Effects of different thermal processing methods on the nutritional components of whole highland barley and its hypoglycemic and hypolipidemic effects: β-glucan and polyphenols.

Hypercholesterolemia is a major driver of cardiovascular disease, a leading cause of premature mortality in patients with chronic kidney disease (CKD). Despite their typically young age, patients with Alport syndrome (AS), the second most prevalent genetic cause of CKD, may face a disproportionately high risk of hypercholesterolemia. This study investigates whether increased albuminuria precipitates hyperlipidemia in this population to a degree comparable with general CKD cohorts, while further delineating the risk factors underlying this development. This was a multicenter, observational, non-interventional, and retrospective study. Among 459 patients with AS, 59.3% had hypercholesterolemia and 58.5% had elevated low-density lipoprotein cholesterol (LDL-C). Despite lower eGFR and higher albuminuria, patients with lipid-lowering therapy (LLT) had significantly lower total cholesterol levels compared to the untreated patients (193.6±55.2mg/dL vs. 208.2±51.0mg/dL; p=0.044). Similarly, LDL-C levels were significantly lower in the treatment group (111.6 ± 51mg/dL, n=59) compared to the untreated group (124.3±40.2mg/dL, n=238; p=0.041). Multivariable regression analysis adjusted for age, gender, BMI, eGFR, and LLT revealed that albuminuria was a significant independent determinant of total cholesterol (β=0.315; p<0.001) and LDL-C levels (β=0.242; p<0.001). Male gender was associated with significantly higher LDL-C and lower HDL-C levels. Conversely, eGFR and BMI were not significant predictors of cholesterol levels. This association was also observed in the pediatric cohort (n=44), where albuminuria was the only independent predictor of cholesterol (β=0.728; p<0.001). Hypercholesterolemia is highly prevalent in young patients with AS and is primarily driven by the severity of albuminuria, rather than other risk factors such as obesity or eGFR decline. These findings highlight a critical gap in current guidelines, support the implementation of early lipid screening and suggest that risk-adapted management may be necessary to prevent long-term cardiovascular complications.

Dietary supplementation with prebiotics such as inulin has been associated with a broad range of health benefits. However, the effects of inulin on the opportunistic fungal pathogen Candida albicans, which resides as a commensal in the gut, have not been characterized. Here, RNA sequencing revealed that inulin affects the expression of C. albicans genes associated with cell wall construction, adhesion, and yeast-hypha morphogenesis. Consistent with these changes in gene expression, inulin inhibited hyphal development, increased adhesion to human Caco-2 and A431 cells, decreased the thickness of the inner layer of the C. albicans cell wall, reduced the exposure of cell wall pathogen-associated molecular patterns [β-(1,3)-glucan and chitin], and affected antifungal drug sensitivity. These changes impacted host immune recognition and cytokine responses, ultimately attenuating the virulence of C. albicans in an invertebrate infection model. Therefore, dietary supplementation with inulin is likely to influence host-fungus interactions.IMPORTANCEThe benefits of prebiotic dietary supplements, such as inulin (a natural plant dietary fiber), are thought to include a healthier gut microbiome, a reduced risk of colon cancer, and lower cholesterol levels. Unsurprisingly, prebiotic usage is increasing rapidly. However, while the effects of prebiotics upon gut bacteria have been characterized, the impacts upon Candida albicans, an opportunistic fungal pathogen that resides in the human gut, have remained obscure. We show that inulin affects the expression of virulence-related phenotypes and antifungal drug sensitivity in Candida. Furthermore, we show that inulin reduces the virulence of this fungus in an invertebrate model, consistent with the idea that inulin may lower the risk of fungal infection in healthy individuals.

Altered lipid profile in mice lacking the DNA repair protein ERCC1.

Elevated levels of the inflammatory cytokine IL-6 and decreased levels of cholesterol in blood and brain tissue have been reported in studies of individuals who attempted or completed suicide. The mechanisms underlying these effects remain unclear. In this review, we discuss a potential mechanistic link between these observations involving lipid raft function and serotonergic signaling. Reduced cholesterol availability may affect lipid raft function and could, potentially through reduced levels of the lipid raft protein S100A10 (p11), result in diminished cell-surface expression of the serotonin receptors 5-HT1B and 5-HT4. Both receptors have been implicated in the suppression of impulsive and aggressive behavior. Lipid rafts are also organizing platforms for GABA, glutamate, and serotonin transporters. Reduced serotonin reuptake could contribute to the often-reported decrease in the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in suicidal individuals. Inflammatory cytokines, including IL-6, may further influence serotonergic signaling by increasing expression of the enzyme indoleamine-2,3-dioxygenase (IDO), which enhances tryptophan degradation through the kynurenine pathway. Reduced tryptophan availability may limit serotonin synthesis and thereby decrease activation of the 5-HT1B and 5-HT4 receptors. These observations suggest that the combined effects of low cholesterol, elevated IL-6 signaling, and reduced tryptophan availability may increase impulsivity and thereby heighten vulnerability to suicidal behavior. This framework accommodates findings from genetic and biomarker studies in suicidal patients. Owing to its effect on lipid raft organization, the fish-oil component docosahexaenoic acid (DHA) might modulate these processes and potentially reduce suicide risk in individuals with low cholesterol levels.

Individuals with phenylketonuria (PKU), caused by different variants of the phenylalanine hydroxylase gene, need to restrict their intake of phenylalanine. This study evaluated dietary patterns and physical activity levels in children with different PKU phenotypes compared to healthy controls. Eighty-two children were recruited (22 classic PKU [cPKU], 21 BH4-responsive PKU, 19 hyperphenylalaninemia, and 20 controls). Anthropometric data, dietary intake, biochemical markers, and physical activity were assessed. Classic PKU (cPKU) subjects exhibited higher carbohydrate and sugar intake than other PKU phenotypes and controls. Notably, 42% of carbohydrate and 17% of sugar intake was from special low-protein foods, and 20% of carbohydrate and 29% of sugar intake was from protein substitutes. Compared to controls, the cPKU group was less physically active and reported a higher frequency of sweet consumption. Ninety percent of PKU had good metabolic control and carbohydrate intake was significantly correlated with HOMA-IR; however, after adjusting for age, only a trend remained (p = 0.08). Participants in the PKU group following a low natural protein diet consumed more carbohydrate and sugars than those on a normal-protein diet. Multivariate regression analysis showed that the low natural protein diet group was significantly associated with higher levels of vitamin B12, linoleic acid, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid, and with lower levels of total cholesterol and HDL-C compared to the normal-protein diet group. In conclusion, children with PKU, particularly those with classical PKU following low-protein diets, showed higher carbohydrate intake and distinct micronutrient and lipid profiles compared with healthy controls.

Five modifiable cardiovascular risk factors-hypertension, diabetes, smoking, hypercholesterolemia, and obesity-account for approximately 50% of the global burden of cardiovascular disease. Recent data from the Global Cardiovascular Risk Consortium show that the absence of diabetes and smoking is associated with the lowest risk in terms of life expectancy and years lived free from cardiovascular disease. A systolic blood pressure below 130 mmHg, lower non-HDL cholesterol levels, and normal body weight are associated with a later onset of cardiovascular disease and a more modest increase in life expectancy. The absence of hypertension is correlated with the greatest number of years lived free from cardiovascular events. Smoking is confirmed as one of the most influential risk factors in terms of its impact on health and longevity. Individuals who eliminate hypertension and smoking in midlife gain the greatest number of additional years of life free from cardiovascular disease and all-cause mortality, respectively. Male sex emerges as a traditional, non-modifiable risk factor independent of modifiable risk factors. Finally, even the absence of all the risk factors considered remains associated with a residual lifetime probability of developing cardiovascular disease.

While atherosclerosis is a disease of vascular hypercholesterolemia, reports have also shown the presence of intracellular hypercholesterolemia in cancer tumor cells. Since the dietary cholesterol in the blood vessel is the major source of intracellular cholesterol, a low blood cholesterol level is maintained in people having carcinogenesis. Because of the variance found in blood cholesterol level, the carotid artery intimal media thickness (CIMT) was considered as a confirmation marker to distinguish these two diseases. 50 patients of each category and 25 disease-free healthy subjects were included in a single-center study. Subjects were classified into two groups viz., normoglycemic and hyperglycemic. Since both atherosclerosis and carcinogenesis are inflammatory, stressful diseases; the relative variations of plasma or serum concentrations of different characteristic discriminating markers related to inflammation and stress were evaluated in this study to compare the severity of stress between these two dreadful diseases. The respective inflammatory and stress markers were Ox-LDL, TNF-α, IL-10, Cortisol, PERK, and NF-kB. ELISA-based commercial kits were used for the assay of the respective parameters. Based on the relative severity of the bio-marker values, subjects were also divided into risk liable sub-groups. Linear regression analysis against serum low density lipoprotein (LDL) concentration for each of the inflammation (Ox-LDL, TNF-α, and IL-10) and stress (Cortisol, PERK, and NF-kB) factors was carried out for a clear outcome of the absolute severity of each component in the pathogenicity of these two disease processes. Calculated fold alarming severity earmarked hyperglycemic carcinogenesis as the most stressful alarming disease over the others.

Residual cardiovascular risk factors and incident myocardial infarction in individuals with low levels of baseline low-density lipoprotein cholesterol: a cohort study.

Gilbert syndrome is a human genetic disorder which affects bilirubin metabolism in the liver and results in unconjugated hyperbilirubinemia. While considered a benign condition with only occasional jaundice and possible alterations of metabolism of certain drugs, Gilbert syndrome can reduce cardiovascular disease (CVD) risk. The objective of this review was to summarize the evidence on the potential effect of Gilbert Syndrome on reducing CVD risk via lowering cholesterol and/or lipid levels in the body and is associated with other protective mechanisms which are related to higher blood levels of unconjugated bilirubin. A systematic review of articles returned from the online database PubMed was conducted using search terms: "Gilbert syndrome", "reduced cardiovascular disease risk", "cardiovascular disease", "cholesterol", and "lipid level". After filtering using the exclusion criteria and removing duplicates, eight articles were identified for the review. This review found that CVD risk was lower for people with Gilbert syndrome when compared to unaffected individuals. The reduced CVD risk was theorized to be due to elevated unconjugated bilirubin levels which lead to reduced concentrations of lipids, reduced inflammation biomarkers, decreased ABCA1 protein, increased serum antioxidant capacity expression, decreased BMI, and lower triglyceride levels. Individuals with Gilbert syndrome have a reduced CVD risk. Given that Gilbert syndrome reduces CVD risk in individuals and that Gilbert syndrome results in elevated serum levels of unconjugated bilirubin; elevation of unconjugated bilirubin could serve as a biomarker to monitor CVD risk reduction in the general population.

Background: abdominal fat is a strong predictor of metabolic problems, which in turn raise the risk of cardiovascular disease and other metabolic disorders. Objective: To compare the effect of ultrasound lipolysis versus cryolipolysis on lipid profile in middle age men. Methods: Two experimental groups pre and post with control. sixty six male, with sedentary life style, body mass index (BMI) &lt; 30 Kg\m2, ranged in age from 40 to 60 years old, and with localized abdominal fat, waist circumference more than 94 cm. The subjects randomized into three equal groups (experimental group A) received ultrasound lipolysis on abdominal area and low caloric diet (1200-1500 cal), for three months, the patient received 60-minute sessions every two weeks on the abdominal area. (experimental group B) received cryolipolysis on abdominal area and low caloric diet (1200-1500 cal), for three months, every subject had cryolipolysis done on the same area of their abdomen every two weeks. (control group C) received low caloric diet (1200-1500 cal). Body mass index, waist circumference, waist hip ratio, skinfold thickness and lipid profile were measured at baseline (T0) and post treatment (T1). Results: All groups showed significant reductions in BMI, WC, WHR, skinfold thickness, cholesterol, TG, and LDL, with a significant increase in HDL levels. Group A showed significantly greater Group B and Group C. Group B also showed significantly greater than Group C. Conclusion: The lipid profile (lower cholesterol, TG, and LDL levels, with increased HDL) and central obesity (WC, WHR, and ST) were both improved by using ultrasonic lipolysis and cryolipolysis, with the ultrasound lipolysis producing superior outcomes.

Importance of the work: Heat stress causes physiological disorders, decreased immunity and increased mortality in quail in tropical regions. Bandotan leaf extract has the potential to address these issues through its antioxidant activity. Objectives: To investigate the effects of bandotan leaf extract on oxidative stress, blood biochemistry and immune status in tropical quail (Coturnix coturnix japonica Temminck &amp; Schlegel, 1848). Materials and Methods: The study involved 200 female quail. Bandotan leaf extract was administered daily to birds through their drinking water at concentrations of 0% (as a control), 1.5%, 3% or 4.5%. The experiment was conducted in a completely randomized design. The parameters measured were: stress indicators (oxygen saturation, heterophil-tolymphocyte ratio, superoxide dismutase activity, glutathione peroxidase and malondialdehyde (MDA) levels); blood biochemistry (cholesterol, glucose); and ex vivo bacterial clearance against Salmonella pullorum. Results: The administration of bandotan leaf extract had a significant effect (p &lt; 0.05) on MDA levels, blood cholesterol and the resistance of quails to S. pullorum. A 3% dose reduced MDA levels by 78.2%, indicating a decrease in oxidative stress and a lowered blood cholesterol level by 15.4%, reflecting improved lipid metabolism. In addition, the extract increased resistance to S. pullorum by 5.7%, indicating an enhanced immune response and a reduction in quail mortality by 71.4%. Main finding: Administering 3% bandotan leaf extract in drinking water reduced oxidative stress, lowered cholesterol, enhanced ex vivo antibacterial clearance against S. pullorum and decreased mortality in female quail, indicating improved physiological resistance during heat exposure.

Identification of a novel HNF4α agonist regulating abnormal metabolism.

Susceptibility to adult metabolic diseases varies significantly across ethnicities. Asian adults exhibit elevated risks associated with obesity at lower body mass index (BMI) levels; whether similar patterns occur in pediatric populations remains unclear. This study aimed to evaluate how metabolic indicators associated with childhood obesity vary across diverse racial/ethnic groups. Age-matched adolescents (12-18 years) from diverse regions across China-along with adolescents from Hispanic, Mexican American (MA), Non-Hispanic Black (NHB), Non-Hispanic White (NHW), and Other ethnic groups from the National Health and Nutrition Examination Survey (NHANES)-were enrolled. Comprehensive demographic, anthropometric and metabolic data-including glycemic parameters, lipid profiles, and insulin resistance indices-were analyzed. Cross-sectional mediation analysis was conducted to explore the potential biological pathways underlying the relationship between obesity (BMI standard deviation score [SDS] as the exposure) and metabolic dysfunction (metabolic indicators as the outcomes), testing cortisol and adrenocorticotropic hormone (ACTH) as potential mediators. Average direct and causal mediation effects were evaluated, with results interpreted as statistical associations consistent with the mediation framework. The study included 632 adolescents (55.22% male, mean age 14.51 ± 1.87 years, median BMI 31.55 kg/m2). Compared to Chinese adolescents, NHB had higher HbA1c, NHW had lower HbA1c; both showed lower HOMA-β. All groups had higher HDL-C, lower total cholesterol and LDL-C levels than Chinese adolescents. HbA1c correlated positively with BMI SDS in Chinese and MA adolescents. Fasting insulin and HOMA-IR correlated positively with BMI SDS in all groups except Hispanic adolescents, while HOMA-β correlated positively in all groups except Hispanic and NHW adolescents. In Chinese adolescents, ACTH mediated the associations of BMI SDS with fasting insulin and HOMA-IR (P = 0.014 and 0.020 for mediation effects, respectively). This first multiethnic pediatric metabolic comparison reveals distinct racial/ethnic patterns, with ACTH emerging as a novel mediator in Chinese adolescents. Findings underscore the need for ethnicity-tailored prevention strategies.

Background: Gallbladder disease is one of the prevalent hepatobiliary disorders, which are often accompanied by metabolic abnormalities, especially dyslipidemia. Nevertheless, in uncomplicated cases, abnormalities in the baseline liver function are not always present. Also, there are temporary changes in liver enzymes after laparoscopic cholecystectomy, although there is limited data of certain region populations. Aims: The purpose of the research was to test the differences in lipid profiles and liver biochemistry between women with the gallbladder disease and healthy control groups, and to determine the changes in liver enzymes in the short term after laparoscopic cholecystectomy surgery in Dhi Qar Governorate. Methods: This was a case control study and prospective observational study. One hundred and thirty-five female patients with a known case of gallbladder disease who are between 30 and 45 years were matched with one hundred and thirty-five healthy seemed controls. All subjects were of regular menstrual cycles and none had a history of chronic psychosis or malignancy. Tests of serum lipid profile and liver functioning were obtained after overnight fasting. They also followed 100 patients who were having elective laparoscopy cholecystectomy and biochemical measurements were conducted before surgery, at 24 and 72 hours of operation. There were statistical analyses of independent and paired t-tests, where p &lt; 0.05 is statistically significant. Results: The patients with gallbladder disease had much higher serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, and much lower levels of high-density lipoprotein cholesterol in comparison with the controls (p &lt; 0.05). There were no significant differences in terms of level of alanine aminotransferase or bilirubin in the two groups. In laparoscopic cholecystectomy AST, ALT, ALP, GGT, and total bilirubin levels were significantly increased at 24hours postoperative (p-value less than 0.05) which began to return to baseline levels after 72 hours. There was no significant postoperative change in the direct bilirubin levels. Conclusions: Gallbladder disease in women of Dhi Qar Governorate is mainly related to dyslipidemia and not baseline liver dysfunction. Laparoscopic cholecystectomy causes temporary and reversible rises in liver enzymes and no signs of long-term hepatocellular damage and biliary dysfunction.

Cholesterol is considered a major factor contributing to cardiovascular diseases. Statins, the most commonly prescribed cholesterol-lowering drugs, are known to have various limitations. Inhibition of Adenosine Triphosphate-Citrate Lyase (ACLY) has been proposed as an alternative therapeutic strategy for managing hypercholesterolemia by lowering cholesterol levels. This has led to the discovery of a cell-permeable small molecule ACLY inhibitor. ACLY enzyme activity was assessed using an ACLY Assay Kit with the ADP-Glo Kinase Assay Kit. HepG2 cells were treated with test compounds to demonstrate cholesterol and fatty acid synthesis. Pharmacokinetic studies were performed on CD-1 mice following a single oral dose of the compounds. Hypercholesterolemia was induced in mice through a High-Fat and High Cholesterol Diet (HFHCD), and drugs were administered orally for six weeks. Serum and hepatic lipid profiles were subsequently analyzed. To increase the pharmacochemical properties, four analogues of BMS-303141, ID0018, ID0023, ID0085, and ID0106, were designed and synthesized. These compounds showed superior ACLY inhibitory activity and dose-dependent suppression of cholesterol and fatty acid synthesis in HepG2 cells. Among the analogues, ID0085 exhibited the most potent ACLY inhibition (IC50: 45 nM, 10-fold lower than BMS- 303141) and achieved near-complete suppression in cholesterol and fatty acid synthesis at the highest concentration. Pharmacokinetic studies revealed improved half-lives and systemic exposures for all analogues. In hypercholesterolemic mouse models, test compounds significantly reduced serum total cholesterol (32.0-57.3%) and low-density lipoprotein cholesterol (67.5-80.2%) levels compared to the vehicle group. Notably, ID0085 also increased high-density lipoprotein cholesterol levels. Among the synthesized analogues, ID0085 exhibited the most potent ACLY inhibition, superior pharmacokinetic properties, and significant improvements in both serum and hepatic cholesterol profiles compared to BMS-303141. Based on the results, ID0085 appears to be the most promising therapeutic candidate for the treatment of hypercholesterolemia.

Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity and mortality. Although lower grip strength has been linked to higher cardiovascular risk in the general population, evidence on its relationship with HDP remains limited. We aimed to prospectively investigate this association in a large cohort of pregnant women. Between March 2017 and January 2020, 6802 pregnant women (mean age ± standard deviation: 26.6 ± 3.7 years) enrolled in the Tongji-Huaxi-Shuangliu Birth Cohort were included in this analysis. Grip strength was measured in early pregnancy (mean gestational week ± standard deviation: 10.3 ± 2.0 weeks) and assessed in three ways: absolute grip strength (AGS) and two relative indices (AGS normalized to body mass index or body weight). Logistic regression models were used to assess the associations between grip strength and the risk of HDP (gestational hypertension or preeclampsia). Multiple metabolic biomarkers (blood lipids, leptin, adiponectin, C-reactive protein, C-peptide, glycated hemoglobin, and homeostatic model assessment of insulin resistance) were measured among 638 women at enrollment. A total of 180 women developed HDP during pregnancy. The adjusted odds ratios (95% confidence intervals) of HDP across increasing quartiles of AGS in early pregnancy were 1.00 (reference), 0.93 (0.63-1.35), 0.67 (0.44-1.00), and 0.35 (0.21-0.56). Odds ratios across quartiles of two relative grip strength (RGS) indices showed similar patterns. Restricted cubic spline analyses indicated a nonlinear association between AGS and HDP risk (P for nonlinearity = 0.014). The risk plateaued at lower AGS levels but showed a linear inverse association above a threshold of 18.1 kg. In contrast, the two relative measures showed linear associations with HDP risk (P for nonlinearity ≥0.164). Additionally, higher RGS was generally correlated with favorable metabolic profiles (e.g., lower levels of low-density lipoprotein cholesterol, triglycerides, and C-reactive protein). Grip strength in early pregnancy was inversely associated with the risk of HDP, and RGS may serve as a simple and useful measure for risk stratification.

Efficacy and safety of activated charcoal in primary gout: A double-blind, double-dummy, randomized controlled trial.

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including low high-density lipoprotein cholesterol (HDL-C) levels. Although HDL-C is an established cardiovascular biomarker, in MetS this marker captures only a fraction of the profound alterations occurring within HDL particles. The cardiometabolic role of HDLs in MetS remains insufficiently understood because the functional properties and molecular components of HDLs, rather than HDL-C alone, are likely key determinants of cardiovascular risk. Since the early 2000s, research has revealed that HDL particles comprise over 280 proteins and more than 300 lipid species, underscoring their biological complexity. Moreover, HDL composition and function are extensively remodelled in MetS, highlighting the importance of characterising the differences in HDL composition between health and disease. In this systematic review, we aimed to examine differences in the HDL lipidome between MetS patients and healthy controls. A comprehensive literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. The PRISMA guidelines for systematic reviews were followed, and four records met the eligibility criteria. Overall, the HDL lipidome was markedly different in MetS compared with healthy individuals. MetS was consistently associated with higher levels of triacylglycerides (TAGs) and phosphatidylinositol, alongside lower levels of several key lipid families, indicating a broad remodelling of HDL composition. These findings indicate that the HDL lipidome is substantially altered in MetS, with potential consequences for HDL functionality. Although the mechanistic implications remain to be fully elucidated, TAG enrichment may contribute to lower HDL levels and changes in HDL surface lipids may impair essential functions such as cholesterol efflux. Further studies are needed to validate these patterns and determine their impact on HDL function and cardiometabolic risk.

The precise contribution of lipids to G protein-coupled receptor (GPCR) signaling remains to be elucidated. Of all the lipids, cholesterol likely plays a special role due to its abundance in different membrane compartments. Here, we assembled the ghrelin receptor GHSR into lipid nanodiscs containing different amounts of cholesterol and leveraged fluorescence spectroscopy to analyze its impact on receptor conformational dynamics and ability to interact with signaling partners. We showed that specific lipid:cholesterol interactions shift the receptor conformational equilibrium toward the active/active-like states, stabilizing the complex the GHSR forms with its cognate Gq protein. In contrast, while low cholesterol levels favored arrestin recruitment through an interaction with the receptor transmembrane core, its C-terminus and the lipid bilayer, increasing the cholesterol-to-phospholipid ratio in the nanodiscs was associated with dissociation of β-arrestin1 from both the membrane and the receptor core, resulting in the formation of a tail-only engaged complex. Taken together, these data highlight the multifaceted role of membrane lipid composition as a possible modulator of the arrangement of the complex the GHSR forms with G proteins and β-arrestins, and thus as a regulator of GHSR selectivity in desensitization, endocytosis, and signaling.