Lower Serum Cholesterol Levels Research Articles

Suitable ratio of dietary L-carnitine and α-ketoglutarate improves growth and health performance in Nile tilapia, Oreochromis niloticus

L-carnitine (LC) and α-Ketoglutarate (AKG) are important growth promoters used in aquafeed. The study aimed to evaluate the incorporation of LC and AKG at different ratios in the diet of tilapia (initial weight 1.38 ± 0.03g) in order to facilitate lipid utilization and protein synthesis. Fish were fed six isonitrogenous (~ 30g/100g CP) and isolipidic (~ 6g/100g CL) diets containing graded LC/AKG ratios of 0 (Control), 0.11, 0.42, 1.00, 2.33 and 9.00 in six treatments for 60days. Fish fed with LC/AKG ratios 2.33 and 9.00 showed significantly (P < 0.05) higher percentage weight gain, specific growth rate and protein efficiency ratio. Feed conversion ratio in fish-fed diets with LC/AKG ratio 9.00 improved significantly (p < 0.05) than other treatments. The whole-body protein content of tilapia and digestive enzyme activity were significantly higher with higher weight gain. The body lipid content was significantly lower in the LC/AKG ratio 9.00. The liver antioxidant parameters and activity of the immune components were significantly higher in the LC/AKG ratio 9 group. The lower serum triglyceride and cholesterol level was also recorded in LC/AKG ratio 9 group. The histology of the intestine and liver showed increased villi area and decreased lipid droplets, respectively, in tilapia fed with higher LC/AKG ratios. It was concluded from the above results that the higher LC and lower AKG (LC/AKG ratio 9.00) combination attributed maximum lipid utilization and higher protein efficiency and thus better growth performance in tilapia. This was also reflected in activity of digestive enzymes, antioxidant enzymes and immune status in tilapia.

Interaction of the pitavastatin with model membranes

Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using 1H, 2H and 31P solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the 31P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.

Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease.

Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.

Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner.

Oxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF-α, IL-α, 4-hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox-LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox-LDL decreased GPx4 and xCT expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox-LDL-induced endothelial cell dysfunction and restored ox-LDL-decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox-LDL-induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox-LDL-induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox-LDL-treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT.

Nutritional Management of Diabetes Mellitus: An appraisal of the role of Medicinal plants

Diabetes mellitus is a heterogeneous metabolic syndrome characterized by chronic hyperglycemia with partial or total lack of insulin secretion and insulin resistance. The most common symptoms are polydipsia, polyuria, blurred vision, slow healing sore, nerve damage. Diabetes, being a metabolic, endocrine disorder is directly connected to carbohydrates, lipid, and protein metabolism. As a result, nutrition therapy forms an integral part of diabetes management. Daily caloric intake of 50% - 55% carbohydrates is recommended. Carbohydrate with low glycaemic index is preferred to those with high glycaemic index. Nonnutritive sweeteners are also encouraged for people with diabetes to add increased variety to their food choices. The protein requirement for persons with diabetes is not different from the general population, 15-20 % of total caloric intake. Both soluble and insoluble fibers are encouraged in amounts similar to the recommendations for the general population (20–35 g). Fibers are useful as they prolong gastric emptying, prevent constipation, lower serum cholesterol level, and reduce nutrients diffusion rates, thus reducing blood glucose response. A low-fat diet is advisable for diabetics in order to reach and maintain good weight and health. As part of a healthy diet, 30% of daily calories should come from fats, and of these less than 10% should be saturated fat, less than 10% polyunsaturated fat and 10- 15% monounsaturated fat. As the general population, people with diabetes have no need for vitamin and mineral supplementation when the dietary intake is adequate. Despite much research on nutritional factors in the etiology and management of diabetes, the risk associated with several individual nutrients is not entirely clear. In order to achieve maximum benefit from nutritional interventions in the management of diabetes changes in government policies and legislation will be needed in addition to individual and community-based programs.

Effect of cage density on growth rate, carcass traits, muscle amino acid profile, and antioxidant biomarkers of commercial rabbits.

The objective of this work was to elucidate the impact of cage density on growth efficiency, carcass yield, and muscle amino acid profile of fattening rabbits. In total, 96 weaned rabbits were assigned into three cage densities: low cage density (LCD) = 1425 cm2/rabbit; medium cage density (MCD) = 850 cm2/rabbit; high cage density (HCD) = 625 cm2/rabbit. Compared with the HCD, the body gain and feed conversion ratio were better in the LCD and MCD groups (P = 0.003 and 0.004, respectively). The MCD and HCD groups had lower hot carcass weight (P = 0.012) and dressing percentage (P = 0.022) than the LCD group. Compared with the HCD group, the LCD and MCD groups exhibited greater serum GSH (P = 0.029) and SOD (P = 0.032), but significantly lower levels of serum cortisol and cholesterol (P = 0.001 and 0.026, respectively). Regarding the amino acid profile of longissimus dorsi and leg muscles, the LCD group had significantly higher levels of muscle lysine and threonine than the HCD and MCD groups (P˂0.05). The current study indicates that the MCD (850 cm2/rabbit) could maintain an acceptable growth performance, carcass traits, and welfare-related parameters. Furthermore, only the low cage density (1425 cm2/rabbit) may preserve the levels of essential (lysine, isoleucine, and threonine) and nonessential (histidine, proline, and glysein) amino acids in the longissimus dorsi and leg muscles of growing rabbits.

Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals

BackgroundHigh milk intake has been associated with cardio-metabolic risk. We conducted a Mendelian Randomization (MR) study to obtain evidence for the causal relationship between milk consumption and cardio-metabolic traits using the lactase persistence (LCT-13910 C > T, rs4988235) variant as an instrumental variable.MethodsWe tested the association of LCT genotype with milk consumption (for validation) and with cardio-metabolic traits (for a possible causal association) in a meta-analysis of the data from three large-scale population-based studies (1958 British Birth Cohort, Health and Retirement study, and UK Biobank) with up to 417,236 participants and using summary statistics from consortia meta-analyses on intermediate traits (N = 123,665–697,307) and extended to cover disease endpoints (N = 86,995–149,821).ResultsIn the UK Biobank, carriers of ‘T’ allele of LCT variant were more likely to consume milk (P = 7.02 × 10−14). In meta-analysis including UK Biobank, the 1958BC, the HRS, and consortia-based studies, under an additive model, ‘T’ allele was associated with higher body mass index (BMI) (Pmeta-analysis = 4.68 × 10−12) and lower total cholesterol (TC) (P = 2.40 × 10−36), low-density lipoprotein cholesterol (LDL-C) (P = 2.08 × 10−26) and high-density lipoprotein cholesterol (HDL-C) (P = 9.40 × 10−13). In consortia meta-analyses, ‘T’ allele was associated with a lower risk of coronary artery disease (OR:0.86, 95% CI:0.75–0.99) but not with type 2 diabetes (OR:1.06, 95% CI:0.97–1.16). Furthermore, the two-sample MR analysis showed a causal association between genetically instrumented milk intake and higher BMI (P = 3.60 × 10−5) and body fat (total body fat, leg fat, arm fat and trunk fat; P < 1.37 × 10−6) and lower LDL-C (P = 3.60 × 10−6), TC (P = 1.90 × 10−6) and HDL-C (P = 3.00 × 10−5).ConclusionsOur large-scale MR study provides genetic evidence for the association of milk consumption with higher BMI but lower serum cholesterol levels. These data suggest no need to limit milk intakes with respect to cardiovascular disease risk, with the suggested benefits requiring confirmation in further studies.

Anti-PCSK 9 antibodies increase the ratios of the brain-specific oxysterol 24S-hydroxycholesterol to cholesterol and to 27-hydroxycholesterol in the serum.

The serum ratios of the brain-specific oxysterol 24S-hydroxycholesterol (24S-OHC) to cholesterol and to 27-OHC reflect brain cholesterol turnover. We studied the effect of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) that enhance low-density lipoprotein receptor activity on serum cholesterol and oxysterol concentrations. Twenty-eight hypercholesterolaemic patients (15 males and 13 females) responding insufficiently to maximally tolerated statin and/or ezetimibe therapy were additionally subcutanously treated biweekly with either the PCSK9ab alirocumab (150 mg, n =13) or evolocumab (140 mg, n =15). Fasting serum cholesterol was measured by gas chromatography and the oxysterols 24S-OHC and 27-OHC using gas chromatography-mass spectrometry before, after 1-month (n =28) and after 3-month (n =13) treatment. As expected, PCSK9ab treatment lowered serum cholesterol and oxysterol levels after 1 month. The serum ratio of 24S-OHC to cholesterol increased after 1 month by 17 ± 28% (mean ± standard deviation; 95% confidence interval [CI]: 5.8 to 28%; P< .01) and 24S-OHC to 27-OHC by 15 ± 39% (95% CI: 0.2 to 30%; P< .01). Within 3 months, 24S-OHC to cholesterol increased by 2.8 μg g-1 mo-1 (95% CI: 2.1 to 3.6; P< .01) and 24S-OHC to 27-OHC by 0.019 mo-1 (95% CI: 0.007 to 0.032; P< .01). The serum ratios of 24S-OHC to cholesterol and to 27-OHC increased after treatment with PCSK9ab. We hypothesize that this is caused by a reduced entrance of 27-OHC into the brain, increased synthesis of brain cholesterol, increased production of 24S-OHC and its secretion across the blood-brain barrier.

High hydrostatic pressure extract of mulberry leaves ameliorates hypercholesterolemia via modulating hepatic microRNA-33 expression and AMPK activity in high cholesterol diet fed rats.

BackgroundMulberry leaf (Morus alba L.) contains multiple bioactive ingredients and has been used in the treatment of obesity, diabetes, inflammation, and atherosclerosis. High hydrostatic pressure (HHP) processing has been developed for the extraction of bioactive compounds from plants. However, the hypocholesterolemic effect of the HHP extract from mulberry leaves and its underlying mechanism have never been investigated.ObjectiveThe specific aim of the present study was to investigate the hypocholesterolemic property of a novel extract obtained from mulberry leaves under HHP in rats.DesignSprague–Dawley rats were divided into four groups and fed either a normal diet (NOR), a high cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), an HC diet containing 0.5% mulberry leaf extract (ML), or a 1% mulberry leaf extract (MH) for 4 weeks.ResultsHigh hydrostatic pressure extract of mulberry leaves significantly reduced the HC-increased serum levels of triglyceride (TG), cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and hepatic contents of TG and TC. The HHP extraction from mulberry leaves also increased the HC-decreased fecal TC and bile acid levels without changing body weight, food intake, liver weight, and serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.05). The mulberry leaf extract significantly enhanced the expression of hepatic genes such as cholesterol 7 alpha-hydroxylase (CYP7A1), liver X receptor alpha (LXRα), and ATP-binding cassette transporters, ABCG5/ABCG8, involved in hepatic bile acid synthesis and cholesterol efflux (P < 0.05). In addition, the HHP extraction of mulberry leaves significantly suppressed hepatic microRNA(miR)-33 expression and increased adenosine monophosphate-activated protein kinase (AMPK) activity.ConclusionThese results suggest that the HHP extract of mulberry leaves lowers serum cholesterol levels by partially increasing hepatic bile acid synthesis and fecal cholesterol excretion through the modulation of miR-33 expression and AMPK activation in the liver.

Associations between Osteocalcin, Calciotropic Hormones, and Energy Metabolism in a Cohort of Chinese Postmenopausal Women: Peking Vertebral Fracture Study

Objective The endocrine function of bone in energy metabolism may be mediated by the osteocalcin (OC). We examined the association between OC and energy metabolism among Chinese postmenopausal women. Design and Setting. A cross-sectional cohort study enrolling 1635 participants was conducted using data from the Peking Vertebral Fracture study. Partial correlation analysis was performed to explore the correlation of OC, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25(OH)D) with glycemic and lipid metabolic parameters. A logistic regression model was used to investigate the association of OC, PTH, or 25(OH)D with the prevalence of diabetes and dyslipidemia. Results Serum levels of OC, PTH, and 25(OH)D were all positively correlated with serum cholesterol levels, whereas only OC was negatively associated with serum glucose level. In the logistic regression model, both OC and PTH were negatively associated with the prevalence of diabetes (odds ratio [OR], 95% confidence interval [95% CI]: 0.967, 0.948–0.986 for OC and 0.986, 0.978–0.994 for PTH). No significant association was found between 25(OH)D and diabetes. Both OC and 25(OH)D, rather than PTH, were associated with abnormalities of high cholesterol levels, such as hypercholesterolemia and high LDL-C levels. Further classifying the population based on the median value of OC and PTH, low OC and low PTH subgroup had the highest OR, 95% CI for diabetes (1.873, 1.287–2.737) and the lowest OR, 95% CI for hypercholesterolemia (0.472, 0.324–0.688) and for high LDL-C (0.538, 0.376–0.771). Conclusion Among Chinese postmenopausal women, a lower serum level of OC was associated with a higher prevalence of diabetes and lower serum cholesterol levels, and a low PTH concentration could magnify these associations.

In Vitro Bile Salt Hydrolase (BSH) Activity Screening of Different Probiotic Microorganisms.

Bile salt hydrolase (BSH) activity in probiotic strains is usually correlated with the ability to lower serum cholesterol levels in hypercholesterolemic patients. The objective of this study was the evaluation of BSH in five probiotic strains of lactic acid bacteria (LAB) and a probiotic yeast. The activity was assessed using a qualitative direct plate test and a quantitative high-performance thin- layer chromatography assay. The six strains differed in their BSH substrate preference and activity. Lactobacillus plantarum DGIA1, a potentially probiotic strain isolated from a double cream cheese from Chiapas, Mexico, showed excellent deconjugation activities in the four tested bile acids (69, 100, 81, and 92% for sodium glycocholate, glycodeoxycholate, taurocholate, and taurodeoxycholate, respectively). In the case of the commercial probiotic yeast Saccharomyces boulardii, the deconjugation activities were good against sodium glycodeoxycholate, taurocholate, and taurodeoxycholate (100, 57, and 63%, respectively). These last two results are part of the novelty of the work. A weak deconjugative activity (5%) was observed in the case of sodium glycocholate. This is the first time that the BSH activity has been detected in this yeast.

Low serum cholesterol levels predict inferior prognosis and improve prognostic index scoring for peripheral T-cell lymphoma, unspecified

Peripheral T-cell lymphomas, unspecified (PTCL−U) is a heterogeneous group of non-Hodgkin lymphomas, arising from the transformation of mature, post-thymic T-cells. Prognostic index for PTCL−U (PIT) is based on Europeans and may not be applicable for Chinese PTCL-U patients. Besides, low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. The purpose of our study was to assess the prognostic value of serum lipid levels in PTCL−U and improve PIT. We screened the prognostic factors associated with progression−free survival (PFS) and overall survival (OS) by multivariate Cox regression analysis in ninety−one enrolled patients. The results showed that low-level high−density lipoprotein cholesterol (HDL−C) and low-density lipoprotein cholesterol (LDL−C) were associated with unfavorable OS. Furthermore, we developed a new risk model, PITC, based on low-level HDL−C, LDL−C and PIT. In Chinese PTCL−U, PITC was superior to PIT in PFS and OS. In conclusion, serum cholesterol levels may be good candidates for predicting prognosis in PTCL−U.

Association Between Total Cholesterol and All-Cause Mortality in Oldest Old: A National Longitudinal Study

Background: In the context of accelerated global aging, blood lipid levels are directly related to the health status of oldest old. The common sense is that lower serum cholesterol levels are better, as higher cholesterol levels increase the risk of cardiovascular disease. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over. Methods: In this retrospective longitudinal study, we selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome of our study was all-cause mortality. The univariate and multivariate cox regression analyses were used to estimate Hazard ratios (HRs) and 95% confidence interval values of all-cause mortality. To analyze further the relationship between total cholesterol and all-cause mortality, we stratified the participants into three groups (<3·40, 3·40-4·39, ≥4·39 mmol/L) base on the restricted cubic splines methods. The survival probability according to total cholesterol category was calculated using the Kaplan-Meier curves, and the log-rank test was performed to analyze differences between the groups. Findings: During the follow-up of three years, 282 participants died, 497 survived and 124 lost to follow-up. When the total cholesterol was used as a continuous variable, there was significant relationship between the total cholesterol and lower risk of all-cause mortality in the univariate (HR=0·85, 95% CI: 0·76-0·96; P=0·011) and multivariate(HR=0·88, 95% CI: 0·78-1·00; P =0·043) cox regression analyses. Based on the restricted cubic splines methods, the total cholesterol was converted from a continuous variable to a categorical variable. The populations were divided into three groups (<3·40, 3·40-4·39, ≥4·39 mmol/L) according to the total cholesterol categorized by cutoff values. Compared to the total cholesterol level of <3·40 mmol/L, populations in the total cholesterol level of 3·40-4·39 mmol/L (HR = 0·72, 95% CI: 0·53-0·97; P =0·029) and ≥4·39 mmol/L (HR =0·71, 95% CI: 0·52-0·96; P =0·029 ) groups had lower all-cause mortality in multivariate cox regression analyses and higher survival probability(log-rank P =0·018) in survival analysis. In addition, populations in the total cholesterol level of ≥3·40 mmol/L (HR = 0·71, 95% CI: 0·54-0·93; P =0·014) groups had a significantly lower risk of all-cause mortality and higher survival probability (log-rank P =0·006) than the populations in the total cholesterol level of <3·40 mmol/L groups. Interpretation: In oldest old aged 85 and older, serum total cholesterol levels are inversely associated with all-cause mortality. Total cholesterol < 3·40 mmol/L increases all-cause mortality risk in this age group, each 1 mmol/L reduction in total cholesterol increases the risk of death by 12% in this group. This finding suggested that total cholesterol should be maintained to acceptable levels ( ≥ 3·40 mmol/L) in oldest old to achieve longevity. Funding: Shanghai Three-year Action Plan for Public Health under Grant(GWV-10.2-XD13, GWV-10.1- XK15, GWV-10.1-XK18); Strategic collaborative innovation team (SSMU-ZLCX20180601); the National Key Research and Development Project (2018YFC1705100, 2018YFC1705103). Declaration of Interest: None to declare. Ethical Approval: The CLHLS study was approved by the research ethics committee of Peking University (IR1052-13074). All participants provided written informed consent.

Association of age-related white matter hyperintensity with brain atrophy and cognitive impairment in patients with Parkinson's disease

Objective: To investigate the association of age-related white matter hyperintensity (WMH) with brain atrophy and cognitive impairment in patients with Parkinson's disease (PD). Methods: Consecutive samples of a prospective PD cohort with complete 3-dimensional magnetic resonance imaging in the Department of Movement Disorders in Beijing Tiantan Hospital, Capital Medical University, from October 2018 to August 2019 was retrospectively analyzed. Cognition was evaluated by Mini-Mental State Scale (MMSE) and Montreal Cognitive Assessment (MoCA). The severity of WMH was semi-quantitatively measured by Fazekas scale (0-6 points), and the mean cortical thickness and thalamus volume were calculated by FreeSurfer software. The demographic and disease characteristics, the severity of WMH, the mean cortical thickness and thalamus volume were respectively compared between PD patients with and without dementia. Moreover, univariate and multivariate generalized linear models were used to analyze the correlation of the severity of WMH with brain atrophy and MoCA. Results: A total of 225 patients with PD were included in the study, with a median age of 66 years old. Comparisons between groups suggested that patients with dementia were with severer WMH, older, and had lower levels of serum cholesterol and low-density lipoprotein and more reduced mean cortical thickness than those without dementia (all P<0.05), but no significant difference in the thalamus volume was found between the two groups. The generalized linear model showed that the cognitive impairment of PD patients was significantly correlated with WMH (β=-0.021, 95%CI:-0.040--0.002, P=0.032), but independent of age, cortical thickness, and levels of serum cholesterol and low-density lipoprotein. Conclusion: WMH may worsen PD cognitive impairment independent of brain atrophy. Clinical prevention and treatment of cerebral small vessel disease may have protective effects on cognitive function in patients with PD.

The Role of Structure and Biophysical Properties in the Pleiotropic Effects of Statins.

Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.

Clinical and genetic analysis of a Chinese pedigree affected with Smith-Lemli-Opitz syndrome

To explore the clinical phenotype and pathogenic variants in a Chinese pedigree affected with Smith-Lemli-Opitz syndrome. Peripheral blood samples were collected from five members, including two affected ones, from the pedigree for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing as well as reverse transcription sequencing at the RNA level. The proband and another affected child from the pedigree showed mental retardation, dyskinesia, microcephaly, micrognathia, anteverted nares, and 2/3 toe syndactyly. The proband also had hypospadia, single upper incisor, and lower serum cholesterol level. Both children were found to harbor a paternally derived c.278C>T (p.T93M) variant and a maternally derived c.907G>A (p.G303R) variant of the DHCR7 gene. Both were known pathogenic mutations. The compound heterozygous mutations of c.278C>T (p.T93M) and c.907G>A (p.G303R) of the DHCR7 gene probably underlay the disease in this pedigree. Above finding has enabled early diagnosis and treatment of Smith-Lemli-Opitz syndrome.

The effect of improved formulation of chitosan-alginate microcapsules of Bifidobacteria on serum lipid profiles in mice

BackgroundProbiotics have been associated with many beneficial effects in human digestive physiology. The aim of this study was to evaluate the effect of improved formulation of chitosan-alginate microcapsules of Bifidobacterium strains on serum triglycerides, cholesterol, HDL, and LDL in mice. MethodsFive approved probiotic strains of Bifidobacterium were tested for anti-proliferative effect and interleukin-8 induction on HT-29 cell lines. Bifidobacterium strains plus five approved Lactobacillus were encapsulated in chitosan-alginate microcapsules and tested for its survival in simulated gastrointestinal conditions. These microcapsules were administered to 4 groups of mice (including 1. Bif (Bifidobacterium strains), 2. Lac (Lactobacillus strains), 3. Bif-Lac (Bifidobacterium plus Lactobacillus strains) and 4. Control) for 8 days. At eighth day, the blood of mice were taken and serum levels of triglycerides, cholesterol, HDL, and LDL of them were determined. ResultsAll of the Bifidobacterium strains significantly (P < 0.001) reduced secretion of IL-8 in HT-29 cells as well as maximum antiproliferative effects (P < 0.001). In addition, all microcapsules showed impressive survival rate in bile (>%94.1) and gastrointestinal (>%78.28) conditions (P < 0.05). Only Bif-Lac group displayed significantly lower serum cholesterol and LDL levels than control group (P < 0.05). Besides, all groups indicate statistically significant weight loss of mice during the 8 days in comparison with the control group (P < 0.05). ConclusionThe results of this study showed that the microencapsulated probiotics with alginate and chitosan had an effective mean of delivery of viable bacterial cells and non-pharmacological interventions use to reduce serum cholesterol and LDL levels in in-vivo condition.

Association between early treatment hospitals, serum cholesterol level and cardiovascular disease risk in dyslipidemia patients.

Studies have shown the importance of managing chronic diseases, such as cardiovascular disease (CVD), at the primary treatment level. Here, we aimed to evaluate the association between medical treatment institutions and health outcomes in patients with dyslipidemia, a major risk of CVD, to provide evidence for increasing chronic disease management at the primary care level in Korea. We used National Health Insurance Sampling cohort data, of which 37506 patients were newly diagnosed with dyslipidemia during 2009-14. CVD risk and changes in serum cholesterol level after dyslipidemia diagnosis were outcome variable examined. A generalized estimating equation model was used to identify associations between initial medical institution, CVD risk and changes in serum cholesterol levels. The Cox proportional-hazard ratio was used to assess the association between initial medical institutions and detailed CVD risk. Subgroup analyses were conducted to assess CVD risk following treatment with prescription medication. Our analyses demonstrate that CVD risk was lower at primary care-level community health centers and clinics compared to tertiary hospitals, with a statistically significant difference observed in clinics. Ischemic heart disease was lower at community health centers and clinics. However, all medical institution types were associated with significantly lower serum cholesterol levels compared to the baseline. Management of patients with dyslipidemia at primary care institutions was associated with reduced CVD risk and decreased serum cholesterol levels. Therefore, policymakers should strengthen the quality of healthcare at primary care institutions and educate patients that these institutions are appropriate for managing chronic disease.

SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics.

The use of statins to lower high serum cholesterol levels may be associated with a number of adverse reactions, including severe myopathy. The solute carrier organic anion transporter 1B1 (SLCO1B1) gene, which encodes the organic anion-transporting polypeptide OATP1B1, is related to the intracellular transport of statins. The aim of this research was to study the association of rs2306283 and rs4149056 genetic polymorphism of the SLCO1B1 gene with the development of statin-induced myopathy in Jordanian diabetics receiving statins. We included 413 patients attending the Diabetes Clinics of the National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan. The study was approved by the Institutional Review Board of NCDEG. Myopathy was defined as the elevation of creatine kinase more than 3 times the upper limit of normal. Every subject signed an informed consent form and donated 3-5 mL of venous blood. Genome DNA was extracted from lymphocytes of peripheral blood. Genotypes were identified using the Tetra Amplification Refractory Mutation System of SLCO1B1. The minor allele frequencies of rs2306283 [G] and rs4149056 [C] were 0.38 and 0.23, respectively. The two SNPs followed the Hardy-Weinberg equilibrium. The development of SIM was significantly associated with the homozygous and heterozygous minor allele genotype of rs4149056 (CC and CT), and the homozygous wild type allele genotype of rs2306283 (AA). There was no linkage disequilibrium between the two SNPs in the studied subgroups. Genetic polymorphism in the SLCO1B1 Gene is a risk factor for the development of SIM in Jordanian patients.

Schistosoma haematobium infection is associated with lower serum cholesterol levels and improved lipid profile in overweight/obese individuals.

Infection with parasitic helminths has been reported to improve insulin sensitivity and glucose homeostasis, lowering the risk for type 2 diabetes. However, little is known about its impact on whole-body lipid homeostasis, especially in obese individuals. For this purpose, a cross-sectional study was carried out in lean and overweight/obese adults residing in the Lambaréné region of Gabon, an area endemic for Schistosoma haematobium. Helminth infection status, peripheral blood immune cell counts, and serum metabolic and lipid/lipoprotein levels were analyzed. We found that urine S. haematobium egg-positive individuals exhibited lower serum total cholesterol (TC; 4.42 vs 4.01 mmol/L, adjusted mean difference [95%CI] -0.30 [-0.68,-0.06]; P = 0.109), high-density lipoprotein (HDL)-C (1.44 vs 1.12 mmol/L, -0.24 [-0.43,-0.06]; P = 0.009) and triglyceride (TG; 0.93 vs 0.72 mmol/L, -0.20 [-0.39,-0.03]; P = 0.022) levels than egg-negative individuals. However, when stratified according to body mass index, these effects were only observed in overweight/obese infected individuals. Similarly, significant negative correlations between the intensity of infection, assessed by serum circulating anodic antigen (CAA) concentrations, and TC (r = -0.555; P<0.001), HDL-C (r = -0.327; P = 0.068), LDL-C (r = -0.396; P = 0.025) and TG (r = -0.381; P = 0.032) levels were found in overweight/obese individuals but not in lean subjects. Quantitative lipidomic analysis showed that circulating levels of some lipid species associated with cholesterol-rich lipoprotein particles were also significantly reduced in overweight/obese infected individuals in an intensity-dependent manner. In conclusion, we reported that infection with S. haematobium is associated with improved lipid profile in overweight/obese individuals, a feature that might contribute reducing the risk of cardiometabolic diseases in such population.