Elevated Total Cholesterol Levels Research Articles

Elevated serum cholesterol levels during pregnancy as predictors for postpartum hypercholesterolemia: A prospective cohort study.

To identify the associations between gestational cholesterol levels and the risk of postpartum hypercholesterolemia, and to establish trimester-specific reference values. Serum lipids at gestational weeks 6-8, 16, 24, and 36, and 42 days postpartum were derived from 905 pregnant women of a prospective cohort. The major outcome was postpartum hypercholesterolemia. Logistic regression and restricted cubic splines were conducted to estimate the associations between cholesterol levels at specific gestational ages and postpartum hypercholesterolemia. Associations of the trend of changes in cholesterol levels during pregnancy with postpartum hypercholesterolemia were evaluated by linear mixed-effect model and linear or logistic regression. Reference values were computed by the receiver operating characteristic curves. Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the ratios of TC/HDL-C and LDL-C/HDL-C all increased during pregnancy and decreased at 42 days postpartum. The elevated levels of TC and LDL-C, decreased levels of HDL-C in pregnancy, and their rapid change rates were positively associated with higher risks of postpartum hypercholesterolemia. The established reference values from the first to the third trimester were below 5.47, 6.35, and 7.22 mmol/L for TC; below 2.83, 3.82, and 4.21 mmol/L for LDL-C; and more than 1.50, 1.55, and 1.50 mmol/L for HDL-C, respectively. Maternal cholesterol levels and their trend of change during pregnancy were predictors of postpartum hypercholesterolemia. Trimester-specific reference values were established in a Chinese population.

Lipid levels and multiple myeloma risk: insights from Meta-analysis and mendelian randomization

BackgroundLipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted.MethodsLiterature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines.ResultsObservational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46–0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators.ConclusionsThe findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM.

The effects of alfalfa powder combined with health education on patients with dyslipidemia: A randomized controlled trial

BackgroundCardiovascular diseases (CVDs) remain the leading cause of global mortality, with dyslipidemia recognized as a significant risk factor. Dyslipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), is associated with an increased lifetime risk of CVD. Although alfalfa’s cholesterol-lowering effects have been demonstrated in animal models, clinical trial data supporting its efficacy in human dyslipidemia treatment are limited. MethodsA randomized controlled trial was conducted from September 20, 2021, to January 12, 2023, involving patients diagnosed with dyslipidemia. Approved by the China Ethics Committee of Registering Clinical Trials, the study included multiple sites in China. Eligible participants were adults aged 18 years or older, meeting criteria from the Chinese Guidelines for the Prevention and Treatment of Adult Blood Lipid Disorders. Participants were randomly assigned to either a health education-only group or a combined alfalfa powder supplementation and health education group for a three-month intervention period. ResultsA total of 160 eligible patients were enrolled and randomized into two groups: the Alfalfa group (n = 80) and the Education group (n = 80). The intervention resulted in significant improvements in key lipid parameters in the Alfalfa group, including reductions in TC, LDL-C, and Apo A1 levels. Although changes in HDL-C levels were not significantly different between the groups, the Alfalfa group exhibited a larger increase. Serum lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the combined intervention did not significantly alter the overall blood lipid metabolome but identified fifteen regulated differential metabolites, with the glycerophospholipid metabolism pathway significantly affecting lipid metabolism levels. ConclusionSupplementation with alfalfa powder combined with health education significantly reduced TC, LDL-C, and Apo A1 levels in patients with dyslipidemia. KEGG pathway analysis suggests an association between the glycerophospholipid metabolism pathway and dyslipidemia. Further research is warranted to validate these findings and explore the underlying mechanisms.

Evaluating the Association of Anthropometric Indices With Total Cholesterol in a Large Population Using Data Mining Algorithms.

Unbalanced levels of serum total cholesterol (TC) and its subgroups are called dyslipidemia. Several anthropometric indices have been developed to provide a more accurate assessment of body shape and the health risks associated with obesity. In this study, we used the random forest model (RF), decision tree (DT), and logistic regression (LR) to predict total cholesterol based on new anthropometric indices in a sex-stratified analysis. Our sample size was 9639 people in which anthropometric parameters were measured for the participants and data regarding the demographic and laboratory data were obtained. Aiding the machine learning, DT, LR, and RF were drawn to build a measurement prediction model. Anthropometric and other related variables were compared between both TC <200 and TC ≥200 groups. In both males and females, Lipid Accumulation Product (LAP) had the greatest effect on the risk of TC increase. According to results of the RF model, LAP and Visceral Adiposity Index (VAI) were significant variables for men. VAI also had a stronger correlation with HDL-C and triglyceride. We identified specific anthropometric thresholds based on DT analysis that could be used to classify individuals at high or low risk of elevated TC levels. The RF model determined that the most important variables for both genders were VAI and LAP. We tend to present a picture of the Persian population's anthropometric factors and their association with TC level and possible risk factors. Various anthropometric indices indicated different predictive power for TC levels in the Persian population.

Clinical Management of Familial Hypercholesterolemia in Children.

Familial Hypercholesterolemia (FH) is one of the best-characterized inborn errors of metabolism, with an estimated prevalence of 1:250 in the general population. Only approximately 10% of the affected subjects are diagnosed and, therefore, under medical care, including drug therapy or, in severe cases, apheresis. Screening at the age of 6-10 years would be useful and cost-effective. There is enough evidence that children and adolescents with FH should be treated in order to reduce elevated Total cholesterol and LDL-c levels and, therefore, avoid the risk of early cardiovascular diseases. As FH was described more than 130 years ago, it is surprising that the knowledge of that very important metabolic disorder is insufficient. The present report describes clinical and pathophysiological characteristics and nutritional and medical therapies in children with familial hypercholesterolemia.

Enhanced atherosclerosis in apolipoprotein E knockout rabbits: role of apoB48-rich remnant lipoproteins.

Apolipoprotein E (apoE) acts as a binding molecule for both the low-density lipoprotein receptor and the lipoprotein receptor-related protein and this function is essential for facilitating the hepatocyte uptake of lipoproteins containing apoB. The absence of apoE leads to increased atherogenicity in both humans and mice, although the precise molecular mechanisms remain incompletely understood. This study aimed to investigate the susceptibility of apoE knockout (KO) rabbits, in comparison with wild-type (WT) rabbits, to diet-induced hyperlipidemia and atherosclerosis. ApoE KO rabbits and WT rabbits were fed a diet containing 0.3% cholesterol for 16 weeks. Plasma lipid levels, lipoproteins, and apolipoproteins were analyzed. Atherosclerosis was evaluated at the endpoint of experiments. In addition, we evaluated the oxidizability of those lipoproteins containing apoB to investigate the possible mechanisms of atherosclerosis. Male apoE KO rabbits showed significantly elevated levels of total cholesterol and triglycerides compared to WT rabbits, while female apoE KO rabbits displayed similar high total cholesterol levels, albeit with significantly higher triglycerides levels than WT controls. Notably, both male (2.1-fold increase) and female (1.6-fold increase) apoE KO rabbits exhibited a significantly augmented aortic lesion area compared to WT controls. Pathological examination showed that the increased intimal lesions in apoE KO rabbits were featured by heightened infiltration of macrophages (2.7-fold increase) and smooth muscle cells (2.5-fold increase). Furthermore, coronary atherosclerotic lesions were also increased by 1.3-fold in apoE KO rabbits. Lipoprotein analysis revealed that apoB48-rich beta-very-low-density lipoproteins were notably abundant in apoE KO rabbits, suggesting that these remnant lipoproteins of intestinal origin serve as the primary atherogenic lipoproteins. Moreover, apoB48-rich remnant lipoproteins isolated from apoE KO rabbits exhibited heightened susceptibility to copper-induced oxidation. The findings indicate that apoB48-rich remnant lipoproteins, resulting from apoE deficiency, possess greater atherogenic potential than apoB100-rich remnant lipoproteins, regardless of plasma TC levels.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Revealing the effect of sea buckthorn oil, fish oil and structured lipid on intestinal microbiota, colonic short chain fatty acid composition and serum lipid profiles in vivo

In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague–Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.Graphical

BIOCHEMICAL IMBALANCE IN ISCHEMIC HEART DAMAGE COMBINED WITH STEATOHEPATOSIS

The development of steatohepatosis in most cases is the primary process and consequence of the metabolic syndrome. This disease has a long asymptomatic course. The connection of steatohepatosis with the development and progression of coronary heart disease occurs when steatohepatosis is associated with metabolic syndrome and obesity. Patients with steatohepatosis usually have signs of metabolic syndrome: arterial hypertension, abdominal obesity, impaired glucose tolerance, atherogenic dyslipidemia, which are considered risk factors for cardiovascular diseases. Biochemical parameters were determined in coronary artery disease complicated by steatohepatosis. 101 people were examined. When examining the serum level of brain natriuretic peptide in patients with ischemic heart disease in combination with steatohepatosis, a higher level was found than in uncomplicated coronary heart disease, which indicates a deeper violation of the functional state of the myocardium in ischemic heart disease in combination with steatohepatosis. When examining the cytolytic syndrome markers LDH, AST and ALT, a probable increase in their activity is observed. The detected activation of LDH is associated with damage, tissue necrosis, which is observed in the case of damage to the myocardium and hepatocytes in the examined groups, which indicates an inflammatory type of pathogenesis. Apparently, activation of transaminases is associated with cytolytic syndrome in myocardial damage and increased energy expenditure of hepatocytes in fatty hepatosis. Signs of impaired glucose tolerance were found in the examined subjects: the fasting glucose level and the postprandial glucose level probably exceeded normal values, the HbA1c level was 1.5 times higher than the control in myocardial ischemia, and 1.7 times higher in coronary heart disease and steatohepatosis (p&lt; 0.05). Disruption of hormonal regulation of carbohydrate metabolism was detected in both examined groups. An elevated level of total cholesterol and dyslipoproteinemia were also found in both groups of examined patients, however, the most pronounced changes are observed in the case of complications of steatohepatosis. The obtained results indicate complex disorders of lipid metabolism in myocardial ischemia and ischemic heart damage in combination with steatohepatosis, which confirms the development of metabolic syndrome.

Dyslipidemia among psychiatric patients with depression – common possible reasons and treatment implications – review

Dyslipidemia is a medical term used to describe an abnormal level of lipids (fats) in the blood. This can include elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high density protein lipoprotein (HDL) cholesterol and serum triglicerides. Depression, also known as depressive disorder, is a common mental illness. It is characterized by a persistent feeling of sadness, loss of pleasure, or lack of interest in activities that are present of at least two weeks and significantly impair patient everyday functioning. Dyslipidemia and depression can co-occur due to a complex interplay of shared risk factors, such as inflammation, metabolic syndrome, medication side effects, and lifestyle changes, suggesting a bidirectional relationship where each condition might contribute to the development or exacerbation of the other. Given these considerations, a comprehensive approach to managing dyslipidemia in psychiatric patients with depression is essential. This should include regular monitoring of lipid profiles and monitoring of anticholesterol and antidepressant drugs. Interestingly, simple lifestyle changes, such as a healthy diet and exercise, have an impact on the treatment of depression and dyslipidemia.

Mechanism of astragaloside Ⅳ modulation of Nrf2/HO-1/GPX4 pathway to inhibit ferroptosis and ameliorate atherosclerosis in ApoE~(-/-) mice

The intervention effect of astragaloside Ⅳ(AS-Ⅳ) on atherosclerosis in apolipoprotein E gene knockout(ApoE)~(-/-) mice was observed based on the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) signaling pathway to explore the potential mechanism of AS-Ⅳ in improving ferroptosis in atherosclerotic mice. This study established an atherosclerosis mouse model by feeding them a high-fat diet. After modeling for 8 weeks, ApoE~(-/-) mice were randomly divided into the model group, AS-Ⅳ group, AS-Ⅳ+Nrf2 inhibitor(ML385) group, and ferrostatin-1(Fer-1) group. Additionally, a blank control group was also established. Corresponding drugs were administered via intraperitoneal injection, with the control group receiving an equivalent amount of normal saline injection as the model group. After the experiment, serum biochemical levels were measured using an automatic blood lipid analyzer, hematoxylin-eosin(HE) staining was used to observe morphological changes in aortic sinus tissues, colorimetric methods were used to detect levels of ferrous ion(Fe~(2+)), malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in mouse serum, immunofluorescence was used to observe the expressions of ferritin heavy chain 1(FTH1) and ferritin light chain(FTL) proteins in the aortic sinus of mice, Western blot was used to detect the protein levels of Nrf2, HO-1, and GPX4 in mouse aortic tissues, and transmission electron microscopy was used to observe ultrastructural changes in aortic tissues. RESULTS:: showed that compared to the control group, the model group of mice had significantly increased calcification and plaque deposition areas in the aortic sinus, increased mitochondrial membrane density, decreased or disappeared mitochondrial cristae, elevated levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), Fe~(2+), and MDA, decreased levels of high-density lipoprotein cholesterol(HDL-C), SOD, and GSH, and significant inhibition of Nrf2, HO-1, GPX4 proteins, as well as iron storage proteins FTH1 and FTL expressions in the aorta. Compared to the model group, AS-Ⅳ treatment resulted in decreased serum TC, TG, LDL-C, Fe~(2+), and MDA levels, increased HDL-C, SOD, and GSH levels, increased expressions of Nrf2, HO-1, and GPX4 proteins, and iron storage proteins FTH1 and FTL, and significant improvement in aortic tissue morphology. Compared to the AS-Ⅳ group, the Nrf2 inhibitor ML385 could reverse the therapeutic effect of AS-Ⅳ on atherosclerosis mice. These findings suggest that AS-Ⅳ can inhibit ferroptosis and improve atherosclerosis in ApoE~(-/-) mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Cardio and Neuroprotective Effects of Naringenin Against Aluminum Chloride-induced Oxidative Stress in Wistar Rats

Background: Plant secondary metabolites have been reported to offer a wide variety of medicinal purposes, including protection against heavy metal toxicity. Objectives: This study aimed to investigate the potentiality of naringenin a flavonoid in ameliorating the antioxidant defense system of neural and cardiac cells against aluminum chloride (AlCl3 ) toxicity in rats. Methods: The rats were divided into control (group 1), AlCl3 -treated (2), AlCl3+Naringenin-treated (3), and Naringenin-treated (4) groups. During experimentation, group 2 received an oral dose of 100 mg/kg/BW of AlCl3 , and group 3 received 100 mg/kg/BW of AlCl3 and 50 mg/ kg/BW of naringenin. In addition, group 4 received 50 mg/kg/BW of naringenin each day, while group 1 and all groups received a normal diet and water ad libitum for 30 days. The animals were sacrificed, and then blood, brain, and heart tissues were collected for biochemical and histological studies. Results: The results revealed that naringenin administration ameliorates the antioxidant defense system (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx], and glutathione transferase) in AlCl3 toxicity in neural and cardiac tissues. AlCl3 caused oxidative tissue damage, showing a significant increase in malondialdehyde (MDA) (P&lt;0.05) in both tissues. The levels of neurotransmitter acetylcholine esterase, nitric oxide, and lactate dehydrogenase (LDH) in the rats of group 3 were significantly (P&lt;0.05) higher compared with AlCl3 -intoxicated rats. Furthermore, the AlCl3 -administered group had significantly (P&lt;0.05) elevated levels of total cholesterol (TC), triglycerides, and low-density lipoprotein-cholesterol, with reduced high-density lipoprotein-cholesterol levels in comparison to the naringenin-treated and control groups. Naringenin treatment normalized the lipid profile. Histological analysis using the hematoxylin and eosin staining method revealed that AlCl3 caused degenerative changes in the cerebellum and cardiac tissues, which were ameliorated by co-treatment with naringenin. Conclusion: Naringenin has the potential to mitigate AlCl3 -induced oxidative stress (OS) in the neural and cardiac tissues of rats by enhancing the antioxidant defense system and reversing tissue injuries in the brain and heart.

Evaluation of Plasma Fibrinogen Level, Platelet Count &amp; Lipid Profile as Predictors of Cardiovascular Disease among Bangladeshi Healthy Male Smokers

Background: Smoking represents a substantial global health challenge, correlating with heightened rates of mortality and morbidity, notably including the onset of cancer. Within tobacco smoke are carcinogenic substances capable of perturbing cellular mechanisms and immune responses, thereby potentially influencing coagulation metrics and lipid profiles. Objective: This study aimed to investigate the plasma fibrinogen level, platelet count &amp; lipid profile as predictors of cardiovascular disease among Bangladeshi healthy male smokers. Methods: A cross-sectional analytical study was conducted at the Department of Physiology, Sir Salimullah Medical College (SSMC) in Dhaka, Bangladesh, from July 1, 2018, to June 30, 2019. Seventy male participants aged 20 to 40 years were enrolled, comprising 35 healthy non-smokers (Group A) and 35 male smokers (Group B). Smokers were further categorized into two groups based on pack year (5-15 pack year for B1 &amp; &gt;15 pack year for B2). Coagulation parameters including plasma fibrinogen and platelet count and lipid profile were assessed. Results: The study comprised 70 subjects, evenly divided into Group A and Group B, with comparable mean ages of 33.17 ± 2.91 years and 34.11 ± 3.18 years, respectively, and similar mean body mass index (BMI) values of 24.36 ± 2.28 kg/m2 and 24.68 ± 2.33 kg/m2. Plasma fibrinogen levels were significantly higher in Group B (315.55 ± 67.79 mg/dL) compared to Group A (222.49 ± 23.03 mg/dL), as were platelet counts (285.14 ± 34.33 x109/L in Group B vs. 235.20 ± 46.83 x109/L in Group A). Further stratification of Group B revealed higher fibrinogen levels in both subgroups, B1 and B2, compared to Group A, with B2 exhibiting the highest fibrinogen levels. Platelet counts followed a similar trend, with both B1 and B2 having significantly higher counts than Group A. Plasma fibrinogen level was positively correlated with pack-years of smoking, while platelet counts showed a positive but statistically non-significant correlation. Smokers exhibited elevated total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) levels, along with decreased high-density lipoprotein (HDL) levels compared to non-smokers. Moreover, there was a significant positive correlation between pack-years of smoking and TC, TG, and LDL levels, while HDL levels exhibited a significant negative correlation. These findings underscore the complex interplay between smoking, coagulation parameters, and lipid profiles, emphasizing the multifaceted impact of smoking on cardiovascular health. Conclusion: In conclusion, the study highlights the intricate relationship between smoking, coagulation parameters, and lipid profiles in a cohort of 70 subjects. Smokers exhibited elevated plasma fibrinogen levels and platelet counts compared to non-smokers, with a significant positive correlation observed between pack-years of smoking and these coagulation parameters. Additionally, smokers demonstrated higher levels of total cholesterol, triglycerides, and low-density lipoprotein, alongside lower levels of high-density lipoprotein, indicative of dyslipidemic state in the direction of increased risk for coronary artery disease. Furthermore, the discovered alterations in plasma fibrinogen, platelet, and lipid profiles serve as early predictors of cardiovascular disease, advocating for proactive management strategies in individuals with a smoking history.

Quercetin Nanoparticles as a Promising Intervention against Ethion‐Induced Hepatic Damage in Wistar Albino Rats.

AbstractThe current study investigated the therapeutic potential of quercetin and quercetin nanoparticles in alleviating liver toxicity induced by ethion in Wistar albino rats. Quercetin nanoparticles were synthesized using the ionic‐gelation method. Rats were exposed to ethion alone (at high and low doses) or in combination with quercetin or quercetin nanoparticles. Ethion exposure led to significant decreases in organ weight, along with elevated levels of glucose, triglycerides, total cholesterol, low‐density lipoprotein, and acid phosphatase, and reduced high‐density lipoprotein in serum. Hepatocellular biomarker enzymes were increased in the ethion‐exposed group, while antioxidant enzyme levels were decreased. Histopathological analysis revealed fatty changes, degeneration, and hemorrhages in the liver. Co‐administration of quercetin nanoparticles mitigated these effects, potentially by neutralizing reactive oxygen species generated by ethion. Molecular docking studies suggested a strong interaction between quercetin and Cyp2E1, implicating a role in detoxification. This study highlights the potential of nanoquercetin as a therapeutic supplement for pesticide intoxication management.

Unraveling Estrogen and PCSK9's Roles in Lipid Metabolism Disorders among Ovariectomized Mice.

We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.

Apolipoprotein E Gene Variation in Pakistani Subjects with Type 2 Diabetes with and without Cardiovascular Complications.

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.

Relationship between hypercholesterolemia and osteoarthritis (preliminary results)

To evaluate the relationship of hypercholesterolemia (HCE) with clinical, instrumental, and laboratory parameters in osteoarthritis (OA) in a multicenter, cross-sectional study. The study included 183 patients aged 40-75 years, with a confirmed diagnosis of stage I-III OA (ACR) of the knee joints, who signed an informed consent. The mean age was 55.6±10.7 years (40 to 75), body mass index was 29.3±6.3 kg/m2, and disease duration was 5 [1; 10] years. For each patient, a case record form was filled out, including anthropometric indicators, medical history, clinical examination data, an assessment of knee joint pain according to VAS, WOMAC, KOOS and comorbidities. All patients underwent standard radiography and ultrasound examination of the knee joints and laboratory tests. HCE was detected in 59% of patients. Depending on its presence or absence, patients were divided into two groups. Patients were comparable in body mass index, waist and hip measurement, and disease duration but differed significantly in age. Individuals with elevated total cholesterol levels had higher VAS pain scores, total WOMAC and its components, an overall assessment of the patient's health, a worse KOOS index, and ultrasound findings (reduced cartilage tissue). HCE patients showed high levels of cholesterol, low-density lipoproteins, triglycerides, STX-II, and COMP (p<0.05). However, after stratification by age, many initial intergroup differences became insignificant, and differences in the WOMAC pain score persisted. The results of the study confirmed the high prevalence of HCE in OA patients (59%). Patients with OA and increased total cholesterol have more intense pain in the knee joints.

Exploring Serum Vitamin D, Sex Hormones, and Lipid Profile Disparities in Women With and Without Polycystic Ovarian Syndrome: A Case-Control Study.

Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by dyslipidemia, hormonal imbalances, and metabolic dysfunctions.Vitamin D deficiency may be implicated in the pathogenesis of PCOS, potentially exacerbating its metabolic syndrome. However, the exact interplay between these factors remains underexplored. Aim This study aimed to evaluate serum levels of vitamin D and its association with modalities of PCOS among women with PCOS and healthy controls. Methods This was a hospital-based case-control study where 60 women newly diagnosed with PCOS and 56 non-PCOS controls were consecutively recruited within a 10-month period. The women aged 20-40 were recruited at the gynecology clinics of Lagos State University Teaching Hospital and Lagos Island Maternity Hospital. PCOS was diagnosed using the Rotterdam's criteria. The biodata, anthropometry, clinical features, serum vitamin D, cortisol, progesterone, testosterone, estradiol, prolactin, anti-Mullerian hormone (AMH), thyroid-stimulating hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin, fasting blood glucose (FBG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and very-low-density lipoprotein cholesterol (VLDL-C) levels of PCOS-diagnosed women were assessed and compared with those of women without PCOS. The exclusion criteria comprised known diabetics, women with gynecological pathologies such as fibroids, and womenon medications affecting the study analytes or hormones. Statistical analyses included chi-square or Fisher's exact tests for categorical variables, student t-test for continuous variables, and Pearson's correlation for assessing relationships between continuous variables. The significance level was set at p<0.05 and a confidence interval of 95%. Results Individuals with PCOS exhibited a younger mean age (26.90±3.73 versus 29.95±5.00 years, p=0.001) and a higher prevalence of irregular menstrual patterns (46.7% versus 14.3%, p=0.0001) and acne (58.3% versus 37.5%, p=0.025). Moreover, PCOS was associated with elevated levels of TC (p = 0.03), TG (p = 0.03), LDL-C (p = 0.014), FBG (p = 0.001), LH:FSH ratio (p = 0.002), AMH (p = 0.0001), and testosterone (p = 0.003), but low progesterone (p = 0.001) and vitamin D (p = 0.033), alongside a higher incidence of vitamin D deficiency (33.3% versus 26.1%) and insufficiency (66.7% versus 56.5%). Additionally, significant but weak correlations were observed between serum vitamin D levels and waist-hip ratio (r = 0.4, p = 0.016) and FBG (r = -0.4, p = 0.036) in the PCOS group, suggesting potential metabolic implications. Conclusion The PCOS subjects in this study had decreased vitamin D and progesterone levels, with elevated concentrations of testosterone, AMH, lipid profile (TC, LDL, and TG), FBG, and LH:FSHratio. Studies on the therapeutic effect of vitamin D administration in managing PCOS will need to be further evaluated.

Associations of multiple hydroxy-polycyclic aromatic hydrocarbons with serum levels of lipids in the workers from coking and non-ferrous smelting industries

Epidemiological evidence indicates that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with certain metabolic diseases. However, the relationship between PAHs and serum lipid profiles in exposed subjects remain unknown. Herein, the associations of multiple (8) urinary hydroxylated PAHs (OH-PAHs) in workers of coking (n = 655) and non-ferrous smelting (n = 614) industries with serum lipid levels (marking lipid metabolism) were examined. Multivariable linear regression, Bayesian kernel machine regression, and quantile g-computation were used. Most urinary OH-PAHs were significantly higher (p < 0.001) in coking workers than in non-ferrous smelting workers. In workers of both industries, OH-PAH exposure was associated with elevated levels of serum total cholesterol, total triglyceride, and low-density lipoprotein, as well as reduced high-density lipoprotein levels. Specifically, urinary 4-hydroxyphenanthrene was significantly positively associated with serum total cholesterol, total triglyceride, and low-density lipoprotein levels in non-ferrous smelting workers; however, the completely opposite association of 4-hydroxyphenanthrene with these lipid levels was observed in coking workers. The results of this pioneering examination suggest that exposure to OH-PAHs may contribute to dyslipidemia in coking and non-ferrous smelting workers, and distinct patterns of change were observed. Further prospective studies involving larger sample sizes are needed to further validate the findings.

IMPACT OF CORONARY ARTERY DISEASE ON STEATOTIC LIVER DISEASE PROGRESSION

Introduction. Metabolic dysfunction-associated steatotic liver disease and coronary artery disease often exacerbate each other, leading to a more severe course of both conditions. The aim of this study is to evaluate the role of coronary artery disease in dislipidemia and liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Forty-six patients with metabolic dysfunction-associated steatotic liver disease were examined. Patients were divided into two groups based on the presence of concomitant coronary artery disease: group I (n=24) included patients with both metabolic dysfunction-associated steatotic liver disease and coronary artery disease, while group II (n=22) included patients with metabolic dysfunction-associated steatotic liver disease only. A third group (Group III) comprised healthy individuals. Specific lipid metabolism parameters, obesity stage, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) activity, and platelet count were examined. Fibrosis stage was evaluated using the FIB-4 score. The findings obtained were statistically processed. Results. Arterial hypertension was more prevalent in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease. In group I, arterial hypertension was observed in 95.8% of cases, whereas in group II, it was observed in 40.9% of cases (χ2=16.35, p=0.00005). Patients with metabolic dysfunction-associated steatotic liver disease exhibited elevated levels of total cholesterol, low-density lipoproteins, and triglycerides, leading to an increased atherogenic index. Conversely, high-density lipoprotein levels were decreased (p&gt;0.05). The degree of fibrosis according to the FIB-4 score was 1.45 times higher in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease compared to those without coronary artery disease.