Search Results (1,345)

Alzheimer’s disease (AD) is a complex neurodegenerative disorder where age, genetic factors and sleep disturbance significantly influence disease risk. Recent genome-wide association studies identified a C/T missense variant (rs141749679) in the sortilin (SORT1) gene linked to heightened AD risk, revealing SORT1’s role as a key player in the disease’s pathophysiology. This type I membrane glycoprotein is implicated in amyloid β (Aβ) accumulation and associated lipid dysregulation, particularly through its interaction with apolipoprotein E (ApoE). SORT1 facilitates the uptake of ApoE-bound polyunsaturated fatty acids (PUFAs), conversion to endocannabinoids (eCBs), and the regulation of anti-inflammatory pathways via peroxisome proliferator-activated receptors (PPARs). Notably, this neuroprotective signaling is contingent on the APOE allele, exhibiting functionality in presence of ApoE3 but disrupted with ApoE4. Additionally, the brain-type fatty acid binding protein, FABP7, mediates this signaling cascade, emphasizing its role in neuron-glia communication. FABP7 is known to regulate sleep across species and binds PUFAs and eCBs. Therefore, dysfunction of the ApoE-SORT1-FABP7 axis may underlie the neuroprotective loss observed in AD, linking sleep disruption and lipid homeostasis to disease progression. This perspective aims to elucidate the intricate neural-glial mechanisms governing the ApoE-SORT1-FABP7 interaction and their implications for targeting therapeutic interventions in Alzheimer’s disease. Full article

Chronic kidney disease (CKD) is a growing global health burden, strongly associated with cardiovascular disease, the leading cause of mortality in this population. Dyslipidemia is a key metabolic abnormality in CKD, but traditional lipid measures such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides often fail to capture the complexity of lipid disturbances in CKD and after kidney transplantation. Apolipoproteins have emerged as more reliable markers of cardiovascular and renal risk. Elevated apolipoprotein B (ApoB), reduced apolipoprotein A1 (ApoA1), and a higher ApoB/ApoA1 ratio are linked to CKD progression, cardiovascular events, and post-transplant complications, including post-transplant diabetes mellitus. Lipoprotein(a), a genetically determined atherogenic lipoprotein, accumulates in CKD due to impaired clearance and further increases cardiovascular risk. Other apolipoproteins, such as APOL1 and APOE, modulate CKD susceptibility through lipid-dependent and independent mechanisms. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of lipid metabolism, and PCSK9 inhibitors may represent a promising therapeutic option, though evidence in advanced CKD and transplant recipients is still limited, especially regarding their effects on apolipoproteins. This review summarizes current evidence on apolipoproteins and PCSK9 in CKD and transplantation, with attention to their potential as biomarkers and therapeutic targets. Full article

Background: Nowadays, there is a lack of reliable and minimally invasive diagnosis methods for the early detection of Alzheimer’s disease. The development and validation of such tools could significantly reduce the dependence on more invasive and costly confirmatory procedures, such as cerebrospinal fluid biomarkers analysis and neuroimaging techniques. Objectives: The main objective of this study is to validate the clinical performance of a previously developed diagnosis model based on plasma biomarkers from patients in a cognitive disorder unit. Methods: A new cohort of patients was recruited from the same cognitive disorder unit (n = 93). Specifically, demographic data (gender, age, and educational level), plasma biomarkers levels, and genotype (glial fibrillary acidic protein, phosphorylated Tau 181, amyloid-beta42/amyloid-beta40, apolipoprotein E) were collected to evaluate both approaches of the previous diagnosis model (one-cut-off, two-cut-off). Results: The one-cut-off approach showed a sensitivity of 74.3%, a specificity of 89.5%, and an area under the curve of 0.888, while the values for the two-cut-off approach were sensitivity of 66.7%, specificity of 99.9%, and area under the curve of 0.867. Conclusions: A multivariate diagnostic tool was temporally validated for implementation in a clinical unit. In fact, satisfactory results were obtained from both approaches (one-cut-off, two-cut-offs), but the two cut-offs approach was more consistent in correctly identifying non-Alzheimer’s disease cases, allowing us to identify a large number of cases with high specificity. Full article

Genetic variants in nutrition-related genes exhibit variable functional consequences; however, systematic characterization across different nutritional domains remains limited. This highlights the need for detailed exploration of variant distribution and functional effects across nutritional gene categories. Therefore, the main objective of this computational study is to delve deeper into the distribution and functional impact of missense variants in nutrition-related genes. We analyzed Genetic polymoRphism variants using Personalized Medicine (GRPM) dataset, focusing on ten groups of nutrition-related genes. Missense variants were characterized using ProtVar for functional/structural impact, Pharos for functional classification, network analysis for pathway identification, and Gene Ontology enrichment for biological process annotation. The analysis of 63,581 Single Nucleotide Polymorphisms (SNP) revealed 27,683 missense variants across 1589 genes. Food intolerance (0.23) and food allergy (0.15) groups showed the highest missense/SNP ratio, while obesity-related genes showed the lowest (0.04). Enzymes predominated in xenobiotic and vitamin metabolism groups, while G-protein-coupled receptors were enriched in eating behavior genes. The vitamin metabolism group had the highest proportion of pathogenic variants. Network analysis identified apolipoproteins as central hubs in metabolic groups and inflammatory proteins in allergy-related groups. These findings offer insights into personalized nutrition approaches and underscore the utility of computational variant analysis in elucidating gene-diet interactions. Full article

The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately with their niche, particularly after the formation of the secondary ossification center, through stage-specific regulatory mechanisms involving several key signaling pathways. This review summarizes the current understanding of gpSSC identity, behavior, and regulation, focusing on how these cells sustain growth plate function through adapting to biomechanical and molecular cues. Full article

Alzheimer’s disease (AD) instantly requires affordable diagnostic tools for targeting the responsible molecular biomarkers. In this review, we briefly discussed the overview of the AD population, performance of different analytical techniques and nanoparticles/composites, molecular biomarkers, and the interest of countries towards the detection of AD biomarkers during 2012–2025. The desired result was attained by lateral flow assay, surface-enhanced Raman scattering, and colorimetric sensor techniques with nanoparticles of magnetic, gold, and carbon-containing silver, and iridium oxide nanoparticles, upon biomarkers of dopamine, amyloid beta41, and Apolipoprotein E, individually. Additionally, the outstanding performance of nanoparticles including gold nanoparticles, carbon-containing nanoparticles, and manganese dioxide with their particle size of 5.7 nm, 35 nm, 37.3 nm, 120 nm, and 220 nm, respectively, has been discussed. Moreover, the percentages of AD-related biomarkers including amyloid beta42 having research articles of 21.2%, amyloid beta1-42 12.1%, amyloid beta oligomer 12.1%, phosphorylated Tau detection 12.1%, amyloid beta1-40 9.09%, Dopamine 9.09%, amyloid beta40 9.17%, apolipoprotein 6.06%, etc., have also been included. Additionally, LOD comparison with respect to applied analytical techniques, investigated through a timeline and electrochemical sensor, was found most suitable. Finally, a portable molecular diagnostic device to combine amyloid beta1-42, amyloid beta1-40, and phosphorylated Tau detection in non-invasive bodily fluid was proposed for the future and clinical diagnosis. Full article

In this study, we aimed to characterize intramuscular fat (IMF) tissue in fattening steers through a comparison with subcutaneous fat (SCF) tissue. The IMF of the longissimus thoracis et lumborum and the SCF of the back fat from three fattening steers (mean body weight of 703.50 ± 11.45 kg) were collected, and the muscle tissue, connective tissue, and fascia were carefully removed. Gene and protein expressions and the lipid contents were assessed via transcriptomic, proteomic, and lipidomic analyses, respectively. Subsequently, tissue-specific factors were identified using integrated analysis. The results revealed that the expressions of sarcoplasmic/endoplasmic reticulum Ca²⁺ transporting 2 (ATP2A2), enolase 3 (ENO3), fructose-bisphosphatase 2 (FBP2), myosin heavy chain 7 (MYH7), myosin light chain 3 (MYL3), myosin light chain kinase (MYLK), glycogen phosphorylase (PYGM), troponin C1 (TNNC1), and tropomyosin 2 (TPM2) significantly increased in IMF at both the mRNA and protein levels, whereas those of fatty acid-binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), and apolipoprotein E (APOE) were reduced. The abundances of both phosphatidylinositol (PI) (18:1/20:4) and phosphatidylcholine (PC) (15:0/18:2) were positively correlated with APOE. Conversely, that of PI (18:1/20:4) was negatively correlated with ENO3 and PYGM, whereas PC (15:0/18:2) was negatively correlated with TNNC1 and MYLK. In conclusion, we identified calcium signaling and glycolysis as key IMF-regulating pathways. ATP2A2, ENO3, FBP2, MYH7, MYL3, MYLK, PYGM, TNNC1, TPM2, and LPE 18:0 were negatively associated with IMF deposition, whereas FABP4, SCD, APOE, PI (18:1/20:4), and PC (15:0/18:2) were positively associated with it. These findings offer underlying IMF-related targets to promote IMF deposition in cattle. Full article

Atherosclerosis (AS), the leading cause of cardiovascular disease (CVD), is the thickening and stiffening of arterial walls, mainly of coronary arteries, the aorta, and the internal carotid artery. Blood flow is restricted by the deposit of lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the inner lining (tunica intima) of arterial walls. Damaged endothelia become inflamed and accumulate macrophages, monocytes, granulocytes, and dendritic cells, which intensifies plaque formation and increases the risk of myocardial infarction (MI) and thrombosis. Many of the anatomical and physiological abnormalities in arterial walls can be linked to colonic bacteria that produce inflammation-inducing metabolites, e.g., succinate, fumarate, fatty acids (FAs), reactive oxygen species (ROS), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO). TMAO triggers platelet formation, inhibits the synthesis of bile acids (BAs), accelerates the formation of aortic lesions, and upregulates the expression of membrane glycoprotein CD36 (also known as platelet glycoprotein 4) on the surface of platelets and epithelial cells. The ability of internal mammary arteries (IMAs) to produce higher levels of apolipoprotein C-III (apo-CIII) and paraoxonase (PON), compared to coronary arteries, prevents plaque buildup. The tunica intima of IMAs is rich in heparin sulfate and endothelial nitric oxide synthase (eNOS). Increased production of NO relaxes VSMCs and suppresses GTP cyclohydrolase (GTPCH), which lowers blood pressure. Higher levels of prostacyclin (PG12) produced by IMAs inhibit platelet aggregation. IMAs are structurally different from coronary arteries by having a thinner, non-fenestrated, tunica intima without a prominent internal elastic lamina. These characteristics render IMAs ideal conduits in coronary artery bypass graft (CABG) surgery. This review provides information that may explain why IMAs are less affected by inflammatory reactions and more resilient to plaque formation. Full article

Apolipoprotein A-IV (ApoA-IV) has been implicated in modulating the gut microbiota. However, chronic high-fat diet (HFD) consumption impairs ApoA-IV signaling and disrupts gut microbial balance, contributing to obesity and insulin resistance. This study aimed to investigate the role of ApoA-IV in shaping the gut microbiota and associated metabolic profiles throughout the lifespan of mice exposed to an HFD. Fecal samples were collected from ApoA-IV knockout (KO) and wild-type mice at five time points for microbiota and metabolite profiling using 16S rRNA gene sequencing and gas chromatography–mass spectrometry, respectively. Lifespan was longest in ApoA-IV-KO mice on a normal diet, while the HFD reduced survival across genotypes. Microbiota analysis revealed diet- and age-dependent shifts, including an elevated Firmicutes/Bacteroidota ratio, altered abundance of Akkermansia and reduced Monoglobus in ApoA-IV-KO mice on the HFD. Metabolic profiling showed a stronger impact of diet than genotype, with early and persistent increases in branched-chain amino acids and reductions in short-chain fatty acids (SCFAs). ApoA-IV deficiency modulated lifespan microbial and metabolic changes and shaped distinct responses to dietary stress. Despite age-related convergence in microbiota structure, genotype-specific differences in metabolite profiles and SCFA-producing bacteria correlations persisted into old age, demonstrating the lasting impact of ApoA-IV on host metabolic adaptation. Full article

Apolipoprotein C3 (apoC3) is a key regulator of triglyceride metabolism and has emerged as a potential therapeutic target for reducing the risk of cardiovascular disease. However, its broader physiological functions are not fully understood. This study investigates the role of apoC3 in platelet function and thrombus formation. Interestingly, human apoC3 was found to rapidly inhibit platelet activation over the tested concentration range of 0.1–10 µg/mL, with significant effects observed at low concentrations and brief pre-incubation times (from 1 min). At a concentration of 10 µg/mL, apoC3 suppressed platelet activation by approximately 70% in response to ADP and by approximately 40% in response to collagen stimulation. Depleting apoC3 from human serum enhanced platelet aggregation by more than 25 % (1.28 ± 0.19 vs. vehicle), indicating an endogenous regulatory function of apoC3. Mechanistically, apoC3 binding to platelets reduced both GPIIb/IIIa activation and P-selectin expression by around 20%. ApoC3 binding to platelets increased when platelets were activated by ADP and was partially mediated by GPIIb/IIIa, implicating this integrin as a functionally relevant receptor. Taken together, these findings reveal a novel link between apoC3 and platelet biology with potential implications for thrombotic risk and vascular homeostasis. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) characterized by oligodendrocyte (OLG) degeneration, myelin loss, and impaired remyelination. Apolipoprotein D (Apo D), a glia-derived lipocalin, has emerged in recent decades as a neuroprotective molecule involved in lipid transport, oxidative stress regulation, and inflammation control during aging and neurodegenerative diseases like MS. However, its role in demyelination/remyelination dynamics remains poorly defined. In this study, we used the cuprizone (CPZ)-induced demyelination model in C57BL/6 mice to analyze Apo D expression patterns in the corpus callosum during de- and remyelination. We also assessed whether the atypical antipsychotic clozapine (CLO), previously shown to upregulate Apo D in vivo, could modulate its expression and influence myelin recovery in this pathological context. Using a combination of magnetic resonance imaging, Luxol fast blue staining, and double immunohistochemistry, we demonstrated that CPZ treatment for 3 or 6 weeks led to significant demyelination, hydrocephalus, and reduced motor cortex thickness, which were partially reversed after treatment cessation. Apo D expression in OLGs was significantly reduced by CPZ exposure, both at the protein level and in terms of immunoreactive cell counts, but was restored following treatment withdrawal. Notably, co-administration of CLO prevented the CPZ-induced reduction in Apo D expression in OLGs, although it did not attenuate myelin loss. In this way, our results reveal a strong correlation between Apo D expression and OLG/myelin integrity in vivo. While CLO did not exert remyelinating effects, it preserved Apo D levels under demyelinating conditions, suggesting a potential indirect neuroprotective mechanism. These findings support the relevance of Apo D in CNS myelin homeostasis and highlight its potential as a molecular target for therapeutic intervention in demyelinating diseases such as MS. Full article

We investigated associations between apolipoprotein E (APOE) alleles and motor manifestations in Alzheimer’s dementia (AD) capitalizing on National Alzheimer’s Coordinating Center data: the baseline evaluations of older adults (≥60 years) with a diagnosis of AD were analyzed. Those with a concomitant diagnosis Parkinson’s disease or other parkinsonian syndrome, and those treated with anti-parkinsonian agents were excluded. Three APOE groups were formed: APOE2 (APOE2 carriers), APOE3 (APOE3/APOE3) and APOE4 (APOE4/APOE4, APOE4/APOE3). UPDRS-III was used to assess the presence or absence of motor signs in 9 domains. Adjusted binary logistic models featuring the three APOE groups as exposures and motor domains as outcomes were estimated. There were 389 individuals in the APOE2, 1799 in the APOE3 and 2791 in the APOE4 groups. Compared to the APOE2 group, individuals in the APOE4 group had lower odds of having at least one motor sign [0.64 (0.50–0.82)]. Among motor signs, rigidity [0.53 (0.34–0.81)], bradykinesia [0.56 (0.40–0.77)], impaired chair rise [0.54 (0.37–0.78)] and impaired posture-gait [0.54 (0.36, 0.81)] exhibited significant associations. Exploratory analyses featuring APOE genotypes suggested dose–response relationships for both APOE2 and APOE4. In conclusion, APOE2 confers a risk towards motor (mainly parkinsonian) signs in AD. APOE4 may have a protective effect. Full article

The mechanism of kidney injury associated with apolipoprotein L1 (APOL1) risk variants has remained elusive. Complicating this issue is the broad clinical spectrum of APOL1 kidney disease, which has engendered speculation that this reflects multiple mechanisms of kidney injury. APOL1 kidney disease can be rapid in onset with heavy proteinuria, associated with viral infections and categorized pathologically as collapsing focal segmental glomerulosclerosis. Alternatively, APOL1 kidney disease also may present as an insidious, slowly progressive disease, with less proteinuria but losses in glomerular filtration rate and with varied pathology. In addition to APOL1 kidney disease, APOL1 risk variants are also associated with preeclampsia and other conditions related to placental insufficiency. The outcome of these APOL1-associated pregnancy complications frequently results in prematurity and low birth weight, both of which are known risk factors for hypertension and kidney disease later in life due to reduced nephron endowment. The significance of APOL1 risk variants on pregnancy complications that predispose to kidney disease should not be overlooked as a central mechanism of APOL1 kidney disease, especially the insidious forms, which are difficult to distinguish from the spectrum of kidney disease attributable to prematurity and low birth weight. If low nephron endowment is a causal mechanism behind some forms of APOL1 kidney disease, this may have an impact on clinical trials evaluating drugs directly inhibiting APOL1, since in these instances, ongoing APOL1 expression may not be driving podocyte loss and progressive kidney dysfunction. Full article

Exposure to persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD) increases metabolic disorder risk. In this study, we show that a single intraperitoneal injection of TCDD (10 μg/kg) in C57BL/6J mice induced body weight gain, lipid accumulation in the liver and adipose tissue, macrophage infiltration, and elevated hepatic and serum triglyceride levels after 12 weeks. Despite serum aryl hydrocarbon receptor (AhR) ligand levels normalizing by 12 weeks, the persistent effects suggest TCDD sequestration in fat tissue. TCDD inhibited the expression of mitochondrial proteins (COX1, TOM20, TFAM, H2AX) and reduced mitochondrial oxygen consumption. Liver-specific AhR knockout ameliorated TCDD-induced mitochondrial dysfunction, lipid accumulation, and macrophage infiltration. Mechanistically, TCDD-induced hepatic plasminogen activator inhibitor-1 (PAI-1) promoted adipocyte hypertrophy. In the liver, PAI-1 disrupted the interaction between tissue-type plasminogen activator (tPA) and apolipoprotein B (ApoB), thereby enhancing very-low-density lipoprotein (VLDL) assembly. These findings reveal that hepatocyte-derived circulating PAI-1, upregulated via hepatic AhR activation, contributes to adipocyte hypertrophy and hepatosteatosis through the intracellular modulation of the tPA–PAI-1 axis. Thus, hepatic AhR activation drives mitochondrial dysfunction and obesity, even after a single TCDD exposure. Full article

Background/Objectives: Atherosclerosis is a major contributor to ischemic cardiovascular diseases (CVDs) such as myocardial infarction and stroke, which are leading causes of mortality and morbidity. The management of atherosclerosis through personalized nutrition has gained importance in recent years due to advancements in nutrigenomics, gut microbiome evaluation, and metabolomics. However, no systematic review has comprehensively evaluated the impact of personalized nutrition interventions on atherosclerotic plaque progression and clinical outcomes in humans. Methods: We adopted a systematic approach based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key databases like PubMed, Cochrane, Google Scholar, and MEDLINE via EBSCOhost were searched using predefined terms related to personalized nutrition, atherosclerosis, nutrigenomics, and clinical outcomes. Results: Evidence evaluation using the framework of Boffetta et al. for cumulative evidence on the joint effects of genes and environments strongly suggested significant diet–gene interactions. Polymorphisms in the apolipoprotein A-II (APOA2) gene have been shown to influence body mass index and lipid levels. Furthermore, studies have demonstrated that omega-3 polyunsaturated fatty acids (PUFAs) can modulate microRNA expression, thereby impacting lipid metabolism. Epigenetic studies showed that dietary components can modify histone acetylation and non-coding RNA activity, which ultimately influence gene expression related to inflammation and lipid metabolism, improving clinical outcomes in atherosclerosis management. Conclusions: Integrating personalized nutrition into clinical practice promises to enhance atherosclerosis outcomes through targeted dietary interventions. Advancements in personalized nutrition offer a promising pathway toward more effective and personalized approaches to cardiovascular health. Full article