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To identify the various profiles of social isolation among 18-59-year-old patients with cancer in Western China and examine their demographic, clinical, and cultural predictors. This cross-sectional study included 300 patients from a tertiary hospital who completed standardized assessments of social isolation (Social Avoidance Scale, UCLA Loneliness Scale) and family functioning. Latent Profile Analysis (LPA) was used to identify the subgroups, and multinomial logistic regression was used to analyze predictors of the profiles. Three distinct latent profiles were identified: "avoidance-dominant" (52.3%), which was characterized by high levels of social avoidance (12.52 ​± ​1.38) and low loneliness (30.87 ​± ​6.89), "loneliness-dominant" (27.0%), which was characterized by high levels of loneliness (53.15 ​± ​6.24) and low social avoidance (2.07 ​± ​1.38), and "balanced" (20.7%), which was characterized by balanced scores on both the measures. Individuals with fatigue, employment status, personality traits, and family dynamics significantly predicted profile membership ( Social isolation was heterogeneous among young and middle-aged patients with cancer. Fatigue significantly predicted distinct patterns of social isolation. Furthermore, exploratory findings indicated a potential role of religious beliefs in the avoidance-dominant profile; however, replication with larger samples is required. Family dynamics may buffer the risk of isolation in patients prone to avoidance, whereas those dominated by loneliness may lack such safeguards. Health care providers can implement tailored interventions to mitigate social isolation based on these varying profiles. Show less

Apolipoprotein B48 (ApoB48) may be an indicator of residual cardiovascular risk beyond conventional lipid measures. However, its performance for detecting coronary artery disease (CAD), alone and in combination with the ankle-brachial index (ABI), remains to be investigated. This cross-sectional study (358 patients; 299 and 59 with and without CAD, respectively) assessed the value of ApoB48 (cutoff: ≥4.5 μg/mL) and ABI (cutoff: <0.9) in detecting CAD. Subgroup analyses were performed for patients with diabetes mellitus, hypertension, dyslipidemia, and low levels of low-density lipoprotein-cholesterol (LDL-C) (<100 mg/dL). Baseline characteristics, including lipid profiles and biomarker levels, were compared between patients with and without CAD. Patients with CAD exhibited significantly higher ApoB48 levels compared to those without (5.1 ± 3.2 vs. 4.0 ± 2.2 μg/mL, respectively, p = 0.001); there were no significant differences in ABI values. The sensitivity and specificity of ABI alone for CAD were 16.7% and 81.4%, respectively, while those for ApoB48 alone were 48.2% and 61.0%, respectively. Combining both markers improved sensitivity to 55.5%, though specificity declined to 47.5%. Subgroup analyses revealed that ApoB48 maintained superior sensitivity across groups with diabetes, hypertension, dyslipidemia, and low levels of LDL-C. Lipid parameters (LDL-C, non-high density lipoprotein-cholesterol, and triglycerides) showed minimal discriminatory power between patients with and without CAD. ApoB48 demonstrates superior sensitivity for CAD detection compared to ABI, particularly in high-risk patients. While combining ApoB48 and ABI enhances sensitivity, it compromises specificity, suggesting the need for balanced diagnostic strategies. ApoB48 may be a valuable marker of residual cardiovascular risk, particularly in patients with well-controlled LDL-C or comorbid metabolic conditions. Show less

Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease characterized by amyloid-beta (Aβ) accumulation in cortical and leptomeningeal blood vessel walls. Reduced Aβ clearance in the vasculature elevates the risk of CAA, while increasing evidence indicates that enhanced Aβ production in neurons also contributes. The impact of Aβ on the diverse cell types of the neurovascular unit (NVU)-including endothelial cells (ECs), pericytes, neurons, vascular smooth muscle cells (VSMCs), and astrocytes-remains unclear. This narrative review proposes that Aβ accumulation in NVUs during CAA drives a transcriptional response that reduces Aβ clearance while activating a neuron-specific post- transcriptional response that enhances Aβ production. Specifically, Aβ in NVUs was found to initiate a transcriptional cascade that destabilizes endothelial cells, increases blood-brain barrier permeability, and damages pericytes, ultimately inducing inflammatory and dysfunctional changes in VSMCs. These changes cause mitochondrial dysfunction and TGFβ deregulation in neurons, activating profibrotic mechanisms. Post-transcriptional regulation by microRNA networks in neurons affects Aβ processing by controlling the balance between amyloidogenic and non-amyloidogenic pathways through BACE1 and ADAM10 expression respectively. This review improves our understanding of Aβ accumulation in neurovascular units in CAA, potentially leading to better diagnostics, early biomarkers, and tools for prognosis and treatment. Show less

Familial hypercholesterolemia (FH) is a prevalent hereditary disorder, with its monogenic form linked to an elevated risk of early-onset ischemic heart disease. Evaluating the prevalence and penetrance of pathogenic and likely pathogenic variants associated with this disorder would provide valuable information supporting routine FH screening of the general population. Such informed screening would facilitate early identification of at-risk individuals, enabling timely intervention and management. We analyzed genetic data from 4,856 individuals with various cardiovascular conditions for pathogenic and likely pathogenic variants in the PCSK9, APOB, and LDLR genes. The evaluation included comprehensive clinical assessments, instrumental examinations, and laboratory tests. All genetic data were obtained through the whole-genome sequencing of blood leukocytes. A total of 1.77% of participants carried pathogenic or likely pathogenic variants in the LDLR or APOB genes, and none in the PCSK9 gene. After adjusting for sex and age, the risk of ischemic heart disease was 1.3 times higher in carriers of pathogenic or likely pathogenic variants [95% CI 1.18-1.46; FH remains significantly underdiagnosed. Only 10.5% of carriers of pathogenic or likely pathogenic variants in the LDLR and APOB genes had a prior diagnosis of FH. Our findings suggest low diagnostic rates for this disorder in Eastern European populations and highlight the need for routine genetic screening of younger individuals. However, further research is needed to assess the clinical applicability and cost-effectiveness of such screening programs. Show less

An increasing body of research indicates an association between lipid-lowering medications and sensorineural hearing loss (SNHL), although there is still controversy. Therefore, the aim of this study is to investigate the genetic correlation between different lipid-lowering therapeutic gene targets and SNHL. The genetic association between lipids, lipid-lowering drug target genes, and SNHL was analyzed using a 2-sample Mendelian randomization approach. The exposures included 5 circulating lipid levels (triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and apolipoprotein B) and 10 target genes simulating the effects of lipid-lowering drugs (HMGCR, PCSK9, Niemann-Pick C1-like 1 [NPC1L1], LDLR, APOB, CETP, LPL, ANGPTL3, APOC3, and PPARA). Summary data from a large-scale genome-wide association study on SNHL from the Finnish database were used as the outcome. The inverse variance-weighted method was employed as the primary approach, with sensitivity tests conducted to evaluate heterogeneity and pleiotropy in the results. The genetic prediction of lipid levels was not significantly associated with SSNL. However, genetic proxies for lowering low-density lipoprotein cholesterol, specifically variants in NPC1L1 (OR = 1.943 [95% CI 1.116-3.383]; P = .018) and LDL receptor (LDLR) (OR = 1.279 [95% CI 1.107-1.477]; P < .001), were associated with an increased risk of SNHL. Similarly, a genetic proxy for lowering triglycerides, the apoprotein C-III (APOC3) variant (OR = 1.174 [95% CI 1.054-1.307]; P = .003), was associated with an increased risk of SNHL. After Bonferroni correction, the genetic variants for LDLR and APOC3 remained significantly associated with an increased risk of SNHL, while the association with the NPC1L1 lipid-lowering variant was no longer significant. This study suggests that lipid-lowering medications potentially have a causal impact on increasing the risk of SNHL through the LDLR and APOC3 pathways. LDLR and APOC3 show potential as candidate drug targets for the prevention of SNHL. However, the results of the study and the potential mechanism of action require further experimental validation and evaluation. Show less

Thrombosis is a life-threatening complication in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study aims to conduct a statistical analysis of the incidence of blood clots and lipid concentrations, and to examine the networks of oxylipins in hospitalised patients with SARS-CoV-2. Serum samples of 1731 hospitalised patients with SARS-COV-2 were used to measure six lipid parameters: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA), and apolipoprotein B (apoB). Additionally, the lipid profiles and oxidative lipidomics characteristics were examined via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) in SARS-COV-2-positive patients with and without thrombosis. The mortality rate in the SARS-COV-2 thrombosis group was significantly higher at 29.6% compared to the SARS-COV-2 non-thrombosis group at 12.1% (P < 0.0001). The levels of the lipid parameters were closely associated with both thrombosis and SARS-COV-2 severity. Patients with SARS-COV-2 admitted to the hospital exhibited significant changes in oxidative lipid metabolites, specifically in the arachidonic acid (ARA) and docosahexaenoic acid (DHA) classes, compared with those in the control group. Among the thrombus group, 28 oxidative lipid metabolites were found to be differentially expressed compared to the non-thrombus group, and with the most notable variations observed in 20-hydroxyPGF2α and 14(15)-EpETE. Enrichment analysis using KEGG revealed that differential oxidized lipid metabolites mainly concentrated in the ARA and serotonergic synapses metabolism signaling pathway. Our findings indicate a close association between lipid mediators and both SARS-COV-2 and thrombi. Specifically, ARA and serotonergic synapses metabolism signaling pathway may be an important pathogenic factor for thrombosis caused by SARS-COV-2. Furthermore, 20-hydroxyPGF2α and 14(15)-EpETE show promise as potential biomarkers for SARS-CoV-2-induced thrombosis. Show less

Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people's physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is a lack of comprehensive analysis of the underlying mechanisms. This study used fully nutritious brown rice as raw material, and after germination under various stress conditions, it significantly increased the levels of gamma aminobutyric acid (GABA, four carbon non protein amino acid), resistant starch, flavonoids, and other components that regulate metabolic diseases. Using rats as experimental subjects, a model of hyperlipidemia and hyperglycemia was constructed, with rice consumption as the control. The experimental period was 8 weeks. Research has found that feeding sprouted brown rice can significantly improve the accumulation of white fat in the liver caused by a high-fat diet, significantly reduce TC, TG, LDL-C, apoB, HL, LPL, and LCAT, significantly increase HDL-C and apoA1, and significantly reduce the levels of inflammatory factors IL-6 and TNF-α. Therefore, consuming sprouted brown rice can reduce the risk of hyperlipidemia, inflammation, and tumor occurrence by promoting fat breakdown, and can also increase the abundance of metabolic-promoting microorganisms (especially Euryarchaeota and Lactobacillus) in the intestine, improving the entire metabolic ecological network of rats. Show less

Apolipoprotein B (apoB) is the primary structural protein in low-density lipoprotein (LDL) and plays a crucial role in atherogenesis. The Framingham Risk Score (FRS) is a widely used tool for assessing cardiovascular disease (CVD) risk. However, the correlation between apoB and FRS in Iraqi individuals remains underexplored. This study aims to evaluate the association between serum apoB levels and FRS, establishing its potential utility as a predictive biomarker for coronary artery disease (CAD) risk. A cross-sectional study was conducted on 201 individuals aged ≥30 years attending a clinical laboratory in Baghdad between November 2022 and October 2023. Serum apoB and lipid profiles were measured, and FRS was calculated for all participants. Correlation analysis between apoB and FRS was performed using Spearman's test, while group comparisons were conducted The median age of participants was 48 years, with males constituting 51.2% of the cohort. Median apoB and FRS values were 130 mg/dL and 4, respectively. A strong positive correlation was observed between serum apoB and FRS ( These findings suggest that apoB may serve as a reliable biomarker for CAD risk assessment in the Iraqi population, where its predictive value has been underexplored. The identified cutoff value (97.75 mg/dL) highlights its potential role in refining risk stratification beyond traditional lipid markers. Further prospective studies are needed to validate these findings and assess their clinical impact. Show less

Memory impairment is frequent among alcohol use disorder (AUD) patients, and we lack specific biomarkers to detect it. Certain apolipoproteins were linked to cognition, and carrying the APOE4 gene is a vulnerability factor to memory impairment in AUD patients. We explored memory deficits in alcohol-dependent male mice and humans versus controls, and their relationship to Apolipoprotein AI (APOAI), apolipoprotein B (APOB), and apolipoprotein E (APOE) plasma levels. Male C57BL/6J mice underwent voluntary alcohol drinking (two-bottle choice, 2BC) and chronic intermittent ethanol vapor exposure (CIE) as a model of alcohol dependence; memory was assessed by the Object Location Test (OLT) and Novel Object Recognition Test (NORT). Additionally, male AUD-diagnosed patients were recruited in Spain during an alcohol dishabituation program and assessed by the Wechsler Memory Scale-IV (WMS-IV). Plasma APOAI, APOB, and APOE levels were checked in mice and humans by ELISA kits and Luminex immunoassay technology. APOAI immunolabeling was quantified in mouse brain in early withdrawal and following alcohol consumption. CIE-2BC mice (n = 8) escalated alcohol consumption compared to Air-2BC controls (n = 11) and showed deficits in spatial memory (OLT) and recognition memory (NORT) while AUD patients (n = 12) showed deficits in verbal and visual memory (WMS-IV) versus controls (n = 16). Higher plasma levels of APOAI were detected in CIE-2BC mice and AUD patients, with no differences in APOB and APOE in animals and humans. Significant negative correlations were found between levels of APOAI, APOB, and APOE and memory function tests/scales in the entire sample, with APOAI showing consistent results in both animals and humans. APOAI immunoreactivity was detected in the mice subfornical organ, but the signal did not differ between experimental groups. Both CIE-2BC mice and AUD patients exhibited elevated plasma levels of APOAI during early abstinence. APOAI correlated with poorer memory performance in both species, suggesting a potential role for this apolipoprotein in the context of alcohol-induced cognitive impairment. Show less

OxPL-apoB (oxidized phospholipids [OxPL] on apoB-100), which include OxPL present on Lp(a) (lipoprotein[a]), are associated with higher cardiovascular risk. Experimental studies suggest that OxPL may influence platelet function. This observational study assessed the association of OxPL-apoB with intrinsic and on‑clopidogrel platelet reactivity and long-term cardiovascular events in patients undergoing coronary angiography with or without percutaneous coronary intervention in 2040 patients in the EXCELSIOR trial (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate). The association of OxPL-apoB to expression of CD62P, CD41, or PAC-1 levels and intrinsic and on-clopidogrel platelet reactivity to collagen and ADP was determined. The relationship of OxPL-apoB and Lp(a) to myocardial infarction-free survival and all-cause mortality at a median of 7 years was assessed using Cox regression models. Elevated levels of OxPL-apoB were associated with the severity of coronary obstruction, and higher prevalence of prior myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft surgery. No significant associations were present between OxPL-apoB and intrinsic or on-clopidogrel platelet reactivity or activation of platelet receptors. Analyzed individually in separate multivariable models, both OxPL-apoB (hazard ratio, 1.022 [95% CI, 1.005-1.040]; In patients undergoing coronary angiography with or without percutaneous coronary intervention, OxPL-apoB was not associated with intrinsic and on-clopidogrel platelet reactivity mediated by collagen or ADP. The association of OxPL-apoB and Lp(a) suggests that the accumulation of OxPL on Lp(a) may be a key determinant of long-term cardiovascular outcomes. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00457236. Show less

A key step in primary prevention is the assessment of atherosclerotic cardiovascular disease (ASCVD) risk. Risk enhancer tests are additional tools used to further improve ASCVD risk assessment over conventional risk markers. Our objective was to determine whether estimated small, dense low-density lipoprotein cholesterol (E-sdLDL-C) can improve risk assessment and serve as a new risk enhancer test. We used a prospective cohort analysis of participants in the UK Biobank study with a median (interquartile range) follow-up of 10 (6.7-12.3) years. We included 271 760 individuals who were not on lipid-lowering medication at baseline and did not have incident ASCVD. The primary study outcome was the incidence of all-cause ASCVD. E-sdLDL-C was strongly associated with ASCVD events with a hazard ratio (HR) of 1.23 (95% CI, 1.22-1.24). After multivariable adjustment for age, sex, systolic blood pressure, hypertension, type 2 diabetes, and blood pressure medications, E-sdLDL-C and ApoB (apolipoprotein B) remained the most significant lipid risk factors (HR, 1.18 [95% CI, 1.16-1.19] and 1.17 [95% CI, 1.16-1.18] per SD, respectively). After further adjustment for ApoB, the association between low-density lipoprotein cholesterol (LDL-C) with all-cause ASCVD was completely reversed with an HR of 0.84 (95% CI, 0.81-0.86), but E-sdLDL-C continued to have a significant positive association with an HR of 1.11 (95% CI, 1.08-1.13). When E-sdLDL-C was discordantly higher than either LDL-C or ApoB, the risk for ASCVD was higher (LDL-C, 31% higher; ApoB, 17% higher). When elevated E-sdLDL-C is coupled with other risk enhancer tests, there is a greater risk for developing ASCVD. In a UK Biobank cohort for primary prevention, the risk of all-cause ASCVD was better captured by E-sdLDL-C than LDL-C. It was also more predictive than LDL-C and ApoB when discordant with these 2 measures. E-sdLDL-C, which can be freely and automatically calculated from a standard lipid panel, can potentially improve ASCVD risk assessment without additional laboratory testing. Show less

Calcific aortic valve stenosis (CAVS) is steadily rising worldwide with no effective pharmacological agents available. Observational studies implicated dyslipidaemia as a risk factor for CAVS. Whether dyslipidaemia is causative for CAVS and the therapeutic potential of different lipid-modifying drug targets for CAVS treatment remains unclear. We appraised the relationship of genetically-proxied lipid traits and 12 lipid-modifying drug targets with CAVS risk using Mendelian randomization (MR). Genetic variants associated with lipid traits and variants in genes encoding lipid-modifying drug targets were retrieved from GLGC. Summary-level data for CAVS were obtained from the TARGET consortium and FinnGen. Validation analyses were performed using genetic instruments retrieved from liver-derived gene expression and circulation plasma levels of targets. Colocalisation and mediation analyses were performed to evaluate the robustness of our findings and explore potential mediators (i.e., lipoprotein a (Lp(a)), body mass index, apolipoprotein B (ApoB)). The MR analyses supported that total cholesterol and LDL-cholesterol level were independent causal risk factors. The drug-target MR analysis suggested that genetic mimicry of PCSK9 inhibition should reduce CAVS risk (OR = 0.63, 95% CI = 0.56-0.70), which was corroborated by colocalisation analysis. Secondary analyses supported a genetically proxied effect of liver-specific PCSK9 expression (OR = 0.94 per SD reduction in PCSK9 expression, 95% CI = 0.88-1.00) and circulating plasma levels of PCSK9 (OR = 0.86 per SD reduction in PCSK9 protein, 95% CI = 0.83-0.88) on CAVS risk. ApoB and Lp(a) mediated 55.9% and 4.5%, respectively, of the total effect of PCSK9 on CAVS risk. Multiple sensitivity analyses supported this observation. Our study supports total cholesterol, LDL-cholesterol as a causal factor for CAVS, and genetically proxied inhibition of PCSK9 may reduced its risk. Show less

The incidence of silent myocardial infarction (SMI) is increasing. Meanwhile, due to the atypical clinical symptoms and signs associated with SMI, the prognosis for patients is often poor. This prediction model used the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analyses to screen variables. Predictive accuracy was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). The clinical decision curve analysis (DCA), alongside the calibration curve and clinical impact curve (CIC) analyses, were used to assess model validity. This study included 174 patients, 64 (36.8%) of whom experienced SMI; logistic regression analysis identified six variables: gender, age, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B/apolipoprotein A1 (ApoB/A1), uric acid (UA), and triglyceride glucose-body mass index (TyG-BMI). The results identified the TyG-BMI as a predictor of SMI (odds ratios (OR) = 1.02, 95% CI: 1.01-1.03; The TyG-BMI is an independent predictor of SMI. A prediction model based on the TyG-BMI showed good predictive ability for SMI. Show less

Apolipoprotein B (APOB) rs676210 polymorphism has been associated with altered lipid metabolism and cardiovascular risk in various populations; however, data from Vietnamese populations remain limited. This study aimed to investigate the association of the APOB rs676210 variant with lipid profiles among Vietnamese individuals newly diagnosed with elevated low-density lipoprotein cholesterol (LDL-C). A cross-sectional study was conducted among 69 Vietnamese adults newly diagnosed with elevated LDL-C (≥130 mg/dL) at a tertiary hospital in Southern Vietnam. Participants were genotyped for APOB rs676210 using real-time polymerase chain reaction (PCR) with allele-specific probes. Lipid profile components, including LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and ApoB, were compared across genotype groups (AA vs GA/GG) and alleles (A vs G). Statistical analyses involved t tests, chi-square tests, and multivariable linear regression adjusted for age, sex, the BMI, and diabetes. P<.05 was considered statistically significant. Of the 69 participants, 32 (46.4%) carried the AA genotype, while 37 (53.6%) carried the GA or the GG genotype. The AA genotype was associated with significantly higher LDL-C (mean 5.19, SD 0.95, vs mean 4.37, SD 0.97, mmol/L; P<.001), non-HDL-C (mean 5.94, SD 1.08, vs mean 5.31, SD 1.22 mmol/L; P=.03), and ApoB (mean 149.5, SD 26.3, vs mean 136.9, SD 15.2, mg/dL; P=.02) and lower HDL-C (mean 1.26, SD 0.31, vs mean 1.44, SD 0.39, mmol/L; P=.03) compared to the GA/GG genotype. Allele-based analysis showed that carriers of the A allele (98/138, 71%) also had higher LDL-C (mean 4.91, SD 1.02, vs mean 4.36, SD 0.97, mmol/L; P=.004) and ApoB (mean 145.6, SD 23.2, vs mean 135.9, SD 16.0, mg/dL; P=.02) than G allele carriers (40/138, 29%). These associations remained significant after multivariate adjustment. APOB rs676210 polymorphism is associated with significant differences in lipid profiles among Vietnamese adults with elevated LDL-C. Specifically, the A allele and the AA genotype confer a more atherogenic profile, suggesting potential utility as a genetic marker in lipid screening and personalized cardiovascular risk management in this population. Show less

Although primarily secreted by the liver, Fibroblast Growth Factor 21 (FGF21) is also expressed in the pancreas, where its function remains unclear. This study aims to elucidate the role of the glucagon-FGF21 interaction in the metabolic benefits of SGLT2 inhibition (SGLT2i) and hypothesizes it is key to enhancing glucose and lipid metabolism in individuals with glucose intolerance or type 2 diabetes (T2D). FGF21, FGF1R, and β-klotho expression in human pancreas was analysed by RNAscope, qPCR and immunofluorescent techniques. Glucose-stimulated insulin secretion (GSIS) assay was used to investigate the effects of recombinant FGF21 (rFGF21) on islets from donors with glucose intolerance or T2D. To explore the role of the glucagon-FGF21 axis in the benefits of SGLT2i, we used WT and Sglt2 knockout (KO) mice fed a chow diet (CD) or a high-fat diet (HFD) and chronically treated with vehicle or dapagliflozin. Chronic rFGF21 treatment enhanced GSIS in islets from donors with glucose intolerance, with increased FGFR1 expression, suggesting FGF21's greater efficacy in the early stages of disease. In diet-induced insulin-resistant mice, dapagliflozin reduced postprandial glycaemia and elevated plasma glucagon and FGF21 levels. Sglt2 KO mice on a CD showed increased fasting plasma glucagon without changes in FGF21. In diet-induced insulin-resistant Sglt2 KO mice, elevated glucagon and FGF21 levels paralleled chronic dapagliflozin treatment, indicating similar metabolic adaptations in both models. Our findings indicate FGF21 as a crucial mediator in liver-pancreas crosstalk, improving lipid and glucose metabolism, enhancing pancreatic function, and potentiating the therapeutic efficacy of SGLT2i, thereby representing a target for prediabetes treatment. Show less

To investigate the relationship between serum lipid levels and the risk of Chronic obstructive pulmonary disease (COPD) in the UK Biobank. We performed this prospective study in 381,938 adults without COPD from UK Biobank. Serum high-density cholesterol (HDL-C), low-density cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA) and apolipoprotein B (ApoB) were measured and classified into quintiles. Restricted cubic spline (RCS) analysis was applied to visualize the dose-response relationship between lipids and COPD risk and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 10,443 incident COPD cases. Nonlinear relationships were found between HDL-C, LDL-C, TC, ApoA, ApoB and COPD risk with RCS analysis (P values for non-linearity < 0.05). Accordingly, multivariable-adjusted regression analysis indicated abnormal HDL-C and ApoA, and low LDL-C, TC and ApoB were associated with increased risk of COPD. Compared to intermediate quintile (Q3) group, both high or low HDL-C and ApoA were associated with risk of COPD. Corresponding HRs (95% CIs) were 1.15 (1.08-1.22), 1.16 (1.09-1.23) in Q1 group and 1.08 (1.01-1.16), 1.07 (1.00-1.14) in Q5 group. For LDL-C, TC and ApoB, there were more than 29% higher risk was observed in Q1 group with HRs (95% CIs) of 1.34 (1.27-1.42), 1.38 (1.30-1.46) and 1.29 (1.21-1.37), while HRs (95% CIs) were 0.88 (0.83-0.94), 0.92 (0.86-0.98) and 0.90 (0.84-0.95) in Q5 groups. We also observed the interactions between specific lipids and age at recruitment, sex and smoking status with stratified analysis. Our study provides the first evidence demonstrating the associations between six major serum lipids and COPD risk, revealing multiple nonlinear relationships. There were U-shaped associations between serum HDL-C, ApoA and COPD risk, and L-shaped associations between LDL-C, TC, ApoB and COPD risk. Show less

The combination of acute pancreatitis (AP), severe hypertriglyceridemia (HTG), and diabetic ketoacidosis (DKA) poses a life-threatening triad. Although DKA is a frequent complication in children, this triad is rare. We report a 10-year-old girl with type 1 diabetes mellitus (T1DM) for 10 months, who presented with DKA, severe HTG, and AP. Her serum was lipemic. She had HTG (1733 mg/dl, 19.5 mmol/L; reference range, 90-129 mg/dl, 1,016-1,456 mmol/L) and severe abdominal pain that did not improve despite treatment for ketoacidosis. She had high lipase levels (1581 U/L, reference range 28-100 U/L), and pancreatitis was detected on abdominal tomography. She recovered with a combination of hydration and insulin therapy. A heterozygous p.N318S (c.953A>G) variant was detected in her lipoprotein lipase (LPL) gene. Her apolipoprotein B (ApoB) was elevated at 1.44 g/L (reference range, 0.6-1.17 g/L, 60-117 mg/dl). It is well established that both the likely pathogenic LPL variants and high ApoB concentrations contribute to an increased risk of cardiovascular complications. Therefore, it is recommended to evaluate for a pathogenic variant in the LPL gene in children with T1DM who do not have dyslipidemia but exhibit the rare triad of AP, HTG, and DKA. Show less

Acute kidney injury is a common complication of sepsis, and its mechanism is very complicated. The purpose of this study was to investigate the mechanism of key differentially expressed proteins and their related signaling pathways in the occurrence and development of acute kidney injury in sepsis through proteomics. Acute kidney injury was induced by intraperitoneal injection of lipopolysaccharide at 10 mg/kg. Renal tissues were analyzed by TMT quantitative proteomic analysis. Differentially expressed proteins (DEPs) were screened. Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed. We obtained 530 DEPs. GO analysis showed that the biological process of DEPs was mainly stress response. The molecular functions of DEPs mainly focus on catalytic activity. The cellular components of DEPs were mainly located in the intracellular and cytoplasm. KEGG analysis showed that DEPs were mainly involved in metabolic pathways. Ten key proteins with interaction degree, such as Isg15, Irf7, Oasl2, Ifit3, Apob, Oasl, Ube2l6, Ifit2, Ifih1 and Ifit1 were identified. Irf7 was significantly up-regulated in rat kidney tissues. The upregulation of Irf7 plays an important role in the mechanism of acute renal injury induced by sepsis. Show less

Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg) fat deposits are associated with apoB levels in general US adults. 4585 participants were enrolled from the US National Health and Nutritional Surveys from 2011 to 2016. Overall and regional body fat were measured using dual-energy X-ray absorptiometry. The associations of total and regional fat with apoB levels were evaluated using linear regression models. Following adjustment for demographic, lifestyle, and clinical risk factors, whole-body fat percentage was positively associated with apoB levels. Additionally, percent trunk fat was positively associated (highest vs. lowest tertile beta = 17.73 for men and 14.89 for women, respectively), whereas percent leg fat was inversely associated (highest vs. lowest tertile beta = - 4.84 for men and - 6.55 for women, respectively) with apoB levels in both sexes. The association for trunk fat and leg fat remained significant after further adjustment for body mass index or waist circumference. Higher percent trunk fat combined with lower percent leg fat was associated with particularly higher apoB. In conclusion, among general US adults, both elevated trunk fat and reduced leg fat are associated with higher levels of apoB. Further research is required to elucidate the underlying pathophysiological mechanisms. Show less

Phytosterols have been recommended as a lifestyle intervention for early lipid management-which has a significant impact on frailty. However, their effect on frailty remains unclear. Studies have shown that genetic proxied total blood phytosterol affects the development of cardiovascular disease through non-HDL-c and apolipoprotein B mediation, which makes phytosterol an underlying risk factor for frailty. The aim of this Mendelian randomization (MR) study was to investigate the genetic associations between phytosterols and frailty. We used univariate Mendelian randomization (UVMR) to assess the causal effects of blood phytosterols on the Frailty Index (FI) and Fried Frailty Score (FFS). We also employed multivariate Mendelian randomization (MVMR) and Two-step MR (TSMR) to evaluate the mediating role of blood lipids in the relationship between blood phytosterols and FI. We used the product of coefficients method to calculate the mediating effect. The inverse-variance weighted method was used as the primary analysis. Genetically proxied higher levels of blood total sitosterol were significantly associated with a higher risk of Frailty Index (OR = 1.035, 95% CI = 1.009-1.061, Show less

Forward genetic screening is a powerful approach to assign functions to genes and can be used to elucidate the many genes whose functions remain unknown. A key step in forward genetic screening is mapping: identification of the gene causing the phenotype. Existing mapping methods use a bioinformatic mapping-by-sequencing approach based on allelic frequency calculations that often identify large genomic regions which contain an intractable number of candidate genes for testing. Here, we describe WheresWalker, a modern mapping-by-sequencing algorithm that identifies a mutation-containing interval and then supports positional cloning to shrink the interval, which drastically reduces the number of potential candidates, allowing for extremely rapid mutation identification. We validated this method using mutants from a forward genetic mutagenesis screen in zebrafish for modifiers of ApoB-lipoprotein metabolism. WheresWalker correctly mapped and identified novel zebrafish mutations in mttp, apobb.1, and mia2 genes, as well as a previously published mutation in maize. Further, we used WheresWalker to identify a previously unappreciated ApoB-lipoprotein metabolism-modifying locus, slc3a2a. Show less

The concurrent rise of childhood obesity and hyperuricemia presents a serious public health concern. These conditions interact through complex metabolic mechanisms and significantly increase long-term risks of cardiometabolic diseases. Machine learning (ML) offers an effective framework for constructing efficient risk prediction models in pediatric populations. This study aimed to develop and evaluate two ML models-Random Forest (RF) and Support Vector Classification (SVC)-to predict the risk of childhood obesity and hyperuricemia by integrating clinical and biochemical variables. A total of 101 children were enrolled, including 60 with obesity and 41 with obesity plus hyperuricemia. Data preprocessing involved recursive feature elimination (RFE), ROSE-based oversampling, and feature standardization. Both RF and SVC models were trained and evaluated using area under the ROC curve (AUC), precision-recall curves, and calibration curves. SHAP (Shapley Additive Explanations) analysis was conducted to interpret feature contributions. Both models demonstrated strong predictive performance, with AUCs reaching 0.96. The SVC model achieved slightly higher average precision and recall, making it more suitable for community- or school-based screening of high-risk children. In contrast, the RF model exhibited superior calibration, suggesting its greater utility in clinical decision-making where probabilistic risk estimation guides personalized follow-up or intervention planning. SHAP analysis identified glomerular filtration rate (GFR), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) as key predictors, some exhibiting nonlinear associations with disease risk. RF and SVC models offer reliable tools for early risk prediction of obesity and hyperuricemia in children, each tailored to distinct clinical scenarios. These findings support early identification and targeted intervention. Future studies will explore the integration of metabolomic data and ensemble approaches to further enhance model performance and clinical applicability. Show less

This study aimed to explore the relationships between serum apolipoprotein A1 (ApoA1) and B (ApoB) levels and the ApoB/A1 ratio with structural and vascular changes in the retinas of patients with diabetic macular edema (DME), as assessed through optical coherence tomography (OCT) and OCT angiography (OCTA). 62 eyes from 38 treatment-naive diabetic retinopathy patients were assessed. Baseline and 6-month evaluations included clinical exams, fundus photography, blood tests for cholesterol, ApoA1, and ApoB, as well as imaging with OCT and OCTA. Associations between apolipoproteins and changes in central retinal thickness (CRT), foveal avascular zone (FAZ), and vessel/perfusion density were analyzed. In DME patients, elevated ApoB levels (>122.5 mg/dL) were significantly linked with increased CRT, FAZ expansion, and reduced perfusion density at the 6-month follow-up (p = 0.026, 0.046, and 0.025). Higher ApoB/A1 ratio (>0.85) was significantly associated with decreased perfusion density (p = 0.011). Elevated ApoB levels and ApoB/A1 ratio were linked with reduced perfusion and vessel density, increased CRT, and FAZ expansion, highlighting their potential as negative biomarkers for OCT-detected retinomacular changes. Show less

The association between low-density lipoprotein (LDL) cholesterol and increased mortality risk has been well-documented, yet apolipoprotein B (apoB) is regarded as a more precise risk indicator. However, a comprehensive analysis integrating both markers in relation to mortality risk remains unreported. This study aimed to investigate the relationship between LDL cholesterol levels and mortality across varying apoB concentrations within the general population. Data from 15,380 participants in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) were utilized to construct Cox regression models and apply restricted cubic splines, assessing the association between LDL cholesterol and mortality across distinct apoB stratifications. The study cohort had a median (IQR) age of 46.0 (32.0, 60.0) years, with 7949 (51.8%) males. During a median follow-up of 101.0 months (IQR: 67-137), 1771 (8.8%) all-cause mortality events were observed; 443 (2.1%) deaths were attributed to cardiovascular diseases, while 109 (0.5%) resulted from cerebrovascular diseases. Low apoB and LDL-cholesterol levels were independently linked to an elevated risk of all-cause and cardiovascular mortality. Compared with participants having apoB <90 mg/dL and LDL-cholesterol levels between 100-129 mg/dL, those with LDL-cholesterol <70 mg/dL (HR, 1.81; 95%CI: 1.39-2.36) and 70-99 mg/dL (HR, 1.28; 95%CI: 1.01-1.62) demonstrated a higher risk of all-cause mortality. Additionally, reduced apoB levels contributed to an increased risk of cardiovascular mortality among individuals with low LDL-cholesterol levels. Low apoB and LDL-cholesterol levels were associated with heightened all-cause and cardiovascular mortality risk in the general population. Conversely, high apoB and low LDL-cholesterol levels did not correlate with increased mortality risk. Show less

Tuberculosis (TB) is still a major health concern. However, each year more than one-third of all global TB cases remain undetected and unreported. On top of that, emergence of drug-resistant TB poses a major challenge. Therefore, a Reliable, Accessible, Cost-Effective, and Easy (RACE) diagnostic modality is crucial for starting suitable treatment of TB and curtailing its transmission. In the last two decades, several advances have been made for improved diagnosis, which include liquid culture and drug susceptibility testing (DST), line probe assay (LPA) for drug resistance detection at the molecular level, and cartridge-based nucleic acid amplification tests (CBNAAT) for rapid diagnosis of TB and rifampicin resistance detection. Newer drugs and treatment regimens have been introduced and vaccines are in the pipeline. Despite these advances and opportunities, a precise, affordable, and accessible diagnostic model is yet to be evolved, especially in rural and difficult-to-reach areas, where the most desirable test would be a test that is easy to perform, accessible to masses, is cost-effective, besides being reliable. Only a point-of-care triage test can meet these requirements, which can be used by an unskilled or minimally trained healthcare worker or even by the patient (self-testing). This test should be able to detect all forms of tuberculosis and latent TB infection. Currently, no such test is available. In this narrative review, we will discuss how such a diagnostic modality can help eliminate TB. Show less

Introduction Insulin resistance (IR) and pancreatic B-cell dysfunction are fundamental disorders in the pathogenesis of type 2 diabetes. Recent evidence suggests that apolipoprotein B (Apo-B) may be related to the onset of type 2 diabetes. However, the mechanism explaining this association is unclear. Methods We analyzed data from 4888 normoglycemic adults pooled from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Participants were categorized by tertiles of Apo-B, and the main outcome measures were IR and pancreatic β-cell function ascertained by homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for beta cell function (HOMA-β), respectively. Poisson and linear regressions were used to generate prevalence ratios (PRs) and β coefficients for IR and β-cell function, respectively. Results Among 4888 participants, the mean Apo-B was 0.85 ± 0.2 g/L, and 532 (10.8%) had IR. After adjusting for demographic variables, the PRs (95% CI) for IR comparing higher tertiles (T2 and T3) with the lowest tertile (T1) of Apo-B were 1.49 (1.19-1.88) and 1.92 (1.54-2.39), respectively. There was a significant increase in log HOMA-β for T2 and T3 compared to T1 of Apo-B, after adjusting for demographic variables (β 0.05 (95% CI: 0.01-0.09) and β 0.15 (95% CI: 0.11-0.19), respectively). Additional adjustment for lifestyle and metabolic variables did not change the significance of these findings. There was a significant graded increase in log HOMA-IR and HOMA-β from T2 to T3 (P for trend <0.001). Conclusion Apo-B was associated with increased IR and pancreatic β-cell function in normoglycemic adults independently of traditional risk factors for diabetes. These findings suggest that Apo-B may be associated with the development of glycemic dysregulation. Show less

To investigate whether the systemic inflammatory response against inflammatory conditions in the periodontium is related to serum apolipoprotein B (ApoB) and A1 (ApoA1) concentrations. The study consisted of the Health 2000 Survey participants (n = 2709) aged 30-49 years. The inflammatory condition of the periodontium was assessed by means of the number of teeth with deepened (≥ 4 mm) and deep (≥ 6 mm) periodontal pockets. Systemic inflammation was measured by serum C-reactive protein (CRP) levels. The role of ApoB and ApoA1 was studied by performing regression analyses and stratified analyses (according to the median values). In logistic regression analyses, the number of teeth with deepened (≥ 4 mm) periodontal pockets was associated with serum CRP levels among those participants whose serum ApoB concentration was ≥ 1.12 g/L. When the participants' ApoB concentration was < 1.12 g/L, such an association between deepened periodontal pockets and CRP was not observed. The direction or strength of the association between periodontal pockets and CRP was not essentially different in the ApoA1 strata. Systemic response against poor periodontal condition varied between individuals. The variation appeared to be related more to the serum concentration of ApoB than ApoA1. Show less

BackgroundAlthough abnormalities in circulating lipids and lipoproteins are associated with increased cancer risk, their specific impact on lung cancer progression and prognosis is still unclear. This study retrospectively assessed the influence of preoperative lipid and lipoprotein levels on non-small cell lung cancer progression and prognosis, stratified by age.MethodsIn this retrospective study, we analyzed 849 patients to investigate the association between lipid markers and lung cancer progression, and examined postoperative prognosis in a subset of 222 patients. Data was analyzed using restricted cubic spline curves, Kaplan-Meier survival analysis, and Cox proportional hazards models.ResultsA significant nonlinear relationship was observed between total cholesterol (TC), high-density lipoprotein (HDL), ApoB, ApoAI, ApoE, and baseline tumor diameter (BSLD) (PTC = 0.025; PHDL < 0.001; PApoB = 0.037; PApoAI =0.001; PApoE < 0.001). In contrast, Lp(a) showed a significant linear relationship with BSLD (P = 0.002). The Cox regression analysis revealed that triglyceride (TG) (hazard ratio (HR) = 0.50, 95% confidence interval (CI): 0.28-0.92, P = 0.025) was significantly negatively associated with lung cancer mortality in patients under 58 years. For patients over 58 years, higher ApoB levels were linked to a reduced risk of lung cancer death (HR = 0.59, 95% CI: 0.36-0.97, P = 0.038).ConclusionThis study reveals a significant negative correlation between ApoAI and HDL levels with BSLD, while Lp(a) shows a positive correlation. In terms of long-term prognosis, high-serum ApoB are associated with a lower mortality risk in all lung cancer patients, and high-serum TG levels associated with reduced mortality risk in patients aged under 58 while high-serum TC levels associated with reduced mortality risk in patients over 58, with high Lp(a) levels indicating a greater risk of mortality in older patients. Show less

Several KRASG12D inhibitors (KRASG12Di) are under clinical evaluation for pancreatic ductal adenocarcinoma (PDAC). However, as seen with other first generation KRAS inhibitors, resistance may limit their long-term efficacy, necessitating combination strategies to enhance therapeutic outcomes. Exportin 1 (XPO1), a nuclear transport protein overexpressed in PDAC, represents a therapeutic vulnerability in KRAS-mutant cancers. Here, we demonstrate that the second-generation XPO1 inhibitor Eltanexor synergizes with MRTX1133 to enhance its efficacy in multiple PDAC models. We generated KRASG12Di-resistant PDAC cells and assessed their response to Eltanexor. The antiproliferative effects of MRTX1133 and Eltanexor combinations were evaluated in 2D and 3D Eltanexor sensitized MRTX1133-resistant PDAC cells to growth inhibition. In both 2D and 3D culture models, the combination of Eltanexor and MRTX1133 significantly reduced cell viability. Mechanistically, the combination treatment suppressed key KRAS downstream signaling molecules, including p-ERK, mTOR, p-4EBP1, DUSP6, and cyclin D1. Kinome analysis further revealed reduced MAPK-related kinase activity. Combining subtherapeutic doses of Eltanexor and MRTX1133 resulted in significant tumor regression and prolonged survival in PDAC xenograft and immunocompetent orthotopic allograft models. Moreover, maintenance therapy with Eltanexor prevented tumor relapse, yielding a durable antitumor response. This study demonstrates that Eltanexor overcomes resistance to MRTX1133 and enhances its efficacy in PDAC. The combination regimen may provide a durable therapeutic response while reducing the required dose of KRASG12D inhibitors, potentially delaying resistance and improving patient outcomes. Show less