Inflammation最新文献_第2页

Exposure to Dietary Nitrite Exacerbates Lupus in MRL/lpr Mice by Enhancing Integrin Alpha M. 饮食中暴露于亚硝酸盐通过增强整合素α M使MRL/lpr小鼠狼疮恶化。

IF 5 2区医学

Inflammation Pub Date : 2025-08-04 DOI: 10.1007/s10753-025-02347-9

Yiwu Qiu, Qingyi Zhang, Xueting Yang, Chengping Wen, Zhixing He, Mingzhu Wang

{"title":"Exposure to Dietary Nitrite Exacerbates Lupus in MRL/lpr Mice by Enhancing Integrin Alpha M.","authors":"Yiwu Qiu, Qingyi Zhang, Xueting Yang, Chengping Wen, Zhixing He, Mingzhu Wang","doi":"10.1007/s10753-025-02347-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02347-9","url":null,"abstract":"There is a recognized longitudinal association between serum nitrogen oxides levels and disease activity in lupus nephritis. Recently, increased exposure to high levels of nitrite has raised significant concerns, though its impact on lupus pathogenesis has not been fully elucidated. Using the MRL/lpr spontaneous lupus model, we employed integrated immunological and transcriptomic approaches to investigate nitrite's effects. Flow cytometry revealed significant elevations in splenic double negative T (DN T) cells, T follicular helper (Tfh) cells, and plasma cells following nitrite intervention, along with a reduction in splenic regulatory T (Treg) cells. ELISA quantification revealed elevated serum anti-double-stranded DNA antibodies (anti-dsDNA), antinuclear antibodies (ANA), and pro-inflammatory cytokines (IL-12p70, TNF-α), correlating with aggravated renal pathology in nitrite-exposed mice. Transcriptome analysis further revealed significant gene expression changes in both spleen and kidney tissues associated with nitrite exposure. Notably, three KEGG pathways, cell adhesion molecules, osteoclast differentiation, and B cell receptor signaling pathway, were consistently enriched in both the spleen and kidney transcriptomes. Subsequent western blot analysis identified that the Itgam (integrin alpha M)-related cell adhesion molecule pathway potentially mediated the mechanism by which nitrite aggravated lupus in MRL/lpr mice. To explore this mechanism, the integrin antagonist lifitegrast was used to inhibit the expression of Itgam in the nitrite-exposed MRL/lpr mice, resulting in attenuation of nitrite-induced lupus exacerbation. Collectively, these findings suggested that nitrite exposure could aggravate lupus by promoting Itgam expression.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775326","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}

引用次数: 0

Large Peritoneal Macrophages Promote the Resolution of Inflammation in Injured Endometrium. 巨噬细胞促进损伤子宫内膜炎症的消退。

IF 5 2区医学

Inflammation Pub Date : 2025-08-02 DOI: 10.1007/s10753-025-02335-z

Jingman Li, Lijie Yin, Jiali Wang, Yuchen Pan, Chen Peng, Yue Dong, Sunan Shen, Yayi Hou, Guangfeng Zhao

{"title":"Large Peritoneal Macrophages Promote the Resolution of Inflammation in Injured Endometrium.","authors":"Jingman Li, Lijie Yin, Jiali Wang, Yuchen Pan, Chen Peng, Yue Dong, Sunan Shen, Yayi Hou, Guangfeng Zhao","doi":"10.1007/s10753-025-02335-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02335-z","url":null,"abstract":"Macrophages play a significant role in the repair of endometrial injuries. While large peritoneal macrophages (LPMs) have been reported to migrate to injured organs and repair tissues within the peritoneal cavity, their involvement in the repair of injured endometrium remains unclear. In this study, we utilize a mouse model of endometrial injury that does not involve laparotomy, a procedure that typically results in a substantial loss of LPMs. Strikingly, we find that LPMs reach the endometrium within 6 h post-modeling. By depleting or supplementing LPMs, our results reveal that these cells are capable of engulfing dead cells in the endometrium and resolving inflammation. Additionally, we observe that the migration efficiency of LPMs is enhanced with increased levels of 17β-estradiol (E2) in mice. In vitro assays further confirm that E2 accelerates the migration of LPMs towards apoptotic endometrial stromal cells. Overall, our findings demonstrate that LPMs rapidly migrate into injured endometrium in relation to E2 levels and facilitate the process of tissue repair.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768615","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}

引用次数: 0

Exosomes Derived from Bone Marrow Dendritic Cells Exhibit Protective and Therapeutic Potential Against Chemically Induced Chronic Pancreatitis in Rats. 骨髓树突状细胞提取的外泌体对化学药物诱导的大鼠慢性胰腺炎具有保护和治疗潜力

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-10-19 DOI: 10.1007/s10753-024-02150-y

Shaimaa M Bashir, Sherine M Rizk, Mohammed M Nooh, Hebatullah S Helmy

{"title":"Exosomes Derived from Bone Marrow Dendritic Cells Exhibit Protective and Therapeutic Potential Against Chemically Induced Chronic Pancreatitis in Rats.","authors":"Shaimaa M Bashir, Sherine M Rizk, Mohammed M Nooh, Hebatullah S Helmy","doi":"10.1007/s10753-024-02150-y","DOIUrl":"10.1007/s10753-024-02150-y","url":null,"abstract":"Background: Chronic pancreatitis (CP) is a specific clinical disorder that develops from pancreatic fibrosis and immune cell dysregulation. It has been proposed that bone marrow dendritic cells (BMDCs) exosomes have significant effects on immune regulation. Thus, the current study acquainted the prophylactic and therapeutic effects of exosomes derived from BMDCs on a rat model of CP.Materials and methods: BMDCs were prepared and identified, and then the exosomes were isolated by differential ultracentrifugation. Prophylactic and therapeutic effects of exosomes were investigated on L-arginine induced CP model.Results: Administration of two tail vein injections of exosomes (200 μg/kg/dose suspended in 0.2 ml PBS) markedly improved the pancreatic function and histology compared to CP group. Moreover, exosomes prominently mitigated the increase in amylase, lipase, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and elevated antioxidant enzymes; catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx).Conclusion: BMDCs exosomes can be considered as a promising candidate, with a high efficacy and stability compared with its parent cell, for management of CP and similar inflammatory diseases.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1728-1744"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464275","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}

引用次数: 0

Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice. 胃饥饿素抑制星形胶质细胞中炎性小体的激活，减轻焦死，并防止脂多糖诱导的小鼠抑郁样行为。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-19 DOI: 10.1007/s10753-024-02190-4

Xiaoou Han, Xiying Fu, Wanxu Guo, Yaqi Liu, Jiangjin Sun, Tian Wang, Wei Yang

{"title":"Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice.","authors":"Xiaoou Han, Xiying Fu, Wanxu Guo, Yaqi Liu, Jiangjin Sun, Tian Wang, Wei Yang","doi":"10.1007/s10753-024-02190-4","DOIUrl":"10.1007/s10753-024-02190-4","url":null,"abstract":"Depression is the leading cause of disability worldwide and places a significant burden on society. Neuroinflammation is closely associated with the pathophysiology of depression. Increasing evidence suggests that astrocytes, as the most abundant glial cells in the brain, are involved in the occurrence and development of depression due to morphological abnormalities and dysfunction. Astrocytes express the NOD-like receptor protein 2 (NLRP2) and NLRP3 inflammasomes, and the activation of inflammasomes induces pyroptosis. Ghrelin, a gastrointestinal peptide, plays vital role in regulating inflammation and alleviating stress. Therefore, we proposed a hypothesis that ghrelin inhibits the activation of inflammasomes on astrocytes, reduces pyroptosis, and consequently prevents depression. We used lipopolysaccharide (LPS)-induced mouse depression model and cultured primary astrocytes in vitro to explore the mechanism of the antidepressant effect of ghrelin. Our results showed that ghrelin effectively inhibited acute inflammatory responses and damage in the hippocampus and prefrontal cortex. The activation of NLRP2 and NLRP3 in astrocytes induced by LPS was significantly inhibited by ghrelin. Pretreatment with ghrelin effectively suppressed LPS-induced upregulation of pyroptosis-related proteins and mRNA. Ghrelin alleviated cell membrane pore formation and cell swelling, ultimately improved LPS-induced depression-like behavior. In vitro, ghrelin prevented the LPS-induced upregulation of pyroptosis-related proteins and mRNA expression in astrocytes, and inhibited the initiation and assembly of NLRP2 and NLRP3. Ghrelin exhibits antidepressant effects, inhibits inflammasomes activation in astrocytes, and prevents pyroptosis, suggesting a novel strategy for treating depression. This groundbreaking study reveals new avenues for targeting potential therapeutic interventions to alleviate depression.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2292-2312"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864263","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}

引用次数: 0

Identification and Construction of a R-loop Mediated Diagnostic Model and Associated Immune Microenvironment of COPD through Machine Learning and Single-Cell Transcriptomics. 通过机器学习和单细胞转录组学鉴定和构建r环介导的COPD诊断模型和相关免疫微环境。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2025-01-11 DOI: 10.1007/s10753-024-02232-x

Jianing Lin, Yayun Nan, Jingyi Sun, Anqi Guan, Meijuan Peng, Ziyu Dai, Suying Mai, Qiong Chen, Chen Jiang

{"title":"Identification and Construction of a R-loop Mediated Diagnostic Model and Associated Immune Microenvironment of COPD through Machine Learning and Single-Cell Transcriptomics.","authors":"Jianing Lin, Yayun Nan, Jingyi Sun, Anqi Guan, Meijuan Peng, Ziyu Dai, Suying Mai, Qiong Chen, Chen Jiang","doi":"10.1007/s10753-024-02232-x","DOIUrl":"10.1007/s10753-024-02232-x","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a prevalent chronic inflammatory airway disease with high incidence and significant disease burden. R-loops, functional chromatin structure formed during transcription, are closely associated with inflammation due to its aberrant formation. However, the role of R-loop regulators (RLRs) in COPD remains unclear. Utilizing both bulk transcriptome data and single-cell RNA sequencing data, we assessed the diverse expression patterns of RLRs in the lung tissues of COPD patients. A lower R-loop score was found in patients with COPD and in neutrophils. 12 machine learning algorithms (150 combinations) identified 14 hub RLRs (CBX8, EHD4, HDLBP, KDM6B, NFAT5, NLRP3, NUP214, PAFAH1B3, PINX1, PLD1, POLB, RCC2, RNF213, and VIM) associated with COPD. A RiskScore based on 14 RLRs identified two distinct COPD subtypes. Patient groups at high risk of COPD (low R-loop scores) had a higher immune score and a significant increase in neutrophils in their immune microenvironment compared to low-risk groups. PD-0325901 and QL-X-138 represent prospective COPD treatments for high-risk (low R-loop score) and low-risk (high R-loop score) patients. Finally, RT-PCR experiments confirmed expression differences of 8 RLRs (EHD4, HDLBP, NFAT5, NLRP3, PLD1, PINX1, POLB, and VIM) in COPD mice lung tissue. R-loops significantly contribute to the development of COPD and constructing predictive models based on RLRs may provide crucial insight into personalized treatment strategies for patients with COPD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2802-2823"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964625","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}

引用次数: 0

Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights. 姜黄素对 IL-17A 介导的 p53 纤溶系统的影响：小鼠蛋白质组学与人类纤维化scRNAseq综合观察。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-10-19 DOI: 10.1007/s10753-024-02167-3

Mahesh Manjunath Gouda, Rex Devasahayam Arokia Balaya, Prashant Kumar Modi, Safwen Kadri, Jaikanth Chanderasekaran, Akarsha Balnadupete, Yashodhar Prabhakar Bhandary

{"title":"Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights.","authors":"Mahesh Manjunath Gouda, Rex Devasahayam Arokia Balaya, Prashant Kumar Modi, Safwen Kadri, Jaikanth Chanderasekaran, Akarsha Balnadupete, Yashodhar Prabhakar Bhandary","doi":"10.1007/s10753-024-02167-3","DOIUrl":"10.1007/s10753-024-02167-3","url":null,"abstract":"Acute lung injury (ALI) is primarily driven by an intense inflammation in the alveolar epithelium. Key to this is the pro-inflammatory cytokine, Interleukin 17 (IL-17), which influences pulmonary immunity and modifies p53 function. The direct role of IL-17A in p53-fibrinolytic system is still unclear, it is important to evaluate this mechanism to regulate the ALI progression to idiopathic pulmonary fibrosis (IPF). C57BL/6 mice, exposed to recombinant IL-17A protein and treated with curcumin, provided insight into IL-17A mechanisms and curcumin's potential for modulating early pulmonary fibrosis stages. A diverse methodology, including proteomics, single-cell RNA sequencing (scRNA-seq) integration, molecular, and Schroedinger approach were utilized. In silico approaches facilitated the potential interactions between curcumin, IL-17A, and apoptosis-related proteins. A notable surge in the expression levels of IL-17A, p53, and fibrinolytic components such as Plasminogen Activator Inhibitor-1 (PAI-I) was discerned upon the IL17A exposure in mouse lungs. Furthermore, the enrichment of pathways and differential expression of proteins underscored the significance of IL-17A in governing downstream regulatory pathways such as inflammation, NF-kappaB signaling, Mitogen-Activated Protein Kinases (MAPK), p53, oxidative phosphorylation, JAK-STAT, and apoptosis. The integration of scRNA-seq data from 20 IPF and 10 control lung specimens emphasized the importance of IL-17A mediated downstream regulation in PF patients. A potent immuno-pharmacotherapeutic agent, curcumin, demonstrated a substantial capacity to modulate the lung pathology and molecular changes induced by IL-17A in mouse lungs. Human IPF single cell data integration confirmed the effects of IL-17A mediated fibrinolytic components in ALI to IPF progression.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1957-1973"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464277","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}

引用次数: 0

Innate Immune Cell Profiling in Peripheral Blood Mononuclear Cells of Patients with Moyamoya Disease. 烟雾病患者外周血单个核细胞的先天免疫细胞谱分析。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-13 DOI: 10.1007/s10753-024-02201-4

Chenglong Liu, Siqi Mou, Bojian Zhang, Yuheng Pang, Liujia Chan, Junsheng Li, Qiheng He, Zhiyao Zheng, Zhikang Zhao, Wei Sun, Xiangjun Shi, Hancheng Qiu, Xiaofeng Deng, Wenjing Wang, Peicong Ge, Jizong Zhao

{"title":"Innate Immune Cell Profiling in Peripheral Blood Mononuclear Cells of Patients with Moyamoya Disease.","authors":"Chenglong Liu, Siqi Mou, Bojian Zhang, Yuheng Pang, Liujia Chan, Junsheng Li, Qiheng He, Zhiyao Zheng, Zhikang Zhao, Wei Sun, Xiangjun Shi, Hancheng Qiu, Xiaofeng Deng, Wenjing Wang, Peicong Ge, Jizong Zhao","doi":"10.1007/s10753-024-02201-4","DOIUrl":"10.1007/s10753-024-02201-4","url":null,"abstract":"Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by stenosis or occlusion of the internal carotid artery, thus leading to ischaemic and haemorrhagic strokes. Although genetic studies have identified ring finger protein 213 (RNF213) as a susceptibility gene, the low disease penetrance suggests that a secondary trigger, such as infection, may initiate disease onset. This study aimed to characterize the innate immune cell profile of peripheral blood mononuclear cells (PBMCs) of MMD patients via mass cytometry (CyTOF). Blood samples from 10 MMD patients and 10 healthy controls were analysed, with a focus on natural killer (NK) cells, monocytes, and dendritic cells (DCs). The results revealed significant changes in the NK and monocyte subpopulations in MMD patients; specifically, there was a decrease in the CD56dimCD16- NK03 subset and an increase in CD163high classical monocytes, thus indicating compromised microbial defences and heightened inflammation. Additionally, significant changes were observed in DC subpopulations, including an increase in CCR7+ mature DCs and a decrease in CD141+ and CD1c+ DCs. Overactivation of the TLR/MyD88/NF-κB pathway was observed in most innate immune cells, thus indicating its potential role in disease progression. These findings provide novel insights into immune dysfunction in MMD and highlight potential therapeutic targets.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2444-2457"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817926","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}

引用次数: 0

TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients. 多发性硬化症患者促炎可溶性细胞因子及其特异性自身抗体分泌。

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-06 DOI: 10.1007/s10753-024-02205-0

Sylvie Carmona, Jehanne Aghzadi, Thierry Vincent, Pierre Labauge, Clarisse Carra-Dallière, Sylvain Lehmann, Sophie Desplat-Jégo, Xavier Ayrignac

{"title":"TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients.","authors":"Sylvie Carmona, Jehanne Aghzadi, Thierry Vincent, Pierre Labauge, Clarisse Carra-Dallière, Sylvain Lehmann, Sophie Desplat-Jégo, Xavier Ayrignac","doi":"10.1007/s10753-024-02205-0","DOIUrl":"10.1007/s10753-024-02205-0","url":null,"abstract":"Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system, where immune dysregulation plays a critical role. We sought to explore the modulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFɑ) and TNF-like weak inducer of apoptosis (TWEAK), along with their respective autoantibodies, TNAb and TWAb, and to decipher potential associations between these and clinical characteristics which could assist personalized therapy in MS. We also assessed the complementarity to leading candidate biomarkers in MS patient monitoring, namely, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). Serum levels of these cytokines and their autoantibodies were measured in 150 MS patients and 186 healthy controls (HC) by ELISA. We found that sTWEAK levels were significantly higher, while sTNFɑ levels were lower in MS patients compared to HC. Additionally, we detected TWAb in 10% of MS patients, a prevalence significantly higher than in HC (4%) and TNAb in only one patient. TWAb-positive patients were significantly younger, had lower EDSS scores, a shorter disease duration, and predominantly presented with the relapsing-remitting form of MS. Together, these results provide new actors to be considered in the development of a biomarker profiling panel to be used in MS patient management. Further research is warranted to elucidate the clinical significance of these autoantibodies and their role in MS neuroinflammatory modulation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2494-2502"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785320","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}

引用次数: 0

F2RL1 Inhibition Alleviates Lipotoxicity-Induced Kidney Injury Through the Hippo Pathway in Diabetic Kidney Disease. F2RL1抑制通过Hippo通路减轻糖尿病肾病中脂毒诱导的肾损伤

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-12-31 DOI: 10.1007/s10753-024-02215-y

Hui Wang, Wei Wang, Yao Jiang, Siyuan Cui, Yulin Kong, Yong Q Chen, Shenglong Zhu

{"title":"F2RL1 Inhibition Alleviates Lipotoxicity-Induced Kidney Injury Through the Hippo Pathway in Diabetic Kidney Disease.","authors":"Hui Wang, Wei Wang, Yao Jiang, Siyuan Cui, Yulin Kong, Yong Q Chen, Shenglong Zhu","doi":"10.1007/s10753-024-02215-y","DOIUrl":"10.1007/s10753-024-02215-y","url":null,"abstract":"Diabetic kidney disease (DKD), which is emerging as a pervasive global health concern and a considerable economic burden, is characterized by a detrimental effect on renal function and structure. Recent research indicates that the progression of DKD is facilitated by lipotoxic injury to tubular epithelial cells (TECs). However, the specific mechanisms that contribute to this cellular damage have yet to be fully elucidated. Our results revealed a significant upregulation of F2RL1 in vivo and in vitro models, which was positively correlated with the expression of inflammatory factors. Knockdown of F2RL1 significantly reduced inflammatory response in palmitate-stimulated HK-2 cells. Mechanistically, F2RL1 might exacerbate lipotoxicity-induced DKD through the modulation of the Hippo signaling pathway. Collectively, these findings suggest that modulating F2RL1 expression may be a strategic approach to mitigate the inflammatory damage to RTECs associated with DKD, potentially through its involvement in the Hippo signaling pathway. Given these findings, F2RL1 merits consideration as a candidate therapeutic target for DKD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2628-2639"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909557","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}

引用次数: 0

Protective Effects of a Dihydrodiazepine Against Endotoxin Shock Through Suppression of TLR4/NF-κB/IRF3 Signaling Pathways. 二氢地西泮通过抑制 TLR4/NF-κB/IRF3 信号通路对内毒素休克的保护作用

IF 5 2区医学

Inflammation Pub Date : 2025-08-01 Epub Date: 2024-10-14 DOI: 10.1007/s10753-024-02160-w

Hamza Hanieh, Manal A Alfwuaires, Maisa S Abduh, Alyaa Abdrabu, Nidal A Qinna, Abdullah M Alzahrani

{"title":"Protective Effects of a Dihydrodiazepine Against Endotoxin Shock Through Suppression of TLR4/NF-κB/IRF3 Signaling Pathways.","authors":"Hamza Hanieh, Manal A Alfwuaires, Maisa S Abduh, Alyaa Abdrabu, Nidal A Qinna, Abdullah M Alzahrani","doi":"10.1007/s10753-024-02160-w","DOIUrl":"10.1007/s10753-024-02160-w","url":null,"abstract":"Sepsis and septic shock are life-threatening systemic inflammatory conditions and among the most frequent causes of morbidity and mortality globally. Preclinical evidence has identified a number of diazepine-based compounds with therapeutic potential in inflammatory diseases. However, the potential anti-inflammatory properties of diazepines in the overwhelming immune response during sepsis have been rarely examined. Thus, the current study aimed to identify a new diazepine compound with therapeutic potential in sepsis. Assessing the inflammatory response of macrophages to Lipopolysaccharides (LPS) in vitro identified 2-[7-(trifluoromethyl)-2,3-dihydro-1H-1,4-diazepin-5-yl]phenol (2-TDDP) as a potential anti-inflammatory agent. It reduced secretion of Interleukin-1β (IL-1β), IL-6, IL-12p70, IL-18, Tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), IFN-β, and increased the secretion of IL-10. In a mouse model of LPS-induced endotoxin shock, 2-TDDP reduced mortality and attenuated inflammation-induced tissue injury in the spleen, liver, kidney, and lung. This was accompanied by reduced serum levels of IL-1β, IL-6, IL-12p70, TNF-α, IFN-γ, IFN-β, and increased levels of IL-10. Importantly, 2-TDDP suppressed the Toll-like receptor 4 (TLR4)/Nuclear factor-κB (NF-κB) and TLR4/Interferon regulatory factor 3 (IRF3) signaling pathways through a reduction in the expression of TLR4, Myeloid differentiation primary response 88 (MyD88), P65, and TNF receptor-associated factor 3 (Traf3). Moreover, 2-TDDP suppressed the expression of CD86, Programmed death-ligand 1 (PD-L1) and C5a receptor (C5aR), but not Major histocompatibility complex II (MHCII). Analysis of splenic lymphocyte populations revealed a decrease in the number of CD4+, CD8+, and B cells. Collectively, these findings introduced the dihydrodiazepine 2-TDDP as a new anti-inflammatory agent with potent therapeutic potential in endotoxin shock, paving an avenue for future clinical application.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1863-1878"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464286","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}

引用次数: 0