International immunopharmacology最新文献

{"title":"Corrigendum to \"Brain-derived extracellular vesicles mediate systemic coagulopathy and inflammation after traumatic brain injury\" [International Immunopharmacology 130 (2024) 111674].","authors":"Fanjian Li, Lei Li, Ruilong Peng, Chuan Liu, Xiao Liu, Yafan Liu, Cong Wang, Jianye Xu, Qiaoling Zhang, Guili Yang, Ying Li, FangLian Chen, Shenghui Li, Weiyun Cui, Li Liu, Xin Xu, Shu Zhang, Zilong Zhao, Jianning Zhang","doi":"10.1016/j.intimp.2025.114514","DOIUrl":"https://doi.org/10.1016/j.intimp.2025.114514","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"114514"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin-mediated protection against Immunosenescence in diabetic cardiomyopathy: The potential roles of GDF-15 and klotho proteins","authors":"Ghada M. Almohaimeed ,&nbsp;Asma S. Alonazi ,&nbsp;Tahani K. Alshammari ,&nbsp;Anfal F. Bin Dayel ,&nbsp;Hanan K. Alghibiwi ,&nbsp;Maha A. Alamin ,&nbsp;Ahmad R. Almotairi ,&nbsp;Nasser A. Aldawsari ,&nbsp;Dalal A. Alkhelb ,&nbsp;Nawal M. Alrasheed ,&nbsp;Wedad S. Sarawi ,&nbsp;Nouf M. Alrasheed","doi":"10.1016/j.intimp.2025.114530","DOIUrl":"10.1016/j.intimp.2025.114530","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM) is a global health concern. However, studies examining the effect of metformin on diabetes-induced cardiac myocyte aging are lacking. This study aimed to investigate the protective effect of metformin against DCM involving modulation of macrophage phenotypes, growth differentiation factor-15 (GDF-15), and the anti-aging protein Klotho. Diabetes was induced in male Wistar rats using streptozotocin. Diabetic and nondiabetic rats were treated with metformin (200 mg/kg/day) and saline (control). DCM, inflammation, adhesion molecules, immunometabolic, and GDF-15 biomarkers were assessed using immunoassays. Western blotting was used to analyze Klotho expression. Macrophage phenotypes, senescence-associated-galactosidase (SA-β-gal), and p16^INK4a were examined using immunohistochemistry, whereas the heart sections were histologically examined. The untreated diabetic rats showed increased serum troponin I and creatine kinase-MB levels, reflecting cardiac damage, which was confirmed via morphological changes and senescence. Klotho expression was decreased, indicating cardiac aging. Treatment with metformin reduced the heart weight-body weight ratio and lowered cardiac injury, inflammation, and adhesion molecule biomarker levels. It also reversed the histopathological changes induced by diabetes. It shifted macrophage polarization toward the M2 phenotype, decreased p16^INK4a and SA-β-gal expression, and enhanced Klotho and GDF-15 expression. These findings revealed that diabetes induces cardiac aging by increasing senescence markers and decreasing the expression of Klotho. Metformin treatment protects against DCM by modulating macrophage phenotypes, attenuating immunosenescence-related dysregulation, and enhancing GDF-15 and Klotho expressions. Thus, metformin has potential clinical implications in alleviating DCM.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114530"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CGA protects against experimental colitis by modulating host purine metabolism through the gut microbiota","authors":"Xiaolin Ye,&nbsp;Xueying An,&nbsp;Tianzhuo Zhang,&nbsp;Yan Kong,&nbsp;Shuangzhen Jia,&nbsp;Jie Wu","doi":"10.1016/j.intimp.2025.114547","DOIUrl":"10.1016/j.intimp.2025.114547","url":null,"abstract":"<div><h3>Objective</h3><div>Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.</div></div><div><h3>Methods</h3><div>A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.</div></div><div><h3>Results</h3><div>CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.</div></div><div><h3>Conclusion</h3><div>CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114547"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and Computational Investigations of Isosteviol 16-oxime for Attenuating Streptozotocin-induced Diabetic Neuroinflammation utilizing rat as Animal Model","authors":"Saud Bashir ,&nbsp;Muhammad Faheem ,&nbsp;Mariam K. Alamoudi ,&nbsp;Aisha Alnami ,&nbsp;Khulood A. Almehmadi ,&nbsp;Abdul Waheed Khan ,&nbsp;Bandar Almutairy","doi":"10.1016/j.intimp.2025.114506","DOIUrl":"10.1016/j.intimp.2025.114506","url":null,"abstract":"<div><div>Diabetic neuropathy (DN) is microvascular issues caused by diabetes mellitus (DM) that damages peripheral nerve system. DN-induced pain progression and persistence occur due to many risk factors, including as increased TNF-α, NF-κB, and COX-2 levels. It was investigated whether Isosteviol 16-oxime (IO) could protect against DM-induced neuropathic pain. For this purpose streptozotocin-induced diabetic rat model was employed. After four weeks of streptozotocin injection, IO was given till the sixth week. On days 28, 31, 35, 38, and 42, behavioral assessments were done before and after Streptozotocin administration. After six weeks of streptozotocin treatment, rats were sacrificed, and spinal cord and sciatic nerve samples were taken for molecular analysis. The interaction kinetics and binding affinities of IO with TNF-α, NF-κB, and COX-2 targets were studied using computational methods. IO intervention significantly (<em>P</em> &lt; 0.001) reduced mechanical allodynia and thermal hyperalgesia. The treatment of IO led to increased GSH, GST, and CAT concentrations in the spinal cord and sciatic nerve, while reducing LPO levels (<em>P</em> &lt; 0.001). IHC and Nissl staining showed that IO successfully reduced DN-induced pathological changes. IO also down regulated the expression of inflammatory mediators TNF-α, NF-κB, and COX-2, suggesting its potential as a neuroprotective drug. In comparison to pregabalin, IO demonstrated enhanced antinociceptive properties and diminished hyperalgesic effects. Consequently, IO exhibits a more pronounced reduction in pain perception and inflammation. Our investigation found that IO may protect against DM-induced neuroinflammation by suppressing cytokines and increasing antioxidant levels. More research is needed to determine the exact mechanism of IO in neuroprotection and pain reduction.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114506"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal cells reduce ferroptosis of podocytes by activating the Nrf2/HO-1/GPX4 pathway in lupus nephritis","authors":"Chang Liu ,&nbsp;Xuanqi Liu ,&nbsp;Yujiao Wang ,&nbsp;Honghong Yu ,&nbsp;Qi Li ,&nbsp;Yuanyuan Zheng ,&nbsp;Yao Fu ,&nbsp;Genhong Yao ,&nbsp;Lingyun Sun","doi":"10.1016/j.intimp.2025.114537","DOIUrl":"10.1016/j.intimp.2025.114537","url":null,"abstract":"<div><h3>Background</h3><div>Ferroptosis has been reported to be involved in the occurrence and development of various kidney diseases. Emerging evidence suggests that ferroptosis also plays a critical role in systemic lupus erythematosus (SLE) and lupus nephritis (LN), contributing to podocyte injury and renal dysfunction. Mesenchymal stromal cells (MSCs) have become an attractive option for podocyte injury repairing in LN. The aim of this research was to determine whether MSCs regulate ferroptosis of podocytes in LN.</div></div><div><h3>Methods</h3><div>MSCs were injected into female MRL/lpr mice <em>via</em> tail vein. The symptoms of LN and the detection of ferroptosis-related biomarkers in podocytes were detected. <em>In vitro</em> validation was conducted by mouse podocyte cell line MPC-5.</div></div><div><h3>Results</h3><div>The occurrence of ferroptosis and involvement of Nrf2/heme oxygenase-1 (HO-1) signaling pathway in podocytes were observed. We found increased expression of the podocyte marker, Wilm's tumor 1 (WT-1) and synaptopodin, following the improvement of lupus-like symptoms after MSC transplantation in MRL/lpr mice. The expression of ferroptosis-related protein glutathione peroxidase 4 (GPX4) and long chain acyl-CoA synthetase 4 (ACSL4) were elevated in renal, along with the Nrf2 and HO-1 activity enhancement. <em>In vitro</em>, MSC treatment maintain a stabilization of podocyte actin stress fibers, leading to an improvement of cell viability. Furthermore, our results showed that puromycin aminonucleoside (PAN) induce accumulation of cellular lipid reactive oxygen species (ROS) and glutathione depletion, and the expression of Nrf2, HO-1 and GPX4 were all downregulated whereas the expression of ACSL4 was upregulated. However, these effects were reversed by MSCs and ferroptosis inhibitor ferrastatin-1 (Fer-1). The promotion of Nrf2 nuclear translocation was observed after the treatment with MSCs.</div></div><div><h3>Conclusion</h3><div>Ferroptosis activation is involved in the development of LN. MSCs could ameliorate podocyte injury in LN by inhibiting ferroptosis through the Nrf2/HO-1/GPX4 pathway, which will provide novel potential therapeutic targets for LN.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114537"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-antiviral therapies for viral infections: Harnessing host mechanisms","authors":"Sruthi Sarvepalli ,&nbsp;Shubhadeepthi Vadarevu","doi":"10.1016/j.intimp.2025.114521","DOIUrl":"10.1016/j.intimp.2025.114521","url":null,"abstract":"<div><div>Despite advancements in the field of directly acting anti-viral (DAA) therapies, viral infections still continue to pose significant global health challenges. The efficacy of DAAs are often hindered by mutations, origin of new strains, development of resistance and lack of broad spectrum effectiveness. Furthermore, patients with advanced-stage diseases may require higher doses and combinations of different DAA therapies, raising concerns about tolerability and safety. To overcome all these constraints, non-antiviral therapies that focuses on host mechanisms (also known as host-focused therapies) are emerging as an innovative approach. Host focused therapy aims to target the host molecules and pathways that are essential for viral infection and disease progression. Along with addressing the above mentioned challenges, these host focused therapies can also modulate excessive inflammatory responses. Recent advancements in understanding host-virus interactions and the pathways involved in the pathogenesis of severe viral infections from viral entry and replication to disease progression, have accelerated the development of host-focused therapies aimed at combating these infections. This review explores the growing rationale and various opportunities for host-focused therapies for severe viral infections including zika virus, dengue, HIV, influenza, and covid-19 to name a few. In addition, current clinical trial information on various classes of host focused therapies are presented, highlighting their therapeutic potential and significance in the field.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114521"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ferroptosis alleviates atherosclerosis and foam cell formation by regulating lipid metabolism via AMPK activation","authors":"Yunfan Yang ,&nbsp;Zhenzhen Chen ,&nbsp;Dandan Song ,&nbsp;Junduo Wu ,&nbsp;Junnan Wang ,&nbsp;YouyouYan","doi":"10.1016/j.intimp.2025.114553","DOIUrl":"10.1016/j.intimp.2025.114553","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a lipid disorder characterised by lipid accumulation in the aortic wall and foam cell formation. Recent studies have shown that excess iron accelerates AS progression and foam cell formation by inducing ferroptosis. GPx4, an anti-erroptotic protein, promotes SCARB1 expression, which inhibits macrophage foam cell formation by interacting with HDL. Thus, a complex association exists between ferroptosis and lipid metabolism. However, the underlying mechanisms remain unclear. AMPK signalling is a key regulator of metabolism and is involved in the regulation of ferroptosis. In this study, we used the ferroptosis inhibitor ferrostatin-1 (Fer-1) to assay the effect of ferroptosis inhibition on AS and foam cell formation and to investigate the underlying mechanism. Our results showed that Fer-1 alleviated AS lesions and foam cell formation both in vivo and in vitro. Additionally, Fer-1 reduced iron content and lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-treated macrophages by upregulating the levels of FTH, GPx4, and SCARB1 via AMPK activation. The inhibition of AMPK reduces the effect of Fer-1 on iron and lipid accumulation in macrophages, which may contribute to a deeper understanding of the pathological process of AS and provide a therapeutic target for AS.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114553"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on the article “Alleviation of obesity cardiomyopathy by Fisetin through the inhibition of NF-κB/MAPK signaling”","authors":"Tianxiao Zhang ,&nbsp;Chengsen Li ,&nbsp;Ning Dong ,&nbsp;Xiangxiang Kong ,&nbsp;Qiuyang Xu","doi":"10.1016/j.intimp.2025.114502","DOIUrl":"10.1016/j.intimp.2025.114502","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114502"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Identification of potential targets regulating neutrophil extracellular traps in acute rejection of kidney transplantation based on transcriptomics and animal experiments\" [Int. Immunopharmacol. Volume 147, 6 February 2025, 114008].","authors":"Jun Pei, Huali Weng, Jinpu Peng, Moudong Wu, Xiong Zhan, Guohua Zhu, Dan Wang, Xingyu Pan, Nini An","doi":"10.1016/j.intimp.2025.114496","DOIUrl":"https://doi.org/10.1016/j.intimp.2025.114496","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"114496"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRM1 mediates ASC nuclear export and inflammasome activation","authors":"Rui Cao ,&nbsp;Bolong Lin ,&nbsp;Hongbin He ,&nbsp;Di Wang ,&nbsp;Xiaqiong Wang ,&nbsp;Yi Huang ,&nbsp;Rongbin Zhou","doi":"10.1016/j.intimp.2025.114503","DOIUrl":"10.1016/j.intimp.2025.114503","url":null,"abstract":"<div><div>Inflammasomes are multiprotein complexes of the innate immune system that sense different pathogens or danger signals, and have been implicated in the pathogenesis of multiple human inflammatory diseases. The translocation of adaptor protein ASC from the nucleus to the cytosol is important for inflammasome assembly and activation, but the mechanism remains unclear. Here we show that pharmacological inhibition or genetic deletion of chromosome region maintenance 1 (CRM1) in macrophages significantly inhibits the activation of NLRP3, AIM2, NLRC4 and pyrin inflammasomes. Mechanistically, CRM1 directly binds to the PYD domain of ASC to promote its nuclear-cytosolic transport. More importantly, treatment with CRM1 inhibitor KPT-330 or deletion of CRM1 in myeloid cells attenuates the pathological symptoms of experimental autoimmune encephalomyelitis (EAE) in mice. Thus, our findings reveal that CRM1 is an essential mediator for ASC nuclear export to promote inflammasome assembly and activation, which provides a potential target for inflammasome-related diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114503"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}