Immunopharmacology and Immunotoxicology最新文献

{"title":"Myricetin attenuates atrazine-induced dysregulation of the hypothalamic-pituitary-adrenal axis of rats via anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms.","authors":"Morris M Akpan, Cynthia N Ikeji, Clementina M Arije, Khadija A Mohammed, Faoziyat A Salaudeen, Isaac A Adedara, Solomon E Owumi, Ebenezer O Farombi","doi":"10.1080/08923973.2026.2662624","DOIUrl":"10.1080/08923973.2026.2662624","url":null,"abstract":"<p><strong>Background: </strong>The hypothalamic-pituitary-adrenal (HPA) axis is an important part of the stress response system that produces a biological reaction to stressful stimuli and can be activated by stressors such as atrazine. Atrazine (ATZ) is a common triazine herbicide used in the management of weeds in corn and sugarcane, and its persistence in the environment through runoff and leaching leads to frequent contamination of soil and water, with subsequent adverse health implications. Myricetin (MYR) is a biologically active compound with various pharmacological potentials against noxious agents.</p><p><strong>Objective and methods: </strong>This study evaluated the effects of MYR on the HPA axis of male Wistar rats sub-chronically exposed to atrazine (ATZ), gavaged with either atrazine (50 mg/kg), myricetin (20 mg/kg), or a combination of both for 45 consecutive days.</p><p><strong>Result: </strong>Exposure to ATZ increased serum levels of adrenocorticotropin-releasing hormone (ACTH) and corticosterone, and significantly decreased the activities of hypothalamic and adrenal antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase, reduced glutathione), and hypothalamic acetylcholinesterase (AChE). More so, ATZ-challenged rats showed increased levels of reactive oxygen species and lipid peroxidation, Nitric oxide, tumor necrosis factor-α, interleukin-1β, and caspase-3 in both tissues. Conversely, treatment with myricetin significantly restored the serum levels of ACTH and corticosterone, enhanced the antioxidant enzyme activities, reduced the oxidative-inflammatory and apoptotic markers in both tissues, and increased the hypothalamic AChE activity of the treated animals. Myricetin also reversed the histological abnormalities that atrazine elicited in the treated animals.</p><p><strong>Conclusion: </strong>Overall, MYR, through its antioxidant, anti-inflammatory, and anti-apoptotic properties, attenuated the ATZ-induced disruption of the HPA axis of rats.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":3.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin and crocin ameliorate DOX-induced cardiotoxicity in rats via activating the Nrf-2/HO-1/NQO1 pathway: a comparative study.","authors":"Anwaar M Shaban, Eman A Ali, Marwa Mohamed Ibrahim Khalil, Marwa Omar, Yousra Ali Rohem Al-Ghalban, Eman I El-Gizawy","doi":"10.1080/08923973.2026.2648210","DOIUrl":"10.1080/08923973.2026.2648210","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin-(DOX-) related cardiotoxicity is a progressive degenerative loss of cardiac muscle mass and strength. This investigation aims to compare the anticipated cardioprotective effects of crocin (Cr) and dapagliflozin (DAPA) against DOX-induced cardiotoxicity, and to assess their effects on apoptosis and the Nrf-2/HO-1/NQO1 pathway.</p><p><strong>Materials and methods: </strong>Forty Wistar male rats were randomly divided into four groups: The control group received distilled water (DW) by oral gavage. The DOX group was given DOX 3 times/week, i.p., 2.5 mg/kg for 3 weeks. The Cr + DOX-treated group was intraperitoneally injected with Cr daily, concomitantly with DOX, for 12 weeks. The DAPA + DOX-treated group received DAPA daily by oral gavage concomitantly with DOX for 12 weeks. Initial fasting blood glucose (FBG), body weight, vital signs, systolic blood pressure (SBP), and electrocardiography (ECG) were recorded and then repeated monthly throughout the study period. After 12 weeks, biochemical analyses were performed. Moreover, histopathological and immunohistochemical examinations of cardiac tissue were conducted.</p><p><strong>Results: </strong>DOX significantly affected FBG and increased oxidative stress markers and proinflammatory cytokines, with hypotension, bradycardia, ECG changes, and downregulation of antioxidant genes (Nrf-2/HO-1/NQO1) mRNA. Besides, cardiac biomarkers deteriorated. Administration of either Cr or DAPA resulted in significant improvements in all tested parameters compared with DOX. However, the DAPA + DOX group showed greater improvement, particularly in some parameters.</p><p><strong>Conclusion: </strong>DAPA is a promising new cardioprotective medication against DOX-related cardiotoxicity. Cardiotoxicity is better controlled with DAPA than Cr by suppressing oxidative stress, apoptosis, and upregulation of the antioxidant Nrf-2/HO-1/NQO1 genes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-18"},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vildagliptin alleviates cardiomyocyte apoptosis and inflammatory responses in the treatment of non-valvular atrial fibrillation by regulating the NO/sGC/cGMP signaling pathway.","authors":"Zhaodi Wang, Zhihan Zhao, Xiaobiao Zang, Lei Wang, Yonghui Zhao","doi":"10.1080/08923973.2026.2639559","DOIUrl":"https://doi.org/10.1080/08923973.2026.2639559","url":null,"abstract":"<p><strong>Aim: </strong>to investigate the therapeutic effects of vildagliptin on non-valvular atrial fibrillation (NVAF) and to determine whether its underlying mechanism of action is associated with modulation of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) signaling pathway.</p><p><strong>Methods: </strong>Thirty clean-grade male Sprague-Dawley (SD) rats were enrolled. Atrial fibrillation was first induced by electrical stimulation of the vagus nerve. After confirming postoperative survival in all animals, the rats were randomly assigned to a normal control group (CG), an atrial fibrillation group (AFG), and a drug-treated group (DG), thereby establishing an NVAF rat model. Myocardial electro-physiological parameters, levels of inflammatory cytokines, the cardiomyocyte apoptosis index (AI), as well as nitric oxide (NO), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and soluble guanylate cyclase (sGC) were measured and compared among the three groups.</p><p><strong>Results: </strong>Compared with the CG, the AFG exhibited significantly reduced effective refractory period (ERP), action potential duration at 90% repolarization (APD90), and the ERP/APD90 ratio, accompanied by markedly elevated levels of inflammatory cytokines and a higher AI. In addition, concentrations of NO, cAMP, and cGMP were significantly decreased, sGC expression was downregulated, and phosphodiesterase 5 A (PDE5A) expression was upregulated (all <i>p</i> < 0.05). In comparison with the AFG, rats in the DG showed significant increases in ERP, APD90, and the ERP/APD90 ratio, along with pronounced reductions in inflammatory cytokine levels and cardiomyocyte AI.</p><p><strong>Conclusion: </strong>Vildagliptin can markedly improve the myocardial electrical and vascular functions and reduce cardiomyocyte apoptosis and inflammatory responses in NVAF.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the nitric oxide signaling pathway induced by ezetimibe on renal injury in streptozotocin-induced diabetic rat: role of anti-oxidative and anti-inflammatory effects.","authors":"Amin Hasanvand, Amin Rezaei Ghaleh, Bahram Delfan, Azita Zafar Mohtashami, Zahra Haghighatian, Elham Goodarzi, Babak Hadian","doi":"10.1080/08923973.2026.2657952","DOIUrl":"https://doi.org/10.1080/08923973.2026.2657952","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes is a disease characterized by impaired insulin secretion and/or function. Ezetimibe is a lipid-lowering drug widely used for the treatment of hypercholesterolemia. This study investigates the impact of ezetimibe on nitric oxide level and its effects on diabetic nephropathy.</p><p><strong>Materials & methods: </strong>Sixty rats were used in the study, divided into the following groups: a control group (healthy rats), a diabetic control group, a diabetic group treated with metformin, a diabetic group treated with ezetimibe, a diabetic group treated with ezetimibe plus L-NAME, and a diabetic group treated with ezetimibe plus L-arginine. After 28 days, blood samples were collected and rats were euthanized to examine nitric oxide levels and kidney histology. The levels of creatinine, urea, glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor (TNF-α), and interleukin (IL-6) were measured.</p><p><strong>Results: </strong>Ezetimibe treatment resulted in decreased levels of urea and creatinine in blood samples, along with reduced TNF-α and IL-6 levels in the kidneys. Additionally, GPx and CAT levels significantly increased following ezetimibe treatment. Our findings showed that the combination of ezetimibe and L-arginine provided protection against nephropathy in the animals, as demonstrated by enhanced antioxidant activity and reduced inflammation. However, the beneficial effects of ezetimibe were reversed by L-NAME.</p><p><strong>Conclusion: </strong>Ezetimibe protected the kidney against diabetic injury mainly by activating the nitric oxide signaling pathway, enhancing antioxidant enzyme activity, and reducing inflammation, suggesting that its nephroprotective effects are NO-dependent.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl-Cyclohexanone as a potential CB2 agonist: <i>in vitro</i> and <i>in silico</i> evidence in inflammatory modulation.","authors":"Tainá Larissa Lubschinski, Luiz Antonio Escorteganha Pollo, Luigi Arruda Nardino, Roberto Gomes de Carvalho Filho, Ziliani da Silva Buss, Louis Pergaud Sandjo, Maique Weber Biavatti, Leonardo Bruno Federico, Eduardo Monguilhott Dalmarco","doi":"10.1080/08923973.2026.2655385","DOIUrl":"10.1080/08923973.2026.2655385","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is an evolutionarily conserved adaptive process essential for host defense against harmful stimuli, aimed at restoring homeostasis. However, exacerbated or dysregulated responses are associated with the progression of several autoimmune and chronic inflammatory diseases, representing a significant clinical challenge. The endocannabinoid system has been described as an important immunomodulatory pathway in which synthetic cannabinoids exert immunosuppressive effects, providing novel therapeutic targets. Aryl-Cyclohexanone (AD) has previously demonstrated anti-inflammatory properties in both <i>in vitro</i> and <i>in vivo</i> models.</p><p><strong>Methods: </strong>Herein we aimed to investigate its immunomodulatory profile <i>in vitro</i>, using lipopolysaccharide (LPS)-induced inflammation in murine macrophages (J774), and its potential agonist action on CB2 receptor using human macrophages (THP-1), as well as confirm the specific and stable connection with cannabinoid receptor type 2 (CB2) through <i>in silico</i> docking and molecular dynamics analyses.</p><p><strong>Results: </strong>In J774 macrophages, AD treatment preserved cell viability, reduced nitric oxide metabolites production, normalized apoptotic events, and enhanced phagocytosis. Additionally, decreased Toll-like receptor 4 and increased mannose receptor (CD206) expressions were observed, along with a significant reduction in pro-inflammatory cytokines production (IL-12p70, TNF-α, IFN-γ, MCP-1, and IL-6). In THP-1 macrophages, the compound maintained its anti-inflammatory activity only in the absence of the selective CB2 inverse agonist (SR144528), preserving cell viability and reducing nitric oxide metabolites and pro-inflammatory cytokine production. These findings indicate that its immunomodulatory effect is directly associated with CB2 receptor interaction. Complementary <i>silico</i> analyses confirmed a specific and stable interaction with CB2 receptor, supporting a relevant agonistic activity observed in <i>in vitro</i> experiments.</p><p><strong>Conclusion: </strong>The results demonstrate that AD exerts significant anti-inflammatory and immunomodulatory effects, associated with CB2 receptor agonism, highlighting its potential as a promising candidate for developing therapeutic strategies for handling inflammatory diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":3.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive pharmacovigilance analysis of lebrikizumab: a real-world safety assessment based on the FDA Adverse Event Reporting System (FAERS) database.","authors":"Maohua Chen, Chengjie Ke, Yaping Huang","doi":"10.1080/08923973.2026.2648209","DOIUrl":"10.1080/08923973.2026.2648209","url":null,"abstract":"<p><strong>Background: </strong>Lebrikizumab is an interleukin-13 antagonist that has been approved for use in adults and pediatric patients aged 12 years and over who weigh at least 40 kg, for the treatment of moderate-to-severe atopic dermatitis (AD) that is inadequately controlled with topical prescription therapies, or for whom such therapies are not suitable. Due to the relatively short duration of existing clinical trials and the absence of real-world postmarketing evidence involving AD patients receiving lebrikizumab, it is crucial to comprehensively characterize its safety profile, including the potential delayed adverse events (AEs).</p><p><strong>Methods: </strong>AE signals were identified using disproportionality analysis with four algorithms: the reporting odds ratio (ROR), the proportional reporting ratio, the information component, and the empirical Bayesian geometric mean. Data were analyzed from the FDA Adverse Event Reporting System, covering the period from the fourth quarter of 2024 to the third quarter of 2025.</p><p><strong>Results: </strong>A total of 791 AEs associated with lebrikizumab were identified. Lebrikizumab was documented in a lower proportion of serious AEs, accounting for 15.68% of cases. The three most frequently reported AEs associated with lebrikizumab were injection site pain, conjunctivitis, and rash. The top three AE signals with ROR values were conjunctivitis, eyelid irritation and dermatitis exfoliative generalized. Specific AEs of lebrikizumab included hypersensitivity, eosinophilia, and injection site reactions.</p><p><strong>Conclusion: </strong>This study provides a comprehensive overview of the safety of lebrikizumab and confirms that it has a favorable and manageable safety profile, supporting its suitability for long-term use in clinical practice.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising efficacy of coenzyme Q10 supplementation as adjunctive therapy in juvenile idiopathic arthritis: a randomized-controlled pilot study.","authors":"Nourhan Elsherif, Ghada Shousha, Nagwa Ali Sabri, May Ahmed Shawki","doi":"10.1080/08923973.2026.2657954","DOIUrl":"10.1080/08923973.2026.2657954","url":null,"abstract":"<p><strong>Background: </strong>Coenzyme Q10 (CoQ10), a potent antioxidant and anti-inflammatory agent, has shown therapeutic promise in adult autoimmune disorders. However, its role in juvenile idiopathic arthritis (JIA) has not been explored.</p><p><strong>Objective: </strong>To evaluate the efficacy and safety of oral CoQ10 in JIA patients.</p><p><strong>Materials and methods: </strong>In this prospective, single-blinded-pilot trial, 58 patients with active JIA were randomized equally to receive either CoQ10 (100 mg/day) or placebo plus standard therapy for 3 months. Clinical outcome was assessed using Juvenile Arthritis Disease Activity Score (JADAS-10). The quality of life (QoL) was evaluated using Childhood Health Assessment Questionnaire (CHAQ). Biochemical markers included tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and glutathione (GSH). All parameters were assessed at baseline and after 3 months.</p><p><strong>Results: </strong>Fifty-one patients completed the study. The median percent change of JADAS score in the CoQ10 group was -49.1 which was significantly lower than the control group with a median percent change of 2, <i>p</i> < 0.001. Within-group and between groups comparisons showed that the QoL significantly improved in the CoQ10 group compared to the control group (median percent change -60 vs. -33 respectively, <i>p</i> < 0.001). Same positive effects were observed on serum biomarkers whereas median percent changes in the CoQ10 group versus control group were -29.1 vs. -4.3, -44.4 vs. 2, and 12.1 vs. -5.1 for TNF-α, MDA and GSH respectively (all <i>p</i> < 0.01). Minor side-effects were reported during the study.</p><p><strong>Conclusion: </strong>CoQ10 significantly improved disease severity, QoL, and inflammatory and oxidative stress markers in JIA patients with an excellent safety profile.</p><p><p><b>Clinical-trials.gov identification number:</b> NCT05871086.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":3.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of nebivolol on bleomycin-induced lung fibrosis via suppressing TLR4/IL-1β/MMP-2 and TGF-β/HSP47 signaling pathways in rats.","authors":"Mohamed A Morsy, Seham A Abdel-Gaber, Mohamed F Abed El Baky, Sara Mohamed Naguib Abdel Hafez, Anroop B Nair, Katharigatta N Venugopala, Pottathil Shinu, Yasmine F Ibrahim","doi":"10.1080/08923973.2026.2655392","DOIUrl":"https://doi.org/10.1080/08923973.2026.2655392","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF), a potentially fatal illness, significantly alters normal lung structure and function, resulting in severe respiratory failure and death. As of yet, no curable remedy has been revealed. Nebivolol is a third-generation β-blocker that has numerous cytoprotective properties and is used to treat heart failure and hypertension. Its potential ability to prevent bleomycin-induced IPF has not been studied. The aim of the current study is to investigate the antifibrotic effect of nebivolol against bleomycin-induced lung fibrosis.</p><p><strong>Methods: </strong>Twenty-four male Wistar rats were randomly divided into four groups (<i>n</i> = 6 per group): control, bleomycin, nebivolol, and nebivolol + bleomycin. Pulmonary fibrosis was induced by bleomycin administration, while nebivolol was given seven days prior to a single intratracheal injection of bleomycin, daily orally for 21 days. At the end of the study, lung injury and fibrosis were evaluated using histopathological analysis, lung wet/dry ratio, bronchoalveolar lavage fluid protein content, oxidative stress markers, inflammatory cytokines, and fibrosis-related signaling.</p><p><strong>Results: </strong>Nebivolol significantly decreased the histopathological injuries demonstrated through lung tissue sections stained by hematoxylin/eosin and silver. It considerably decreased the lung wet/dry ratio, as well as the total protein level in bronchoalveolar lavage fluid. Further, nebivolol restored superoxide dismutase activity and suppressed elevated malondialdehyde levels, rebalancing the disrupted oxidative indicators. Nebivolol is additionally known to have anti-inflammatory effects, as demonstrated by a decrease in cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), while boosting the secretion of the anti-inflammatory mediator endothelial nitric oxide synthase. In addition, nebivolol's anti-inflammatory properties were obvious by its suppressing effect on Toll-like receptor 4 (TLR4) level and the matrix metalloproteinase-2 (MMP-2) expression. Finally, nebivolol mitigated the progression of the fibrotic cascade, as indicated by reducing the elevated levels of transforming growth factor beta (TGF-β) and heat shock protein 47 (HSP47).</p><p><strong>Conclusion: </strong>Nebivolol treatment exhibited remarkable protective effects on bleomycin-mediated IPF in rats <i>via</i> suppressing TLR4/IL-1β/MMP-2 and TGF-β/HSP47 signaling pathways. This study might provide an innovative therapeutic approach to prevent the devastating lung scarring associated with IPF.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-13"},"PeriodicalIF":3.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicarpin suppresses thyroid cancer progression by inhibiting the AKT/NF-κB pathway and enhancing CD8⁺ T cell-mediated antitumor immunity.","authors":"Zhitao Zhang, Xu Zhang, Yinping Yu, Xiaoming Zhang","doi":"10.1080/08923973.2026.2652318","DOIUrl":"https://doi.org/10.1080/08923973.2026.2652318","url":null,"abstract":"<p><strong>Background: </strong>Poorly differentiated and anaplastic thyroid cancers exhibit resistance to treatment and immune evasion. Medicarpin (MED), a natural pterocarpan derived from leguminous plants, has shown anticancer activity in multiple tumor models. This study investigated the effects of MED on thyroid cancer progression.</p><p><strong>Methods: </strong>Thyroid cancer cell lines (8505 C, TPC-1) and normal thyroid epithelial cells (Nthy-ori 3-1) were treated with varying concentrations of MED. Proliferation, apoptosis, and protein expression were evaluated using CCK-8, Hoechst staining, flow cytometry, ELISA, Western blot, and immunofluorescence. Tumor-immune interactions were assessed <i>via</i> co-culture with CD8⁺ T cells. The AKT activator SC79 was used to verify the involvement of the pathway. <i>In vivo</i> effects were analyzed in humanized NOG mice bearing subcutaneous 8505 C xenografts.</p><p><strong>Results: </strong>No cytotoxicity was observed in Nthy-ori 3-1 cells treated with MED at concentrations ≤80 μM. but MED reduced cell viability in 8505 C and TPC-1 cells (IC₅₀: 62.20 μM for 8505 C, 70.84 μM for TPC-1). Apoptosis was confirmed by nuclear fragmentation and an increase in cleaved caspase-3. MED suppressed PD-L1 expression and CD8⁺ T cell apoptosis, while enhancing IFN-γ, TNF-α, and Granzyme B secretion. MED reduced phosphorylation and nuclear translocation of NF-κB <i>via</i> AKT inhibition, which SC79 partially reversed. <i>In vivo</i>, MED reduced tumor growth in humanized NOG mice, decreased PD-L1 and AKT/NF-κB signaling, enhanced CD8⁺ T-cell activation (CD69, IFN-γ), indicating immune-dependent antitumor activity.</p><p><strong>Conclusions: </strong>MED suppresses thyroid cancer progression by inhibiting proliferation and immune evasion through the inactivation of AKT/NF-κB, supporting its potential as a therapeutic candidate.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of oncostatin M and its receptor in the inflammatory pathogenesis of Graves' orbitopathy.","authors":"Jeong Woo Park, Soo Hyun Choi, Dongheon Surl, Jaesang Ko, Jin Sook Yoon","doi":"10.1080/08923973.2026.2654604","DOIUrl":"https://doi.org/10.1080/08923973.2026.2654604","url":null,"abstract":"<p><strong>Purpose: </strong>Oncostatin M (OSM) and its receptor (OSMR) are implicated in chronic inflammatory diseases. The role of OSM in Graves' orbitopathy (GO) pathogenesis remains unclear. Here, we investigated the role of OSM-OSMR signaling in GO pathogenesis and assessed its potential as a therapeutic target.</p><p><strong>Methods: </strong>Orbital tissues from GO patients and healthy controls were analyzed for OSM, OSMR, and leukemia inhibitory factor receptor (LIFR) expression levels using quantitative real-time PCR. Cultured orbital fibroblasts were treated with recombinant human OSM (rhOSM) and interleukin (IL)-1β to evaluate changes in inflammatory mediator levels and intracellular signaling pathway. OSMR expression was silenced using small interfering RNA. Western blotting was used to assess cytokine and adipogenic marker levels and pathway activation. Adipogenic differentiation was quantified using Oil Red O staining and spectrophotometry.</p><p><strong>Results: </strong>GO orbital tissues showed significantly increased OSM, OSMR, and LIFR expression. IL-1β stimulation induced time-dependent upregulation of OSM and OSMR expression in orbital fibroblasts. rhOSM pretreatment enhanced IL-1β-induced IL-6, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and cyclooxygenase-2 expression while selectively suppressing IL-8 expression. OSMR silencing reduced inflammatory mediator expression and decreased phosphorylation of Janus kinase 2 and mitogen-activated protein kinase components (JNK, ERK, and p38). OSMR knockdown impaired adipogenic differentiation and downregulated terminal adipocyte marker levels, including adipocyte protein 2 and adiponectin.</p><p><strong>Conclusion: </strong>OSM-OSMR signaling amplifies IL-1β-induced inflammatory responses and promotes terminal adipogenic differentiation in GO orbital fibroblasts. This dual regulatory function suggests OSMR as a novel therapeutic target for modulating inflammation and tissue remodeling in GO.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-13"},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}