Search Results (47,741)

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive stage of metabolic dysfunction-associated steatotic liver disease characterized by lipid dysregulation, oxidative stress, inflammation, and fibrosis. Because these processes occur simultaneously, compounds targeting multiple pathways may offer therapeutic benefit. Naringin, a citrus-derived flavonoid, has reported antioxidant and anti-inflammatory properties, but its integrated effects in MASH remain unclear. In this study, the effects of naringin were evaluated using combined in silico analysis and in vivo experiments. Network pharmacology and molecular docking predicted targets related to lipid metabolism, oxidative stress, inflammation, and fibrosis, which were validated in a methionine- and choline-deficient diet-induced mouse model. Naringin reduced hepatic lipid accumulation and improved serum AST and ALT levels. It modulated oxidative stress-related genes, attenuated inflammatory responses, and reduced fibrogenic markers. Naringin also decreased Ly6Chigh inflammatory monocytes and Kupffer cell activation, and reduced hypothalamic microglial activation. These findings suggest that naringin exerts multi-target effects across hepatic, systemic, and central pathways, supporting its potential as a therapeutic candidate for MASH. Full article

Capsule endoscopy (CE) is evolving from a primarily small-bowel imaging modality into a broader diagnostic platform that increasingly incorporates artificial intelligence (AI), robotic technologies, biosensing capabilities, and decentralized models of care. The REFLECT symposium brought together an international, multidisciplinary audience of clinicians, engineers, scientists, and healthcare stakeholders to critically evaluate the present and future role of CE across a range of gastrointestinal (GI) applications, including inflammatory bowel disease, GI bleeding, coeliac disease, and colorectal cancer screening. Discussions explored the clinical impact of panenteric and colon capsule endoscopy, the potential of AI to enhance diagnostic performance and streamline workflows, innovations in capsule hardware, and the design of patient-centred diagnostic pathways. While conventional endoscopy continues to serve as the benchmark in many clinical scenarios, CE was recognized for its ability to improve access, acceptability, and scalability when deployed in appropriately selected populations. The symposium also identified key barriers to broader implementation, such as reinvestigation rates, absence of standardized quality indicators, limited real-world evidence for AI tools, and ongoing economic and environmental challenges. Overall, the meeting highlighted the importance of gradual, evidence-driven integration of CE, supported by robust validation, standardized metrics, close clinician-engineer collaboration, and meaningful incorporation of patient experience, to support the development of a safe, equitable, and sustainable pathway. Full article

Background: Advanced glycation end products (AGEs) accumulate in tissues with age and are associated with the risk of chronic diseases. However, evidence regarding lifestyle factors related to AGE accumulation in healthy adolescents is limited. The aim of this study was to explore dietary and lifestyle factors that may attenuate tissue AGE accumulation, using skin autofluorescence (SAF) as a noninvasive proxy marker, in healthy Japanese early adolescent girls. Methods: This cross-sectional study included 315 first-year junior high school girls aged 12–13 years from a private school in Japan. SAF was measured on the volar forearm using an AGE Reader MU. Dietary intake was assessed using a validated brief diet history questionnaire (BDHQ-15y). Lifestyle factors, including weekday sleep duration, were assessed using a self-administered questionnaire. Health-related variables (including weight-loss dieting) were also collected. Associations between SAF and each factor were analyzed using generalized linear models and nonparametric tests, with multivariable adjustment for potential confounders. Results: The mean SAF was 1.06 ± 0.13 arbitrary units. No significant associations were observed between SAF and health-related characteristics, nutrient intakes, or major food-group intakes. Longer weekday sleep duration was significantly associated with lower SAF (p for trend = 0.019) and remained significant after multivariable adjustment (p for trend = 0.018). A similar association was observed for better perceived restorative sleep (p for trend = 0.033; adjusted p for trend = 0.048). Conclusions: In healthy early adolescent girls, longer weekday sleep duration and better perceived restorative sleep were associated with lower SAF, whereas dietary intake was not. Given the largely irreversible age-related accumulation of AGEs, promoting healthy sleep during adolescence may help attenuate AGE accumulation early in life and reduce long-term AGE-related disease risk. Prospective studies with more detailed dietary assessments are needed to clarify dietary influences and confirm temporality. Full article

Background/Objectives: Alzheimer’s disease (AD) remains a progressive neurodegenerative disorder with limited therapeutic options. This study aimed to develop an integrative multi-omics computational pipeline to identify diagnostic biomarkers and prioritize druggable therapeutic targets for AD. Methods: We integrated transcriptomic data from 1047 samples (547 AD, 500 controls) using weighted gene co-expression network analysis (WGCNA) and three machine learning algorithms (LASSO, Random Forest, SVM) with strict separation of training, feature selection, and evaluation. Single-cell RNA sequencing of 48,481 nuclei from entorhinal cortex, two-sample Mendelian randomization (MR) with Bayesian colocalization, and structure-based molecular docking with triplicate 500 ns molecular dynamics (MD) simulations were also employed. Results: Machine learning identified 10 consensus biomarker genes involved in synaptic vesicle cycling, ion transport, and calcium homeostasis (internal test AUC = 0.891, 95% CI: 0.836–0.946; external validation on GSE48350: AUC = 0.847, 95% CI: 0.798–0.896). Covariate-adjusted differential expression and MR with Bayesian colocalization converged on eight immune-related therapeutic targets including APOE, TREM2, and TYROBP ($p<0.05$; Bonferroni-corrected threshold $p<0.00625$). Single-cell analysis revealed oligodendrocyte expansion in AD (28.5% versus 24.8%), with target genes predominantly expressed in microglia and astrocytes. Virtual screening of 2634 FDA-approved drugs prioritized 10 exploratory repurposing candidates; indomethacin–TREM2 and celecoxib–CSF1R are primary exploratory candidates given structurally validated binding pockets. Triplicate MD simulations (15 $\mathsf{\mu }$s aggregate) showed force-field-consistent structural stability (RMSD ≤ 3.2 Å). A quantitative multi-omics convergence framework identified four Tier 1 targets (APOE, TREM2, TYROBP, CX3CR1) supported by ≥5 analytical layers ($P_{\mathrm{perm}}=0.0003$; note: three of five layers share the same transcriptomic input). Conclusions: These findings provide a multi-evidence computational framework linking diagnostic biomarkers and druggable neuroinflammatory targets for AD. All predictions require experimental validation in biochemical and cellular models before clinical conclusions can be drawn. Full article

Background/Objectives: Renal scarring in children is linked to long-term complications, including hypertension and chronic kidney disease. Although dimercaptosuccinic acid (DMSA) scintigraphy is the reference standard, routine use is limited due to radiation exposure. This study evaluated whether multiparametric ultrasound combined with machine learning could predict DMSA-detected renal scarring in pediatric patients. Methods: In this retrospective study, 192 children undergoing renal ultrasound and DMSA scintigraphy were included. Renal morphometric and volumetric parameters, along with shear wave elastography, were analyzed. Supervised machine learning models were trained to predict renal scarring. A validated data augmentation framework addressed class imbalance and limited sample size. Model performance was assessed using standard classification metrics. Results: Kidney volume indexed to body surface area and the asymmetry index were strongly associated with renal scarring. Elastography alone had limited discriminatory power in conventional analyses but improved predictive performance when incorporated into machine learning models after data augmentation. Ensemble-based models achieved the highest accuracy and area under the receiver operating characteristic curve. Conclusions: Multiparametric ultrasound with machine learning shows potential as a noninvasive tool for predicting renal scarring in children. While not a replacement for DMSA scintigraphy, this approach may aid risk stratification and clinical decision-making, potentially reducing unnecessary radiation exposure. Full article

Background/Objectives: Cervical cancer, primarily driven by persistent high-risk HPV infection, remains a major global health issue. Xiao-ai-fei honey ointment, a traditional Uyghur multi-ingredient preparation, has shown clinical promise in cancer treatment, but its mechanisms against cervical cancer are not fully understood. This study aimed to investigate the potential molecular mechanisms of ethanolic extract of Xiao-ai-fei honey ointment (XAFHO) in cervical cancer using network pharmacology, single-cell RNA sequencing, and experimental validation. Methods: Differentially expressed genes (DEGs) in cervical cancer were identified from TCGA database. Active components and corresponding targets of XAFHO were retrieved from the TCMSP database, and disease targets were obtained from GeneCard, OMIM, and the TTD. Intersection targets were subjected to multivariate Cox and LASSO regression to construct a prognostic model. Immune infiltration, TMB, and MSI were compared between risk groups. Single-cell RNA-seq data were analyzed to determine cellular origins and inter-cellular communication. In vitro assays were performed on HeLa and SiHa cells to assess the anti-cancer activity of XAFHO. Molecular docking evaluated binding affinities between active compounds and core targets. The expression and functional roles of FASN and SPP1 were further validated by RT-qPCR, Western blotting, and siRNA transfection. Results: Sixty-three potential XAFHO targets were identified, and an 11-gene prognostic model was established, effectively stratifying patients into high- and low-risk groups with significantly different overall survival (AUC > 0.7). The high-risk group exhibited an immunosuppressive microenvironment and higher TMB. Single-cell analysis revealed that FASN and ACACA were predominantly expressed in tumor cells, while SPP1 was enriched in macrophages/monocytes. Tumor cells communicated with immune cells via the TGFB1–TGFβR1/R2 axis, promoting immune evasion. In vitro, XAFHO significantly inhibited proliferation, colony formation, migration, and invasion of cervical cancer cells. Molecular docking confirmed the strong binding of quercetin, kaempferol, and isorhamnetin to FASN and SPP1 (binding energy < –6.0 kcal/mol). Functional validation indicated that upregulated FASN and SPP1 contribute to malignant behaviors in cervical cancer cells. Conclusions: This study integrates network pharmacology with single-cell and experimental approaches to demonstrate that XAFHO exerts multi-target and multi-cell anti-cervical cancer effects, potentially by modulating lipid metabolism and immune-related pathways via FASN and SPP1. These findings provide a scientific basis for the therapeutic application of XAFHO in cervical cancer. Full article

Background/Objectives: Hyperkalemia is common in patients with chronic kidney disease (CKD). However, its epidemiology may be evolving due to population aging, new therapeutic developments and novel estimated glomerular filtration rate (eGFR) equations. We have re-evaluated the epidemiology of hyperkalemia in a contemporary cohort in which eGFR was assessed using the EKFC equation recommended by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Methods: We analyzed 190,579 laboratory tests with serum potassium values corresponding to individual outpatients in Primary or Specialty Care from a single laboratory in 2023, representing 42% of the catchment area population. Results: Hypokalemia (<3.5 mmol/L) was present in 0.3% patients, hyperkalemia (≥5.0 mmol/L) in 10.5% (11.5% of men, 9.7% of women). Hyperkalemia was mostly mild (9.4%) but was severe in 0.1% overall and in 10.5% of CKD G5. One in four patients with hyperkalemia had CKD. Hyperkalemia was more common among patients with CKD G3–G5 defined using the CKD-EPI2009 equation than defined using the EKFC equation (20.5 vs. 18.6%, p < 0.0001). Using EKFC, hyperkalemia prevalence increased with decreasing eGFR from G1 (6.6%) to G2 (10.8%) and, especially in CKD G3–G5 (G3 17.2% to G5 47.5%). In multivariate logistic analysis, worse renal function, worse diabetes control, older age, and surrogates for release of intracellular potassium during sample processing (red blood cell counts or size, platelet counts, elevated calcium levels) were independently associated with hyperkalemia. This multivariate model yielded an area under the curve (AUC) of the Receiver Operating Characteristic (ROC) curve for hyperkalemia of 0.678 (95% CI 0.674–0.682). Random forest also identified GFR as the most important feature associated with hyperkalemia and generally concurred with logistic analysis findings. Conclusions: Hyperkalemia remains common, especially in CKD G5. While hyperkalemia is mainly associated with low eGFR, sample processing should be optimized. Full article

Mesenchymal stem/stromal cells (MSCs) are widely recognized as potent modulators of inflammation and immune function in bacterial and viral infections. However, their roles in fungal disease remain comparatively under-defined despite the growing clinical burden of invasive and opportunistic mycoses. This Feature Review synthesizes emerging evidence that MSCs influence antifungal outcomes through two complementary axes: (i) host-directed effects, including modulation of immune responses, particularly macrophage responses, and tissue/barrier conditioning; and (ii) fungus-directed effects (direct antifungal activity mediated by contact-dependent mechanisms and secreted antimicrobial factors). We will summarize how MSCs reshape cytokine and chemokine networks and tune innate immune effector functions, with emphasis on macrophage polarization, pattern-recognition receptor signaling, and downstream phagocytic and fungicidal pathways. In parallel, we will review data suggesting that MSCs can interact more directly with fungal pathogens through sensing, physical engagement, and secretion of antimicrobial mediators while highlighting mechanistic uncertainties and model-dependent limitations. A dedicated section will address MSC-derived secretome products (conditioned media, extracellular vesicles) as a cell-free strategy to enhance antifungal immunity. We will critically evaluate conflicting findings across studies, highlighting that outcomes depend on pathogen and host context. Clarifying these context dependencies is essential to rationally develop MSC or secretome-based interventions that are safe, reproducible, and tailored to specific fungal pathogens and patient populations. Full article

Background/Objectives: Chronic glomerulonephritis (CGN) is a progressive chronic kidney disease that can ultimately advance to end-stage renal disease (ESRD). Zhuangyang Bushen Pill (ZYBSW) is a traditional Chinese herbal formulation derived from the Yi ethnic medicine of Yunnan Province, and it has been widely employed in folk practice for the amelioration of chronic nephritis and renal dysfunction. This study was designed to evaluate the therapeutic efficacy of ZYBSW against CGN and to provide preliminary insights into its underlying mechanisms of action. Methods: The nephropathy model was induced in mice by tail vein injection of ADR (10 mg/kg). Renal function was evaluated by measuring relevant biochemical parameters, and renal histopathological alterations were examined using HE staining. Chemical constituents of ZYBSW were analyzed by LC-MS/MS. Its mechanisms of action were investigated using network pharmacology, WGCNA, molecular docking, multiplex immunofluorescence, and Western blotting. Results: ZYBSW significantly reduced ACR by 88.9%, SCr by 56.4%, and BUN by 30.4%, increased ALB by 32.4%, and alleviated renal histopathological damage (all p < 0.01). LC-MS/MS analysis identified 419 chemical constituents in ZYBSW. Network pharmacology, WGCNA, and molecular docking experiments identified EGFR and DUSP1 as potential targets, and indicated the MAPK pathway as a key pathway. Mechanistic studies revealed that ZYBSW significantly inhibited EGFR expression in renal tissue, enhanced DUSP1 expression, and reduced the phosphorylation levels of ERK, JNK, and p38. Conclusions: This study reveals ZYBSW can effectively alleviate CGN, with EGFR and DUSP1 as likely therapeutic targets, and its mechanism of action primarily involves regulating the MAPK signaling pathway. Full article

Prion diseases are fatal neurodegenerative disorders that affect humans and animals, caused by the conformational conversion of the normal cellular prion protein (PrP^C) into its misfolded, infectious isoform PrP^Sc. Recently, camel prion disease (CPrD) was identified in dromedary camels (Camelus dromedarius) in Algeria. Due to the potential implications for animal and human health, as well as the possible socio-economic impact in Mediterranean regions where camels play a pivotal role as a source of food, in-depth characterization of camel prions is important to increase our understanding of camel prion disease. We developed a neuronal cell line model for studying the molecular features of camel prion infection. We genetically edited mouse neuronal CAD5 cells to generate CAD5 PrP knockout (KO) cells. We then used lentiviral transduction to generate CAD5 cells expressing camel PrP (CAD5-camel-PrP). Following infection of these cells with a CPrD-positive camel brain homogenate, we observed PrP^Sc signals at various passages, as indicated by immunoblotting analysis. RT-QuIC (Real-Time Quaking-Induced Conversion) assays further supported these findings, demonstrating transient prion conversion activity in the CPrD-infected CAD5-camel-PrP cells. Taken together, our data describe the first neuronal cell line permissive to camel prion infection, a novel in vitro tool for mechanistic studies of camel prion disease. Full article

Background/Objectives: Osteoarthritis (OA) is an age-related degenerative joint disease whose pathogenic mechanisms remain poorly understood. Experimental evidence implicates dysregulated mechanotransduction mediated by Piezo1 and TRPV4 channels, but how their interaction with inflammation may drive pathogenic state transitions remains unknown. Here, we aimed to study whether a Piezo1–TRPV4 network can intrinsically produce distinct stable physiological and pathological regimes. Methods: Based on literature data, we developed a nonlinear dynamical model describing closed-loop interactions involving Piezo1, TRPV4, and inflammation. The system was translated into a set of ordinary differential equations and studied using stability and bifurcation analysis. Results: Computational analysis revealed bistability, allowing the system to shift from a physiological to a pathogenic regime in response to specific stimuli. Critical bifurcation parameters were linked to Piezo1 and inflammation, suggesting that the bidirectional interaction between these two components represents a key node for interventions aimed at preventing or reversing transitions from non-pathogenic to pathogenic states. Conclusions: Our results suggest that OA pathogenesis may emerge from the intrinsic nonlinear dynamics of Piezo1/TRPV4/inflammation interactions. Bifurcation analysis indicates the sensitivity of TRPV4 to the inhibitory effect of Piezo1 as a key target for preventing or reversing pathogenic state transitions. Further investigations in preclinical and clinical settings are warranted to validate the model. Full article

Objectives: This systematic review aims to evaluate the effects of Edible Bird’s Nest (EBN) extract on cognitive function and neuroprotection in animal models and systematically review the relevant research evidence. Methods: A systematic search was conducted in the databases of PubMed, Scopus, Web of Science, EMBASE, Taylor Francis, Wiley, and Cochrane Library for relevant research published up to October 2025. Search terms included “Edible Bird’s Nest”, “Bird’s Nest Extract”, “EBN”, “Swiftlet nest”, “Collocalia”, “Cognitive”, “Memory”, “Learning”, “Neuroprotection”, “Brain”, “Neural”, “Neurotrophic”, “Animal”, “Mice”, “Mouse”, “Rat”, “Rats”, “In vivo”, and “Model”. Two researchers independently screened all the relevant articles, extracted relevant data, and assessed the quality of included studies using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias assessment tool. Results: This systematic review included 11 animal studies, primarily focused on rodent models. Preclinical evidence suggests that Edible Bird’s Nest extract (EBN) may improve performance in several cognitive function tests. Animals treated with EBN appeared to show enhanced spatial memory and learning abilities in experimental settings. At the molecular level, the EBN treatment group showed improved antioxidant capacity and reduced neuroinflammation. Additionally, EBN promoted the expression of neuroprotective factors and enhanced synaptic plasticity. Research suggests that appropriate doses of EBN may have beneficial effects on cognitive enhancement and can alleviate cognitive dysfunction and neuropathological changes. Conclusions: Preliminary evidence from this systematic review suggests that EBN appears to show protective and potentially enhancing effects on cognitive function in animal models. EBN works through multiple mechanisms, including antioxidant and anti-inflammatory effects, as well as promoting the expression of neurotrophic factors and synaptic plasticity. These findings provide initial support for further investigation of EBN as a potential neuroprotective agent and cognitive enhancer. However, there is heterogeneity and methodological limitations in the research, and more standardized studies and preclinical translational research are needed to further validate the application potential of EBN in neuroprotection. These results provide an important reference for developing EBN-based functional foods and supplements for the prevention and adjuvant treatment of cognitive impairment and neurodegenerative diseases. Full article

Chest radiography remains a cornerstone in the diagnosis of thoracic diseases. However, differences in image acquisition—particularly projection type—may influence the apparent prevalence and detectability of radiographic findings. Such differences may represent a potential source of bias in large imaging datasets used for clinical research and artificial intelligence. Importantly, projection type is closely associated with the patient’s condition and may therefore reflect both technical imaging factors and underlying clinical characteristics, including disease severity. A total of 120,120 chest radiographs were available in the dataset. After applying inclusion criteria, 112,104 images were included in the primary analysis. Multivariable logistic regression models were used to assess the association between projection type and the presence of radiographic findings, adjusted for age and sex. Subgroup and interaction analyses were performed to evaluate effect modification by demographic factors. Given the large sample size, emphasis was placed on effect sizes and confidence intervals rather than statistical significance alone. Compared with posteroanterior projection, anteroposterior projection was associated with higher odds of detecting consolidation (aOR 3.27; 95% CI 3.07–3.48), infiltration (aOR 1.90; 95% CI 1.84–1.96), pleural effusion (aOR 1.66; 95% CI 1.60–1.72), atelectasis (aOR 1.63; 95% CI 1.57–1.70), and cardiomegaly (aOR 1.19; 95% CI 1.10–1.28). These associations were consistent across age and sex strata. A significant interaction between projection type and sex was observed for infiltration (p = 0.01). Projection type is associated with substantial differences in the detection of thoracic abnormalities on chest radiographs. These associations should be interpreted with caution, as they likely reflect a combination of technical imaging effects and residual confounding related to patient severity and clinical context. Projection may therefore act as a marker of dataset heterogeneity rather than a purely causal factor. Accounting for projection metadata is therefore essential to improve clinical interpretation and to ensure the robust development and validation of artificial intelligence models. Full article

Background: The Xiao Zhong Zhi Tong Patch (XZZTP) has been extensively utilized in China to alleviate many diseases associated with bacterial inflammation. However, its pharmacological mechanism and active components remain unclear. Methods: The anti-inflammatory effects of XZZTP were evaluated in vivo and in vitro models. The characterization of XZZTP and its transdermal components was performed using LC-MS/MS. The underlying pharmacological mechanism was predicted through network pharmacology using the identified transdermal components and verified by Western blotting. Molecular docking and molecular dynamics simulations were performed on key targets to screen active components. Results: XZZTP showed a swelling inhibition rate of 45.96% in xylene-induced ear edema mice in vivo. In vitro, the inflammatory mediators NO, TNF-α, and PGE2 were concentration-dependently reduced by XZZTP in the LPS-induced RAW 264.7 macrophages model, with inhibition rates of 56.53%, 53.75%, and 48.49% at 200 µg/mL, respectively. LC-MS/MS identified 126 chemical components (97 newly reported) in XZZTP, including 52 transdermal potential active components, among which a new iridoid and its isomer were reported for the first time. Network pharmacology analysis demonstrated that XZZTP mainly downregulated the PI3K/AKT/HIF-1 signaling pathway to alleviate bacterial inflammation. The protein expression of core targets p-PI3K, p-AKT, and HIF-1α in the LPS-induced RAW 264.7 macrophages was significantly reduced after XZZTP intervention. Eight active components were screened via molecular docking, and molecular dynamics simulations of three representative complexes validated stable binding interactions, supporting their therapeutic potential. Conclusions: These findings provide a theoretical basis for XZZTP as a potential agent to ameliorate bacterial inflammation-related diseases, serving as a reference for its further application. Full article

Background: Endoscopic remission is a central therapeutic target in inflammatory bowel disease (IBD); however, histologic inflammation may persist despite apparent mucosal healing. The biological mechanisms underlying endoscopic–histologic discordance remain incompletely defined. We aimed to characterize systemic cytokine patterns associated with discordant disease. Methods: In this prospective cross-sectional study, 59 patients with IBD undergoing clinically indicated colonoscopy underwent concurrent endoscopic and histologic assessment. Endoscopic remission was defined as a Mayo endoscopic subscore ≤ 1 for ulcerative colitis and SES-CD ≤ 2 for Crohn’s disease. Histologic healing was defined as a Geboes score < 2.0. Patients were classified into concordant remission, discordant disease (endoscopic remission with persistent histologic activity), and concordant active disease. Circulating interleukin (IL)-10, IL-23, and C-reactive protein (CRP) levels were compared across phenotypes using nonparametric methods. Associations with discordant disease were evaluated using Firth penalized logistic regression, and model discrimination was assessed using receiver operating characteristic (ROC) analysis with bootstrap internal validation. Results: Among 36 patients in endoscopic remission, 14 (38.9%) exhibited persistent histologic activity. Discordant patients demonstrated significantly lower IL-10 and higher IL-23 concentrations compared with concordant remission (both p < 0.001), whereas CRP did not differ significantly. Across phenotypes, IL-10 decreased progressively, while IL-23 increased stepwise (both p < 0.001). In multivariable analysis, lower IL-10 (OR 0.0014; 95% CI 0.000003–0.576; p = 0.032) and higher IL-23 (OR 16.94; 95% CI 1.90–151.32; p = 0.011) were independently associated with discordant disease. A model incorporating IL-10 and CRP demonstrated strong discrimination (AUC 0.925), with further improvement after inclusion of IL-23 (AUC 0.994), although these estimates should be interpreted with caution given the limited sample size. Conclusions: Endoscopic–histologic discordance is associated with a distinct systemic cytokine profile characterized by reduced IL-10 and elevated IL-23 levels, despite low CRP concentrations. These findings suggest incomplete restoration of immune regulatory balance and highlight the potential role of circulating cytokines, particularly IL-10, in identifying ongoing microscopic inflammation. These results are exploratory and hypothesis-generating and require validation in larger, prospective cohorts before clinical application. Full article