Search Results (1,566)

Background/Objectives: Osteoarthritis (OA) is characterized by cartilage degeneration, extracellular matrix (ECM) disruption, inflammation, and impaired joint function. A standardized phytosterol-rich avocado/soybean unsaponifiable preparation (CHL) was examined in monosodium iodoacetate (MIA)-induced OA in Sprague–Dawley rats. Methods: Rats were orally administered low-, medium-, or high-dose CHL for 2 weeks before and 4 weeks after MIA induction. Results: CHL attenuated MIA-induced weight-bearing deficits and structural joint abnormalities. CHL also reduced cartilage degradation markers, including cartilage oligomeric matrix proteins and the C-terminal crosslinked telopeptide of type II collagen. CHL alleviated systemic inflammation by reducing serum interleukin-6, tumor necrosis factor-α, and prostaglandin E2 levels. Furthermore, CHL decreased the serum levels of matrix metalloproteinases (MMP)-1, MMP-2, MMP-9, and MMP-13, indicating reduced matrix-degrading responses. In joint cartilage tissues, CHL suppressed the mRNA expression of pro-inflammatory mediators and catabolic genes, such as Mmp1, Mmp3, and Mmp9. Additionally, CHL modulated cartilage anabolism and ECM-related markers by reducing collagen type I alpha 1 chain expression and enhancing SRY-box transcription factor 9, tissue inhibitor of metalloproteinase 1, and collagen type II alpha 1 chain expression. High-resolution liquid chromatography-mass spectrometry profiling of CHL revealed several tentatively identified compounds, such as (+)-discodermolide, epicoccamide, and brasilicardin C. Conclusions: Overall, these findings indicate that CHL may attenuate MIA-induced OA-associated functional impairment, structural alterations, inflammation, and cartilage matrix degradation, with medium doses showing the strongest protective effects. However, because CHL administration was initiated before OA induction, these findings primarily reflect preventive/protective effects and may not directly represent the therapeutic efficacy of CHL in established OA. Full article

Chronic stress is associated with changes in cognitive performance involving oxidative stress and inflammatory responses. This study investigated the bioactive compounds, antioxidant and acetylcholinesterase (AChE) inhibitory activities, and potential effects of Dictyophora indusiata (D. indusiata) on cognitive performance in an unpredictable chronic mild stress (UCMS) mouse model. D. indusiata extracts contained phenolics, flavonoids, polysaccharides, and ergosterol. These extracts exhibited in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities. Oral administration of D. indusiata powder improved performance on cognitive tasks in UCMS mice, as assessed using the Y-maze test, novel object recognition test, and Morris water maze test. These improvements were accompanied by upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, downregulated Kelch-like ECH-associated protein 1 (Keap1) mRNA expression, increased superoxide dismutase (SOD) and catalase (CAT) activities, and reduced malondialdehyde (MDA) levels in the frontal cortex and hippocampus, suggesting potential involvement of the Keap1–Nrf2 signaling pathway. Furthermore, D. indusiata reduced mRNA expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Taken together, these findings suggest potential involvement of antioxidant defense and inflammatory responses in the effects of D. indusiata on cognitive performance under chronic stress, while the relevance of in vitro AChE inhibition warrants further investigation. Full article

Background/Objectives: This study examined whether dexamethasone (Dex) and decanoic acid (DA) exert complementary effects on inflammatory signaling, catabolic gene expression, and peroxisome proliferator-activated receptor gamma (PPARγ) activation in human chondrocytes. Methods: Two donor-specific primary human chondrocyte models, each derived from a single knee donor, were used, in which cells were treated with Dex (≤0.1 µM), DA (≤500 µM), or combinations thereof. Acute Interleukin-1β(IL-1β)-induced PGE₂ release was evaluated in normal donor cells, whereas prolonged transcriptional responses and PPARγ DNA-binding activity were evaluated in OA donor cells. IL-1β-induced prostaglandin E₂ (PGE₂) release was measured by competitive ELISA after 24 h. Glyceraldehyde-3-phosphate dehydrogenase-normalized transcription of Collagen type II alpha 1, Collagen type I alpha 1, Aggrecan, SRY-Box Transcription Factor 9, Runt-Related Transcription Factor 2, and Matrix Metalloproteinase 13 (MMP13) was assessed by qRT-PCR at 7, 10–14, and 20–28 days. In addition, PPARγ DNA-binding activity was measured after 1 week. Interactions were evaluated by Loewe additivity and highest single agent (HSA) analyses. Results: Dex and DA each reduced PGE₂ release, whereas co-treatment increased potency and maximal inhibition, with a Loewe combination index of 0.4 at 1 nM Dex plus 19 µM DA. In the temporal analysis, Dex plus DA showed a positive MMP13 ΔCt difference versus Dex at 10–14 days (2.42 ± 2.14; p = 0.065) and a more consistent difference at 20–28 days (1.11 ± 0.25; p = 0.016). This agreed with fixed-dose HSA findings at 14 and 28 days (ΔHSA ≈ −75 for 0.1 µM Dex plus 100 µM DA versus Dex). Co-treatment was also associated with increased PPARγ activation beyond the HSA reference (ΔHSA ≈ 0.09 for 0.1 µM Dex plus 100–250 µM DA versus Dex). Conclusions: Dex plus DA co-treatment produced complementary effects on acute PGE₂ inhibition, as well as late-onset MMP13 suppression and PPARγ activity in the donor-specific chondrocyte models studied. These hypothesis-generating findings provide an in vitro rationale for future evaluation of this combination as a corticosteroid-sparing strategy. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation. Full article

Allergic asthma is characterized by Th2-driven airway inflammation. Indoleamine 2,3-dioxygenase (IDO) maintains immune tolerance, but its role in modulating the anti-inflammatory actions of Curcumin (CN) is unclear. This study investigated whether CN retains efficacy in a rat model of Ovalbumin (OVA)-induced airway inflammation under pharmacological IDO inhibition. Rats were sensitized and challenged with OVA and treated with methylprednisolone (MP, 15 mg/kg), CN (200 mg/kg), the IDO inhibitor 1-MT (70 mg/kg), or CN+1-MT. Assessments included systemic and pulmonary leukocyte profile, delayed-type hypersensitivity (DTH), OVA-specific IgE, bronchoalveolar lavage fluid (BALF) inflammatory cells and nitric oxide (NO) levels, lung wet/dry weight ratio, gene expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-6, Cxcr2 and transcription factor Nfkb1 and lung histopathology. CN alone or combined with 1-MT normalized leukocyte counts, suppressed eosinophilic and neutrophilic infiltration, restored BALF NO levels, reduced DTH response and OVA-specific IgE, decreased pulmonary edema, and preserved pulmonary vascular integrity. CN significantly attenuated TNF-α, IL-4, IL-6, and Cxcr2 gene expression despite pharmacological IDO inhibition. Histopathology revealed reduced inflammatory infiltration and maintained alveolar structure. CN maintains anti-inflammatory, immunomodulatory and tissue-protective efficacy in allergic airway inflammation despite pharmacological IDO inhibition. These findings call for future research on CN as a potential adjunctive therapy method for inflammatory airway diseases. However, to elucidate the underlying processes, more research on IDO activity and downstream immunometabolic pathways is needed. Full article

Objective: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. Methods: Thirty-six Sprague–Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson’s trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α $\mathrm{T}\mathrm{N}\mathrm{F}-\mathsf{\alpha }$ interleukin-1β $\mathrm{I}\mathrm{L}-1\mathsf{\beta }$, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson–Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of −14.74, −14.92, −17.58, −23.04, and −16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. Conclusions: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms. Full article

Severe pediatric asthma remains a significant clinical challenge despite advances in conventional therapy. Some children continue to experience persistent symptoms, recurrent exacerbations, and substantial morbidity despite optimized treatment with inhaled corticosteroids and long-acting bronchodilators. Advances in the understanding of asthma immunopathology, particularly type 2 (T2) inflammation, have led to the development of targeted biologics that modulate key inflammatory pathways. Several monoclonal antibodies are now approved for pediatric use, including the anti-immunoglobulin E (IgE) agent omalizumab, anti-interleukin (IL)-5 therapies such as mepolizumab, and the IL-4 receptor antagonist dupilumab. These biologics significantly reduce exacerbation rates, improve lung function, and decrease dependence on systemic corticosteroids in selected pediatric populations. Their effective use, however, requires careful assessment of clinical phenotypes and biomarkers, including blood eosinophils, serum IgE, and fractional exhaled nitric oxide. Uncertainties remain regarding treatment sequencing, duration, long-term safety, and cost-effectiveness. Agents targeting upstream epithelial cytokines, including tezepelumab, are broadening the therapeutic landscape. Despite this progress, pediatric evidence remains fragmented across age groups, biologic agents, study designs, and real-world cohorts, while many reviews focus on individual therapies or partly extrapolate from adult data. This review synthesizes pediatric evidence on efficacy, safety, biomarker-guided selection, age-related indications, and implementation challenges across approved and emerging biologics. It aims to provide clinicians with a practical framework for treatment selection and monitoring while identifying priorities for future pediatric research. Full article

Cystic kidney disease is characterized by progressive structural remodeling of renal parenchyma and altered cellular signaling. Inflammatory mediators may contribute to disease biology; however, data on interleukin-15 (IL-15) in pediatric cystic kidney disorders remain limited. The aim of this study was to assess serum and urinary IL-15 concentrations in children with cystic kidney disease and to evaluate their association with renal function. Methods: This study included 47 children with cystic kidney disease and 41 controls without renal cystic disease or other systemic, inflammatory, or immunological disorders. Serum and urinary IL-15 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Renal function was assessed using the estimated glomerular filtration rate (eGFR). Statistical analyses included non-parametric comparisons, logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: Children with cystic kidney disease demonstrated significantly elevated serum and urinary IL-15 concentrations compared with controls. IL-15 levels were not associated with eGFR and did not differ between cystic disease subtypes. In logistic regression analysis, IL-15 remained significantly associated with disease status. ROC analysis suggested high diagnostic ability of serum and urinary IL-15. Conclusions: IL-15 concentrations are increased in children with cystic kidney disease independently of current renal function. These findings suggest that IL-15 may reflect early inflammatory or epithelial signaling rather than established functional impairment. Full article

Immune dysregulation characterized by persistent myeloid activation and associated impairment of regulatory T cell (Treg) function contributes to inflammatory signaling across peripheral and central compartments in neurodegenerative diseases. We evaluated whether combining a glucagon-like peptide-1 receptor agonist (GLP-1RA; semaglutide) with low-dose interleukin-2 (LD-IL2) could modulate myeloid-associated transcript expression and enhance Treg-associated regulatory transcripts in a subacute lipopolysaccharide (LPS)-induced model of systemic and CNS inflammation. Mice received LPS once daily for 5 days, while GLP-1RA, LD-IL2, or combination treatment was initiated 24 h after LPS onset and continued daily. Splenic immune populations were quantified, and transcript expressions were assessed in magnetically enriched CD11b⁺ myeloid cells and CD4⁺CD25⁺ Tregs, as well as in cortex and hippocampus. As monotherapies, GLP-1RA reduced myeloid expansion with modest modulation of pro-inflammatory and anti-inflammatory myeloid transcripts, whereas LD-IL2 selectively enhanced Treg numbers and increased transcripts associated with Treg stability and suppressive regulation, including Il2ra (CD25), Foxp3, Ctla4, Ikzf2 (HELIOS), Entpd1 (CD39), and Nt5e (CD73). Combination treatment significantly reduced LPS-induced myeloid Il6, Il1b, and Tnf expression and increased Arg1 expression. Combination treatment further enhanced Treg-associated Il2ra (CD25), Tgfb1, and Ctla4 expression relative to monotherapies. In cortical and hippocampal tissues, combination treatment produced more robust modulation of inflammatory transcripts compared with effects observed with monotherapies, including reductions in Il6 and Il1b and increases in Cd163 and Mrc1 (CD206) expression. Together, these findings demonstrate coordinated and complementary changes in peripheral immune-cell populations and myeloid inflammatory and Treg-associated regulatory transcripts and warrant further evaluation of this combination in inflammation-driven neurodegenerative disease. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

Topical non-steroidal anti-inflammatory drugs (NSAIDs) such as flurbiprofen and benzydamine may be used for the symptomatic relief of pharyngitis, triggered by infections. The onset and spectrum of anti-inflammatory activity of both drugs were compared in human tonsil (HTEpiC) and bronchial epithelial (BEAS-2B) cells stimulated with poly I:C against key inflammatory mediators. Cells were stimulated with poly I:C for 24 h and treated with flurbiprofen or benzydamine for 20 s, 2 min and 5 min. Production of prostaglandin E2 (PGE₂), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), interleukin-8 (IL-8), interleukin-18 (IL-18), monocyte chemotactic protein-3 (MCP-3) and C-X-C motif chemokine ligand 10 (CXCL10), as well as cyclooxygenase-2 (COX-2) protein expression, was evaluated. Flurbiprofen significantly (p < 0.05) reduced PGE₂ production and COX-2 expression in both cell types within 20 s of treatment and maintained these effects at 2 and 5 min. However, benzydamine produced delayed, inconsistent inhibition. Although both drugs reduced poly I:C induced IL-6, IL-1β, IL-8 and IL-18 production, the magnitude and onset were greater with flurbiprofen. Flurbiprofen also reduced MCP-3 and CXCL10 in both cell types, alongside significant inhibition of caspase-1 activity. Benzydamine showed limited or no effect and less inhibition of caspase-1. With rapid suppression of the COX-2/PGE₂ pathway, rapid onset and a broad inhibition spectrum, flurbiprofen more comprehensively modulates inflammatory processes in epithelial respiratory models. Full article

Food allergy is a growing global health concern associated with significant dietary restrictions, impaired quality of life, and risk of severe allergic reactions. Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor alpha (IL-4Rα), inhibits IL-4 and IL-13 signaling and has demonstrated efficacy across multiple type 2 inflammatory diseases. This systematic review aimed to evaluate the effects of dupilumab on food allergy outcomes in pediatric and adult patients. Across studies, dupilumab treatment was consistently associated with reductions in total immunoglobulin E (IgE) and food-specific IgE levels, indicating modulation of allergic sensitization and type 2 inflammation. However, these immunologic improvements were not consistently accompanied by clinically meaningful desensitization or acquisition of food tolerance. In a phase II trial of peanut allergy, dupilumab monotherapy reduced immunologic markers but did not improve oral food challenge outcomes. When combined with oral immunotherapy, dupilumab modestly enhanced desensitization rates but did not substantially reduce treatment-related allergic reactions. Current evidence suggests that dupilumab favorably affects immunologic markers associated with food allergy, particularly total and allergen-specific IgE levels. Nevertheless, there is insufficient evidence to conclude that dupilumab alone induces sustained clinical tolerance to food allergens. Larger randomized controlled trials incorporating standardized oral food challenges and long-term follow-up are required to clarify the clinical role of dupilumab in food allergy management. Full article

The integration of digital therapeutics (DTx), wearable electronic devices, and artificial intelligence (AI) represents a significant advancement in personalized healthcare. The primary purpose of this structured narrative review is to evaluate the convergence of these technologies, providing a consolidated framework that bridges the gap between raw biometric data acquisition and actionable, AI-driven clinical insights. This paper synthesizes the latest literature on the intersection of mobile health (mHealth), machine learning (ML), and physiological tracking, with a primary focus on heart rate variability (HRV) and associated biochemical markers, such as cortisol, salivary alpha-amylase, and interleukins. Instead of viewing wearable outputs simply as raw data, we critically evaluate the technical verification and clinical validation required to define them as true “digital biomarkers.” By evaluating multimodal sensor technologies and advanced predictive algorithms, this paper outlines the clinical utility of digital biomarkers in diagnosing and proactively managing cardiovascular, neurological, metabolic, and psychiatric conditions, noting classification accuracies frequently exceeding 85% in controlled settings. However, we strongly caution that internally validated performance in controlled settings does not inherently demonstrate external clinical utility. The clinical relevance of this study lies in its holistic approach to identifying how continuous monitoring can broaden healthcare accessibility while improving precision medicine. Furthermore, it deeply addresses the technical challenges of highly variable ambulatory data quality, the necessity for robust artifact reduction (e.g., via LSTM and GAN architectures), and the limitations of small, homogeneous training datasets. We highlight the essential need for demographic-aware algorithmic models, external validation, and decentralized privacy-preserving models (e.g., federated learning) in diverse populations to ensure the safe, equitable clinical translation of DTx, mHealth, ML, and AI technologies. Full article

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder frequently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers reflecting immune activation and endothelial dysfunction, respectively. However, their differential associations with IR in PCOS, particularly in the context of central obesity, remain incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, systolic blood pressure (SBP), and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), or sCD40L. In adjusted regression models, fasting glucose independently predicted sCD40L (β = −0.27, 95% confidence interval (CI): −0.50 to −0.04, p = 0.020), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, 95% CI: 0.17 to 0.65, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. Assessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women. Full article

Background: This study aimed to investigate the effects of E. stephanianum-derived polyphenols on preventing the progression of collagen-induced arthritis (CIA) in mice and its associated metabolic alterations. Methods: The E. stephanianum plant was extracted, fractionated, and screened in vitro for anti-inflammatory, antibacterial, and antioxidant potential. Fraction 5 (identified as ellagic acid by nuclear magnetic resonance) exhibited the most potent activity and was selected for in vivo study. In the in vivo study, male DBA/1JGpt mice were randomized into five groups: control (CON), CIA (Model), low-dose extract (ES-L), high-dose extract (ES-H), and ellagic acid group. ES-L, ES-H, and ellagic acid were administered by daily oral gavage at 375, 750, and 250 mg/kg body weight, respectively, for 8 weeks. Arthritis severity was evaluated based on paw thickness, clinical score, ankle joint histopathology, and serum proinflammatory cytokine levels. To reveal the associated metabolic alterations, serum metabolites were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results: Both the whole extract and ellagic acid revealed pronounced anti-inflammatory, antibacterial, and antioxidant properties. In vivo treatment with ES-L, ES-H, or ellagic acid similarly and significantly ameliorated CIA severity, showing smaller paw swelling, reduced clinical arthritis scores, milder joint histopathological injury, and lower serum tumor necrosis factor-α and interleukin-6 concentrations than the model group. Untargeted metabolomics identified 20 differential metabolites, mainly including triacylglycerols (containing n-3 fatty acids), pro-inflammatory phospholipids, and spermic acid 1. Moreover, the treatments significantly altered amino acid and purine metabolism. Conclusions:E. stephanianum derived polyphenols, like ellagic acid, significantly prevented the progress of CIA in mice. These effects were associated with the alteration of metabolic profiles. Full article