Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Serum cholesterol level as a predictive biomarker for prognosis of Neuroblastoma.

BACKGROUND: Neuroblastoma (NB), a type of solid tumor in children, has a poor prognosis. Few blood biomarkers can accurately predict the prognosis, including recurrence and survival, in children with NB. In this study, we found that the serum total cholesterol (Tchol) level was associated with the prognosis of patients through a retrospective study. METHODS: Multivariate Cox regression model was used to identify the independent risk factors in the children with NB. Kaplan-Meier method was used to analyze the correlation between the common biomarkers, including the serum Tchol level, and the prognosis of the patients. ROC curves were used to predict the accuracy of the International Neuroblastoma Staging System (INSS) stage and Children's Oncology Group (COG) risk stratification after adding the serum Tchol level. RESULTS: Compared with the other patients, serum Tchol level was significantly increased in the relapsed and died patients (P < 0.05). Subsequently, serum Tchol level was found as an independent risk factor to affect the outcome of patients (P < 0.05). Finally, we added serum Tchol level into traditional stage and risk classification system to form the new INSS stage and COG risk classification system. It was found that the areas under the ROC curve (AUC) of recurrence-free survival in the new INSS stage and COG risk classification system were increased to 0.691 (95%CI: 0.535-0.847) and 0.748 (95%CI: 0.622-0.874), respectively. Moreover, the AUC areas of overall survival in the new INSS stage and COG risk classification system were increased to 0.722 (95%CI: 0.561-0.883) and 0.668 (95%CI: 0.496-0.819), respectively. CONCLUSION: We found that serum Tchol level, a clinical biomarker, is a risk factor for recurrence and death among the children with NB. The serum Tchol level could significantly increase the accuracy of the prediction for NB prognosis.

Effects of Serum Cholesterol on Severity of Stroke and Dosage of Statins on Functional Outcome in Acute Ischemic Stroke.

Background: A high dose of statin is used to obtain an intensive lipid-lowering in stroke patients, even in patients with normal lipid levels. There are limited data on effect of dosage of statins and functional outcome in stroke patients. Objectives: To compare serum cholesterol levels with severity of stroke measured by infarct volume. To compare functional outcome measured by mRS at day 90 with the dose of statin. Materials and Methods: This retrospective observational study was conducted in KMC Hospital Manipal, India between 2016 and 2018. Result: A total of 100 consecutive patients were included in the study, out of which 60 (60.0%) were males. Hyperlipidemia was present in 65 (65.0%) patients. On comparing the serum cholesterol levels with infarct volume using MRI, patients with low volume of ≤70 ml had higher mean serum total cholesterol concentration (223.83 mg/dl), whereas patients with high volume of >70 ml had low mean cholesterol level (218.70 mg/dl). The patients were divided into those who received low dose (≤20 mg) versus high dose (≥40 mg equivalent) of Atorvastatin. On comparing the mRS values at baseline and on day 90 with the dose of statins, patients who received a higher dosage had a statistically significant fall in mRS (p-0.045) at day 90. Conclusion: It was found that serum cholesterol levels were inversely related to the stroke severity. However, a higher the dose of statins resulted in better functional outcome and survival in post-stroke patients, possibly due to its neuroprotective effect.

Habitual low carbohydrate high fat diet compared with omnivorous, vegan, and vegetarian diets.

Background: Dietary patterns which exclude whole food groups, such as vegetarian, vegan and low carbohydrate high fat diet (LCHF), are increasingly popular in general public. When carefully planned, all these diets have some known benefits for health, but concerns are also raised in particular for LCHF. The quality of LCHF diet which individuals follow in real life without supervision is not known. Methods: One hundred thirty healthy individuals with stable body mass following LCHF, vegan, vegetarian and omnivorous diet for at least six months, were compared in a cross-sectional study. Diet was analyzed through 3-day food records and FFQ, anthropometric measurements were performed and serum metabolic biomarkers determined from fasting blood. Results: Participants on LCHF diet had the intakes of micronutrients comparable to other groups, while the intakes of macronutrients differed in line with the definition of each diet. The intakes of saturated fats, cholesterol and animal proteins were significantly higher and the intakes of sugars and dietary fibers were lower compared to other groups. Healthy eating index 2015 in this group was the lowest. There were no differences in the levels of glucose, triacylglycerols and CRP among groups. Total and LDL cholesterol levels were significantly higher in LCHF group, in particular in participants with higher ketogenic ratio. Fatty acids intakes and intakes of cholesterol, dietary fibers and animal proteins explained 40% of variance in total cholesterol level, with saturated fatty acids being the strongest positive predictor and monounsaturated fatty acids a negative predictor. Conclusion: None of the self-advised diets provided all the necessary nutrients in optimal levels. Due to the detected increased levels of serum cholesterols, selection of healthy fat sources, higher intake of dietary fibers and partial replacing of animal sources with plant sources of foods should be recommended to the individuals selecting LCFH dietary pattern.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04347213.

Prognostic Value for Perioperative Serum Total Cholesterol Level on Postoperative Long-Term Prognosis of Pancreatic Cancer: A Retrospective Clinical Study.

Cholesterol correlates with occurrence and progression of pancreatic cancer and has predictive value for postoperative prognosis in various cancers. Our study intended to reveal the relationship between perioperative serum total cholesterol (TC) level and postoperative prognosis of pancreatic cancer. We retrospectively analyzed the data of pancreatic cancer patients who underwent surgical treatment at our hospital from January 2015 to December 2021. ROC curves between serum TC level at each time point and 1-year survival rate were drawn, from which study object and optimal cutoff value was determined. Patients were divided into low and high-TC groups, and perioperative data and prognosis were compared. Risk factors for poor postoperative prognosis were identified by univariate and multivariate analysis. Overall survival rates at postoperative 1, 2 and 3 years in the low and high-TC groups were 52.9%, 29.4%, and 15.6% and 80.4%, 47.2%, and 33.8% (p = 0.005), respectively. Multivariate analysis confirmed tumor differentiation degree (RR = 2.054, 95% CI: 1.396-3.025), pTNM stage (RR = 1.595, 95% CI: 1.020-2.494), lymph node metastasis (RR = 1.693, 95% CI: 1.127-2.544), and postoperative 4-week serum TC level (RR = 0.663, 95% CI: 0.466-0.944) as independent risk factors for prognosis of pancreatic cancer. We conclude that postoperative 4-week serum TC level has certain predictive value for long-term postoperative prognosis of pancreatic cancer.

Blood group in relation to oral Fordyce's granules and serum cholesterol level.

BACKGROUND: The ABO and Rh systems are the most commonly used blood-group systems used to classify blood group globally. A number of studies have shown that ABO blood groups may be associated with an increased serum cholesterol levels which in turn may be related to the presence of oral Fordyce spots or granules. Oral Fordyce's granules are ectopic sebaceous glands within the oral cavity and are visible through epithelium. The aim of this study was to assess the relationship between ABO and Rhesus blood groups and the presence of oral Fordyce's granules and serum cholesterols level by gender. METHODS: Following ethical approval and informed consent, 124 subjects were recruited into this cross-sectional study. Clinical oral examination assessed the number of Fordyce's granules and blood samples were collected to determine the serum cholesterol and ABO/Rh blood-group systems of individual subjects. RESULTS: Blood group AB+ showed the highest mean of oral Fordyce's granules number and serum cholesterol level but this was not statistically significant compared to other blood groups. Female subjects in this study who were AB+ were had significantly higher serum cholesterol levels than males. CONCLUSION: This study indicates an association between ABO blood group, serum cholesterol level and mean number of oral Fordyce's granules. A larger sample size in a future study is required to ascertain whether number of Fordyce's granules is an important measure of serum cholesterol, but the study does show that for AB+ individuals, females may have higher serum cholesterol than males.

Urinary Neutrophil Gelatinase Associated Lipocalin: A Novel Biomarker Determining Steroid Responsiveness in Nephrotic Syndrome.

BACKGROUND: Urinary Neutrophil Gelatinase Associated Lipocalin (uNGAL) has been demonstrated to be a powerful marker of progression in chronic kidney disease. The present study was done to find out the ability of uNGAL as a biomarker to differentiate steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS) from each other. METHOD: The cross-sectional study included 45 patients with Idiopathic Nephrotic Syndrome (INS) (15 each of SSNS, SDNS, and SRNS). uNGAL was measured by ELISA. Demographic profile of patients with INS, lab parameters including Serum albumin, cholesterol, urinary albumin, creatinine, etc., were estimated using standard laboratory methods. Various statistical methods were used to assay the usefulness of NGAL as a diagnostic marker. RESULTS: Among the three groups, the median value of uNGAL was 8.68 ng/ml in SSNS, higher in SDNS (32.8 ng/ml), and highest in the SRNS group (50 ng/ml). The receiver operating curve (ROC) was generated for uNGAL to differentiate between SDNS and SSNS. Cut-off 13.26 ng/ml had a sensitivity of 86.7% and specificity of 97.4%, PPV 92.9%, and NPV 87.5 % with an area under the curve (AUC) of 0.958. Another ROC was generated for uNGAL to differentiate between SRNS and SDNS, and cut-off 40.02 ng/ml had a sensitivity of 80% and specificity of 86.7% with an AUC of 0.907. A similar result was observed when ROC was generated to differentiate SRNS from SSNS and SDNS combined. CONCLUSION: uNGAL can distinguish between SSNS, SDNS, and SRNS.

Detection of Porcine Deltacoronavirus RNA in the Upper and Lower Respiratory Tract and Biliary Fluid and the Effect of Infection on Serum Cholesterol Levels and Blood T Cell Population Frequencies in Gnotobiotic Piglets.

Porcine deltacoronavirus (PDCoV) was first identified approximately a decade ago, but much is still obscure in terms of its pathogenesis. We aimed to further characterize PDCoV infection by investigating the presence of virus in respiratory and biliary tissues or fluids; T cell population frequencies in blood; and altered serum cholesterol levels. Twelve, 6-day-old, gnotobiotic piglets were inoculated oronasally with PDCoV OH-FD22 (2.6 × 107 FFU/pig). Six control piglets were not inoculated. Rectal swab (RS), nasal swab (NS), nasal wash (NW), bronchoalveolar lavage (BAL), and biliary fluid (BF) samples were collected at 2, 4, and 7 days post-inoculation (DPI) and tested for PDCoV RNA by RT-qPCR. Blood T cell populations and serum cholesterol levels were determined by flow cytometry and a colorimetric assay, respectively. Moderate to high, and low to moderate titers of PDCoV RNA were detected in RS and in NS, NW, BAL, and BF samples, respectively, of inoculated piglets. There were trends toward decreased CD4+CD8-, CD4-CD8+, and CD4+CD8+ blood T cell frequencies in inoculated piglets. Furthermore, serum cholesterol levels were increased in inoculated piglets. Overall, we found that PDCoV infection does not exclusively involve the intestine, since the respiratory and biliary systems and cholesterol metabolism also can be affected.

The Prognostic Implications of Perioperative Serum Cholesterol Levels in Patients With Gastric Cancer.

BACKGROUND/AIM: Although cholesterol is an important indicator of nutritional status, it is also involved in cancer progression. In this study, we investigated the clinical significance of the dynamics of perioperative total cholesterol (T-Cho) levels in patients with gastric cancer (GC). PATIENTS AND METHODS: A total of 212 patients with pathological stage II/III disease who underwent gastrectomy between 2004 and 2020 were enrolled in this retrospective study. The preoperative and postoperative serum T-Cho levels were measured in these patients. RESULTS: Increased serum T-Cho levels were significantly correlated with low preoperative serum albumin levels (p<0.001). Patients with increased serum T-Cho levels after surgery had significantly lower overall and recurrence-free survival rates (p=0.030 and p=0.013, respectively; log-rank test). Cox proportional hazards model revealed that increased serum T-Cho levels (p=0.040), advanced pathological stage (p<0.001), and the provision of adjuvant chemotherapy (p=0.006) were independent prognostic factors for recurrence-free survival in patients with GC. CONCLUSION: Increased serum T-Cho levels after gastrectomy may be an independent prognostic factor in patients with GC.

Design, synthesis, in silico studies, and antidiabetic activity of several sulfanilamide incorporated 2,3-disubstitut-ed thiazolidin-4-ones

A panel of 2,3-disubstituted thiazolidin-4-ones 4a-n was synthesised from Schiff bases 3a-n derived from sulfanilamide, by reaction with thioglycolic acid. The compounds were characterised by means of IR, NMR, and Mass spectral data. Compounds 4a-n were screened for DPPH scavenging assay and compounds 4e, 4h, 4i, and 4n exhibited moderate activity. Compounds 4e, 4h, and 4i were tested at 200 mg/kg and 4e at 50 mg/kg b.w. orally for antidiabetic activity in fructose induced diabetic rats. They exhibited significant antidiabetic activity compared to the control group. Pioglitazone was used as a standard drug. The tested compounds exhibited better and ignificant serum cholesterol lowering activity when compared with the control and standard groups. They also reduced the triglyceride level after the 21st day; however, it was insignificant when compared to the control group. Compound 4n displayed the highest binding energy when docked with PPAR-γ followed by compounds 4e, 4h, and 4i when compared to pioglitazone. The physicochemical, drug likeness and ADME properties of the title compounds were found to be satisfactory.

Se sintetizó un panel de tiazolidinas-4-onas 2,3-disustituidas 4a-n a partir de las bases de Schiff 3a-n derivadas de la sulfanilamida por reacción con ácido tioglicólico. Los compuestos se caracterizaron por IR, RMN y datos espectrales de masa. Los compuestos 4a-n se analizaron para DPPH y los compuestos 4e, 4h, 4i y 4n mostraron una actividad moderada. Los compuestos 4e, 4h y 4i se probaron a 200 mg/kg y 4e a 50 mg/kg b.w. oralmente para la actividad antidiabética en ratas diabéticas, inducida por fructosa. Los compuestos mostraron una actividad antidiabética muy significativa en comparación con el grupo control. La pioglitazona se utilizó como fármaco estándar. Los compuestos ensayados mostraron una mejor y significativa actividad reductora del colesterol sérico en comparación con los grupos control y estándar. Estos compuestos también redujeron el nivel de triglicéridos después del 21° día, aunque fue insignificante en comparación con el grupo control. El compuesto 4n mostró la mayor afinidad de unión cuando se acopló a PPAR-γ, seguido de 4e, 4h y 4i en comparación con la pioglitazona. Las propiedades fisicoquímicas, la similitud con el fármaco y las propiedades ADME de los compuestos fueron satisfactorias, lo que los convierte en útiles agentes antidiabéticos.

Um painel de 2,3-disubstituído thiazolidina-4-ones 4a-n foram sintetizados a partir de bases Schiff 3a-n derivado da sulfanilamida por reacção com ácido tioglicólico. Os compostos eram caracterizado por IR, NMR e dados espectrais de massa. Os compostos 4a-n foram rastreados para O ensaio DPPH de limpeza radical e os compostos 4e, 4h, 4i e 4n exibiram actividade moderada. Os compostos 4e, 4h e 4i foram testados a 200 mg/kg e 4e a 50 mg/kg de peso corporal por via oral para antidiabéticos. actividade em ratos diabéticos induzidos por frutose. Exibiram uma actividade antidiabética altamente significativa actividade em comparação com o controlo. A pioglitazona foi utilizada como droga padrão. Os compostos testados exibiu uma melhor e significativa actividade de redução do colesterol sérico quando comparado comde triglicéridos após o 21° dia; no entanto, foi insignificante quando comparado com o controlo. O composto 4n mostrou a maior afinidade de ligação quando acoplado com PPAR-γ seguido de 4e, 4h, 4i quando comparado com pioglitazona. O propriedades físico-químicas, de semelhança com drogas e ADME dos compostos do título de propriedade também foram encontrados paraser satisfatórios, tornando-os agentes antidiabéticos úteis.

Is the cholesterol-perfluoroalkyl substance association confounded by dietary fiber intake?: a Bayesian analysis of NHANES data with adjustment for measurement error in fiber intake.

BACKGROUND: Serum concentrations of total cholesterol and related lipid measures have been associated with serum concentrations of per- and polyfluoroalkyl substances (PFAS) in humans, even among those with only background-level exposure to PFAS. Fiber is known to decrease serum cholesterol and a recent report based on National Health and Nutrition Examination Survey (NHANES) showed that PFAS and fiber are inversely associated. We hypothesized that confounding by dietary fiber may account for some of the association between cholesterol and PFAS. METHODS: We implemented a Bayesian correction for measurement error in estimated intake of dietary fiber to evaluate whether fiber confounds the cholesterol-PFAS association. The NHANES measure of diet, two 24-h recalls, allowed calculation of an estimate of the "true" long-term fiber intake for each subject. We fit models to the NHANES data on serum cholesterol and serum concentration of perfluorooctanoic acid (PFOA) and two other PFAS for 7,242 participants in NHANES. RESULTS: The Bayesian model, after adjustment for soluble fiber intake, suggested a decrease in the size of the coefficient for PFOA by 6.4% compared with the fiber-unadjusted model. CONCLUSIONS: The results indicated that the association of serum cholesterol with PFAS was not substantially confounded by fiber intake.

High-Molecular-Weight Dextran-Type Exopolysaccharide Produced by the Novel Apilactobacillus waqarii Improves Metabolic Syndrome: In Vitro and In Vivo Analyses.

Metabolic syndrome is a leading medical concern that affects one billion people worldwide. Metabolic syndrome is defined by a clustering of risk factors that predispose an individual to cardiovascular disease, diabetes and stroke. In recent years, the apparent role of the gut microbiota in metabolic syndrome has drawn attention to microbiome-engineered therapeutics. Specifically, lactic acid bacteria (LAB) harbors beneficial metabolic characteristics, including the production of exopolysaccharides and other microbial byproducts. We recently isolated a novel fructophilic lactic acid bacterium (FLAB), Apilactobacillus waqarii strain HBW1, from honeybee gut and found it produces a dextran-type exopolysaccharide (EPS). The objective of this study was to explore the therapeutic potential of the new dextran in relation to metabolic syndrome. Findings revealed the dextran's ability to improve the viability of damaged HT-29 intestinal epithelial cells and exhibit antioxidant properties. In vivo analyses demonstrated reductions in body weight gain and serum cholesterol levels in mice supplemented with the dextran, compared to control (5% and 17.2%, respectively). Additionally, blood glucose levels decreased by 16.26% following dextran supplementation, while increasing by 15.2% in non-treated mice. Overall, this study displays biotherapeutic potential of a novel EPS to improve metabolic syndrome and its individual components, warranting further investigation.

Association between Abnormal Serum Lipid Levels in Early Pregnancy and Development of Preeclampsia.

BACKGROUND: Accurate early biomarkers of oxidative stress, placenta perfusion and vascular resistance and endothelial platelet interaction for prediction of preeclampsia have not been shown to be beneficial for routine clinical use. The study of association between abnormal lipid levels in early pregnancy and preeclampsia is thus necessary in a bid to reduce the progression and severity of complications of preeclampsia. OBJECTIVE: To determine the association between abnormal lipid levels in early pregnancy and the development of preeclampsia. MATERIALS AND METHODS: A prospective longitudinal study involving 184 pregnant women with singleton pregnancy who met the inclusion criteria and recruited from the antenatal clinic at gestational age of < 20weeks. Their fasting blood samples were collected for the measurement serum lipid profile. They were monitored until delivery for the development of preeclampsia. The mean values of serum lipid profile were analyzed for association with pre-eclampsia using the statistical package for social sciences (SPSS) version 21.0 and P value of < 0.05 was considered statistically significant. RESULTS: Out of 184 participants, 3 had spontaneous miscarriage and were excluded while 5 were lost to follow up. This left a total of 176 participants who completed the study, 11 of which developed preeclampsia. There was a statistically significant increase in the levels of total cholesterol (TC) and low-density lipoprotein (LDL) in the preeclamptic group. The mean serum lipid levels were 4.8 mmol/L for total cholesterol, 1.87 mmol/L for total triglycerides, 1.3 mmol/L for high-density lipoprotein and 2.67 mmol/L for low-density lipoprotein. Age and parity also showed a causal association with development of preeclampsia. CONCLUSION: There was an association between elevated serum total cholesterol and low-density lipoprotein with development of preeclampsia later in pregnancy.

CONTEXTE: Les biomarqueurs précoces précis du stress oxydatif, de la perfusion et de la résistance vasculaire du placenta et de l'interaction endothéliale-plaquettaire pour la prédiction de la prééclampsie ne se sont pas révélés avantageux pour l'utilisation clinique courante. L'étude de l'association entre les taux anormaux de lipides en début de grossesse et la prééclampsie est donc nécessaire pour réduire la progression et la gravité des complications de la prééclampsie. OBJECTIF: Déterminer l'association entre des taux de lipides anormaux en début de grossesse et le développement de la pré- éclampsie. MATÉRIEL ET MÉTHODES: Une étude longitudinale prospective impliquant 184 femmes enceintes avec une grossesse unique qui répondaient aux critères d'inclusion et qui ont été recrutées à la clinique prénatale à l'âge gestationnel de < 20 semaines. Des échantillons de sang à jeun ont été prélevés pour mesurer le profil lipidique sérique. Elles ont été suivies jusqu'à l'accouchement pour le développement de la pré-éclampsie. Les valeurs moyennes du profil lipidique sérique ont été analysées pour leur association avec la pré-éclampsie à l'aide du progiciel statistique pour les sciences sociales (SPSS) version 21.0 et une valeur P de < 0,05 a été considérée comme statistiquement significative. RÉSULTATS: Sur les 184 participantes, 3 ont fait une fausse couche spontanée et ont été exclues, tandis que 5 ont été perdues de vue. Il restait donc un total de 176 participantes qui ont terminé l'étude, dont 11 ont développé une prééclampsie. On a constaté une augmentation statistiquement significative des taux de cholestérol total (CT) et de lipoprotéines de basse densité (LDL) dans le groupe prééclamptique. Les taux moyens de lipides sériques étaient de 4,8 mmol/L pour le cholestérol total, 1,87 mmol/L pour les triglycérides totaux, 1,3 mmol/L pour les lipoprotéines de haute densité et 2,67 mmol/L pour les lipoprotéines de basse densité. L'âge et la parité ont également montré une association causale avec le développement de la prééclampsie. CONCLUSION: Il y avait une association entre un taux élevé de cholestérol total sérique et de lipoprotéines de basse densité et le développement de la prééclampsie plus tard dans la grossesse. Mots clés: Association, Prééclampsie, Cholestérol sérique, Lipoprotéines de basse densité, Lipoprotéines de haute densité, Triglycérides, Lipides sériques.

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma.

Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients.

Impact of maternal dyslipidemia on infant neurodevelopment: The Japan Environment and Children's Study.

BACKGROUND: Various genetic and environmental influences have been studied for developmental disorders; however, the precise cause remains unknown. This study assessed the impact of maternal serum total cholesterol (TC) level in early pregnancy on early childhood neurodevelopment. METHODS: The fixed data of 31,797 singleton births from a large national birth cohort study that commenced in 2011 were used to identify developmental disorders as estimated by Ages and Stages Questionnaire, third edition (ASQ-3) scores of less than -2 standard deviations at 12 months of age. Multiple logistic regression analysis was employed to search for correlations between possibility of developmental disorders and maternal TC levels in early pregnancy classified into 4 groups based on quartile (Q1-Q4) values. RESULTS: After controlling for potential confounding factors in 27,836 participants who ultimately underwent multivariate analysis, we observed that elevated TC levels were significantly associated with a higher risk of screen positive status for communication (Q4: adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.05-1.37) and gross motor (aOR 1.13, 95% CI 1.03-1.25) ASQ-3 domain scores. CONCLUSION: This large nationwide survey revealed a possible deleterious effect of hypercholesterolemia in early pregnancy on infant neurodevelopment and age-appropriate skill acquisition at 12 months age.

Thalamo-hippocampal dysconnectivity is associated with serum cholesterol level in drug-naïve patients with first-episode schizophrenia.

Hippocampal deficits and metabolic dysregulations such as dyslipidemia have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. Hippocampus is particularly susceptible to environmental challenges including metabolism and inflammation. However, evidence linking hippocampal alterations and metabolic dysregulations are quite sparse in drug-naïve schizophrenia. A total of 166 drug-naïve patients with first-episode schizophrenia (FES) and 78 healthy controls (HC) underwent measures for several serum metabolic markers, structural and resting-state functional magnetic resonance imaging (rs-fMRI), as well as diffusion tensor imaging (DTI). Seed-to-voxel functional connectivity (FC) and probabilistic tractography were performed to assess the functional and microstructural connectivity of the bilateral hippocampi. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale (PANSS). Patients with FES showed significantly decreased total cholesterol (Chol) level. Patients showed elevated FC between the left hippocampus and bilateral thalami while showing decreased microstructural connectivity between the left hippocampus and bilateral thalami. Multiple regression analyses showed that FC from the left hippocampus to the right superior frontal gyrus (SFG), bilateral frontal pole (FP), and right thalamus were negatively associated with the Chol level, while no association was observed in the HC group. Our study validated alterations in both functional and microstructural thalamo-hippocampal connectivities, and abnormal cholesterol level in FES. Moreover, decreased cholesterol level is associated with elevated thalamo-hippocampal functional connectivity in patients with FES, suggesting that dyslipidemia may interact with the hippocampal dysfunction in FES.

Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis.

BACKGROUND: Despite substantial research highlighting the importance of exogenous dietary cholesterol intake and endogenous serum cholesterol level in human health, a thorough evaluation of the associations is lacking. Our study objective was to examine overall and cause-specific mortality in relation to dietary and serum cholesterol, as well as egg consumption, and conduct an updated meta-regression analysis of cohort studies. METHODS: We conducted a prospective analysis of 27 078 men in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). Multivariable-controlled cause-specific Cox proportional hazards regression models were used to calculate hazard ratios and 31-year absolute mortality risk differences. A systematic review and meta-analysis of cohort studies was also performed (PROSPERO [URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021272756]). RESULTS: Based on 482 316 person-years of follow-up, we identified 22 035 deaths, including 9110 deaths from cardiovascular disease (CVD). Greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Hazard ratios for each additional 300 mg cholesterol intake per day were 1.10 and 1.13 for overall and CVD-related mortality, respectively; for each additional 50-g egg consumed daily, hazard ratios were 1.06 and 1.09, respectively, for overall and CVD-related mortality (all P values<0.0001). After multivariable adjustment, higher serum total cholesterol concentrations were associated with increased risk of CVD-related mortality (hazard ratios per 1 SD increment, 1.14; P<0.0001). The observed associations were generally similar across cohort subgroups. The updated meta-analysis of cohort studies on the basis of 49 risk estimates, 3 601 401 participants, and 255 479 events showed consumption of 1 additional 50-g egg daily was associated with significantly increased CVD risk (pooled relative risk, 1.04 [95% CI, 1.00-1.08]; I2=80.1%). In the subgroup analysis of geographic regions (Pinteraction=0.02), an increase of 50-g egg consumed daily was associated with a higher risk of CVD in US cohorts (pooled relative risk, 1.08 [95% CI, 1.02-1.14]) and appeared related to a higher CVD risk in European cohorts with borderline significance (pooled relative risk, 1.05), but was not associated with CVD risk in Asian cohorts. CONCLUSIONS: In this prospective cohort study and updated meta-analysis, greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Our findings support restricted consumption of dietary cholesterol as a means to improve long-term health and longevity.

Association of serum cholesterol with Parkinson's disease in a cohort of statin-free individuals.

INTRODUCTION: The role of serum cholesterol in the pathogenesis of Parkinson's disease (PD) remains unclear. The objective of this study was to assess the association between serum cholesterol and PD in a cohort of statin-free newly diagnosed PD patients. METHODS: This retrospective study used fasting lipid profiles obtained from 672 consecutive statin-free newly diagnosed PD individuals and 540 controls. These PD individuals were identified from three medical institutions during 2017-2021, and the controls were identified from three physical examination centers during the same time period. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment of age, sex, and tobacco use history. RESULTS: Among 672 PD individuals, 112 were excluded in accordance with the current criteria, leaving 560 PD patients. The multivariate binary logistic regression analysis showed that LDL-C was the only variable contributing to the occurrence of PD (OR 1.39, 95% CI: 1.07-2.31, p < .001) after adjusting for age, sex, and tobacco use history; this association persisted following further adjustment for TC and HDL-C. In the subgroup analysis of the adjusted results of LDL-C after correcting for TC and HDL-C, lower LDL-C was associated with a higher risk of PD. CONCLUSION: Among selected populations of statin-free newly diagnosed PD individuals, low LDL-C might be associated with the occurrence of PD.

The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review.

Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.

An Oat ß-Glucan Beverage Reduces LDL Cholesterol and Cardiovascular Disease Risk in Men and Women with Borderline High Cholesterol: A Double-Blind, Randomized, Controlled Clinical Trial.

BACKGROUND: High-molecular-weight (MW) oat ß-glucan (OBG), consumed at 3-4 g/d, in solid foods reduces LDL cholesterol by a median of ∼6.5%. OBJECTIVES: We evaluated the effect of a beverage providing 3 g/d high-MW OBG on reduction of LDL cholesterol (primary endpoint) when compared with placebo. METHODS: We performed a parallel-design, randomized clinical trial at a contract research organization; participants, caregivers, and outcome assessors were blinded to treatment allocation. Participants with LDL cholesterol between 3.0 and 5.0 mmol/L, inclusive [n = 538 screened, n = 260 ineligible, n = 23 lost, n = 48 withdrawn (product safety); n = 207 randomly assigned, n = 7 dropped out, n = 9 withdrawn (protocol violation); n = 191 analyzed; n = 72 (37.7%) male, mean ± SD age: 43.3 ± 14.3 y, BMI: 29.7 ± 5.2 kg/m2], were randomly assigned to consume, 3 times daily for 4 wk, 1 g OBG (n = 104, n = 96 analyzed) or rice powder (Control, n = 103, n = 95 analyzed) mixed into 250 mL water. Treatment effects were assessed as change from baseline and differences analyzed using a 2-sided t test via ANOVA with baseline characteristics as covariates. RESULTS: After 4 wk, change from baseline least-squares-mean LDL cholesterol on OBG (-0.195 mmol/L) was less than on Control (0.012 mmol/L) by mean: 0.207 mmol/L (95% CI: 0.318, 0.096 mmol/L; P = 0.0003); the following secondary endpoints were also reduced as follows: total cholesterol (TC) (0.226 mmol/L; 95% CI: 0.361, 0.091 mmol/L; P = 0.001), TC:HDL cholesterol ratio (0.147; 95% CI: 0.284, 0.010; P = 0.036), non-HDL cholesterol (0.194 mmol/L; 95% CI: 0.314, 0.073 mmol/L; P = 0.002), and Framingham cardiovascular disease (CVD) risk (0.474; 95% CI: 0.900, 0.049, P = 0.029). Changes in HDL cholesterol, triglycerides, glucose, and insulin did not differ between treatment groups (P > 0.05). Lipid treatment effects were not significantly modified by age, sex, BMI, or hypertension treatment. There were no major adverse events, but both treatments transiently increased gastrointestinal symptoms. CONCLUSIONS: Consuming a beverage containing 1 g high-MW OBG 3 times daily for 4 wk significantly reduced LDL cholesterol by ∼6% and CVD risk by ∼8% in healthy adults with LDL cholesterol between 3 and 5 mmol/L.This trial was registered at clinicaltrials.gov as NCT03911427.