Inflammation最新文献_第4页

4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-22 DOI: 10.1007/s10753-025-02268-7

You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li

{"title":"4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway.","authors":"You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li","doi":"10.1007/s10753-025-02268-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02268-7","url":null,"abstract":"Bone marrow mesenchymal stem cells (BMSCs) play an important role in bone metabolism and tissue repair, and their ability to differentiate into osteoblasts is crucial in the treatment of bone diseases such as postmenopausal osteoporosis (PMOP). However, the function of BMSCs may be affected by ferroptosis. Ferroptosis is a cell death mode characterized by excess Fe2+ and lipid peroxidation, which significantly affects the survival rate and differentiation ability of BMSCs. This study investigated the effect of exogenous itaconate derivative 4-octyl itaconate (4-OI) on Erastin-induced BMSCs ferroptosis. The results showed that 4-OI significantly inhibited Erastin-induced BMSCs ferroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, reduced reactive oxygen species levels and oxidative damage, and restored antioxidant capacity. At the same time, 4-OI promoted the osteogenic differentiation of BMSCs. Further experiments showed that Nrf2-IN-1, an inhibitor of the Nrf2 pathway, could reverse the protective effect of 4-OI. In vivo, 4-OI was shown to reduce bone loss in ovariectomized (OVX) mice, as assessed by Micro-CT analysis. Immunofluorescence staining further revealed increased GPX4 and Nrf2 expression in vertebral tissues following 4-OI treatment. These results indicate that 4-OI improves ferroptosis of BMSCs and enhances osteogenic differentiation ability by activating the Nrf2 pathway, providing new research ideas and potential targets for the treatment of PMOP.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472479","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

High-Resolution Untargeted Metabolomics Reveals Alternate-Day Fasting May Attenuate Diabetic Kidney Disease Progression in BTBR ob/ob Mice by Affecting the HCA, IPA and Reducing Inflammation.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-21 DOI: 10.1007/s10753-025-02263-y

Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li

{"title":"High-Resolution Untargeted Metabolomics Reveals Alternate-Day Fasting May Attenuate Diabetic Kidney Disease Progression in BTBR ob/ob Mice by Affecting the HCA, IPA and Reducing Inflammation.","authors":"Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li","doi":"10.1007/s10753-025-02263-y","DOIUrl":"https://doi.org/10.1007/s10753-025-02263-y","url":null,"abstract":"Diabetic kidney disease (DKD) is one of the most severe complications of diabetes mellitus, with limited effective therapeutic interventions. Alternate-day fasting (ADF) shows potential in treating DKD, though its mechanisms are not fully understood. In this study, BTBR ob/ob mice underwent 12 weeks of ADF, and high-resolution untargeted metabolomics were performed to uncover the underlying mechanisms. After 12 weeks of ADF, the BTBR ob/ob mice exhibited weight loss, lower blood glucose and LDL-C levels, reduced 24-h urinary protein excretion, and decreased renal collagen deposition. A total of 44 metabolites were differentially expressed, with 25 up-regulated and 19 down-regulated. Notably, hyocholic acid (HCA) and indole-3-propionic acid (IPA), both products of intestinal bacteria, can modulating inflammation were differentially expressed. Furthermore, the kidneys of BTBR ob/ob mice showed significantly lower NF-κB pathway activity and reduced inflammation after 12 weeks of ADF. This study indicates that ADF may alleviate DKD progression by modulating HCA, IPA, and decreasing inflammation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467901","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

The Vitamin E Derivative Garcinoic Acid Suppresses NLRP3 Inflammasome Activation and Pyroptosis in Murine Macrophages. 维生素 E 衍生物甘草酸可抑制小鼠巨噬细胞中 NLRP3 炎症小体的活化和嗜热症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-21 DOI: 10.1007/s10753-025-02269-6

Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert

{"title":"The Vitamin E Derivative Garcinoic Acid Suppresses NLRP3 Inflammasome Activation and Pyroptosis in Murine Macrophages.","authors":"Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert","doi":"10.1007/s10753-025-02269-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02269-6","url":null,"abstract":"Excessive inflammation in cells are a common cause of inflammation-related diseases such as cardiometabolic diseases. The cellular multiprotein complex nucleotide-binding domain and leucine-rich repeat pyrin domain 3 (NLRP3) inflammasome is a cellular key modulator of inflammatory processes. In addition to classic medications, phytochemicals are known for their anti-inflammatory potential. In African folk medicine the seeds of Garcinia kola are used to support the treatment of inflammatory diseases. Of particular interest is the phytochemical garcinoic acid (GA, trans-13'-carboxy-δ-tocotrienol), which is isolated from the Garcinia kola seeds. This derivative and potential metabolite of the vitamin E congener δ-tocotrienol (T3) shows anti-inflammatory properties in vitro. However, the underlying mechanisms are largely unknown. To get better insights into the molecular mode of action, murine J774A.1 macrophages were stimulated with lipopolysaccharides (LPS) only or in combination with adenosine triphosphate (ATP), which led to canonical activation of the NLRP3 inflammasome and subsequent pyroptosis. A combined treatment with GA resulted in significantly reduced stimulation of the transcription factor nuclear factor 'ĸ-light-chain-enhancer' of activated B-cells (NF-ĸB), decreased expression of inflammasome-related genes and marked downregulation of autoproteolytic cleavage of caspase-1 (Casp-1). Consequently, GA had an inhibitory effect on pyroptosis. The results have been validated using the well-known NLRP3 inflammasome inhibitor MCC950. In conclusion, GA was shown to have relevant effects on the regulation of the NLRP3 inflammasome and pyroptosis in vitro. Our study provides new mechanistic insights into the anti-inflammatory mode of action of GA and highlights its relevance as a potential phytochemical drug for the treatment of inflammation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467904","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

Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02248-x

Xiaoyu Zi, Huanhuan Yan, Baochen Li, Chong Gao, Xiaofeng Li, Jing Luo, Caihong Wang

{"title":"Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis.","authors":"Xiaoyu Zi, Huanhuan Yan, Baochen Li, Chong Gao, Xiaofeng Li, Jing Luo, Caihong Wang","doi":"10.1007/s10753-025-02248-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02248-x","url":null,"abstract":"Aberrant number and/or dysfunction of regulatory T cells (Tregs) is associated with the development of rheumatoid arthritis (RA). This study aimed to assess the frequencies of naive Tregs (nTregs) and memory Tregs (mTregs) in the peripheral blood of RA patients and to explore their relationships with cytokine levels. This study involved 97 RA patients categorized into three groups based on Disease Activity Score 28 (DAS28) and 50 healthy controls (HCs). Flow cytometry was employed to quantify Treg subsets in peripheral blood, while serum cytokine concentrations were measured using a flow cytometry bead array. The findings revealed that three RA groups, stratified by disease activity, all exhibited a significant decrease in both the count and percentage of nTregs and an increase in the percentage of mTregs compared to HCs. Notably, the group with high RA disease activity displayed a higher percentage of mTregs than the remission group. Additionally, correlation analysis indicated that IL-2 concentrations were negatively correlated with total T, CD4 + T and Th17 cell counts, and positively correlated with the absolute count of nTregs. This study demonstrated that the count of mTregs in RA patients increased with escalating disease activity, while the count of nTregs remained unchanged. Moreover, IL-2 concentrations were positively correlated with the numbers of Tregs and nTregs, suggesting that IL-2 plays a significant role in modulating Treg subsets. Further studies on targeted therapies aligned with the distribution of mTregs and nTregs in RA patients with varying disease activity could potentially achieve effective remission.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457607","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

Uridine Phosphorylase 1 as a Biomarker Associated with Glycolysis in Acute Lung Injury.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02270-z

Congkuan Song, Qingqing Li, Jinjin Zhang, Weidong Hu

引用次数: 0

Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-19 DOI: 10.1007/s10753-025-02266-9

Lin Miao, Haowei Wang, Xue Yang, Lisha Xu, Ruike Xu, Hanxin Teng, Yue Zhang, Yingjie Zhao, Genmeng Yang, Xiaofeng Zeng

{"title":"Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome.","authors":"Lin Miao, Haowei Wang, Xue Yang, Lisha Xu, Ruike Xu, Hanxin Teng, Yue Zhang, Yingjie Zhao, Genmeng Yang, Xiaofeng Zeng","doi":"10.1007/s10753-025-02266-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02266-9","url":null,"abstract":"Objective: Human immunodeficiency virus (HIV)-infected individuals who abuse methamphetamine (METH) exhibit more severe neurotoxicity and cognitive impairment. Pyroptosis, a programmed cell death pathway mediated by the inflammasome, has been implicated in various neurological diseases. This study aimed to elucidate the role of the AIM2 inflammasome in METH- and HIV-1 Tat-induced pyroptosis in human brain tissue and in vitro models.Methods: Postmortem brain tissue from HIV-infected individuals with a history of METH abuse was analyzed for pyroptosis markers and AIM2 inflammasome components using immunohistochemistry, immunofluorescence, and Western blotting. BV2 microglial cells were lentivirally transduced to knockdown AIM2 expression. DNA damage was assessed using Western blotting and the comet assay. Expression of pyroptosis-related proteins was evaluated by electron microscopy, Western blotting, and immunofluorescence. Cell viability was measured using the CCK8 assay.Results: Elevated levels of pyroptosis markers and AIM2 inflammasome components were observed in brain tissue from HIV-infected METH users. METH and Tat synergistically induced pyroptosis in BV2 cells in a time- and concentration-dependent manner, accompanied by DNA damage and activation of the AIM2 inflammasome. Knockdown of AIM2 significantly reduced the expression of pyroptosis-related proteins.Conclusion: METH and HIV-1 Tat proteins synergistically induce microglial pyroptosis by activating the AIM2 inflammasome through dsDNA damage. These findings suggest that targeting the AIM2 inflammasome may be a promising therapeutic strategy for HIV-associated neurocognitive disorder (HAND).","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448941","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

Nrg4 Secreted by Brown Adipose Tissue Suppresses Ferroptosis of Sepsis-Induced Liver Injury.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-17 DOI: 10.1007/s10753-024-02230-z

Linqi Feng, Jun Cui, Wenlong Chen, Lei Zhu, Panpan Li, Haitao Zhou, Yang Sun, Wei Yi

引用次数: 0

Inhibition of SLC3A2 Deletion-Mediated Ferroptosis by Bone Marrow Stromal Cells to Alleviate Inflammation and Fibrosis in Diabetic Kidney Disease.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-17 DOI: 10.1007/s10753-025-02261-0

Yang Fan, Ya-Ling Li, Li-Lan Huang, Ji Yang, Yue-Yuan Hou, Yi-Hua Bai

{"title":"Inhibition of SLC3A2 Deletion-Mediated Ferroptosis by Bone Marrow Stromal Cells to Alleviate Inflammation and Fibrosis in Diabetic Kidney Disease.","authors":"Yang Fan, Ya-Ling Li, Li-Lan Huang, Ji Yang, Yue-Yuan Hou, Yi-Hua Bai","doi":"10.1007/s10753-025-02261-0","DOIUrl":"https://doi.org/10.1007/s10753-025-02261-0","url":null,"abstract":"Renal fibrosis and inflammatory infiltration are common pathological features of diabetic kidney disease (DKD). Bone marrow mesenchymal stem cells (BMSCs) are recognized for their anti-fibrotic and anti-inflammatory properties. The objective of this study was to assess the effects of BMSCs on DKD and elucidate their potential mechanisms of action. To assess the role of BMSCs, a DKD model was induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) combined with a high-fat diet, and a human kidney-2 (HK-2) cell damage model was established using high glucose. To investigate the mechanism of the impact of BMSCs on DKD at the genetic level, transcriptome sequencing of the treated HK-2 cells was conducted, identifying the differentially expressed gene SLC3A2, which is related to ferroptosis. A HK-2 cell damage model with SLC3A2 knockout was then constructed to assess the effects of BMSCs on ferroptosis, inflammation, and fibrosis. Also, the potential relationship between BMSCs and the mitogen-activated protein kinase (MAPK) signaling pathway was assessed. In vivo and in vitro studies demonstrated that BMSCs enhanced inflammation and fibrosis in DKD by inhibiting ferroptosis. Knockdown of SLC3A2 promoted ferroptosis, inflammation, and fibrosis, while BMSCs reversed these effects, likely through the inhibition of the MAPK signaling pathway. This research demonstrated that ferroptosis and the activation of the MAPK signaling pathway can promote the onset and progression of DKD. It revealed the therapeutic role of BMSCs in DKD treatment and proposed that SLC3A2 might serve as a potential target for DKD therapy, thereby providing a theoretical foundation for the treatment of DKD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440719","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

SIRT5 Alleviated Eosinophilic Asthma Through ROS Inhibition and Nrf2/HO-1 Activation.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-13 DOI: 10.1007/s10753-025-02257-w

Yuwei Xie, Yingzhi He, Juan Liang, Jie Liu, Chuanghong Ke, Xiaohuan Mo, Cizheng Zeng, Sijie Wang, Xuemei Chen, Dang Ao, Jinfeng Tang, Wen Li

{"title":"SIRT5 Alleviated Eosinophilic Asthma Through ROS Inhibition and Nrf2/HO-1 Activation.","authors":"Yuwei Xie, Yingzhi He, Juan Liang, Jie Liu, Chuanghong Ke, Xiaohuan Mo, Cizheng Zeng, Sijie Wang, Xuemei Chen, Dang Ao, Jinfeng Tang, Wen Li","doi":"10.1007/s10753-025-02257-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02257-w","url":null,"abstract":"Asthma is a prevalent chronic disease with high morbidity and mortality in both children and adults, imposing a burden on the physical and mental well-being of patients, as well as their families. Inhaled corticosteroids and long-acting β2 agonists are mostly used to control asthma, these therapies are not suitable for patients with severe asthma. Approximately 80% of severe uncontrolled asthma cases are classified as eosinophilic asthma (EA). Oxidative stress and inflammation play crucial roles in the pathology and development of asthma, with SIRT5 being important in the process of anti-oxidation and anti-inflammation. However, little is known about the role of SIRT5 in EA and its regulatory mechanism on substrate protein and biological function. In this study, we investigated the role of SIRT5 in ovalbumin (OVA)-induced EA mouse models and house dust mite (HDM)-induced asthmatic cell models, while exploring its potential mechanisms. We found that SIRT5 alleviated EA by inhibiting reactive oxygen species and activating Nrf2/HO-1 pathways. Interestingly, overexpression of SIRT5 attenuated the inflammatory response in EA. Taken together, these results suggest that SIRT5 may serve as a promising target for managing asthma symptoms.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407038","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

Sirtuin1 Deficiency Could Exacerbate Melanocyte Apoptosis Under Endoplasmic Reticulum Stress.

IF 4.5 2区医学

Inflammation Pub Date : 2025-02-08 DOI: 10.1007/s10753-025-02255-y

Jing Zhu, Youming Guo, Lingling Luo, Xin Huang, Tianqi Wei, Baiyi Zuo, Guanying Liu, Wenbo Bu, Chengrang Li

引用次数: 0