Search Results (1,366)

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

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

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

Olfactory perception depends on soluble proteins in the perireceptor environment that support odorant transport, mucosal protection, and tissue homeostasis. In insects, odorant-binding proteins (OBPs) in the sensillum lymph are indispensable for odor detection, whereas in humans the indispensability of OBPs (OBP2A/2B) remains unclear because they are inconsistently detected in nasal mucus. Consequently, it remains unclear whether other soluble proteins compensate for this function or how they contribute to odorant processing and signal transmission within the olfactory mucus. Accumulating evidence indicates that OBP-like lipocalins (LCN1, LCN2, LCN15) and apolipoprotein D, together with bactericidal/permeability-increasing (BPI)-fold proteins, act as major mediators of odorant solubilization, antimicrobial defense, oxidative stress regulation, and extracellular matrix (ECM) remodeling. Alterations in those proteins and ECM organization are linked to idiopathic and age-related smell loss, chronic rhinosinusitis, and neurodegenerative disorders, underscoring their broad relevance at the interface of chemosensation, mucosal defense, and brain health. Major unresolved issues include the functional indispensability of human OBPs, the receptor-specific contributions of OBP-like proteins, and the mechanistic relationships linking olfactory proteome remodeling, sensory signaling, and disease progression. This review provides an integrative overview of structural and mechanistic insights, highlights current controversies, and proposes future research directions, including receptor–protein mapping, integrated structural–functional studies, structural–functional analysis of OBP–ECM networks, and clinical validation of OBP-related biomarkers. 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

Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, and utility. A guide for selecting the most appropriate model to study specific stages of dietary fat absorption is also presented. Ultimately, because each model carries inherent methodological constraints, integrative experimental strategies that combine complementary will be necessary to link mechanistic insights with physiological relevance. 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

Recent progress in laboratory medicine provides powerful tools for the detailed evaluation of cardiovascular risk in military populations. This study aimed to characterize cardiometabolic biomarker profiles across four Polish military groups through chemometric analysis. The study included 392 participants (336 men, 56 women, aged 19–56 years). In total, 23 serum biomarkers from lipid, metabolic, hepatic, hormonal, and bone axes, and lactate dehydrogenase (LDH) were analyzed. Random forest (RF) modeling and effect-size profiling identified group-specific signatures. Group 4 (exposed to extreme acceleration forces and ionizing radiation) exhibited a systemic stress and metabolic-load profile with higher N-terminal pro-B-type natriuretic peptide (NT-proBNP, 36.7 ± 48.2 pg/mL) and calcium (Ca, 10.4 ± 0.88 mg/dL), and lower parathyroid hormone (PTH, 15.4 ± 10.1 pg/mL) and C-terminal telopeptide of type I collagen (β-CTX, 0.22 ± 0.19 ng/mL). Group 2 (exposed to fuels and exhaust gases) and group 3 (exposed to vibration, noise, ionizing radiation) showed an atherogenic–hepatometabolic axis with elevated apolipoprotein B (apoB, 1.04 ± 0.31; 0.97 ± 0.29 g/L), non-high-density lipoprotein cholesterol (N-HDL, 151.0 ± 46.7; 147.0 ± 41.4 mg/dL), and alanine aminotransferase (ALT). Group 1 (exposed to a biological hazard) displayed higher glucose (Glu, 96.0 ± 25.6 mg/dL) and triglycerides (TG, 151.0 ± 113.0 mg/dL) with lower magnesium (Mg, 2.03 ± 0.27 mg/dL). RF modeling confirmed these constellations. This study was exploratory in nature, providing a foundation for future longitudinal research. These findings provide a rationale for tailored cardiovascular surveillance, although causal inference is limited by the cross-sectional design. Full article

Cardio-kidney-metabolic (CKM) syndrome represents an integrated clinical and molecular continuum encompassing metabolic dysfunction, cardiovascular disease and chronic kidney disease. This multidimensional disorder arises from interdependent biological pathways that extend beyond conventional risk factors. Emerging evidence highlights a group of adipokines and vascular modulators—including retinol-binding protein 4 (RBP4), lipocalin 2 (LCN2), apolipoprotein M (ApoM), Klotho and matrix Gla protein (MGP)—emerging molecular modulators with potential involvement in CKM pathophysiology. Pro-inflammatory adipokines such as RBP4 and LCN2 contribute to insulin resistance, oxidative stress and endothelial dysfunction. In contrast, protective molecules including ApoM and Klotho preserve nitric oxide bioavailability, lipid metabolism and antioxidant defense. MGP modulates vascular calcification and adipose remodeling, with its inactive form (dp-ucMGP) linked to vascular stiffness and renal decline. The combined dysregulation of these molecules sustains cycles of inflammation, oxidative stress and tissue remodeling that drive CKM progression. Collectively, current data support their dual role as biomarkers and therapeutic targets. Nonetheless, clinical translation remains limited, emphasizing the need for standardized assays, longitudinal validation, and integrative multimarker approaches within precision medicine frameworks for CKM syndrome. Full article

Human Immunodeficiency Virus (HIV) infection is associated with a wide spectrum of urological manifestations, reflecting both the direct effects of viral infection and the indirect consequences of immunosuppression, opportunistic infections, malignancies and long-term combined antiretroviral therapy (cART). This narrative review provides a contemporary, multifaceted overview of the clinical and pathological presentations of urological conditions in people living with HIV (PLWHIV), based on articles published between 1989 and 2025. Conditions discussed include HIV-associated nephropathy (HIVAN), opportunistic genitourinary infections, malignancies such as Kaposi sarcoma and lymphoma, as well as non-infectious complications such as HIV-associated nephropathy and erectile dysfunction (ED). The review highlights the evolving epidemiology of these conditions in the cART era, with a noted decline in opportunistic infections but a rising burden of chronic kidney disease and malignancies, largely due to improved survival and ageing of the HIV-positive population. Pathological insights are explored and discussed, including mechanisms of HIV-associated renal injury, such as direct viral infection of renal epithelial cells and genetic predispositions linked to Apolipoprotein L1 (APOL1) variants. In addition, psychosocial factors, including anxiety, stress, stigma, and alcohol use, are discussed, as they may contribute to late presentation to clinical urology services. The review also considers the challenges faced in low and middle-income countries, the impact of HIV on urological services, and the important role of palliative care in advanced disease. Ultimately, this review underscores the need for early recognition, comprehensive diagnostic and surgical evaluation, and integrated social, psychological, and palliative management strategies tailored to the unique needs of PLWHIV. A deeper understanding of the interplay between HIV, cART, psychosocial determinants, and urological health is essential for improving patient outcomes and guiding future research in this evolving field. Full article

This study aimed to investigate the role and underlying mechanism of apolipoprotein C2 (APOC2) in the progression of clear cell renal cell carcinoma (ccRCC). Analysis of The Cancer Genome Atlas (TCGA) datasets, combined with validation in ccRCC cell lines, revealed that APOC2 was markedly upregulated in ccRCC tissues and cells and was associated with poor patient prognosis. Functional assays demonstrated that APOC2 knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistic studies showed that silencing APOC2 reduced the phosphorylation levels of key components of the JAK-STAT signaling pathway, including Jak1/2 and STAT3, without affecting their total protein expression. Gene enrichment analysis further indicated the involvement of JAK-STAT signaling, and functional rescue experiments using the STAT3 agonist Colivelin partially reversed the decreased cell viability and increased apoptosis caused by APOC2 knockdown, confirming the pathway’s mediating role. Collectively, these findings suggest that APOC2 promotes ccRCC cell proliferation and inhibits apoptosis, at least in part, through activation of the JAK-STAT signaling pathway, highlighting APOC2 as a novel oncogenic regulator and potential therapeutic target, and providing new insight into the metabolic–inflammatory axis in ccRCC progression. Clinically, APOC2 may serve as a biomarker to identify ccRCC patients with hyperactivated JAK-STAT signaling and could potentially guide combination therapies involving JAK/STAT inhibitors or metabolic-targeted agents. Full article

Astaxanthin has attracted considerable interest, owing to its potent antioxidant and pigmentation properties. To investigate its effects of astaxanthin on body color variation in Lutjanus erythropterus, fish were divided into a control group and a treatment group fed an astaxanthin-supplemented diet. Body color parameters, growth performance, and liver antioxidant enzyme activities were measured at the end of the experiment. Tissues, including skin, intestine, liver, and blood, were subsequently collected for transcriptome sequencing. The results demonstrate that the astaxanthin-treatment group exhibited significantly enhanced body coloration alongside improved body length, body weight, and specific growth rate compared to the control group (p < 0.05). Specifically regarding the red–green value (a*), the treatment group showed significantly higher values on the ventral skin, dorsal skin, and gill cover (p < 0.05). The yellow–blue (b*) and lightness (L*) values were also significantly elevated in the ventral skin and gill cover (p < 0.05), although no significant differences were observed in the dorsal skin (p > 0.05). The skin was identified as the tissue with the highest total carotenoid content. Astaxanthin supplementation enhanced liver antioxidant capacity, evidenced by significantly elevated total superoxide dismutase (T-SOD) activity and significantly reduced malondialdehyde (MDA) levels in the treatment group (p < 0.05). Catalase (CAT) activity did not differ significantly between groups (p > 0.05). Transcriptomic analysis identified several coloration-associated genes, such as bco1, bco2, gstt1, and gstz1. It also revealed significant enrichment in key metabolic pathways (fatty acid, cholesterol, and retinol metabolism) and signaling pathways (PPAR and PI3K-Akt). Furthermore, the expression of multiple solute-carrier family members and apolipoproteins was detected, with notable enrichment in lipid digestion and absorption, cholesterol metabolism, and several key immune-related signaling pathways. These findings provide a theoretical basis for understanding the molecular mechanisms of carotenoid-mediated pigmentation in L. erythropterus. Full article

Extracellular vesicles (EVs) are nanosized structures involved in intercellular communication that have high potential as disease biomarkers and for the delivery of therapeutic cargos. However, translation to the clinic is hampered by time-consuming, low-yield, and poorly reproducible EV isolation methods. We describe a cryogel-based immunoaffinity chromatography system that exploits single-domain VHH antibodies as capture elements for the selective isolation of EVs from human plasma. Supermacroporous cryogels functionalized with five unique anti-EV VHHs (total immobilization capacity ~500 µg/g) were prepared, yielding a highly permeable and hydrophilic support. They were captured and eluted under mild conditions, and their morphology and identity were confirmed by SEM, AFM, NTA, and flow cytometry. Proteomic profiling of the isolated samples identified 234 proteins, of which 63% were ExoCarta-listed exosomal proteins; contaminants such as albumin and apolipoproteins were also identified. The purification method provided samples with ~2 × 10⁹ EVs/mL, with EV median size of 135 nm and consistent protein-to-lipid ratio across three independent isolations (CV < 10%). This study demonstrates that VHH-functionalized cryogels (VHH-SMC) are a rapid and reproducible EV purification method that represents a promising alternative to conventional ultracentrifugation- or precipitation-based protocols. While optimization of nanobody density and reduction in plasma protein carryover are still necessary, the platform holds potential for scalable EV enrichment, a condition that can significantly speed up biomarker research and clinical diagnostics. Full article

Insulin resistance (IR) contributes to atherogenic dyslipidemia and elevated ASCVD risk. Apolipoprotein A1 (ApoA1)-associated lipoproteins have diverse anti-atherogenic functions, but it is unclear whether IR drives adverse changes in their proteomic composition. We hypothesized that IR is associated with an atherogenic ApoA1 proteome and that insulin-sensitizing interventions would improve its composition. We studied 861 participants without diabetes (age 47 ± 12 years, 65.5% female). IR was directly measured using the steady-state plasma glucose (SSPG) concentration via the insulin suppression test. ApoA1-associated proteins were quantified by mass spectrometry. A subset underwent interventions for 3 months (N total 108): pioglitazone, PIO n = 38 or weight loss, WL n = 70). Paired t-tests assessed pre- and post-intervention changes. At baseline, several ApoA1-associated proteins significantly correlated with SSPG. Both interventions improved IR (p < 0.01). PIO led to significant increases in 14 ApoA1-associated proteins, including ApoC1–C4, ApoA2, ApoA4, ApoD, ApoE, LCAT, and PON1/3. WL increased several ApoA1-associated proteins, including ApoA4, ApoD, ApoM, and PON1/3. In conclusion, IR is associated with a pro-atherogenic ApoA1 proteome, and both interventions improve this profile. However, PIO has a broader proteomic impact. These findings highlight the potential of targeting the ApoA1 proteome to reduce residual ASCVD risk. Full article