Immunopharmacology and Immunotoxicology最新文献

Adenosine A2B receptor mediates cyclosporine counteraction of inflammatory and renal consequences of sepsis in rats. 腺苷A2B受体介导大鼠脓毒症的炎症和肾脏后果的环孢素拮抗。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-19 DOI: 10.1080/08923973.2025.2521005

Simone A Salama, Marwa Y Sallam, Sahar M El-Gowilly

{"title":"Adenosine A2B receptor mediates cyclosporine counteraction of inflammatory and renal consequences of sepsis in rats.","authors":"Simone A Salama, Marwa Y Sallam, Sahar M El-Gowilly","doi":"10.1080/08923973.2025.2521005","DOIUrl":"https://doi.org/10.1080/08923973.2025.2521005","url":null,"abstract":"Introduction: The immunosuppressant drug cyclosporine A (CsA) demonstrates anti-inflammatory properties in numerous pathological conditions. It acts through modulating T-cell receptor signaling, reducing the expression of inflammatory cytokines, and inhibiting mitochondrial permeability, besides modulating vascular response. These features make it a potential drug to prevent or treat septic acute kidney injury (AKI).Objective: In this study, we investigated whether CsA exerts a protective effect against hemodynamic, inflammatory, and renovascular consequences of sepsis and whether these effects are modulated by adenosine receptor signaling.Material and methods: Cecal ligation and puncture (CLP) was utilized to induce sepsis 24 h before hemodynamic and renovascular studies were implicated. Renal vasoconstrictions and vasodilatations were induced by cumulative bolus injections of phenylephrine (PE, 0.41-900 ng) and acetylcholine (ACh, 0.01-7.29 nmol), respectively.Results: The data showed that CsA abrogated CLP-evoked hypotension, tachycardia, and impaired renovascular responsiveness. Similarly, the elevation in kidney biomarkers together with the pro-inflammatory cytokines (Tumor necrosis factor-alpha (TNFα) and Interleukin-6 (IL-6)) were also blunted after CsA administration. Likewise, the elevation in nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and decrease in A2BRs renal tubular expression in sepsis was reversed in CsA-treated rats. These advantageous effects of CsA disappeared upon concurrent exposure to the selective A2BR antagonist, Alloxazine.Conclusion: These results suggest a key role for functional A2BR in CsA counteracting CLP-induced hemodynamic, inflammatory, and renal dysfunction in rats.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325584","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}

引用次数: 0

Effect of dapagliflozin on sepsis-induced kidney injury in a rat model: modulation of the NLRP3 pathway. 达格列净对脓毒症肾损伤大鼠模型的影响：NLRP3通路的调节。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-18 DOI: 10.1080/08923973.2025.2519597

Ilter Ilhan, Nasıf Fatih Karakuyu, Pınar Karabacak, Adem Milletsever, Oznur Kolay, Gül Baysal, Halil Ascı

{"title":"Effect of dapagliflozin on sepsis-induced kidney injury in a rat model: modulation of the NLRP3 pathway.","authors":"Ilter Ilhan, Nasıf Fatih Karakuyu, Pınar Karabacak, Adem Milletsever, Oznur Kolay, Gül Baysal, Halil Ascı","doi":"10.1080/08923973.2025.2519597","DOIUrl":"https://doi.org/10.1080/08923973.2025.2519597","url":null,"abstract":"Introduction: Sepsis-induced acute kidney injury (AKI) is a major cause of mortality in critically ill patients. Inflammation, oxidative stress, and apoptosis are key contributors to sepsis-related renal damage. Dapagliflozin (DPG), an SGLT2 inhibitor, has demonstrated anti-inflammatory and nephroprotective effects. This study aimed to investigate the renoprotective effects of DPG in a lipopolysaccharide (LPS)-induced sepsis model, focusing on inflammation, oxidative stress, and apoptosis in the kidneys.Methods: Thirty-two male Wistar albino rats were divided into four equal groups: (1) Control group, which received saline for 5 days; (2) LPS group, which received oral saline for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (3) LPS+DPG group, which received oral DPG (10 mg/kg/day) for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (4) DPG group, which received oral DPG (10 mg/kg/day) for 5 days. At the end of the experiment, samples were collected for histopathological, immunohistochemical, biochemical, and genetic analyses.Results: DPG significantly reduced serum urea and creatinine levels, indicating improved renal function. Histopathological analysis of the kidney tissues revealed reduced inflammation, hemorrhage, and necrosis in the LPS+DPG group compared to the LPS group. Also, DPG lowered the expression of pro-inflammatory markers (APAF-1, TNF-α, VCAM-1), reduced oxidative stress (decreased OSI), and downregulated NLRP3, caspase-1, IL-1β, and IL-18 gene expression.Conclusion: Prophylactic DPG administration exerts notable renoprotective effects in sepsis-induced AKI by mitigating inflammation, oxidative stress, and apoptosis. These findings highlight its potential as a preventive strategy, warranting further investigation in therapeutic contexts.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325585","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}

引用次数: 0

Assessing the effectiveness of camrelizumab plus anti-angiogenesis drug for the treatment of advanced liver cancer: a single‑center retrospective study. 评估camrelizumab联合抗血管生成药物治疗晚期肝癌的有效性：一项单中心回顾性研究

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-16 DOI: 10.1080/08923973.2025.2513481

Fang Lu, Fanrong Wu

{"title":"Assessing the effectiveness of camrelizumab plus anti-angiogenesis drug for the treatment of advanced liver cancer: a single‑center retrospective study.","authors":"Fang Lu, Fanrong Wu","doi":"10.1080/08923973.2025.2513481","DOIUrl":"https://doi.org/10.1080/08923973.2025.2513481","url":null,"abstract":"Background: Camrelizumab has shown encouraging efficacy in advanced liver cancer, either as monotherapy or in combination with chemotherapy; however, there is currently insufficient empirical support for the use of camrelizumab therapy in conjunction with anti-angiogenic drugs to treat intermediate and advanced hepatocellular carcinoma.Methods: Clinical information was gathered retrospectively from patients with intermediate- to advanced-stage hepatocellular carcinoma who were treated with camrelizumab and certain anti-angiogenic drugs at Shanghai Hospital between July 2019 and May 2023.Results: This trial comprised 60 patients with intermediate and advanced hepatocellular carcinoma. Patients receiving first-line therapy had an objective remission rate of 25% (9/36) and a disease control rate of 58.3% (21/36), while those administered second-line therapy and beyond had rates of 12.5% (3/24) and 33.3% (8/24), respectively. Moreover, the median overall survival was 15.17 months (95% CI 12.067, 18.267) and 13 months (95% CI 11.644, 14.356), whereas the median progression-free survival was 7.1 months (95% CI 3.846, 10.354) and 4.67 months (95% CI 2.492, 6.842), respectively. The predominant treatment-emergent adverse events observed during therapy included: elevated total bilirubin in 28 cases (46.7%), proteinuria in 19 cases (31.7%), gastrointestinal reactions in 19 cases (31.7%), and thrombocytopenia in 16 cases (26.7%).Conclusion: Based on real-world data, individuals with intermediate and advanced primary liver cancer undergoing systemic therapy may benefit from camrelizumab combined with anti-angiogenic drugs.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301984","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}

引用次数: 0

Dichapetalin-type triterpenoids inhibits macrophage interferon expression by regulating the cGas-STING pathway, suggesting potential application in immunosuppression. dichapetalin型三萜通过调节cGas-STING通路抑制巨噬细胞干扰素的表达，提示其在免疫抑制中的潜在应用。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-09 DOI: 10.1080/08923973.2025.2513476

Chuan Zhao, Yi-Ming Sun, Guo-Rong Li, Yue Wang, Yu-Rong Da, Sheng-An Tang, Long Li

{"title":"Dichapetalin-type triterpenoids inhibits macrophage interferon expression by regulating the cGas-STING pathway, suggesting potential application in immunosuppression.","authors":"Chuan Zhao, Yi-Ming Sun, Guo-Rong Li, Yue Wang, Yu-Rong Da, Sheng-An Tang, Long Li","doi":"10.1080/08923973.2025.2513476","DOIUrl":"10.1080/08923973.2025.2513476","url":null,"abstract":"Background: Dichapetalin-type triterpenoids (DTs) derived from Dichapetalum longipetalum (Turcz.) Engl. have attracted extensive attention due to their novel structure, as well as potent anti-tumor and anti-inflammatory activities. In this study, the immunosuppressive effect of Dichapetalin-type triterpenoids on mouse peritoneal macrophages (MPMs) was studied.Methods: MPMs were stimulated with HSV-1 or LPS for the inflammation model. The cytokines and inflammatory mediators were detected by RT-PCR. Western blotting was carried out to determine the phosphorylation of TBK1 and IRF3.Results: Our results showed that DTs inhibited the expression of IFN-β in MPMs infected with HSV-1, and also inhibited the expression of Il-1β and Il-6 in LPS-stimulated MPMs. In addition, compound 1 (dichapetalin A) down regulated the phosphorylation of Tbk1 and Irf3 in HSV-1-infected MPMs.Conclusion: Taken together, this study suggests that DTs isolated from the Dichapetalum longipetalum (Turcz.) Engl. inhibits macrophage activation through the cGas-STING pathway in MPMs, which would be potential for the treatment of autoimmune diseases.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181491","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}

引用次数: 0

Immune checkpoint inhibitors and immunosuppressive tumor microenvironment: current challenges and strategies to overcome resistance. 免疫检查点抑制剂和免疫抑制肿瘤微环境：当前的挑战和克服耐药性的策略。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-05 DOI: 10.1080/08923973.2025.2504906

Gurpreet Singh Gill, Simmi Kharb, Gitanjali Goyal, Prasenjit Das, Kailash Chand Kurdia, Ruby Dhar, Subhradip Karmakar

{"title":"Immune checkpoint inhibitors and immunosuppressive tumor microenvironment: current challenges and strategies to overcome resistance.","authors":"Gurpreet Singh Gill, Simmi Kharb, Gitanjali Goyal, Prasenjit Das, Kailash Chand Kurdia, Ruby Dhar, Subhradip Karmakar","doi":"10.1080/08923973.2025.2504906","DOIUrl":"10.1080/08923973.2025.2504906","url":null,"abstract":"Objectives: Immune checkpoint inhibitors (ICIs) are shown to improve cancer treatment effectiveness by boosting the immune system of the patient. Nevertheless, the unique and highly suppressive TME poses a significant challenge, causing heterogeneity of response or resistance in a considerable number of patients. This review aims to explore the challenges posed by the immunosuppressive tumor microenvironment (TME) in response to immune checkpoint inhibitors (ICIs) and discusses potential strategies to overcome resistance.Material & methods: A comprehensive review of existing literature was conducted to analyze the immunosuppressive features of the TME, including the role of immunosuppressive cells, cytokine and chemokine signaling, metabolic alterations, and overexpression of immune checkpoint molecules (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA). Additionally, strategies to overcome resistance-such as targeting immunosuppressive cells, normalizing tumor vasculature, dual or triple checkpoint blockade, and combining ICIs with vaccines, oncolytic viruses, and metabolic inhibitors-are elaborated. The need for predictive biomarkers to stratify patients and assess treatment response was also discussed.Results: The review highlights that the immunosuppressive TME contributes significantly to resistance against ICIs, mediated through various mechanisms. Potential strategies to overcome resistance include modulating the TME by targeting immunosuppressive components, combination therapies, and the identification of predictive biomarkers. Further research and innovative approaches are required to fully understand TME-ICI interactions and change the face of cancer treatment.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077827","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}

引用次数: 0

Punicalagin ameliorates lipopolysaccharide-induced inflammatory response in dental pulp cells via inhibition of the NF-κB/Wnt5a-ROR2 pathway. Punicalagin通过抑制NF-κB/Wnt5a-ROR2通路改善脂多糖诱导的牙髓细胞炎症反应。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-01 Epub Date: 2025-03-06 DOI: 10.1080/08923973.2025.2470343

Yumeng Yang, Ke Deng, Shan Jiang, Xiaolan Guo, Yiming Zhong, Buling Wu, Liu Wei

{"title":"Punicalagin ameliorates lipopolysaccharide-induced inflammatory response in dental pulp cells via inhibition of the NF-κB/Wnt5a-ROR2 pathway.","authors":"Yumeng Yang, Ke Deng, Shan Jiang, Xiaolan Guo, Yiming Zhong, Buling Wu, Liu Wei","doi":"10.1080/08923973.2025.2470343","DOIUrl":"10.1080/08923973.2025.2470343","url":null,"abstract":"Introduction: Punicalagin (PCG) is a major polyphenolic component with potent anti-inflammatory, anti-atherogenic, anti-cancer, and antioxidant activities. This study aimed to investigate the impact and underlying mechanisms of PCG on lipopolysaccharide (LPS)-induced dental pulpitis.Methods: A rat pulpitis model was constructed, and the infected pulp was covered with a PCG collagen sponge. In vitro, dental pulp cells (DPCs) were isolated, and the effects of LPS and PCG on cell viability were assessed. The expression levels of inflammation-related factors were investigated by qRT-PCR and ELISA. The Nuclear Factor kappa B (NF-κB) transcription factors and Wnt family member 5a-Receptor tyrosine kinase like Orphan Receptor 2 (Wnt5a-ROR2) levels were evaluated by immunofluorescence staining and Western blotting.Results: We demonstrated that the PCG collagen sponge effectively reduced the infiltration of inflammatory cells in the pulp. PCG significantly alleviated the inflammatory response by reducing the mRNA expression levels of IL-1β, IL-6, IL-8, ICAM-1, and VCAM-1 and the secretion of IL-6 and IL-8 in a concentration-dependent manner. Immunofluorescence staining showed that the activation of the NF-κB pathway was hindered by PCG, which affected with the nuclear translocation of P65. PCG reduced the phosphorylation levels of P65 and IκBα and suppressed the expression levels of Wnt5a and ROR2 induced by LPS. The NF-κB inhibitor Bay11-7082 reduced the activation of the NF-κB/Wnt5a-ROR2 pathway and the inflammatory response; the application of PCG significantly augmented this inhibitory effect.Discussion: PCG demonstrated an anti-inflammatory effect in LPS-induced DPCs by targeting the NF-κB/Wnt5a-ROR2 signaling pathway.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"317-327"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491896","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}

引用次数: 0

Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats. 维格列汀通过激活Nrf2/HO-1和SIRT1以及抑制NF-κB信号来减弱大鼠阿霉素诱导的肝毒性。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1080/08923973.2025.2482863

Heba M Mahmoud, Emad H M Hassanein, Marwa M Khalaf

{"title":"Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats.","authors":"Heba M Mahmoud, Emad H M Hassanein, Marwa M Khalaf","doi":"10.1080/08923973.2025.2482863","DOIUrl":"10.1080/08923973.2025.2482863","url":null,"abstract":"Background: Doxorubicin (DOX) is an anticancer commonly employed in cancer treatment. However, the clinical application of DOX is associated with hepatotoxicity. Vildagliptin is an anti-hyperglycemic agent that inhibits the dipeptidyl peptidase-4 enzyme. Besides being used in managing type-2 diabetes, vildagliptin showed potential anti-inflammatory, antioxidant, and other activities.Objective: Our investigation targeted the hepatoprotective effects of vildagliptin against DOX-induced hepatotoxicity.Methods: Vildagliptin was given in a dose of 30 mg/kg, once daily; p.o. for 2 weeks while DOX was injected in a single dose of 30 mg/kg, i.p.Results: Vildagliptin effectively decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, while it effectively elevated serum total protein (TP) level. Histologically, vildagliptin administration resulted in significant hepatoprotective efficacy with abundant figures of normal hepatocytes. Moreover, vildagliptin considerably decreased lipid peroxidation biomarker malondialdehyde (MDA), and the cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2, while it remarkably boosted the antioxidative defenses of glutathione (GSH) and catalase (CAT). Dual antioxidant and anti-inflammatory activities were mediated by upregulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2), silent information regulator 1 (SIRT1), and heme oxygenase (HO-1) and suppressing the nuclear factor kappa B (NF-κB) signals. Finally, vildagliptin alleviated apoptosis by downregulating hepatic p53 and cytochrome (Cyt)-C.Conclusion: Our findings suggest that vildagliptin improved hepatocellular architecture and reduced hepatic oxidative injury, inflammation, and apoptosis associated with DOX treatment.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"364-374"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730081","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}

引用次数: 0

Mavorixafor: a CXCR4 antagonist for WHIM syndrome. Mavorixafor：用于WHIM综合征的CXCR4拮抗剂。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-01 Epub Date: 2025-04-14 DOI: 10.1080/08923973.2025.2491551

Canyu Chen, Bo Xu, Weiyi Li, Jixiang Chen, Zunbo He, Jiecan Zhou

{"title":"Mavorixafor: a CXCR4 antagonist for WHIM syndrome.","authors":"Canyu Chen, Bo Xu, Weiyi Li, Jixiang Chen, Zunbo He, Jiecan Zhou","doi":"10.1080/08923973.2025.2491551","DOIUrl":"10.1080/08923973.2025.2491551","url":null,"abstract":"Background: WHIM syndrome is a rare primary immune deficiency and chronic neutropenia caused by overactivation of the C-X-C motif chemokine receptor 4/C-X-C motif chemokine ligand 12 (CXCR4/CXCL12) signaling pathway. On April 26th, 2024, Xolremdi (mavorixafor) capsules received its approval from US FDA, is the first targeted treatment specifically for patients aged ≥12 years with WHIM syndrome. Mavorixafor, as a selective CXCR4 antagonist, is able to increase the number of mature neutrophils and lymphocytes in the blood.Objective: This review is to describe the pharmacological properties of mavorixafor and evaluate its clinical efficacy and safety profile.Methods: A literature search was conducted using keywords mavorixafor, XOLREMDI, AMD070, AMD11070, X4P-001, WHIM Syndrome, and CXCR4/CXCL12 on Web of Science, Google Scholar, and PubMed. Drug information was obtained from the FDA website.Results: In the pivotal 52-week phase III trial, time above absolute neutrophil count threshold (TATANC) values in the mavorixafor group were higher than those in the placebo group at 4 different time points (15.04 h vs 2.75 h; p < 0.0001), and mavorixafor group had lower infection frequency, severity and duration. The most common adverse events are thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.Conclusion: Mavorixafor 400mg daily effectively increases WBC count, reduces disease symptoms and infection burden in WHIM syndrome patients ≥12 years. Future clinical programs will continue to evaluate the safety and efficacy of mavorixafor in patients with chronic neutropenic disease.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"385-391"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002951","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}

引用次数: 0

The anti-inflammatory effects of vitamin B6 on neuroinflammation and neuronal damage caused by 1,2-diacetylbenzene in BV2 microglial and sH-SY5Y cells. 维生素 B6 对 BV2 小胶质细胞和 sH-SY5Y 细胞中 1,2- 二乙酰苯引起的神经炎症和神经元损伤的抗炎作用

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-01 Epub Date: 2025-03-16 DOI: 10.1080/08923973.2025.2469216

Hai Duc Nguyen, Won Hee Jo, Ngoc Hong Minh Hoang, Min-Sun Kim

{"title":"The anti-inflammatory effects of vitamin B6 on neuroinflammation and neuronal damage caused by 1,2-diacetylbenzene in BV2 microglial and sH-SY5Y cells.","authors":"Hai Duc Nguyen, Won Hee Jo, Ngoc Hong Minh Hoang, Min-Sun Kim","doi":"10.1080/08923973.2025.2469216","DOIUrl":"10.1080/08923973.2025.2469216","url":null,"abstract":"Background: The pathophysiology of cognitive impairment has recently focused on 1,2-Diacetylbenzene (DAB), B vitamins, tau hyperphosphorylation, and neuroinflammation. While past evidence shows that vitamin B6 influences the immune system, the molecular processes behind DAB-induced neuroinflammation and cognitive impairment remain largely unknown. This study aimed to assess the protective roles of vitamin B6 against DAB-induced toxicity in BV2 microglial and SH-SY5Y cells.Methods: In vitro approaches included Western blot, qRT-PCR, cell viability assays, immunocytochemistry, reactive oxygen species, and nitrite assays. For in silico analysis, we utilized Metascape, Cytoscape, MIENTURNET, and molecular docking.Results: Vitamin B6 suppressed the TLR4/NF-κB pathway and the TREM-1/DAP12/NLRP3/caspase-1/IL1B pathway in DAB-activated BV2 cells. Additionally, it reduced reactive oxygen species and nitric oxide levels while increasing Nrf2 and IL10 production. In SH-SY5Y cells, vitamin B6 inhibited GSK-3β Tyr216, tau hyperphosphorylation, and β-amyloid production. The in silico analysis identified 'positive regulation of NF-κB transcription factor activity,' 'regulation of IL-6 production,' and 'positive regulation of adaptive immune response' as key molecular mechanisms linked with DAB-induced cognitive impairment and targeted by vitamin B6. Core genes, miRNAs, and transcription factors included IL1β, IL6, IL10, TNF, hsa-miR-155-5p, hsa-miR-203a-3p, hsa-miR-106a-5p, hsa-miR-26a-5p, CEBPB, and PXR.Conclusion: Our findings indicate that vitamin B6 may protect against DAB-induced cognitive impairment by attenuating key inflammatory pathways, reducing oxidative stress, and inhibiting tau hyperphosphorylation, β-amyloid production, and GSK-3β Tyr216 phosphorylation. This highlights its potential as a therapeutic agent for cognitive impairment.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"273-286"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648434","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}

引用次数: 0

Evaluating the impact of amitriptyline on Nitric Oxide signaling in rat models of neuropathic pain. 评估阿米替林对神经性疼痛大鼠模型中一氧化氮信号传导的影响。

IF 2.9 4区医学

Immunopharmacology and Immunotoxicology Pub Date : 2025-06-01 Epub Date: 2025-04-02 DOI: 10.1080/08923973.2025.2481870

Hamid Reza Mohammadi, Zahra Haghighatian, Behrouz Beiranvand, Peyman Amanolahi Baharvand, Amin Hasanvand

{"title":"Evaluating the impact of amitriptyline on Nitric Oxide signaling in rat models of neuropathic pain.","authors":"Hamid Reza Mohammadi, Zahra Haghighatian, Behrouz Beiranvand, Peyman Amanolahi Baharvand, Amin Hasanvand","doi":"10.1080/08923973.2025.2481870","DOIUrl":"10.1080/08923973.2025.2481870","url":null,"abstract":"Introduction: Nitric oxide (NO) plays a crucial role in the induction of neuropathic pain by stimulating the production of inflammatory cytokines. Additionally, research indicates that amitriptyline can inhibit nitric oxide production. In this study, we examined the inhibitory role of the nitric oxide signaling pathway through the administration of amitriptyline in the treatment of neuropathic pain.Methods: Forty rats were randomly assigned to five groups, with eight animals in each group: (1) Sham-operated, (2) Chronic constriction injury (CCI), (3) CCI plus amitriptyline, (4) CCI plus amitriptyline and L-arginine, and (5) CCI plus amitriptyline and L-NAME. Behavioral tests, including thermal hyperalgesia, cold allodynia, and mechanical allodynia, were conducted on the fourth, seventh, and fourteenth days following CCI induction. On the final day, spinal cord samples were collected to assess the levels of inflammatory cytokines. Additionally, the sciatic nerve was isolated on the same day for histological examination.Results: The results indicated that the administration of amitriptyline can reduce levels of inflammatory cytokines and improve symptoms of neuropathic pain. It should be noted that the simultaneous use of L-NAME and amitriptyline increases the therapeutic impacts of amitriptyline. However, the beneficial effects of amitriptyline are reduced by the nitric oxide stimulation induced by L-arginine.Conclusion: It was determined that one of the mechanisms by which amitriptyline ameliorates neuropathic pain is the inhibition of the nitric oxide signaling pathway. In this study, this effect was associated with a reduction in the release of inflammatory cytokines and a decrease in inflammation surrounding the nerve.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"345-353"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772239","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}

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