Search Results (2,720)

In this study, the rank of multifaceted activity of catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG) was addressed. Their antioxidant activity was determined by the differential pulse voltammetry (DPV), whereas their ability to inhibit angiotensin-converting enzyme (ACE) activity, acetylcholinesterase activity (AChE), and formation of the advanced glycation end-products (AGEs) was performed in a model system to show their importance against hypertension, Alzheimer-type dementia, and diabetic’s complication, respectively. The order of the antioxidant potential of catechins in comparision to gallic acid (GA) was EGCG > ECG > EC > EGC ≈ C > GA, whereas the order of the ACE inhibitory activity was EGCG > ECG > EGC > EC > C, thus indicating the importance of the structure–activity relationship. The correlation between IC₅₀ for ACE inhibition of catechins and their antioxidant activity had the value r = −0.60. The order of the AChE enzyme inhibitory activity was EGCG ≈ EGC > ECG > EC > C, and the weak positive correlation between IC₅₀ and the first anodic peak potential (E_pa1) values was noted (r = 0.67). The ranking of the anti-AGE activities was EGCG ≈ ECG > EGC > EC > C, and a negative correlation between the inhibitory activity of catechins against AGE formation and their antioxidant activity was r = −0.82, whereas a positive correlation (r = 0.88) was noted between their first anodic peak potential (E_pa1) values. The provided results expand our knowledge on the multifaceted activity of catechins, indicating EGCG and ECG as the most active antioxidants against inhibition of ACE and AChE as well as towards AGE formation. Full article

Background/Objectives: Advanced glycation end products (AGEs) accumulate in long-lived extracellular matrix proteins and have been implicated in skin aging and tissue remodeling, particularly in photo-exposed skin. High-frequency ultrasound (HFU) offers a non-invasive assessment of structural skin parameters that may reflect these changes. This study aimed to explore the associations between serum AGEs and HFU-derived structural parameters of cervico-facial skin, with a focus on UV-exposed dermal tissue. Methods: This cross-sectional study included 113 adults recruited in Cluj-Napoca, Romania. Fasting serum samples were analyzed for fructosyl-lysine (FruLys), pyrraline (Pyr), methylglyoxal-derived hydroimidazolone-1 (MG-H1), carboxyethyl-lysine (CEL), carboxymethyl-lysine (CML), arginine (Arg), and lysine (Lys). HFU, using a 22 MHz probe, was performed on the left zygomatic area to assess epidermal depth and density, UV-exposed dermal damage depth and density, dermis depth and density, and subcutaneous tissue depth and density. Associations between serum AGEs and HFU parameters were evaluated using Spearman correlation, with Benjamini–Hochberg false discovery rate (FDR) correction for multiple testing. Results: After FDR correction, epidermal depth was inversely correlated with serum CML (r = −0.402, adjusted p = 0.018). UV-exposed dermal density was inversely correlated with serum Pyr (r = −0.547, adjusted p < 0.019), Arg (r = −0.369, adjusted p < 0.019), and Lys (r = −0.270, adjusted p < 0.019). Subcutaneous tissue depth was also inversely correlated with serum CML (r = −0.290, adjusted p = 0.020). Conclusions: The study showed that higher levels of specific serum AGEs were associated with selected HFU-derived structural alterations in cervico-facial skin, particularly in UV-exposed dermal tissue. These exploratory findings support the biological plausibility that systemic glycation may be reflected by non-invasive skin ultrasound parameters. Full article

Background/Objectives: Vitamin D plays an important role in glucose metabolism, lipid regulation, and inflammatory processes, and has been implicated in cardiometabolic health. However, its associations with specific metabolic biomarkers remain inconsistent, particularly in older adults. This study aimed to examine whether vitamin D deficiency is differentially associated with multiple metabolic biomarkers in a nationally representative sample of older adults. Methods: This cross-sectional study used data from the 2024 Korea National Health and Nutrition Examination Survey, including 1806 adults aged ≥65 years. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D levels < 20 ng/mL. Metabolic biomarkers included fasting glucose, glycated hemoglobin (HbA1c), triglycerides, C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), waist circumference, and body mass index (BMI). Complex sample linear regression analyses were performed with sequential adjustment for sociodemographic factors, health behaviors, and comorbidities. Results: In unadjusted analyses, vitamin D deficiency was associated with adverse metabolic profiles, including higher fasting glucose, HbA1c, triglycerides, waist circumference, and CRP levels, and lower HDL-C levels. After adjustment for sociodemographic factors, health behaviors, and comorbidities, significant associations remained for HbA1c (β = 0.10, p = 0.034), triglycerides (β = 0.10, p = 0.003), and waist circumference (β = 1.21, p = 0.040). No significant associations were observed for fasting glucose, HDL-C, CRP, or BMI. Conclusions: Vitamin D deficiency was independently associated with poorer long-term glycemic status, hypertriglyceridemia, and central adiposity in older adults, but not with other metabolic markers after adjustment. These findings suggest that the metabolic correlates of vitamin D deficiency may be domain-specific rather than generalized. Longitudinal and interventional studies are needed to clarify causality and underlying mechanisms. Full article

The degradation of plastic waste leads to the release of numerous chemical additives, including phthalate plasticizers, which have been implicated in the pathogenesis of metabolic disorders. Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer whose primary metabolite, mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), has been associated with multiple metabolic diseases. In this study, we applied an integrated approach combining network toxicology and molecular docking to systematically investigate the potential mechanistic role of MECPP in metabolic dysregulation. Our strategy included multi-platform target prediction, disease gene association analysis, functional enrichment, protein–protein interaction network construction, and molecular docking analysis. The results suggested that MECPP may be associated with six common core targets, including BCL2, BCL2L1, MAPK14, MMP2, MMP9, and TNFRSF1A, which are mainly involved in apoptosis, inflammatory regulation, and extracellular matrix remodeling. Pathway enrichment analysis further indicated the potential involvement of several disease-overlapping pathways, including insulin resistance, neuroactive ligand–receptor interaction, efferocytosis, advanced glycation end product–receptor for advanced glycation end product (AGE–RAGE) signaling, phospholipase D signaling, and renin secretion. Overall, these findings suggest that MECPP may contribute to metabolic dysregulation through overlapping molecular mechanisms across multiple diseases. This study provides a computational basis for future experimental validation and environmental risk assessment. Full article

Leucine-rich repeat kinase 2 (LRRK2) is a multidomain serine/threonine kinase and a major genetic contributor to Parkinson’s disease (PD). Although LRRK2 has been extensively studied in neurodegeneration, emerging evidence indicates that it also plays a critical role in systemic metabolism. LRRK2 regulates glucose homeostasis through modulation of insulin signaling, vesicle trafficking, mitochondrial function, and inflammatory responses. Studies using LRRK2 knockout and knock-in models, including the pathogenic G2019S mutation, have revealed abnormalities in insulin sensitivity, adipose tissue inflammation, hepatic glucose production, and skeletal muscle metabolism. Mechanistically, LRRK2 phosphorylates Rab GTPases, thereby controlling insulin receptor trafficking and GLUT4 translocation. In addition, LRRK2 influences mitochondrial dynamics and reactive oxygen species production, linking metabolic stress to inflammatory signaling. Importantly, LRRK2 also regulates innate immune pathways, including TLR4–NFκB signaling and inflammasome activation, thereby connecting peripheral metabolic dysfunction to neuroinflammation. Here, we propose an integrated metabolic–neuroinflammatory crosstalk model in which LRRK2 functions as a molecular coordinator linking peripheral metabolic dysfunction to central neurodegeneration. In this framework, systemic metabolic stress—characterized by insulin resistance, chronic inflammation, advanced glycation end product (AGE) accumulation, and blood–brain barrier disruption—drives microglial activation and neurodegenerative processes. Understanding this systemic axis may provide new therapeutic opportunities targeting both metabolic dysfunction and neurodegeneration in PD. Full article

Benign prostatic hyperplasia (BPH) is an age-related disorder increasingly linked to chronic inflammation and redox imbalance, yet its systemic oxidative and nitrosative profile remains insufficiently characterized. In this cross-sectional study, fasting serum samples were collected from 47 men with clinically confirmed BPH scheduled for transurethral resection of the prostate and 40 healthy controls. We assessed antioxidant status (thiols, total antioxidant capacity), lipid peroxidation (malondialdehyde, 4-hydroxynonenal), protein nitration (3-nitrotyrosine), glycoxidation markers (Amadori products, advanced glycation end products (AGE)-associated fluorescence), and tryptophan metabolism indices (tryptophan, kynurenine, N′-formylkynurenine). Compared with controls, BPH patients showed significantly lower antioxidant capacity and thiol levels, together with increased lipid peroxidation and protein nitration. AGE-associated fluorescence was modestly elevated, whereas Amadori products and advanced oxidation protein products did not differ significantly. Tryptophan metabolism was markedly altered, with lower tryptophan and higher kynurenine and N′-formylkynurenine, indicating activation of the kynurenine pathway. After false discovery rate correction, most redox biomarkers remained significant. Multivariable logistic regression confirmed independent associations of lipid peroxidation, nitrosative stress, and kynurenine pathway activation with BPH after adjustment for age and metabolic parameters. These findings support a role for systemic oxidative and inflammatory mechanisms in BPH pathophysiology, although confirmation in age-matched and longitudinal studies is needed. Full article

Diabetes mellitus affects an estimated 589 million adults globally, and cutaneous manifestations occur in up to 70% of affected individuals during the course of the disease. The objective of this narrative review is to examine the intersection of diabetes mellitus, skin aging, cosmetic dermatologic procedures, and regenerative therapies, with an emphasis on evidence-based best practices and clinical considerations. While the impaired wound healing associated with diabetes has been extensively studied, the aesthetic implications of diabetic skin disease remain comparatively underexplored. Individuals with diabetes frequently exhibit features of accelerated cutaneous aging, including premature wrinkling, dyschromia, xerosis, alopecia, and other cosmetically significant dermatoses that may negatively impact quality of life. In parallel, the demand for aesthetic dermatologic procedures among patients with diabetes has increased substantially; however, evidence-based recommendations guiding the safe and effective use of cosmetic interventions in this population remain limited. Diabetic skin demonstrates accelerated biological aging driven by complex pathophysiological mechanisms, including the accumulation of advanced glycation end products, chronic low-grade inflammation, oxidative stress, microvascular dysfunction, and neuropathy. These processes partially overlap with chronological aging and photoaging but are mechanistically distinct and may influence tissue repair, inflammatory responses, and the safety profile of commonly performed aesthetic procedures such as chemical peels, laser resurfacing, dermal fillers, neuromodulators, and microneedling. Emerging regenerative approaches, including platelet-rich plasma, platelet lysate, and mesenchymal stromal cell-derived products such as exosomes and secretomes, have attracted increasing attention as biologically targeted strategies for cutaneous rejuvenation. Nevertheless, clinical evidence specifically addressing aesthetic interventions in diabetic populations remains limited. A diabetes-informed approach to aesthetic dermatology that considers metabolic status, procedure selection, and post-procedural monitoring is therefore essential to optimize safety and therapeutic outcomes. Full article

Impaired wound healing is a major cause of morbidity among patients with diabetes. Human α1-antitrypsin (hAAT) promotes the resolution of injured tissues. In hyperglycemic conditions, circulating hAAT is likely to undergo glycation, yet it is unknown whether its reparative properties are preserved. We hypothesized that clinical-grade hAAT treatment, but not deliberately glycated hAAT (gly-hAAT), would promote wound repair under hyperglycemic conditions. Mice were rendered hyperglycemic, excisional wounding was performed, and wounds were treated with topical albumin or hAAT every three days. The wound area was assessed, and samples were collected for histology and gene expression analysis. Gly-hAAT was generated from clinical-grade hAAT, after which in vitro RAW 264.7 macrophage responses and re-epithelialization of A549 cells were assessed. Gap closure was further assessed using sera from a human cohort (prospective samples from 10 patients with poorly controlled diabetes at Soroka University Medical Center, Beer-Sheva, Israel, 2018). Group comparisons were performed using one-way ANOVA with Tukey’s post hoc test. hAAT accelerated in vivo wound closure and in vitro A549 cell gap closure, accompanied by an anti-inflammatory IL-1Ra/IL-1β gene expression profile. In contrast, gly-hAAT inhibited normoglycemic mouse wound closure, evoked an inflammatory response in macrophages, and interfered with A549 cell gap closure; concomitant hAAT treatment improved gap closure. Similarly, patient serum inhibited A549 gap closure, and concomitant hAAT treatment improved gap closure. Importantly, inferential statistical analysis was not performed on this outcome due to the small and heterogeneous human cohort. In conclusion, hAAT accelerated wound closure in hyperglycemic mice and in A549 cells, whereas gly-hAAT promoted inflammatory responses and impaired wound closure, a trend reversed by native hAAT. These findings support the concept that glycation undermines the beneficial functions of circulating hAAT and provides a mechanistic insight into the pathophysiology of diabetic wound healing. Further studies are warranted to evaluate clinical-grade hAAT as a potential therapeutic for hyperglycemia-associated impaired wound healing. Full article

Background: Obstructive sleep apnea (OSA) is a common but underrecognized sleep-related breathing disorder characterized by intermittent hypoxemia and autonomic dysfunction. OSA prevalence and clinical relevance in Type 1 Diabetes Mellitus (T1DM), particularly in relation to diabetes-related vascular complications, remain insufficiently explored. Objective: The aim of this study was to evaluate the prevalence of high-risk OSA in adults with T1DM and controls, and to investigate the association between high-risk OSA and microvascular complications among individuals with T1DM. Methods: In this cross-sectional case–control study, 102 adults with T1DM and 126 controls were included. OSA risk was assessed using the modified Berlin Questionnaire (mBQ). Analyses of vascular complications were restricted to participants with T1DM. Multivariable logistic regression models adjusted for age and sex were used to assess associations, with additional adjustments for body mass index, hypertension, current smoking, alcohol use and glycated hemoglobin A1c. Results: High-risk OSA was identified in 18.6% of individuals with T1DM and 11.9% of controls, with no significant difference between groups. Among participants with T1DM, the prevalence of microvascular complications (retinopathy and/or neuropathy) was substantially higher in those with high-risk OSA compared with those at low risk (68.4% vs. 18.07%, p <0.001). In univariate logistic regression analysis, high-risk OSA was significantly associated with microvascular complications (odds ratio [OR] 4.85; 95% confidence interval [CI] 1.65–14.24; p = 0.004). This association remained significant in the fully adjusted model (OR 5.55; 95% CI 1.36–22.65; p = 0.017). Conclusions: High-risk OSA is not more prevalent in adults with T1DM compared with controls; however, among individuals with T1DM, high-risk OSA is strongly and independently associated with microvascular complications. Given the potential contribution of diabetic microvascular and autonomic neuropathy to upper airway dysfunction, the relationship between OSA and vascular complications in T1DM may be bidirectional, warranting further longitudinal investigation. Full article

Background/Objectives: Chronic diseases pose a major challenge for healthcare systems, requiring integrated, patient-centered approaches that combine clinical management, prevention, and self-care. Lifestyle Medicine (LM) and lifestyle in general offers complementary frameworks to address these needs. However, the potential integration of LM within community nursing—particularly through the role of Family and Community Nurse (FCN)—has not been comprehensively synthesized. This narrative review aimed to synthesize international evidence on the role of community nursing—particularly FCN—in integrating chronic care management and LM view. Methods: For quality assessment, a narrative review was conducted in accordance with the SANRA criteria to enable the integration of heterogeneous evidence and a comprehensive synthesis of this complex topic. Literature searches were performed in the PubMed–Medline database, and the final screening of references from included studies was used to identify relevant manuscripts. Primary studies published in English over the past ten years were screened and analyzed using the PICOS framework. Sixteen eligible studies were included in the final synthesis. Results: The included studies indicated that nurse-led community interventions in LM view were associated with improvements in self-management, treatment adherence, and selected clinical outcomes, such as blood pressure, glycated hemoglobin, and physical activity levels. Empowerment-based approaches and the use of digital or telehealth tools supported patient engagement and health literacy. At the organizational level, multidisciplinary collaboration, shared protocols, and professional leadership emerged as key factors in sustaining continuity and quality of care, while organizational fragmentation and limited training in behavioral counseling were commonly reported barriers. Conclusions: Community nursing, particularly through FCNs, plays a relevant role in integrating chronic care management and LM approaches, contributing to improved self-management, treatment adherence, and selected clinical outcomes. The evidence highlights the importance of empowerment-based interventions, digital support tools, and multidisciplinary collaboration in enhancing care continuity and patient engagement. Addressing organizational barriers and strengthening behavioral counseling training remain essential to support effective implementation in community settings. Full article

Glycation of superoxide dismutase 1 (SOD1) has been shown to modulate the cytosolic levels of phosphorylated TAR DNA-binding protein 43 (TDP-43), a hallmark of amyotrophic lateral sclerosis (ALS) pathology. In this study, we investigated the interaction between TDP-43 and SOD1 and assessed how methylglyoxal (MGO)-induced glycation and the ALS-associated G93A SOD1 mutation affect this interplay in H4 cells. MGO exposure reduced SOD1 activity and TDP-43 phosphorylation in cells expressing WT SOD1, but not in those expressing G93A SOD1. Both WT and mutant SOD1 interacted with TDP-43 in the nucleus and cytosol; however, cytosolic interactions were more prevalent in G93A-expressing cells. Although MGO did not significantly alter the overall interaction between TDP-43 and WT SOD1, it induced cytosolic inclusion formation at 0.4 mM, a concentration associated with reduced cell viability. These inclusions did not colocalize with stress granules, indicating alternative aggregation pathways. Treatment with cyclosporin A, which inhibits the phosphatase calcineurin, decreased both TDP-43–WT SOD1 inclusions and cytosolic interactions between TDP-43 and G93A SOD1. Together, these findings suggest that SOD1 damage, induced by glycation or ALS-linked mutation, may affect TDP-43 phosphorylation status and promote its cytosolic mislocalization and aggregation, providing new insights into ALS-associated proteinopathy. Full article

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) is a prevalent metabolic disorder associated with major cardiovascular and metabolic complications. Regular physical activity is recommended for glycaemic management, but barriers such as obesity, joint pain, and impaired mobility may limit participation in land-based exercise. Aquatic exercise may provide a feasible alternative as water buoyancy reduces joint loading while allowing aerobic and resistance training. This systematic review and meta-analysis evaluated the effects of aquatic exercise interventions on glycaemic control in adults with T2DM. Methods: The review followed the PRISMA 2020 guidelines. MEDLINE, Cochrane CENTRAL, Scopus, Web of Science, and IEEE Xplore databases were searched. Randomised and non-randomised longitudinal studies involving adults aged ≥35 years with T2DM participating in structured aquatic exercise programmes were eligible. The primary outcome was glycated haemoglobin (HbA1c). Risk of bias was assessed using RoB 2 and RoBANS 2, and certainty of evidence was evaluated using GRADE. Random-effects meta-analysis calculated mean differences (MDs) with 95% confidence intervals. Results: Eleven randomised controlled trials involving 335 participants were included. Aquatic exercise significantly reduced HbA1c compared with passive control conditions (MD = −0.76%; 95% CI −1.21 to −0.32), although heterogeneity was high. No significant differences were observed between aquatic and land-based exercise interventions. Eight studies used wearable heart-rate monitors to regulate exercise intensity. Conclusions: Aquatic exercise may improve glycaemic control compared with sedentary conditions and yields effects comparable to those of land-based exercise in adults with T2DM. Further high-quality trials are needed to clarify optimal exercise dose–response and evaluate more advanced wearable technologies. Full article

The aim of this study was to evaluate the feasibility of inducing non-enzymatic browning using enzymatic collagen hydrolysates from turkey knee cartilage and chondroitin sulfate disaccharides derived from turkey and shark cartilage. Glycation was carried out in aqueous solutions at 60–120 °C for 3 h. After glycation, furosine content and browning intensity were determined as indicators of intermediate and final Maillard reaction products. FTIR spectra, color parameters, and antioxidant properties were also analyzed. The results showed that chondroitin sulfate disaccharides were more reactive with collagen hydrolysates than glucose and produced glycation products with higher antioxidant activity. The sulfation site on the N-acetylgalactosamine residue linked to glucuronic acid influenced the characteristics of the Maillard reaction products, including higher antioxidant activity and increased redness in products derived from turkey chondroitin sulfate disaccharides compared with those derived from shark cartilage, despite very similar FTIR spectral characteristics. Full article

Diagnosis and monitoring of type 2 diabetes mellitus (T2DM) typically rely on invasive blood-based biomarkers. To explore non-invasive alternatives, this study examined tongue coating metabolites to identify metabolic signatures linked to diabetes progression. A case-control observational study categorized participants into control, prediabetes, and diabetes groups. Tongue coating samples were analyzed using liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were correlated with clinical parameters, including HbA1c, BMI, and eGFR. Distinct metabolic profiles emerged across groups, with significant differences in five endogenous metabolites (phenylpyruvic acid, propionylcarnitine, pyridoxal 5′-phosphate, phenethylamine, phenethylamine glucuronide) and four amino acids (isoleucine, lysine, phenylalanine, tyrosine). Diabetic subjects showed elevated phenylpyruvic acid and phenethylamine, while propionylcarnitine, pyridoxal 5′-phosphate, and phenethylamine glucuronide were reduced. Phenethylamine was positively correlated with HbA1c; propionylcarnitine and phenethylamine glucuronide showed negative correlations with HbA1c and BMI. Detected total amino acids were inversely correlated with eGFR. Additionally, a diabetes index derived from these metabolic features also holds potential for discriminating disease states. These findings underscore the potential of tongue coating metabolites as a relatively non-invasive approach for evaluating T2DM states. The observed metabolic alterations provide valuable insights into diabetes-associated dysregulation, including protein glycation, obesity-related metabolic shifts, and renal impairment. Full article

Protein glycation is a nonenzymatic modification that links sugar chemistry to molecular aging and chronic disease. Sequential reactions involving Schiff bases, Amadori products, and reactive α dicarbonyl intermediates generate advanced glycation end products (AGEs) that irreversibly alter protein structure and function. AGEs also act as ligands for the receptor for advanced glycation end products (RAGE), initiating oxidative stress, inflammation, and tissue remodeling. This review synthesizes the molecular pathways of AGE formation, their structural diversity, and the biological factors influencing glycation kinetics. Advances in analytical detection methods—including fluorescence spectroscopy, LC–MS/MS, and immunochemical approaches—are highlighted for their role in monitoring AGE accumulation. Particular attention is given to the contribution of glycation to diabetes, cardiovascular disease, neurodegeneration, and cancer, alongside emerging therapeutic strategies to limit AGE formation or block AGE–RAGE signaling. Glycation thus represents a central mechanism in human disease pathogenesis and an emerging therapeutic frontier. Full article