Search Results (11,292)

Dietary factors, including the consumption of isoflavones-rich foods of plant origin, may contribute to the reduced incidence of prostate cancer. Isoflavones, natural phytoestrogens often found in legumes, can modulate estrogen and androgen receptor signaling. This study aimed to evaluate the biological potential of isoflavone-rich extracts obtained from twelve species from the Fabaceae family, targeting prostate cancer cell viability, proliferation, inflammatory markers, prostate-specific antigen secretion, and 5α-reductase activity. The tested extracts showed moderate cytotoxic activity against prostate cancer cell lines, apart from highly susceptible PC3 cells, and only weak toxicity to normal prostate epithelial cells. Significant antiproliferative activity was observed, especially for Cytisus scoparius, Ononis arvensis, and Genista tinctoria, while most extracts reduced prostate-specific antigen (PSA) secretion in normal prostate cells. Furthermore, the extracts showed anti-inflammatory properties by reducing the pro-inflammatory cytokine interleukin 6 (IL-6) and improving cytokine balance indices. Multivariate analyses revealed correlations between total isoflavone content and antiproliferative activity. Full article

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal barrier disruption and dysregulated immune responses. While Intravenous Immunoglobulin (IVIG) is widely used for its immunomodulatory effects in various autoimmune conditions, its specific therapeutic mechanisms and molecular targets in colitis remain to be fully elucidated. Objective: To elucidate the therapeutic mechanisms of IVIG in dextran sodium sulfate (DSS)-induced colitis, with a focus on pyroptosis regulation via the NOD-like receptor (NLR) signaling pathway. Methods: Colitis was induced in mice via DSS administration. IVIG was administered intravenously during disease progression. Colon tissues underwent proteomic profiling, and key targets (GBP5, NLRP3, Pro-Caspase-1, GSDMD) were validated by Western blotting (WB), while interleukin (IL)-1β and IL-18 levels were quantified via ELISA. Results: IVIG significantly attenuated weight loss, Disease Activity Index (DAI) scores, colon shortening, and histopathological damage. Proteomics analysis identified 172 differentially expressed proteins between DSS and DSS + IVIG groups, with pronounced downregulation of GBP5 and NLR pathway components. IVIG suppressed GBP5/NLRP3/CASP1 activation, reduced GSDMD cleavage, and significantly decreased IL-1β production (while showing a decreasing trend for IL-18). Conclusions: IVIG ameliorates colitis by inhibiting the GBP5/NLRP3/CASP1-mediated pyroptosis pathway, highlighting its potential as a targeted therapy for ulcerative colitis. Full article

Background: Diabetes mellitus (DM) and chronic kidney disease (CKD) are major contributors to global morbidity and mortality, with disease progression being closely linked to persistent inflammation, oxidative damage, and apoptotic pathways. Icariin (ICA), a bioactive flavonoid compound isolated from Epimedium brevicornum Maxim, has attracted considerable interest because of its diverse pharmacological properties. We evaluated the effect of ICA on streptozotocin (STZ)-induced diabetic rats with or without adenine-induced CKD. This combined model reproduces several key structural and functional characteristics observed in human diabetic kidney disease and advanced CKD. Methods: Male Wistar rats were allocated to five treatment groups and followed for 35 days. Group 1 served as the untreated control and received standard chow; Group 2 was administered streptozotocin (STZ); Group 3 received STZ together with icariin (ICA); Group 4 received a combination of adenine and STZ; and Group 5 was treated with adenine, STZ, and ICA. ICA was administered at a dose of 200 mg/kg by oral gavage. Biochemical, oxidative stress and inflammatory markers were assessed. Results: Rats treated with STZ, with or without adenine, exhibited significant hyperglycemia, elevated plasma levels of cystatin C and indoxyl sulphate, increased urinary levels of N-acetyl-β-D-glucosaminidase (NAG) and NAG/creatinine ratio, and reduced creatinine clearance. Additionally, there were significant decreases in renalase activity and urine osmolality, significant increases in interleukins IL-1β and IL-6 and TNF-alpha levels, and a decrease in IL-10 level. Oxidative stress biomarkers were also significantly impaired in both groups, along with significant renal histopathological changes. ICA significantly ameliorated these alterations in both experimental groups. Conclusion: These findings demonstrate that ICA exerts renoprotective and anti-inflammatory effects in a clinically relevant model of advanced diabetic CKD. Further studies are warranted to elucidate the underlying mechanisms and determine the translational relevance of these findings. Full article

Major depressive disorder (MDD) is clinically heterogeneous, and peripheral inflammatory biomarkers may help clarify early biological mechanisms before illness chronicity or pharmacologic treatment confound interpretation. This systematic review synthesized evidence on peripheral inflammatory biomarkers in first-episode, drug-naïve major depressive disorder (FEDN-MDD) compared with healthy controls and examined associations with clinical severity. Following PRISMA 2020, searches of PubMed/MEDLINE, Embase, PsycINFO, and Scopus from inception to 19 March 2026 identified 313 records; after screening, 16 publications were included in qualitative synthesis. Studies varied in age group, biological matrix, assay platform, and statistical reporting, precluding meta-analysis. The most frequently assessed biomarkers were IL-1β, TNF-α, IL-6, and CRP/hs-CRP. IL-6 showed the clearest recurrent tendency toward elevation in FEDN-MDD, whereas CRP/hs-CRP findings were partially positive but methodologically limited. TNF-α and IL-1β findings were mixed, and clinical correlations with depressive severity were sparse and inconsistent. Overall, the evidence supports heterogeneous early immune dysregulation in a subset of patients with FEDN-MDD rather than a single reproducible inflammatory signature. Peripheral inflammatory biomarkers should currently be considered research tools for biological stratification and mechanistic hypothesis generation, pending larger standardized longitudinal studies. Full article

Interleukin-13 receptor α2 (IL-13Rα2) has traditionally been considered a decoy receptor; however, its cellular functions beyond the immune system remain unclear. We aimed to investigate the role of IL-13Rα2 in C2C12 myoblast proliferation and differentiation. IL-13Rα2 expression was knocked down in C2C12 cells using siRNA. Myogenic differentiation was evaluated by myosin heavy chain (MyHC) immunostaining and by quantifying the expression of myogenic regulatory and fusion-related genes. Myoblast proliferation was assessed using BrdU incorporation and cell number analyses, and signaling events induced by IL-13Rα2 knockdown were analyzed via immunoblotting and immunocytochemical analysis. IL-13Rα2 knockdown did not alter myogenic differentiation or the expression of fusion-associated genes. In contrast, IL-13Rα2 knockdown significantly increased BrdU incorporation and cell number, accompanied by increased Akt phosphorylation and decreased ERK phosphorylation. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) levels were also increased. Akt inhibition abolished the enhanced proliferation and normalized Cyclin D1/CDK4 levels, whereas ERK activation did not further modify the knockdown-associated phenotype. These findings demonstrate that IL-13Rα2 negatively regulates myoblast proliferation by modulating the Akt–Cyclin D1–CDK4 signaling pathway, while being dispensable for myogenic differentiation. Full article

In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the ‘obesity paradox’ and the association between body composition and inflammation. This study assessed the relationship between body composition, traditional inflammatory markers, the new NETosis indicators (neutrophil extracellular traps), and their association with 12-month mortality. The study included 99 maintenance hemodialysis (HD) patients. Their body composition was assessed using bioelectrical impedance analysis. Blood serum was tested for inflammatory markers (hs-CRP-high sensitive c-reactive protein, IL-6 interleukin-6, TNF-α tumor necrosis factor alfa, IL-1β interleukin-1 beta), NETosis markers (citrullinated histone CH3, myeloperoxidase -MPO, elastase), and nutritional status parameters (albumin, transferrin). No correlation between BMI -body mas index and inflammation was demonstrated. Higher adipose tissue, particularly visceral, was significantly positively correlated with IL-6 and hs-CRP levels, while muscle mass was negatively correlated with inflammation. Dialysis catheter use was associated with higher CH3 levels (NETosis indicator) and lower albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Body composition, rather than BMI, is associated with the severity of inflammation. Visceral obesity is positively correlated with increased inflammation, while muscle mass shows an inverse association. Dialysis catheters are linked to higher NETosis markers and lower albumin levels, which are associated with a poorer prognosis. Full article

Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the olfactory cleft, but is now considered to be multifactorial, involving conductive, inflammatory, and sensorineural mechanisms as well. Type-2 inflammatory response (high interleukins IL-4, IL-5, IL-13), eosinophilia, and increased IgE are involved in epithelial damage, impaired neurogenesis, and persistent olfactory loss, especially in chronic rhinosinusitis with nasal polyps (CRSwNP). In addition, peripheral chronic inflammation may also play a role in central neural remodeling, which may potentially affect olfactory function. Objective psychophysical testing is necessary to accurately assess olfactory function because self-reports may lack reliability. Management strategies aim at reducing inflammation and restoring sinonasal ventilation. First-line therapy with intranasal corticosteroids and short courses of systemic corticosteroids may be useful for symptomatic relief. Biologic agents directed against type-2 inflammation have demonstrated significant benefits in selected cases. Functional Endoscopic Sinus Surgery (FESS) plays an important role in the treatment of refractory CRS to restore the airflow and to improve the delivery of topical drugs. Olfactory outcomes following surgery, however, are variable and often incomplete, reflecting underlying inflammation and neuroepithelial damage. Disease recurrence, especially in type-2–driven CRS, affects long-term outcomes, underscoring the necessity to incorporate surgery in an individualized, endotype-informed treatment strategy. Full article

The failure of therapy in muscle invasive bladder cancer (MIBC) is primarily attributed to tumor heterogeneity and therapy resistance. We propose a novel approach targeting interleukin-13 receptor subunit alpha 2 (IL-13Rα2), which is expressed on bladder cancer (BC) cells but absent in normal urothelial cells. We investigated the therapeutic effects of WPD101a immunotoxin (IL-13-DT390) on IL-13Rα2-expressing BC cells in relation to BC cell phenotype and functional characteristics in vitro using both 2-dimensional (2D) and 3-dimensional (3D) models. Cell phenotype and IL-13Rα2 expression were assessed using flow cytometry, immunofluorescence, and Western blot analysis. The biological effects of WPD101a were evaluated by measuring cell viability and proliferation using the MTT, sulforhodamine B (SRB), CellTiter-Glo and Live/Dead assays. Apoptosis was assessed using Annexin V/propidium iodide (PI) staining, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of CASP genes expression. We found that the reference BC cell lines TCC-SUP, JMSU-1 and UM-UC-3 express IL-13Rα2 at various level in contrast to RT-4, HCV-29 and 5637 cells. Cells expressing IL-13Rα2 were sensitive to WPD101a at lower concentrations in the 2D model (0.1 ng/mL) compared to the 3D model (1.0 ng/mL). IL-13Rα2-negative cells remain resistant to the immunotoxin. WPD101a induces apoptosis in BC cells expressing IL-13Rα2 as confirmed by the presence of apoptotic cells, increase the proportion of cells in the subG1 phase, and by the effector CASP3, CASP7, and initiator CASP8, CASP9 genes expression. This study confirmed receptor-dependent cytotoxic effects of WPD101a and the ability and specificity to inhibit growth and apoptosis induction in MIBC cells expressing IL-13Rα2. Full article

Cross-presentation of exogenous antigens by dendritic cells (DCs) relies on the cytosolic pathway, enabling proteasomal processing and subsequent loading of antigenic peptides onto major histocompatibility complex class I (MHC-I) molecules. Although this pathway is central to CD8⁺ T-cell activation, the molecular mechanisms that regulate intracellular antigen processing and redistribution during cross-presentation remain incompletely defined. In this study, we investigated the contribution of the large-pore channel Pannexin-1 (Panx1) to antigen handling during cross-presentation. Using confocal microscopy and quantitative image analysis in granulocyte–macrophage colony-stimulating factor/interleukin-4 (GM-CSF/IL-4)-derived inflammatory bone marrow-derived dendritic cell (BMDC)-like cellsexposed to ovalbumin (OVA)–Alexa Fluor 488, we observed time-dependent changes in intracellular antigen distribution that were altered upon pharmacological inhibition of Panx1 with the blocking peptide 10Panx1. In parallel, functional assays revealed that Panx1 inhibition significantly reduced SIINFEKL peptide-dependentactivation of B3Z CD8⁺ T-cell hybridomas following pulsing with full-length OVA. Similar effects were observed in the cross-presentation-competent MUTU1940 dendritic cell line. Importantly, Panx1 inhibition did not significantly affect dendritic-cell viability or LPS-induced activation under the experimental conditions tested. In contrast, pharmacological inhibition or genetic deficiency of P2X7 receptor (P2X7) did not produce comparable reductions in cross-presentation, and combined inhibition did not result in additive effects under the experimental conditions tested. Together, these findings provide functional evidence supporting a role for Panx1 in regulating intracellular antigen redistribution associated with cross-presentation. While not establishing direct genetic causality, our data identify Panx1 as a modulatory component influencing antigen-processing events that culminate in CD8⁺ T-cell activation, thereby expanding the current framework of intracellular antigen-processing mechanisms involved in dendritic-cell-mediated cross-presentation. Full article

Background: Gentamicin-induced nephrotoxicity limits clinical pharmacotherapy and involves multiple converging stress-response pathways. Ellagic acid (EA) has renoprotective potential, yet its role in coordinating endoplasmic reticulum (ER) stress-mediated apoptosis, autophagy, and inflammation remains unclear. We hypothesized that EA co-treatment would protect the kidney by modulating ER stress-dependent pathways and associated inflammatory and adaptive signaling. Methods: For an integrated mechanistic analysis in a rat model of gentamicin nephrotoxicity, 40 male Sprague-Dawley rats were assigned to control, gentamicin (100 mg/kg), EA (100 mg/kg), and gentamicin + EA groups for 14 days. Renal function, oxidative stress, inflammatory mediators, ER stress markers, apoptosis, autophagy, tubular injury markers, and histopathological changes were assessed. Results: Gentamicin induced renal dysfunction, tubular injury, and ER stress across all unfolded protein response (UPR) branches (IRE1α, PERK, ATF6), C/EBP homologous protein (CHOP)-associated apoptosis, dysregulated autophagy, and upregulated kidney injury molecule-1 (KIM-1). A selective inflammatory signature was observed, with increased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), whereas tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) remained unchanged. Co-administration of ellagic acid with gentamicin significantly improved renal function markers compared to the gentamicin group. In contrast, ellagic acid alone did not show significant differences compared to the control group. Notably, gentamicin induced compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression, while ellagic acid co-treatment attenuated this compensatory upregulation, likely secondary to reduced oxidative stress burden. Conclusions: This study provides integrated evidence that ER stress is closely associated with gentamicin nephrotoxicity. The key novel findings include selective suppression of IL-6, modulation of the apoptosis-autophagy balance, and attenuation of Nrf2/HO-1 signaling without direct reactive oxygen species (ROS) scavenging, demonstrating a multi-target framework for EA’s renoprotective effects. These findings suggest that ellagic acid mitigates renal injury in a context-dependent manner rather than confirming a direct causal mechanism. Full article

Background/Objectives: Obesity-related insulin resistance is accompanied by chronic low-grade inflammation, but the extent to which weight loss modifies circulating cytokines in a sex-specific manner remains insufficiently understood. The aim of this study was to assess sex-specific cytokine responses and metabolic adaptation in adults with obesity and insulin resistance following a six-month weight-reduction program (WRP). Methods: Thirty-six participants (24 women and 12 men) with a value of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2 underwent an individualized low-calorie diet combined with moderate physical activity and health education. Anthropometric, body composition, biochemical, oxidative stress, and cytokine parameters were evaluated before and after the intervention. Results: Both women and men showed significant reductions in body mass, Body Mass Index (BMI), waist circumference, visceral fat area (VFA), body fat mass (BFM), fasting glucose, HOMA-IR, modified Atherogenic Index of Plasma (new-AIP), malondialdehyde (MDA), and Oxidative Stress Index (OSI). Women additionally showed significant decreases in fat-free mass (FFM), skeletal-muscle mass (SMM), total body water (TBW), glycated hemoglobin A_1c (HbA1c), and triacylglycerols, whereas cholesterol in high-density lipoproteins (HDL-C) increased significantly in men. Cytokine changes were selective rather than uniform. Interleukin-1 receptor antagonist (IL-1ra), Interleukin 6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α) decreased in both women and men. In sex-stratified analyses, IL-1β decreased significantly only in women, whereas IL-7 decreased significantly only in men. ClinicalTrials.gov Registration: [NCT07645105] (retrospectively registered on [11 June 2026]). Conclusions: A 6-month lifestyle-based weight-reduction program in adults with overweight or obesity and insulin resistance was associated with metabolic improvement, reduced oxidative stress, and partial attenuation of obesity-related low-grade inflammation. The observed cytokine and metabolic changes suggest sex-related patterns of immunometabolic adaptation to weight reduction. However, these findings should be interpreted cautiously because of the relatively small sex-stratified subgroups and the number of cytokine endpoints analyzed, and they require confirmation in larger, sex-balanced studies. Full article

We aimed to investigate the potential antidiabetic effects of an ethanol extract derived from the fruit of Malus floribunda (MF) on insulin resistance, oxidative stress, inflammation, and apoptosis associated with diabetes. In our study, diabetes was induced through the administration of a 10% fructose solution and 40 mg/kg Streptozotocin (STZ). Once diabetes had been induced, metformin (Met) 300 mg/kg and the MF extract (250 mg/kg and 500 mg/kg) were administered orally once daily for 30 days. At the end of the experiment, markers of insulin resistance, oxidative stress, inflammation and apoptosis were evaluated in the serum, muscle and liver tissues of the different groups. The MF extract significantly improved the levels of HOMA-IR, insulin receptor (InR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4)—key components of peripheral insulin resistance associated with type 2 diabetes. Fructose/streptozotocin induced oxidative stress, inflammation, and apoptosis were mitigated by increasing Nuclear factor erythroid 2-related factor 2 (NRF2) expression, which restored antioxidant levels (Superoxide dismutase (SOD) and Glutathione (GSH)), significantly improved cytokine levels (Tumor necrosis factor alpha (TNF-α) and Interleukin-1 beta (IL-1β)), and downregulated apoptotic proteins (caspase-3 and caspase-9). We demonstrated the antidiabetic effect of MF extract using a fructose/streptozotocin-induced type 2 diabetes model. MF extract shows promise for future use in herbal medicine. Full article

Diabetes mellitus (DM) fundamentally disrupts the oral microbiome, initiating a dysbiotic shift that drives progressive periodontal tissue breakdown. This transition is mediated by complex, bidirectional immune crosstalk, primarily centering on the upregulation of the Th17/Interleukin-17 (IL-17) inflammatory pathway. This systematic review and meta-analysis quantified the specific impact of this diabetic microbiota on immune activation and periodontal destruction. A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library was conducted for studies published up to 2026. Eligible studies included assessing oral/salivary microbiome shifts and their localized or systemic immunological consequences in diabetic periodontitis. A random-effects meta-analysis synthesized standardized mean differences (Hedges’ g) to evaluate the magnitude of these effects. Quantitative synthesis of preclinical data (four studies yielding eight discrete comparisons) revealed that exposure to a diabetic/dysbiotic microbiota significantly increased overall immune activation and periodontal inflammation relative to eubiotic controls (pooled Hedges’ g = 3.73, 95% CI 2.96–4.51). Subgroup analyses confirmed profound, statistically significant effects specifically on the Th17/IL-17 axis (g = 4.03) and periodontal bone destruction pathways (g = 3.37). Preclinical murine data suggests diabetes-associated oral dysbiosis may contribute to periodontal destruction by upregulating the Th17/IL-17 immune axis. However, direct extrapolation to humans is restricted, necessitating further clinical studies to validate these findings. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent and biologically aggressive subtype of renal cell carcinoma, characterized by pronounced immunogenicity and extensive remodeling of the tumor microenvironment. Chronic inflammation and dysregulated cytokine signaling contribute substantially to tumor progression. Signal transducer and activator of transcription 3 (STAT3) represents a central molecular hub integrating cytokine- and hypoxia-driven pathways. This review aims to summarize current evidence on the cytokine–STAT3 signaling axis in ccRCC and to evaluate its translational relevance for biomarker development. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases. Experimental, translational, and clinical studies addressing cytokine signaling, STAT3 activation, tumor microenvironment interactions, and biomarker development in ccRCC were evaluated. Particular attention was given to studies analyzing cytokine profiles in tumor tissue, plasma, and urine, as well as their associations with STAT3 activation and clinicopathological parameters. Results: Accumulating evidence indicates that ccRCC exhibits a complex, compartment-specific cytokine signature involving interleukins, chemokines, and tumor necrosis factor (TNF)-related cytokines. Among these mediators, IL-6, IL-8, and selected chemokines such as CXCL10 appear particularly relevant due to their associations with tumor progression, immune modulation, and clinical outcome. Many of these mediators converge on persistent STAT3 activation, which promotes tumor cell survival, angiogenesis, immune suppression, and metastatic potential. Tissue-based analyses demonstrate correlations between altered cytokine expression and STAT3 activation, while urinary cytokine profiles reflect tumor-associated inflammatory processes in a non-invasive manner. Plasma cytokines appear to capture broader systemic inflammatory responses. Conclusions: The cytokine–STAT3 axis represents a biologically plausible signaling network associated with tumor progression and immune modulation in ccRCC. By integrating evidence from cytokine profiling in tumor tissue, plasma, and urine with current knowledge of STAT3 signaling, this review highlights the importance of compartment-specific inflammatory signatures in understanding ccRCC biology and their potential relevance for biomarker discovery. Integrative approaches combining cytokine profiling with functional assessment of STAT3 activation may improve disease characterization and support the development of diagnostic and prognostic biomarkers, although rigorous clinical validation remains necessary. Full article

Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg⁻¹·day⁻¹ for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8⁺ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal. Full article