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We investigated the effect of the NaCl concentration (0.3–2M) on the structure and dynamics of hen egg yolk at room temperature and during thermal gelation at temperatures in the range of 66–90 °C utilizing low-dose x-ray photon correlation spectroscopy in ultra-small angle x-ray scattering geometry. With an increase in the salt concentration, we observe progressive structural and dynamic changes at room temperature, indicating the disruption of yolk components such as yolk-granules and yolk-plasma proteins. Temperature- and salt-dependent structural and dynamic investigations suggest a delay in the gel formation and aggregation of yolk low-density lipoproteins with increasing ionic strength. However, the time–temperature superposition relationship observed in all samples suggests an identical mechanism underlying protein aggregation–gelation with a temperature-dependent reaction rate. The sol–gel transition time extracted from kinetic and dynamic information follows Arrhenius's behavior, and the activation energy (460 kJ/mol) is found to be independent of the salt concentration. [ABSTRACT FROM AUTHOR]

Several computational studies on different water models reported evidence of a phase transition in supercooled conditions between two liquid states of water differing in density: the high-density liquid (HDL) and the low-density liquid (LDL). Yet, conclusive experimental evidence of the existence of a phase transition between the two liquid water phases could not be obtained due to fast crystallization in the region where the phase transition should occur. For the same reason, the investigation of possible transition mechanisms between the two phases is committed to computational investigations. In this work, we simulate an out-of-equilibrium temperature-induced transition from the LDL to the HDL-like state in the TIP4P/2005 water model. To structurally characterize the system relaxation, we use the node total communicability (NTC) we recently proposed as an effective order parameter to discriminate the two liquid phases differing in density. We find that the relaxation process is compatible with a spinodal-like scenario. We observe the formation of HDL-like domains in the LDL phase and we characterize their fluctuating behavior and subsequent coarsening and stabilization. Furthermore, we find that the formation of stable HDL-like domains is favored in the regions where the early formation of small patches of highly connected HDL-like molecules (i.e., with very high NTC values) is observed. Besides characterizing the LDL- to HDL-like relaxation from a structural point of view, these results also show that the NTC order parameter can serve as an early-time predictor of the regions from which the transition process initiates. [ABSTRACT FROM AUTHOR]

The bulk water density data are studied in a very large temperature–pressure range, from stable liquid to glass in the frame of water polymorphism. Because this thermodynamic variable evidences a crossover T*, above which the hydrogen bond (HB) is unable to arrange tetrahedral networks, the T-dependence of their isobars was considered. Such an analysis also shows pressure, P*, around which their thermal behaviors are completely different: concave below P* (with maxima and minima) and convex above (without extremes). Having ρ's measured values of the bimodal structures of the liquid phase, HDL (ρHDL), made of not-bonded monomers (ρNHB) and partially bonded dimers plus trimers (ρNHB), and LDL tetramers (ρLDL) the isobars of the relative distributions [W(P, T)] of the three species (WLDL, WPHB, and WNHB) have been evaluated. The results were studied by means of a logistic function (LF) that details the evolutions of the relative polpulations of the water LDL and HDL phases by decreasing T (for the isobars, in the range of 0.1–400 MPa). The LFs analysis obtained by proposing a full connection between liquid water from its supercooled metastable phase to the stable up to the boiling temperature identifies the Widom line quite satisfactorily and fully supports the presence of the liquid–liquid critical point in the deep supercooled region, located at about 190 K and in the range 200 > P > 180 MPa. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the intricate relationship between serum metabolomics and lifestyle factors, shedding light on their impact on health in the context of breast cancer risk. Detailed metabolic profiles of 2283 female participants in the Trøndelag Health Study (HUNT study) were obtained through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). We show that lifestyle-related variables can explain up to 30% of the variance in individual metabolites. Age and obesity were the primary factors affecting the serum metabolic profile, both associated with increased levels of triglyceride-rich very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), amino acids and glycolysis-related metabolites, and decreased levels of high-density lipoproteins (HDL). Moreover, factors like hormonal changes associated with menstruation and contraceptive use or education level influence the metabolite levels. Participants were clustered into three distinct clusters based on lifestyle-related factors, revealing metabolic similarities between obese and older individuals, despite diverse lifestyle factors, suggesting accelerated metabolic aging with obesity. Our results show that metabolic associations to cancer risk may partly be explained by modifiable lifestyle factors. Lifestyle-related factors account for up to 30% of serum metabolic variance, with age and obesity as key factors. Metabolic similarities in obese and older women suggest that modifiable lifestyle factors may affect breast cancer risk. [ABSTRACT FROM AUTHOR]

Excess cholesterol accumulation induces the accumulation of foam cells, eventually accelerating atherosclerosis progress. Historically, the mechanisms of macrophage-derived foam cells have attracted attention because of their central role in plaque development, which was challenged by lineage tracing in union with single-cell sequencing (sc-seq). Accumulated studies have uncovered how vascular smooth muscle cells (VSMCs) proliferate and migrate to the vascular intima and accumulate, then transform into foam cells induced by surplus lipids, finally accounting for 30% to 70% of the total foam cells within the plaque of both mice and humans. Therefore, the mechanisms of VSMC-derived foam cells have received increasing attention. The review intends to summarize the transformation mechanism of VSMCs into foam cells induced by oxidized low-density lipoproteins (ox-LDL) in atherosclerosis. [ABSTRACT FROM AUTHOR]

Iron overload results in lipid peroxidation (LPO) and the oxidative modification of circulating lipoproteins, which contributes to cardiovascular complications in patients with β-thalassemia. Investigating LPO may provide opportunities for the development of novel therapeutic strategies; however, the chemical pathways underlying iron overload-induced LPO in β-thalassemia lipoproteins remain unclear. In this study, we identified various species of lipid radicals (L•), the key mediators of LPO, and oxidized cholesteryl esters (oxCE) derived from the in vitro oxidation of major core lipids, cholesteryl linoleate (CE18:2) and cholesteryl arachidonate (CE20:4); the levels of these radical products in low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were measured and compared between β-thalassemia patients and healthy subjects by using a specific fluorescent probe for L• with a liquid chromatography-tandem mass spectrometric method. Our results demonstrated that iron overload substantially decreased the levels of CE18:2 and CE20:4 substrates and α-tocopherol, resulting in higher levels of full-length and short-chain truncated L• and oxCE products. In particular, CE epoxyallyl radicals (•CE-O) were observed in the lipoproteins of β-thalassemia, revealing the pathological roles of iron overload in the progression of LPO. In addition, we found that intermission for two weeks of iron chelators can increase the production of these oxidized products; therefore, suggesting the beneficial effects of iron chelators in preventing LPO progression. In conclusion, our findings partly revealed the primary chemical pathway by which the LPO of circulating lipoproteins is influenced by iron overload and affected by iron chelation therapy. Moreover, we found that •CE + O shows potential as a sensitive biomarker for monitoring LPO in individuals with β-thalassemia. [Display omitted] • Iron overload results in the production of various lipid radicals and oxidized cholesteryl esters species in lipoproteins. • Short-term intermission of iron chelators significantly increases the level of iron-dependent lipid peroxidation products. • CE epoxyallyl radicals (•CE-O) show potential as new biomarkers for monitoring lipid peroxidation in β-thalassemia. [ABSTRACT FROM AUTHOR]

This review focuses on the epigenetic factors that play a vital role in the formation of plaques and lead to atherosclerosis and related diseases in humans during current times. Apart from the epigenetics there are plenty more factors that influence the atherosclerotic risk in the older population of the current era. Lack of physical activities has become one of the most commonly found traits that causes obesity in people especially the middles aged adults. People working 9 - 5 in an office, or an IT firm tend spend idle time with their computer for 4 - 5 consecutive hours with barely changing their position. Lack of exercise tends to affect not only the physical health but also stress a person mentally. Chronic inflammatory diseases like atherosclerosis have a major role in the morbidity and mortality from cardiovascular disease worldwide. Atherosclerotic plaques are created by the pathophysiological process of lipids, inflammatory cells and fibrous components gradually accumulating within artery walls. Endothelial dysfunction signals the start of atherosclerosis and allows low-density lipoproteins (LDL) to enter the subendothelial region. Oxidative stress-induced changes in retained low-density lipoprotein (LDL) set off an inflammatory cascade that draws T cells and monocytes to the site of the lesion. The interaction of these immune cells with the local vascular cells encourages the production of foam cells, which fills the plaque's centre with lipids. Smooth muscle cells multiply and help produce fibrous caps as the lesion ages, which affects the stability of the plaque. Studies shows how the brain responds to physical labour and how differently the effectively the enzymes and hormones are secreted, and their actions are vastly guided based on the physical stress an individual undergoes. Among the most prominent causes of atherosclerosis epigenetics has been focused majorly in this review, where we focus on the underlying genetic factors that play a vital role in atherosclerosis and related cardiovascular diseases and also the genetic approach to a treatment is also elaborated. A number of miRNAs are involved in the cause/cure for the atherosclerosis, the following tables give an outlook regarding the same. This review aims to focus on the causes, risk factors, pathophysiology and the treatment and therapies that are currently available all the way concentrating on the genetic approach in the above-mentioned perspective. [ABSTRACT FROM AUTHOR]

Context Polyphenols are plant-based compounds with potential anti-inflammatory, antioxidant, and anti-obesogenic properties. However, their effects on health outcomes remain unclear. Objective To evaluate the effects of polyphenols on anthropometric and cardiometabolic markers. Data Sources Six electronic databases—namely, EMBASE, CINAHL, PubMed, Scopus, The Cochrane Library (reviews only), and Web of Science—were searched for relevant systematic reviews with meta-analyses (SRMAs). Data Extraction Three reviewers performed the data extraction via a data-extraction Microsoft Excel spreadsheet. Data Analysis An umbrella review and meta-analysis of existing SRMAs was conducted. Eighteen SRMAs published from 2015 to 2023, representing 445 primary studies and 838 unique effect sizes, were identified. Meta-analyses were conducted using random-effects models with general inverse variance. Polyphenol-containing foods were found to significantly improve weight (-0.36 kg; 95% confidence interval [CI]: −0.62, 0.77 kg; P  < 0.01, I 2 = 64.9%), body mass index (−0.25 kg/m2; 95% CI: −0.34, −0.17 kg/m2; P  < 0.001, I 2 = 82.4%), waist circumference (−0.74 cm; 95% CI: −1.34, −0.15 cm; P  < 0.01, I 2 = 99.3%), low-density-lipoprotein cholesterol (−1.75 mg/dL; 95% CI: −2.56, −0.94; P  < 0.001, I 2 = 98.6%), total cholesterol (−1.23 mg/dL; 95% CI: −2.00, −0.46; P  = 0.002, I 2 = 94.6%), systolic blood pressure (−1.77 mmHg; 95% CI: −1.77, −0.93 mmHg; P  < 0.001, I 2 = 72.4%), diastolic blood pressure (−1.45 mmHg; 95% CI: −2.09, −0.80 mmHg; P  < 0.001, I 2 = 61.0%), fat percentage (−0.70%; 95% CI: −1.03, −0.36%; P  < 0.001, I 2 = 52.6%), fasting blood glucose (−0.18 mg/dL; 95% CI: −0.35, −0.01 mg/dL; P  = 0.04, I 2 = 62.0%), and C-reactive protein (CRP; including high-sensitivity-CRP [hs-CRP]) (−0.2972 mg/dL; 95% CI: −0.52, −0.08 mg/dL; P  = 0.01, I 2 = 87.9%). No significant changes were found for high-density-lipoprotein cholesterol (−0.12 mg/dL; 95% CI: −1.44, 0.69; P  = 0.67, I 2 = 89.4%) and triglycerides (−1.29 mg/dL; 95% CI: −2.74, 0.16; P  = 0.08, I 2 = 85.4%). Between-study heterogeneity could be explained by polyphenol subclass differences. Conclusion The findings of this umbrella review support the beneficial effects of polyphenols on anthropometric and metabolic markers, but discretion is warranted to determine the clinical significance of the magnitude of the biomarker improvements. Systematic Review Registration International Prospective Register of Systematic Reviews no. CRD42023420206. [ABSTRACT FROM AUTHOR]

Summary: Background: Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non‐alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo‐Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie‐restricted diet (CRD) in Indian overweight children and adolescents with biopsy‐proven NAFLD. Methods: Thirty‐nine consecutive biopsy‐proven NAFLD children between the ages of 8 and 18 years were randomized into either IMD or CRD for 180 days, and various parameters were evaluated at baseline and then after 180 days (NCT05073588). Results: A total of 34 subjects (18 in IMD and 16 in CRD group) completed the study. There was a significantly higher decrease in controlled attenuation parameter (CAP) values (as a marker of hepatic steatosis; on transient elastography) (95% CI: 4.2–73.4, p = 0.042), weight (95% CI: 0.75–5.5, p = 0.046) and body mass index (BMI) (95% CI: 0.21–2.05, p = 0.014) (but not in Pediatric NAFLD Fibrosis Index or PNFI; as a marker of hepatic fibrosis) in IMD group compared to the CRD group. Liver stiffness measurement, serum cholesterol and low‐density lipoprotein levels and HOMA‐IR decreased only in the IMD group (p < 0.001). Our statistical model showed that delta‐Weight was the only independent variable associated with delta‐CAP. Conclusion: Both IMD and CRD can improve the various anthropometric, clinical, imaging and biochemical parameters but IMD was superior to CRD in terms of reducing CAP values and weight/BMI over 180 days in overweight/obese NAFLD children. [ABSTRACT FROM AUTHOR]

This prospective cohort study evaluated the efficacy of omega-3 fatty acid supplementation on arteriovenous fistula patency and systemic inflammation in 220 hemodialysis patients undergoing ultrasound and digital subtraction angiography-guided balloon dilation. The participants were randomized into an intervention group receiving 2,000 mg of omega-3 fatty acids daily and a placebo group. The primary outcome measures were arteriovenous fistula patency at 12- and 24-months post- dilation, while secondary outcomes included thrombosis incidence, changes in inflammatory markers (c-reactive protein and interleukin-6), lipid profiles, and health-related quality of life (HRQoL). Results indicated a significant improvement in arteriovenous fistula patency in the omega-3 group at 24 months (80.9 vs. 68.2%, P < 0.05). Additionally, there was a significant reduction in thrombosis rates (7.3 vs. 16.4%, P < 0.05) and inflammatory markers (c-reactive protein and interleukin-6) in the omega-3 group compared to the placebo. Lipid profile analysis showed a decrease in total cholesterol and low-density lipoprotein levels with omega-3 supplementation, with significant changes at 12 months (P < 0.05). HRQoL scores also improved significantly in the omega-3 group at both 12 and 24 months (P < 0.05). These findings suggest that omega-3 fatty acids can enhance arteriovenous fistula functionality and reduce cardiovascular risk factors in hemodialysis patients. And its integration into standard care protocols for patients with arteriovenous fistulas would improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents. [ABSTRACT FROM AUTHOR]

Label distribution learning(LDL) has been received widespread attention as an effective learning paradigm in the field of data mining. However, existing feature selection algorithms for LDL are performed under static conditions or semi-dynamic conditions, and the dynamic information of data is not considered sufficiently. To address these issues, a feature selection algorithm for LDL under dynamic conditions is proposed, which takes full use of dynamic information from data. Specially, a novel rough set model called F-double-fuzzy rough set is created to handle dynamic LDL data, which is extended from F-fuzzy rough set. Then, F-fuzzy-condition entropy is defined to fuse information together in F-double-fuzzy rough set, which is considered as a measure for feature selection. Thirdly, a dynamic feature selection algorithm for LDL is proposed with the F-fuzzy-condition entropy. Fourthly, a novel method of covering set is proposed to simulate dynamic LDL data, and its merits are explained intuitively. At last, experiments on 14 datasets with six widely used metrics demonstrate that the performance of the proposed algorithm has advantages over the state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is the root cause of numerous chronic conditions, leading to high mortality rates around the globe. Spirulina (Arthrospira platensis) microalgae serve as a promising reservoir of bioactive compounds with diverse pharmacological properties. The current study examined the nutritional profile of spirulina powder in relation to strict glycemic control, specifically focusing on its potential to lower lipid levels. In an in vivo investigation, normal healthy male Wistar albino rats (n = 60) were divided into two groups: a negative control group (NC) of ten rats and a high-fat diet group (n = 50) that were fed a cholesterol-rich diet until their cholesterol levels reached or exceeded 250 mg/dL. Subsequently, the hypercholesterolemic rats were then randomly allocated to several treatment groups: a positive control (PC); a standard treatment diet (STD) involving fenofibrate at a dose of 20 mg/kg body weight; and three experimental groups (T1, T2, and T3) that received spirulina powder supplementation at doses of 300, 600, and 900 mg per kg body weight, respectively, for the period of 12 weeks. Blood samples were analyzed for oxidative stress biomarkers, insulin levels, lipid profiles, liver function, and expression of gene levels in the diabetogenic pathway. The study utilized spectrophotometric colorimetric methods to identify oxidative stress biomarkers, serum kit methods to measure lipid profiles and liver enzymes, and the assessment of qPCR for mRNA quantity. According to the research findings, spirulina powder has certain noteworthy features. It had the greatest quantity of chlorogenic acid (4052.90 µg/g) among seven phenolics and two flavonoid compounds obtained by HPLC-UV analysis. Furthermore, the proximate analysis demonstrated that spirulina is high in protein (16.45 ± 0.8%) and has a significant energy yield of 269.51 K-calories per 100 g. A maximal spirulina dose of 900 mg/kg/wt significantly lowered oxidative stress, cholesterol, triglyceride, low-density lipoproteins (LDL), and insulin levels (p ≤ 0.05). In contrast, high-density lipoprotein (HDL) and total antioxidant capacity (TAC) levels increased significantly (p ≤ 0.05) compared to all other groups, except the NC group. The study provides remarkable proof about the pharmacological impact of spirulina powders. Significant reductions (p ≤ 0.05) in liver enzymes {alanine aminotransferase (ALT) and aspartate aminotransferase (AST)} were observed across all treatment groups, with the exception of the NC, compared to the positive control. The treatment groups had significantly greater gene expression levels of INS-1, PDX-1, IGF-1, and GLUT-2 than the positive control group (p ≤ 0.05). These findings highlight spirulina's potential as a long-term regulator of hyperglycemia in rat models with induced hyperlipidemia, owing to its phenolic bioactive components that serve as antioxidants. [ABSTRACT FROM AUTHOR]

This study examined the effect of succinylation on protein oxidation–aggregation and the formation of off-flavors in heated egg yolks (EYs). The sensory evaluation, content of volatile compounds, stability of low-density lipoprotein (LDL) particles, and oxidation of lipid and protein at six levels of succinylated EY (0.25%, 0.5%, 1%, 2%, 5%, and 10%, w/w) were determined. The results showed that the succinylated thermal EY's concentration of volatiles and off-flavors was reduced. Oil exudation and lipid and protein oxidation decreased with the improved succinylation degree. Succinylation also reduced the LDL particle size and changed the secondary structure (decreased the β-sheets and increased the α-helices) of protein in LDL particles. Meanwhile, succinylation could effectively change the thermal oxidation–aggregation of LDL protein by introducing succinyl groups with negative charges, thus increasing the stability of LDL particles in succinylated EY during heating. These results further revealed the relationship between the oxidation–aggregation of LDL and the formation of off-flavors in heated EY. These results also help improve the flavor quality of heat-treated EY and expands the application scope of egg products. [ABSTRACT FROM AUTHOR]

Background: Central obesity is a well-recognized risk factor for diabetes, yet the potential role of lipids in the diabetes risk associated with central obesity remains unclear. This study aimed to explore the possible mediating role of 11 lipid parameters [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), remnant cholesterol (RC), and ratios of Non-HDL-C/HDL-C, RC/HDL-C, LDL/HDL-C, TG/HDL-C, TC/HDL-C] in the association of central obesity with diabetes risk. Methods: We utilized data from 15,453 participants in the NAGALA longitudinal cohort to assess the association of baseline central obesity indicators [waist-height ratio (WHtR), waist circumference (WC)] and the 11 lipid parameters with diabetes risk. Mediation analysis models were constructed to explore the mediating role of lipid parameters in the association of WC/WHtR with diabetes. Results: Confirmatory associative analysis using multivariable Cox regression showed that, except for Non-HDL-C, TC and LD-C, the remaining eight lipid parameters were significantly associated with WC/WHtR and diabetes risk. Mediation analysis indicated that TG, RC, HDL-C, and lipid ratios such as Non-HDL-C/HDL-C ratio, RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio and LDL/HDL-C ratio are potential lipids affecting the diabetes risk related to central obesity. Among these, the RC/HDL-C ratio seemed to contribute the most in the WC/WHtR-related diabetes risk association, with a mediation percentage of about 37%. Additionally, lipid ratio parameters appeared to play a more mediating role in the association of central obesity-related diabetes risk than individual lipids. Conclusions: In central obesity-related diabetes risk, most lipids, especially lipid ratio parameters, play a significant mediating role. Given these findings, we advocate for increased efforts in multifactorial risk monitoring and joint management of diabetes. The evaluation of lipids, particularly lipid ratio parameters, may be holds substantial value in the prevention and management of diabetes risk under close monitoring of central obesity. [ABSTRACT FROM AUTHOR]

Introduction: Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this. Methods: This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily. Results: After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness. Conclusion: This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known. [ABSTRACT FROM AUTHOR]

Purpose: This research employed Mendelian randomization (MR) methods to explore whether metabolites are causally associated with embolic stroke of undetermined source (ESUS). Methods: Genome-Wide Association Study (GWAS) data regarding metabolites and ESUS were downloaded from the database. Metabolites were employed as exposure factors, ESUS served as the outcome variable, and single nucleotide polymorphisms (SNPs) exhibiting significant association with ESUS were chosen as instrumental variables. The causal association between exposure factor metabolites and the outcome variable ESUS was assessed using two methods: MR-Egger regression and inverse variance-weighted (IVW) analysis. Results: A causal relationship was observed between X-11593--Omethylascorbate* and ESUS, indicating a protective factor. Moreover, a causal relationship was identified between cholesterol esters in large very-low-density lipoprotein (VLDL), cholesterol esters in medium low-density lipoprotein (LDL), concentration of medium LDL particles, phospholipids in medium LDL, phenylalanine, total cholesterol in small LDL, total lipids in medium LDL and ESUS, representing risk factor. Funnel plots exhibited a symmetrical distribution of SNPs, while pleiotropic tests (p > 0.05) and leave-one-out tests indicated that the results were relatively stable. Conclusion: Metabolites are causally associated with ESUS. LDL and VLDLrelated metabolites are identified as risk factors for ESUS. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. Method: This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a 'sequential feature selector' and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs' scores to determine the importance of the original variables in contracting COVID-19. Results: HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. Conclusion: The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) remain a malignancy with incompletely understood risk factors. To address this knowledge gap, we employed mendelian randomization study to investigate potential protective and risk elements associated with endometrial cancer. Methods: We conducted a two-sample Mendelian randomization (MR) study using genetic association data for overall EC and its subtypes from a large-scale genome-wide association study (GWAS). This GWAS encompassed 12,906 EC patients and 108,979 healthy controls. The EC cases were further categorized into 8758 endometrioid and 1230 non-endometrioid subtypes. To serve as instrumental variables, we identified independent genetic variants strongly associated with 5 lifestyle factors and 14 metabolic factors from relevant GWASs. Subsequently, we conducted univariable Mendelian randomization (MR) analyses. Results: Our study revealed the relationship among EC with lifetime smoking index (OR: 1.43; 95% CI 1.05–1.96), frequency of alcohol consumption (OR:1.23; 95% CI 1.04–1.45), body mass index (BMI) (OR:1.82; 95% CI 1.64–2.01), type 2 diabetes mellitus (T2DM) (OR:1.06; 95% CI 1.00–1.12), and fasting insulin (OR:1.97; 95% CI 1.30–2.98). Conversely, inverse associations with EC were observed for education level (OR:0.72, 95% CI 0.62–0.83), moderate-level physical exercise (OR 0.35, 95% CI 0.15–0.84), and low-density lipoproteins (LDL) (OR 0.91, 95% CI 0.84–0.99). Conclusions: Our findings underscore a causal association between genetically predicted lifetime smoking index, alcohol intake frequency, BMI, T2DM, and fasting insulin with EC risk. Furthermore, our study highlights the potential protective effects of a high education level, moderate-intensity physical exercise, and LDL reduction against EC risk. This MR analysis provided valuable insights into underlying EC risk mechanisms and paved new ways for EC prevention strategies. [ABSTRACT FROM AUTHOR]

Aims: The association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis. Methods and results: Wild type (WT), PCSK9−/−, and LDLR−/− C57BL/6 mice were used in this study. Eleven week-old male mice were fed high-fat diet (HFD) for 12 weeks or kept on normal diet until old age (22-months). Cardiac function was assessed by ultrasound, cholesterol was quantified with a colorimetric kit and circulating EVs were measured using flow cytometry. Plaques were analysed post-mortem using Oil-Red-O staining of the aortic arch. EVs were measured from platelet free blood plasma samples of normal and hypercholesterolaemic clinical patients. Based on annexin V and CD63 staining, we found a significant increase in EV levels in LDLR−/− and PCSK9−/− mice after HFD, but CD81 showed no significant change in either group. There was no significant change in plaque formation after HFD. PCSK9−/− mice show a favourable cardiac function after HFD. Blood cholesterol levels progressively increased during HFD, with LDLR−/− mice showing high levels while PCSK9−/− were significantly lowered compared to WT animals. In mice at old age, similar cholesterol levels were observed as in young mice. In old age, LDLR−/− mice showed significantly increased plaques. At old age, ejection fraction was decreased in all groups of mice, as were CD63+ EVs. Similarly to mice, in patients with hypercholesterolaemia, CD63+ EVs were significantly depleted. Conclusions: This research demonstrates an inverse relationship between circulating EVs and cholesterol, making EVs a potential marker for cardiovascular disease (CVD). HFD causes reduced cardiac function, but atherosclerotic development is slowly progressing in hypercholesterolaemic models and only observed with old animals. These results also bring further evidence for the benefit of using of PCSK9 inhibitors as therapeutic agents in CVD. [ABSTRACT FROM AUTHOR]

Background: Sinetrol® Xpur is a polyphenolic ingredient rich in citrus flavonoids that has shown weight loss effects in previous studies. The dose dependent nature, gut microbial actions of this product has not been explored previously, thus presented in this study. Methods: In this open label study, we evaluated the effect of Sinetrol® Xpur supplementation on healthy but overweight/obese adults (20–50 yrs) for 16 weeks. Participants (n = 20) were randomly allocated to a high dose group (HD, 1800 mg/day) or low dose group (LD, 900 mg/day) of the product for 16 weeks. Fat composition, gut microbial composition, were evaluated using MRI and 16S rDNA sequencing respectively at week 1 and 16. Results: We observed HDL, HbA1C, LDL and leptin improved significantly over 16 weeks, irrespective of the dosage. There was a trend for decrease in visceral adipose tissue (VAT), BMI over time and body weight displayed a trend for dose dependent decrease. Eubacterium xylanophilum, Ruminococcacea UCG-004 genus which increased in HD and LD respectively were negatively associated to VAT. Both doses increased butyrate producers such as Eubacterium ruminantium and Ruminococcaceae NK4A214 genus. Conclusions: Overall chronic supplementation of Sinetrol® Xpur, irrespective of their dose improved HDL, HbA1c, LDL and leptin and tended to decrease visceral adipose tissue via changes in gut microbiota. Trial registration number NCT03823196. [ABSTRACT FROM AUTHOR]

Background/objectives: Considering the diverse symptomatology of COVID-19—ranging from mild to severe cases—multi-professional interventions are crucial for enhancing physical recovery, nutritional status, and mental health outcomes in affected patients. Thus, this study aimed to investigate the effects of such an intervention on health-related physical fitness and biomarkers in overweight COVID-19 survivors with varying degrees of symptom severity after 8 weeks and 16 weeks. Methods: This non-randomized clinical trial included 59 overweight COVID-19 survivors (32 males and 27 females) divided into three groups: mild (n = 31), moderate (n = 13), and severe/critical (n = 15). The participants underwent a multi-professional program and were assessed for anthropometric and body composition (primary outcome), as well as physical fitness and biochemical markers (secondary outcome) 8 and 16 weeks before the intervention. Results: After 8 weeks, time effects were observed for the maximum isometric handgrip strength (p < 0.001), maximum isometric lumbar-traction strength (p = 0.01), flexibility (p < 0.001), abdominal strength–endurance (p < 0.001), the sit-and-stand test (p < 0.001), maximum oxygen consumption (p < 0.001), and distance covered in the 6 min walk test (p < 0.001). Additionally, time effects were also observed for fat mass (p = 0.03), body fat percentage (p = 0.02), abdominal circumference (p = 0.01), total cholesterol (p < 0.001), low-density lipoproteins (p < 0.001), and glycated hemoglobin (p < 0.001), with lower values after multi-professional interventions. After 16 weeks, the systolic and diastolic blood pressure showed significant reductions independently of the intervention group (p < 0.001). Conclusion: These findings suggest that multi-professional interventions can provide substantial benefits for post-COVID-19 patients, regardless of the severity of their initial symptoms. [ABSTRACT FROM AUTHOR]

The article in the National Science Review explores the relationship between cord blood ceramides and childhood metabolic health. The study analyzes sphingolipidome in umbilical cord blood to identify functional sphingolipids associated with birth weight. The research suggests that cord blood ceramides, particularly those with medium to very long fatty acyl chains, are linked to unhealthy birth weights. Additionally, the study demonstrates the predictive potential of cord blood ceramides for childhood metabolic health, highlighting the importance of monitoring and potentially adjusting intrauterine fetal growth to optimize long-term metabolic outcomes. [Extracted from the article]

Introduction: Maternal overweight or obesity has been associated with metabolic syndrome through 1 year postpartum, but it remains unknown whether a culturally-modified, motivationally-targeted, and individually-tailored Lifestyle Intervention could improve postpartum cardiometabolic health among Hispanic women with overweight or obesity. Methods: Proyecto Mamá was a randomized controlled trial conducted in Western Massachusetts from 2014 to 2020 in which Hispanic women with overweight/obesity were randomized to a Lifestyle Intervention (LI) involving diet and exercise or to a comparison Health and Wellness Intervention (HW). Biomarkers of cardiovascular risk (i.e., lipids, C-reactive protein) and insulin resistance (fasting insulin, glucose, HbA1c, homeostasis model assessment [HOMA-IR], leptin, adiponectin) were measured at baseline (early pregnancy), mid-pregnancy, and 6 weeks, 6 months, and 12 months postpartum. Generalized linear mixed effect models were used to evaluate differences in the change in biomarkers over the course of postpartum follow-up time. Results: In intent-to-treat analyses among eligible women (LI; n=51, HW; n=58) there were no significant differences in changes in biomarkers of CVD risk or insulin resistance over the postpartum year; for example, the intervention effect for total cholesterol was 6.98 (SE: 6.36, p=0.27) and for HbA1c was −0.01 (SE: 0.4, p=0.85). In pooled analyses, regardless of intervention arm, women who participated in any vigorous activity had less of an increase in HbA1c (intervention effect = −0.17, SE: 0.05, p=0.002) compared to those with no vigorous activity, and similarly beneficial associations with other cardiovascular risk biomarkers (p<0.05). Discussion: Women who participated in vigorous activity, regardless of their assigned intervention arm, had more favorable changes in biomarkers of insulin resistance. Significance: Women with overweight/obesity during pregnancy are at an increased risk of adverse cardiometabolic profiles and future development of type 2 diabetes and cardiovascular disease. Hispanic women are disproportionately affected by cardiometabolic disorders but have largely been excluded from lifestyle intervention studies. Although providing a lifestyle intervention to Hispanic women with overweight/obesity resulted in no significant differences in postpartum cardiometabolic biomarkers, women who articipated in vigorous activity, regardless of their assigned intervention arm, had favorable changes in insulin resistance biomarkers. These findings suggest that the intensity of physical activity may be important for improving postpartum cardiometabolic biomarkers among high-risk, Hispanic women. [ABSTRACT FROM AUTHOR]

Background: Breastfeeding provides benefits for both mothers and babies. However, many women experience postpartum weight gain, unfavorable lipid profiles, and other postpartum problems that can adversely impact their overall quality of life (QoL). Objective: To examine the effect of adding aerobic and resistive exercise to faradic stimulation and nutritional counseling on lipid profile and QoL in overweight breastfeeding women. Subjects and Methods: Fifty‐four breastfeeding women were randomly allocated into two equally sized groups. Group A underwent abdominal faradic stimulation along with nutritional counseling for 12 weeks, whereas Group B received identical faradic stimulation and nutritional counseling and engaged in a combined aerobic and resistive exercise program for the same duration. Before and after treatment, the following anthropometric measurements were evaluated: body mass index (BMI), waist‐to‐hip ratio (W/H); lipid profile analysis, such as high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and triglycerides (TG); and the Short Form 36 Health Survey Questionnaire (SF‐36). Results: All outcome measures demonstrated significant improvements within the two groups (p < 0.05). Group B showed more significant reductions in BMI, W/H ratio, and LDL, along with greater significant increases in the SF‐36 domain scores for physical functioning, physical health problems, bodily pain, general health, energy/fatigue, social activity, mental health, and the total SF‐36 score (p < 0.05) compared to group A post‐treatment. However, there were no significant differences in HDL, TG, and the score of the emotional wellbeing domain of the SF‐36 between the groups after treatment (p > 0.05). Conclusion: 12‐week aerobic and resistive exercise is effective in reducing the BMI, W/H ratio, and LDL levels and enhancing the QoL in overweight breastfeeding women. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE−/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE−/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis. [ABSTRACT FROM AUTHOR]

In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechanisms of these processes in human umbilical vein endothelial cells (HUVECs) are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls. As shown by RQ-MSP, the upstream DNA methylation level of the miR-520e promoter region was considerably increased in ACS patients. miR-520e was markedly downregulated in ACS patients compared with healthy controls. In the oxidized low-density lipoprotein (ox-LDL)-induced HUVECs injury model, DNA methylation of the upstream region of miR-520e was significantly increased. With increasing concentrations of the methylase inhibitor 5-Aza, miR-520e expression was upregulated. The silence of methyltransferase DNMT1, rather than DNMT3a or DNMT3b, abolished the influence of miR-520e expression by ox-LDL treatment in HUVECs. A dual luciferase reporter assay revealed that miR-520e regulated the TGFBR2 3′-untranslated region region. After silencing TGFBR2, the promoting effect of miR-520e inhibitor on cell proliferation and migration may be attenuated. In conclusion, the expression of miR-520e is modified by its promoter region DNA methylation, and miR-520e and its promoter region DNA methylation may be potential biomarkers in atherosclerosis. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the association between genetic variants and the risk of GCA via large-scale genome-wide association studies (GWAS). In addition, to assess the causal effect of a specific molecule by employing the obtained GWAS results as genetic epidemiological tools. Methods We applied additional variant quality control to the publicly available GWAS results from the biobanks of the UK (UKBB) and Finland (FinnGen), which comprised 532 cases vs 408 565 controls and 884 cases vs 332 115 controls, respectively. We further meta-analysed these two sets of results. We performed two-sample Mendelian randomization (MR) to test the causal effect of low-density lipoprotein (LDL) cholesterol on the risk of GCA. Results The MHC class II region showed significant associations in UKBB, FinnGen and the meta-analysis. The VLDLR region was associated with GCA risk in the meta-analysis. The T allele of rs7044155 increased the expression of VLDLR, decreased the LDL cholesterol level and decreased the disease risk. The subsequent MR results indicated that a 1 s. d. increase in LDL cholesterol was associated with an increased risk of GCA (odds ratio 1.21, 95% CI 1.01–1.45; P  = 0.04). Conclusions Our study identified associations between GCA risk and the MHC class II and VLDLR regions. Moreover, LDL cholesterol was suggested to have a causal effect on the risk of developing GCA. [ABSTRACT FROM AUTHOR]

Purpose: Telemedicine has been essential during the coronavirus disease 2019 (COVID-19) pandemic. In March 2020, pharmacist-led chronic disease state management services at our family care centers and primary care clinics were converted to telemedicine. This study aimed to determine the impact of expanding telemedicine services on appointment adherence, clinical outcomes, and financial reimbursement. Methods: This was a single-center, retrospective, quasi-experimental study of the impact of expanding telemedicine services on adult patients with diabetes, hypertension, and/or hyperlipidemia. The study included patients scheduled with a pharmacist at a hospital-based (HB) or physician-based (PB) clinic. The primary outcome was the difference in the mean no-show rate. The secondary outcomes were differences in mean change in HbA1c, LDL, blood pressure, and reimbursement. Mean differences between pre- and post-telemedicine groups of each clinic were measured for all outcomes. Results: The mean difference (SE) in the no-show rate in the HB clinic was -12.09% (4.862; P =.014), compared to 2.88% (3.656; P =.431) in the PB clinic. The mean difference (SE) in the change in HbA1c in the HB clinic was.00% (.338; P =.992), compared to.01% (.239; P =.945) in the PB clinic. The mean difference (SE) in reimbursement in the HB clinic was $1.93 (4.209; P =.647), compared to $20.46 (3.210; P <.0001) in the PB clinic. Conclusion: Expansion of pharmacy telemedicine services provided evidence for improved appointment adherence in the HB clinic and increased reimbursement in the PB clinic. No change in healthcare outcomes was observed. [ABSTRACT FROM AUTHOR]

Background: The hypothesized link between low‐density lipoprotein (LDL) and oncogenesis has garnered significant interest, yet its explicit impact on lung adenocarcinoma (LUAD) remains to be elucidated. This investigation aims to demystify the function of LDL‐related genes (LRGs) within LUAD, endeavoring to shed light on the complex interplay between LDL and carcinogenesis. Methods: Leveraging single‐cell transcriptomics, we examined the role of LRGs within the tumor microenvironment (TME). The expression patterns of LRGs across diverse cellular phenotypes were delineated using an array of computational methodologies, including AUCell, UCell, singscore, ssGSEA, and AddModuleScore. CellChat facilitated the exploration of distinct cellular interactions within LDL_low and LDL_high groups. The findmarker utility, coupled with Pearson correlation analysis, facilitated the identification of pivotal genes correlated with LDL indices. An integrative approach to transcriptomic data analysis was adopted, utilizing a machine learning framework to devise an LDL‐associated signature (LAS). This enabled the delineation of genomic disparities, pathway enrichments, immune cell dynamics, and pharmacological sensitivities between LAS stratifications. Results: Enhanced cellular crosstalk was observed in the LDL_high group, with the CoxBoost+Ridge algorithm achieving the apex c‐index for LAS formulation. Benchmarking against 144 extant LUAD models underscored the superior prognostic acuity of LAS. Elevated LAS indices were synonymous with adverse outcomes, diminished immune surveillance, and an upsurge in pathways conducive to neoplastic proliferation. Notably, a pronounced susceptibility to paclitaxel and gemcitabine was discerned within the high‐LAS cohort, delineating prospective therapeutic corridors. Conclusion: This study elucidates the significance of LRGs within the TME and introduces an LAS for prognostication in LUAD patients. Our findings accentuate putative therapeutic targets and elucidate the clinical ramifications of LAS deployment. [ABSTRACT FROM AUTHOR]

Background: Approximately 11.3% of the US population has diabetes. The burden of diabetes is higher in older adults and African Americans (AAs), such that 40% of adults aged 50 years and older have diabetes; African Americans are 60% more likely to be diagnosed with diabetes compared to non-Hispanic Whites (NHWs). Structural racism has resulted in fewer economic and educational opportunities for AAs, higher social risks, and unmet basic needs, which result in financial instability, housing instability, food insecurity, and a lack of transportation compared to NHWs. The presence of these unmet basic needs is a driver of poor adherence to diabetes self-management in older AAs. Aim: To test the preliminary efficacy of a nurse case-manager, telephone-delivered intervention that provides foundational diabetes self-management education and skills training, while also addressing and resolving the unmet social needs of older AAs with poorly controlled type 2 diabetes mellitus (T2DM). The primary hypothesis is that older AAs with T2DM randomized to the DM Social Needs intervention will have significantly lower hemoglobin A1C (HbA1C), blood pressure, and LDL levels compared to the usual care arm at 6 months post randomization. Methods: This is a three-year prospective, randomized clinical trial that will enroll 100 AAs aged 50 and older with type 2 diabetes (T2DM) and HbA1C ≥ 8% into one of the following two groups: (1) a nurse case-manager, telephone-delivered intervention that provides foundational diabetes self-management education and skills training, but also addresses and resolves unmet social needs; or (2) an enhanced usual care group that will receive mailed diabetes education materials. Participants will be followed for 6 months to determine the effect of the intervention on HbA1C, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. Results: Baseline characteristics will be presented by study group, and within- and between-group changes in primary outcomes from baseline to 6 months will be reported. Conclusion: The results from this study will provide insights into the efficacy of a combined diabetes education and skills training and social needs resolution intervention for older African Americans with poorly controlled type 2 diabetes and will inform strategies to improve diabetes outcomes for this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG. Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk. [ABSTRACT FROM AUTHOR]

APOE is a major genetic factor in late-onset Alzheimer's disease (LOAD), with APOE4 increasing risk, APOE3 acting as neutral, and APOE2 offering protection. APOE also plays key role in lipid metabolism, affecting both peripheral and central systems, particularly in lipoprotein metabolism in triglyceride and cholesterol regulation. APOE2 is linked to Hyperlipoproteinemia type III (HLP), characterized by mixed hypercholesterolemia and hypertriglyceridemia due to impaired binding to Low-Density Lipoproteins receptors. To explore the impact of human APOE isoforms on LOAD and lipid metabolism, we developed Long-Evans rats with human APOE2, APOE3, or APOE4 in place of rat Apoe. These rats were crossed with those carrying a humanized App allele to express human Aβ, which is more aggregation-prone than rodent Aβ, enabling the study of human APOE-human Aβ interactions. In this study, we focused on 80-day-old adolescent rats to analyze early changes that may be associated with the later development of LOAD. We found that APOE2hAβ rats had the highest levels of APOE in serum and brain, with no significant transcriptional differences among isoforms, suggesting variations in protein translation or stability. Aβ43 levels were significantly higher in male APOE4hAβ rats compared to APOE2hAβ rats. However, no differences in Tau or phosphorylated Tau levels were observed across the APOE isoforms. Neuroinflammation analysis revealed lower levels of IL13, IL4 and IL5 in APOE2hAβ males compared to APOE4hAβ males. Neuronal transmission and plasticity tests using field Input-Output (I/O) and long-term potentiation (LTP) recordings showed increased excitability in all APOE-carrying rats, with LTP deficits in APOE2hAβand APOE4hAβ rats compared to ApoehAβ and APOE3hAβ rats. Additionally, a lipidomic analysis of 222 lipid molecular species in serum samples showed that APOE2hAβ rats displayed elevated triglycerides and cholesterol, making them a valuable model for studying HLP. These rats also exhibited elevated levels of phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine. Minimal differences in lipid profiles between APOE3hAβ and APOE4hAβ rats reflect findings from mouse models. Future studies will include comprehensive lipidomic analyses in various CNS regions and at older ages to further validate these models and explore the effects of APOE isoforms on lipid metabolism in relation to AD pathology. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt. Results: This study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades. Conclusion: MRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

Background: Obesity is a pathological condition and a major risk factor for dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease. Recent research highlighted the association of non-invasive serum markers with these conditions but the clinical utility of ALT APRI in obesity and its relationship with dyslipidemia remain unexplored. Methods: We examined the association of ALT APRI in 165 non-diabetic adults stratified by BMI and serum lipid parameters. Results: Obese subjects had significantly higher APRI than lean subjects, with an area under the curve (AUC) of 0.65 (p = 0.019). Medians of APRI were significantly increased in subjects with high TG, TG/HDL, TC/HDL, and LDL/HDL and low HDL. Notably, all lipid parameters and ratios were significantly elevated in the highest APRI tertile, compared with patients in the lowest tertile. APRI was weakly yet significantly correlated with BMI (R2 = 0.032, p = 0.022), HDL (R2 = 0.071), TG/HDL (R2 = 0.031), TC/HDL (R2 = 0.063), LDL/HDL (R2 = 0.072), and TyG index (R2 = 0.081). While APRI only showed a discriminating capacity for HDL (AUC: 0.69, p = 0.003), TG/HDL (AUC: 0.63, p = 0.020), LDL/HDL (AUC: 0.68, p < 0.001), and TyG index (AUC: 0.65, p = 0.037), the highest diagnostic performance of APRI was observed with TC/HDL (AUC: 0.74, p < 0.001). Additionally, APRI was a risk factor for high TG (OR: 1.6, p = 0.028), low HDL (OR: 2.7, p = 0.0002), high TG/HDL (OR: 1.94, p = 0.0011), high TC/HDL (OR: 2.3, p < 0.0001), high LDL/HDL (OR: 2.2, p = 0.0001), and high TyG index (OR: 2.1, p = 0.008). Conclusions: Our findings argue for the role of APRI as a potential marker for obesity and dyslipidemia, which requires further confirmation in longitudinal studies. [ABSTRACT FROM AUTHOR]

The Lamiaceae plant family has a positive impact on metabolic diseases. This study meta‐analyzed the data of different clinical trial studies on the impacts of these plants on blood lipid biomarkers including cholesterol, triglyceride, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL). A comprehensive search was conducted using PubMed, Scopus, ISI Web of Science, ProQuest, Scientific Information Database, MagIran, and Google Scholar to identify relevant published research up to December 20, 2023. The meta‐analysis revealed that the Lamiaceae family significantly reduced cholesterol (p < .001), triglyceride (p = .003), and LDL (p < .001) levels. The rise in HDL levels was not significantly impacted (p = .069). Subgroup studies revealed that Lamiaceae plants improve all lipid parameters for a short duration (≤8 weeks) while in a longer duration (>8 weeks) only LDL level is improved in the blood (p < .05). In addition, Lamiaceae plants specifically decreased LDL and cholesterol levels in diabetic patients and only LDL levels in the individuals who were hyperlipidemic or overweight/obese. Within the Lamiaceae family, the genera Satureja and Coleus had the most significant effects in decreasing triglyceride and LDL/cholesterol levels, respectively. Origanum was the only genus within the Lamiaceae family that significantly improved three lipid parameters (cholesterol, LDL, and HDL). The meta‐analysis confirmed that Lamiaceae plants could improve the levels of lipid parameters (triglyceride, cholesterol, and LDL) in patients with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. Methods: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. Results: The agreement between capillary and laboratory venous blood was moderate (0.64–0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. Conclusions: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions. [ABSTRACT FROM AUTHOR]

Human emotional states encompass both basic and compound facial expressions. However, current works primarily focus on basic expressions, consequently neglecting the broad spectrum of human emotions encountered in practical scenarios. Compound facial expressions involve the simultaneous manifestation of multiple emotions on an individual's face. This phenomenon reflects the complexity and richness of human states, where facial features dynamically convey a combination of feelings. This study embarks on a pioneering exploration of Compound Facial Expression Recognition (CFER), with a distinctive emphasis on leveraging the Label Distribution Learning (LDL) paradigm. This strategic application of LDL aims to address the ambiguity and complexity inherent in compound expressions, marking a significant departure from the dominant Single Label Learning (SLL) and Multi‐Label Learning (MLL) paradigms. Within this framework, we rigorously investigate the potential of LDL for a critical challenge in Facial Expression Recognition (FER): recognizing compound facial expressions in uncontrolled environments. We utilize the recently introduced RAF‐CE dataset, meticulously designed for compound expression assessment. By conducting a comprehensive comparative analysis pitting LDL against conventional SLL and MLL approaches on RAF‐CE, we aim to definitively establish LDL's superiority in handling this complex task. Furthermore, we assess the generalizability of LDL models trained on RAF‐CE by evaluating their performance on the EmotioNet and RAF‐DB Compound datasets. This demonstrates their effectiveness without domain adaptation. To solidify these findings, we conduct a comprehensive comparative analysis of 12 cutting‐edge LDL algorithms on RAF‐CE, S‐BU3DFE, and S‐JAFFE datasets, providing valuable insights into the most effective LDL techniques for FER in‐the‐wild. [ABSTRACT FROM AUTHOR]

Purpose American College of Cardiology/American Heart Association guidelines recommend high-intensity statin therapy and consideration for nonstatin therapy for patients with peripheral vascular disease (PVD); however, utilization rates remain suboptimal. The primary objective of this study was to determine whether pharmacist intervention for patients with PVD could improve the percentage of patients discharged on a high-intensity statin. Methods The study used a single-center pre/post design and included patients with PVD who underwent peripheral bypass during their admission. Postintervention patients managed with an order set including a preselected consult for a pharmacy lipid protocol were compared to preintervention patients managed using the order set without the consult. The primary outcome was the percentage of patients discharged on a high-intensity statin. Secondary outcomes included intensification of statin therapy, the addition of ezetimibe, and referral to an outpatient lipid clinic. Results A total of 175 patients were included in the analysis, with 94 patients in the preintervention group and 81 patients in the postintervention group. The primary outcome met statistical significance, with an increase in the percentage of patients discharged on a high-intensity statin in the postintervention group (70.4%) compared to the preintervention group (38.3%) (P < 0.001; 95% confidence interval, 1.37-2.46). Secondary outcomes that met statistical significance included an increase in the percentage of patients with any increase in statin intensity (35.8% vs 20.2%; P = 0.02). Conclusion The addition of a pharmacist consult led to an increase in the percentage of patients discharged on a high-intensity statin and an increase in overall statin intensification. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate the clinical significance of the loudness discomfort level (LDL) test in tinnitus patients and its relationship with pure-tone audiometry, tinnitogram, and questionnaires. Methods: We retrospectively reviewed the medical records of 320 tinnitus patients who visited a tertiary university hospital's tinnitus clinic and completed LDL tests between March 2020 and December 2022. Epidemiological data and psychoacoustic test results were collected. Results: The LDL showed no significant differences between frequencies for both ears. The mean LDL did not correlate with mean pure-tone average or hearing thresholds at each frequency. The hearing loss group had a higher LDL at 8 kHz compared to the normal hearing group (p < 0.01). Objective sound intolerance was found in a quarter, correlating with subjective hyperacusis, anxiety, and depression. Weak negative correlations were found between most of questionnaire's scores and LDL on the left side. Tinnitus loudness weak negatively correlated with LDL at most frequencies, except 8 kHz. Discussion/Conclusion: Our findings suggest a notable association between LDL levels and emotional factors in tinnitus patients, rather than with auditory thresholds. While lateralized differences in LDL responses were observed, specifically on the left side, these preliminary results do not confirm a causal link and thus do not warrant changes to current clinical testing protocols without further research. [ABSTRACT FROM AUTHOR]

Background: In our study, we aimed to compare the Friedewald, Martin/Hopkins, and Sampson formulae with direct LDL-cholesterol (d-LDL-C) measurement. Methods: The study was a retrospective investigation by the Department of Medical Biochemistry of the Ankara Training and Research Hospital between January 1, 2021, and December 31, 2022. Our study evaluated the results of 6297 patients aged 18–95 years who underwent cholesterol panel TC, TG, HDL-C, and direct LDL-C in our laboratory. The estimated LDL-C was calculated according to Friedewald, Martin/Hopkins, and Sampson formulae. Results: All three formulae showed a stronger positive correlation with d-LDL-C (0.905, 0.897, and 0.886, respectively, for all data, p<0.001). In addition, when we compared the total median difference (1st–3rd quartile) of all formulae, it was -0.69 (-1.62 to 0.39) for Friedewald, 0.034 (-0.74 to 1.14) for Martin/Hopkins and -0.40 (-1.19 to 0.55) for Sampson. According to Passing Bablok regression analyses, the intercept was determined as -0.97 (95% CI=-1.01 to -0.93), 0.41 (95%=0.37 to 0.44) and -0.05 (-0.08 to -0. 03) and slopes were calculated as 1.083 (95% CI=1.07–1.09), 0.88 (0.88 to 0.89) and 0. 90 (95%=0.89 to 0.90) for Friedewald, Martin/Hopkins and Sampson, respectively. Conclusions: Our findings suggest that the Martin/Hopkins formula performed better than the Friedewald and Sampson formulas. We figured out utilizing the Martin/ Hopkins formula as a good alternative for estimated LDL-C in Turkish adults. [ABSTRACT FROM AUTHOR]

Atherosclerosis cardiovascular disease (ASCVD) has become one of the leading death causes in humans. Low-density lipoprotein (LDL) is an important biomarker for assessing ASCVD risk level. Thus, monitoring LDL levels can be an important means for early diagnosis of ASCVD. Herein, a novel electrochemical aptasensor for determination LDL was designed based on nitrogen-doped reduced graphene oxide-hemin-manganese oxide nanoparticles (NrGO-H-Mn3O4 NPs) integrated with clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR/Cas12a) system. NrGO-H-Mn3O4 NPs not only have a large surface area and remarkable enhanced electrical conductivity but also the interconversion of different valence states of iron in hemin can provide an electrical signal. Nonspecific single-stranded DNA (ssDNA) was bound to NrGO-H-Mn3O4 NPs to form a signaling probe and was immobilized on the electrode surface. The CRISPR/Cas12a system has excellent trans-cleavage activity, which can be used to cleave ssDNA, thus detaching the NrGO-H-Mn3O4 NPs from the sensing interface and attenuating the electrical signal. Significant signal change triggered by the target was ultimately obtained, thus achieving sensitive detection of the LDL in range from 0.005 to 1000.0 nM with the detection limit of 0.005 nM. The proposed sensor exhibited good stability, selectivity, and stability and achieved reliable detection of LDL in serum samples, demonstrating its promising application prospects for the diagnostic application of LDL. [ABSTRACT FROM AUTHOR]

Understanding the characteristics and behavior of low-density lipoprotein (LDL) particles provides insights into the atherogenic risk of elevated LDL cholesterol in hypercholesterolemia, cardiovascular disease risks. Studying LDL particles helps identify specific LDL subtypes [e.g., small dense LDL particles (sdLDL)] that may be atherogenic and, consequently, potential targets for therapeutics. This study cohort consists of African Americans (AAs), a population disproportionately affected by cardiovascular diseases, thereby accentuating the importance of the investigation. Differential expression (DE) analysis was undertaken using a dataset comprising 17,947 protein-coding mRNAs from the whole blood transcriptomes of 416 samples to identify mRNAs associated with low-density lipoprotein cholesterol (LDL-C) and sdLDL plasma levels. Subsequently, mediation analyses were used to investigate the mediating role of sdLDL particles on the relationship between LDL-C levels and mRNA expression. Finally, pathway enrichment analysis was conducted to identify pathways involving mRNAs whose relationship with LDL-C is mediated by sdLDL. DE analysis revealed 1,048 and 284 mRNA transcripts differentially expressed by LDL-C and sdLDL levels, respectively. Mediation analysis revealed that the associations between LDL-C and 33 mRNAs were mediated by sdLDL. Of the 33 mRNAs mediated by sdLDL, 18 were mediated in both males and females. Nine mRNAs were mediated only in females, and six were mediated only in males. Pathway analysis showed that 33 mRNAs are involved in pathways associated with the immune system, inflammatory response, metabolism, and cardiovascular disease (CVD) risk. In conclusion, our study provides valuable insights into the complex interplay between LDL-C, sdLDL, and mRNA expression in a large sample of AAs. The results underscore the importance of incorporating sdLDL measurement alongside LDL-C levels to improve the accuracy of managing hypercholesterolemia and effectively stratify the risk of CVD. This is essential as differences in sdLDL modulate atherogenic properties at the transcriptome level. NEW & NOTEWORTHY: The study investigated the interplay between LDL-C and mRNA expression, focusing on the role of small dense LDL (sdLDL) particles and sex differences. Differential expression analysis identified 1,048 and 284 mRNAs associated with LDL-C and sdLDL levels, respectively. Mediation analysis revealed that sdLDL mediates the relationship between LDL-C and 33 mRNAs involved in immune, inflammatory, and metabolic pathways. These findings highlight the significance of sdLDL in cardiovascular disease risk assessment and underscore sex-specific differences in lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Currently, most studies on the health benefits of traditional Chinese exercises on type 2 diabetes mellitus have explored the effects of a single type of traditional Chinese exercise on type 2 diabetes. Although a previous study evaluated the combined clinical effects of traditional Chinese exercises on type 2 diabetes, the studies included in that review were deficient in their study design. In addition, previous studies have not explored the ideal exercise dose that should be taken by patients with type 2 diabetes when performing traditional Chinese exercises. Objective: To understand whether the findings of previous systematic reviews and meta-analyses are still applicable and to try to address the deficiencies in the previous review, this review conducted a meta-analysis of existing randomized controlled trials to investigate the impact of traditional Chinese exercises on glycemic control with type 2 diabetes. Methods: The literature was searched in seven Chinese and English databases. Randomized controlled trials published in English and Chinese, from database inception to March 2023, were included in this review. Two reviewers independently reviewed the search results, extracted the data, and assessed the risk of bias. A meta-analysis of the included studies was conducted using Rev Man 5.4 and Stata 15.1 software. Heterogeneity was investigated using a sensitivity analysis, a subgroup analysis, and a meta-regression analysis. Pre-determined subgroups included the duration of the intervention, frequency of exercise, and duration of the single exercise session. Results: A total of 31 randomized controlled trials (2077 subjects) were selected in this review. The meta-analysis revealed that traditional Chinese exercises were more effective than control groups in lowering glycated hemoglobin (Z = 6.06; mean difference [MD] = − 0.64, 95% confidence interval [CI] − 0.85, − 0.44; P < 0.00001), fasting blood glucose (Z = 7.81; MD = − 0.82, 95% CI − 1.03, − 0.62; P < 0.00001), 2-h plasma glucose (Z = 5.61; MD = − 1.03, 95% CI − 1.39, − 0.67; P < 0.00001), total cholesterol (Z = 4.23; MD = − 0.37, 95% CI − 0.54, − 0.20; P < 0.0001), high-density lipoprotein cholesterol (Z = 5.94; MD = 0.12, 95% CI 0.08, 0.16; P < 0.00001), low-density lipoprotein cholesterol (Z = 6.20; MD = − 0.34, 95% CI − 0.44, − 0.23; P < 0.00001), and triglyceride levels (Z = 3.74; MD = − 0.44, 95% CI − 0.67, − 0.21; P = 0.0002) among patients with type 2 diabetes. Conclusions: Traditional Chinese exercises can significantly improve blood glucose and lipid levels in patients with type 2 diabetes. When performing traditional Chinese exercise interventions for type 2 diabetes, it is recommended that exercise programs are designed for 30–50 min/session, 4–5 sessions/week for at least 3 months. [ABSTRACT FROM AUTHOR]

This study was to investigate the therapeutic effect of Bacillus amyloliquefaciens (Ba) on atherosclerosis (AS). THP-1 monocyte was differentiated to THP-1 macrophage (THP-M) through phorbol 12-myristate 13-acetate. After pre-treatment by 108 cfu/ml Ba lasting 6 h, THP-M was induced with 100 mg/l ox-LDL lasting 48 h to form macrophage foam cell (THP-F). RT-qPCR and flow cytometry were employed to determine the polarization of THP-M and THP-F. ApoE−/− mice with high-fat and high-cholesterol diet were used for constructing an AS model to evaluate the effect of Ba on AS. Our in vitro results showed that Ba vegetative cells pre-treatment distinctly inhibited the levels of iNOS and CD16/CD32 (M1 macrophage markers), and increased the levels of FIZZ1, Ym1, Arg1, CD163, and CD206 (M2 macrophage markers), indicating that Ba pre-treatment promoted anti-inflammatory M2-like polarization both in THP-M and THP-F. Meanwhile, it also suppressed cholesterol uptake, esterification, and hydrolysis, and efflux by THP-M and THP-F. Additionally, our animal experiments demonstrated that Ba vegetative cells treatment suppressed high cholesterol, hyperglycemia, hyperlipidemia, and the release of inflammatory factors (TNF-α, IL-6 and IL-1β) in ApoE−/− AS mice. In a word, our results indicated that Ba may protect against AS through alleviating foam cell formation and macrophage polarization through targeting certain stages of AS. [ABSTRACT FROM AUTHOR]

Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3‐compartment model with 4‐compartment transit absorption and first‐order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) concentrations. The maximum stimulatory effect of obicetrapib on LDL‐C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL‐C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL‐C and HDL‐C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision‐making throughout the development lifecycle. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome (MetS) and insulin resistance (IR) are associated with diabetes. Insulin therapy in type 1 diabetes (T1DM) may complicate the diagnosis of both these conditions. Therefore, investigation of the diagnostic efficacy of MetS and IR components is important in paediatric population with type 1 diabetes mellitus (T1DM). Methods: SCOPUS, Web of Science, and PubMed were searched for studies that have MetS and IR in paediatric populations with T1DM. We assessed the strength of association for MetS and IR components. A random effect model was used for the meta-analysis and the effect size was reported in terms of Hedge's g. Results: A total 30 studies were identified relevant to our systematic search. Insulin dosage and HbA1c, markers for glycemic condition showed very small effect on MetS with T1DM. In the lipid profile, triglyceride (TG) and low-density lipoprotein (LDL) showed better effect size than high-density lipoprotein (HDL). In case of IR, heterogeneous nature of studies made it difficult to carry out a meta-analysis. A descriptive review of existing and novel markers is thus provided. Conclusion: In children with T1DM, lack of association between markers of glycemic condition suggested that MetS may develop independent of glycemic level. Other than TG and HDL, LDL may be used in the diagnosis of MetS. A universally accepted diagnosis protocol would enhance accuracy and comparability across research and clinical settings, as observed in the descriptive review. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hamster model lacking both LCAT and LDL receptor (DKO) was successfully constructed in the present study. • A significant reduction in plasma LDL-C and HDL-C levels with increased triglyceride and free cholesterol levels was observed in DKO hamsters on a regular chow diet. • Dyslipidemia contributed to HFD-induced atherosclerosis and fatty liver independent on LDL levels in DKO hamsters. • Lipid metabolism was impaired in primary peritoneal macrophages from DKO hamsters. Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia. [ABSTRACT FROM AUTHOR]