Search Results (1,491)

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with lymph node metastasis (LNM) being a key predictor of recurrence and poor prognosis. Preoperative detection of LNM remains challenging due to the limitations of imaging modalities, leading to inadequate surgical resection in 20–30% of patients. While immune checkpoint molecules have been implicated in PTC progression, the heterogeneity of CD8⁺ T cell exhaustion subsets and their specific association with LNM remain poorly defined. In this study, we aimed to perform an exploratory characterization of the distinct immune landscape of PTC prone to LNM, with a focus on terminal immune exhaustion, in order to generate hypotheses for improved risk stratification and therapeutic strategies. Methods: Fresh PTC tissues from 40 patients (22 LNM-positive and 18 LNM-negative) were analyzed via flow cytometry (FCM) to quantify immune cell subsets, inflammatory cytokines, and chemokines. Immunohistochemistry (IHC) validated CD45⁺ immune cell infiltration. Transcriptomic and clinical data from 448 PTC patients in The Cancer Genome Atlas (TCGA-PTC) cohort were used for bioinformatic analysis consistent with the observed phenotype, including Gene Set Variation Analysis (GSVA) of terminal exhaustion gene signatures. Results: LNM-positive PTC exhibited a unique inflammatory milieu with significantly elevated IL-6, IL-1ra, CCL5, and IL-9 levels (all p < 0.05) in tumor interstitial fluid. FCM analysis revealed that LNM-positive PTC had increased infiltration of total CD45⁺ immune cells, CD3⁺ T cells, and CD3⁺CD8⁺ T cells (all p < 0.05). Critically, terminally exhausted PD-1^hiTIM-3⁺ CD8⁺ T cells were significantly enriched in LNM-positive PTC (p = 0.022) and positively correlated with extrathyroidal extension (p = 0.044). Additionally, LNM risk was associated with increased CD4⁺ regulatory T (Treg) cell frequency (p = 0.023) and elevated CTLA-4 expression on CD4⁺ T cells (p = 0.047). In TCGA-PTC validation, the terminal exhaustion gene signature was predominantly enriched in LNM-positive (p < 0.0001) and advanced-stage PTC (p < 0.001) and strongly correlated with BRAF mutation (predominantly V600E) (p < 0.0001)—the most common oncogenic driver in aggressive PTC. Conclusions: Our findings suggest a terminal immune exhaustion phenotype (characterized by PD-1^hiTIM-3⁺ CD8⁺ T cells and Treg enrichment) as a potential key feature associated with LNM-prone PTC. This phenotype shows consistency across clinical samples and TCGA datasets, linking BRAF mutation (predominantly V600E) to immune suppression and metastatic potential. These insights provide a novel exploratory immune-based biomarker for LNM risk stratification and support the potential of combining anti-PD-1/TIM-3 therapy with BRAF inhibitors for high-risk PTC, which should be confirmed in future studies. Full article

Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system. 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

CA, a major bioactive component of cinnamon essential oil, possesses broad-spectrum antibacterial, anti-inflammatory, and antioxidant activities and is widely recognized as a safe food additive. In the context of exploring natural plant extracts for the prevention and alleviation of bovine mastitis, it is noteworthy that research and clinical reports on the use of cinnamon essential oil for bovine mastitis are relatively limited. In this study, S. aureus isolates recovered from subclinical bovine mastitis were used to establish a mastitis infection model, and the antioxidant and anti-inflammatory effects of CA were preliminarily investigated in both mouse mastitis models and mammary epithelial cells (MAC-T). Studies have demonstrated that in a mouse model of mastitis, CA reduces inflammatory cell infiltration, decreases myeloperoxidase (MPO) activity, and inhibits S. aureus colonization in mammary tissue. CA alleviates oxidative stress by lowering malondialdehyde (MDA) levels, enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and activating the Nrf2/HO-1/xCT antioxidant pathway. In addition, CA suppresses the activation of the TLR4/NF-κB signalling pathway and modulates the expression of Bax and Bcl-2, accompanied by reduced levels of pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), ultimately ameliorating mastitis in mice. In the MAC-T cell infection model, CA significantly inhibited S. aureus adhesion and invasion and decreased the production of pro-inflammatory cytokines and mediators. CA also activated the Nrf2/HO-1/xCT antioxidant pathway, which led to decreased intracellular reactive oxygen species (ROS), concurrently inhibited the TLR4/NF-κB pathway, and downregulated apoptotic protein expression, ultimately attenuating inflammation in MAC-T cells. Collectively, these findings demonstrate that CA exerts protective effects against inflammation and oxidative damage in both mammary tissues and epithelial cells infected with S. aureus. Thus, this study provides a theoretical and practical basis for further exploring CA as a candidate therapy for bovine mastitis. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as critical regulators of gene expression and key cellular processes in cancer, including tumor cell proliferation, survival, metastasis, and both innate and adaptive immune responses within the tumor microenvironment. Through their ability to modulate immune cell development, differentiation, polarization, antigen presentation, cytokine signaling and immune checkpoint expression, miRNAs play a vital role in shaping immune responses and represent attractive therapeutic candidates for remodeling the tumor immune microenvironment. This review provides a comprehensive overview of the mechanisms through which miRNAs regulate anti-tumor immunity and contribute to immune evasion with particular emphasis on their role in modulating major immune checkpoint pathways, including PD-1/PD-L1, CTLA-4, LAG-3, TIM-3 and CD28-mediated signaling. We further examine the contribution of miRNAs to therapeutic resistance and discuss their potential integration with immune checkpoint blockade, chemotherapy, PARP inhibitors and targeted therapies to enhance antitumor efficacy and overcome treatment resistance. Recent advances in spatial transcriptomics and computational approaches have expanded our understanding of miRNA-mediated regulatory networks at single-cell and tissue levels and provide new insights into tumor–immune interactions. In addition, we evaluate the current progress in the clinical development of miRNA-based therapeutics, including miRNA mimics and inhibitors and discuss the major challenges associated with efficient delivery, off-target effects, immunogenicity and patient heterogeneity. Collectively, the evidence highlights the growing potential of miRNAs as diagnostic biomarkers, therapeutic targets and therapeutic tools in cancer immunotherapy. Continued advances in RNA therapeutics, delivery technologies and multi-omics approaches are expected to accelerate the clinical translation of miRNA-based strategies for personalized cancer therapy. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition with substantial global burden and rising incidence, requiring an expanding range of advanced therapies. This focused narrative review examines the mechanistic rationale, comparative clinical evidence, and translational implications of approved and emerging targeted therapies for adult IBD. A structured literature search was conducted in PubMed, Scopus, and Web of Science for publications from January 2021 to March 2026. Thirty-eight articles were selected as the core evidence set with landmark trials and clinical guidelines added when needed for historical or practice context. Evidence was synthesised narratively, with an explicit distinction between direct head-to-head comparisons, placebo-controlled trials, indirect network comparisons, and observational data. In UC, VARSITY showed higher week-52 clinical remission and endoscopic improvement with vedolizumab than adalimumab; in CD after anti–tumour necrosis factor (anti-TNF) failure, SEQUENCE showed risankizumab noninferior to ustekinumab for week-24 clinical remission and superior for week-48 endoscopic remission. Agents targeting tumour necrosis factor-like cytokine 1A (TL1A) have shown encouraging activity in phase 2/2b trials, but long-term effectiveness and safety remain uncertain. The current evidence supports mechanism-informed rather than biomarker-defined treatment selection. Confidence in comparative conclusions is greatest when supported by direct randomised evidence, whereas observational and indirect comparisons require caution because of confounding, heterogeneity, and differences in populations and outcome definitions. Clinical translation therefore requires the integration of the disease phenotype, prior treatment exposure, safety risks, and patient preference, with objective reassessment after therapy initiation. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by rapid motoneuron degeneration. Hydrogen sulfide (H₂S), a signaling molecule that regulates post-translational modification, has recently been implicated in the pathophysiology of ALS. Our study aimed to design, synthesize, and investigate the potential effects of (2S)-2-aminopentanethioic S-acid (POM16), an isomer of the slow-releasing H₂S donor thiovaline, in a genetic ALS model. FUS [1-359]-tg mice, which recapitulate ALS syndrome, and their wild-type (WT) littermates received POM16 (at a dose of 50/mg/kg) or standard ALS therapy riluzole (at a dose of 8 mg/kg/day) dissolved in drinking water, or vehicle, for six weeks starting at nine weeks of age. The onset of paralysis, physiological and motor functions, muscle atrophy, density of spinal cord motoneurons, gene expression of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF), and concentration of oxidative stress marker malondialdehyde (MDA) in the spinal cord were studied. POM16-treated mutants displayed significant improvements in body weight, water and diet intake, as well as behavior in the rotarod, wire, and pole tests. The percentage of mice with paralysis on the 6th week of dosing was reduced from 48% in vehicle-treated mutants to 16% in POM16-treated FUS [1-359]-tg mice, while in the riluzole-treated group, it was 38%, not reaching significance. Notably, muscle weight was not significantly improved by the latter treatment, unlike the dosing with POM16. In comparison with vehicle-treated FUS [1-359]-tg mice, POM16-treated mutants had significantly higher motor neuron density in the spinal cord, lower MDA levels, and reduced muscle atrophy ranking. Thus, new compound POM16 has a therapeutic potential to counteract ALS pathology that is likely mediated via anti-oxidative stress mechanisms. Given that any effective treatment of this devastating disease is currently lacking, it is hoped that POM16 can be a promising therapy for ALS. Full article

Background: While live-cell therapies face significant translational hurdles, cell-free secretomes derived from fetal progenitor cells offer a unique, scalable approach natively programmed for scarless tissue repair. Methods: This GLP-compliant study evaluated the therapeutic efficacy spectrum of an off-the-shelf, clinical-grade, intratracheal lyophilized FE002-Lu lung fibroblast conditioned medium (LFCM) across five controlled Wistar rat models of induced lung injury: bleomycin (5 mg/kg), asbestos (100 µg/rat), hyperoxia (100% oxygen exposure), silica (30 mg/rat), and lipopolysaccharide (LPS, 4 mg/kg). Following lung injury induction and symptom onset, symptomatic rats were randomized to receive intratracheal LFCM (low, mid, or high dose) or a vehicle control every 4 days for 28 days. Results: The intervention demonstrated an exceptional safety profile, maintaining 100% survival with no severe procedural toxicity across all cohorts. Across all study arms, LFCM effectively attenuated pulmonary inflammation, reducing pro-inflammatory markers (IL-1β, IL-6, TNF-α, and CINC-1) in bronchoalveolar lavage fluid. Concurrently, high LFCM doses consistently elevated the anti-inflammatory cytokine IL-10. Within the lung tissue, mid- and high doses significantly reduced key pro-fibrotic drivers, including TGF-β1, TIMP-1, WISP-1, and hydroxyproline. Treatments consistently decreased α-SMA expression and pro-fibrotic gene mRNA levels, mitigating pulmonary myofibroblast activation. This correlated with reduced Ashcroft scores and collagen deposition, thereby preserving lung architecture. Notably, the FE002-Lu LFCM treatment exerted a biphasic regulation of extracellular matrix turnover: it elevated Cathepsin-D and MMP-12 in the bleomycin arm to actively clear newly deposited fibrotic debris, while reducing these markers in the hyperoxia and LPS arms to prevent acute collateral degradation of the native lung matrix. In both particulate models (asbestos and silica), the LFCM mid-dose established an optimal therapeutic threshold, avoiding the localized secretome saturation and pro-fibrotic exacerbation occasionally observed at higher doses. Conclusions: Lyophilized FE002-Lu LFCM acts as a potent, pleiotropic biologic that effectively resolves acute pulmonary inflammation and arrests progressive fibrotic remodeling across multiple distinct in vivo models. By overcoming the cold-chain and delivery limitations inherent to pulmonary live-cell therapies, this stable, cell-free secretome represents a highly scalable, “off-the-shelf” candidate poised for non-invasive, aerosolized clinical translation. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, pancreatic β-cell dysfunction, and dysregulated glucose and lipid metabolism. Sustained hyperglycemia and hyperlipidemia promote excessive reactive oxygen species (ROS) production, antioxidant defense depletion, and chronic low-grade inflammation, thereby aggravating insulin signaling impairment, β-cell injury, and diabetes-related complications. Although current glucose-lowering therapies have improved glycemic control, weight management, and cardiorenal outcomes, oxidative stress and inflammation remain incompletely addressed in many individuals with T2DM. Curcumin, a natural polyphenol derived from Curcuma longa L., exhibits antioxidant, anti-inflammatory, lipid-regulating, insulin-sensitizing, and tissue-protective activities. Evidence suggests that curcumin may alleviate T2DM-associated oxidative stress by suppressing ROS generation, reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, modulating the advanced glycation end-product/receptor for advanced glycation end-product (AGE/RAGE) axis, activating nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling, preserving mitochondrial homeostasis, and protecting β-cells. It may also inhibit nuclear factor-κB (NF-κB) and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signaling, decrease pro-inflammatory cytokines and C-reactive protein (CRP), improve metabolic tissue inflammation, and attenuate gut-derived inflammation by regulating gut microbiota and intestinal barrier function. However, current clinical evidence mainly supports modest improvements in metabolic, inflammatory, oxidative stress-related, and selected complication-related biomarkers rather than definitive disease-modifying outcomes. Moreover, formulation heterogeneity, low bioavailability, limited pharmacokinetic reporting, and insufficient long-term endpoint data remain major translational barriers. This review summarizes the molecular mechanisms, clinical evidence, formulation-dependent interpretation, safety considerations, and translational limitations of curcumin as a candidate adjunctive intervention for T2DM, rather than as a replacement for evidence-based antidiabetic therapy. Full article

The emergence of SARS-CoV-2 variants and antiviral resistance highlights the need for improved therapeutic strategies against COVID-19 and other coronavirus infections. By pairing direct-acting antivirals with repurposed host-modulating drugs, combination therapy approaches may enhance antiviral efficacy while mitigating inflammation. In this study, we evaluated the effects of combining Nirmatrelvir (a SARS-CoV-2 main protease inhibitor) with Ivermectin, Azithromycin or Doxycycline—using a murine hepatitis virus (MHV) infection model of RAW264.7 macrophages. Checkerboard assays demonstrated that the Nirmatrelvir–Ivermectin combination exhibited strongly synergistic antiviral activity. This combination achieved potent inhibition of live virus titer of at least 5 to 6 log₁₀ and reduction in viral RNA load of 3 log₁₀, at drug concentrations much lower than the respective monotherapies. The Nirmatrelvir–Ivermectin combination treatment affected the coronavirus replication cycle at the same time-point of 8 h as Nirmatrelvir monotherapy. Moreover, multiplex cytokine protein profiling revealed that Nirmatrelvir–Ivermectin markedly suppressed key pro-inflammatory cytokines and chemokines associated with the cytokine storm, including IL-6, TNF-α, IL-1β, and MCP-1. Conversely, the combinations of Nirmatrelvir with Azithromycin or Doxycycline exhibited only additive or mildly additive effects, with alterations in certain cytokine levels. These findings support the potential of Nirmatrelvir–Ivermectin as a promising novel combination therapy with both antiviral and anti-inflammatory benefits, warranting further in vivo validation and clinical investigation. Full article

The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article

Inflammation can either encourage or suppress tumor growth, thus having a two-sided effect on cancer development. This depends on the balance between pro-tumor and anti-tumor immune responses within the tumor microenvironment (TME). Pro-tumor inflammation, driven by specific immune cells, enhances blood flow and nutrient supply to tumors, promoting the activation of dormant cancer cells (DCCs). Conversely, antitumor inflammation hinders blood flow and can force active cancer cells into a state of dormancy. Tumors actively shift this balance towards pro-tumor inflammation to create a favorable environment for growth. Therefore, anti-inflammatory therapy may be an integral part of comprehensive cancer immunotherapy. This review explores how different anti-inflammatory medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, anti-leukotrienes, statins, drugs that block pro-inflammatory cytokines, agents that inhibit oxidative phosphorylation, antioxidant vitamins, anti-angiogenic drugs, and low-dose chemotherapy, can be used to combat cancer. Granulocyte counts and erythrocyte sedimentation rate (ESR) can be used to assess inflammation levels and the effectiveness of anti-inflammatory treatments. We advocate for a paradigm shift in cancer treatment, moving away from aggressive tumor destruction, which triggers uncontrolled tumor regeneration, toward long-term immunological control of tumor growth while preserving the patient’s overall health. Full article

Prostate cancer is common in older men, yet mechanisms linking aging to tumor progression remain incompletely defined. Beyond genetic alterations, aging reshapes the prostate microenvironment through cellular senescence, chronic low-grade inflammation, immune dysfunction, stromal remodeling, metabolic stress, and impaired tissue repair, collectively promoting inflammaging. This persistent inflammatory state may create a permissive niche for tumor initiation, progression, immune evasion, and treatment resistance. Senescent epithelial and stromal cells release cytokines, chemokines, growth factors, matrix-remodeling enzymes, and extracellular vesicles through the senescence-associated secretory phenotype (SASP). In parallel, immune aging alters T-cell subsets, myeloid cells, macrophages, and anti-tumor surveillance. This review summarizes how SASP programs, Th17/Treg imbalance, IL-17/IL-23 signaling, myeloid remodeling, stromal aging, metabolic stress, and immune–stromal–epithelial crosstalk shape prostate cancer biology. We further discuss therapeutic implications, including cytokine modulation, senescence-directed therapy, metabolic intervention, and biomarker-guided strategies. This review highlights key knowledge gaps and proposes a framework for age-aware prostate cancer research, biomarker development, and therapeutic strategies. Full article

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), remains a major global health challenge. The prolonged duration of treatment and the emergence of multidrug-resistant strains have highlighted the need for alternative therapeutic strategies. This study investigated the therapeutic potential of Ag85A aptamer-conjugated PEGylated niosomes encapsulating ethanolic extract of propolis (Ag85A-PEGNio/EEP) using Mtb-infected macrophage model. Ag85A-PEGNio/EEP exhibited efficient cellular uptake, with more than 99.8% internalization by macrophages, and trafficked host phagolysosome, facilitating targeted delivery of EEP to intracellular Mtb. Ag85A-PEGNio/EEP treatment showed an anti-mycobacterium efficacy by reducing intracellular Mtb viability by approximately 51.2% compared with untreated controls. Moreover, Ag85A-PEGNio/EEP modulated macrophage immune responses by significantly increasing the expression of the pro-inflammatory cytokines IL-12 (8.4-fold) and IL-6 (3.8-fold), while markedly decreasing the expression of the anti-inflammatory cytokine IL-10 (6.4-fold). Protein–protein interaction (PPI) network analysis further revealed the association of proteins with immune regulation and antioxidant responses in treated cells. These findings suggest that Ag85A-PEGNio/EEP functions as a dual-action therapeutic platform by enhancing intracellular anti-mycobacterial activity while balancing host immune responses. This targeted nano-delivery system represents a promising candidate for host-directed TB therapy and further investigations are needed to validate these outcomes and explore their potential applications against TB treatment challenges. Full article

Background/Objectives: Acute inflammatory episodes demand rapid symptom control while limiting systemic exposure. We assessed whether co-therapy with the selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib and the corticosteroid betamethasone provides antinociceptive and anti-edema activity in a rat model with complete Freund’s adjuvant-induced arthritis (AIA). Methods: Male Wistar rats (n = 10/group) were allocated to seven groups: Intact, AIA disease control, indomethacin 5 mg/kg, etoricoxib 8 mg/kg, betamethasone 0.022 mg/kg, low-dose combination (4 + 0.011 mg/kg), and full-dose combination (8 + 0.022 mg/kg), administered orally once daily from Days 4 to 28. Paw edema, von Frey withdrawal thresholds, and clinical arthritis score were assessed longitudinally as area under the curve (AUC) values. Terminal joint tissues were profiled for cytokines, prostaglandin pathway mediators, and immune cell markers. Results: Both combinations reduced edema and improved mechanical thresholds. The full-dose combination exceeded either monotherapy regarding mechanical sensitivity and the arthritis index, consistent with additive activity. The low-dose combination matched full-dose monotherapies, consistent with a dose-reduction effect. Biomarker shifts indicated attenuated prostaglandin signaling and a pro-resolving cytokine balance. Conclusions: These findings support the further evaluation of etoricoxib–betamethasone co-therapy for acute inflammatory conditions. Full article