Immunopharmacology and Immunotoxicology最新文献

{"title":"Sevoflurane induces cognitive dysfunction by modulating PER2 methylation to block AKT pathway-suppressed NLRP3 inflammatory vesicle in microglia.","authors":"Shuangjiang Li, Bin Wang","doi":"10.1080/08923973.2025.2496666","DOIUrl":"https://doi.org/10.1080/08923973.2025.2496666","url":null,"abstract":"<p><strong>Background: </strong>The anesthetic sevoflurane can cause cognitive dysfunction and may be involved in mediating DeoxyriboNucleic Acid (DNA) methylation. In this study, we dig into the mechanism of sevoflurane inducing cognitive dysfunction <i>via</i> DNA methylation pathway.</p><p><strong>Methods: </strong><i>In vivo</i> and <i>in vitro</i> experiments were performed in sevoflurane-induced rat models and microglia. <i>In vivo</i> experiments included Morris water maze, Western blot, methylation analysis and immunofluorescence, while <i>in vitro</i> experiments consisted of quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. MK2206 was used as a protein kinase B (AKT) inhibitor.</p><p><strong>Results: </strong>Sevoflurane induced cognitive dysfunction in rats, promoted levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Interleukin (IL)-18, IL-1β, and ionized calcium-binding adapter molecule 1 (Iba-1) proteins, and inhibited Period2 (PER2) expression by enhancing methylation modification. PER2 was found to be located in microglia. Sevoflurane activated DNA methyltransferases (DNMTs) expression and suppressed PER2 <i>in vitro</i>. PER2 overexpression reduced NLRP3 inflammasomes-related protein expressions and restored AKT activation in sevoflurane-treated cells. Furthermore, MK2206 reversed the inhibitory effect of PER2 overexpression on cellular inflammation and AKT pathway activation.</p><p><strong>Conclusion: </strong>Sevoflurane affects AKT pathway-suppressed NLRP3 inflammasomes in microglia by modulating PER2 methylation, thereby contributing to cognitive dysfunction.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182110","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":"Therapeutic efficacy of tofacitinib in PDSAg-induced chronic experimental autoimmune uveitis in Wistar rat.","authors":"Berru Yargi-Ozkocak, Ozlem Tugce Cilingir-Kaya, İrem Peker Eyuboglu, Can Erzik, Haner Direskeneli, Hande Celiker","doi":"10.1080/08923973.2025.2508278","DOIUrl":"https://doi.org/10.1080/08923973.2025.2508278","url":null,"abstract":"<p><strong>Purpose: </strong>Tofacitinib, a small molecule pan-JAK inhibitor, targets key inflammatory pathways that play a pivotal role in the pathophysiology of uveitis. Its ability to inhibit multiple cytokine signaling pathways makes it a promising candidate for the treatment of ocular inflammation. This study aimed to investigate the effect of oral tofacitinib on peptide-derived S-antigen (PDSAg)-induced chronic experimental autoimmune uveitis (EAU) in rats.</p><p><strong>Materials and methods: </strong>Nineteen albino Wistar rats were divided into five groups. Groups 1-3 (5 rats each) were immunized with 15 micrograms PDSAg to induce EAU; Group 2 received tofacitinib (5 mg/kg) by gavage twice daily. Group 3 received saline in the same manner as Group 2. Group 4 (2 rats) was a healthy control group. Group 5 (2 rats) received only tofacitinib. Uveitis development and treatment efficacy were evaluated using clinical scoring based on the the signs of anterior segment inflammation and histological scoring based on the deterioration of the retinal architectural structure.</p><p><strong>Results: </strong>Uveitis confirmed based on histological evidence was observed in all EAU groups (Groups 1-3) compared to the healthy control group (Group 4) (<i>p</i> < 0.001, <i>Mann-Whitney U test</i>). Tofacitinib significantly delayed the onset of uveitis in Group 2 when compared with Groups 1 and 3, which did not receive tofacitinib (<i>p</i> < 0.001, <i>Mann-Whitney U test</i>). Histological scores also showed a trend toward reduction (<i>p</i> = 0.393, <i>Mann-Whitney U test</i>).</p><p><strong>Conclusions: </strong>Oral tofacitinib delayed uveitis onset and reduced clinical and histological findings, suggesting its potential as an alternative treatment for uveitis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158419","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":"<i>In vitro</i> anti-tumor activities of a novel recombinant immunotoxin targeting differentially overexpressed Leucine-rich repeat-containing G-protein-coupled receptor 5 in cervical cancer.","authors":"Marc Henry, Takunda Ngwegya, Nkhasi Lekena, Stefan Barth","doi":"10.1080/08923973.2025.2504904","DOIUrl":"10.1080/08923973.2025.2504904","url":null,"abstract":"<p><strong>Objective: </strong>The study aims to develop a novel recombinant anti-LGR5 immunotoxin candidate based on a truncated form of <i>Pseudomonas</i> exotoxin A (ETA).</p><p><strong>Methods: </strong>To develop this LGR5-specific recombinant immunotoxin, a corresponding single chain antibody fragment (αLGR5(scFv)) fused to ETA, was expressed under osmotic stress in the presence of compatible solutes in <i>Escherichia coli</i> BL21 DE3 cells. Expression was monitored by Western blot analysis facilitated by an N-terminal 10x-His tag. Purification was done using immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC). The recombinant immunotoxin (rIT) was assessed for cell surface binding on cervical cancer cell lines using confocal microscopy and flow cytometry. The rIT was then used in an XTT cell viability assay to assess targeted cell killing.</p><p><strong>Results and discussion: </strong>Upon confirmation of full-length protein by Western blot, purified protein was used to confirm binding on LGR5-positive cervical cancer cell lines <i>via</i> confocal microscopy and flow cytometry using anti-His PE antibody as a secondary antibody. Selective cell-killing of this novel recombinant immunotoxin was illustrated by the dose-dependent reduction in cell viability at IC50 values in nanomolar concentrations on antigen-positive but not antigen-negative cell lines.</p><p><strong>Conclusions: </strong>In conclusion, the rIT described is a promising candidate to treat cervical cancer, which however, would finally need to be confirmed by preclinical <i>in vivo</i> studies.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077826","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":"Alpha-cyperone ameliorates renal fibrosis and inflammation in mice with chronic kidney disease <i>via</i> NF-κB and Akt/Nrf2/HO-1 pathways.","authors":"Wei Chen, Jiansong Mao, Chun Li, Jinlian Ke","doi":"10.1080/08923973.2025.2507129","DOIUrl":"https://doi.org/10.1080/08923973.2025.2507129","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis is a hallmark feature of chronic kidney disease (CKD) and contributes to local inflammation and impaired renal function. The study aimed to investigate the effects of an active compound, alpha-cyperone, on renal fibrosis, inflammation, and oxidative stress in CKD mice.</p><p><strong>Methods: </strong>After subtotal nephrectomy, mice were administered with alpha-cyperone (5, 10, and 20 mg/kg) or captopril (the positive control) daily <i>via</i> oral gavage. Masson trichrome staining and periodic Acid-Schiff staining were performed to measure fibrotic areas and renal histopathological changes. An enzyme-linked immunosorbent assay was conducted to measure inflammatory cytokine levels in mouse serum samples. Superoxide anion concentrations, reactive oxygen species (ROS) level, and superoxide dismutase (SOD) activity were analyzed. Immunohistochemistry was performed to detect inflammatory and oxidative stress markers (Ly6G and 8-OHdG) in mouse renal tissues. Protein levels of factors involved in NF-κB signaling and Akt/Nrf2/HO-1 signaling were quantified by western blotting.</p><p><strong>Results: </strong>Alpha-cyperone at the dose of 10 mg/kg significantly improved renal functions in CKD model mice and alleviated tubulointerstitial fibrosis, with effects comparable to those of captopril. After CKD modeling, serum levels of inflammatory mediators, Ly6G levels, superoxide anion activity, ROS levels, and 8-OHdG levels were markedly increased, while the activity of antioxidant enzyme SOD was reduced. All these changes were ameliorated by alpha-cyperone or captopril treatment. Moreover, alpha-cyperone inhibited the NF-κB signaling and activated the Akt/Nrf2/HO-1 signaling in renal tissues of CKD mice.</p><p><strong>Conclusion: </strong>Alpha-cyperone ameliorates renal fibrosis in CKD mice by inhibiting inflammation and oxidative stress <i>via</i> NF-κB and Akt/Nrf2/HO-1 pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142369","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":"Unexplained lymphadenopathy following adjuvant immunotherapy in a non-small cell lung cancer patient: a literature review and a rare case report.","authors":"Lila Liu, Ying Wei, Qijiu Chen, Hanlin Liang","doi":"10.1080/08923973.2025.2507130","DOIUrl":"https://doi.org/10.1080/08923973.2025.2507130","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have shown significant advantages in the treatment of lung cancer. Several studies have reported immune-related adverse events (irAEs) induced by ICIs. However, in clinical practice, irAEs occasionally cause lymphadenopathy, which can be mistaken for tumor progression, making it more challenging to accurately assess the patient's condition.</p><p><strong>Case presentation: </strong>This research report documents a rare clinical case of a patient with early-stage non-small cell lung cancer (NSCLC) who developed systemic lymphadenopathy during treatment with a PD-1 ICI following surgical resection. The patient developed widespread lymphadenopathy during postoperative PD-1 antibody maintenance therapy, accompanied by a series of irAEs, including persistent low cortisol levels, sluggish responses, memory loss, and stiffness in distal limbs and shoulder joints. Given the clinical presentation, the possibility of lymph node metastasis from lung cancer could not be entirely excluded. However, lymph node biopsy revealed reactive hyperplasia. After receiving corticosteroid treatment, the enlarged lymph nodes significantly reduced in size, and the associated low cortisol symptoms disappeared. During subsequent follow-up, the patient showed significant improvement and maintained a relatively stable condition.</p><p><strong>Results: </strong>In cases of postoperative generalized lymphadenopathy in NSCLC patients, if tumor recurrence is suspected, careful consideration is needed, especially in the era of ICI therapy. Postoperative PD-1 antibody maintenance therapy may induce reactive lymphadenopathy, including mediastinal lymph nodes. It is hypothesized that PD-1 antibodies cause T-cell activation in the lymph nodes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-5"},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119612","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":"Zerumbone modulates the expression of inflammatory mediators and antioxidant enzymes in TNF-α-stimulated human periodontal ligament cells.","authors":"Risa Okamoto, Yoshitaka Hosokawa, Ikuko Hosokawa, Kazumi Ozaki, Keiichi Hosaka","doi":"10.1080/08923973.2024.2445724","DOIUrl":"10.1080/08923973.2024.2445724","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontal disease is a chronic inflammatory disease caused by periodontopathogenic bacteria, and its progression leads to periodontal tissue destruction and tooth loss. Zerumbone is a bioactive substance found in ginger (<i>Zingiber zerumbet</i>) and is known to have bioactive effects such as anticancer effects, but there have been no attempts to use it for periodontitis treatment. In addition, there have been no reports examining its effects on periodontal tissue component cells. In this experiment, we aimed to determine whether zerumbone affects the production of inflammatory mediators induced by tumor necrosis factor (TNF)-α in human periodontal ligament cells (HPDLCs), including its effects on signaling pathways.</p><p><strong>Methods: </strong>HPDLCs were stimulated by TNF-α (10 ng/ml) with or without zerumbone (6.25, 12.5, or 25 µM). Cytokine production in supernatant was determined using ELISA. Activation of signal transduction pathways and intracellular protein expression were investigated using the western blot analysis.</p><p><strong>Results: </strong>Zerumbone significantly suppressed TNF-α-induced production of CC chemokine ligand 2 (CCL2), CCL20, CXC chemokine ligand 10 (CXCL10), and interleukin-6 (IL-6) in HPDLCs. In addition, zerumbone decreased intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2) expression in TNF-α-stimulated HPDLCs. Furthermore, zerumbone suppressed activation of nuclear factor (NF)-κB and signal transducer and activator of transcription 3 (STAT3) pathways in TNF-α-treated HPDLCs. Finally, zerumbone enhanced the production of heme oxygenase-1 (HO-1), an antioxidant enzyme, in HPDLCs.</p><p><strong>Conclusion: </strong>These results suggest that zerumbone suppressed the production of several inflammatory mediators by inhibiting the NF-κB and STAT3 pathways in HPDLCs.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"176-181"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921577","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":"Efficacy and safety of ibuprofen and naproxen in the treatment of oligoarticular juvenile idiopathic arthritis: bi-national cohort study.","authors":"Orly Ohana, Itay Marmor, Rina Ferguson, Yoel Levinsky, Shiri Rubin, Kevin Baszis, Rotem Tal, Liora Harel, Orit Peled, Gil Amarilyo","doi":"10.1080/08923973.2024.2421523","DOIUrl":"10.1080/08923973.2024.2421523","url":null,"abstract":"<p><strong>Objectives: </strong>Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections are first-line therapy for oligoarticular JIA. NSAIDs Adverse events (AEs) include gastrointestinal ulcers/bleeding and impaired renal function. The most prescribed NSAIDs for oligoarticular JIA are ibuprofen and naproxen. However, direct comparison between these drugs is lacking. We aimed to compare the efficacy and safety of ibuprofen versus naproxen for oligoarticular JIA.</p><p><strong>Methods: </strong>This is a bi-national retrospective study of oligoarticular JIA patients treated with either ibuprofen or naproxen as first-line therapy. Efficacy was defined as patients that achieved complete response (no evidence for arthritis). Safety was assessed by the occurrence of adverse events during follow-up.</p><p><strong>Results: </strong>Of 164 patients, 103 were treated in the Israeli group and 61 in the US group. The study population had a mean age of 4.49 ± 3.55 years, with F:M ratio of ∼2.5:1. No significant difference was found in drug efficacy [Complete response was observed in 15% of the ibuprofen group <i>vs</i>. 17.3% in naproxen group (<i>p</i> = 0.7)]. Treatment duration > 28 days was associated with significantly higher odds for complete response (<i>p</i> = 0.021). For safety, 12 AEs were associated with naproxen, whereas no AEs were associated with ibuprofen (<i>p</i> = 0.004). Treatment was discontinued in all AEs cases.</p><p><strong>Conclusions: </strong>Ibuprofen and naproxen showed similar albeit low efficacy which emphasizes their role as bridging therapy until IACI is achieved. However, ibuprofen showed better safety profile naproxen and therefore should be considered as first-line therapy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"141-146"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948211","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":"Effect of biological treatment on the thiol/disulfide parameters in patients with axial spondyloarthritis.","authors":"Semra Fırat, Şükran Erten, Serdar Can Güven, Sezen Tutar, Yüksel Maraş, Salim Neşelioğlu, Selçuk Akan, Ahmet Kor, Berkan Armağan, Kevser Orhan, İsmail Doğan, Orhan Küçükşahin, Özcan Erel","doi":"10.1080/08923973.2025.2469211","DOIUrl":"10.1080/08923973.2025.2469211","url":null,"abstract":"<p><strong>Objective: </strong>Aim of this study is to compare the thiol/disulfide variables before treatment, at the 3^rd and 6^th months of biologic treatment in patients with axSpA.</p><p><strong>Materials & methods: </strong>Consecutive patients with axial spondyloarthritis to whom biologic treatment was initiated in our clinic were enrolled upon consent. Demographics, clinical characteristics, laboratory parameters and treatment agents were collected. Disease activity scores and thiol-disulfide balance parameters were recorded at baseline and 3^rd, 6^th months of treatment. Statistical analyses were performed in all patients and in subgroups of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients.</p><p><strong>Results: </strong>In all patients, total thiol levels were significantly increased at 6^th month in comparison to baseline values (470.5 ± 74.7 vs 491.9 ± 69.6, <i>p</i> = 0.047). Native thiol levels were increased at 6^th month close to significance (438.9 ± 70.4 vs 458.8 ± 63.7, <i>p</i> = 0.060). Moderately strong negative correlations were observed between native thiol levels and disease activity parameters (BASDAI: <i>p</i> = 0,019; ASDAS-CRP: <i>p</i> = 0,035; ASDAS-ESR: <i>p</i> = 0,030), and between total thiol levels and disease activity parameters (BASDAI: <i>p</i> = 0,031; ASDAS-CRP: <i>p</i> = 0,020; ASDAS-ESR: <i>p</i> = 0,026) at 6^th month evaluation.</p><p><strong>Discussion & conclusions: </strong>Our results demonstrated oxidative stress reducing effect of biologics in axSpA patients parallel to suppression of disease activity at 6^th month of the treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"228-233"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467899","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":"Evaluation of the inhibitory effect of different molecular weights chitosan on MRGPRX2-mediated mast cell degranulation and the pseudo-allergic reaction.","authors":"Dewu Zhang, Ruiqi Li, Liping Liu, Ruijuan Lu, Juan Li, Yajing Hou","doi":"10.1080/08923973.2025.2457971","DOIUrl":"10.1080/08923973.2025.2457971","url":null,"abstract":"<p><strong>Objectives: </strong>Chitosan is widely used in medicine to regulate immune responses in T cells and dendritic cells. However, research on the regulation of mast cells (MCs) is scarce. Mas-related G-protein-coupled receptor X2 (MRGPRX2) is a key receptor that mediates MC activation. However, the inhibitory effects of chitosan on MRGPRX2 activation have not yet been reported. The aim of this study was to determine whether chitosan inhibits MRGPRX2-mediated MC activation and the molecular weight of chitosan with the best inhibitory effect.</p><p><strong>Methods: </strong>Cytotoxic and activating effects of chitosan on LAD2 cells were evaluated <i>in vitro</i>. An <i>in vitro</i> MC degranulation reaction model and <i>in vivo</i> C48/80-induced local passive anaphylaxis mouse model were used to evaluate the inhibitory effect of chitosan on MRGPRX2 activation.</p><p><strong>Key findings: </strong>Chitosan inhibited MC degranulation mediated by MRGPRX2 <i>in vitro</i> and reduced histamine, β-hexosaminidase, and cytokine release. Chitosan inhibited local pseudo-allergy and inflammatory mediator release by inhibiting MRGPRX2-mediated MC activation. Moreover, low-molecular-weight chitosan exhibited superior inhibitory activity against MRGPRX2.</p><p><strong>Conclusions: </strong>Chitosan inhibited MRGPRX2-mediated MC degranulation <i>in vivo</i> and <i>in vitro</i>. Low molecular weight chitosan has the potential to be developed as a functional drug or food to assist in the treatment of MRGPRX2-regulated diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"213-221"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023293","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":"Ruxolitinib enhances gastric cancer to chemotherapy by suppressing JAK/STAT3 and inducing mitochondrial dysfunction and oxidative stress.","authors":"Yang Yao, Jun Zhou, Jing Song, Cheng Chen","doi":"10.1080/08923973.2025.2470344","DOIUrl":"10.1080/08923973.2025.2470344","url":null,"abstract":"<p><strong>Objective: </strong>Chemoresistance in gastric cancer poses a major challenge in treatment, necessitating the development of novel therapeutic strategies. This study evaluates the efficacy of ruxolitinib, a JAK1/2 inhibitor, in both sensitive and resistant gastric cancer cell lines.</p><p><strong>Materials and methods: </strong>Gastric cancer cell lines, including sensitive (N87 and AGS) and resistant (N87-R and AGS-R) variants, were treated with ruxolitinib alone or in combination with chemotherapeutic agents. Apoptosis induction, mitochondrial function, oxidative stress, and key signaling pathways were analyzed. Tumor growth, p-STAT3 levels, and overall survival were evaluated in xenograft models.</p><p><strong>Results: </strong>Ruxolitinib induced dose-dependent mitochondrial-mediated apoptosis in resistant cells and enhanced cytotoxicity in combination with chemotherapy in sensitive cells. The treatment inhibited phosphorylation of STAT3, Akt, and mTOR. Additionally, ruxolitinib reduced basal and maximal respiration rates while increasing ROS levels, suggesting mitochondrial dysfunction and oxidative stress. Resistant cells exhibited increased mitochondrial DNA content, elevated respiration rates, and higher ROS levels compared to sensitive cells, indicating alterations in mitochondrial biogenesis and redox homeostasis. These findings were supported by changes in gene expression related to mitochondrial function. In vivo, ruxolitinib significantly inhibited tumor growth and reduced p-STAT3 levels in resistant gastric cancer xenografts without causing significant weight loss. Furthermore, ruxolitinib treatment significantly prolonged overall survival in mice.</p><p><strong>Conclusion: </strong>Ruxolitinib demonstrates potential in overcoming chemoresistance in gastric cancer by targeting mitochondrial function, oxidative stress, and key survival pathways. These findings support further investigation into its clinical application as an adjunct therapy for chemoresistant gastric cancer.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"263-271"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515375","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}