Search Results (2,096)

Background: Apolipoprotein E4 (APOE4) represents a major genetic risk factor for Alzheimer’s disease. Objectives: We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and APOE genotypes in individuals of predominantly African descent aged 55 years and more. Genotyping of two single-nucleotide polymorphisms, rs7412 and rs429358, of the APOE gene was performed. Results: Among 310 individuals, the mean age was 75.64 years, the mean BMI was 25.94 kg/m², and the prevalence of CI was 18.1%. Most subjects were ε3/ε3 carriers (49%), while ε2-carriers and ε4-carriers represented 14.5% and 36.5%, respectively. Older age, the presence of undernutrition, and APOE4 carriers were more frequently found in underweight vs. non-underweight individuals and in those with CI vs. those without CI. The adjusted odds ratios for prevalent CI were nearly four times higher for underweight individuals compared to obese individuals. Those carrying two ε4 alleles exhibited three times the odds of CI (OR = 3.31 (95% CI: 1.15–9.91), p = 0.026) compared to those with no ε4 alleles. Conclusions: In this cross-sectional study, being underweight and carrying the ApoE ε4 allele were independently associated with cognitive impairment. These findings suggest that monitoring weight changes and APOE genotypes in older adults may have clinical significance. Full article

Rice husk ash (RHA) offers an eco-friendly way to improve concrete. Owing to the complex mix design of RHA concrete, accurately predicting its strength remains a challenge. This study addresses this need by compiling a dataset of 291 compressive strength records for RHA concrete. Using seven key input variables (e.g., cement, water, and RHA content), three novel hybrid models were developed by integrating the XGBoost algorithm with advanced metaheuristic optimizers: Northern Goshawk Optimization (NGO), Arctic Puffin Optimization (APO), and Catch Fish Optimization Algorithm (CFOA). These hybrid models were compared against classic Random Forest (RF), and Support Vector Regression (SVR), and unoptimized XGBoost models. The results demonstrated that all hybrid models significantly outperformed the unoptimized classic models. The APO–XGBoost model achieved the highest prediction accuracy on the testing set (RMSE = 3.5462, R² = 0.9579 on testing set), followed by CFOA–XGBoost and NGO–XGBoost. Cement content was revealed to be the most influential parameter on compressive strength, as determined by a sensitivity analysis, ahead of both water and coarse aggregate content. This research confirms the superiority of metaheuristic-optimized hybrid models for predicting the strength of RHA concrete, providing a reliable data-driven tool to support its mix design and promote its application in sustainable construction. Full article

The subject of the study were carotenoids, especially xantophylls in the fruits of various species/cultivars of raspberries, including those cultivated in Poland and those originating from other regions of the world (China, Finland): Rubus occidentalis (5 cultivars); Rubus idaeus (2 cultivars red fruited and 3 cultivars yellow fruited); Rubus chamaemorus; and Rubus chingii and hybrids: R. occidentalis/R. idaeus (2) and R. idaeus/R. occidentalis (1). Based on spectrophotometric analysis, the highest carotenoid content was found in cloudberry (Rubus chamaemorus) fruits, while the lowest was recorded for black raspberry cultivars. Similar carotenoid content results were obtained using thin-layer chromatography (TLC). The xantophyll profiles in the plant material studied were characterized—depending on the species/cultivar or hybrid—by the presence of β-apo-10′-luteinal, trans-lutein, and zeaxanthin. In addition, the antioxidant activity of the obtained hexane–acetone extracts were evaluated using DPPH, ABTS, and FRAP assays, as well as using the TLC-DB with DPPH radical. bioautography test. Full article

Inflammation is a hallmark of atherosclerosis (AS), a complex chronic vascular disease. This study investigates the anti-atherosclerotic effects of the frog skin antimicrobial peptide(AMP) C-1b(3-13) in vitro and in vivo, focusing on the anti-inflammatory mechanism mediated by the miR-590-5p/KLF12/p300 axis in ox-LDL-induced PMA-THP-1 foam cells. MicroRNA(miRNA) sequencing was used to investigate the effects of AMP C-1b(3-13) on miRNA expression in ox-LDL-induced foam cells. Pro-inflammatory cytokine secretion regulated by miR-590-5p was detected by ELISA. Potential targets of miR-590-5p were bioinformatically predicted and validated through dual-luciferase reporter and RNA Immunoprecipitation(RIP)-qPCR assays. Western blot was used to assess the effects of C-1b(3-13) on Krüppel-like factor 12(KLF12), nuclear p300, and nuclear factor kappa B(NF-κB) pathway proteins; ApoE^−/− mice were utilized to establish the AS mouse model. Oil Red O (ORO) and hematoxylin and eosin (H&E) staining detected plaque formation and morphological changes in the aortic root. Immunohistochemistry analyzed CD68⁺(M1) and CD206⁺(M2) macrophage distribution within arterial plaques. miR-590-5p significantly suppressed pro-inflammatory cytokine secretion in ox-LDL-induced foam cells. Mechanistically, miR-590-5p directly targeted the 3′-untranslated region of KLF12 mRNA, inhibiting KLF12 expression, reducing nuclear p300 accumulation, and subsequently attenuating NF-κB signaling pathway activation. Furthermore, AMP C-1b(3-13) treatment effectively attenuated inflammatory responses by upregulating miR-590-5p, which downregulated KLF12 expression, diminished nuclear p300 levels, and inhibited NF-κB signaling. In ApoE^−/− AS mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, and suppressed inflammatory responses through the same signaling axis. These findings reveal a novel miR-590-5p-mediated regulatory mechanism in AS and identify AMP C-1b(3-13) as a promising therapeutic agent targeting miR-590-5p/KLF12/p300/NF-κB pathway. Full article

Background: Apolipoprotein B (apo B), apolipoprotein C-II (apo C-II), and apolipoprotein C-III (apo C-III) play important roles in very low-density lipoprotein (VLDL) metabolism. Whether they influence the relationship between intra-pancreatic fat deposition (IPFD) and VLDL is unknown. The aim was to investigate whether the association between VLDL cholesterol (VLDL-C) and IPFD varies between individuals with and without dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III. Methods: Abdominal magnetic resonance imaging at 3T was performed to quantify IPFD. VLDL-C was measured using the Quantimetrix Lipoprint^® system, whereas apo B, apo C-II, and apo C-III levels were analysed using the MILLIPLEX^® (xMAP) assay. Dysapolipoproteinemia was defined as apolipoprotein levels above the upper quartile of the overall cohort. Univariable and multivariable linear regression analyses were performed, adjusting for age, sex, ethnicity, waist-to-hip ratio, high-density lipoprotein cholesterol, and insulin resistance. Results: A total of 32 individuals had dysapolipoproteinaemia, whereas 96 had normoapolipoproteinaemia. Among those with dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III, VLDL-C levels were significantly and positively associated with IPFD. In the fully adjusted model, each unit increase in VLDL-C corresponded to a 0.82% (p = 0.011), 1.05% (p = 0.003), and 1.00% (p = 0.005) increase in IPFD, respectively. No significant association between VLDL-C and IPFD was observed in individuals with normoapolipoproteinaemia. Conclusions: Altered apolipoprotein profiles influence the association between VLDL-C and IPFD. Full article

Sweet taste receptors (STRs) are class C G protein-coupled receptors (GPCRs) that function as heterodimers of TAS1R2 and TAS1R3. These receptors possess multiple binding sites and can be activated by a wide range of sweet-tasting compounds. Interestingly, TAS1R2 alone or even its extracellular domain-truncated form (TAS1R2-TMD), can act as a functional receptor. Previous studies demonstrated that the sweetener S819 and the sweet inhibitor amiloride act through the transmembrane domain (TMD) of TAS1R2; however, the molecular mechanisms underlying these ligand-specific effects remain unclear, largely due to the historical lack of experimentally determined full-length STR structures. Recent breakthroughs in cryo-EM structural determination of the full-length TAS1R2/TAS1R3 complex now offer an unprecedented opportunity to elucidate receptor activation mechanisms at atomic resolution. In this study, we investigated ligand-induced conformational dynamics of hTAS1R2-TMD using microsecond-scale molecular dynamics (MD) simulations on three systems: hTAS1R2-TMD/S819 (agonist-bound), hTAS1R2-TMD/amiloride (antagonist-bound), and hTAS1R2-TMD (apo). Comparative analyses revealed that agonist and antagonist binding distinctly modulate key structural switches, including the conserved ionic lock (E6.35-R3.50), which stabilizes the inactive state and disrupts upon activation. Notably, we identified a novel salt bridge (D7.32-R3.32) that forms preferentially in the active state, potentially serving as a unique molecular switch for TAS1R2. Additional analyses uncovered ligand-specific rearrangements in hydrogen-bonding and hydrophobic interaction networks. These results provide atomistic insights into how agonists and antagonists differentially modulate TAS1R2 activation and lay a structural foundation for designing novel sweeteners and taste modulators. Full article

Background/Objectives: Atherosclerosis (AS)-related cardiovascular diseases are a major global health threat, with vascular smooth muscle cells (VSMCs) phenotypic switching, abnormal proliferation, and migration as key progression drivers. Nuclear receptor coactivator 4 (NCOA4), a core ferritinophagy mediator overexpressed in AS plaques, may promote VSMCs ferroptosis by perturbing mitochondrial iron metabolism and ROS homeostasis, but precise mechanisms remain unclear. The classic Chinese herbal combination “Gualou-Xiebai” (GLXB) has anti-AS effects, yet how it modulates NCOA4-mediated ferroptosis to inhibit VSMCs’ functions is unknown. This study addresses this gap to advance GLXB’s therapeutic potential and identify AS targets. Methods: An AS model was established in ApoE^−/− mice by 12-week high-fat diet feeding, with model validation confirmed via ultrasound monitoring and H&E staining. NCOA4 was genetically modulated (knockdown and overexpression) to assess its role in plaque formation and lipid deposition using H&E staining, aortic imaging, immunofluorescence, and Western blotting. In vitro, VSMCs were stimulated with ox-LDL to induce proliferation and migration. NCOA4 was silenced using siRNA to examine associated ferroptosis levels and molecular mechanisms. Protein interactions between NCOA4 and the mitochondrial iron storage protein FTMT were evaluated by Co-IP and GST pull-down assays, while mitochondrial ROS (mitoROS) levels were measured to explore functional relationships. The extent of ferroptosis and the underlying regulatory mechanisms were assessed following treatment with GLXB-containing serum or transfection with small interfering RNA targeting LOX-1 (si-LOX-1). Results: NCOA4 knockdown reduced aortic lipid deposition, plaque burden, VSMC proliferation/migration, and mitochondrial ferroptosis. NCOA4 bound and suppressed FTMT, inducing mitochondrial iron overload, ROS accumulation, membrane depolarization, and ferroptosis. Combining NCOA4 silencing with FTMT inhibition elevated mitoROS, confirming the axis’s role in iron homeostasis. GLXB attenuated VSMCs dysregulation in vivo and in vitro, an effect abrogated by LOX-1 overexpression. Conclusions: NCOA4 promotes AS by binding FTMT, disrupting mitochondrial iron homeostasis, and triggering VSMCs ferroptosis. GLXB inhibits LOX-1-mediated NCOA4 expression, mitigating ferroptosis and VSMCs dysregulation, supporting its potential as a targeted anti-AS therapy. Full article

There is a subgroup of people infected with the SARS-CoV-2 virus who manifest lingering sequelae (LongC), with neurological symptoms (nLongC). We recruited 86 COVID-19 volunteers, 35 of whom were fully recovered (Cov) and 51 who had neurological symptoms (nLongC) 4–53 months after infection and compared them to 51 healthy pre-pandemic controls (HC). Thirty-five percent of nLongC individuals carried the apolipoprotein E4 (APOE4) gene, compared to 11% of Cov. Four plasma proteins, interleukin 1 beta (IL-1β), interleukin 8 (IL-8), glial fibrillary acidic protein (GFAP), and hemopexin, continued to be elevated in both Cov and nLongC compared to HC. Soluble CD14 was elevated in nLongC but not Cov. As a group, IL-1β decreased over time in Cov but not nLongC. Two of the elevated proteins, IL-8 and GFAP, correlated with age, with both Cov and nLongC showing higher levels than HC. Using a combination of four plasma proteins, along with age, body mass index, and APOE4 presence, we were able to achieve an area under the curve (AUC) of 0.81. These results suggest that SARS-CoV-2 infection causes a low-grade inflammatory process that, even months or years after infection, does not return to pre-COVID-19 levels, which may contribute to neurologic sequelae and accelerated aging. Full article

Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death primarily in patients over 65 years old, with an increasing incidence, especially in Eastern European countries. Primary and secondary prevention protocols are based on a large number of cardiovascular (CV) risk factors, but low-density lipoprotein cholesterol (LDL-C) remains the main treatment target and one of the central determinants of CV risk. Apolipoprotein B (apoB) is the main structural protein in all atherogenic lipoproteins, and, unlike LDL-C, which only reflects the cholesterol content of LDL, apoB directly quantifies the total number of all circulating atherogenic particles. Over the past decade, a growing amount of data has supported the utility of apoB for CV risk assessment; however, its superiority over LDL-C remains unclear. Our study aimed to investigate the predictive value of apoB for both the presence and the severity of CAD in a statin-treated cohort from an Eastern European hospital and to compare it with standard lipid biomarkers. Methods: A total of 121 statin-treated patients, who were evaluated using coronary angiography, were consecutively enrolled and subdivided into three groups: 52 patients with significant coronary artery disease (S-CAD), 36 patients with non-significant coronary artery disease (NS-CAD), and 33 patients without coronary atherosclerosis (N-CAD). Apolipoprotein B was measured at the moment of enrollment using the immunoturbidimetric assay. Results: The mean values of LDL-C, TC, non-HDL-C, and apoB increased progressively across the three studied groups. Unlike traditional lipid biomarkers, apoB levels differed significantly not only between N-CAD and S-CAD, but also between N-CAD and NS-CAD. The diagnostic superiority of apoB extended beyond group mean differences, as it also demonstrated the strongest correlation with CAD severity. ApoB showed a moderate correlation with the Gensini score (r = 0.43, p < 0.001), which was markedly higher compared to LDL-C, TC, or non-HDL-C, all of which presented only a weak correlation (r = 0.26, r = 0.23, and r = 0.28, respectively). Additionally, in a logistic regression analysis, apoB demonstrated the highest predictive power for the presence of significant CAD (per SD increase: OR 2.386, 95% CI 1.52–3.75, p = 0.000), and it was the only biomarker able to predict left main disease (per SD increase: OR 2.433, 95% CI 1.38–4.30, p = 0.002) and three vessel disease (per SD increase: OR 1.639, 95% CI 1.012–2.654, p = 0.044). Residual apoB was also calculated and remained significantly associated with the presence of coronary atherosclerosis. Conclusions: ApoB proved to be a reliable predictor for CAD, independent of LDL-C. Compared to standard lipid biomarkers, apoB was superior in detecting NS-CAD and showed a better correlation with the severity of CAD. Additionally, in our study, only apoB was significantly correlated with left main disease and three vessel disease. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major metabolic disorder and is frequently accompanied by liver steatosis. Apolipoprotein J (ApoJ) is a glucose-regulated molecular chaperone that has been implicated in hepatic lipid deposition under nutrient overload. This study aimed to investigate the role of hepatocyte-specific ApoJ deletion in hepatic metabolism under diabetic conditions. Methods: A T2DM mouse model with hepatocyte-specific ApoJ knockout (HKO) was established through a high-fat diet combined with streptozotocin injection. Hepatic metabolic profiles were analyzed using untargeted metabolomics with UHPLC–MS/MS. Differential metabolites were subjected to KEGG pathway and Sankey diagram analyses to identify biologically relevant pathways. Results: In total, 140 metabolites showed significant differential abundance in HKO mouse liver, primarily encompassing organic acids and derivatives as well as lipids and lipid-like molecules. KEGG analysis revealed that ApoJ deletion enhanced pathways related to vitamin digestion and absorption, thiamine metabolism, amino acid biosynthesis, lysine degradation, and 2-oxocarboxylic acid metabolism. In contrast, pathways associated with galactose metabolism, cysteine and methionine metabolism, purine metabolism, and the pentose phosphate pathway were suppressed. Sankey diagram analysis further demonstrated that ApoJ deletion markedly reshapes hepatic metabolic networks in T2DM. Conclusions: Given the central role of hepatic dysmetabolism in the pathogenesis of diabetes and its complications, targeting ApoJ may represent a promising therapeutic approach for restoring hepatic metabolic homeostasis and preventing diabetes-associated steatosis. Full article

Previous studies suggested a certain efficiency of proteinogenic branched-chain amino acid (BCAA) and magnesium supplementations in reducing cardiovascular risk and increasing quality of life. This investigation assessed the anti-atherogenic and anti-calcific effects of BCAA (55 mg/day, corresponding to a human equivalent dose of 13.5 g/day) and magnesium citrate (MgCit, 1.85 mg/day, corresponding to a human equivalent dose of 450 mg/day) intake in male and female ApoE-knockout mice, with the treatment initiation at either 1, 3, or 6 months of age. At the 12-month time point, lipid retention and calcium deposition in the aortic valve, lipid burden in the aorta, and serum ionized calcium were evaluated. The early BCAA intake (from 1/3 to 12 months of age) significantly reduced lipid retention in the aortic valve, whilst MgCit decreased ionized calcium. Both of these protective effects were higher in male than in female mice. Furthermore, it was tested whether human serum albumin (HSA) or MgCit can be applied to decrease the serum calcification propensity in 100 patients with myocardial infarction. A dual supplementation with HSA and MgCit reduced serum calcification propensity in 68% of cases. Collectively, these results highlight the potential benefits of BCAA/HSA and magnesium supplementations for cardiovascular prevention and justify further clinical trials in this regard. Full article

Background: Atherosclerosis, a leading cause of cardiovascular disease, involves complex interactions between vascular and immune cells. The role of lymphatic endothelial cells (LECs) in this process remains incompletely characterized, limiting our understanding of disease mechanisms. This study aimed to delineate the phenotypic and functional dynamics of LECs during atherosclerosis progression. Methods: We performed single-cell RNA sequencing on aortic cells from ApoE-/- mice on a high-fat diet at baseline, 8 weeks (early disease), and 16 weeks (late disease). Bioinformatic analyses, including clustering, differential expression, trajectory inference, and cell-cell communication analysis, were applied to characterize LEC subpopulations and their transcriptional reprogramming. Results: Our analysis identified two LEC subpopulations that exhibited a biphasic numerical response: expansion at the early stage followed by a decline by the late stage. Early-disease LECs displayed altered immunomodulatory capacity, with features of reduced T cell tolerance and enhanced activation via IL-7/IL-7R signaling, coupled with a downregulation of key lipid-handling genes (Ldlr, Abca1). Trajectory analysis suggested multiple cellular origins, including a conventional but delayed differentiation path from vascular endothelial cells and an atherosclerosis-specific transdifferentiation path from fibroblasts observed only in early disease. Conclusions: Our findings indicate that LECs undergo substantial phenotypic and functional alterations during atherosclerosis. The maladaptive differentiation and acquired dysfunction in lipid transport and immune regulation may contribute to disease progression. This study provides a foundational transcriptional atlas for understanding lymphatic involvement in vascular disease and highlights potential contexts for therapeutic modulation. Full article

Background: Plant-based diets are associated with reduced cardiometabolic risk, yet the influence of lifestyle behaviors on these benefits remains insufficiently understood. Objective: To assess the combined impact of dietary patterns and lifestyle behaviors on body composition, lipid profiles, and inflammatory biomarkers in healthy young adults. Methods: In this cross-sectional study, 155 participants aged 18–39 years were categorized into four dietary groups: vegans (n = 48), vegetarians (n = 49), pescatarians (n = 23), and omnivores (n = 35). Body composition was measured using bioelectrical impedance analysis. Blood samples were analyzed for lipid parameters, apolipoproteins, lipoprotein(a), and inflammatory markers (IL-6, TNF-α, and hsCRP). Participants were further stratified based on behavioral factors, including physical activity, sleep duration, smoking, and alcohol consumption. Results: Vegans demonstrated the lowest body fat and visceral adipose tissue, along with the second-highest skeletal muscle mass. Significant intergroup differences were observed in total cholesterol (p = 0.032), HDL-C (p = 0.006), and triacylglycerols (p = 0.005). Among vegans, suboptimal lifestyle behaviors were associated with elevated LDL-C, non-HDL-C, and homocysteine levels (p < 0.05). Positive correlations were identified between ApoB and BMI (r = 0.517) and between IL-6 and waist–to–hip ratio (ρ = 0.499). Conclusions: A vegan diet, when combined with healthy lifestyle behaviors, is associated with favorable body composition and lipid profiles. Regardless of dietary pattern, maintaining a healthy body weight and minimizing visceral adiposity are essential for reducing cardiovascular and inflammatory risk. These research findings underscore the importance of integrating high-quality plant-based diets with lifestyle modifications and advanced modeling approaches. Full article

Background: Chronological age is an imprecise proxy for cognitive aging. The Cognitive Age Delta (CAD)—the difference between predicted cognitive age and chronological age—offers a scalable, individualized marker of functional brain aging. We examined determinants of CAD in cognitively unimpaired (CU) adults stratified by Alzheimer’s disease (AD) and vascular biomarkers. Methods: We analyzed 177 CU participants from the Gipuzkoa Alzheimer Project (Basque Country, Northern Spain) classified as amyloid-negative/vascular-negative (CUA−V−, n = 140), amyloid-positive (CUA+, n = 23), or vascular-positive (CUV+, n = 14) using CSF and MRI criteria; vascular burden was defined as Fazekas ≥ 2 on T2-FLAIR or ≥4 microbleeds on SWI, excluding non-traumatic superficial siderosis and established ischemic lesions. MRI was used solely for vascular classification. Associations with demographic, genetic, lifestyle, and reserve measures were tested with General Linear Models. Results: CAD did not differ across biomarker groups (Kruskal–Wallis H(2) = 0.17, p = 0.91). Median (IQR) CAD values were 0.28 (−4.13, 4.69) for CUA−V−, −0.14 (−3.15, 2.87) for CUA+, and 0.77 (−2.22, 3.76) for CUV+, indicating comparable distributions. Higher vocabulary scores (proxy of cognitive reserve) related to a younger cognitive age in CUA−V− (β = −1.39, p < 0.001) and CUA+ (β = −2.08, p = 0.054). In CUA+, greater sedentary time—particularly computer-based sitting—was also associated with lower CAD (daily sitting β = −2.13, p = 0.009; workday computer sitting β = −2.32, p = 0.015). CAD showed no associations with CSF Aβ42, p-tau or t-tau, APOE ε4 load, or vascular risk factors (all p > 0.05). Conclusions: CAD captures interindividual resilience-related variability beyond classical AD biomarkers. Vocabulary, a marker of lifelong enrichment, emerged as a robust determinant of a younger cognitive age, while amyloid and vascular pathology exerted limited influence at preclinical stages. These findings support CAD as a sensitive, scalable endpoint for identifying protective factors and guiding personalized prevention in early Aging. Full article