Search Results (168)

Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE in hyperlipidemic ApoE^−/− mice treated with streptozotocin (50 mg/kg) and fed a high-fat diet (17% lard oil, 1.2% cholesterol). AE fractions F1 or F2 (0.65 mg/kg) were administered for 8 weeks. AE significantly reduced serum LDL-C, HDL-C, triglycerides, and glucose, improved cognitive and memory function, and protected hippocampal neurons. AE also lowered oxidative stress markers (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and modulated neuronal nuclei (NeuN) and doublecortin (DCX) expression. In vitro, AE promoted neurite outgrowth and neuronal differentiation in retinoic acid (RA)-differentiated human SH-SY5Y cells under metabolic stress (glucose and palmitate), alongside the upregulation of heme oxygenase-1 (HO-1), Nuclear factor-erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). These findings suggest AE may counter cognitive decline via oxidative stress regulation and the enhancement of neuronal differentiation. Full article

The aromatic C₁₃ apocarotenoid β-ionone is a high-value natural-flavor and -fragrance compound derived from the oxidative cleavage of carotenoids. Carotenoid cleavage dioxygenases (CCDs) play a pivotal role in the biosynthesis of volatile apocarotenoids, particularly β-ionone. In this study, we report the identification, cloning, and functional characterization of two CCD1 homologs: OeCCD1 from Olea europaea and InCCD1 from Ipomoea nil. These two species, which, respectively, represent a woody perennial and a herbaceous annual, were selected to explore the potential functional divergence of CCD1 enzymes across different plant growth forms. These CCD1 genes were synthesized using codon optimization for Escherichia coli expression, followed by heterologous expression and purification using a GST-fusion system. In vitro assays confirmed that both enzymes cleave β-carotene at the 9,10 (9′,10′) double bond to yield β-ionone, but only OeCCD1 exhibits detectable activity on zeaxanthin; InCCD1 shows no in vitro cleavage of zeaxanthin. Kinetic characterization using β-apo-8′-carotenal as substrate revealed, for OeCCD1, a K_m of 0.82 mM, V_max of 2.30 U/mg (k_cat = 3.35 s⁻¹), and k_cat/K_m of 4.09 mM⁻¹·s⁻¹, whereas InCCD1 displayed K_m = 0.69 mM, V_max = 1.22 U/mg (k_cat = 1.82 s⁻¹), and k_cat/K_m = 2.64 mM⁻¹·s⁻¹. The optimization of expression parameters, as well as the systematic evaluation of temperature, pH, solvent, and metal ion effects, provided further insights into the stability and functional diversity within the plant CCD1 family. Overall, these findings offer promising enzymatic tools for the sustainable production of β-ionone and related apocarotenoids in engineered microbial cell factories. Full article

Perioperative neurocognitive disorder (PND) is a concern following anesthesia, particularly in individuals at risk for Alzheimer’s disease (AD). This study compared the cognitive and pathological effects of propofol and remimazolam in a mouse model with AD following surgery. Five-month-old male ApoE4-KI mice underwent abdominal surgery under either propofol (170 mg/kg) or remimazolam (85 mg/kg) anesthesia. Cognitive function was assessed using the Morris water maze and Y-maze, and neuronal apoptosis and amyloid-beta (Aβ) deposition in the CA3 and dentate gyrus (DG) of the hippocampus were evaluated preoperatively and at 2, 4, and 7 days postoperatively. Both groups showed similar postoperative cognitive functions, with increased relative escape latency at day 2 and decreased relative spontaneous alternation at days 4 and 7. However, the neuropathological analysis revealed that propofol-induced significantly more neuronal death in the CA3 (days 4 and 7) and DG (days 2, 4, and 7), and greater Aβ accumulation in the CA3 (days 2 and 4) and DG (days 2 and 7) compared to remimazolam (p < 0.05). Propofol was associated with more pronounced neuropathologic changes in the hippocampus compared to remimazolam. These findings suggest remimazolam may be a safer anesthetic for patients at risk for neurodegenerative disorders, as it is associated with less severe hippocampal pathology, which is characteristic of AD. Full article

Riboswitches regulate gene expression through intricate dynamic conformational transitions, with divalent cation Mg²⁺ and their ligands playing pivotal roles in this process. The dynamic structural mechanism by which the S-adenosyl-L-methionine (SAM) responsive SAM-VI riboswitch (riboSAM) regulates the downstream SAM synthase gene translation remains unclear. In this study, we employed position-selective labeling of RNA (PLOR) to incorporate Cy3-Cy5 into designated positions of riboSAM, applying single-molecule Förster resonance energy transfer (smFRET) method to track its conformational switches in response to Mg²⁺ and SAM. smFRET analysis revealed that in the absence of Mg²⁺ and ligand, riboSAM predominantly adopted a translation-activating apo conformation. Physiological concentrations of Mg²⁺ induced riboSAM to fold into dynamic transit-p and holo-p states, creating a transient and structurally pliable binding pocket for ligand binding. SAM binding locks the dynamic transit-p and holo-p states into their final stable transit and holo conformations through conformational selection, turning off downstream cis-gene expression and completing feedback regulation of cellular SAM concentration. The observed synergistic regulatory effect of Mg²⁺ ions and ligand on riboSAM’s conformational dynamics at single-molecule resolution provides new mechanistic insights into gene regulation by diverse riboswitch classes. Full article

Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer’s disease and related dementias (AD/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD/ADRD in women. Women have unique risk factors for late onset of AD/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women’s vulnerability to AD/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD/ADRD in women for developing preventive measures. Full article

Background: Apolipoprotein B (ApoB), a key component of atherogenic lipoproteins, has been increasingly implicated in cardiometabolic disorders beyond dyslipidemia. However, its role in glycemic dysregulation remains unclear. This study aimed to investigate the association between ApoB levels and glycemic parameters, including fasting glucose, insulin resistance, and glycated hemoglobin (HbA1c), in individuals without diagnosed diabetes. Methods: This study was conducted at the National Research Cardiac Surgery Center (Kazakhstan) over the period between 2023 and 2024 as a cross-sectional analysis. Adults aged ≥ 20 years without diagnosed diabetes and with complete data on their ApoB and glycemic markers were included. Associations between ApoB and fasting plasma glucose (FPG), HbA1c, and HOMA-IR were assessed using multivariable linear and logistic regression models adjusted for demographic, lifestyle, and metabolic covariates. Results: Higher ApoB levels were significantly associated with increased fasting glucose (β = 2.07 mg/dL per 1-SD increase in ApoB, p < 0.001), higher HbA1c (β = 0.06%, p < 0.001), and elevated HOMA-IR (β = 0.54, p < 0.001). Participants in the highest ApoB quartile had 53% higher odds of prediabetes (adjusted OR = 1.53; 95% CI: 1.22–1.91; p < 0.001) compared to the lowest quartile. These associations remained significant after adjusting for BMI, lipid levels, and other confounders. Conclusions: Elevated ApoB is independently associated with adverse glycemic profiles in nondiabetic individuals, suggesting its potential role in early glucose metabolism disturbances. Full article

Background: Hyper-LDL-cholesterolemia is a key contributor to cardiovascular diseases (CVDs), and both genetic predisposition and lifestyle influence it. This study aimed to develop personalized strategies for managing hyper-LDL-cholesterolemia by integrating polygenic risk scores (PRSs), genetic variants, and bioactive compound interactions, leveraging a precision medicine approach. Methods: A cohort of 58,701 Korean adults, including 8966 individuals with hyper-LDL-cholesterolemia (LDL ≥ 160 mg/dL) or undergoing treatment with hypocholesterolemic agents, was analyzed to investigate the interplay between genetic risk and lifestyle factors. The PRS was constructed using three key variants: PCSK9 (rs151193009), CELSR2 (rs11102967), and APOE (rs7412). Gene–lifestyle interactions were assessed, focusing on energy intake and physical activity. Computational molecular docking was utilized to investigate how bioactive compounds differentially interact with the wild-type and mutant forms of PCSK9 (Arg93Cys) and APOE (Arg176Cys), focusing on variations in binding affinity. Results: Hyper-LDL-cholesterolemia was associated with a 1.3-fold increased risk of CVD. The PRS showed a significant association with a 3.45-fold higher likelihood of developing both elevated LDL cholesterol and reduced HDL cholesterol levels. Lifestyle interactions revealed that high energy intake and physical inactivity significantly amplified the genetic risk (p < 0.05). In silico analysis demonstrated that bioactive compounds, notably prodelphinidin trimer, exhibited enhanced binding affinity with wild-type PCSK9 (Arg93Cys), while several compounds preferentially targeted the mutated PCSK9, suggesting potential avenues for genotype-specific therapies. Conclusions: This study emphasizes the combined influence of genetic predispositions and lifestyle behaviors on developing hyper-LDL-cholesterolemia, and highlights potential bioactive compounds as personalized therapeutic targets. By integrating genomic data, lifestyle analysis, and molecular docking, this research provides a foundation for precision interventions tailored to an individual’s genetic and metabolic profile, paving the way for more effective and personalized management of dyslipidemia and associated CVD risk. Full article

Background/Objectives: Chronic kidney disease (CKD) is associated with increased mortality, with cardiovascular disease (CVD) being the primary cause of death. Proper lipid regulation may reduce CVD risk and slow CKD progression. While there is evidence that a higher plant protein intake could ameliorate lipid levels in the general population, the effects of this dietary regimen within the CKD population remain uncertain, with studies providing conflicting results. We aim to investigate the impact of increased plant protein intake on the lipid levels of CKD patients. Methods: Two electronic databases (PubMed, Scopus) were reviewed for controlled clinical trials assessing the effect of increased plant protein intake versus the usual CKD animal-based diet in CKD patients, published until June 2024. Results: Eleven trials, encompassing 248 patients, were included in this meta-analysis. Overall, compared to the usually recommended CKD diet, increased plant protein intake was associated with statistically significant reductions in total cholesterol (−24.51 mg/dL, 95% CI −40.33, −8.69), low-density lipoprotein (LDL) (−21.71 mg/dL, 95% CI −38.32, −5.1), triglycerides (− 21.88 mg/dL, 95% CI −35.34, −8.40), and Apolipoprotein B levels (−11.21 mg/dL, 95% CI −18.18, −4.25). No significant changes were observed in high-density lipoprotein (HDL) (0.09 mg/dL, 95% CI −1.82, 1.99) and Apolipoprotein A levels (0.04 mg/dL, 95% CI −7.14, 7.21). Conclusions: Increased plant protein intake, mainly from soy, reduces total cholesterol, LDL, triglycerides, and ApoB in adult CKD patients. Further research is needed to assess these effects in dialysis patients and explore non-soy plant sources. Full article

Introduction and Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipid metabolism that is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and a high risk of atherosclerotic cardiovascular disease. Familial hypercholesterolemia is typically caused by mutations in the LDL receptor gene (LDLR), although other alterations may be found. The aim of this study was to perform a genetic study on a population identified through a new population-based diagnostic screen program for FH. Methods: Genetic variants in LDLR, apolipoprotein B (APOB), apolipoprotein E (APOE), proprotein convertase subtilisin/kexin type 9 (PCSK9), signal transducing Adaptor Family Member 1 (STAP1), low density lipoprotein receptor adaptor protein 1 (LDLRAP1) and lipase A, and lysosomal acid type lipase A (LIPA), as well as a genetic risk score, were evaluated in 84 individuals with a clinical diagnosis of FH based on the Dutch Lipid Clinics Network criteria (DLCN ≥ 6). These individuals were selected from a cohort of 752 patients with an abnormal lipid profile, obtained by screening existing centralized analytics. Results: A clinical diagnosis of FH was established in 17.9% of the patients evaluated, with mean LDL-C levels of 305.7 mg/dL (95% CI 250.4–360.9). Genetic variants were detected in 70.2% of these patients, with 50 different mutations identified, mainly in the LDLR. The most frequent pathogenic variants were c.1342C>T and c.313+1G>C. Null variants exhibited a more severe phenotype, and the risk score indicates that patients carrying genetic alterations have a 42% higher risk of developing cardiovascular disease. Conclusions: A high rate of genetic alterations was detected in patients with severe FH. In most cases, the phenotypic findings did not predict the genetic results, which provide important information regarding the cardiovascular risk of patients. Full article

Background/Objectives: Little is currently known of the impact of heated tobacco on health. The aim of this study is to evaluate the impact of heated tobacco use on selected health assessment parameters among people aged 18–30 to determine the effect on health status. Methods: A case-control study was conducted from April 2022 to February 2025. A total of 195 young, healthy adult residents of Lodz, Poland, took part. The participants were divided into three groups: IQOS (I-Quit-Ordinary-Smoking) smokers who had never smoked or who had quit smoking six months previously (n = 65); daily smokers who had smoked at least five cigarettes per day for at least one year and had not used any other smoking substitutes for at least one year (n = 65); and people who have never smoked or used tobacco products (n = 65). Blood samples from 37 IQOS users (57%), 28 traditional cigarette smokers (43%), and 45 non-smokers (69%) were submitted for laboratory analysis. The tested parameters were determined in the diagnostic laboratory of the Bonifratów Hospital in Lodz. Results: No significant differences (p > 0.05) were found between the groups with regard to blood count (white blood cell count (WBC), red blood cell count (RBC), lymphocytes, monocyte number (MONO), hemoglobin concentration (HGB)), biochemical biomarkers (C-reactive protein (CRP), fibrinogen, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), glucose), or lipid profile (total cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL)). The cigarette smokers demonstrated significantly higher uric acid levels compared to the IQOS users and non-smokers: 5.22 vs. 4.77 vs. 4.40 mg/dL (p < 0.01). The IQOS users demonstrated significantly higher platelet count levels compared to cigarette smokers and non-smokers: 290.27 vs. 267.14 vs. 256.33 × 10³/ μL (p < 0.05). Among the IQOS users (n = 37), the level of glucose (ρ = −0.47; p = 0.01), WBC (ρ = −0.36; p = 0.03), lymphocytes (ρ = −0.38; p = 0.02), and uric acid (ρ = −0.34; p = 0.04) was negatively correlated with the daily number of heated tobacco sticks. The HDL level was positively correlated (ρ = 0.39; p = 0.02) with the daily number of heated tobacco sticks. Conclusions: Further cohort studies assessing the health status of young users of heated nicotine products and prospective analyses are necessary. Full article

Background: Cardiometabolic comorbidities are common in multiple sclerosis (MS), and lifestyle interventions are effective in managing these conditions in the general population, though evidence in the MS patient population is limited. Objective: To evaluate the effect of a multimodal lifestyle intervention on serum apolipoproteins (Apo), creatine kinase (CK), glucose, and insulin in people with progressive MS (PwPMS). Methods: This study included n = 19 PwPMS who participated in a 12-month multimodal lifestyle intervention (including a modified Paleolithic diet, exercise, neuromuscular electrical stimulation, supplements, and stress reduction). Lipid profile (ApoA1, B, and E), CK, glucose, and insulin were obtained at baseline and after 12 months under fasting conditions. Results: At 12 months, there was a marginally significant decrease in ApoB (mean change: −7.17 mg/dL; 95% CI: −14.4, 0.12; p = 0.06), while no significant changes were observed for ApoA1 (mean change: −1.28 mg/dL; 95% CI: 12.33, 9.76; p = 0.80), ApoE (mean change: +0.12 mg/dL; 95% CI: −0.27, 0.52; p = 0.51), CK (mean change: +13.19 U/L; 95% CI: −32.72, 59.11; p = 0.55), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (mean change: −0.44; 95% CI: −1.11, 0.22; p = 0.17), and HOMA-β (mean change: +45.62; 95% CI: −95.6, 186.9; p = 0.50). A positive association was observed between changes in HOMA-IR and fatigue changes at 12 months (β = 0.81, p = 0.02), suggesting that an increase in HOMA-IR was linked to increased fatigue, which was no longer significant following the exclusion of outliers (β = 0.71, p = 0.16). Conclusions: A multimodal lifestyle intervention did not negatively impact glycemic and lipid profiles. While improvements were observed in serum biomarkers, these changes were not statistically significant, highlighting the need for stronger evidence from larger, controlled studies to confirm the cardiometabolic health benefits in PwPMS. Full article

Background/Objective: Atherosclerosis is one of the leading causes of cardiovascular diseases and mortality around the world. One exciting strategy for atherosclerosis treatment is immunotherapy, especially active immunization. Active immunization relies on the delivery of antigens in a vaccine platform to introduce humoral and cellular immunity, alleviating atherosclerotic progression. Transient receptor potential channel isoform M2 (TRPM2) is an ROS-activated Ca²⁺-permeable ion channel that can promote atherosclerosis via stimulating vascular inflammation. In the present study, we developed a strategy of active immunization with the TRPM2 E3 domain peptide in a vaccine platform, aiming to induce the endogenous production of anti-TRPM2 blocking antibody in mice in vivo, consequently inhibiting TRPM2 channel activity to alleviate atherosclerotic progression. Methods: ApoE knockout mice were fed with a high cholesterol diet to develop atherosclerosis. The mice were injected with or without the E3 peptide vaccines, followed by analysis of atherosclerotic lesion by en face Oil Red O staining of the whole aorta and histologic analysis of thin tissue sections from aortic roots. Results: The results show that immunization with a pig TRPM2 E3 region-based peptide (P1) could effectively alleviate high cholesterol diet-induced atherosclerosis in ApoE knockout mice. We worked out the best vaccine formulation for the most effective atheroprotection, namely P1 at the dose of 67.5 µg per mouse (2.5 mg/kg body weight) with aluminum salts as adjuvant. Conclusions: The present study provides a novel target TRPM2 for peptide vaccine-based anti-atherosclerotic strategy and lays the foundation for future preclinical/clinical trials using TRPM2 E3 P1 vaccine for a potential therapeutic option against atherosclerosis. Full article

Background: Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are intermediary products in NAD+ metabolism. NMN and NR supplementation can elevate NAD+ levels in tissues, addressing health issues associated with aging and obesity. However, the impact of NMN and NR on atherosclerosis remains incompletely elucidated. Methods: C57BL/6J and Apolipoprotein E knockout (ApoE^−/−) mice were used to explore the impact of NMN and NR supplementation on serum lipids, fatty liver, and atherosclerosis. Additionally, various suppliers, administration protocols, and doses on ApoE^−/− mice were investigated. Results: The intragastric administration of NMN (300 mg/kg) and NR (230 mg/kg) reduced body weight, serum lipids, and fatty liver but aggravated atherosclerosis in ApoE^−/− mice after 4 months of administration with different suppliers. Atherosclerosis also deteriorated after 2 months of different NMN administration protocols (intragastric and water administration) in ApoE^−/− mice with existing plaques. The effects of NMN were dose-dependent, and doses around 100 mg/kg had little harmful effects on atherosclerosis. Conclusions: NMN and NR improve dyslipidemia and fatty liver but promote atherosclerosis in ApoE^−/− mice. These findings emphasize the safe dosage for the clinical trials of NMN. Full article

Pyranoanthocyanins exhibit greater bioactivity compared to monomeric anthocyanins, yet the lipid-lowering effects of pyranoanthocyanin Vitisin A, a primary derivative found in aged red wines, have not been extensively studied in vivo. This study evaluated the triglyceride-lowering effects of Vitisin A and its anthocyanin counterpart Cyanidin-3-O-glucoside (C3G) in both free fatty acid -induced HepG2 cells and high-fat diet-fed ApoE^-/- mice, with a focus on their roles in lipid metabolism. In vitro, Vitisin A significantly reduced triglyceride levels and lipid accumulation in HepG2 cells compared to C3G at equivalent concentrate. In vivo, dietary supplementation with 100 mg/kg of Vitisin A reduced body weight gain and plasma triglyceride levels by 19.6% and 29.5%, respectively, whereas no significant effects were observed with C3G. Mechanistically, Vitisin A markedly inhibited hepatic de novo lipogenesis (DNL) by activating the AMPK/ACC signaling pathway and downregulating FASN expression. Concurrently, Vitisin A enhanced fatty acid β-oxidation more robustly than C3G by upregulating CPT-1A via AMPK/SIRT1/PGC-1α and PPAR-α/PGC-1α pathways. Both Vitisin A and C3G driving peroxisomal β-oxidation of very-long-chain fatty acids. In summary, Vitisin A demonstrated superior triglyceride-lowering effects compared to C3G, primarily through dual mechanisms of inhibiting hepatic DNL and enhancing fatty acid β-oxidation. Full article

The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS in tricuspid aortic valve patients, the studies on the BAV population are lacking. We aimed to evaluate the association between selected lipid markers and the occurrence of AS in BAV patients. Methods: The study included 76 adults (21 female) with a BAV diagnosed by echocardiography, divided by age and AS diagnosis. Biochemical parameters concentrations in serum were measured: high density lipoprotein cholesterol (HDL-C) levels by standard enzymatic colorimetric tests, low density lipoprotein cholesterol (LDL-C) levels by the Friedewald formula, apolipoprotein A-I (Apo AI) and apolipoprotein B (Apo B) serum concentration by the nephelometric method, and paraoxonase-1 activity (PON-1 ASE) and arylesterase activity (PON-1 ARE) based on paraoxon and phenyl acetate hydrolysis. Results: A total of 54 patients (15 female) were more than 45 years old and 22 (6 female) were 45 or less years old. BAV patients with AS aged ≤45 had higher levels of Apo B, compared to those without AS [110.5 (102–132) vs. 95.6 (77–101) mg/d; p 0.044]. Similarly, Apo B/Apo AI ratio was higher in BAV patients with AS aged ≤45, compared to those without AS [(0.8 (0.7–1) vs. 0.6 (0.5–0.7); p 0.029]. In the group aged ≤45, Apo B showed a positive correlation with the aortic valve peak transvalvular velocity (AV Vmax) measurement (R Spearman 0.6, p 0.004). We found also that, among young BAV patients, those with AS had a lower level of PON-1 ARE compared to the cohort without AS [63.4 (52–80) vs. 85.3 (70–102); p 0.012]. We did not find any differences in lipid parameters in patients aged >45. Conclusions The metabolic link between Apo B level and Apo B/AI ratio with AS presence in BAV patients under 45 years of age suggests a significant impact of these parameters on the earlier development of AS in the BAV population. Molecules associated with high density lipoprotein and its antioxidant function, such as PON1, are valuable markers for AS development, compared to HDL-C and LDL-C levels. Full article