This study aimed to evaluate the effects of phytosterols (PSs) alone and in combination with phospholipids (PLs) on blood lipid levels, erythrocyte membrane fluidity (EMF) and lipid profiles in subjec Show more
This study aimed to evaluate the effects of phytosterols (PSs) alone and in combination with phospholipids (PLs) on blood lipid levels, erythrocyte membrane fluidity (EMF) and lipid profiles in subjects with borderline hyperlipidemia in a randomized, double-blind, placebo-controlled clinical trial. Among 144 initially screened participants, 87 were enrolled and randomly assigned to three groups receiving PSs (2 g of PSs), PSs and PLs (2 g of PSs plus 0.825 g of PLs), or placebo for 60 days, respectively. A total of 83 subjects completed the entire trial. After 60 days of intervention, the levels of total cholesterol (TC) and apolipoprotein B (ApoB) in the combined PSs and PLs group decreased by 7.8% and 6.4% ( Show less
Apolipoprotein B-100 (apoB-100) is the main structural protein of apoB-containing lipoproteins including low-density lipoprotein (LDL). Its organization or lipidation process in an apoB-containing lip Show more
Apolipoprotein B-100 (apoB-100) is the main structural protein of apoB-containing lipoproteins including low-density lipoprotein (LDL). Its organization or lipidation process in an apoB-containing lipoprotein particle is still unclear. To understand its organization in a LDL particle, the combination of atomic force microscopy (AFM) with lipid depletion by Nonidet P-40 (NP-40) or methyl-ÎČ-cyclodextrin (MÎČCD) was utilized for the first time to in situ visualize LDL delipidation process and lipid-poor/-free apoB-100 at a physiological condition. During LDL delipidation process, different morphologies/structures were visualized successively including spheroidal structure with a smaller size than native LDL, spheroidal structure with one or more holes, closed annular/circular structure, opened annular/circular structure, C/U-shaped (or horseshoe-shaped) structure, and V/S/I-shaped structure. Based on the concentration-dependent structural distributions, these structures probably reflect 5 stages of LDL delipidation (e.g., a slightly delipidated LDL stage, a partially delipidated LDL stage, a neutral lipid-poor/-free apoB-100 stage, a lipid-poor apoB-100 stage, and a lipid-free apoB-100 stage, respectively). Our findings could provide structural evidence to reconcile the previous controversy and provide potential evidence/clues/implications for understanding apoB-100 lipidation and the organization of apoB-100 in apoB-containing lipoprotein particles. Potentially, this study also can provide new structural insights into the design of food-grade lipid carriers. Moreover, the combination of AFM with lipid depletion, which has many advantages over traditional electron microscopy (e.g., label-free, in situ, and real-time imaging under physiological conditions, etc.), is a potentially ideal novel strategy for studying the structure of apolipoproteins or lipoproteins. Show less
Apolipoprotein B (apoB) is a well-known risk factor for atherosclerosis. However, studies examining its relation to atrial fibrillation (AF) have produced conflicting results and suggested possible se Show more
Apolipoprotein B (apoB) is a well-known risk factor for atherosclerosis. However, studies examining its relation to atrial fibrillation (AF) have produced conflicting results and suggested possible sex-specific differences. This study investigated the sex-specific associations between serum apoB concentrations and incident AF and offer insight into the inconsistencies in previous research. A prospective analysis of 26,803 participants without pre-existing AF was performed using data from the Malmö Diet and Cancer Study. Sex-specific associations between apoB and AF were assessed using multivariable Cox proportional hazards models. To ensure the robustness of the results, several sensitivity analyses, such as restricted cubic spline modeling, competing risks regression, alternative adjustment strategies, subgroup analyses, follow-up time restrictions, and multiple imputation for missing data, were conducted. For median follow-up periods of 21.2 and 24.8 years in men and women, respectively, 2,768 and 2,968 incident cases of AF were recorded, respectively. Among women, unadjusted models showed a strong positive association between apoB and AF, with the highest versus lowest quartile showing a hazard ratio (HR) of 1.65 (95% confidence interval [CI] 1.49â1.84; Results show sex-specific observational links between apoB concentrations and risk of AF. In women, higher apoB levels were linearly inversely associated with AF, whereas in men, the association was borderline non-linear, with inverse effects seen mainly at lower apoB concentrations. These sex differences in AF susceptibility may partly reflect underlying atrial electrophysiological variations and hormonal influences, though whether these factors directly mediate the apoB-AF association remains speculative. The online version contains supplementary material available at 10.1186/s12944-026-02905-6. Show less
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial Show more
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial was conducted to investigate the acute effects of a single episode of alcohol ingestion on various biomarkers in healthy individuals. A total of 45 male participants were recruited and randomized into an alcohol group (nâ=â40) and a control group (nâ=â5) at an 8:1 ratio. Volunteers in the alcohol group ingested 40% Absolut vodka within 15 min. Blood pressure, heart rate, and blood oxygen saturation were measured at 0 h, 1 h, 3 h, 5 h, 12 h, and 24 h. Venous blood samples were drawn at 0 h, 1 h, 5 h, 12 h, and 24 h after alcohol intake. Our results showed that levels of liver function markers, including α-fucosidase (AFU), albumin (ALB), and alkaline phosphatase (ALP), were significantly increased in the alcohol group compared to the control group. The 24-h area under curve (AUC) of AFU, ALB, and ALP were significantly higher in the alcohol group. The liver fibrosis maker collagen type â Ł (â Ł-C) tended to be higher at 1 h and 12 h in the alcohol group compared to the control group. Lipid levels, including triglycerides (TG), apolipoprotein A1 (APOA1), and the APOA1/APOB, were significantly elevated after alcohol ingestion, particularly at 5 h and 12 h. The 24 h-AUC of TG, APOA1, and APOA1/APOB were higher in the alcohol group than in the control group. Additionally, cardiac function indicators, including heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were significantly elevated in the alcohol group. SBP and DBP remained higher 24 h after alcohol ingestion compared to the control group. This study demonstrated that even a single episode of binge drinking could induce significant alterations of biomarkers related to liver function, cardiac function, and lipid profiles. These findings provided valuable insights into the short-term impact of alcohol on health and highlighted the importance of further research to explore the long-term implications of repeated acute alcohol exposure. Given the very small control group, these results should be interpreted as preliminary and confirmed in larger, more balanced randomized trials. The online version contains supplementary material available at 10.1038/s41598-026-40028-1. Show less
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine lea Show more
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine learning (ML) algorithms. A total of 1608 AMI patients admitted to the First Hospital of Lanzhou University during 2023 and 2024 were retrospectively enrolled in this study. The 851 patients from 2023 were randomly divided into a training set ( LASSO regression initially identified 13 candidate features, while the random forest (RF) model demonstrated the best predictive performance in the training set. Following Boruta refinement, seven key features were retained, leading to the construction of an updated RF model. This model achieved an AUROC of 0.906, an accuracy of 0.977, a precision of 0.900, a sensitivity of 0.643, a specificity of 0.996, and a F1 score of 0.750 on the internal validation set. Temporal external validation at the same center showed an AUROC of 0.988, an accuracy of 0.967, a precision of 0.701, a sensitivity of 0.904, a specificity of 0.972, and a F1 score of 0.790. Furthermore, the model demonstrated excellent calibration, with a Brier score of 0.023 and 0.027. The SHAP analysis ranked feature importance as Killip class, D-dimer (DD), creatinine (Crea), alanine aminotransferase (ALT), apolipoprotein B/A (APOB/A), diastolic blood pressure (DBP) and lactate (Lac). We developed and validated a RF model based on seven key variablesâKillip class, DD, Crea, ALT, APOB/A, DBP and Lacâthat serves as a predictive tool for identifying the risk of in-hospital CS in AMI patients post-PCI. Additionally, we created an online prediction application using Streamlit, which facilitates the implementation of this model into clinical practice. Show less
The objective of this research was to investigate the association between non-traditional lipid parameters and optical coherence tomography (OCT)-characterized high-risk plaques in patients with acute Show more
The objective of this research was to investigate the association between non-traditional lipid parameters and optical coherence tomography (OCT)-characterized high-risk plaques in patients with acute myocardial infarction (AMI). This retrospective study included 249 first-episode AMI patients admitted to the First Affiliated Hospital of Lanzhou University between January 2022 and December 2024. All patients underwent OCT-guided assessment of culprit lesions before revascularization. High-risk plaques were defined by more than two of the following features: lipid arc â„90â °, fibrous cap thickness <65 ÎŒm, or plaque rupture/thrombus. Lesions with fewer than two of these criteria were classified as non-high-risk plaques. Clinical and laboratory data were collected, and a comprehensive lipid profile was calculated, including traditional indicators [e.g., non-HDL cholesterol (non-HDL-C)] and non-traditional ratios [e.g., apolipoprotein B/A1 ratio (ApoB/A1)]. Spearman correlation was used to assess relationships between lipid parameters and high-risk plaques. After excluding collinear variables, logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed. Model discrimination and clinical value were evaluated using receiver operating characteristic (ROC) curves, the DeLong test, integrated discrimination improvement (IDI), net reclassification index (NRI), and decision curve analysis (DCA). Among 249 AMI patients, 137 (55.0%) exhibited OCT-characterized high-risk plaques. These patients were more often male (89.8%) and presented with STEMI (84.7%). They had elevated levels of myoglobin, LDL-C, non-HDL-C, ApoB, ApoB/A1, remnant lipoprotein cholesterol (RLP-C), non-HDL-C/HDL-C ratio (NHHR), and TC/HDL-C (all Both the non-traditional ApoB/A1 ratio and the traditional lipid marker non-HDL-C were independently and linearly associated with OCT-characterized high-risk plaques in AMI. Their combined assessment enhanced the identification of high-risk plaques morphology. Show less
Qinying Chen, Dali Chen, Zhihao Liu+12 more · 2026 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Rapid platelet inhibition is essential for effective management during emergency percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). However, the oral dosage form Show more
Rapid platelet inhibition is essential for effective management during emergency percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). However, the oral dosage form of clopidogrel (CLP) commonly used in clinical practice shows a delayed onset due to gastrointestinal absorption, first-pass metabolism, and the requirement for hepatic cytochrome P450 (CYP450)-mediated bioactivation, which limits its applications in urgent scenarios and complicating post-PCI bleeding management. To address these challenges, we developed an intravenous micellar formulation (CLP/PM) using FDA-approved mPEG-PLA copolymers to promote rapid hepatic exposure and metabolic activation. By tuning the PLA chain length, micellar core density and PEG conformation were modulated, thereby influencing protein corona (PC) formation and liver-affinity interactions. Proteomic profiling revealed that micelles with intermediate PLA length selectively recruited liver-affinity apolipoproteins (ApoM, ApoH, ApoA1, and ApoB), which are known ligands of LDLR and SR-BI, while minimizing adsorption of inflammatory and opsonization proteins. The optimized CLP/PM (3.9Â k) exhibited a hepatotropic-like PC that was associated with hepatocyte-enriched uptake in primary liver cell analyses. In vivo biodistribution showed rapid liver-level signal, and pharmacokinetic studies supported enhanced CYP450-mediated activation, achieving a higher C Show less
To analyze the correlation between lipid levels and the severity of polycystic ovary syndrome (PCOS) and its predictive value for pregnancy outcome. This retrospective study included 275 PCOS patients Show more
To analyze the correlation between lipid levels and the severity of polycystic ovary syndrome (PCOS) and its predictive value for pregnancy outcome. This retrospective study included 275 PCOS patients treated with ovulation induction therapy and 234 healthy controls (used only for baseline comparisons). Lipid levels were correlated with disease phenotype and sex hormones using Spearman/Pearson coefficients. Binary logistic regression and ROC curves assessed the predictive value of lipid levels for pregnancy failure. There were statistically significant differences between the two groups in glycemic indexes (fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR)) and sex hormone indexes (testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), anti-MĂŒllerian hormone (AMH)). The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) were significantly elevated in patients with PCOS and were closely correlated with the severity of the disease. In addition, these four lipid parameters were significantly positively correlated with T, LH, FSH, and AMH, and significantly negatively correlated with E2. Elevated levels of T, LH, TG, LDL-C, and Apo B were independent risk factors for pregnancy failure after ovulation induction treatment. TG assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.861 (sensitivity 75.61%, specificity 85.53%); LDL-C assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.868 (sensitivity 75.61%, specificity 83.55%); and Apo B assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.836 (sensitivity 74.80%, specificity 86.84%). Lipid levels were significantly correlated with the severity of disease in PCOS patients, and TG, LDL-C, and Apo B levels assisted in predicting the occurrence of pregnancy failure after ovulation induction therapy. Show less
Hypothyroidism, the most prevalent endocrine disorder globally, is associated with increased cardiovascular risk. This study aims to evaluate cardiovascular risk factors-including serum oxidized low-d Show more
Hypothyroidism, the most prevalent endocrine disorder globally, is associated with increased cardiovascular risk. This study aims to evaluate cardiovascular risk factors-including serum oxidized low-density lipoprotein (ox-LDL), serum homocysteine (Hcy), and lipid profiles-and their correlations with thyroid-stimulating hormone (TSH) levels. Early identification of these risk predictors may reduce the incidence and mortality of cardiovascular disease in hypothyroid patients. This cross-sectional study included 676 participants. Subjects were stratified into four groups: three corresponding to TSH quartiles within the reference range and a fourth comprising subclinical hypothyroidism (SCH) patients with TSH levels above this range. All participants underwent physical examinations and provided fasting blood samples for measurement of TSH, free thyroxine (FT4), free triiodothyronine (FT3), blood glucose, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a) [Lp(a)], ox-LDL, and Hcy. Across the four subgroups, LDL-C, ApoB, ox-LDL, and Hcy levels exhibited significant increasing trends (all The observed correlations between ox-LDL, Hcy, and dyslipidemia in subclinical hypothyroidism may indicate a proatherogenic state. Elevated ox-LDL and Hcy emerge as independent factors associated with accelerated atherosclerosis in this condition. Show less
Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects i Show more
Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects in MASLD; however, whether AITC alleviates MASLD through VDR remains unclear. To clarify the function and underlying mechanisms of AITC in MASLD AML-12 cells were exposed to 300 ÎŒM palmitate acid (PA) for 24 hours to establish an To establish an AITC provides a robust molecular basis for improving MASLD by activating hepatic VDR and driving the downstream HNF-4α/MTTP/ApoB signaling pathway. This pathway reduces hepatic lipid accumulation, promotes FA ÎČ-oxidation, and improves insulin resistance, establishing AITC as a promising treatment for MASLD. Show less
This study aims to investigate the underlying pathophysiological relationship between obesity and osteoporosis (OP) in obese individuals, involving lipid metabolism, inflammation, and bone mineral den Show more
This study aims to investigate the underlying pathophysiological relationship between obesity and osteoporosis (OP) in obese individuals, involving lipid metabolism, inflammation, and bone mineral density (BMD). Data from 318 patients diagnosed OP at our hospital between January 2023 to December 2025 were collected and analyzed. The basic information of the patient included gender, age, BMI, drinking and smoking history, diabetes, hypertension and bone mineral density (T-scores) were recorded. Baseline peripheral blood was employed to calculate lipid markers and inflammatory cytokines. Linear regression and mediation analyses were employed to assess the relevance and differences. Increased level of blood lipids and inflammatory cytokines were associated with increased risks of OP in obesity. Compared to normal-weight individuals, obese subjects exhibited significantly lower BMD. Dysregulated lipids (TC, TG, HDL-C, ApoB) negatively correlated with BMD in obesity. Pro-inflammatory cytokines (TNF-α, IL-1ÎČ, IL-6, IL-8) inversely associated with BMD, while anti-inflammatory IL-10 showed positive association. Hyperlipidemic obese individuals had elevated inflammatory cytokines (TNF-α, IL-1ÎČ) and exacerbated BMD loss. Mediation analysis revealed TNF-α mediated 41.91% and IL-6 mediated 33.20% of the TC-BMD association; TNF-α and IL-6 mediated 28.76% and 37.38% of HDL-C-BMD effects, respectively. Obesity-associated dyslipidemia drives BMD loss partly through inflammation-mediated pathways. Key inflammatory cytokines significantly mediate lipid metabolismâs impact on bone health. Targeting lipid-inflammatory crosstalk may optimize OP management in obese populations. Show less
Pingfeng Wang, Xiaoyu Chen, Yanjin Song · 2026 · Liver international : official journal of the International Association for the Study of the Liver · Blackwell Publishing · added 2026-04-24
Zeyu Chen, Yan Wang, Bo Chen · 2026 · Journal of cardiothoracic surgery · BioMed Central · added 2026-04-24
Non-fasting blood lipid indexes and Cystatin C (CysC) are related to coronary artery stenosis, while the predictive value of their combination is unknown. This study aimed to investigate the ability o Show more
Non-fasting blood lipid indexes and Cystatin C (CysC) are related to coronary artery stenosis, while the predictive value of their combination is unknown. This study aimed to investigate the ability of their combination to predict the degree of coronary artery stenosis. Totally, 194 patients who underwent coronary angiography were included. Data on non-fasting blood lipid indexes, including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and ApoB/ApoA1, as well as CysC were collected. A degree of coronary artery stenosisââ„â70% was considered as severe coronary artery stenosis. There were 101 (52.1%) patients with severe coronary artery stenosis. HDL-C ( Non-fasting blood lipid indexes and CysC are associated with severe coronary artery stenosis in patients who undergo coronary angiography, and the combination of ApoB/ApoA1 and CysC is enough to show a promising predictive value for predicting severe coronary artery stenosis. The online version contains supplementary material available at 10.1186/s13019-026-03855-x. Show less
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly r Show more
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs. Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibited comparable HFpEF susceptibility regardless of genotype, developing hallmark phenotypes including diastolic dysfunction (E/E'), myocardial hypertrophy (heart weight/tibia length), cardiac fibrosis, and hepatic steatosis. Particularly, due to the reduced ejection fraction in KO mice, combined with HFD/L-NAME, the HF phenotype was ultimately manifested as impaired diastolic function and slightly reduced ejection fraction (with the characteristics of HFpEF and HFmrEF). Mechanistically, KO-HF females displayed significant estrogen axis disruption (plasma estradiol and the expression of ERα, ERÎČ, ESRRA, and PELP1 expression). OVX in WT females validated the importance of estrogen for HFpEF resistance. Transcriptomic profiling identified convergent targets across cardiac (ITGAD, ITGAM, FGA, and FGB) and hepatic tissues (APOA1 and APOB), revealing miR-30a-5p's orchestration of extracellular matrix remodeling (via ITGAD/ITGAM mechanotransduction),fibrinogen-mediated microvascular homeostasis, and APOB-driven metabolic dysregulation. Notably, OE intervention failed to mitigate OVX-induced cardiac/hepatic pathology, implicating estrogen-dependent miR-30a-5p functionality. These findings establish miR-30a-5p as a crucial sex-specific regulator of HF (mainly HFpEF), operating through estrogen signaling to balance cardiac compliance and metabolic adaptation. Show less
This network meta-analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid-lowering ef Show more
This network meta-analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid-lowering efficacy and safety. We systematically identified randomized controlled trials employing the frequentist NMA method to assess reductions in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp[a]), alongside treatment-emergent adverse events (TEAEs) and serious TEAEs. A total of eight trials with 3,975 Chinese patients were included. Ongericimab 150âmg every 2 weeks (Q2W) ranked first in all efficacy outcomes, demonstrating pronounced effects in LDL-C, ApoB, and Lp(a) reduction versus placebo, with mean differences of -74.21% (95% confidence interval [CI]: -79.69% to -68.73%), -64.36% (95% CI: -68.58% to -60.13%), and -50.93% (95% CI: -56.24% to -45.61%), respectively. All interventions exhibited safety profiles comparable with placebo, with no significant differences in TEAEs or serious TEAEs incidence. The analyses suggested that a portion of the evidence base was robust and reliable. These findings positioned ongericimab 150âmg Q2W as a clinically optimal PCSK9 inhibitor with robust lipid-lowering capacity. The results highlight the potential of next-generation PCSK9 monoclonal antibodies, particularly in East Asian populations, while underscoring the need for large-scale multinational trials to validate ethnic-specific responses. Show less
The effects of lipid traits on colorectal cancer (CRC) risk and the extent to which obesity may modify these effects remain unclear. To examine the associations between lipid traits and CRC risk using Show more
The effects of lipid traits on colorectal cancer (CRC) risk and the extent to which obesity may modify these effects remain unclear. To examine the associations between lipid traits and CRC risk using an observational study and Mendelian randomization (MR) analyses, and the role of weight status in the potential associations. In the Guangzhou Biobank Cohort Study (GBCS), lipid profiles were measured during 2003-2008, and CRC events were identified through record linkage with the cancer registry. MR analyses assessed the causal effects of lipid traits on CRC using a genome-wide association study meta-analysis of 185,616 Europeans. Among 28,576 GBCS participants followed until 2020, 599 CRC events occurred. Participants in the highest quartile of apolipoprotein B (apoB) had a higher CRC risk (hazard ratio [HR] 1.43, 95% CIÂ 1.02-2.01). This association remained in those with overweight/obesity (HR 2.21, 95% CI 1.28-3.83). MR analyses supported a detrimental effect of apoB on CRC (odds ratio 1.12 per 1 SD, 95% CI 1.02-1.22). MR analyses also showed positive associations for total cholesterol and the apoB/apolipoprotein A-I ratio, which were not significant in the observational study. Higher apoB levels were associated with an increased CRC risk in both observational and MR analyses, suggesting a potential role of apoB in CRC prevention, especially among participants with overweight/obesity. However, the limitations of single-time lipid measurements and the use of different ancestries across study designs indicate the need for further research to confirm the robustness and generalizability of the findings. Show less
The mechanisms by which Polycyclic Aromatic Hydrocarbons (PAHs) induce lipid metabolic disorder and inflammation in marine invertebrates remain poorly understood. This study utilized the clam Ruditape Show more
The mechanisms by which Polycyclic Aromatic Hydrocarbons (PAHs) induce lipid metabolic disorder and inflammation in marine invertebrates remain poorly understood. This study utilized the clam Ruditapes philippinarum during its reproductive stage as a model organism, integrating high-throughput omics, computational simulation, and confocal microscopy to elucidate the accumulation characteristics and toxicological pathways of PAHs. The results demonstrated that PAHs significantly accumulated in the digestive gland and gonads, primarily sequestered within lipid droplets. This tissue distribution was found to be dependent on a lipid-dependent transport mechanism mediated by ApoB, FATP, and FABP4. Mechanistically, PAHs activated SREBP1 and PPARα, ÎČ nuclear receptors by interfering with the neuroendocrine system and endoplasmic reticulum stress pathways. This activation resulted in dysregulated lipid metabolism (favoring synthesis over degradation) and subsequent abnormal lipid (TG, PL) deposition. Furthermore, PAHs induced low-grade inflammation by synergistically activating the NF-ÎșB and AP-1 pathways, a response driven by both lipotoxicity and cellular organelle stress. This finding provides important scientific evidence for contaminant risk assessment in aquatic organisms. Show less
Dyslipidemia is common in patients with MASLD, but the frequency and significance of inherited disorders of dyslipidemia are unclear. We investigated the prevalence and significance of pathogenic vari Show more
Dyslipidemia is common in patients with MASLD, but the frequency and significance of inherited disorders of dyslipidemia are unclear. We investigated the prevalence and significance of pathogenic variants associated with selected monogenic disorders of dyslipidemia in 3358 patients with well-characterised MASLD. We identified clinically relevant variants in APOB, MTTP, PCSK9, ANGPTL3, LDLR and LDLRAP1 genes which can cause hypobetalipoproteinemia (HBL) and familial hypercholesterolemia (FH). Using ClinVar annotations as initial variant selection, we identified 2027 variants in those 6 genes which are reported as 'pathogenic' or 'likely pathogenic' (P/LP). We first assessed for the presence of P/LP variants in the study cohort and then investigated the effect of carrying P/LP variants on liver histology, by comparing ~4 matched controls for each APOB and LDLR carrier. As interpretative analyses, we also looked at the difference between liver enzymes, lipid measures and outcomes between the carriers and matched controls. Twenty-two variants among these 2027 P/LP variants were present in 24 out of 3358 patients (12 ApoB, 10 LDLR, 1 ANGPTL3 and 1 MTTP variant carriers). Compared to controls, APOB carriers had higher steatosis grade (2.4 vs. 1.7, p-value 0.0028), higher NAFLD activity score (NAS) (4.9 vs. 3.8, p-value 0.04), and numerically higher but statistically not significant fibrosis stage (1.2 vs. 1.1, p-value 0.75) and ALT (87.4 vs. 58.1âU/L, p-value 0.06). Their LDL-c (51 vs. 147.8âmg/dL, p-value 6.1E-09) and triglycerides (91.5 vs. 160.6âmg/dL, p-value 2.8E-03) were significantly lower. Compared to controls, LDLR carriers had numerically higher steatosis grade, NAS, fibrosis stage and LDL-c levels, but these were not statistically different. Monogenic disorders of dyslipidemia are rarely present in patients with MASLD and are sometimes associated with worse liver histology. Testing for these conditions may be considered on a case-by-case basis. Show less
Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (L Show more
Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies. To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy. This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least a moderate- or high-intensity statin) and either an LDL-C level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease or an LDL-C level of 70 mg/dL or greater without a history of major atherosclerotic cardiovascular disease. The trial was conducted at 59 sites across 17 countries; the first participant was screened on August 8, 2023, and the last follow-up visit occurred on April 7, 2025. Participants were randomized (2:1) to 20 mg of enlicitide (nâ=â202) or placebo (nâ=â101) once daily for 52 weeks. The primary outcome was the mean percentage change in LDL-C level at week 24. The secondary outcomes included the mean percentage change in LDL-C level at week 52, the mean percentage change at week 24 in levels of non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, and the median percentage change at week 24 in lipoprotein(a). Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial. The mean LDL-C level was 119.0 mg/dL (SD, 41.0 mg/dL) at baseline, all had statin current use (81.5% were taking a high-intensity statin), and 64.4% were taking ezetimibe. The mean percentage change in LDL-C level at week 24 was -58.2% in the enlicitide group vs 2.6% in the placebo group (between-group difference, -59.4% [95% CI, -65.6% to -53.2%]; Pâ<â.001). The mean percentage change in LDL-C level at week 52 was -55.3% in the enlicitide group vs 8.7% in the placebo group (between-group difference, -61.5% [95% CI, -69.4% to -53.7%]; Pâ<â.001). At week 24, the mean percentage change in non-HDL-C level was -52.3% in the enlicitide group vs 2.1% in the placebo group (between-group difference, -53.0% [95% CI, -58.5% to -47.4%]; Pâ<â.001), the mean percentage change in apolipoprotein B level was -48.2% vs 1.8%, respectively (between-group difference, -49.1% [95% CI, -54.0% to -44.3%]; Pâ<â.001), and the median percentage change in lipoprotein(a) level was -24.7% vs -1.6% (between-group difference, -27.5% [95% CI, -34.3% to -20.6%]; Pâ<â.001). The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups. Among adults with HeFH, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a). ClinicalTrials.gov Identifier: NCT05952869. Show less
Dysregulation of low-density lipoprotein (LDL) cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease. Endogenous molecules targeting LDL clearanc Show more
Dysregulation of low-density lipoprotein (LDL) cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease. Endogenous molecules targeting LDL clearance play crucial roles in the progression of liver steatosis. Human cathelicidin LL-37 can form complexes with lipoproteins, but whether these complexes regulate lipoprotein-driven cholesterol metabolism is not clear. Here, we find that cathelicidin LL-37 binds to LDL via apolipoprotein (Apo)B-100 domains, enhancing the solubility of ApoB-100 and inhibiting the modifications and aggregation of LDL. LL-37-LDL interaction promotes LDL uptake through LDL receptor (LDLR) both in hepatocytes and macrophages. This interaction also promotes LDL cholesterol clearance by facilitating cholesterol excretion and cholesterol efflux. In Apoe Show less
Primary renal small cell carcinoma (PRSCC) is a rare, poorly differentiated neuroendocrine carcinoma, and its clinicopathological features and the gene mutation spectrum associated with its pathogenes Show more
Primary renal small cell carcinoma (PRSCC) is a rare, poorly differentiated neuroendocrine carcinoma, and its clinicopathological features and the gene mutation spectrum associated with its pathogenesis remain to be elucidated. The present study aimed to characterize the genetic mutation spectrum associated with the pathogenesis of PRSCC, identify novel driver and predisposing genes for the disease, reveal its histopathological features associated with genetic mutations and systematically summarize the clinicopathologic characteristics and prognostic factors of PRSCC patients to provide a theoretical basis for molecularly targeted therapy and prognostic assessment of PRSCC. Whole-exome sequencing (WES) was performed on PRSCC samples to characterize the spectrum of genetic mutations and the results were validated using Sanger sequencing. Immunohistochemistry (IHC) was performed to reveal the histopathological features associated with these mutations. Furthermore, based on the published literature, a population-based study was conducted by searching PubMed and EMBASE databases to systematically summarize the clinicopathologic characteristics and prognostic factors of patients with PRSCC. WES identified 113 somatic single-nucleotide variants, 26 somatic insertions and deletions and mutations in 8 predisposing genes (DST, OR10H3, PTK2B, APOBR, ZNF606, CCN4, ADCK1, and MYH2) and 10 driver genes (KRTAP10-9, HYDIN, ZNF665, KRTAP10-2, GPAM, MUC12, KRT9, CCDC168, DUSP27 and MDC1). Sanger sequencing of germline DNA identified a germline A/G variant in the HYDIN sequence, first reported in PRSCC. Furthermore, IHC analysis indicated that PRSCC was positive for CD56, Syn, insulinoma associated protein 1, CgA and neuron specific enolase. In the population-based study, the majority of patients with PRSCC were elderly (57.92±15.75 years), with a pathological tumor (T) 3/4 stage (68.3%) and presented with lymph node involvement (51.7%) and distant metastasis (51.7%). T stage was an independent prognostic factor for overall survival in patients with PRSCC (P=0.004). Driver mutations in the HYDIN gene may be a key factor in the pathogenesis of PRSCC. HYDIN may serve as a prognostic marker and a target for immunotherapy in the management of PRSCC. However, due to the extreme rarity of PRSCC, the WES analysis in the present study was based solely on individual cases. To ensure the reliability and generalizability of genetic alterations detected by WES, additional PRSCC samples, along with cell and animal experiments, are warranted to confirm the role of these genetic variants (particularly HYDIN) in PRSCC pathogenesis. The functional role of HYDIN mutations in PRSCC pathogenesis requires further validation in future research. Show less
Ischemic heart failure (IHF) is one of the leading causes of death in the world. Plasma apolipoprotein C3 (ApoC3) levels are significantly elevated in patients with heart failure and positively associ Show more
Ischemic heart failure (IHF) is one of the leading causes of death in the world. Plasma apolipoprotein C3 (ApoC3) levels are significantly elevated in patients with heart failure and positively associated with the incidence of ischemic heart disease (IHD). However, the causal association between ApoC3 and IHD development is unclear. ApoC3 expression changes were assessed in plasma from IHF patients/healthy donors and cardiac tissue from rodent models. 10-week-old male human ApoC3 transgenic (ApoC3 Overexpression of human ApoC3 in ApoC3 ApoC3 overexpression could activate cardiac TLR2/NF-ÎșB to trigger the inflammation, oxidation, and apoptosis pathways, finally aggravating IHF in mice. Inactivation of ApoC3 could significantly alleviate IHF in hamsters. Show less
Vascular calcification (VC) is prevalent in patients with chronic renal failure (CRF), and it is closely related to the morbidity and mortality of cardiovascular diseases; however, no medical treatmen Show more
Vascular calcification (VC) is prevalent in patients with chronic renal failure (CRF), and it is closely related to the morbidity and mortality of cardiovascular diseases; however, no medical treatments are available for this condition. Recent clinical studies have shown that plasma apolipoprotein C3 (ApoC3) levels are positively correlated with VC. However, whether ApoC3 is involved in VC remains unclear. Sections of calcified renal arteries from CRF patients were immunostained to measure calcium deposition and ApoC3 expression. VC was induced in ApoC3 transgenic (Tg) and knockout (KO) mice by both 5/6 nephrectomy and vitamin D ApoC3 expression levels were increased in calcified arteries from mice and patients with CRF. ApoC3 overexpression exacerbated calcium deposition in the calcified aortas from Tg mice in vivo, and in calcified aortic rings of Tg mice ex vivo and VSMCs infected by adenovirus of ApoC3 in vitro. Consistently with these findings, ApoC3 deficiency alleviated these effects. Furthermore, ApoC3 overexpression increased ferroptosis in calcified aortas and VSMCs, whereas ApoC3 deficiency suppressed ferroptosis. Further investigation revealed that ApoC3 inhibited the AMPK/NRF2 signaling pathway through toll-like receptor 2 (TLR2) in calcified VSMCs, downregulated the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), subsequently increased lipid peroxidation and promoted ferroptosis, ultimately exacerbating calcification in the VSMCs. Furthermore, we found that knockdown of ApoC3 by siRNA remarkably attenuated calcification of renal arterial rings in humans. We demonstrated that ApoC3 exacerbated VC and increased the osteogenic transdifferentiation in VSMCs by increasing ferroptosis. ApoC3 might be a potential target for VC treatment. Show less
Canine hepatocellular carcinoma (HCC) requires further molecular characterization to identify diagnostic and therapeutic targets, and to establish whether dogs with this condition can model the human Show more
Canine hepatocellular carcinoma (HCC) requires further molecular characterization to identify diagnostic and therapeutic targets, and to establish whether dogs with this condition can model the human disease. Accordingly, we aimed to identify differentially expressed genes (DEGs) in canine HCC and evaluate cross-species transcriptomic dysregulation in canine and human HCC. Liver tissue samples from three dogs with HCC and three healthy dogs were subjected to next-generation sequencing, followed by RT-qPCR validation. Identified DEGs were then targeted in bioinformatics analyses (pathway enrichment, protein-protein interaction network, and hub gene analyses) for molecular characterization and comparison with human HCC datasets. We identified 975 DEGs (upregulated: 604; and downregulated: 371). Extracellular matrix-receptor interaction, focal adhesion, cell adhesion molecule, PI3K/Akt signaling, and cytokine/chemokine-related pathways were enriched. C1R, APOC3, C1QA, APOA1, C1QB, ACTG1, C1QC, CRP, ANXA5, and ANXA2 were identified as hub genes. Canine and human HCCs share 118 DEGs, highlighting conserved alterations in metabolic pathways, PI3K-Akt signaling, focal adhesion, and PPAR signaling pathways. Based on human HCC data, SPP1, NQO1, RRM2, APOA1, APOC3, ALDOB, and IGF1 were identified as prognosticators indicating poor overall survival. This study presents the first cross-species transcriptomic analysis of canine HCC, revealing significant molecular resemblances to human HCC, indicating it may be a promising comparative model for studying tumor biology, drug responses, and novel therapeutic interventions. Show less
BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations Show more
BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations with being dementia-free at age 85 (DF85).MethodsWe examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAFââ€â1%) coding and non-coding variants in DF85 participants (nâ=â3657) against individuals who were not DF85 (nâ=â20,010). We verified associations using a stricter control set who developed dementia before age 85 (nâ=â5552).ResultsWe observed an association at Show less
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Ath Show more
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Atherosclerotic plaques accumulated in the aorta and aortic sinus after HFD, while statin and high-dose GP alleviated this burden. TC, TG, LDL-C, MCP-1, MCP-3 and IL-2 showed significant increase after HFD, while statin and GP decreased LDL-C, MCP-1 and MCP-3. The goblet cells, ZO-1 and Occludin decreased after HFD, while statin and GP increased them, indicating that the intestinal barrier integrity was improved. Additionally, the composition of gut microbiota was modulated by GP. Some candidate taxa were identified, such as This study suggests that GP is beneficial for alleviating atherosclerosis in HFD-induced ApoE Show less
Shuhui Chai, Yihang Zhang, Yi Guo+17 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Atherosclerosis is the inflammatory consequence of lipid accumulation with plaque formation in the vascular intima and is a common condition to develop into various cardiovascular diseases. Current th Show more
Atherosclerosis is the inflammatory consequence of lipid accumulation with plaque formation in the vascular intima and is a common condition to develop into various cardiovascular diseases. Current therapies do not always lead to satisfactory treatment outcomes. Enterolactone, a mammalian lignan produced by bacterial transformation from plant lignans, has a preventive effect against cardiovascular disease. However, its effect on atherosclerosis and the underlying mechanism of action remain unclear. To explore the therapeutic effect of ENL on atherosclerosis and elucidate the underlying mechanism. We established a model of atherosclerosis on ApoE-/- C57BL/6 mice by high fat diet. The aortic root was collected and sectioned to assess arterial plaque area, collagen fibrillar proliferation, and lipid content. RT-qPCR was used to determine the inflammatory response in the artery of mice. The serum from mice was isolated to measure lipid levels, and the fecal microbiota was analyzed by 16S rDNA. H In the animals, enterolactone significantly improved lipid metabolism, attenuated ferroptosis occurring in the intima, facilitated the antioxidant mechanisms, and promoted healing of the endothelial lesions, by interacting with Nrf2. Of great importance, enterolactone massively altered the gut microbiota toward a curative outcome by elevating the abundance of beneficial bacteria, such as the SCFA-producing taxa. Additionally, ENL suppresses lipid peroxidation and inflammatory activation in HUVECs by regulating the Keap1/Nrf2/GPX4 pathway, and knocking down Nrf2 attenuates the treatment effect of ENL. Enterolactone effectively resolves intimal inflammation and redresses atherosclerosis by ameliorating the gut microbiome and modulating lipid metabolism via the Keap1/Nrf2/GPX4 pathway. Show less
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To addre Show more
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To address this, we performed multi-tissue metabolomic profiling (liver, heart, and serum) in apolipoprotein E-deficient (ApoE-/-) mice subjected to CR. Metabolomic analyses of the multiple tissues revealed that glycerophospholipid metabolism pathway was consistently modulated by CR. To explore its relevance in vascular diseases, we performed serum metabolomic profiling in an abdominal aortic aneurysm (AAA) model induced by angiotensin â Ą (Angâ Ą) infusion in ApoE-/- mice. The level of lysophosphatidylethanolamine (LPE) (16:0/0:0), a metabolite in the glycerophospholipid metabolism pathway, was elevated during AAA progression and significantly reduced by CR intervention, suggesting its potential as a vascular disease risk factor. Notably, glycerophospholipid metabolism and LPE (16:0) were significantly associated with vascular diseases and aging-related indicators in human multi-omics data, including public transcriptomic and lipidomic, and our serum multi-omics profiling of 76 healthy aged individuals. Collectively, our findings establish glycerophospholipid metabolism and LPE (16:0) as systemic signatures of CR with diagnostic potential. They highlight a crucial link between systemic metabolism and vascular remodeling and remodeling-associated vascular diseases, while also functioning as indicators of systemic aging. Show less
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical d Show more
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and C16orf95/MAP1LC3B. Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2. We also demonstrate that these variants have significant association with Alzheimer's disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE, coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation. Show less