Elevated Total Cholesterol Levels Research Articles

6-PPD triggered lipid metabolism disorder and inflammatory response in larval zebrafish (Danio rerio) by regulating PPARγ/NF-κB pathway.

As a synthetic rubber antioxidant, the environmental monitoring concentrations of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD) have exceeded the risk threshold, attracting widespread attention. Although investigations into the harmful effects on zebrafish have commenced, a comprehensive exploration of its toxicological impacts and underlying molecular mechanisms remains to be conducted. By using zebrafish as a model, this study systematically evaluated 6-PPD-induced lipid metabolism disorders and inflammation response following environmental exposure. Bioinformatics analysis revealed that 6-PPD target genes enriched in the hepatitis B pathway, indicating potential hepatic toxicity via inflammatory pathways. Therefore, we hypothesize that 6-PPD could trigger hepatotoxicity through the crosstalk between lipid metabolism and inflammation. Further experiments substantiated this hypothesis by showing lipid accumulation in the liver following 6-PPD exposure, along with elevated triglyceride (TG) and total cholesterol (TC) levels, and imbalanced expression of lipid metabolism-related marker genes. Additionally, 6-PPD exposure induced the accumulation of reactive oxygen species (ROS) and inhibited the differentiation and maturation of immune cells, resulting in immune evasion. Most of these abnormalities were exacerbated in a dose-dependent manner with increasing concentrations of 6-PPD. The addition of the PPARγ pathway agonist puerarin (PUE) or NF-κB pathway inhibitor quinazoline (QNZ) to 6-PPD exposure group mitigated these toxic effects, validating our conjecture that lipid metabolism disorder and inflammatory responses may result from the regulation of the PPARγ/NF-κB pathway.

Concentrations of Serum Per- and Polyfluoroalkyl Substances and Lipid Health in Adolescents: A Cross-Sectional Study from the Korean National Environmental Health Survey 2018–2020

Emerging evidence indicates that environmental exposure to per- and polyfluoroalkyl substances (PFASs) may influence lipid metabolism, though studies on adolescents remain scarce. This study aimed to investigate the association between PFAS mixture exposure and lipid profiles in Korean adolescents. Using data from the Korean National Environmental Health Survey (2018–2020), we analyzed 824 adolescents aged 12–17 years. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDeA), and lipid profiles were assessed. In multivariate regression models, PFDeA and PFNA were positively associated with elevated total cholesterol and low-density lipoprotein cholesterol levels, and PFDeA was associated with hypercholesterolemia risk in boys. In girls, PFDeA was associated with higher high-density lipoprotein cholesterol and lower triglycerides, though no significant association with hypercholesterolemia risk was observed. Bayesian kernel machine regression demonstrated positive associations between PFAS mixture exposure and hypercholesterolemia risk in boys but not in girls. The quantile g-computation model also demonstrated an odds ratio (OR) of 1.47 (95% CI: 0.99–2.19, p = 0.057) for PFAS mixture exposure in boys, suggesting borderline statistical significance. These findings suggest that PFAS exposure may disrupt lipid metabolism, elevating hypercholesterolemia risk in adolescents, particularly boys.

Correlation of dyslipidemia characterized by abnormal cholesterol in first trimester with early pregnancy loss: a retrospective study.

Dyslipidemia has been linked to adverse pregnancy outcomes in observational studies. This study aimed to explore how variations in lipid levels during the first trimester might influence early pregnancy loss (EPL). Blood samples from pregnant women were analyzed to examine the relationship between EPL and lipid metabolism using logistic regression and restricted cubic splines (RCS). Sensitivity analysis was conducted to verify the robustness of the results. Elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels at most times of 4-9weeks of gestation were associated with a higher risk of EPL, regardless of whether the control group was successful pregnancy or live birth. Specifically, taking the successful pregnancy group as a control example, increased EPL risks were observed in the highest quartile of plasma TC at 4weeks (OR = 2.18, 95%: 1.14-4.21) and 7weeks (OR = 4.30, 95%: 1.87-9.93) of pregnancy. Significant EPL risks were also noted in the third (Q3) and fourth (Q4) quartiles of LDL-C at 4weeks (Q3, OR = 2.98, 95%: 1.47-6.08; Q4, OR = 2.66, 95%: 1.27-5.55) and 7weeks (Q3, OR = 3.12, 95%: 1.44-6.73; Q4, OR = 5.17, 95%: 2.14-12.49). High TC levels (> 3.25-3.78mmol/L) and high LDL-C levels (> 1.92-2.04mmol/L) were linked to an increased risk of EPL compared to lower levels of TC (≤ 2.91-3.05mmol/L) and LDL-C (≤ 1.64-1.75mmol/L).RCS analysis further confirmed this finding that plasma TC and LDL-C levels at 4 and 7weeks of gestation may have a linear relationship with the risk of EPL. By the way, triglyceride levels at 6 and 8weeks of gestation were associated with a higher risk of EPL, whereas high-density lipoprotein cholesterol (HDL-C) levels at 5 and 9weeks of gestation have a completely opposite relationship with EPL risk. Elevated cholesterol levels during the first trimester are associated with an increased risk of early pregnancy loss, emphasizing the need for lipid monitoring during pregnancy and even before pregnancy.

The relationship between cholesterol levels and thyroid eye disease.

Thyroid eye disease (TED) is the most prevalent extrathyroidal manifestation of Graves' disease (GD). Emerging evidence suggests a relationship between elevated total and low-density lipoprotein (LDL) cholesterol levels and TED. This study aimed to investigate this correlation in the Brazilian population by analyzing data from two tertiary care centers. Data were collected from GD patients treated with methimazole between 1999 and 2021, excluding those receiving other treatments. Laboratory results and information on smoking habits, statin use and medications affecting lipid profiles during the euthyroid state were analyzed. Smoking and elevated LDL cholesterol levels were significantly associated with TED activity and severity. Logistic regression revealed correlations between higher LDL cholesterol, total cholesterol and increased clinical activity score (P < 0.01, OR: 1.012, 95% CI: 1.003-1.021; P < 0.01, OR: 1.010, 95% CI: 1.002-1.018). These were also associated with more severe disease forms as defined by EUGOGO (P < 0.01, OR: 1.015, 95% CI: 1.006-1.024; P < 0.005, OR: 1.011, 95% CI: 1.004-1.019). Multiple regression confirmed that TED activity was significantly correlated with LDL cholesterol (P < 0.01) and smoking status (P < 0.01). Disease severity was associated with reduced HDL cholesterol (P < 0.05, OR: 0.973, 95% CI: 0.948-0.999), elevated LDL cholesterol (P < 0.005, OR: 1.013, 95% CI: 1.004-1.023) and active smoking (P < 0.05, OR: 2.881, 95% CI: 1.190-6.971). Elevated LDL cholesterol may serve as a potential indicator of TED. Further research is needed to determine whether lipid-lowering interventions could reduce TED risk or improve its management.

The role of lysosomal acid lipase deficiency in dyslipidemia and liver disorders.

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene, leading to reduced lysosomal acid lipase activity, cholesterol ester accumulation, and systemic manifestations including liver dysfunction and dyslipidemia. We report the case of a 25-year-old male presenting with subacute jaundice, hyperbilirubinemia (total bilirubin 51 mg/dL, predominantly direct), and dyslipidemia characterized by elevated total cholesterol and low HDL cholesterol levels. Initial diagnostic workup for acute hepatitis and liver dysfunction, including serological and imaging studies, was unremarkable. Liver biopsy revealed canalicular cholestasis and T-lymphocyte infiltration without fibrosis, raising suspicion for a metabolic or genetic etiology. Genetic analysis confirmed a heterozygous pathogenic mutation (c.894 G>A) in the LIPA gene, establishing the diagnosis of CESD. The patient required advanced management with a molecular adsorbent recirculating system to address refractory hyperbilirubinemia. CESD often mimics other metabolic and hepatic conditions, such as familial hypercholesterolemia or non-alcoholic fatty liver disease, necessitating high clinical suspicion and genetic confirmation for diagnosis. This case underscores the importance of recognizing CESD in patients with atypical dyslipidemia and persistent hepatic abnormalities, as early identification enables targeted therapeutic interventions, including Sebelipase alfa enzyme replacement therapy.

Evaluation of Serum Lipids, Biochemical Parameters, Selected Antioxidant Elements and Oxidative Stress Profiles in Late Pregnant Jennies with Hyperlipemia.

Donkeys are particularly at risk of hyperlipemia. Hyperlipemia is a metabolic disease caused by the mobilization of fatty acids from adipose tissue, which often impacts pregnant and lactating jennies (female donkeys) during periods of negative energy balance. This study aimed to evaluate the levels of lipids, biochemical parameters, selected antioxidant elements and oxidative stress parameters in late pregnant jennies affected by hyperlipemia. Compared with the healthy jennies, the hyperlipemic animals exhibited significantly elevated levels of triglycerides (TGs), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (p < 0.05), coupled with reduced levels of high-density lipoprotein cholesterol and albumin (ALB) (p < 0.05). The serum levels of biochemical parameters related to liver function, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (AKP) and cholinesterase (CHE), showed a significant increase in the hyperlipemia group compared to the healthy group (p < 0.05). The serum level of selenium was significantly lower (p < 0.05) and positively correlated with TGs (r = 0.85) and ALB (r = 0.73) in the hyperlipemia group. The hyperlipemic jennies showed diminished serum levels of antioxidant capacity and increased levels of malondialdehyde (MDA). The area under the curve values for T-CHO, ALB, AKP, CHE, total superoxide dismutase, glutathione and MDA were relatively high. Thus, our findings reflect metabolic disorders, liver dysfunction and oxidative stress in late pregnant hyperlipemic jennies, providing a basis for the improvement of clinical diagnostic methods and early prevention and control of hyperlipemia in jennies.

Patterns of Dyslipidemia Among Patients with Diabetes Mellitus

Background: Diabetes mellitus presents a prevalent endocrine and metabolic challenge globally. Type-2 diabetic patients exhibit a heightened incidence of dyslipidemia, characterized by elevated low-density lipoprotein (LDL), diminished high-density lipoprotein (HDL), or increased triglycerides (TG) levels. This phenomenon poses a significant public health concern both internationally and within our nation. Objective: This study aimed to assess the patterns of dyslipidemia among diabetes patients. Methods: This cross-sectional observational study was conducted at the Outpatient Department (OPD) of Shaheed Ziaur Rahman Medical College Hospital, Bogura, from July 2018 to June 2019. Both male and female patients with Type2 diabetes were considered as the study population. A total of 90 patients were selected as study subjects through purposive sampling.The study included 45 diabetic patients on therapy, divided into male (A1, n=19) and female (A2, n=26) subgroups. Additionally, 45 newly diagnosed diabetic patients were categorized into male (B1, n=15) and female (B2, n=30) subgroups.Analysis was performed by using SPSS (Statistical Package for Social Science) version 22.0. Results: The study found similar ages and BMI among groups. Elevated serum TC was noted in 31.6%, 19.2%, 26.7%, and 30% of subjects in A1, A2, B1, and B2 respectively. High serum TG levels were observed in 36.8%, 38.5%, 40%, and 66.7% of subjects in the respective groups. Dyslipidemia prevalence varied, with A1 at 57.9%, A2 at 53.8%, B1 at 46.7%, and B2 at 76.7%. High HbA1C was prevalent in B1 and B2 (100%). Conclusion: Dyslipidemia patterns among diabetes patients exhibit significant variability, with elevated serum total cholesterol, triglycerides, and low-density lipoprotein levels, alongside reduced high-density lipoprotein levels, commonly observed. These findings underscore the importance of tailored lipid management strategies in mitigating cardiovascular risk in this high-risk population. J Rang Med Col. September 2024; Vol. 9, No. 2: 78-83

Characterization of tea polysaccharides from Tieguanyin oolong tea and their hepatoprotective effects via AMP-activated protein kinase-mediated signaling pathways.

In the present study, we succeeded in extracting tea polysaccharide (TPS) from Tieguanyin oolong tea, and the TPS was characterized. TPS is an acidic heteropolysaccharide containing rhamnose, arabinose, galactose, glucose (Glc), xylose, mannose, galacturonic acid, and guluronic acid. We found that TPS supplementation partially reversed the elevated levels of serum alanine aminotransferase, total cholesterol, and low-density lipoprotein cholesterol in high-fat diet (HD)-induced nonalcoholic fatty liver disease (NAFLD) mice (p<0.05), and hepatic steatosis and impaired Glc tolerance were also ameliorated. After HD intervention, the activity of Adenosine 5'-monophosphate-activated protein kinase (AMPK) and its downstream genes, including Sirtuin 1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP1c), acetyl-coenzyme A carboxylase 1 (ACC1), and adipose triglyceride lipase (ATGL), was significantly inhibited (p<0.05). TPS can increase the expression of these genes. The hepatoprotective effects of TPS in AMPK-/- mice almost completely disappeared. Moreover, the expression levels of SIRT1, SREBP1c, ACC1, and ATGL did not significantly change after TPS supplementation (p>0.05). Therefore, our findings suggest that TPS protects the liver from hepatic glucolipid metabolism disorders in HD-induced NAFLD mice by activating AMPK-mediated signaling pathways.

Supplementation of diet with Astaxanthin and DHA prevents gestational and lactational undernourishment-induced metabolic derangements in dams: a metabolomic approach.

Nutrition is the critical nongenetic factor that has a major influence on the health status of an organism. The nutritional status of the mother during gestation and lactation plays a vital role in defining the offspring's health. Undernutrition during these critical periods may induce chronic metabolic disorders like obesity and cardiovascular diseases in mothers as well as in offspring. The present study aims to evaluate the impact of undernutrition during gestational and lactational periods on the plasma metabolic profile of dams. Additionally, we investigated the potential synergistic mitigating effects of astaxanthin and docosahexaenoic acid (DHA) on dysregulated plasma metabolic profiles. Evaluation of plasma lipid profile revealed that undernourishment resulted in elevated levels of total cholesterol, triglycerides, low density and very low-density lipoproteins in dams. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomics illustrated that pathways related to lipid metabolism, such as cholesterol metabolism, steroid biosynthesis and metabolism of amine-derived hormones, were dysregulated by undernourishment. Additionally, pathway enrichment analysis predicted that there is a high incidence of development of desmosterolosis, hypercholesterolaemia, lysosomal acid lipase deficiency and Smith-Lemli-Opitz syndrome in the offspring, reflecting predisposition in mothers. However, synergistic supplementation of astaxanthin and DHA ameliorated these adverse effects by regulating a separate set of metabolic pathways associated with lipid metabolism. They included branched chain amino acid degradation such as valine, leucine and isoleucine, metabolism of alpha-linolenic acid, lipoic acid, lysine degradation, biosynthesis, elongation and degradation of fatty acids.

Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.

Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls. The FC level demonstrated a positive correlation with the ALT level in both patients and mice. Mechanistic studies revealed that FC elevated reactive oxygen species level, impaired the function of lysosomes, and disrupted lipophagy process, consequently inducing cell apoptosis. We then found that DhT protected mice on an HCD diet, independent of gut microbiota. DhT functioned as a potent ligand for peroxisome proliferator-activated receptor α (PPARα), stimulating its transcriptional function and enhancing catalase expression to lower reactive oxygen species (ROS) level. Notably, the protective effect of DhT was nullified in mice with hepatic PPARα knockdown. Thus, these findings are the first to report the detrimental role of FC in NAFLD, which could lead to the development of new treatment strategies for NAFLD by leveraging the therapeutic potential of DhT and PPARα pathway.

Impact of diabetes mellitus on the risk of Alzheimer’s disease: a mendelian randomization study

BackgroundThe impact of diabetes on the risk of Alzheimer’s disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach.MethodsInstrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data. These data were derived from multiple European cohorts and included 31,684 to 810,865 subjects respectively. The two-sample MR, multivariate MR, and summary-data-based Mendelian randomization (SMR) methods were employed to determine the associations of these traits or genes with the risk of Alzheimer’s disease.ResultsThe two-sample MR showed that elevated fasting insulin and total cholesterol levels were associated with an increased risk of dementia in Alzheimer’s disease (P = 0.022, P = 0.041). Elevated systolic and diastolic blood pressure levels were associated with a decreased risk of dementia in Alzheimer’s disease (P = 0.036, P = 0.025). The multivariate MR reported that adjusting for telomere length (a well-established biomarker of aging) did not change these findings (P < 0.05). Additionally, the two-sample MR showed that type 1 and type 2 diabetes did not affect the risk of Alzheimer’s disease. The SMR also indicated that the diabetic genes did not affect the risk of this disease.ConclusionMultiple MR approaches concluded that fasting insulin, total cholesterol, and blood pressure, rather than diabetes, were potential metabolic variables that had an impact on the risk of Alzheimer’s disease. However, aging might not be involved in these correlations.

The effectiveness of liver transplantation in reducing lipid levels in Saudi children with homozygous familial hypercholesterolemia.

The lipid profiles of patients aged <15 years who have been diagnosed with homozygous familial hypercholesterolemia (HoFH) at King Faisal Specialist Hospital & Research Center (Riyadh) were examined. The total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels of 17 patients were measured on initial presentation and compared with the levels measured after pharmacological treatment and then again after liver transplantation. At the end of the pharmacological treatment, the total cholesterol levels decreased by an average of 3.79 mmol/L (reduced by 15.40%) (P < 0.001), and LDL-C levels decreased on average by 2.73 mmol/L (reduced by 13.46%) (P = 0.014). However, in two patients, LDL-C levels increased by 5.42% and 9.03% after pharmacological treatment. Conversely, the lipid values measured after liver transplantation decreased significantly nearly to within normal and borderline limits. The post-transplant total cholesterol and LDL-C levels declined by a mean of 19.96 mmol/L (reduced by 81.04%) and 17.47 mmol/L (reduced by 84.27%), respectively (P < 0.001 for both). These findings suggest that liver transplantation provides a more effective means to reduce elevated total cholesterol and LDL-C levels in patients with HoFH. Although liver transplantation is considered a better treatment for FHoH, risks, complications, and donor organ shortage may present problems.

Phenotypic and genotypic features of children with familial hypercholesterolemia

Dyslipidemia is a metabolic disorder in which the ratio of lipid particles in the blood changes. It is often associated with other conditions and diseases during childhood. Lipid metabolism disorders in children can be divided into two categories: primary, which are inherited from parents or occur de novo, and secondary, which occur during life. Familial hypercholesterolemia is the most common type of primary disorder, characterized by an increase in blood lipoprotein levels. However, the lipid composition in children with established familial hypercholesterolemia can vary. One factor that may contribute to higher lipid levels in these children is the presence of mutations in the apolipoprotein E gene.Purpose of the study was to investigate the phenotypic and genotypic features of children with familial hypercholesterolemia in order to better understand this condition.Materials and methods. Children with a clinical diagnosis of familial hypercholesterolemia underwent DNA sequencing to identify mutations in genes related to LDLR, APOB, LDLRAP1, and APOE genes.Results. Children with familial hypercholesterolemia most often carry the polymorphism c.388T&gt;C in the ApoE gene (g.45411941T&gt;C, p.Cys130Arg, rs429358). Also, 24.1% of children were found to be isolated carriers of various ApoE haplotypes, which are risk factors for dyslipidemia. In children with a pathogenic mutation characteristic of familial hypercholesterolemia and carriage of polymorphisms in the ApoE gene, the LDL level was statistically higher compared to non-carriers.Conclusion. Carriage of various polymorphisms in the ApoE gene in children with familial hypercholesterolemia may lead to an increase in the already elevated levels of LDL and total cholesterol.

Serum lipid profile of patients with gallstone disease in rural Western Uttar Pradesh

IntroductionGallstone disease is a common gastrointestinal disorder with varying prevalence across regions. This study explores the demographics and lipid profiles of individuals with cholelithiasis, emphasizing the association between metabolic syndrome and gallstone formation.MethodologyA prospective study was conducted, including 100 outpatients with cholelithiasis. Demographic data, lipid profiles, and comorbidities were recorded, and statistical analysis was performed.ResultsA higher prevalence of gallstones was recorded in the 20–29 age group and among females. Lipid profiles revealed elevated levels of total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides in individuals with metabolic syndrome. High-density lipoprotein (HDL) levels were notably lower in those with metabolic syndrome. Age and gender disparities in metabolic syndrome prevalence were observed, with statistical significance noted in gender-based differences. Serum thyroid-stimulating hormone (TSH) levels did not significantly differ between individuals with and without metabolic syndrome.ConclusionThe findings indicated elevated lipid profiles, particularly low HDL, are associated with metabolic syndrome in gallstone patients. Further understanding of these associations can aid in preventive strategies and targeted interventions.

Decoding the Lipid-Angiogram Link: Can Serum Lipid Profile Help Predict Your Clogged Arteries?

Objective In this study, we aimed to analyze the correlation between lipid profile and angiographic profile in terms of vessel involvement, segment involvement, andangiographic severity in patients with acute coronary syndrome (ACS). Methods One hundred patients diagnosed with ACS for the first time and undergoing coronary catheterization were included. Fasting samples for lipids profile were obtained. Data were analyzed to determine if lipid parameters were related to the severity of coronary artery disease (CAD), as measured by the SYNTAX score, and the number and location of affected vessels. The SYNTAX score offers a robust and reliable method for assessing the severity of CAD. By providing a comprehensive and quantitative evaluation, it empowers clinicians to make informed decisions about patient management and optimize treatment outcomes. Results Total cholesterol (TC), non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein (Apo) B/Aratio correlated positively with the number of vessels involved, i.e., single, double, or triple vessel disease(SVD, DVD, and TVD). Apo B/A also showed a significant relationship with left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) involvement. RCA involvement had a significant association with TC and non-HDL levels. TC, non-HDL, and Apo B/A showed a significant relationship with mid-segment involvement. Apo A1 was found to have a significant inverse correlation, while Apo B, Apo B/A, and TC/HDL had asignificant positive correlation with SYNTAX score class severity. Conclusions Our study revealed a strong association between lipid parameters and CAD severity, particularly in terms of vessel involvement and SYNTAX score. Elevated levels of TC, non-HDL cholesterol, and Apo B/A were linked to more extensive disease.

CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin

BackgroundA single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians.ObjectiveThis research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.MethodsIn this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.ResultsThe allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations.ConclusionsThe CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin.Graphical

Comparison of lipid profile alterations in chronic hepatitis b patients receiving tenofovir alafenamide or tenofovir disoproxil fumarate

This study aimed to compare the serum lipid profiles between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in the long-term treatment of chronic hepatitis B (CHB). We analyzed data from treatment-naïve CHB patients administered with TDF or TAF, collected from electronic medical records between May 2017 and September 2022. Serum lipid indices, including total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL), and their ratios (TC/HDL, LDL/HDL), were assessed at baseline, and at 48 and 96 weeks. Propensity score matching (PSM) adjusted for baseline differences between groups. From 2344 patients initially screened, 418 were included for the 48-week analysis (265 on TDF, 153 on TAF) and 292 for the 96-week analysis (238 on TDF, 54 on TAF). At 48 weeks, comparing the serum lipid indicators between the pre- and post-treatment, TDF significantly reduced TC and TC/HDL, whereas TAF induced widespread dyslipidemia, characterized by elevated levels of TC, TG, LDL, LDL/HDL, and TC/HDL, and reduced HDL (P < 0.05). After PSM grouping, TAF remained significantly associated with higher TC, TG, LDL, LDL/HDL, and TC/HDL compared to TDF (P < 0.05). Over 48 weeks, TAF treatment was associated with significant increases in TC, TG, and LDL, whereas TDF treatment led to decreases (P < 0.05). TC/HDL and LDL/HDL increased in both groups, but more significant in TAF (P < 0.05). At 96 weeks, the TAF group continued to exhibit significantly higher levels of TC, LDL, and LDL/HDL compared to the TDF group (P < 0.05). Notably, LDL levels were 115.65 ± 28.07 mg/dL in TAF versus 96.07 ± 23.97 mg/dL in TDF. The increase in TC/HDL ratio in the TAF group was higher than in the TDF group, though not statistically significant. Furthermore, TAF treatment was associated with significant increases in LDL (18.58 ± 24.35 mg/dL) and LDL/HDL ratio (0.41 ± 0.95) over 96 weeks, while TDF treatment showed reductions in TC (-8.13 ± 30.86 mg/dL). Between 48 and 96 weeks, most lipid changes in the TDF group were not statistically significant, except for increases in LDL and LDL/HDL. In the TAF group, an increasing trend of LDL and TC/HDL was noted, although LDL showed a slight turnover after 48 weeks. This real-world study provides new evidence that TAF can induce dyslipidemia, while TDF exhibits a lipid-lowering effect in CHB. Patients at high risk for hepatic steatosis and cardiovascular diseases should consider these effects when choosing between TAF and TDF.

Comparative Transcriptome Analysis Reveals the Impact of a High-Fat Diet on Hepatic Metabolic Function in Tilapia (Oreochromis niloticus).

Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a normal control (Ctr)-fed group and a high-fat diet (HFD)-fed group. Serum biochemical analyses revealed that HFD feeding led to liver damage and lipid accumulation, characterized by elevated levels of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), triglycerides (TGs), and total cholesterol (TC). Transcriptome analysis showed that 538 genes were significantly downregulated, and 460 genes were significantly upregulated in the HFD-fed fish. Gene Ontology (GO) enrichment analysis showed that these differentially expressed genes (DEGs) were apparently involved in the lipid metabolic process and monocarboxylic acid metabolic process. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated significant alterations in pathways of steroid biosynthesis, porphyrin metabolism, terpenoid backbone biosynthesis, and retinol metabolism after HFD feeding. Additionally, results from Gene Set Enrichment Analysis (GSEA) revealed that gene expression patterns in pathways including oxidative phosphorylation, protein export, protein processing in the endoplasmic reticulum, and ribosome biogenesis were positively enriched in the HFD-fed tilapia. These findings provide novel insights into the mechanisms underlying HFD-induced hepatic dysfunction in fish, contributing to the optimization of feeding strategies in aquaculture.

Cross-sectional analysis of dyslipidemia risk in coal mine workers: from epidemiology to animal models

Objective: To investigate the association between coal dust exposure and the occurrence of dyslipidemia in coal mine workers, and identify relevant risk factors. Methods: We selected a population who underwent occupational health examinations at Huainan Yangguang Xinkang Hospital from March 2020 to July 2022. Participants were divided into two groups based on the presence or absence of dyslipidemia, and their baseline information was collected, including records of coal dust exposure. We employed single-factor analysis to identify risk factors for dyslipidemia and adjusted for confounding factors in the adjusted models. Additionally, we explored the effects in different populations using stratified analysis, smooth curve fitting, and propensity score matching. Finally, we confirmed the causal relationship between coal dust exposure and dyslipidemia by examining tissue sections and lipid-related indicators in a mouse model of coal dust exposure. Results A total of 5,657 workers were included in the study, among whom 924 individuals had dyslipidemia and 4,743 individuals did not have dyslipidemia. The results of the single-factor analysis revealed that dust exposure, age, BMI, blood pressure, and smoking were statistically significant risk factors for dyslipidemia (p < 0.05). Additionally, the three multivariate models, adjusted for different confounders, consistently showed a significant increase in the risk of dyslipidemia associated with coal dust exposure (Model 1: OR, 1.869; Model 2: OR, 1.863; Model 3: OR, 2.033). After conducting stratified analysis, this positive correlation remained significant. Furthermore, propensity score matching analysis revealed that with increasing years of work, the risk of dyslipidemia gradually increased, reaching 50% at 11 years. In the mouse model of coal dust exposure, significant coal dust deposition was observed in the lungs and livers of the mice, accompanied by elevated levels of total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and low-density lipoprotein cholesterol (LDL-C). Conclusion Exposure to coal dust significantly increases the risk of developing dyslipidemia, and this positive correlation exists in different populations, particularly with increasing years of work, resulting in a higher risk. Keywords: Dust, occupational health, dyslipidemia, risk factors, cross-sectional study.

Antisense Oligonucleotides in Dyslipidemia Management: A Review of Clinical Trials.

Elevated serum total cholesterol levels, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, or a decreased serum high-density lipoprotein cholesterol concentration characterize dyslipidemia. Antisense Oligonucleotide therapy in dyslipidemia targets apolipoprotein B (ApoB), an essential component of low-density lipoprotein (LDL) associated with atherosclerosis development. This review aims to critically evaluate the efficacy and safety of this group of medications in mitigating dyslipidemia in at-risk individuals and its potential role in advancing personalized medicine in the management of dyslipidemias. A detailed search was conducted from multiple databases adhering to the PRISMA guidelines. Clinical trials and randomized controlled trials on antisense oligonucleotides for management of dyslipidemias were included, excluding non-English studies, case reports and all forms of reviews. Data was screened, with duplicates removed, and key findings were synthesized using a narrative approach. The potential of antisense oligonucleotides (ASOs) to treat dyslipidemia and other disorders has attracted much interest. Several studies and clinical trials have been conducted on the safety and tolerability of ASOs for dyslipidemia. Although statins are the mainstay management of hypercholesterolemia, there is evidence from clinical trials that ASOs can even be more effective with little to no side effects. Novel therapeutic approaches such as antisense oligonucleotides (ASOs) offer tailored therapeutic alternatives. ASOs such as Mipomersen and Volanesorsen provide additional treatment options for patients with inherited lipid abnormalities by lowering certain atherogenic lipoproteins such as apo B and ApoC-III, respectively.