2,644 results on '"Lipoprotein"'
Search Results
2. Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure.
- Author
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Wang, Yi, Liu, Xiaoli, Wu, Baochuan, Tan, Xi, Chen, Lin, Chu, Heyu, Zhou, Zeyu, Bao, Xue, Xu, Biao, and Gu, Rong
- Subjects
OBESITY paradox ,HDL cholesterol ,LDL cholesterol ,HEART failure patients ,APOLIPOPROTEIN B ,HEART failure - Abstract
Background: Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. Methods: The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. Results: In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p<0.001, obese vs underweight), cardiovascular mortality (HR=0.46, 95%CI 0.30~0.73, p<0.001, obese vs underweight) and the incidence of MACCEs (HR=0.68, 95%CI 0.53~0.88, p=0.003, obese vs underweight). Mediation analysis revealed that TG was the strongest mediator between BMI and endpoints, with proportions of mediated effects of 6.6% (95%CI 2.2%~18.0%, p=0.0258, in all-cause death),7.0% (95%CI 2.3%~18.9%, p=0.0301, in cardiovascular death) and 10.2% (95%CI 3.3%~27.4%, p=0.0185, in MACCEs). Conclusions: There is an "obesity paradox" in patients with heart failure, and lipoprotein levels especially triglyceride mediate the association between BMI and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
3. The effect of glucomannan supplementation on lipid profile in adults: a GRADE-assessed systematic review and meta-analysis.
- Author
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Musazadeh, Vali, Rostami, Rogheye Yaraee, Moridpour, Amir Hossein, Hosseini, Zahra Bokaii, Nikpayam, Omid, Falahatzadeh, Maryam, and Faghfouri, Amir Hossein
- Subjects
LDL cholesterol ,HDL cholesterol ,APOLIPOPROTEIN A ,RANDOM effects model ,GLUCOMANNAN - Abstract
Background: Glucomannan has been studied for various health benefits, but its effects on lipid profile in adults are not well understood. This meta-analysis aims to evaluate the impact of glucomannan supplementation on serum/plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), Apo B1, Apo A1, APO-B/ A1 ratio, and LDL-C/ HDL-C in adults. Methods: A comprehensive search was conducted across Scopus, PubMed, Embase, and Web of Science from inception to June 2024 to identify randomized controlled trials (RCTs) assessing glucomannan supplementation on lipid profile in adults. Data were extracted and analyzed using random effects model to determine the standardized mean differences (SMDs) and 95% confidence intervals (CIs) for each biomarker. Results: Glucomannan supplementation significantly decreased TC (SMD: -3.299; 95% CI: -4.955, -1.664, P < 0.001; I
2 = 95.41%, P-heterogeneity < 0.001), LDL-C (SMD: -2.993; 95% CI: -4.958, -1.028; P = 0.006; I2 = 95.49%, P-heterogeneity < 0.001), and Apo B1 (SMD: -2.2; 95% CI: -3.58, -0.82; P = 0.01). However, glucomannan did not alter the levels of TG (SMD: -0.119; 95% CI: -1.076, 0.837, P = 0.789; I2 = 91.63%, P-heterogeneity < 0.001), Apo A1 (SMD: -0.48; 95% CI: -6.27, 5.32; P = 0.76), APO-B/ A1 ratio (SMD: -1.15; 95% CI: -2.91, 0.61; P = 0.11), and LDL-C/ HDL-C ratio (SMD: -2.2; 95% CI: -7.28, 2.87; P = 0.2). Conclusions: Glucomannan supplementation has a beneficial effect on the level of TC and LDL-C. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Evaluating the efficacy of GIPR agonists on non-alcoholic fatty liver disease: A Mediation Mendelian Randomization Study.
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Xie, Siyuan, Chen, Delong, Cai, Yangke, Xu, Liyi, Liao, Oulan, Jia, Xuan, Ji, Xiaowei, Chen, Hanwen, Mao, Jianshan, and Cai, Jianting
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24–0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07–0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85–0.92], P < 0.01) and HDL-C (0.85, [0.80–0.90], P < 0.01). Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Acceleration of HDL-Mediated Cholesterol Efflux Alleviates Periodontitis.
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Tran, T.-T., Lee, G., Huh, Y.H., Chung, K.-H., Lee, S.Y., Park, K.H., Kim, J.-H., Kook, M.-S., Ryu, J., Kim, O.-S., Lim, H.-P., Koh, J.-T., and Ryu, J.-H.
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HDL cholesterol ,HIGH cholesterol diet ,BONE resorption ,APOLIPOPROTEIN A ,LOGISTIC regression analysis - Abstract
Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. In the current study, we demonstrated that hypercholesterolemia is a predisposing factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data from in vivo (PD mouse model subjected to a high cholesterol diet) and in vitro (cholesterol treatment of gingival fibroblasts [GFs]) experiments showed that excess cholesterol influx into GFs potentially contributes to periodontal inflammation and, subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed GFs. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Proatherogenic Disorders of Blood Lipid and Lipoprotein Metabolism in Patients with Rheumatoid Arthritis.
- Author
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Gerasimova, Elena V., Popkova, Tatiana V., Shalygina, Maria V., and Gerasimova, Daria A.
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BLOOD lipids ,BLOOD lipoproteins ,LIPID metabolism ,LIPID metabolism disorders ,HIGH density lipoproteins - Abstract
Disorders of blood lipids and lipoproteins are a global problem and a high-risk factor for atherosclerosis in patients with rheumatoid arthritis (RA). This article presents data on the influence of inflammation on proatherogenic disorders of lipid and lipoprotein metabolism, with an emphasis on proinflammatory cytokines. It analyzes the blood lipid profile in RA patients and identifies the need to study subfractions of high-density lipoproteins and their function in reverse cholesterol transport in RA patients as a more promising direction for clarifying cardiovascular risk. Depending on their type and metabolites, lipids may either promote disease progression or protect against RA. Supported by the close connection between altered lipid metabolism and chronic autoimmune inflammation, specific lipid profiles are emerging as unique disease biomarkers with diagnostic, predictive, and prognostic potential. Studying the influence of the immunoinflammatory process on lipids and lipoproteins in the blood of patients with RA will not only deepen knowledge about the pathogenesis of chronic inflammation but also expand understanding of the pathogenetic and prognostic significance of lipids, allowing for early diagnosis of dyslipidemia in RA at a qualitatively new level. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Helicobacter pylori HP0018 Has a Potential Role in the Maintenance of the Cell Envelope.
- Author
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Rosinke, Kyle, Starai, Vincent J., and Hoover, Timothy R.
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EXTRACELLULAR vesicles , *CELL envelope (Biology) , *HELICOBACTER pylori , *GREEN fluorescent protein , *CELL morphology - Abstract
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, where it can cause a variety of diseases. H. pylori uses a cluster of sheathed flagella for motility, which is required for host colonization in animal models. The flagellar sheath is continuous with the outer membrane and is found in most Helicobacter species identified to date. HP0018 is a predicted lipoprotein of unknown function that is conserved in Helicobacter species that have flagellar sheaths but is absent in Helicobacter species that have sheath-less flagella. Deletion of hp0018 in H. pylori B128 resulted in the formation of long chains of outer membrane vesicles, which were most evident in an aflagellated variant of the Δhp0018 mutant that had a frameshift mutation in fliP. Flagellated cells of the Δhp0018 mutant possessed what appeared to be a normal flagellar sheath, suggesting that HP0018 is not required for sheath formation. Cells of the Δhp0018 mutant were also less helical in shape compared to wild-type cells. A HP0018-superfolder green fluorescent fusion protein expressed in the H. pylori Δhp0018 mutant formed fluorescent foci at the cell poles and lateral sites. Co-immunoprecipitation assays with HP0018 identified two enzymes involved in the modification of the cell wall peptidoglycan, AmiA and MltD, as potential HP0018 interaction partners. HP0018 may modulate the activity of AmiA or MltD, and in the absence of HP0018, the unregulated activity of these enzymes may alter the peptidoglycan layer in a manner that results in an altered cell shape and hypervesiculation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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8. Dyslipidemia characterized by low density lipoprotein cholesterol and risk of preterm Birth: A Mendelian randomization study.
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Zhang, Wei, Liu, Ling, Yang, Xin, Wang, Kexin, Yao, Hui, and Wang, Fang
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LDL cholesterol , *GENOME-wide association studies , *GENETIC pleiotropy , *PREMATURE labor , *BLOOD lipids , *CHOLESTERYL ester transfer protein - Abstract
Preterm birth is the leading cause of neonatal mortality worldwide, and dyslipidemia is associated with preterm birth in observational studies. We use Mendelian randomization (MR) analyses to uncover the causal association between blood lipid levels and preterm birth. We extracted uncorrelated (R2 < 0.001) single-nucleotide polymorphisms strongly associated (p < 5 × 10–8) with blood lipids from genome wide association studies of FinnGen database and UK Biobank participants. Inverse variance weighted method was the main MR analysis. Sensitivity analyses including genetic pleiotropy, heterogeneity, and directionality of causality were conducted. The study included 115,082 participants with lipid measurements, 8,507 patients with preterm birth. Increasing apolipoprotein B (odds ratio (OR), 1.12[95 % CI, 1.02–1.23]; p = 0.019), low-density lipoprotein cholesterol (OR, 1.11[95 % CI, 1.00–1.22]; p = 0.040), non-high-density lipoprotein cholesterol (OR, 1.12[95 % CI, 1.01–1.24]; p = 0.026), remnant cholesterol (OR, 1.11[95 % CI, 1.00–1.23]; p = 0.047) and total free cholesterol (OR, 1.11[95 % CI, 1.01–1.23]; p = 0.037) were associated with increased risk of preterm delivery. Moreover, triglycerides in low-density lipoprotein were causally associated with the risk of PTB. Our sensitivity analysis yielded robust results, uncovering no evidence of horizontal pleiotropy or reverse causal relationships. Our investigation unveils the adverse impact of dyslipidemia on preterm birth, with a particular emphasis on the detrimental effect of elevated low-density lipoprotein cholesterol. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.
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Guardiola, Montse, Rehues, Pere, Amigó, Núria, Arrieta, Francisco, Botana, Manuel, Gimeno‐Orna, José A., Girona, Josefa, Martínez‐Montoro, José Ignacio, Ortega, Emilio, Pérez‐Pérez, Antonio, Sánchez‐Margalet, Víctor, Pedro‐Botet, Juan, Ribalta, Josep, Aguilar Diosdado, Manuel, Arrieta, Francisco J., Becerra Fernández, Antonio, Botana López, Manuel Antonio, Campos Pastor, María del Mar, Durán García, Santiago, and Fornos Pérez, José Antonio
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TYPE 2 diabetes , *DYSLIPIDEMIA , *CARDIOVASCULAR diseases risk factors , *LDL cholesterol , *HDL cholesterol , *NUCLEAR magnetic resonance - Abstract
The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1—the information provided by routine clinical biochemistry, 2—advanced nuclear magnetic resonance (NMR)‐based lipoprotein profiling and 3—the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein‐related information into population‐based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large‐scale determination of these sets of methodologically diverse parameters. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Low LDL-C/HDL-C Ratio is Associated with Poor Clinical Outcome After Intracerebral Hemorrhage: A Retrospective Analysis of Multicenter, Prospective Cohort Data in China.
- Author
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Wu, Lei, Wang, Anxin, Kang, Kaijiang, Zhang, Xiaoli, Zhao, Xingquan, and Wang, Wenjuan
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LDL cholesterol , *CEREBRAL hemorrhage , *REGRESSION analysis , *INTRACRANIAL hemorrhage , *BLOOD lipids - Abstract
Background: The association between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and the clinical outcomes of acute intracranial hemorrhage (ICH) remains unclear. In this study, we attempt to investigate whether low LDL-C/HDL-C ratio is associated with poor clinical outcomes in patients with ICH. Methods: The database was collected from a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. A total of 1,964 patients with ICH were initially screened in our database. Next, we selected patients with admission serum lipid information for retrospective analysis. Patients were categorized into four groups based on LDL-C/HDL-C ratio quartiles. The main outcomes were 30-day and 90-day poor functional outcome, which is defined as modified Rankin Scale score of 3 to 6, and 90-day all-cause death. Logistic regression was used to assess the association between LDL-C/HDL-C ratio and 30-day or 90-day poor functional outcome. Kaplan–Meier survival analysis and Cox regression were used to assess the association between LDL-C/HDL-C ratio and 90-day all-cause death. Restricted cubic splines were used to explore the nonlinear association between LDL-C/HDL-C ratio and the outcome of patients with ICH. Results: A total of 491 patients with spontaneous ICH were finally enrolled in our study. The mean age was 57.6 years old, and 72.1% (357/491) were men. After adjustment for confounders, patients in the lowest LDL-C/HDL-C quartile (< 1.74) had a significantly higher risk of 30-day and 90-day poor functional outcome compared with those in the highest quartile (> 3.16; 30-day: adjusted odds ratio 3.61, 95% confidence interval 1.68–7.72; 90-day: adjusted odds ratio 2.82, 95% confidence interval 1.33–5.95). Restricted cubic splines depicted a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcomes, indicating LDL-C/HDL-C ratio of 3.1–3.5 was correlated with better 90-day functional outcome. However, no significant correlation was found between low LDL-C/HDL-C ratio and 90-day all-cause death. Conclusions: Lower LDL-C/HDL-C ratio (< 1.74) is independently associated with an increased risk of poor functional outcome in patients with ICH. In the population of patients whom we studied, there is a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcome, and patients with an LDL-C/HDL-C ratio of 3.1 to 3.5 tend to have the lowest risk of 90-day poor functional outcome. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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11. Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure
- Author
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Yi Wang, Xiaoli Liu, Baochuan Wu, Xi Tan, Lin Chen, Heyu Chu, Zeyu Zhou, Xue Bao, Biao Xu, and Rong Gu
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Heart failure ,Obesity ,Lipoprotein ,Mediating effect ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. Methods The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. Results In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p
- Published
- 2024
- Full Text
- View/download PDF
12. The effect of glucomannan supplementation on lipid profile in adults: a GRADE-assessed systematic review and meta-analysis
- Author
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Vali Musazadeh, Rogheye Yaraee Rostami, Amir Hossein Moridpour, Zahra Bokaii Hosseini, Omid Nikpayam, Maryam Falahatzadeh, and Amir Hossein Faghfouri
- Subjects
Glucomannan ,Lipid profile ,Lipoprotein ,Dyslipidemia ,Meta-analysis ,Systematic review ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Glucomannan has been studied for various health benefits, but its effects on lipid profile in adults are not well understood. This meta-analysis aims to evaluate the impact of glucomannan supplementation on serum/plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), Apo B1, Apo A1, APO-B/ A1 ratio, and LDL-C/ HDL-C in adults. Methods A comprehensive search was conducted across Scopus, PubMed, Embase, and Web of Science from inception to June 2024 to identify randomized controlled trials (RCTs) assessing glucomannan supplementation on lipid profile in adults. Data were extracted and analyzed using random effects model to determine the standardized mean differences (SMDs) and 95% confidence intervals (CIs) for each biomarker. Results Glucomannan supplementation significantly decreased TC (SMD: -3.299; 95% CI: -4.955, -1.664, P
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- 2024
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13. Glucagon-like peptide (GLP)-1 regulation of lipid and lipoprotein metabolism
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Hoffman Simon and Adeli Khosrow
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glucagon-like peptide-1 ,lipid ,lipoprotein ,intestine ,neuroendocrine ,Medicine - Abstract
Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins. Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity, metabolic syndrome, and type 2 diabetes. Evidence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dyslipidemia is the overproduction of hepatic and intestinal apolipoprotein (apo)B-containing lipoprotein particles. These particles are catabolized down into highly proatherogenic remnants, which can be taken up into the arterial intima and promote plaque development. Several gut-derived peptides have been identified as key regulators of energy metabolism; one such peptide is the incretin hormone glucagon-like peptide (GLP)-1. Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion. Moreover, we have demonstrated that GLP-1 receptor (GLP-1R) agonists can ameliorate diet-induced dyslipidemia. Recently, we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects. Furthermore, we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein production. Overall, ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein production and identifies other gut-derived peptides as novel regulators of postprandial lipemia. Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of diabetic dyslipidemia.
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- 2024
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14. A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets
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Sudarshan Ramachandran, Amro Maarouf, Karen Mitchell, Tony Avades, Peter Smith, Lee Boulton, Jennifer Kelly, Nitasha Vekaria, and Elizabeth Hughes
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adenosine triphosphate ,bempedoic acid ,cholesterol ,hydroxymethylglutaryl coa reductases ,hypercholesterolaemia ,lipoprotein ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Methods: Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Results: Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC)
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- 2024
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15. Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial
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David Benaiges, Albert Goday, Anna Casajoana, Juana A. Flores-Le Roux, Montserrat Fitó, Oscar J. Pozo, Carme Serra, Manuel Pera, Gemma Llauradó, Elisenda Climent, Montserrat Villatoro, Iolanda Lazaro, Olga Castañer, and Juan Pedro-Botet
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Roux-en-Y gastric bypass ,Sleeve gastrectomy ,LDL cholesterol ,Hypercholesterolemia ,Bariatric surgery ,Lipoprotein ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). Methods In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol
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- 2024
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16. High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study
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Han Na Jung, Ji Hye Huh, Eun Roh, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, and Sung-Hee Ihm
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Remnant-cholesterol ,End-stage renal disease ,Korean national health insurance service ,Lipoprotein ,Triglyceride ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. Methods Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. Results ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50–1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20–29 years, HR 4.07 [95% CI 2.85–5.83]; 30–39 years, HR 2.39 [95% CI 1.83–3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16–1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. Conclusions Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.
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- 2024
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17. Phospholipid biomarkers of coronary heart disease
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Shin-ya Morita
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Phospholipid ,Cholesterol ,Triglyceride ,Lipoprotein ,Coronary heart disease ,Atherosclerosis ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Abstract Coronary heart disease, also known as ischemic heart disease, is induced by atherosclerosis, which is initiated by subendothelial retention of lipoproteins. Plasma lipoproteins, including high density lipoprotein, low density lipoprotein (LDL), very low density lipoprotein, and chylomicron, are composed of a surface monolayer containing phospholipids and cholesterol and a hydrophobic core containing triglycerides and cholesteryl esters. Phospholipids play a crucial role in the binding of apolipoproteins and enzymes to lipoprotein surfaces, thereby regulating lipoprotein metabolism. High LDL-cholesterol is a well-known risk factor for coronary heart disease, and statins reduce the risk of coronary heart disease by lowering LDL-cholesterol levels. In contrast, the relationships of phospholipids in plasma lipoproteins with coronary heart disease have not yet been established. To further clarify the physiological and pathological roles of phospholipids, we have developed the simple high-throughput assays for quantifying all major phospholipid classes, namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol + cardiolipin, and sphingomyelin, using combinations of specific enzymes and a fluorogenic probe. These enzymatic fluorometric assays will be helpful in elucidating the associations between phospholipid classes in plasma lipoproteins and coronary heart disease and in identifying phospholipid biomarkers. This review describes recent progress in the identification of phospholipid biomarkers of coronary heart disease.
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- 2024
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18. Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response.
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Theusch, Elizabeth, Ting, Flora Y., Qin, Yuanyuan, Stevens, Kristen, Naidoo, Devesh, King, Sarah M., Yang, Neil V., Orr, Joseph, Han, Brenda Y., Cyster, Jason G., Chen, Yii-Der I., Rotter, Jerome I., Krauss, Ronald M., and Medina, Marisa W.
- Subjects
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STATINS (Cardiovascular agents) , *ZINC-finger proteins , *LDL cholesterol , *LYMPHOBLASTOID cell lines , *HDL cholesterol , *CELL lines - Abstract
Background: Statins lower circulating low-density lipoprotein cholesterol (LDLC) levels and reduce cardiovascular disease risk. Though highly efficacious in general, there is considerable inter-individual variation in statin efficacy that remains largely unexplained. Methods: To identify novel genes that may modulate statin-induced LDLC lowering, we used RNA-sequencing data from 426 control- and 2 µM simvastatin-treated lymphoblastoid cell lines (LCLs) derived from European and African American ancestry participants of the Cholesterol and Pharmacogenetics (CAP) 40 mg/day 6-week simvastatin clinical trial (ClinicalTrials.gov Identifier: NCT00451828). We correlated statin-induced changes in LCL gene expression with plasma LDLC statin response in the corresponding CAP participants. For the most correlated gene identified (ZNF335), we followed up in vivo by comparing plasma cholesterol levels, lipoprotein profiles, and lipid statin response between wild-type mice and carriers of a hypomorphic (partial loss of function) missense mutation in Zfp335 (the mouse homolog of ZNF335). Results: The statin-induced expression changes of 147 human LCL genes were significantly correlated to the plasma LDLC statin responses of the corresponding CAP participants in vivo (FDR = 5%). The two genes with the strongest correlations were zinc finger protein 335 (ZNF335 aka NIF-1, rho = 0.237, FDR-adj p = 0.0085) and CCR4-NOT transcription complex subunit 3 (CNOT3, rho = 0.233, FDR-adj p = 0.0085). Chow-fed mice carrying a hypomorphic missense (R1092W; aka bloto) mutation in Zfp335 had significantly lower non-HDL cholesterol levels than wild-type C57BL/6J mice in a sex combined model (p = 0.04). Furthermore, male (but not female) mice carrying the Zfp335R1092W allele had significantly lower total and HDL cholesterol levels than wild-type mice. In a separate experiment, wild-type mice fed a control diet for 4 weeks and a matched simvastatin diet for an additional 4 weeks had significant statin-induced reductions in non-HDLC (−43 ± 18% and −23 ± 19% for males and females, respectively). Wild-type male (but not female) mice experienced significant reductions in plasma LDL particle concentrations, while male mice carrying Zfp335R1092W allele(s) exhibited a significantly blunted LDL statin response. Conclusions: Our in vitro and in vivo studies identified ZNF335 as a novel modulator of plasma cholesterol levels and statin response, suggesting that variation in ZNF335 activity could contribute to inter-individual differences in statin clinical efficacy. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Impact of Maternal Pre-Pregnancy Underweight on Cord Blood Metabolome: An Analysis of the Population-Based Survey of Neonates in Pomerania (SNiP).
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Lichtwald, Alexander, Ittermann, Till, Friedrich, Nele, Lange, Anja Erika, Winter, Theresa, Kolbe, Claudia, Allenberg, Heike, Nauck, Matthias, and Heckmann, Matthias
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CORD blood , *HDL cholesterol , *BLOOD testing , *FETAL growth retardation , *PREGNANCY , *WEIGHT gain , *UMBILICAL cord clamping , *OCHRATOXINS - Abstract
Intrauterine growth restriction leads to an altered lipid and amino acid profile in the cord blood at the end of pregnancy. Pre-pregnancy underweight is an early risk factor for impaired fetal growth. The aim of this study was to investigate whether a pre-pregnancy body mass index (ppBMI) of <18.5 kg/m2, as early as at the beginning of pregnancy, is associated with changes in the umbilical cord metabolome. In a sample of the Survey of Neonates in Pomerania (SNIP) birth cohort, the cord blood metabolome of n = 240 newborns of mothers with a ppBMI of <18.5 kg/m2 with n = 208 controls (ppBMI of 18.5–24.9 kg/m2) was measured by NMR spectrometry. A maternal ppBMI of <18.5 kg/m2 was associated with increased concentrations of HDL4 cholesterol, HDL4 phospholipids, VLDL5 cholesterol, HDL 2, and HDL4 Apo-A1, as well as decreased VLDL triglycerides and HDL2 free cholesterol. A ppBMI of <18.5 kg/m2 combined with poor intrauterine growth (a gestational weight gain (GWG) < 25th percentile) was associated with decreased concentrations of total cholesterol; cholesterol transporting lipoproteins (LDL4, LDL6, LDL free cholesterol, and HDL2 free cholesterol); LDL4 Apo-B; total Apo-A2; and HDL3 Apo-A2. In conclusion, maternal underweight at the beginning of pregnancy already results in metabolic changes in the lipid profile in the cord blood, but the pattern changes when poor GWG is followed by pre-pregnancy underweight. [ABSTRACT FROM AUTHOR]
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- 2024
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20. The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis.
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Batista-Dantas, Francisca Elda, Ozak, Christiane Yumi, Gomes Santana, Kelly, Nunes, Valéria Sutti, Uscata, Bernardina Amorin, Siess-Portugal, Cinthia, Campos Reis, Luiza, Yamashiro-Kanashiro, Edite H., Tafuri, Wagner Luiz, Duarte-Neto, Amaro Nunes, Sotto, Mirian Nacagami, Hiro Goto, and Cazita, Patrícia Miralda
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CHOLESTERYL ester transfer protein ,CUTANEOUS leishmaniasis ,B cells ,TRANSGENIC mice ,LEISHMANIASIS - Abstract
Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair. [ABSTRACT FROM AUTHOR]
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- 2024
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21. The Impact of Metabolic and Bariatric Surgery on Apo B100 Levels in Individuals with high BMI: A Multi-Centric Prospective Cohort Study.
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Jaliliyan, Ali, Madankan, Ahmad, Mosavari, Hesam, Khalili, Pantea, Pouraskari, Bahador, Lotfi, Saeed, Honarfar, Andia, Fakhri, Elham, and Eghbali, Foolad
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BARIATRIC surgery ,SLEEVE gastrectomy ,GASTRIC bypass ,LIVER enzymes ,COHORT analysis ,LONGITUDINAL method - Abstract
Background: Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS. Methods: 121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively. Results: Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05). Conclusion: Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial.
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Benaiges, David, Goday, Albert, Casajoana, Anna, Flores-Le Roux, Juana A., Fitó, Montserrat, Pozo, Oscar J., Serra, Carme, Pera, Manuel, Llauradó, Gemma, Climent, Elisenda, Villatoro, Montserrat, Lazaro, Iolanda, Castañer, Olga, and Pedro-Botet, Juan
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LDL cholesterol , *SLEEVE gastrectomy , *GASTRIC bypass , *CLINICAL trials , *BARIATRIC surgery , *SURGICAL complications - Abstract
Background: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). Methods: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. Results: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ −15.2 µg/mg, 95% CI −30.2 to −0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. Conclusion: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. Trial registration: Clinicaltrials.gov number, NCT03975478). [ABSTRACT FROM AUTHOR]
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- 2024
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23. High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study.
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Jung, Han Na, Huh, Ji Hye, Roh, Eun, Han, Kyung-Do, Kang, Jun Goo, Lee, Seong Jin, and Ihm, Sung-Hee
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CHRONIC kidney failure , *LDL cholesterol , *HDL cholesterol , *NATIONAL health insurance , *CHOLESTEROL , *COHORT analysis , *BLOOD cholesterol - Abstract
Background: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. Methods: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. Results: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50–1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20–29 years, HR 4.07 [95% CI 2.85–5.83]; 30–39 years, HR 2.39 [95% CI 1.83–3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16–1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. Conclusions: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Association between hepatic steatosis and lipoprotein(a) levels in non-alcoholic patients: A systematic review.
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Masson, Walter, Barbagelata, Leandro, Godinez-Leiva, Eddison, Genua, Idoia, and Nogueira, Juan Patricio
- Abstract
Background and Objectives: It is well known that lipid abnormalities exist in the context of non-alcoholic fatty liver disease (NAFLD). The association between lipoprotein(a) [Lp(a)] levels and NAFLD is poorly understood. The main objective of the present study was to assess the association between Lp(a) levels and NAFLD. Methods: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42023392526). A literature search was performed to detect studies that evaluated the association between Lp(a) levels, NAFLD and steatohepatitis (NASH). Results: Ten observational studies, including 40,045 patients, were identified and considered eligible for this systematic review. There were 9266 subjects in the NAFLD groups and 30,779 individuals in the respective control groups. Five studies evaluated patients with NAFLD (hepatic steatosis was associated with lower Lp(a) levels in four studies, while the remaining showed opposite results). Two studies evaluating NASH patients showed that Lp(a) levels were not different compared to controls. However, the increment of Lp(a) levels was correlated with liver fibrosis in one of them. In addition, one study analyzed simultaneously patients with NAFLD and NASH, showing a neutral result in NAFLD patients and a positive relationship in NASH patients. Two studies that included patients with the new definition of metabolic-associated fatty liver disease (MAFLD) also showed neutral results. Conclusion: Although there could be an association between Lp(a) levels and hepatic steatosis, the results of the studies published to date are contradictory and not definitive. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Are We Using Ezetimibe As Much As We Should?
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Manolis, Antonis A, Manolis, Theodora A, Mikhailidis, Dimitri P, and Manolis, Antonis S
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EZETIMIBE , *LDL cholesterol , *STATINS (Cardiovascular agents) , *LOW density lipoproteins , *CONTRAST media - Abstract
Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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26. Phospholipid biomarkers of coronary heart disease.
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Morita, Shin-ya
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CORONARY disease ,CHOLESTERYL ester transfer protein ,HIGH density lipoproteins ,BLOOD lipoproteins ,MYOCARDIAL ischemia ,BIOMARKERS - Abstract
Coronary heart disease, also known as ischemic heart disease, is induced by atherosclerosis, which is initiated by subendothelial retention of lipoproteins. Plasma lipoproteins, including high density lipoprotein, low density lipoprotein (LDL), very low density lipoprotein, and chylomicron, are composed of a surface monolayer containing phospholipids and cholesterol and a hydrophobic core containing triglycerides and cholesteryl esters. Phospholipids play a crucial role in the binding of apolipoproteins and enzymes to lipoprotein surfaces, thereby regulating lipoprotein metabolism. High LDL-cholesterol is a well-known risk factor for coronary heart disease, and statins reduce the risk of coronary heart disease by lowering LDL-cholesterol levels. In contrast, the relationships of phospholipids in plasma lipoproteins with coronary heart disease have not yet been established. To further clarify the physiological and pathological roles of phospholipids, we have developed the simple high-throughput assays for quantifying all major phospholipid classes, namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol + cardiolipin, and sphingomyelin, using combinations of specific enzymes and a fluorogenic probe. These enzymatic fluorometric assays will be helpful in elucidating the associations between phospholipid classes in plasma lipoproteins and coronary heart disease and in identifying phospholipid biomarkers. This review describes recent progress in the identification of phospholipid biomarkers of coronary heart disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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27. The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to ovaries in Drosophila.
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Carrera, Pilar, Odenthal, Johanna, Risse, Katharina S., Jung, Yerin, Kuerschner, Lars, and Bülow, Margret H.
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FAT , *CD36 antigen , *DROSOPHILA , *LIPOPROTEIN receptors , *DROSOPHILA melanogaster , *ADIPOGENESIS , *LIPIDS - Abstract
Lipid distribution in an organism is mediated by the interplay between lipoprotein particles, lipoprotein receptors and class B scavenger receptors of the CD36 family. CD36 is a multifunctional protein mediating lipid uptake, mobilization and signaling at the plasma membrane and inside of the cell. The CD36 protein family has 14 members in Drosophila melanogaster, which allows for the differentiated analysis of their functions. Here, we unravel a role for the so far uncharacterized scavenger receptor Bez in lipid export from Drosophila adipocytes. Bez shares the lipid binding residue with CD36 and is expressed at the plasma membrane of the embryonic, larval and adult fat body. Bez loss of function lowers the organismal availability of storage lipids and blocks the maturation of egg chambers in ovaries. We demonstrate that Bez interacts with the APOB homolog Lipophorin at the plasma membrane of adipocytes and trace the Bez-dependent transfer of an alkyne-labeled fatty acid from adipocytes to Lipophorin. Our study demonstrates how lipids are distributed by scavenger receptor-lipoprotein interplay and contribute to the metabolic control of development. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Lipolysis products from triglyceride‐rich lipoproteins induce stress protein ATF3 in osteoblasts.
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Rutkowsky, Jennifer M., Wong, Alice, Toupadakis, Chrisoula A., Rutledge, John C., and Yellowley, Clare E.
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HEAT shock proteins , *LIPOPROTEINS , *CHYLOMICRONS , *LIPOLYSIS , *OSTEOBLASTS , *HIGH-fat diet - Abstract
High fat diets overwhelm the physiological mechanisms for absorption, storage, and utilization of triglycerides (TG); consequently TG, TG‐rich lipoproteins (TGRL), and TGRL remnants accumulate, circulate systemically, producing dyslipidemia. This associates with, or is causative for increased atherosclerotic cardiovascular risk, ischemic stroke, fatty liver disease, and pancreatitis. TGRL hydrolysis by endothelial surface‐bound lipoprotein lipase (LPL) generates metabolites like free fatty acids which have proinflammatory properties. While osteoblasts utilize fatty acids as an energy source, dyslipidemia is associated with negative effects on the skeleton. In this study we investigated the effects of TGRL lipolysis products (TGRL‐LP) on expression of a stress responsive transcription factor, termed activating transcription factor 3 (ATF3), reactive oxygen species (ROS), ATF3 target genes, and angiopoietin‐like 4 (Angptl4) in osteoblasts. As ATF3 negatively associates with osteoblast differentiation, we also investigated the skeletal effects of global ATF3 deletion in mice. TGRL‐LP increased expression of Atf3, proinflammatory proteins Ptgs2 and IL‐6, and induced ROS in MC3T3‐E1 osteoblastic cells. Angptl4 is an endogenous inhibitor of LPL which was transcriptionally induced by TGRL‐LP, while recombinant Angptl4 prevented TG‐driven Atf3 induction. Atf3 global knockout male mice demonstrated increased trabecular and cortical microarchitectural parameters. In summary, we find that TGRL‐LP induce osteoblastic cell stress as evidenced by expression of ATF3, which may contribute to the negative impact of dyslipidemia in the skeleton. Further, concomitant induction of Angptl4 in osteoblasts might play a protective role by reducing local lipolysis. [ABSTRACT FROM AUTHOR]
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- 2024
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29. The nonvesicular sterol transporter Aster-C plays a minor role in whole body cholesterol balance.
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Banerjee, Rakhee, Hohe, Rachel C., Shijie Cao, Jung, Bryan M., Horak, Anthony J., Ramachandiran, Iyappan, Massey, William J., Varadharajan, Venkateshwari, Zajczenko, Natalie I., Burrows, Amy C., Dutta, Sumita, Goudarzi, Maryam, Mahen, Kala, Carter, Abigail, Helsley, Robert N., Gordon, Scott M., Morton, Richard E., Strauch, Christopher, Willard, Belinda, and Gogonea, Camelia Baleanu
- Subjects
CHOLESTEROL ,CHOLESTEROL metabolism ,DIETARY cholesterol ,BILE acids ,STEROID hormones - Abstract
Introduction: The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions. Method: Age-matched Gramd1c
+/+ and Gramd1c-/- mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterolderived metabolites were assessed in the feces, liver, and plasma. Results: Compared to wild type controls (Gramd1c+/+ ) mice, mice lackingGramd1c (Gramd1c-/- ) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c+/+ controls, Gramd1c-/- mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c-/- mice. Bulk RNA sequencing in the liver showed that Gramd1c-/- mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions. Discussion: Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited. [ABSTRACT FROM AUTHOR]- Published
- 2024
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30. A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver steatosis
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Yang Jin, Darby Kozan, Eric D. Young, Monica R. Hensley, Meng-Chieh Shen, Jia Wen, Tabea Moll, Jennifer L. Anderson, Hannah Kozan, John F. Rawls, and Steven A. Farber
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apolipoproteins ,lipoprotein ,adipocytes ,liver ,dietary cholesterol ,hepatic steatosis ,Biochemistry ,QD415-436 - Abstract
Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are available, there has yet to be a uniformly adopted zebrafish HCD protocol. In this study, we have developed an improved HCD protocol and thoroughly tested its impact on zebrafish lipid deposition and lipoprotein regulation in a dose- and time-dependent manner. The diet stability, reproducibility, and fish palatability were also validated. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LPs) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae for 8 days produced hepatic steatosis that became more stable and sever after 1 day of fasting and was associated with an opaque liver phenotype (dark under transmitted light). Unlike larvae, adult fish fed HCD for 14 days followed by a 3-day fast did not develop a stable fatty liver phenotype, though the fish had higher ApoB-LP levels in plasma and an upregulated lipogenesis gene fasn in adipose tissue. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease.
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- 2024
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31. Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network
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Faron, M., Naman, A., Delahousse, J., Hescot, S., Hadoux, J., Castinetti, F., Drui, D., Renoult-Pierre, P., Libe, R., Lamartina, L., Leboulleux, S., Al-Ghuzlan, A., Lombès, M., Paci, A., and Baudin, E.
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- 2024
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32. Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study
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Xia, Xue, Han, Xinsheng, Xia, Guangxin, Zhao, Xingquan, and Wang, Anxin
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- 2024
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33. Surgical Treatment of Multiple Large Tuberous and Tendinous Xanthoma Secondary to Familial Hypercholesterolaemia: A Case Report
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Guan H, Zhang G, Li Q, Lian J, Dong Z, Zhu L, and Xiao K
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soft-tissue tumors ,lipoprotein ,atorvastatin ,foam cells ,lipid-lowering therapy ,Dermatology ,RL1-803 - Abstract
Haonan Guan,* Guoyou Zhang,* Qiqi Li, Jie Lian, Zhaoyang Dong, Lian Zhu, Kaiyan Xiao Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaiyan Xiao, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People’s Republic of China, Tel +86 021 23271699, Fax +86 021 63136856, Email xky7026@163.comAbstract: Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.Keywords: soft-tissue tumors, lipoprotein, atorvastatin, foam cells, lipid-lowering therapy
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- 2024
34. MicroRNAs and Oxidative Stress Markers as Additional Diagnostic Criteria for Coronary Heart Disease
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Oksana Yu. Marchenko, Nadiya M. Rudenko, and Dmytro S. Krasnienkov
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mirna-122 ,glutathione ,lipoprotein ,biomarker ,atherosclerosis ,ischemic heart disease ,Surgery ,RD1-811 - Abstract
The aim. To examine the significance of microribonucleic acids (miRNAs) and oxidative stress markers in predicting the onset of atherosclerosis and the connection between oxidative stress levels and miRNAs in individuals with coronary heart disease. Materials and methods. Initially, 40 patients were divided as follows: 10 subjects without any lesions in coronary arteries (group 0), 4 patients with non-stenotic atherosclerosis (group 1), and 26 patients with significant multivessel atherosclerotic lesions (group 2). Various biochemical parameters were analyzed, including miRNA expression levels and common oxidative stress markers. Results. The groups were comparable in terms of the patients’ age, but there was unequal distribution of males and females in the angio-groups as per Fisher’s exact test. We also analyzed the data separately for females, but no significant difference was found. There were significant differences in miRNA-122 levels, N-terminal prohormone of brain natriuretic peptide levels, lipid profiles, and oxidative stress markers between group 0 and groups with atherosclerotic lesions. Specifically, miRNA-122 levels were elevated in group 0, along with N-terminal prohormone of brain natriuretic peptide, triglycerides, ratio of triglycerides to high-density lipoprotein cholesterol, and oxidative stress markers. Conversely, compared to group 0, total cholesterol, high-density lipoprotein cholesterol, bilirubin, and specific glutathione levels decreased in patients with coronary lesions. Conclusions. The study demonstrated the potential of miRNAs, particularly miRNA-122, as predictive biomarkers for atherosclerosis. Further research with larger cohorts is warranted to validate these findings and explore additional miRNA candidates and therapeutic interventions for cardiovascular diseases.
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- 2024
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35. Study of metabolic association between elevated fasting blood glucose and cognitive deterioration
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WU Lirong, CHEN Ruihua, CHAO Xiaowen, GUO Yuhuai, SUN Tao, LI Mengci, and CHEN Tianlu
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hyperglycemia ,cognitive impairment ,metabolomics ,risk factor ,lipoprotein ,Medicine - Abstract
Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose (FBG) and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were downloaded, and the samples with FBG and follow-up data were selected from the database. Clinical information, including age, gender, body mass index, education years, apolipoprotein E4 (APOE4) genotype and race, and corresponding metabolic indicator data, including amino acids, fatty acids, proteins and others were obtained. Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease, the subjects were categorized into four groups: normal FBG without/with cognitive deterioration, and elevated FBG without/with cognitive deterioration. The univariate analysis method, the Cox proportional hazards model, orthogonal projections to latent structures discriminant analysis (OPLSDA), and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included, among which 1 153 had normal FBG level (>3.9 mmol/L and
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- 2024
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36. Dissection of an ABC transporter LolCDE function analyzed by photo-crosslinking.
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Tao, Kazuyuki, Narita, Shin-ichiro, Okada, Ui, Murakami, Satoshi, and Tokuda, Hajime
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ATP-binding cassette transporters , *PHOTOCROSSLINKING , *ESCHERICHIA coli , *LIPOPROTEINS , *DISSECTION , *CROSSLINKED polymers - Abstract
The envelope of Escherichia coli contains approximately 100 different species of lipoproteins, most of which are localized to the inner leaflet of the outer membrane. The localization of lipoprotein (Lol) system, consisting of five Lol proteins, is responsible for the trafficking of lipoproteins to the outer membrane. LolCDE binds to lipoproteins destined for the outer membrane and transfers them to the periplasmic chaperone LolA. Although the cryo-EM structures of E. coli LolCDE have been reported, the mechanisms by which outer membrane lipoproteins are transferred to LolA remain elusive. In this study, we investigated the interaction between LolCDE and lipoproteins using site-specific photo-crosslinking. We introduced a photo-crosslinkable amino acid into different locations across the four helices which form the central lipoprotein-binding cavity, and identified domains that crosslink with peptidoglycan-associated lipoprotein (Pal) in vivo. Using one of the derivatives containing the photo-crosslinkable amino acid, we developed an in vitro system to analyze the binding of lipoproteins to LolCDE. Our results indicate that compound 2, a LolCDE inhibitor, does not inhibit the binding of lipoproteins to LolCDE, but rather promotes the dissociation of bound lipoproteins from LolCDE. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Homeostasis Model Assessment for Insulin Resistance Mediates the Positive Association of Triglycerides with Diabetes.
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Wang, Yutang, Fang, Yan, and Vrablik, Michal
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INSULIN resistance , *TRIGLYCERIDES , *INSULIN sensitivity , *LDL cholesterol , *HOMEOSTASIS - Abstract
Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43–0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, −0.13; 95% CI, −0.31–0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, −0.003–0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Modulatory actions of Echinococcus granulosus antigen B on macrophage inflammatory activation.
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Maite Folle, Ana, Lagos Magallanes, Sofía, Fló, Martín, Alvez-Rosado, Romina, Carrión, Federico, Vallejo, Cecilia, Watson, David, Julve, Josep, González-Sapienza, Gualberto, Pristch, Otto, González-Techera, Andrés, and María Ferreira, Ana
- Subjects
ECHINOCOCCUS granulosus ,MACROPHAGE activation ,ANTIGENS ,IMMUNOAFFINITY chromatography ,CARRIER proteins ,LIPIDS - Abstract
Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1β, IL-6, IL-12p40, IFN-β) secretion and ·NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid’s effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB´s ability to regulate the inflammatory activation of macrophages. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Conventional HDL Subclass Measurements Mask Thyroid Hormone-dependent Remodeling Activity Sites in Hypothyroid Individuals.
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Bagdade, John D and McCurdy, Carrie E
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CHOLESTERYL ester transfer protein ,NUCLEAR magnetic resonance spectroscopy ,BLOOD lipoproteins ,BLOOD lipids ,THYROID gland ,HIGH density lipoproteins - Abstract
Context Earlier nuclear magnetic resonance spectroscopy (NMR) studies of plasma lipoproteins estimated by size as small, medium, and large particles, demonstrated hypothyroidism was associated with increases in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) subclass particle number but variable changes in the high-density lipoprotein (HDL) subclasses. These disparate changes in HDL might be explained by reduced activity of the thyroid hormone-dependent remodeling proteins whose subclass specificity may be obscured when the 5 HDL subclasses identified by NMR are combined by size. Objective This work aimed to determine whether directional changes in particle number of individually measured HDL subclasses correlate with reduced activity of their thyroid hormone–dependent remodeling proteins in hypothyroid individuals. Methods VLDL, LDL, IDL, and HDL subclasses were measured by NMR in 13 thyroidectomized individuals 1 month following thyroid hormone withdrawal and 3 months after replacement. Changes in particle numbers in each subclass were compared when expressed individually and by size. Results Following thyroid hormone withdrawal, plasma lipids and VLDL, LDL, and IDL subclass particle number increased. HDL particle number nearly doubled in very small HDL-1 (P =.04), declined in small HDL-2 (P =.02), and increased 2-fold in HDL-5 (P =.0009). Conclusion The increment in HDL-1 and decline in HDL-2 subclasses is consistent with their precursor-product relationship and reduced lecithin cholesterol acyltransferase activity while the almost 2-fold increase in large HDL-5 is indicative of diminished action of hepatic lipase, phospholipid transfer protein, and endothelial lipase. These findings are inapparent when the 5 subclasses are expressed conventionally by size. This linking of specific HDL subclasses with HDL remodeling protein function provides new details about the specificity of their interactions. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Lipoprotein signal peptidase‐deficient Streptococcus pneumoniae exhibits impaired Toll‐like receptor 2‐stimulatory activity.
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Domon, Hisanori, Hirayama, Satoru, Isono, Toshihito, Saito, Rui, Yanagihara, Katsunori, and Terao, Yutaka
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STREPTOCOCCUS pneumoniae ,TOLL-like receptors ,PEPTIDASE ,STREPTOCOCCAL diseases ,COMMUNITY-acquired pneumonia ,PHASE separation - Abstract
Streptococcus pneumoniae is a causative agent of community‐acquired pneumonia. Upon pneumococcal infection, innate immune cells recognize pneumococcal lipoproteins via Toll‐like receptor 2 and induce inflammation. Here, we generated a strain of S. pneumoniae deficient in lipoprotein signal peptidase (LspA), a transmembrane type II signal peptidase required for lipoprotein maturation, to investigate the host immune response against this strain. Triton X‐114 phase separation revealed that lipoprotein expression was lower in the LspA‐deficient strain than in the wild‐type strain. Additionally, the LspA‐deficient strain decreased nuclear factor‐κB activation and cytokine production in THP‐1 cells, indicating impaired innate immune response against the strain. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Bottlenecks in the Investigation of Retinal Sterol Homeostasis.
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Ramachandra Rao, Sriganesh and Fliesler, Steven J.
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HOMEOSTASIS , *RETINA , *PHYTOSTEROLS , *LIPOPROTEINS , *RETINAL degeneration - Abstract
Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intratissue, intercellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Correlation analysis of plasma lipid profiles and the prognosis of head and neck squamous cell carcinoma.
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Wang, Siyu, Wang, Li, Li, Huan, Zhang, Jiayu, Peng, Jianmin, Cheng, Bin, Song, Ming, and Hu, Qinchao
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BIOMARKERS , *RESEARCH , *LIPOPROTEINS , *DISEASE progression , *ACADEMIC medical centers , *SPECIALTY hospitals , *MULTIVARIATE analysis , *HEAD & neck cancer , *RETROSPECTIVE studies , *CELL receptors , *LDL cholesterol , *RISK assessment , *CANCER patients , *GENE expression , *CELLULAR signal transduction , *CANCER treatment , *APOLIPOPROTEINS , *CANCER genes , *DESCRIPTIVE statistics , *RESEARCH funding , *STATISTICAL correlation , *PROGRESSION-free survival , *LIPIDS , *SQUAMOUS cell carcinoma , *DIETARY fats - Abstract
Purpose: This study aims to clarify whether blood lipid profiles are indicators of prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Methods: This retrospective study included 512 T1/2N0M0 HNSCC patients. The correlation between blood lipid profiles and progression‐free survival (PFS) and disease‐specific survival (DSS) was analyzed by multivariate analysis. The data from TCGA was also analyzed to investigate the expression levels and prognostic values of different lipoprotein receptors essential for specific lipid uptake. Results: A high level of low‐density lipoprotein cholesterol (LDL‐C) indicated better PFS and DSS, and a low level of apolipoprotein A‐I (Apo A‐I) indicated better PFS, while a high level of apolipoprotein B (Apo B) indicated poorer PFS and DSS. The Apo A‐I receptor gene SCARB1 was upregulated and associated with poor survival in HNSCC patients. Activation of SCARB1 was implicated in a series of tumor‐promoting pathways. There was no significant correlation between the expression of LDL‐C and Apo B‐related receptors and prognosis. Conclusion: A high level of LDL‐C and a low level of Apo A‐I are protective factors for HNSCC, while a high level of Apo B is a risk factor. The upregulation of SCARB1 may participate in the progression of HNSCC. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Identification of biomarkers for vascular dementia: a literature review.
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Jamali, Qutub, Akinfala, Akinloye, and Upendram, Amulya
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LITERATURE reviews , *VASCULAR dementia , *ALZHEIMER'S disease , *BIOMARKERS - Abstract
SUMMARY: Alzheimer's disease and vascular dementia are the two most common types of dementia. It becomes difficult to distinguish between the two, especially when there are no specific genetic causes or vascular changes apparent. The aim of this review was to identify specific biomarkers supporting the diagnosis of vascular dementia by conducting a literature search for systematic reviews and observational studies. We found seven studies meeting our inclusion/exclusion criteria, and from these we identified four specific biomarkers supporting the diagnosis of vascular dementia: high levels of thyroid-stimulating hormone, lipoprotein(a), homocysteine and N-terminal prosomatostatin. However, the studies were small and a well-conducted study with larger populations is recommended to strengthen the evidence base. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Bioinspired Lipoproteins of Furoxans–Gemcitabine Preferentially Targets Glioblastoma and Overcomes Radiotherapy Resistance.
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Sun, Maoyuan, Xie, Honglei, Zhang, Wenli, Li, Xianlu, Jiang, Zhan, Liang, Yiyu, Zhao, Guanjian, Huang, Ning, Mao, Jinning, Liu, Guodong, and Zhang, Zhiwen
- Subjects
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TUMOR growth , *LIPOPROTEINS , *GLIOBLASTOMA multiforme , *DNA repair , *RADIOTHERAPY , *REVERSE transcriptase - Abstract
Radiotherapy (RT) resistance is an enormous challenge in glioblastoma multiforme (GBM) treatment, which is largely associated with DNA repair, poor distribution of reactive radicals in tumors, and limited delivery of radiosensitizers to the tumor sites. Inspired by the aberrant upregulation of RAD51 (a critical protein of DNA repair), scavenger receptor B type 1 (SR‐B1), and C‐C motif chemokine ligand 5 (CCL5) in GBM patients, a reduction‐sensitive nitric oxide (NO) donor conjugate of gemcitabine (RAD51 inhibitor) (NG) is synthesized as radio‐sensitizer and a CCL5 peptide‐modified bioinspired lipoprotein system of NG (C‐LNG) is rationally designed, aiming to preferentially target the tumor sites and overcome the RT resistance. C‐LNG can preferentially accumulate at the orthotopic GBM tumor sites with considerable intratumor permeation, responsively release the gemcitabine and NO, and then generate abundant peroxynitrite (ONOO−) upon X‐ray radiation, thereby producing a 99.64% inhibition of tumor growth and a 71.44% survival rate at 120 days in GL261‐induced orthotopic GBM tumor model. Therefore, the rationally designed bioinspired lipoprotein of NG provides an essential strategy to target GBM and overcome RT resistance. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Association between exposure to air pollution and blood lipids in the general population of Spain.
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Valdés, Sergio, Doulatram‐Gamgaram, Viyey, Maldonado‐Araque, Cristina, García‐Escobar, Eva, García‐Serrano, Sara, Oualla‐Bachiri, Wasima, García‐Vivanco, Marta, Garrido, Juan Luis, Gil, Victoria, Martín‐Llorente, Fernando, Calle‐Pascual, Alfonso, Castaño, Luis, Delgado, Elías, Menéndez, Edelmiro, Franch‐Nadal, Josep, Gaztambide, Sonia, Girbés, Joan, Chaves, F. Javier, Galán‐García, José L., and Aguilera‐Venegas, Gabriel
- Subjects
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AIR pollution , *BLOOD lipids , *AIR pollutants , *PARTICULATE matter , *AIR quality - Abstract
Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain. Methods: We included 4647 adults (>18 years), participants in the national, cross‐sectional, population‐based di@bet.es study, conducted in 2008–2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1H‐NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM10), <2.5 μm (PM2.5) and nitrogen dioxide (NO2), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry‐transport model). Results: In multivariate linear regression models, each IQR increase in PM10, PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL‐c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL‐p) concentrations (p <.001 for all associations). In multivariate logistic regression, there was a significant association between PM10, PM2.5 and NO2 concentrations and the odds of presenting low HDL‐c (<40 mg/dL), low HDL‐p (
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- 2024
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46. The effect of Green green tea consumption on body mass index, lipoprotein, liver enzymes, and liver cancer: An updated systemic review incorporating a meta-analysis.
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Li, Mingzhen, Duan, Yunjie, Wang, Ying, Chen, Lei, Abdelrahim, Mohamed E. A., and Yan, Jun
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GREEN tea , *BODY mass index , *LIVER enzymes , *ASPARTATE aminotransferase , *LIVER cancer , *SUSTAINABLE consumption - Abstract
Green tea is related to the reduction of liver enzymes, lipoprotein, and body mass index. However, some reports related green tea to the risk of developing liver cancer, but their outcomes were conflicting. Hence, the present study aimed to determine the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer. A systematic literature search up to January 2022 was performed and 22 studies with a total of 169599 subjects participated in the studies with 97316 subjects of them used green tea intake. Odds ratio (OR) or standardized mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer using the dichotomous or the contentious method with a random effect model. Green tea intake significantly lowered the risk of developing liver cancer (OR, 0.85; 95% CI, 0.74 to 0.97, p = 0.02), and body mass index (MD, −0.69; 95% CI, −0.95to −0.42, p < 0.001) compared to no green tea intake. Also, there was a significant lowering effect of green tea intake on liver enzymes including alanine aminotransferase (MD, −0.65; 95% CI, −0.92 to −0.38, p < 0.001), and aspartate aminotransferase (MD, −0.77; 95% CI, −1.40 to −0.14, p = 0.02) compared to no green tea intake. There was also a significant lowering effect of green tea intake on lipoprotein including triglycerides (MD, −0.70; 95% CI, −1.35 to −0.04, p = 0.04), total cholesterol (MD, −0.39; 95% CI, −0.74 to −0.04, p = 0.03) and law-density lipoprotein (MD, −0.44; 95% CI, −0.69- −0.19, p < 0.001) compared to no green tea intake. However, no significant different was found between green tea intake and no green tea intake on high-density lipoprotein (MD, 0.16; 95% CI, −0.11 to 0.44, p = 0.24). Based on this meta-analysis, green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea may be added to the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups. [ABSTRACT FROM AUTHOR]
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- 2024
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47. PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response.
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Asoudeh, Monireh, Nguyen, Nicole, Raith, Mitch, Denman, Desiree S., Anozie, Uche C., Mokhtarnejad, Mahshid, Khomami, Bamin, Skotty, Kaitlyn M., Isaac, Sami, Gebhart, Taylor, Vaigneur, Lauren, Gelgie, Aga, Dego, Oudessa Kerro, Freeman, Trevor, Beever, Jon, and Dalhaimer, Paul
- Subjects
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PHAGOCYTOSIS , *IMMUNE response , *LIPOPROTEIN receptors , *BLOOD proteins , *MACROPHAGES , *HIGH density lipoproteins , *ENDOTHELIAL cells , *MACROPHAGE colony-stimulating factor - Abstract
Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP – macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP – macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP – macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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48. 空腹血糖升高与认知功能恶化的代谢关联研究.
- Author
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吴丽蓉, 陈瑞华, 晁筱雯, 郭雨槐, 孙涛, 李梦慈, and 陈天璐
- Abstract
To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose (FBG) and the metabolic clues associated with changes in the risk of cognitive deterioration. Methods Data from the Alzheimer's Disease Neuroumaging Initiative (ADNI) database were downloaded, and the samples with FBG and follow-up data were selected from the database. Clinical information, including age, gender, body mass index, education years, apolipoprotein E4 (APOE4) genotype and race, and corresponding metabolic indicator data, including amino acids, fatty acids, proteins and others were obtained. Based on the FBG levels and diagnosis of cognitive impairment stages im Alzheimer's disease, the subjects were categorized into four groups, normal FBG without with cognitive deterioration, and elevated FHG without with cognitive deterioration. The univariate analysis method, the Cox proportional hazards model, orthogonal projections to latent structures discriminant analysis (OPLSDA), and Spearman correlation analysis were employed for data analysis. Results A total of 1 317 subjects were included, among which 1 153 had normal FBG level (3.9 mmol/L and 6.1 mmol/L) and 164 had elevated FBG level (26.1 mmol/L). In the normal FBG group. 275 subjects showed cognitive deterioration, while in the elevated FBG group, 53 subjects showed cognitive deterioration. Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group, and significant differences in age, gender, and APOE4 genotype between the groups with and without cognitive deterioration (all P<0.05). Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity, zlevated FBG, and increasing age in order (HR-222,HR-1.38, HR-1.02; all P<0.05). In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration, as well as metabolic indicators hefore and after cognitive deterioration at different FBG levels, the results of the analysis of variance revealed that in the cognitively deteriorated population, the ratio of phospholipids carried by high-density lipoproteins (HDL) to total lipids was significantly higher, low-density lipoprotein (LDL) particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration. Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau (pTau) level in the plasma in the cognitively deteriorated population. Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid (CSF). Conclusinn-Compared to the individuals with normal FBG level, those with high FBG level have a significantly higher risk of cognitive deterioration. Additionally, different metabolic indicators show significant differences between the groups without and with cognitive deterioration, as well as metabolic indicators before and after cognitive deterioration at different FBG levels. Overall, LDL and its lipid content, and HDL-carried phospholipids show an increasing trend during cognitive deterioration, and the branched- chain amino acids valine and leucine are significantly correlated with plan levels in CSF and plasma, suggesting that these metabolic markers may play an important role in cognitive deterioration. [ABSTRACT FROM AUTHOR]
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- 2024
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49. The Efficacy of Lactobacillus delbrueckii ssp. bulgaricus Supplementation in Managing Body Weight and Blood Lipids of People with Overweight: A Randomized Pilot Trial.
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Chu, Pei-Yi, Yu, Ying-Chun, Pan, Yi-Cheng, Dai, Yun-Hao, Yang, Juan-Cheng, Huang, Kuo-Chin, and Wu, Yang-Chang
- Subjects
LACTOBACILLUS delbrueckii ,BODY weight ,WEIGHT loss ,PROBIOTICS ,BLOOD lipids ,OVERWEIGHT persons ,FAT - Abstract
This study aimed to evaluate the efficacy of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) in improving body weight, obesity-related outcomes, and lipid profiles of overweight people. Thirty-six overweight participants were randomly assigned to either a probiotic or a placebo group. A placebo powder or L. bulgaricus powder (containing 1 × 10
8 colony-forming unit (CFU) of the probiotic) was administered daily for 12 weeks. Body composition was determined, and blood tests were performed before and after the intervention. L. bulgaricus supplementation under the present condition did not affect the body weight, fat percentage, or body mass index (BMI) of the participants, while it resulted in a notable decrease in blood triglyceride (TG) levels, which corresponded to a lowering of the TG proportion in the composition of large VLDL (L–XXL sized fractions) and HDL (M and L fractions) in the probiotic-treated group. These results suggest that L. bulgaricus supplementation under the current conditions may not be helpful for losing weight, but it has the potential to decrease blood TG levels by modulating TG accumulation in or transport by VLDL/HDL in obese patients. L. bulgaricus supplements may have health-promoting properties in preventing TG-related diseases in overweight people. [ABSTRACT FROM AUTHOR]- Published
- 2024
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50. Lipoprotein lipase as a target for obesity/diabetes related cardiovascular disease
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Rui Shang and Brian Rodrigues
- Subjects
cardiomyopathy ,lipoprotein ,atherosclerosis ,fatty acid metabolism ,cardiomyocytes ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Worldwide, the prevalence of obesity and diabetes have increased, with heart disease being their leading cause of death. Traditionally, the management of obesity and diabetes has focused mainly on weight reduction and controlling high blood glucose. Unfortunately, despite these efforts, poor medication management predisposes these patients to heart failure. One instigator for the development of heart failure is how cardiac tissue utilizes different sources of fuel for energy. In this regard, the heart switches from using various substrates, to predominantly using fatty acids (FA). This transformation to using FA as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has grave end results. This is because toxic by-products are produced by overuse of FA, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating FA delivery to the heart, and its function during diabetes has not been completely revealed. In this review, the mechanisms by which LPL regulates fuel utilization by the heart in control conditions and following diabetes will be discussed in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, research on LPL may assist in drug development that exclusively targets fuel utilization by the heart and lipid accumulation in macrophages to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.
- Published
- 2024
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