4 and 95.8% of the population without lipid-lowering treatment were eligible for statin therapy, respectively. Globally, only 9.1 and 10.6% of the patients with high or very high risk achieved the suggested lipid goals. Conclusion: A large proportion of patients with CKD showed considerable cardiovascular risk and were eligible for statin therapy according to the two strategies evaluated. However, observed statin use was deficient and current lipid goals were not achieved in most cases. [ABSTRACT FROM AUTHOR]

Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84–4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12. [ABSTRACT FROM AUTHOR]

Background: This cross-sectional research was undertaken to determine the serum levels of asprosin, a novel white adipose tissue-derived glucogenic adipokine, in epileptic patients on valproic acid treatment. Methods: Sixty-six patients diagnosed with idiopathic tonic–clonic generalized epilepsy were divided into three groups: those treated with valproic acid (n = 22), those treated with lamotrigine (n = 22), and twenty-two newly diagnosed or untreated patients. A control group was twenty-two, healthy volunteers with a similar distribution of gender and age. Body mass index (BMI) and fasting serum levels of asprosin, glucose, glycohemoglobin (HbA1c), insulin, and lipid profile were measured for both patients and control groups. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated for the investigated groups. Results: The mean BMI values and fasting serum levels of glucose, HbA1c, insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride were much higher in subjects treated with valproic acid than those in the other study groups. Furthermore, a higher number of participants in the valproic acid group fulfilled the insulin resistance criterion (defined as HOMA-IR > 2.5) compared with those in other study groups. The mean fasting serum asprosin concentration was also significantly higher in the valproic acid group than in other study groups. This was while the values of the study parameters were comparable in the healthy, un-treated, and lamotrigine groups. Conclusions: Our finding suggested that elevated asprosin level might be one of the pathological mechanisms involved in the development of obesity, insulin resistance, and metabolic disturbances related to valproic acid treatment. [ABSTRACT FROM AUTHOR]

Cardiovascular risk is common among resettled refugees from Southeast Asia, but the association with refugee status is unclear. This study investigated the lipid levels of Burmese refugees as compared to the general population of Burma. This observational study included adult refugees from Burma undergoing domestic medical examination at a clinic in Minnesota (n = 127). The cholesterol levels of the refugee cohort were compared to a survey of Burmese residents sampled by the World Health Organization (WHO). The primary variable of interest, mean LDL, was 118.9 mg/dL in the refugee cohort. Adjusting for sex and age-group, this was 18.5 mg/dL higher than the WHO cohort (95% CI 10.0–27.1 mg/dL, p < 0.001). This study confirmed previous studies showing elevated lipid levels among Asian refugees. This work added to prior studies by including a refugee cohort that was newly-resettled and comparing it to the general population. [ABSTRACT FROM AUTHOR]

Introduction: Lifestyle changes present a fundamental role in cardiovascular prevention. Nutraceuticals also supplementing diet could help in controlling the cardiometabolic risk. Aim: (1) to evaluate acute effects of a combination of nutraceuticals (cNUT) on vascular function, BP, metabolism in dyslipidaemic patients before and after smoking; (2) to evaluate 12 weeks effects of the cNUT on lipid profile, insulin resistance and vascular function in patients with hypercholesterolemia not on statins. Methods: After 14 d run-in period, 33 patients assumed a cNUT [patented formula containing: berberine (531.25 mg), red yeast rice powder (220 mg, 3.3 mg monacolin K) and leaf extract of Morus alba (200 mg) (LopiGLIK®, Akademy Pharma)]. To evaluate acute effects, cNUT or cNUT + smoking (in smoking subjects) on the morning of the first day of the study and then 26 patients prolonged 12 weeks effects. Results: In non smokers, cNUT improved FMD (p = 0.041 for treatment). In smokers, FMD decreased after smoking, this was counteracted by intake of cNUT. In smokers, DBP increased after smoking a cigarette (p = 0.042 for treatment), counteracted by the cNUT intake. In non smokers, thermogenesis was increased after cNUT administration (p < 0.0001 for treatment). After 12 weeks of cNUT, FMD significantly increased (p < 0.05) and SBP (p = 0.04), total cholesterol and LDL cholesterol (p = 0.03) decreased. Conclusions: Our study suggests benefits of cNUT on cardiovascular prevention in hypercolesterolemic patients, non statin treated, that goes beyond the cholesterol and insulin resistance reduction protecting the subject from negative effects induced by smoking too. [ABSTRACT FROM AUTHOR]

Lipids and lipoproteins are a diverse group of substances and their interactions with the blood-brain barrier (BBB) is similarly diverse. Some lipoproteins such as high density lipoprotein (HDL), apolipoprotein (apo) A-I, apoJ, some free fatty acids, and triglycerides cross the BBB whereas others such as apoE do not. Some forms of cholesterol can cross the BBB and others do not. Lipids can have effects on BBB preservation and function: HDL may protect the BBB during multiple sclerosis, cholesterol can disrupt the BBB, and triglycerides inhibit the transport of leptin across the BBB and the activation of the hypothalamic leptin receptor. ApoE is associated with many effects on the BBB, with the specific isoform apoE4 having detrimental effects. In summary, the diverse ways in which lipids, lipoproteins, and apolipoproteins interact with the BBB is important in both health and disease. [ABSTRACT FROM AUTHOR]

Purpose: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels. Methods: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0–8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks. Results: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05). Conclusions: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels. Trial registered: The trial has been registered at ClinicalTrials.gov (NCT02990637). [ABSTRACT FROM AUTHOR]

Bisphosphonates are the first-choice treatment of osteoporosis and Paget's disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget's disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations. [ABSTRACT FROM AUTHOR]

The naked mole-rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years, but the mechanism(s) underlying increased longevity in NMRs remains unclear. In the present study, we report unique mechanisms underlying cholesterol metabolism in NMR cells, which may be responsible for their anti-senescent properties. NMR fibroblasts expressed β-catenin abundantly; this high expression was linked to increased accumulation of cholesterol-enriched lipid droplets. Ablation of β-catenin or inhibition of cholesterol synthesis abolished lipid droplet formation and induced senescence-like phenotypes accompanied by increased oxidative stress. β-catenin ablation downregulated apolipoprotein F and the LXR/RXR pathway, which are involved in cholesterol transport and biogenesis. Apolipoprotein F ablation also suppressed lipid droplet accumulation and promoted cellular senescence, indicating that apolipoprotein F mediates β-catenin signaling in NMR cells. Thus, we suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in NMRs. Woei-Yaw Chee et al. explore the molecular mechanisms of β-catenin involvement in cholesterol metabolism suppressing cellular senescence in naked mole-rat cells. The results of this study suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in naked mole rats. [ABSTRACT FROM AUTHOR]

1-(3-Butyn-1-ylthio)-1,2-dicarba-closo-dodecaborane was synthesized by the alkylation of 1-mercapto-1,2-dicarba-closo-dodecaborane trimethylammonium salt with butyn-3-yl methanesulfonate. The deboronation reaction of this compound gave the corresponding derivative based on nido-carborane, namely, 7-(3-butyn-1-ylthio)-7,8-dicarba-undecaborate anion. 1,4-Disubstituted 1,2,3-triazoles based on closo- and nido-carboranes were synthesized by the CuI-catalyzed 1,3-dipolar [3+2] cycloaddition reaction of the acetylene derivatives of closo- and nido-carboranes with azidocholesterol. [ABSTRACT FROM AUTHOR]

Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle–Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20–0.48 for TG; MD = -0.05, 95% CI: -0.08–-0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16–0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10–-0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07–0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14–0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08–0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49–-0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32–-0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28–0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14–0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20–1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02–1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75–0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00–1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources. [ABSTRACT FROM AUTHOR]

Aim and objective: The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid. Materials and methods: Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper. Conclusion: Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Pore-forming toxins are proteins expressed by bacteria to primarily cause infections in the host cell. Cholesterol-dependent cytolysins (CDCs) are a class of proteins whose pore-forming ability requires the presence of cholesterol in the membrane. Upon binding to the target cell, cholesterol-recognizing residues in the membrane binding D4 subdomain assist in stabilizing both the pre-pore and pore states which occur during protein oligomerization on the cell membrane. Super resolution-stimulated emission depletion (STED) microscopy experiments (Sarangi et al. in Langmuir, 32:9649–9657, 2016) on supported lipid bilayers have shown that listeriolysin (LLO), a CDC expressed by Listeria monocytogenes, a food-borne pathogen, induces both spatial and dynamic heterogeneity in bilayer membranes. Here, we use all-atom molecular dynamics simulations to explore molecular details of the induced membrane reorganization by considering two distinct states of the oligomerized LLO protein in a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC): cholesterol membrane. In the membrane bound (MB) state, four D4 subunits are placed at the bilayer interface in a pre-pore configuration and the membrane-inserted (MI) state consists of a tetrameric arc-like pore configuration. By analyzing lipid-order parameters, mobilities, and diffusion coefficients, we examine the induced spatial heterogeneity that occurs in both the MB and MI states. This heterogeneity is primarily driven by the local density enhancement of cholesterol in the vicinity of the MB, D4 subunits leading to distinct differences in lipid and cholesterol mobility across the two leaflets as well as enhanced lipid mobilities in regions where cholesterol is depleted. The leaflet-induced heterogeneity is greater for the MB state when compared with the MI state and the dynamic variations are more pronounced in the extracellular leaflet when compared with the cytosolic leaflet. Our study provides molecular-level insights into the inhomogeneity and perturbation induced in bilayer membranes upon LLO binding and pore formation and is expected to represent trends across PFTs in the broad CDC subclass of proteins. [ABSTRACT FROM AUTHOR]

Bird feather lipids are usually attributed to the oily secretion product of the uropygial (preen) gland. We have observed, however, that feathers exhibit a strong reaction with osmium tetroxide (OsO4), even after treatment with detergents. This leads us to postulate the existence of endogenous feather lipids distinct from preen gland lipids. In order to substantiate our hypothesis, we investigated down feathers from a 1-day-old chicken as their uropgygial gland is not functionally active. The results confirmed the osmiophilic reaction, which was concentrated in the center of barbs and strongly reduced after lipid extraction. In these lipid extracts, we identified using thin layer chromatography, cholesterol, various ceramides, glycolipids, phospholipids, and fatty acids, which closely resembled the lipid composition of the water barrier in the chicken-cornified epidermal envelope. This composition is clearly distinct from chicken uropygeal gland secretion (UGS) known to consist of fatty alcohols as part of aliphatic monoester waxes and of free, predominantly saturated, fatty acids. A filter assay showed a strong reactivity between OsO4 and the fatty acids C18:1 and C18:2 and with feather lipid extracts, but not with UGS. These observations were confirmed by gas chromatography detecting unsaturated fatty acids including C18:1 and C18:2 as well as cholesterol exclusively in chicken feathers. Our results indicate that (1) endogenous lipids are detectable in chicken feathers and distinct from UGS and (2) in analogy to the morphogenesis of the cornified envelope of chicken feather lipids that may have derived from cellular feather-precursors, apparently enduring the specific cell death during developmental feather cornification. [ABSTRACT FROM AUTHOR]

Background and aims: Existing evidence on the possible effects of synbiotics on lipid profile is inconclusive. The aim of the present systematic review was to clarify the effects of synbiotics consumption on lipid profile. Methods: A systematic literature search of online databases PubMed, Scopus, ISI Web of science, Cochrane's library and Google Scholar was conducted up to January 2019. Randomized controlled trials (RCTs) investigating the effects of synbiotics on lipid profile in adults were included. The overall effect was presented as weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis model. Results: A total of 23 RCTs with 1338 participants were included. Synbiotic consumption resulted in a significant decrease in plasma concentrations of total cholesterol (WMD = − 10.17 mg/dL; 95% CI − 15.74 to − 4.60; p < 0.001), triglyceride (WMD = − 14.30 mg/dL; 95% CI − 25.32 to − 3.28; p = 0.01), low-density lipoprotein cholesterol (WMD = − 8.32 mg/dL; 95% CI − 13.21 to − 3.43; p < 0.001), and an increase in plasma high-density lipoprotein cholesterol (WMD = 1.3 mg/dL; 95% CI 0.03 to 2.56; p = 0.04) levels compared to control (placebo supplements/control foods/conventional products). The effects are more pronounced when synbiotics supplements are consumed for > 8 weeks. Conclusion: Synbiotic supplements may be beneficial to improve lipid profile, especially when they are consumed for > 8 weeks. [ABSTRACT FROM AUTHOR]

Purpose: Mushrooms are reported to have a variety of health-promoting activities. However, little information is available on the effects of intake of polysaccharides from Pleurotus eryngii on obesity. In this study, we investigated the effects of P. eryngii polysaccharides on obesity and gut microbiota in mice fed a high-fat diet. Methods: Soluble polysaccharides were extracted from P. eryngii using hot water. C57BL/6J mice were fed a standard diet (ST), a high-fat diet (HF), or HF with 1% or 5% P. eryngii polysaccharide fraction (LP or HP) for 16 weeks. Adipose tissues were weighed and blood parameters were measured. Expression of genes involved in fatty acid and cholesterol metabolism was assessed by real-time quantitative PCR. The gut microbiota composition was analysed by 16S rRNA gene sequencing. Results: Body weight gain and mesenteric fat tissue were lower in the HP group than in the HF group. In the HP group, serum total cholesterol and LDL cholesterol levels decreased, and lipid and total bile acids in faeces increased. Mice in the HP group showed increased expression of the LDLR gene in the liver and GPR43 in fat. The relative abundance of Firmicutes was significantly higher in the HF and HP groups than in the ST group. The abundance of some short-chain fatty acid-producing gut bacteria was altered by P. eryngii polysaccharides. Conclusions: These results provide the first evidence that P. eryngii polysaccharides have anti-obesity and LDL cholesterol-lowering effects in obese mice through increased excretion of bile acids and lipids and altered microbiota. [ABSTRACT FROM AUTHOR]

Purpose: This study was to see the effects of a balanced Korean diet (BKD) on metabolic risk factors in overweight or obese Korean adults, comparing with those of a typical American diet (TAD) and a diet recommended by the 2010 Dietary Guidelines for Americans (2010DGA). Methods: The study was designed as a randomized crossover controlled trial, in which 61 overweight or obese volunteers were divided into six groups and each consumed the BKD, 2010DGA, and TAD in a random order for 4 weeks separated by 2-week washout intervals. Anthropometric indices, blood pressure, blood lipid content, fasting blood glucose, and blood insulin level were measured at the beginning and end of each diet period. Results: A total of 54 participants completed the trial. The BKD caused more significant reductions of body mass index (BMI) (p < 0.001), body fat percent (p < 0.001), blood total cholesterol (p < 0.001), and low-density lipoprotein (LDL) cholesterol (p = 0.007) compared with the 2010DGA or TAD (all p values for differences between diets < 0.05). All three diets significantly lowered blood triglyceride levels (p < 0.05). The BKD decreased high-density lipoprotein (HDL) cholesterol (p = 0.001) and increased fasting blood glucose (p = 0.018), whereas TAD and 2010DGA increased HDL cholesterol and did not affect blood glucose levels. Furthermore, the BKD significantly decreased the proportion of individuals with elevated total cholesterol (p < 0.001) and LDL cholesterol (p < 0.01), whereas the 2010DGA significantly reduced the number of obese individuals (p < 0.05), and the TAD decreased the number of participants with elevated triglyceride levels (p < 0.05), but increased that of those with elevated LDL cholesterol (p < 0.05). Conclusions: The Korean diet based on dietary guidelines improved metabolic risk factors such as BMI, body fat percent, and blood lipid profiles in overweight or obese Korean adults. These results provide evidence to recommend the Korean diet for preventing various metabolic diseases. Clinical trial registration: The trial was registered at the Clinical Research Information Service (CRIS) in Korea, the primary registry of the World Health Organization (WHO) international clinical trial registry platform, under number KCT0002437. [ABSTRACT FROM AUTHOR]

Purpose: Consumption of the algae spirulina (Arthrospira platensis or maxima) and wakame (Undaria pinnatifida) has been shown to lower LDL cholesterol concentrations in animals and humans, possibly due to the inhibition of intestinal cholesterol absorption. This mechanism, however, has never been investigated in humans. Therefore, we examined in non-hypercholesterolemic men and women the effects of spirulina and wakame consumption on serum markers for intestinal cholesterol absorption. Methods: Thirty-five healthy men and women without hypercholesterolemia consumed in a random order daily 4.8 g spirulina, wakame or placebo for 17 days, separated by 14-day washouts. After 17 days, serum cholesterol-standardized campesterol, sitosterol and cholestanol, and lathosterol concentrations were measured as markers for intestinal cholesterol absorption and cholesterol synthesis, respectively. Concentrations of serum total cholesterol, LDL and HDL cholesterol, triacylglycerol, and plasma glucose, and blood pressure were measured as well. Results: Compared with placebo, spirulina or wakame did not affect serum cholesterol-standardized campesterol (CI − 0.23 to 0.10 μmol/mmol, P = 0.435 and CI − 0.14 to 0.19 μmol/mmol, P = 0.729, respectively), sitosterol (P = 0.314 and P = 0.112), cholestanol (P = 0.610 and P = 0.809), or lathosterol (P = 0.388 and P = 0.102) concentrations. In addition, serum lipid and plasma glucose concentrations, and blood pressure were not changed. Conclusions: Daily consumption of 4.8 g spirulina or wakame for 17 days did not affect plasma markers for intestinal cholesterol absorption or cholesterol synthesis in non-hypercholesterolemic men and women. Serum lipid and glucose concentrations, and blood pressure were also not altered. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear whether habitual intake of soy or isoflavones induces long-term changes in the concentrations of blood lipids and glycaemia. We examined the associations of soy food and isoflavone consumption with changes in blood lipids and HbA1c concentrations over 5 years among Japanese adults. Methods: This cohort study included 7252 subjects with no known history of major chronic disease at baseline. Soy intake was measured using a food frequency questionnaire; while the concentrations of serum lipids and HbA1c were measured using standard laboratory methods. We used multivariable linear mixed-effects models to examine the associations of changes in lipids and HbA1c concentrations with intakes of soy food and isoflavones. Results: Among the participants, mean age was 61 years, 67% were females and median intakes of soy and isoflavones were 95.3 g/day and 47.4 mg/day, respectively. Soy food and isoflavone intakes were not associated with 5-year changes in blood lipids or HbA1c concentrations. However, stratified analyses showed inverse associations between fermented soy intake and serum lipids among obese/overweight subjects. In particular, intake of 20 g/day of natto was associated with a reduction of 1.4 (95% CI 0.3, 2.5) mg/dL in TC, 1.5 (95% CI 0.4, 2.6) mg/dL in non-high-density lipoprotein cholesterol, 1.0 (95% CI − 0.0, 2.0) mg/dL in low-density lipoprotein cholesterol and 4.0 (95% CI 0.6, 7.5) mg/dL in triglycerides. Conclusions: Overall, habitual consumption of soy or isoflavones was not associated with changes in serum lipids or HbA1c concentrations. The negative associations between intake of natto and changes in serum lipids among overweight/obese subjects deserve further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the effects of leptin and leptin receptor polymorphisms on lipid changes during pregnancy. The aims of this study were to evaluate the associations between the single nucleotide polymorphisms (SNPs) of leptin and leptin receptor genes and the lipid concentrations during pregnancy; and to test whether dietary intake is a mediator in these associations. Methods: A prospective cohort of 154 pregnant women was followed up in Rio de Janeiro, Brazil during the following gestational periods: 5–13th, 20–26th and 30–36th weeks. HDL-C, total cholesterol (TC) and triglyceride (TG) were measured by the enzymatic colorimetric method, and LDL-C was calculated. DNA was extracted by the phenol–chloroform method, and leptin (G2548A, rs7799039) and leptin receptor SNPs (Q223R; rs1137101 and K109R; rs1137100) were genotyped using real-time PCR. Statistical analyses included linear mixed-effect models. Results: Women with the AA genotype of G2548A polymorphism reported a higher fat and total energy intake and had a higher increase in TG concentration during pregnancy than women with AG or GG genotype. The association between G2548A SNP and TG concentrations was not attenuated by adjusting for total lipid (g) and energy (kcal) intake. We did not observe significant associations between the Q223R and K109R SNPs and the lipid concentrations. Conclusions: Women homozygous for the A allele of the leptin SNP (G2548A) had a higher increase in TG concentrations per gestational week compared with women with the AG or GG genotype. This is an exploratory and hypothesis-generating study, and the results need confirmation in studies with larger sample sizes.' [ABSTRACT FROM AUTHOR]

Purpose: Maternal high-fat diet affects offspring and can induce metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies are being investigated as way to prevent or attenuate this condition. The objective of this study was to evaluate the effect of açaí supplementation in the maternal high-fat diet on dams and offspring lipid metabolism. Methods: Female Fisher rats were divided in four groups and fed a control diet (C), a high-fat diet (HF), an açaí supplemented diet (CA) and a high-fat diet supplemented with açaí (HFA) 2 weeks before mating, during gestation and lactation. The effects of açaí were evaluated in the male offspring after birth (P1) and weaning (P21). Results: HFA reduced relative liver weight, fat and cholesterol liver content in dams and improved liver steatosis as confirmed by histological analyses. HFA increased serum cholesterol and expression of Srebpf1 and Fasn genes. In offspring, HFA decreased relative liver weight, and serum cholesterol only in P21. An increase in the Sirt1, Srebpf1 and Fasn genes expression was observed in P21. Conclusions: These results suggest that açaí supplementation may attenuate NAFLD in dams and protect offspring from the detrimental effects of lipid excess from a maternal high-fat diet. [ABSTRACT FROM AUTHOR]

In this study, a lipid bilayer membrane model was used, in which the bilayer is tethered to a solid substrate with molecular tethers. The V-I characteristics of the lipid bilayers were found to be non-linear which suggests the presence of pores that are voltage-dependent. At high applied voltages, the conductance reached a limiting value, presumably indicating a limit on the maximum pore size. A decrease in the spacing between tethers (increasing tether density) caused a decrease in the membrane's conductance at high applied voltage, which is consistent with the maximum pore size being determined by the spacing between the tethers. The inclusion of 10 M% cholesterol within the membrane lipid caused a decrease in the membrane conductance. However, the inclusion of higher levels of cholesterol increased the membrane conductance. [ABSTRACT FROM AUTHOR]

Stratum corneum (SC), the outermost layer of the skin, contains large variety of lipids, endowing them with the amphiphilic properties, needed to fulfil their key role in skin's barrier function. The individual role of lipid types in the barrier function is difficult to understand due to the immense heterogeneity and complexity of the lipid's organization within the SC. The lipid organization is being explored using both computational (molecular dynamics simulations) and experimental (neutron diffraction) techniques. Even though atomistic simulations provide unprecedented atomic level details, the major limitation is time and length scale that can be achieved with decent computational facility. Alternatively, coarse-grain (CG) models are currently being used to capture physics at bigger time and length scale without losing essential underlined structural information. In this study, a CG model of α-hydroxy phytosphingosines (CER[AP]) is developed based on philosophy of MARTINI force field. At first, the model is validated with various atomistic simulations and available experimental data. Later on, the model's compatibility with other major skin lipids, cholesterol, and free fatty acid (palmitic acid) is checked by simulating a mixture of lipid multilayer in presence and absence of water. The developed model of CER[AP] is able to predict key structural properties within the acceptable error limits. The phenomena of ceramide conformation transformation, cholesterol flip-flop, and specificity of lipid arrangement within the multilayered systems is observed during the simulation. This signifies the importance of model in capturing higher order structural transformations. [ABSTRACT FROM AUTHOR]

The nucleophilic ring-opening reaction of tetrahydropyran derivative of the closo-dode-caborate dianion with sodium azide in the presence of tetrabutylammonium bromide led to the novel azido-derivatives of[B12H12]2−. A Cu-catalyzed 1,3-dipolar [3+2] cycloaddition reaction of the closo-dodecaborate dianion azido-derivatives with alkynyl-cholesterol led to 1,4-disubstituted 1,2,3-triazoles with the closo-dodecaborate fragment at position 1. The resulting conjugates are potentially suitable for the development of liposomal drugs to selectively deliver boron into a tumor cell for boron neutron capture therapy of cancer. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine if 15 weeks of resistance training (RT) can alter the levels of blood lipids, body iron status, and oxidative stress in postmenopausal women with vasomotor symptoms. Postmenopausal women enrolled in a randomised controlled trial were allocated to either a sedentary control group (n = 29) or a RT group (n = 26). Blood samples were taken at week-0 and week-15 for all participants. Blood lipids and iron status were measured via routine clinical analyses. Immunoassays were used to measure oxidative stress markers. The RT group, with good compliance, was associated with significant reductions in ferritin, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein cholesterol. Moreover, ferritin was positively correlated with atherogenic lipids while negatively correlated with high-density lipoprotein in RT women. This occurred without alterations in serum iron, transferrin, transferrin-saturation, C-reactive protein and oxidative stress markers. No differences were found in control women. This study suggests that RT in postmenopausal women both reduces levels of ferritin and counteracts atherogenic lipid profiles independent of an apparent oxidative mechanism. RT may be a beneficial intervention in postmenopausal women via an interaction between ferritin and lipids; however, further investigation in a larger cohort is essential. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to inspect the interactions between an anti-breast cancer, TAM, with model of lipid membranes composed of either zwitterionic DPPC LUVs or anionic DPPG LUVs and how they depend on ionic strength and cholesterol. Methods: The Kp of TAM into DPPC and DPPG LUVs were determined at three different NaCl concentrations by second derivative UV-Vis spectrophotometry. The effect of cholesterol incorporated into these LUVs on TAM's Kp was also assessed. The ATR-FTIR measurements were carried out to verify structural changes within the acyl chain and head group regions of the liposomes upon TAM partitioning. Results: Increasing salt concentration produced negligible impact on the partitioning of TAM into DPPC bilayer as its Kp remained unaffected whilst induced outstanding reduction of TAM's Kp into DPPG liposomes. Furthermore, TAM was found to disorder the lipids' acyl chains, which could result in an increase in the membrane fluidity, a necessary piece of information to refer to when prescribing TAM dosage for administration. Additionally, cholesterol showed astoundingly opposite contribution to the partitioning of TAM into the LUVs, as its Kp value reduced in DPPC/Chol bilayer yet increased in DPPG/Chol liposomes. Conclusion: Ionic strength and cholesterol play a noteworthy role in regulation of TAM partitioning into lipid membranes as they could obstruct or promote such action. [ABSTRACT FROM AUTHOR]

Background: Catecholamine excess in patients with pheochromocytomas or paragangliomas (PPGLs) can lead to hypertension, diabetes and hyperlipidemia. The aim was to investigate the prevalence of hyperlipidemia and the effect of surgical resection. Methods: One hundred and thirty-two patients with PPGLs underwent an operation at the National Institutes of Health from 2009 to 2016, of which 54 patients met the inclusion criteria. Clinical demographics, BMI, genetic mutations, tumor size, perioperative catecholamine levels and perioperative lipid panels were retrospectively reviewed. Spearman correlation between catecholamines and lipid levels was evaluated. Paired Wilcoxon and paired t test were used to analyze differences in pre- and postoperative lipid levels. Results: Preoperatively, 51 patients (94.4%) had elevated catecholamines, thirteen (24.1%) had elevated total cholesterol (TC) (>200 mg/dL), nine (16.6%) had elevated LDL (>130 mg/dL) and ten (18.5%) had elevated triglycerides (>150 mg/dL). Serum and urinary metanephrine levels were positively associated with TC (r = 0.2792, p = 0.0372 and r = 0.4146, p = 0.0031, respectively) and LDL levels (r = 0.2977, p = 0.0259 and r = 0.4434, p = 0.0014, respectively). Mean TC decreased from 176.4 to 166.3 mg/dL (p = 0.0064) and mean HDL decreased from 56.7 to 53.2 mg/dL (p = 0.0253) after PPGL resection (median 3.1 months (range 1.3–50.2) between lipid panels). Most patients with elevated TC (76.9%) had improvement with mean TC decreasing from 225 to 200.2 mg/dL (p = 0.0230). Of patients with elevated LDL, 66.7% had improvement with mean LDL decreasing from 149 to 131.1 mg/dL (p = 0.0313). Conclusions: The prevalence of hyperlipidemia in patients with PPGLs is 46%. Future prospective studies are needed to determine whether surgical resection improves TC and/or LDL levels. [ABSTRACT FROM AUTHOR]

Transmembrane electric potentials and membrane curvature have always provided pathways to mediate different cellular processes. We present results of molecular dynamics (MD) simulations of lipid monolayer composed of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol (CHOL) under a transverse electric field to monitor the effect of electric field on membrane containing ganglioside monosialo 1 (GM1). Four systems were studied with membrane monolayer in the presence and absence of GM1 with and without applying electric field along the normal of the monolayer. The applied transmembrane electric field was 0.4 mV/Å which corresponds to the action potential of animal cell. Our results indicate that the electric field induces a considerable lateral stress on the monolayer in the presence of GM1, which is evident from the lateral pressure profiles. It was found that due to the application of electric field major perturbation was caused to the system containing GM1, manifested by the bending of the monolayer. We believe this study provides correlation between electric field and spontaneous membrane bending, specially based on the membrane composition. The consequences of these MD simulations provide considerable insights to different biological phenomenon and lipid membrane models. [ABSTRACT FROM AUTHOR]

When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a "corona". This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP. [ABSTRACT FROM AUTHOR]

Background: The study aimed to establish reference intervals for serum lipids and apolipoproteins in pregnant women depending on trimester and parity, and to investigate the influence of various factors on lipid and apolipoprotein concentrations.Materials and Methods: A total of 748 pregnant women (n = 683 in the second trimester, n = 676 in the third trimester) were included in the study and reference intervals for total cholesterol (TC), HDL, LDL, triglycerides (TG), apoA1 and apoB were determined as empirical quantiles. The measurement of serum lipids was performed using a validated specific homozygous enzymatic color test. Hierarchical models were used to investigate hypothesized relations.Results: Except for apoA1, all serum lipids levels showed a significant change from the second to the third trimester. This increase was most pronounced for TGs. Especially in the third trimester, the concentrations of serum lipids exceeded the currently accepted reference values for non-pregnant women by a factor of 2.5. Reference intervals of serum lipids at the second and third trimesters in healthy pregnant women were as following: TC 4.45-8.99 and 4.83-9.71 mmol/l, HDL 1.33-3.06 and 1.16-3.13 mmol/l, LDL 2.14-6.11 and 2.35-6.98 mmol/l, TG 0.92-3.0 and 1.37-4.76 mmol/l as well as apoB 0.69-1.93 and 0.85-2.21 g/l. Parity and nutrient intake were not significantly associated with changes in lipid concentration. Prematurity was associated with a significant decrease in TC and TG levels.Conclusion: Detailed reference values for serum lipids and apolipoproteins in pregnancy are now available for a Caucasian cohort. Further, long-term studies are still needed to assess the effect of the extensive concentration changes of serum lipids in pregnancy and their atherogenic risk definitively. [ABSTRACT FROM AUTHOR]

Purpose: The comparative effects of different whole grains and brans on blood lipid are still not totally elucidated. We aimed to estimate and rank the effects of different whole grains and brans on the control of blood lipid. Methods: We performed a strategic literature search of PubMed, EMBASE and the Cochrane Library for relevant trials. Both pairwise meta-analyses and network meta-analyses were conducted to compare and rank the intervention strategies of whole grains and brans for the control of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). Results: Fifty-five eligible trials with a total of 3900 participants were included. Cumulative ranking analyses showed that oat bran was the most effective intervention strategy for TC and LDL-C improvements, with significant decreases of − 0.35 mmol/L (95% CI − 0.47, − 0.23 mmol/L) and − 0.32 mmol/L (95% CI − 0.44, − 0.19 mmol/L) in TC and LDL-C compared with control, respectively. In comparison with control, oat was associated with significant reductions in TC by − 0.26 mmol/L (95% CI − 0.36, − 0.15 mmol/L) and LDL-C by − 0.17 mmol/L (95% CI − 0.28, − 0.07 mmol/L), which was ranked as the second best treatment. Barley, brown rice, wheat and wheat bran were shown to be ineffective in improving blood lipid compared with control. Conclusions: This network meta-analysis suggests that oat bran and oat are ranked higher than any other treatments for the regulations of TC and LDL-C, indicating that increasing oat sources of whole grain may be recommended for lipid control. [ABSTRACT FROM AUTHOR]

Purpose: Fatalities due to heart and cerebrovascular diseases caused by uncontrolled hyperlipidaemia increase every year; on the other hand, lipid-lowering drugs are known to cause side effects. The gut microbiota has been thoroughly investigated by researchers and consumers, because they have unique functional properties and littler side effects. However, the effects of the gut microbiota remain controversial. We conducted a meta-analysis to assess the effects of products designed to modulate the gut microbiota on various hyperlipidaemias. Methods: We systematically searched PubMed, Embase, Cochrane Library (Central), and Web of Science for randomized controlled trials (published before June 2017, and those only in English) to compare treatment (products designed to modulate the gut microbiota) versus placebo. Our main endpoints were total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in serum. We assessed pooled data using a fixed effects model. Results: Of 1337 identified studies, 21 were eligible and included in our analysis (n = 1436 participants). The combined estimate of effect size for the impact of products designed to modulate the gut microbiota on serum TC (WMD − 11.07 mg/dL, 95% CI − 13.72 to − 8.43, p < 0.001), LDL-C (WMD − 10.96 mg/dL, 95% CI − 13.37 to − 8.56, p < 0.001), and HDL-C (WMD 0.72 mg/dL, 95% CI 0.06–1.38, p = 0.032) were statistically significant, while no significant effect was found on TG concentrations (WMD − 0.56 mg/dL, 95% CI − 5.59 to 4.47, p = 0.828). Subgroup analysis showed parallel trials, probiotics, and long-term intervention had better effects on lowering blood lipid levels. Conclusion: Products designed to modulate the gut microbiota results in changes of the plasma lipid concentrations and these changes may protect against cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is a key regulatory process that links hypercholesterolemia and immune mechanisms promoting atherosclerosis. Inflammatory biomarkers may be helpful to better define the atherosclerotic burden in patients with high cholesterol levels such as familial hypercholesterolemia (FH). Our aim was to evaluate the concentration of S100A12 protein in FH patients and its association with pulse wave velocity (PWV). Methods: We measured glucose and lipid profile, S100A12, sRAGE, esRAGE and PWV in 39 patients with a genetically confirmed diagnosis of FH and 39 hypercholesterolemic subjects without a clinical diagnosis of FH (Dutch score ≤ 3). All subjects were on statin treatment at the time of the enrollment. Results: No difference of glucose and lipid profile was found in the two groups. FH patients had higher S100A12 plasma levels than non-FH subjects (12.87 ± 4.82 vs. 8.57 ± 4.87 ng/mL, p < 0.01). No difference of hs-CRP, sRAGE and esRAGE was found between the two groups. Also, PWV was higher in FH patients than non-FH subjects (8.63 ± 0.92 vs. 6.68 ± 0.73 m/s, p < 0.05). Finally, S100A12 was independently correlated with age (p < 0.01), genetic mutation (p < 0.01) and PWV (p < 0.001). Conclusions: FH patients exhibited higher S100A12 levels than non-FH subjects. A novel vascular inflammation pathway, other than hs-CRP, might be useful to better characterize cardiovascular risk profile. [ABSTRACT FROM AUTHOR]

Purpose: Despite the lack of evidence, a growing number of people are using herbal medicine to attenuate the burden of diabetes. There is an urgent need to investigate the clinical potential of herbs. Preliminary observations suggest that American ginseng (Panax quinquefolius [AG]) may reduce postprandial glycemia. Thus, we aimed to evaluate the efficacy and safety of AG as an add-on therapy in individuals with type 2 diabetes (T2DM) controlled by conventional treatment. Methods: 24 individuals living with T2DM completed the study (F:M = 11:13; age = 64 ± 7 year; BMI = 27.8 ± 4.6 kg/m2; HbA1c = 7.1 ± 1.2%). Utilizing a double-blind, cross-over design, the participants were randomized to receive either 1 g/meal (3 g/day) of AG extract or placebo for 8 weeks while maintaining their original treatment. Following a ≥ 4-week washout period, the participants were crossed over to the opposite 8-week treatment arm. The primary objective was HbA1c, and secondary endpoints included fasting blood glucose and insulin, blood pressure, plasma lipids, serum nitrates/nitrites (NOx), and plasominogen-activating factor-1 (PAI-1). Safety parameters included liver and kidney function. Results: Compared to placebo, AG significantly reduced HbA1c (− 0.29%; p = 0.041) and fasting blood glucose (− 0.71 mmol/L; p = 0.008). Furthermore, AG lowered systolic blood pressure (− 5.6 ± 2.7 mmHg; p < 0.001), increased NOx (+ 1.85 ± 2.13 µmol/L; p < 0.03), and produced a mean percent end-difference of − 12.3 ± 3.9% in LDL-C and − 13.9 ± 5.8% in LDL-C/HDL. The safety profiles were unaffected. Conclusions: AG extract added to conventional treatment provided an effective and safe adjunct in the management of T2DM. Larger studies using physiologically standardized ginseng preparations are warranted to substantiate the present findings and to demonstrate therapeutic effectiveness of AG. ClinicalTrials.gov Identifier: NCT02923453. [ABSTRACT FROM AUTHOR]