Search Results (1,041)

Inflammatory bowel disease (IBD) is characterized by excessive oxidative stress, mitochondrial dysfunction, and persistent activation of pro-inflammatory signaling pathways. Danthron, a natural anthraquinone derivative from rhubarb, has been reported to possess anti-inflammatory and antioxidant properties, yet its regulatory mechanisms in intestinal inflammation remain unclear. In this study, we combined network pharmacology, transcriptomic profiling, cell-based assays, intestinal organoids, and a dextran sulfate sodium (DSS)-induced colitis model to determine the protective effects of Danthron against oxidative injury. Integrated target prediction and RNA-seq analysis identified EGFR–PI3K–AKT and Nrf2–HO-1 as key signaling axes modulated by Danthron. In macrophages and intestinal epithelial cells, Danthron markedly suppressed LPS- or H₂O₂-induced ROS accumulation, lipid peroxidation, and mitochondrial membrane potential collapse, while restoring superoxide dismutase activity and reducing malondialdehyde levels. Danthron also inhibited M1 macrophage polarization, preserved epithelial tight-junction proteins, and maintained transepithelial electrical resistance. CETSA, DARTS, and molecular docking confirmed direct engagement of Danthron with components of both the EGFR–PI3K–AKT and Nrf2–HO-1 pathways. In vivo, Danthron significantly ameliorated DSS-induced colitis, reducing inflammatory cytokines, epithelial apoptosis, oxidative stress, and myeloid cell infiltration while improving mucosal architecture and enhancing organoid regenerative capacity. These findings demonstrate that Danthron exerts potent antioxidant and anti-inflammatory effects through coordinated inhibition of EGFR–PI3K–AKT signaling and activation of the Nrf2–HO-1 axis, suggesting its promise as a multi-target therapeutic candidate for IBD. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Periostin is a matricellular protein induced by type 2 cytokines. It has been shown to play important roles in airway inflammation and tissue remodeling. Although periostin has been studied in asthma and chronic rhinosinusitis, its role in allergic rhinitis (AR) and nasal hyperresponsiveness (NHR) is unclear. This study aimed to determine whether periostin is involved in the development of NHR in AR. A murine AR model was established by sensitization and repeated intranasal challenges with Japanese cedar pollen (JCP). In this animal model of AR, an increase in nasal responsiveness to histamine was observed 24 h after the last JCP challenge, indicating the development of NHR. RT-qPCR analysis revealed that the JCP-induced NHR was accompanied by increased periostin gene expression. Immunohistochemical examinations demonstrated the expression of integrin subunits α_V (Itgav), β₃ (Itgb3) and β₅ (Itgb5), which are known as receptors for periostin, in the nasal mucosa, especially in the mucosal epithelium. Notably, repeated intranasal administration of recombinant periostin to healthy I mice reproduced the NHR phenotype, as observed in AR model mice. These findings suggest that periostin upregulation in the nasal mucosa plays a causal role in the development of NHR, a key feature of AR. Full article

Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays. The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm² after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups. Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of Staphylococcus aureus. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α. The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis. Full article

Growing evidence suggests that persistent oral infectious diseases (OIDs) contribute to systemic disease, highlighting the importance of understanding their pathogenic mechanisms. Conventional dental treatments, primarily mechanical debridement, surgical intervention, or antimicrobial therapy, often struggle to fully control inflammation or prevent progressive tissue destruction. The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immunity, mediating the maturation of proinflammatory cytokines (IL-1β and IL-18) and the pyroptosis-inducing protein gasdermin D. Dysregulated or excessive activation of NLRP3 contributes to the initiation and progression of major oral diseases, including periodontitis, peri-implantitis, pulpitis, and oral mucosal inflammation. Despite growing interest in NLRP3, comprehensive and up-to-date reviews integrating its pathogenic mechanisms and therapeutic potential remain limited. This review summarizes current and past evidence on the role of the NLRP3 inflammasome in oral disease development, highlights emerging pharmacological strategies, and outlines future research directions. Existing studies demonstrate that microbial components and danger signals from injured tissues activate NLRP3, thereby amplifying inflammation, tissue degradation, and bone resorption. Preclinical studies indicate that inflammasome inhibitors and several natural compounds reduce tissue damage; however, their clinical translation remains limited. These findings emphasize the need for deeper understanding of NLRP3-mediated pathways, with translational and clinical research offering promising therapeutic opportunities for oral diseases. Full article

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article

Background: Pediatric inflammatory bowel disease (pIBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation and fibrosis. Identifying molecular mediators involved in inflammation and tissue repair is critical for improving disease management. Objective: To examine the expression of periostin, TGF-β, and SLUG in pIBD and assess their potential roles in intestinal inflammation, fibrosis, and mucosal healing. Methods: Intestinal biopsies from 33 pediatric patients (11 CD, 22 UC) and 10 healthy controls were analyzed immunohistochemically. Quantitative PCR evaluated POSTN, TGF-β1, and SNAI2 expression in 22 patients and 6 controls. Correlations with fecal calprotectin, the Pediatric Crohn’s Disease Activity Index (PCDAI), and the Pediatric Ulcerative Colitis Activity Index (PUCAI) were determined. Results: Periostin, TGF-β, and SLUG expression were significantly increased in pIBD compared with controls. Periostin levels were higher in CD than in UC. All markers correlated positively at mRNA and protein levels. Notably, periostin showed an inverse correlation with fecal calprotectin and PCDAI scores. Conclusions: Periostin, TGF-β, and SLUG may represent biomarkers of pIBD activity. Periostin appears to mediate inflammation and promote mucosal fibrosis or repair, and its inverse association with disease activity suggests a potential therapeutic role in pIBD. Full article

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes. Full article

The nasal microbiome represents a complex and dynamic microbial ecosystem that contributes to mucosal defense, epithelial homeostasis, immune regulation, and olfactory function. Increasing evidence indicates that this microbial community actively interacts with host physiology, while alterations in its composition are associated with chronic inflammation, oxidative stress, and olfactory impairment. Such changes have been reported in conditions including chronic rhinosinusitis, allergic rhinitis, and post-viral anosmia. Beyond local effects, chronic nasal inflammation has been hypothesized to influence neuroinflammatory processes and protein aggregation pathways involving α-synuclein and tau, potentially linking nasal microbial imbalance to neurodegenerative mechanisms. However, current evidence remains largely indirect and does not support a causal relationship. This narrative review summarizes current clinical and immunological evidence on the role of the nasal microbiome in olfactory function and dysfunction, highlighting limitations of existing studies and outlining future research directions. Full article

Sexual violence against women is a global issue with profound health consequences, including elevated HIV risk due to genital tract inflammation and injury. However, limited research has examined the influence of mental health on HIV-related immunity after violence. We analyzed longitudinal data from female survivors of past-month rape (N = 25) to explore associations between mental health (perceived stress, depression, post-traumatic stress disorder [PTSD], and resilience) and HIV-associated immune biomarkers in the female genital tract. In bivariate analyses, mental health improved over the three-month follow-up period. Immune biomarker levels remained largely stable, except for TNF-α and SLPI. At baseline, depression was significantly correlated with TNF-α, IL-6, and IL-1β. In regression analyses, depression was associated with TNF-α (β = −0.133 to −0.152) and IL-6 (β = −0.171 to −0.207). PTSD was significantly associated with IL-1α (β = 0.576 to 1.681). Depression and resilience were negatively associated with percent HIV inhibition in adjusted models. These findings suggest that depression and PTSD are associated with genital tract inflammation following sexual violence, which may compromise mucosal immunity and enhance HIV risk. This highlights the importance of integrated mental health and immunological care for survivors and the need for further research into psychoneuroimmune pathways influencing HIV risk after trauma. Full article

Brachycephalic obstructive airway syndrome is a group of abnormalities that primarily affect the upper respiratory tract, particularly in dogs—especially in English and French bulldogs, pugs, and Boston terriers. The description and the consequences of these anomalies are well known. We performed a detailed histopathological analysis of soft palate samples taken from brachycephalic dogs with BOAS III. We examined the impact of the severity and composition of inflammatory infiltrates on individual histological structures, such as mucosal membrane, serosal and mucosal glands, and muscles. The study was conducted on 50 samples of soft palate tissue collected from pugs and French bulldogs. The sections were then stained with haematoxylin and eosin (HE) and Masson–Goldner trichrome. In general, both lymphocytic and plasmocytic inflammation were observed. Plasmacytic inflammation was more commonly associated with more advanced changes, including glandular fibrosis, muscle degeneration, and waxy necrosis of the muscles. Therefore, inflammatory infiltration—particularly plasmocytic infiltration—is associated with more severe clinical symptoms and a poorer prognosis in BOAS III dogs. Full article

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

Background: Chronic kidney disease (CKD) represents a state of persistent, sterile low-grade inflammation in which sustained innate immune activation accelerates renal decline and cardiovascular complications. Diet-induced gut dysbiosis and intestinal barrier dysfunction lower mucosal immune tolerance, promote metabolic endotoxemia, and position the gut as an upstream modulator of systemic inflammatory signaling along the gut–kidney axis. Scope: Most studies address microbiota-derived metabolites, food-derived bioactive peptides, or omega-3 fatty acids separately. This review integrates evidence across these domains and examines their convergent actions on epithelial barrier integrity, immune polarization, oxidative-inflammatory stress, and inflammasome-dependent pathways relevant to CKD progression. Key mechanisms: CKD-associated dysbiosis is characterized by reduced short-chain fatty acid (SCFA) production and increased generation and accumulation of uremic toxins and co-metabolites, including indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and altered bile acids. Reduced SCFA availability weakens tight junction-dependent barrier function and regulatory immune programs, favoring Th17-skewed inflammation and endotoxin translocation. Bioactive peptides modulate inflammatory mediator networks and barrier-related pathways through effects on NF-κB/MAPK signaling and redox balance, while omega-3 fatty acids and specialized pro-resolving mediators support resolution-phase immune responses. Across these modalities, shared control points include barrier integrity, metabolic endotoxemia, oxidative stress, and NLRP3 inflammasome activation. Conclusions: Although evidence remains heterogeneous and largely preclinical, combined nutritional modulation targeting these convergent pathways may offer greater immunomodulatory benefit than isolated interventions. Future multi-omics-guided, factorial trials are required to define responder phenotypes and translate precision immunonutrition strategies into clinical CKD care. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Innate-like T cells (iLTCs) are rapid sentinels at epithelial surfaces, yet their spatial organisation and tissue-linked programmes in psoriatic inflammation remain incompletely defined. Spatial transcriptomics from independent cohorts maps γδT and mucosal-associated invariant T cells (MAIT) niches across psoriatic skin and reveals sharply divergent skin-layer arrangements. Psoriatic plaques show expansion of both niches, with γδT transcriptional signatures present in dermis and epidermis and MAIT signatures strongly enriched in the epidermis. Their compartment-specific positioning is mirrored by distinct transcriptional activities that support dermal-sentinel behaviour for γδT-enriched niches and epithelial-retention programmes for MAIT niches. Clinical severity associates with opposite niche dynamics, marked by decreasing dermal γδT frequencies and increasing epidermal MAIT abundance. Functional profiles reinforce this divergence, as dermal γδT niches display rising exhaustion-associated features with greater severity, whereas epidermal MAIT niches show stronger inflammatory and proliferation-related signals. Peripheral CITE-seq profiling identifies parallel systemic patterns, with reduced γδT frequencies and increased MAIT frequencies in blood, along with exhaustion-associated features in γδT cells and MAIT-specific trafficking cues that align with their behaviour in psoriatic tissue. Together the findings define a spatially imbalanced γδT–MAIT axis in psoriatic inflammation that is linked to layer-specific organisation to local inflammatory cues, systemic immune engagement and clinical severity. Full article