Lipids in Health and Disease最新文献

Background: Homocysteine (Hcy) and the proprotein convertase subtilisin/kexin type 9 (PCSK9) significantly contribute to atherosclerosis (AS) as well as coronary lesion severity. Our previous work demonstrated that Hcy upregulates PCSK9, accelerating lipid accumulation and AS. A PCSK9 antagonist reduces plasma Hcy levels in ApoE^-/- mice. These findings suggest complex roles for both Hcy and PCSK9 in AS. This study investigated the mutual mediating influence of Hcy together with PCSK9 on coronary lesion severity among individuals diagnosed with acute coronary syndrome (ACS), focusing on their interplay with inflammatory and lipid-related markers.

Methods: This cross-sectional study encompassed 617 individuals diagnosed with ACS. Baseline characteristics, including inflammatory and lipid-related markers, were compared between individuals with non-severe (SYNTAX score ≤ 22) and severe (SYNTAX score > 22) coronary lesions. To evaluate both the impacts of Hcy and PCSK9 on coronary lesions severity, multivariate logistic regression along with mediation analyses were utilized. The robustness of the findings was validated by conducting subgroup analyses and sensitivity tests.

Results: Patients with severe conditions showed higher levels of Hcy, PCSK9, and inflammatory markers compared to non-severe cases. Both Hcy and PCSK9 levels were independently linked to a heightened risk of severe coronary lesions(ORs: 1.03-1.04 and 1.01-1.02, respectively, all P < 0.001). PCSK9 mediated 34.04% of Hcy's effect on coronary lesion severity, whereas Hcy mediated 31.39% of PCSK9's effect, indicating significant mutual mediation between these biomarkers. Subgroup analyses revealed consistent associations, with notable interactions based on creatinine levels for Hcy and gender, smoking status, and diagnosis for PCSK9. Sensitivity analyses confirmed the robustness of the mediation effects.

Conclusions: These findings emphasize the mutual mediating effects of Hcy and PCSK9 on coronary lesion severity in patients suffering from ACS. These results highlight the complex interactions between lipid metabolism and inflammation in the pathophysiology of ACS, suggesting that targeting both Hcy and PCSK9 may offer novel therapeutic strategies to mitigate severe coronary lesions among high-risk patients.

Background: Primary healthcare (PHC) plays a key role in hyperlipidemia (HL) management yet lacks adequate monitoring and feedback. This study aims at identifying pragmatic measures out from routinely collected electronic records to enable automatic monitoring and inform continuous optimization of HL-management at PHC settings.

Methods: The study used randomly selected electronic records of PHC (from the province-wide data center of Anhui-province, China) as the main data source and generated both procedure-based and encounter-based measures for assessing HL-management. The procedure-based measures were derived from specific quality-facts of 21 stages/procedures (e.g., lipid lowering medication prescription) using self-designed algorithms. While the encounter-based measures included number or rate of visits for HL, currently-noticed hyperlipidemia (CNHL, or HL noticed during the current consultation), and ever-diagnosed hyperlipidemia (EDHL). Analysis of these measures employed mainly simple descriptives and linear regression modeling.

Results: The study revealed interesting findings including: low and varied rates of visits for HL(from 0.01 to 1.43%) and visits by patients with EDHL/CNHL(from 0.13 to 20.54% or from 0.02 to 2.99%) between regions; large differences (5.14 to 22.20 times) between the mean or cumulative proportions of visits by patients with EDHL versus CNHL among clinician groups; consistent increase in the ratio of visits for HL in all cause visits over the study period (from 0.087 to 1.000%) accompanied with relatively stable proportions of patients with CNHL/EDHL; Relatively low scores in the procedure-based measures (ranged from 0.00 to 36.08% for specific procedures by seasons).

Conclusions: The measures identified are not only feasible from real-world PHC records but also give some useful metrics about how well current HL-management is going and what future actions are needed.

Background: The ABO blood group system has shown an association with cardiovascular disease. The susceptibility to CVD is proposed to be partly mediated by dyslipidaemia in non-O individuals. Previous studies are scarce for the RhD blood group, but we recently showed that RhD - young individuals are associated with subclinical atherosclerosis. Hence, we sought to examine whether the ABO blood groups and RhD factor are associated with dyslipidaemia.

Methods: All participants were part of the VIPVIZA study, including 3532 individuals with available plasma lipid levels. Lipids were assessed as total, LDL, HDL, remnant, non-HDL cholesterol and triglycerides. Information about ABO and RhD was retrieved by linking VIPVIZA with the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.

Results: For the ABO blood groups, no significant differences in lipid levels between non-O and O individuals were seen. In 40-year-old males, RhD - individuals compared to RhD + had higher levels of non-HDL cholesterol, LDL cholesterol, and remnant cholesterol, with ratios of geometric means of 1.21 (CI95% 1.03; 1.43), 1.20 (1.02; 1.41) and 1.38 (1.00; 1.92), respectively. No differences in lipid levels depending on the RhD blood group were seen in women or the older age groups.

Conclusion: Our study indicates that younger RhD - men have increased non-HDL, LDL, and remnant cholesterol levels. Thus, the RhD blood group, but not ABO, seems to be associated with dyslipidaemia and may act as a future possible risk marker of cardiovascular disease.

Background: Cardiovascular disease (CVD) is a major cause of mortality worldwide, necessitating more refined strategies for risk assessment. Recently, lipoprotein(a) [Lp(a)] has gained attention for its distinctive role in atherosclerosis, yet its prevalence and impact for cardiovascular risk assessment are not well-documented in the Portuguese population. This study aimed to characterize Lp(a) levels in a real-world Portuguese cohort, investigating its prevalence and association with CVD risk.

Methods: Retrospective and cross-sectional study of adults who underwent serum Lp(a) analysis in a Portuguese hospital between August 2018 and June 2022. Demographic and anthropometric data, laboratory values, relevant comorbidities and lipid-lowering medication were collected.

Results: Of 1134 participants, 28.7% had elevated Lp(a) levels (> 125 nmol/L). A higher prevalence was observed in those with atherosclerotic cardiovascular disease (ASCVD) (45.9%) or a family history of premature CVD (41.9%). Additionally, a significant association was found between elevated Lp(a) levels and traditional CVD risk factors, including hypertension, dyslipidemia, and diabetes mellitus. Among those classified as having low-to-moderate CVD risk by (Systematic COronary Risk Evaluation 2) SCORE2, 55.7% exhibited high Lp(a) levels (> 75 nmol/L), suggesting a potential higher risk of CVD disease.

Conclusions: The prevalence of elevated Lp(a) in Portugal, notably among those with ASCVD or premature CVD history, is concerning. This study underscores the potential of Lp(a) assessment for a more comprehensive approach to cardiovascular risk assessment. This could improve the stratification of CVD risk and identify individuals who could benefit from early intensive management of their risk factors, ultimately reducing the burden of CVD and cardiovascular-related mortality.

Background: Depression presents sexual dimorphism, and one important factor that increases the frequency of depression and contributes to sex-specific variations in its presentation is obesity. The conventional use of Body Mass Index (BMI) as an indicator of obesity is inherently limited due to its inability to distinguish between fat and lean mass, which limits its predictive utility for depression risk. Implementation of dual-energy X-ray absorptiometry (DXA) investigated sex-specific associations between body composition (fat mass, appendicular lean mass) and depression.

Methods: Data from the NHANES cycles between 2011 and 2018 were analyzed, including 3,637 participants (1,788 males and 1,849 females). Four body composition profiles were identified in the subjects: low adiposity-low muscle (LA-LM), low adiposity-high muscle (LA-HM), high adiposity-low muscle (HA-LM) and high adiposity-high muscle (HA-HM). After accounting for confounding variables, the associations between fat mass index (FMI), appendicular skeletal muscle mass index (ASMI), body fat percentage (BFP), body composition phenotypes, and depression risk were assessed using restricted cubic spline (RCS) curves and multivariable logistic regression models. We further conducted interaction analyses for ASMI and FMI in females.

Results: RCS curves indicated a U-shaped relationship between ASMI and the risk of depression in males. Logistic regression analysis revealed that in males, the second (OR = 0.43, 95%CI:0.22-0.85) and third (OR = 0.35, 95%CI:0.14-0.86) quartile levels of ASMI were significantly negatively associated with depression risk. In females, increases in BFP (OR = 1.06, 95%CI:1.03-1.09) and FMI (OR = 1.08, 95% CI:1.04-1.12) were significantly associated with an increased risk of depression. Additionally, compared to females with a low-fat high-muscle phenotype, those with LA-LM (OR = 3.97, 95%CI:2.16-7.30), HA-LM (OR = 5.40, 95%CI:2.34-12.46), and HA-HM (OR = 6.36, 95%CI:3.26-12.37) phenotypes were more likely to develop depression. Interestingly, further interaction analysis of ASMI and FMI in females revealed an interplay between height-adjusted fat mass and muscle mass (OR = 4.67, 95%CI: 2.04-10.71).

Conclusion: The findings demonstrate how important it is to consider body composition when estimating the risk of depression, particularly in females. There is a substantial correlation between the LA-LM, HA-LM, and HA-HM phenotypes in females with a higher prevalence of depression. It is advised to use a preventative approach that involves gaining muscle mass and losing fat.

Background: Bladder cancer is one of the most common malignancies of the urinary system. Despite significant advances in diagnosis and treatment, the compromised therapeutic effect of chemotherapeutic agents, such as Oxaliplatin (OXA), remains a major clinical challenge. Thus, a combination therapy is required to enhance the OXA's therapeutic effectiveness and improve patient outcomes.

Methods: The thin film hydration method was used to prepare the liposomes. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the SRT3025-loaded cell membrane hybrid liposomes (3025@ML). Bladder cancer cell lines T24 and 5637 were cultured in McCoy's 5 A and RPMI 1640 medium, respectively. The Cell Counting Kit-8 assay was used to determine the cell viability by treating cells with a medium containing either the vehicle solution (control), the cell membrane hybrid liposomes (ML), 3025@ML, or compound 3 K. The antiproliferative activities were investigated after treating cells with OXA + 3025@ML and compound 3 K + OXA. Cell death and apoptosis were quantified by trypan blue and Annexin V-APC/PI apoptosis assay after treating cells with control, OXA, OXA + 3025@ML, and 3025@ML. Western blot analysis was performed after treating cells with 3025@ML, OXA, 3 K, 3025@ML + OXA, and 3 K + OXA to determine the protein levels of pyruvate kinase M2 (PKM2) and fatty acid synthase (FASN), etc. RESULTS: The present study demonstrated that 3025@ML enhances the chemotherapeutic effect of OXA. 3025@ML + OXA treated T24 and 5637 cells showed that combination therapy significantly reduced cell viability and increased cell death rate. Flow cytometry analysis showed that the combination of 3025@ML and OXA significantly increased the percentage of apoptotic cells in T24 cells. 3025@ML and compound 3 K reduced the levels of FASN in T24 and 5637 cells and increased the anti-tumor activity of OXA. Mechanistic studies showed that 3025@ML inhibited the PI3K/AKT/mTOR signaling pathway and reduced the expression of key metabolic regulators PKM2 and FASN. Furthermore, this study demonstrated that targeting lipid metabolism and inhibiting FASN can effectively overcome the compromised therapeutic effect of OXA.

Conclusion: The study demonstrated that 3025@ML significantly enhances the anti-tumor activity of OXA. This novel drug delivery system inhibits key metabolic pathways, which increase DNA damage and tumor cell apoptosis. The results indicate that 3025@ML is a promising therapeutic strategy for overcoming OXA's compromised therapeutic effect and potentially improving cancer treatment outcomes.

Background: This study aimed to investigate the association between relative fat mass (RFM) and asthma, as well as to explore the mediating role of Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI).

Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey from 2007 to 2018. Associations between RFM and asthma were tested using multivariable logistic regressions, restricted cubic splines, subgroup analyses, and interaction tests, with mediation analysis for SII and SIRI. The inflection point was determined by the two-piecewise linear regression. Sensitivity analysis and propensity score matching (PSM) was applied to validate the stability of the associations.

Results: Higher RFM was positively associated with asthma, with an inflection point at 34.08. Below this threshold, each unit increase in RFM was positively associated with a 2% increase in the odds of asthma (Odds ratio (OR) 1.02, 95% Confidence interval (CI): 1.00-1.03), while above it, the association strengthened, with a 5% increase in the odds per unit (OR 1.05, 95% CI: 1.04-1.07). The association was consistent across subgroups. The association between RFM and asthma is stronger in current asthma patients than in ever had asthma ones. Mediation analyses showed that SII and SIRI partially mediated 7.48% and 3.88% of the RFM-asthma association, respectively. The findings remained robust after sensitivity analyses and adjusting for confounding bias using PSM.

Conclusions: RFM is positively associated with the prevalence of asthma in the U.S., particularly among individuals with current asthma, with systemic inflammation partially mediating this relationship.

Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, and resistance to therapy. Pancreatic cancer (PC) is a highly aggressive malignancy of the gastrointestinal tract that has a dismal 5-year survival rate of less than 10%. Given the essential function of the pancreas in digestion, cancer progression severely disrupts its function. Standard treatments for PC such as surgical resection, chemotherapy, and radiotherapy. However, these therapies often face significant challenges, including biochemical recurrence and drug resistance.Given these limitations, new therapeutic approaches are being developed to target tumor metabolism. Dysregulation of cholesterol biosynthesis and alterations in fatty acids (FAs), such as palmitate, stearate, omega-3, and omega-6, have been observed in pancreatic cancer. These lipids serve as energy sources, signaling molecules, and essential components of cell membranes. Their accumulation fosters an immunosuppressive tumor microenvironment that supports cancer cell proliferation and metastasis.Moreover, lipid metabolism dysregulation within immune cells, particularly T cells, impairs immune surveillance and weakens the body's defenses against cancer. Abnormal lipid metabolism also contributes to drug resistance in PC. Despite these challenges, targeting lipid metabolism may offer a promising therapeutic strategy. By enhancing lipid peroxidation, the induction of ferroptosis-a form of regulated cell death-could impair the survival of PC cells and hinder disease progression.

Background: The connection between lipid-related obesity indices and severe headache or migraine in young and middle-aged people aged 20-60 remains ambiguous, and there are gaps in the discriminative ability of different indicators for severe headaches or migraines. Consequently, we set out to look into this association utilizing National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004.

Methods: After the values of waist-to-height ratio (WHtR), body-mass index (BMI), body roundness index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose index (TyG), cardiac metabolism index (CMI), waist triglyceride Index (WTI), conicity index (CI) and weight-adjusted waist index (WWI) were estimated, with minimal sufficient adjustment for confounders determined by directed acyclic graph (DAG), weighted univariable and multivariable logistic regression analyses were carried out to ascertain the relationship between them and migraine. Stratified analysis and cross-effect analysis were implemented to examine the variability of intergroup correlations. Restricted cubic splines (RCS) and receiver operating characteristic (ROC) were then employed to examine nonliner relationships and its discriminatory ability for severe headache or migraine, respectively.

Results: 3354 United States adults were involved in our study, of whom 839 (25.01%) had severe headache or migraine. After adjusting for relevant covariables, WHtR, BRI, BMI, LAP, WTI and VAI were all associated with migraine and WHtR (OR = 6.38, 95% CI: 2.25,18.09, P < 0.01) showed the best predictive ability. Additionally, WHtR, BMI, and BRI demonstrated linear dose-response relationships with the prevalence of migraine (all P_overall < 0.05, P_{non-linearity} > 0.05).

Conclusions: Among those ten lipid-related obesity indicators evaluated in the study, WHtR, BMI and BRI demonstrated linear positive dose-response relationships with the prevalence of migraine in young and middle-aged individuals within the United States and WHtR showed the best predictive ability. Our study can provide important insight into epidemiological research and comprehensive management of obese patients with migraine.