Search Results (923)

Background/Objectives: Cholesterol is vital in various bodily functions, such as maintaining cell membranes, producing hormones, etc. However, imbalances, like hypercholesterolemia, can lead to diseases such as cancer, kidney disease, non-alcoholic fatty liver disease, and cardiovascular conditions. This study explores the impact of kiwifruit consumption, specifically Actinidia arguta cultivar Geneva and Actinidia deliciosa cultivar Hayward, on cholesterol and lipid metabolism in rat liver. Methods: Rats were divided into groups: a 1% cholesterol control group (Ch), a 5% Geneva kiwifruit-supplemented group (ChGENE), and a 5% Hayward kiwifruit-supplemented group (ChHAYW). Gene expression was analyzed using Gene Spring v.14. Gene ontology, pathway analysis, miRNA, and transcription factor prediction were performed using DAVID, Reactome, and miRNet. In addition, we used Agilent Literature Search software to gain further insights. Results: Statistical analysis identified 72 genes in ChGENE-Ch and 2 genes in ChHAYW-Ch comparison. Key genes involved in cholesterol metabolism pathways, including PCSK9, SCD1, SLC27A5, HMGCR, and DHCR24, showed lower expression in the kiwifruit-supplemented groups. The genes mentioned above showed lower expression in the kiwifruit-supplemented group, probably contributing to the liver lipid level reduction. Further analysis identified miRNA-26a, miRNA-29a/b/c, miRNA-33a/b, and miRNA-155 targeting hub genes. Conclusions: Our findings suggest that dietary supplementation with kiwifruit, particularly the Geneva cultivar, reduces fat accumulation in the liver of rats with hypercholesterolemia, likely through downregulation of critical genes involved in cholesterol metabolism. These studies highlight the potential of kiwifruit as a part of a dietary strategy to manage cholesterol levels. Full article

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today, we are talking about a new paradigm—cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, an unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies. Full article

Background/Objectives: Incidence of cardiovascular disease (CVD) is increasing in low- and middle-income countries because of changing lifestyles. Since dyslipidaemia is a major independent cardiovascular risk factor, its correct identification is critical to implement specific interventions for CVD prevention. This study aimed to characterise the lipid profile of the Portuguese population. Methods: Overall, 1688 individuals from the general population (e_COR study, 2012–2014) were included. Population-specific percentiles for ten lipid biomarkers were estimated by bootstrapping methods to ensure national representativity. Statistical analyses were performed using RStudio. Results: The 50th percentile estimated for total cholesterol (TC), LDL-C, and non-HDL-C are similar to scientific societies recommended values for the general (low or moderate risk) population. National prevalence of having lipid parameters above recommended values was 64.6%, 66.9%, 51.3%, 68.9%, 17.8%, and 21.1% for TC, LDL-C, apoB, non-HDL-C, triglycerides, and Lp(a), respectively; these values are generally higher in men and increasing with age, except for Lp(a). A high prevalence of severe dyslipidaemia (>90th percentile) was identified, highest for small dense LDL-C (31.3%), apoB (30.4%), and LDL-C (30.3%). The national prevalence of CVD events was 5%. Three individuals were genetically identified with familial hypercholesterolemia, a high CVD risk condition. Conclusions: We provide for the first-time lipid biomarker percentiles for the general Portuguese population. Our results highlight that hypercholesterolemia is a neglected cardiovascular risk factor with over half of the population with TC, LDL-C, and apoB above recommended values. Since hypercholesterolemia is a modifiable risk factor, strategies to increase adherence to changes in lifestyle habits and medication need to be urgently discussed. Full article

Cardiac troponin serum concentration is a marker of myocardial injury, but NT-pro BNP is a marker of myocardial insufficiency. The purpose of this study was to determine binary logistic regression models to verify the possible association of cardiovascular risk indicators, pre-pandemic history, the number of times participants were infected with SARS-CoV-2, and vaccination against these biomarkers. A total of 281 residents of Trujillo city (Peru) participated between September and December 2023. We found a high prevalence of abdominal obesity of 55.2%; glycemia > 100 m/dL in 53%; hypercholesterolemia in 49.8%; low HDL in 71.9%; and LDL > 100 mg/dL in 78.6%. A total of 97.5% were vaccinated against COVID-19, and 92.2% had three or more doses. Also, 2.5% had cTnI > 0.05 ng/mL, and 3.3% had NT-proBNP > 125 pg/mL. The number of COVID-19 infections versus cTnI > 0.05 ng/mL presented an OR = 3.513 (p = 0.003), while for NT-proBNP > 125 pg/mL, the number of comorbidities presented an OR = 2.185 (p = 0.025) and LDL an OR = 0.209 (p = 0.025). A regression model was obtained in which there is an association between a higher number of COVID-19 infections and elevated cTnI values and a model implying an association of the number of comorbidities and LDL with the NT-proBNP level in a direct and inverse manner, respectively. Both models contribute to the prevention of cardiac damage. Full article

Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder. Full article

Background and Objectives: The rising incidence of modifiable lifestyle risk factors and cardiovascular diseases, driven by poor diet, inactivity, excessive alcohol use, and smoking, may influence the development and rupture of intracranial aneurysms (IA). This study aimed to examine the impact of lifestyle-related and cardiovascular risk factors on IA rupture and patient outcomes. Materials and Methods: We developed the “MARVIN” (Metabolic and Adverse Risk Factors and Vices Influencing Intracranial Aneurysms) model and conducted a retrospective analysis of 303 patients with 517 IAs, treated between 2007 and 2020. Of these, 225 patients were analyzed for rupture status and 221 for clinical outcomes. The analysis focused on hypertension, diabetes, hypercholesterolemia, vascular diseases, nicotine and alcohol abuse, obesity, aneurysm rupture status, and clinical outcomes. Logistic regression was used to evaluate the impact of these risk factors. Results: Among those with risk factors, 24.9% (56/225) and 25.3% (56/221) had one, 32.0% (72/225) and 30.8% (68/221) had two, 20.0% (45/225) and 20.4% (45/221) had three, 12.0% (27/225) and 12.2% (27/221) had four, 4.0% (9/225) and 4.1% (9/221) had five, 0.9% (2/225) had six in both groups, and 0.4% (1/225) and 0.5% (1/221) had seven risk factors, respectively. Strong relationships were found between lifestyle-related vascular risk factors, indicating multiple comorbidities in patients with unhealthy habits. Smokers with ruptured aneurysms had higher WFNS (World Federation of Neurosurgical Societies) scores, but nicotine abuse did not affect long-term outcomes. The most significant predictors for poor outcomes were WFNS score and age, while age and a history of vascular diseases were protective against rupture. Despite the high prevalence of modifiable risk factors, they did not significantly influence rupture risk. Conclusions: The findings suggest a need for multifactorial risk assessment strategies in managing IA patients. Future studies with larger cohorts are required to confirm these results and better understand IA progression. Full article

Background: Vestibular Neuritis (VN) can induce unilateral acute vestibular syndrome (AVS). This study aimed to identify predictive factors of recovery from vestibular neuritis considering total restitution and/or compensation. Methods: In this longitudinal study, 40 patients were included. The initial assessment, performed within 36 to 72 h from the onset (T0), included medical history taking (general and specific), including screening for cardiovascular risk factors (CVRFs), and a battery of diagnostic vestibular tests, comprising the bithermal caloric test (BCT), video head impulse test (VHIT), and skull vibration-induced nystagmus (SVIN) test. All patients also completed a Dizziness Handicap Inventory (DHI). All assessments were repeated 90 ± 15 days later (T3). Subjective compensation criteria were based on the DHI total score, and objective compensation criteria were based on laboratory test results. Four groups of patients (A, B, C, D) were delineated by combining patients with normal vs. abnormal vestibular tests and patients with normal vs. abnormal DHI. Results: CVRFs (but not age or body mass index (BMI)) were associated with a poorer recovery of symptoms. The BCT (lateral semicircular canal paresis %), VHIT (lateral semicircular canal gain), and SVINT (nystagmus slow phase velocity) recovered to normal values in 20%, 20%, and 27% of patients, respectively, at T3. Conclusions: Vascular risk factors (hypercholesterolemia) are correlated with patients who do not recover their symptoms via either total restitution or compensation. There was no significant difference between high- and low-frequency vestibular tests in patients recovering from their symptoms. Some patients with objective recovery may continue to have persistent subjective symptoms. Full article

Background/Objectives: Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL–cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels. Methods: We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk. Results: The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = −0.67, p < 0.05). Conclusions: Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH. Full article

Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug–drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg. The dicarboxylic acid is enzymatically activated by conjugation with coenzyme A (CoA) to form the pharmacologically active thioester (bempedoic acid–CoA). This process is catalyzed by very-long-chain acyl-CoA synthetase 1 (ACSVL1), expressed almost exclusively at the hepatic level. Bempedoic acid–CoA is a potent and selective inhibitor of ATP citrate lyase (ACL), a key enzyme in the biosynthetic pathway of cholesterol and fatty acids. The drug reduces low-density lipoprotein–cholesterol (LDL-C) (20–25%), non-high-density lipoprotein–cholesterol (HDL-C) (19%), apolipoprotein B (apoB) (15%), and total cholesterol (16%) in patients with hypercholesterolemia or mixed dyslipidemia. The drug has a favorable pharmacokinetics profile. Bempedoic acid and its metabolites are not substrates or inhibitors/inducers of cytochrome P450 (CYP450) involved in drug metabolism. On the other hand, bempedoic acid–glucuronide is a substrate for organic anion transporter 3 (OAT3). Bempedoic acid and its glucuronide are weak inhibitors of the OAT2, OAT3, and organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3). Thus, bempedoic acid could inhibit (perpetrator) the hepatic uptake of OATP1B1/3 substrate drugs and the renal elimination of OAT2 and OAT3 substrates and could suffer (victim) the effect of OAT3 transporter inhibitors, reducing its renal elimination. Based on these pharmacological characteristics, here, we describe the potential DDIs of bempedoic acid with concomitant medications and the possible clinical implications. Full article

Hepatic lipase deficiency is a rare genetic condition caused by biallelic loss-of-function variants in the LIPC gene encoding hepatic lipase. These variants reduce or abolish the protein’s lipolytic activity, resulting in elevated plasma lipids. The condition is classified as autosomal recessive, since dyslipidemia is inconsistently observed in heterozygous patients with only one LIPC variant. However, this has been concluded from historical studies encompassing a few families and having very small sample sizes. Here, we conduct a retrospective chart review of 46 heterozygous subjects, each harboring one rare pathogenic LIPC variant. We compare plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B to those of matched controls without LIPC variants. Variant pathogenicity is classified according to the guidelines of the American College of Medical Genetics and Genomics. We observe that levels of total cholesterol, LDL-C, and triglycerides are significantly elevated in the LIPC variant heterozygotes, but HDL-C and apolipoprotein B are not. When filtering solely with respect to pathogenic or likely pathogenic variants, all lipid variables emerge as significantly elevated compared to controls. Thus, hepatic lipase deficiency may not necessarily be a recessive condition, but perhaps semi-dominant since individuals with one variant are phenotypically distinct from the controls. These hypothesis-generating findings regarding LIPC genetic variations observed in a clinical cohort should be evaluated in larger populations and databases. Full article

Background: Several Previous studies indicate that consuming krill oil may aid in reducing hypercholesterolemia and improving cholesterol metabolism. Therefore, our study was designed to investigate the effectiveness of Antarctic krill oil (Euphausia superba) (ESKO) in combating obesity and lowering fat/lipid/cholesterol levels. Methods: The study aimed to investigate the molecular docking model targeting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) using ESKO-derived eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and astaxanthin. In this study, histological alterations in the liver of the obesity model (ICR male mouse), obesity-related or antioxidant markers in both liver and serum, the molecular mechanisms in HepG2 cells and liver tissue, and HMGCR activity were analyzed. Results: Our findings revealed that a high-fat diet (HFD) significantly led to increased oxidative stress, obesity-related indicators, and cardiovascular-associated risk indices. However, ESKO effectively mitigated HFD-induced oxidative stress, fat accumulation, and the suppression of low-density lipoprotein receptor (LDLR) or activation of related molecular pathways. This was achieved through improvements in metabolic parameters, including CD36/liver X receptor α (LXRα)/sterol regulatory element-binding protein 1c (SREBP1c), proprotein convertase subtilsin/kexin type 9 (PCSK-9), and HMGCR, ultimately ameliorating HFD-induced hypercholesterolemia and obesity. Conclusions: These beneficial findings indicate that ESKO might have significant potential for preventing and treating obesity-related disorders. Full article

(1) Background: This study investigated the impact of in vitro adaptations to acid and bile stress on the cholesterol-lowering activity of the probiotic Lactobacillus kefir M20. (2) Methods: Lactobacillus kefir M20 was extracted from fermented dairy products in Xinjiang, China, and isolated using MRS medium. The lactic acid bacteria were cultured for stress resistance to acid and bile salts and then gavaged into mice for animal experiments. (3) Results: The adaptation to bile stress treatment resulted in a notable enhancement of the cholesterol-lowering capacity of Lactobacillus kefir M20, with reductions of 16.5% and 33.1% in total and non-HDL cholesterol, respectively, compared to the untreated strain. Furthermore, the daily fecal total bile acid excretion was 9.2, 5.4 and 5.0 times higher in the M20-BSA group compared to the HC, M20 and M20-ASA groups, respectively. (4) Conclusions: This study suggests that targeted probiotics have the potential for application in the next generation of functional foods and probiotic formulations aimed at combating hypercholesterolemia. Full article

Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. Full article

Natural compounds are important source of desired biological activity which helps to improve nutritional status and brings many health benefits. Ilex paraguariensis St. Hill. which belongs to the family Aquifoliaceae is a plant rich in bioactive substances (polyphenols, saponins, alkaloids) with therapeutic potential including hepatic and digestive disorders, arthritis, rheumatism, and other inflammatory diseases, obesity, hypertension, hypercholesterolemia. In terms of phytochemical research I. paraguariensis has been the subject of most intensive investigations among Ilex species. Therefore, we concentrated on other available Ilex varieties and focused on the content of fatty acids of these shrubs. The fatty acid compounds present in Ilex sp. samples were analyzed by GC-MS. 27 different fatty acids were identified in the extracts. The results showed that many constituents with significant commercial or medicinal importance were present in high concentrations. The primary component in all samples was α linolenic acid(18:3 Δ9,12,15). Differences of this component concentration were observed between cultivars and extensively analyzed by PCA, one- way ANOVA and Kruskal-Wallis ANOVA. Significant correlations between compound concentrations were reported. Full article

Background/Objectives: Dietary habits are among the most significant determinants of health. The aim of this study was to assess the nutritional quality and cardiovascular profiles of individuals following plant-based diet. Methods: The study population comprised 199 individuals (136 women, 63 men; mean age 33.9  ±  8.9 years) including vegans (VG; n = 50), vegetarians (VN; n = 101) and omnivores (OV; n = 48). In this analysis the following procedures were assessed: a questionnaire interview, anthropometric and blood pressure measurements, and a blood sample collection. Dietary patterns were evaluated using the Food Frequency Questionnaire and a 24-h dietary recall. Results: Vegans exhibited the lowest protein intake relative to the other groups (p < 0.05) and a significantly higher intake of polyunsaturated fatty acids and lower intake of cholesterol compared to VN and OV (p < 0.05). Vegans had significantly lower levels of serum cholesterol, LDL cholesterol, and triglycerides, fasting glucose and high-sensitivity C-reactive protein (p < 0.05). No cases of overweight or obesity were observed among VN and VG participants. No instances of impaired fasting glucose or elevated blood pressure were noted among vegans. Hypercholesterolemia was identified in 56.2% of OV, 26.7% in VN and 16.0% in VG (p < 0.05), elevated blood pressure was recorded in one vegetarian and in 6.2% of OV participants. Conclusions: Our research indicates that plant-based diets are associated with a better cardiovascular profile compared to traditional diets. Moreover, suboptimal intake of essential nutrients, underscores the need for more effective public health interventions and improved nutrition education regardless of dietary patterns. Full article