Search Results (473)

Traffic-related air pollution (TRAP) is known to contribute to oxidative stress in the central nervous system (CNS) and has been linked to increased risk of Alzheimer’s disease (AD). Alterations in the renin–angiotensin system (RAS), specifically increased angiotensin II (Ang II) signaling via the angiotensin II type 1 (AT₁) receptor, are implicated in increased oxidative stress in the CNS via activation of NADPH oxidase (NOX). As exposure to TRAP may further elevate AD risk, we investigated whether exposure to inhaled mixed gasoline and diesel vehicle emissions (MVE) promotes RAS-dependent expression of factors that contribute to AD pathophysiology in an apolipoprotein E-deficient (ApoE^−/−) mouse model. Male ApoE^−/− mice (6–8 weeks old) on a high-fat diet were treated with either an ACE inhibitor (captopril, 4 mg/kg/day) or water and exposed to filtered air (FA) or MVE (200 µg PM/m³) for 30 days. MVE exposure elevated plasma Ang II, inflammation, and oxidative stress in the hippocampus, associated with increased levels of Aph-1 homolog B (APH1B), a gamma-secretase subunit, and beta-secretase 1 (BACE1), involved in Aβ production. Each of these endpoints was normalized with ACEi treatment. These findings indicate that TRAP exposure in ApoE^−/− mice drives a RAS- and NOX-dependent oxidative and inflammatory response and shifts Aβ processing towards an amyloidogenic profile before overt Aβ deposition, suggesting a potential therapeutic approach for air pollution-induced AD risk. Full article

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype–phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations. Full article

Background/Objectives: Variants in the lipoprotein lipase (LPL) gene have been associated with lipid level variability and obesity; however, their role in energy homeostasis remains unclear. The aim of this study was to investigate the association of LPL single-nucleotide variants (SNVs) with lipid parameters and leptin concentrations in a cohort of prepubertal children. The sample population comprised 635 boys and 631 girls, with available information on lipid profiles and leptin levels. Methods: Five LPL SNVs (rs258, rs316, rs326, rs320, and rs328) were genotyped by Real-Time PCR using predesigned TaqMan™ Genotyping Assays. Results: An association of the LPL SNV rs258 was found with non-esterified fatty acid (NEFA) levels in males and with leptin concentrations in both sexes. On the other hand, an association of the LPL SNV rs326 was observed with low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B) levels, displaying opposite trends in males and females. No significant associations with any of the parameters under study were observed for the remaining LPL SNVs. Conclusions: These results suggest that functional differences among LPL SNVs may either be related to an enhancement of catalytic activity or modulation of lipoprotein binding affinity, influencing the efficiency of remnant lipoprotein clearance. Full article

Objectives: Emerging evidence suggests that bilirubin, beyond being a metabolic byproduct, may exert protective effects against metabolic and cardiovascular diseases due to its antioxidant properties. However, its relationship with hyperlipidemia remains unclear. This study investigated the relationship between hyperbilirubinemia and hyperlipidemia in a large, community-based cohort. Methods: Data from 8464 participants in the Jidong Community Cohort were analyzed using a cross-sectional design. Hyperbilirubinemia was defined as serum total bilirubin (STB) ≥ 17.1 μmol/L, whereas hyperlipidemia was determined based on a prior diagnosis or elevated lipid profile. Results: Of all participants, 31.6% had hyperbilirubinemia and 51.8% had hyperlipidemia. Multivariable logistic regression revealed a significant inverse association between hyperbilirubinemia and hyperlipidemia [odds ratio (OR) = 0.764, 95% confidence interval (CI) = 0.686–0.851]. This association was significant in participants aged <65 years (OR = 0.762, p < 0.0001) but not in those aged ≥65 years. Stratified analysis by smoking status further revealed a 29% reduced risk of hyperlipidemia among never-smokers (OR = 0.708, p < 0.001), but not among current (OR = 0.831, p = 0.087) or former smokers (OR = 0.685, p = 0.175). Hyperbilirubinemia was also negatively associated with TC (p < 0.0001), TGs (p < 0.0001), LDL-C (p = 0.0061), very LDL-C (VLDL-C; p = 0.0043), and apolipoprotein B (ApoB; p < 0.0001) levels, as well as the ApoB/apolipoprotein A1 (ApoA1) ratio (p = 0.0003). Restricted cubic spline analysis revealed an inverse relationship of high STB levels with the TC, TG, LDL-C, VLDL-C, and ApoB levels, as well as the ApoB/ApoA1 ratio. Moreover, elevated STB levels were inversely linked to obesity (OR = 0.747, p < 0.0001), arterial stenosis (OR = 0.806, p = 0.0462), and metabolic syndrome (OR = 0.784, p = 0.0008). Conclusions: hyperbilirubinemia may be an independent factor protective against hyperlipidemia and related lipid abnormalities; these results provide insights for the prevention and management of lipid-related diseases. Full article

Cardiovascular disease (CVD) is influenced by disturbances in lipoprotein composition and metabolism, including triglyceride-rich lipoproteins (TRLs) and elevated lipoprotein (a) (Lp(a)). While interactions between Lp(a) and very-low-density lipoproteins (VLDL) have been studied in hypertriglyceridemic and CVD populations, data in normotriglyceridemic individuals without CV events are limited. Seventy normotriglyceridemic adults with triglycerides < 150 mg/dL and no CV events were enrolled and divided into two groups based on Lp(a) concentration: <30 mg/dL and ≥30 mg/dL. VLDL was isolated by ultracentrifugation, and concentrations of Lp(a), lipids (triglycerides, cholesterol), and apolipoproteins (apo B, apo C-II, apo C-III, apo E) were measured in serum and VLDL. Serum lipid and apolipoprotein concentrations did not differ between the groups. Individuals with Lp(a) ≥ 30 mg/dL had significantly higher VLDL concentrations of triglycerides (+71%), cholesterol (+54%), apo B (+28%), apo C-II (+36%), and apo C-III (+33%). Ratios of lipids and apolipoproteins to apo B indicated unchanged VLDL particle composition, suggesting that differences reflected increased particle number rather than altered composition. In normotriglyceridemic subjects with Lp(a) ≥ 30 mg/dL, VLDL particles are more abundant but compositionally unchanged. Redistribution of lipids and apolipoproteins toward VLDL may contribute to VLDL residual cardiovascular risk, underscoring the need for further studies on VLDL-Lp(a) interactions. Full article

Background: The diagnosis of hypercholesterolemia relies on the laboratory assessment of lipid parameters. This study aimed to evaluate differences in the distribution of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) concentrations according to the presence and type of lipid-lowering therapy (LLT). Methods: This retrospective analysis included consecutive patients who had at least one measurement of LDL-C, apoB, and non-HDL-C between March and November 2024 in a high-volume tertiary hospital. All lipid fractions were expressed as the percentages of measurements above or below cut-off values established by the recent ESC guidelines. Subgroup analysis based on LLT type was performed, with patients categorized as receiving either single or combined LLT. Results: A total of 5048 patients were included in the analysis. Among patients receiving LLT, most were on statin monotherapy (77.3%), predominantly atorvastatin. Combined therapy, primarily statin plus ezetimibe, was used in 22.7% of treated patients. Discordance between on-target apoB levels and elevated LDL-C concentrations occurred in 26.6% of untreated and 13.6% of all treated patients, and in 15.1% and 8.6% of single and combined-LLT patients, respectively. Similarly, discordance between on-target non-HDL-C and elevated LDL-C levels was observed in 13.5% of untreated and 7.5% of all treated patients, and in 8.4% and 4.8% of single and combined-LLT patients, respectively. Conclusions: Classification of hyperlipidemia based on LDL-C, non-HDL-C, and apoB concentrations reveals significant discrepancies between these markers, especially between LDL-C and apoB. LLT reduces these discrepancies with combined LLT being particularly effective. Full article

Background: Lipid overaccumulation in the liver predisposes ducks to metabolic disorders. The molecular mechanism of oleic acid (OA)-induced hepatic steatosis in ducks is not fully elucidated. Methods: A cellular model of steatosis was established by treating primary duck hepatocytes with OA. Transcriptome sequencing was performed to identify key signaling pathways and candidate genes. The role of Apolipoprotein A1 (APOA1) was investigated through overexpression and knockdown experiments. Intracellular triglycerides (TGs) were quantified commercially; lipid droplets were visualized by Oil Red O staining. Results: Intracellular TG accumulation was induced by OA treatment in a dose-dependent manner. Through transcriptome analysis, 1045 differentially expressed genes (DEGs) were identified, with APOA1 being recognized as a key candidate within the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The content of TGs and lipid droplets was increased by APOA1 overexpression, whereas these effects were suppressed by APOA1 knockdown. The expression of acetyl-CoA carboxylase alpha (ACACA) and fatty acid synthase (FASN) was upregulated by APOA1. Conversely, the expression of carnitine O-palmitoyltransferase 1 (CPT1), acyl-CoA oxidase 1 (ACOX1), and apolipoprotein B (APOB) was downregulated. Conclusions: This study demonstrates that OA upregulates APOA1, suggesting the involvement of the PPAR pathway and providing a theoretical basis for modulating hepatic fat deposition. Full article

Gingival crevicular fluid (GCF) reflects both local periodontal inflammation and systemic conditions. This review highlights the role of oxidative stress, oxidised low-density lipoprotein (oxLDL), and apolipoprotein B (apoB) as molecular links between periodontitis and metabolic disorders. Elevated GCF levels of oxLDL and apoB indicate enhanced vascular permeability and local oxidative modification, particularly in diabetes. Furthermore, oxLDL promotes the formation of neutrophil extracellular trap (NET) via connecting oxidative stress with immune-mediated tissue injury. These insights establish GCF as a valuable, non-invasive biomarker for understanding the interplay between periodontal and systemic diseases. Full article

Background: Apolipoprotein B (apo B), apolipoprotein C-II (apo C-II), and apolipoprotein C-III (apo C-III) play important roles in very low-density lipoprotein (VLDL) metabolism. Whether they influence the relationship between intra-pancreatic fat deposition (IPFD) and VLDL is unknown. The aim was to investigate whether the association between VLDL cholesterol (VLDL-C) and IPFD varies between individuals with and without dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III. Methods: Abdominal magnetic resonance imaging at 3T was performed to quantify IPFD. VLDL-C was measured using the Quantimetrix Lipoprint^® system, whereas apo B, apo C-II, and apo C-III levels were analysed using the MILLIPLEX^® (xMAP) assay. Dysapolipoproteinemia was defined as apolipoprotein levels above the upper quartile of the overall cohort. Univariable and multivariable linear regression analyses were performed, adjusting for age, sex, ethnicity, waist-to-hip ratio, high-density lipoprotein cholesterol, and insulin resistance. Results: A total of 32 individuals had dysapolipoproteinaemia, whereas 96 had normoapolipoproteinaemia. Among those with dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III, VLDL-C levels were significantly and positively associated with IPFD. In the fully adjusted model, each unit increase in VLDL-C corresponded to a 0.82% (p = 0.011), 1.05% (p = 0.003), and 1.00% (p = 0.005) increase in IPFD, respectively. No significant association between VLDL-C and IPFD was observed in individuals with normoapolipoproteinaemia. Conclusions: Altered apolipoprotein profiles influence the association between VLDL-C and IPFD. Full article

Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death primarily in patients over 65 years old, with an increasing incidence, especially in Eastern European countries. Primary and secondary prevention protocols are based on a large number of cardiovascular (CV) risk factors, but low-density lipoprotein cholesterol (LDL-C) remains the main treatment target and one of the central determinants of CV risk. Apolipoprotein B (apoB) is the main structural protein in all atherogenic lipoproteins, and, unlike LDL-C, which only reflects the cholesterol content of LDL, apoB directly quantifies the total number of all circulating atherogenic particles. Over the past decade, a growing amount of data has supported the utility of apoB for CV risk assessment; however, its superiority over LDL-C remains unclear. Our study aimed to investigate the predictive value of apoB for both the presence and the severity of CAD in a statin-treated cohort from an Eastern European hospital and to compare it with standard lipid biomarkers. Methods: A total of 121 statin-treated patients, who were evaluated using coronary angiography, were consecutively enrolled and subdivided into three groups: 52 patients with significant coronary artery disease (S-CAD), 36 patients with non-significant coronary artery disease (NS-CAD), and 33 patients without coronary atherosclerosis (N-CAD). Apolipoprotein B was measured at the moment of enrollment using the immunoturbidimetric assay. Results: The mean values of LDL-C, TC, non-HDL-C, and apoB increased progressively across the three studied groups. Unlike traditional lipid biomarkers, apoB levels differed significantly not only between N-CAD and S-CAD, but also between N-CAD and NS-CAD. The diagnostic superiority of apoB extended beyond group mean differences, as it also demonstrated the strongest correlation with CAD severity. ApoB showed a moderate correlation with the Gensini score (r = 0.43, p < 0.001), which was markedly higher compared to LDL-C, TC, or non-HDL-C, all of which presented only a weak correlation (r = 0.26, r = 0.23, and r = 0.28, respectively). Additionally, in a logistic regression analysis, apoB demonstrated the highest predictive power for the presence of significant CAD (per SD increase: OR 2.386, 95% CI 1.52–3.75, p = 0.000), and it was the only biomarker able to predict left main disease (per SD increase: OR 2.433, 95% CI 1.38–4.30, p = 0.002) and three vessel disease (per SD increase: OR 1.639, 95% CI 1.012–2.654, p = 0.044). Residual apoB was also calculated and remained significantly associated with the presence of coronary atherosclerosis. Conclusions: ApoB proved to be a reliable predictor for CAD, independent of LDL-C. Compared to standard lipid biomarkers, apoB was superior in detecting NS-CAD and showed a better correlation with the severity of CAD. Additionally, in our study, only apoB was significantly correlated with left main disease and three vessel disease. Full article

Olfactory perception depends on soluble proteins in the perireceptor environment that support odorant transport, mucosal protection, and tissue homeostasis. In insects, odorant-binding proteins (OBPs) in the sensillum lymph are indispensable for odor detection, whereas in humans the indispensability of OBPs (OBP2A/2B) remains unclear because they are inconsistently detected in nasal mucus. Consequently, it remains unclear whether other soluble proteins compensate for this function or how they contribute to odorant processing and signal transmission within the olfactory mucus. Accumulating evidence indicates that OBP-like lipocalins (LCN1, LCN2, LCN15) and apolipoprotein D, together with bactericidal/permeability-increasing (BPI)-fold proteins, act as major mediators of odorant solubilization, antimicrobial defense, oxidative stress regulation, and extracellular matrix (ECM) remodeling. Alterations in those proteins and ECM organization are linked to idiopathic and age-related smell loss, chronic rhinosinusitis, and neurodegenerative disorders, underscoring their broad relevance at the interface of chemosensation, mucosal defense, and brain health. Major unresolved issues include the functional indispensability of human OBPs, the receptor-specific contributions of OBP-like proteins, and the mechanistic relationships linking olfactory proteome remodeling, sensory signaling, and disease progression. This review provides an integrative overview of structural and mechanistic insights, highlights current controversies, and proposes future research directions, including receptor–protein mapping, integrated structural–functional studies, structural–functional analysis of OBP–ECM networks, and clinical validation of OBP-related biomarkers. Full article

Background: Plant-based diets are associated with reduced cardiometabolic risk, yet the influence of lifestyle behaviors on these benefits remains insufficiently understood. Objective: To assess the combined impact of dietary patterns and lifestyle behaviors on body composition, lipid profiles, and inflammatory biomarkers in healthy young adults. Methods: In this cross-sectional study, 155 participants aged 18–39 years were categorized into four dietary groups: vegans (n = 48), vegetarians (n = 49), pescatarians (n = 23), and omnivores (n = 35). Body composition was measured using bioelectrical impedance analysis. Blood samples were analyzed for lipid parameters, apolipoproteins, lipoprotein(a), and inflammatory markers (IL-6, TNF-α, and hsCRP). Participants were further stratified based on behavioral factors, including physical activity, sleep duration, smoking, and alcohol consumption. Results: Vegans demonstrated the lowest body fat and visceral adipose tissue, along with the second-highest skeletal muscle mass. Significant intergroup differences were observed in total cholesterol (p = 0.032), HDL-C (p = 0.006), and triacylglycerols (p = 0.005). Among vegans, suboptimal lifestyle behaviors were associated with elevated LDL-C, non-HDL-C, and homocysteine levels (p < 0.05). Positive correlations were identified between ApoB and BMI (r = 0.517) and between IL-6 and waist–to–hip ratio (ρ = 0.499). Conclusions: A vegan diet, when combined with healthy lifestyle behaviors, is associated with favorable body composition and lipid profiles. Regardless of dietary pattern, maintaining a healthy body weight and minimizing visceral adiposity are essential for reducing cardiovascular and inflammatory risk. These research findings underscore the importance of integrating high-quality plant-based diets with lifestyle modifications and advanced modeling approaches. Full article

Recent progress in laboratory medicine provides powerful tools for the detailed evaluation of cardiovascular risk in military populations. This study aimed to characterize cardiometabolic biomarker profiles across four Polish military groups through chemometric analysis. The study included 392 participants (336 men, 56 women, aged 19–56 years). In total, 23 serum biomarkers from lipid, metabolic, hepatic, hormonal, and bone axes, and lactate dehydrogenase (LDH) were analyzed. Random forest (RF) modeling and effect-size profiling identified group-specific signatures. Group 4 (exposed to extreme acceleration forces and ionizing radiation) exhibited a systemic stress and metabolic-load profile with higher N-terminal pro-B-type natriuretic peptide (NT-proBNP, 36.7 ± 48.2 pg/mL) and calcium (Ca, 10.4 ± 0.88 mg/dL), and lower parathyroid hormone (PTH, 15.4 ± 10.1 pg/mL) and C-terminal telopeptide of type I collagen (β-CTX, 0.22 ± 0.19 ng/mL). Group 2 (exposed to fuels and exhaust gases) and group 3 (exposed to vibration, noise, ionizing radiation) showed an atherogenic–hepatometabolic axis with elevated apolipoprotein B (apoB, 1.04 ± 0.31; 0.97 ± 0.29 g/L), non-high-density lipoprotein cholesterol (N-HDL, 151.0 ± 46.7; 147.0 ± 41.4 mg/dL), and alanine aminotransferase (ALT). Group 1 (exposed to a biological hazard) displayed higher glucose (Glu, 96.0 ± 25.6 mg/dL) and triglycerides (TG, 151.0 ± 113.0 mg/dL) with lower magnesium (Mg, 2.03 ± 0.27 mg/dL). RF modeling confirmed these constellations. This study was exploratory in nature, providing a foundation for future longitudinal research. These findings provide a rationale for tailored cardiovascular surveillance, although causal inference is limited by the cross-sectional design. Full article

Astaxanthin has attracted considerable interest, owing to its potent antioxidant and pigmentation properties. To investigate its effects of astaxanthin on body color variation in Lutjanus erythropterus, fish were divided into a control group and a treatment group fed an astaxanthin-supplemented diet. Body color parameters, growth performance, and liver antioxidant enzyme activities were measured at the end of the experiment. Tissues, including skin, intestine, liver, and blood, were subsequently collected for transcriptome sequencing. The results demonstrate that the astaxanthin-treatment group exhibited significantly enhanced body coloration alongside improved body length, body weight, and specific growth rate compared to the control group (p < 0.05). Specifically regarding the red–green value (a*), the treatment group showed significantly higher values on the ventral skin, dorsal skin, and gill cover (p < 0.05). The yellow–blue (b*) and lightness (L*) values were also significantly elevated in the ventral skin and gill cover (p < 0.05), although no significant differences were observed in the dorsal skin (p > 0.05). The skin was identified as the tissue with the highest total carotenoid content. Astaxanthin supplementation enhanced liver antioxidant capacity, evidenced by significantly elevated total superoxide dismutase (T-SOD) activity and significantly reduced malondialdehyde (MDA) levels in the treatment group (p < 0.05). Catalase (CAT) activity did not differ significantly between groups (p > 0.05). Transcriptomic analysis identified several coloration-associated genes, such as bco1, bco2, gstt1, and gstz1. It also revealed significant enrichment in key metabolic pathways (fatty acid, cholesterol, and retinol metabolism) and signaling pathways (PPAR and PI3K-Akt). Furthermore, the expression of multiple solute-carrier family members and apolipoproteins was detected, with notable enrichment in lipid digestion and absorption, cholesterol metabolism, and several key immune-related signaling pathways. These findings provide a theoretical basis for understanding the molecular mechanisms of carotenoid-mediated pigmentation in L. erythropterus. Full article

This study aimed to investigate whether knockout of the ApoB48 gene improves lipid metabolism disorders induced by a high-fat diet (HFD) in mice. Clustered regularly interspaced short palindromic repeats–Cas9 gene editing technology was used to knock out the ApoB48 gene in C57BL/6J mice, and genotype identification showed heterozygosity (HE, ApoB48 +/−). Subsequently, eight HE and eight wild-type (WT) mice were fed a HFD for 12 weeks. Fasting blood glucose, and insulin levels were decreased in ApoB48 +/− mice. The intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test showed mild insulin resistance. Moreover, it delayed the development of atherosclerosis and intestinal tissue damage. Differential metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate were identified using liquid chromatography–mass spectrometry, and differentially expressed proteins, including ceramide synthase 6 (CerS6), protein phosphatase 2A (PP2A), and protein kinase B (AKT), were indicated by the Kyoto Encyclopaedia of Genes and Genomes. Therefore, decreased expression of ApoB48 can ameliorate lipid metabolism disorders induced by an HFD, which may be related to the CerS6/PP2A/AKT pathway. This might represent a new approach for exploring methods to treat hyperlipidaemia. Full article