Inflammation最新文献_第3页

Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis. 乙酰基 11-Keto β-乳香酸能改善多发性硬化症小鼠模型的神经功能。

IF 4.5 2区医学

Inflammation Pub Date : 2024-11-02 DOI: 10.1007/s10753-024-02176-2

Saeed Karima, Seyyed Hossein Khatami, Sajad Ehtiati, Sara Khoshtinatnikkhouy, Reza Ataei Kachouei, Ali Jahanbazi Jahan-Abad, Abbas Tafakhori, Hadis Firoozpour, Farzaneh Salmani

{"title":"Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis.","authors":"Saeed Karima, Seyyed Hossein Khatami, Sajad Ehtiati, Sara Khoshtinatnikkhouy, Reza Ataei Kachouei, Ali Jahanbazi Jahan-Abad, Abbas Tafakhori, Hadis Firoozpour, Farzaneh Salmani","doi":"10.1007/s10753-024-02176-2","DOIUrl":"https://doi.org/10.1007/s10753-024-02176-2","url":null,"abstract":"Acetyl-11-keto-β-boswellic acid is one of the main active components of Boswellia sp. resin with the most potent anti-inflammatory activity. In recent years, herbal therapy has received considerable attention for the treatments of inflammatory and demyelinating diseases such as Multiple sclerosis (MS). Studies have shown that herbal compounds could enhance myelin repair and suppress inflammation. This study was designed to investigate the therapeutic effects of intraperitoneal administration of AKBA in Experimental Autoimmune Encephalomyelitis (EAE), as an animal model of MS. Following EAE induction in female C57BL/6J mice, animals were treated with AKBA and the levels of different serum inflammatory mediators, as well as motor functions, myelination, and inflammatory cell infiltration were assessed. Our results revealed that the application of AKBA alleviated EAE clinical severity, and suppressed inflammation, demyelination, leukocyte infiltration, and gliosis in EAE mice. Our findings suggest that the therapeutic effects of AKBA are likely a consequence of its neuroprotective and anti-inflammatory properties. The beneficial effects of AKBA may therefore provide new insights in various neuroinflammatory diseases such as MS and thereby could serve as a potential treatment candidate.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564381","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

Atorvastatin Alleviates Age-Related Macular Degeneration via AIM2-Regulated Pyroptosis. 阿托伐他汀通过 AIM2 调控的裂解作用缓解老年性黄斑变性

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-31 DOI: 10.1007/s10753-024-02179-z

Jing Lu, Yuxia He, Yong Du, Long Zhao, Ping Wu, Qinxin Shu, Hui Peng, Xing Wang

{"title":"Atorvastatin Alleviates Age-Related Macular Degeneration via AIM2-Regulated Pyroptosis.","authors":"Jing Lu, Yuxia He, Yong Du, Long Zhao, Ping Wu, Qinxin Shu, Hui Peng, Xing Wang","doi":"10.1007/s10753-024-02179-z","DOIUrl":"10.1007/s10753-024-02179-z","url":null,"abstract":"The underlying causes of age-related macular degeneration (AMD) remain elusive and treatment options of it are limited, while atorvastatin (AT) is expected to improve AMD. Our study sought to uncover the specific mechanisms that initiate pyroptosis in AMD and elucidate whether AT ameliorates Aβ1-40-induced retinal damage by inhibiting pyroptosis. An animal model of AMD was triggered by Aβ1-40, and the therapeutic efficacy of AT was evaluated by hematoxylin and eosin staining (H&E), Optical Coherence Tomography (OCT), Electroretinogram (ERG) and other methods. Utilizing network pharmacology in conjunction with transcriptomics, we identified potential therapeutic pathways. we employed Western blotting (WB) and quantitative real-time PCR (qPCR) methodologies to evaluate the levels of pyroptosis. In vitro system of retinal pigment epithelium (RPE) cells injury was caused by Aβ1-40 and subsequently treated with AT or JC2-11. The extent of pyroptosis was quantified using enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and WB. Cell morphological changes were examined using light microscopy and scanning electron microscopy. Network pharmacology and transcriptomics identified AIM2/Caspase-1/GSDMD as the key pathway. AT improved the retinal morphological and functional damage caused by Aβ1-40, and decreased the production of AIM2, Asc, Caspase-1, GSDMD-N, Cleaved Caspase-1 and cytokines to exert an anti-inflammatory effect. In addition, AT improved the ruptured membrane of RPE cells caused by Aβ1-40. The use of JC2-11 further demonstrated that AT inhibits pyroptosis of RPE via AIM2/Caspase-1/GSDMD pathway activated by Aβ1-40. These discoveries illuminate the retinal conservation role of AT by effectively hindering the progression of pyroptosis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557737","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

Nicotinamide N-oxide Inhibits Microglial Pyroptosis by Upregulating Mitophagy and Alleviates Neural Damage in Rats after TBI. 烟酰胺 N-氧化物通过上调噬丝分裂抑制小胶质细胞嗜热性并缓解大鼠创伤性脑损伤后的神经损伤

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-30 DOI: 10.1007/s10753-024-02171-7

Xiaoyan Li, Lan Luo, Pengyu Duan, Yonghong Bi, Yao Meng, Xiaoqian Zhang, Weiyu Feng, Zhehao Jin, Kun Zuo, Xiangcheng Zhao, Bing Zhang

{"title":"Nicotinamide N-oxide Inhibits Microglial Pyroptosis by Upregulating Mitophagy and Alleviates Neural Damage in Rats after TBI.","authors":"Xiaoyan Li, Lan Luo, Pengyu Duan, Yonghong Bi, Yao Meng, Xiaoqian Zhang, Weiyu Feng, Zhehao Jin, Kun Zuo, Xiangcheng Zhao, Bing Zhang","doi":"10.1007/s10753-024-02171-7","DOIUrl":"https://doi.org/10.1007/s10753-024-02171-7","url":null,"abstract":"Traumatic brain injury (TBI) is a severe injury characterized by neuroinflammation and oxidative stress. NAMO (Nicotinamide n-oxide) has anti-inflammatory and inhibits microglial overactivation in neurological disorders. However, the role and mechanism of NAMO in microglial pyroptosis after TBI are unknown. The aim of this study was to investigate the effects of NAMO on TBI and its potential mechanisms through in vivo and in vitro models. In this study, western blot assays were performed by extracting brain tissue mitochondria, and the results showed that NAMO promoted the expression of mitophagy-associated proteins (p62, LC3B, and TOMM20), reduced ROS levels, and inhibited pyroptosis-associated proteins (NLRP3, GSDMD, GSDMD-N, and Caspase-1) and inflammatory cytokines (IL-1β and IL-18). We followed up with immunofluorescence co-localization of GSDMD and IBA 1, which showed that NAMO inhibited microglial pyroptosis. In addition, NAMO promoted neurological recovery after TBI. In vitro experiments showed that NAMO upregulated mitophagy, improved mitochondrial dysfunction, and reduced ROS levels in microglia following lipopolysaccharide (LPS) + adenosine triphosphate (ATP) stimulation in HMC3 cells. We also found that NAMO inhibited pyroptosis-related proteins. To further illustrate whether NAMO affects pyroptosis through mitophagy, we applied the mitophagy inhibitor Mdivi-1 in both in vivo and in vitro models. The results showed that Mdivi-1 reversed NAMO's inhibitory effect on microglial pyroptosis. Taken together, our findings demonstrate that NAMO improves neurological recovery by inhibiting microglial pyroptosis through upregulation of mitophagy, suggesting that NAMO could be a potential therapeutic agent for TBI.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545278","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

Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis. 药理抑制磷酸甘油酸激酶 1 可降低氧化应激并恢复实验性急性胰腺炎中受损的自噬功能

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-29 DOI: 10.1007/s10753-024-02173-5

Lin Chen, Zhihao Wang, Yuyan Zhang, Qingtian Zhu, Guotao Lu, Xiaowu Dong, Jiajia Pan, Keyan Wu, Weijuan Gong, Weiming Xiao, Yanbing Ding, Yanyan Zhang, Yaodong Wang

{"title":"Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis.","authors":"Lin Chen, Zhihao Wang, Yuyan Zhang, Qingtian Zhu, Guotao Lu, Xiaowu Dong, Jiajia Pan, Keyan Wu, Weijuan Gong, Weiming Xiao, Yanbing Ding, Yanyan Zhang, Yaodong Wang","doi":"10.1007/s10753-024-02173-5","DOIUrl":"https://doi.org/10.1007/s10753-024-02173-5","url":null,"abstract":"Damage to pancreatic acinar cells (PAC) and intracellular metabolic disturbances play crucial roles in pancreatic necrosis during acute pancreatitis (AP). Phosphoglycerate kinase 1 (PGK1) is a crucial catalytic enzyme in glycolysis. However, the impact of PGK1-involving glycolysis in regulating metabolic necrosis in AP is unclear. Transcriptome analysis of pancreatic tissues revealed significant changes in the glycolysis pathway and PGK1 which positively correlated with the inflammatory response and oxidative stress injury in AP mice. Furthermore, we observed a substantial increase in PGK1 expression in damaged PAC, positively correlating with PAC necrosis. Treatment with NG52, a specific PGK1 inhibitor, ameliorated pancreatic necrosis, inflammatory damage, and oxidative stress. Transcriptomic data before and after NG52 treatment along with the Programmed Cell Death database confirmed that NG52 protected against PAC damage by rescuing impaired autophagy in AP. Additionally, the protective effect of NG52 was validated following pancreatic duct ligation. These findings underscore the involvement of PGK1 in AP pathogenesis, highlighting that PGK1 inhibition can mitigate AP-induced pancreatic necrosis, attenuate inflammatory and oxidative stress injury, and rescue impaired autophagy. Thus, the study findings suggest a promising interventional target for pancreatic necrosis, offering novel strategies for therapeutic approaches to clinical AP.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545279","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

Identification of Key Genes Related to Immune-Lipid Metabolism in Skin Barrier Damage and Analysis of Immune Infiltration. 鉴定皮肤屏障损伤中与免疫脂质代谢相关的关键基因并分析免疫渗透。

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-28 DOI: 10.1007/s10753-024-02174-4

Ying Tu, Hua Gu, Na Li, Dongjie Sun, Zhenghui Yang, Li He

{"title":"Identification of Key Genes Related to Immune-Lipid Metabolism in Skin Barrier Damage and Analysis of Immune Infiltration.","authors":"Ying Tu, Hua Gu, Na Li, Dongjie Sun, Zhenghui Yang, Li He","doi":"10.1007/s10753-024-02174-4","DOIUrl":"https://doi.org/10.1007/s10753-024-02174-4","url":null,"abstract":"Several physical and chemical factors regulate skin barrier function. Skin barrier dysfunction causes many inflammatory skin diseases, such as atopic dermatitis and psoriasis. Activation of the immune response may lead to damage to the epidermal barrier. Abnormal lipid metabolism is defined as abnormally high or low values of plasma lipid components such as plasma cholesterol and triglycerides. The mouse skin barrier damage model was used for RNA sequencing. Bioinformatics analysis and validation were performed. Differently expressed genes (DEGs) related to immune and lipid metabolism were screened by differentially expressed gene analysis, and the enriched biological processes and pathways of these genes were identified by GO-KEGG. The interactions between DEGs were confirmed by constructing a PPI network. GSEA, transcription factor regulatory network, and immune infiltration analyses were performed for the 10 genes. Expression validation was performed by public datasets. The expression of key genes in mouse skin tissue was detected by qPCR. The expression of differentially expressed immune cell markers in the skin was detected by immunofluorescence. Based on the trans epidermal water loss (TEWL) score, the expression of key genes was detected by qPCR before skin barrier injury, at 4h and 7d, and at recovery from injury. Il17a, Il6, Tnf, Itgam, and Cxcl1 were immune-related key genes. Pla2g2f, Ptgs2, Plb1, Pla2g3, and Pla2g2d were key genes for lipid metabolism. Database validation and experimental results revealed that the expression trends of these genes were consistent with our analyses. The research value of these genes has been demonstrated through mouse datasets and experimental validation, and future therapeutic approaches may be able to mitigate the disease by targeting these genes to modulate the function of the skin barrier.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499558","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

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response. 非 T2 型哮喘的特征：表明 Th2 反应减弱的关键途径和分子含义。

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-28 DOI: 10.1007/s10753-024-02159-3

Jyh-Hong Lee, Yao-Hsu Yang, Yu-Tsan Lin, Li-Chieh Wang, Hsin-Hui Yu, Ya-Chiao Hu, Bor-Luen Chiang

{"title":"Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.","authors":"Jyh-Hong Lee, Yao-Hsu Yang, Yu-Tsan Lin, Li-Chieh Wang, Hsin-Hui Yu, Ya-Chiao Hu, Bor-Luen Chiang","doi":"10.1007/s10753-024-02159-3","DOIUrl":"https://doi.org/10.1007/s10753-024-02159-3","url":null,"abstract":"Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5 IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1 IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521833","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 Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7. 被忽视的细胞因子信号抑制因子（SOCS）：SOCS4-7。

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-26 DOI: 10.1007/s10753-024-02163-7

Juber Herrera-Uribe, Orla Convery, Daniah ALmohammadi, Fabienne Ingrid Weinberg, Nigel J Stevenson

{"title":"The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7.","authors":"Juber Herrera-Uribe, Orla Convery, Daniah ALmohammadi, Fabienne Ingrid Weinberg, Nigel J Stevenson","doi":"10.1007/s10753-024-02163-7","DOIUrl":"https://doi.org/10.1007/s10753-024-02163-7","url":null,"abstract":"SOCS proteins are essential for the regulation of oncogenic, anti-pathogenic, and proinflammatory signalling cascades, including the JAK/STAT and NF-kB pathways, where they act as negative feedback regulators. Given their powerful role in a broad spectrum of biological processes, it is surprising that the functions of many SOCS proteins have not been widely explored. While the mechanisms of action of CIS, SOCS1-3 are well-documented, information regarding SOCS4-7 remains limited. However, recent studies have begun to elucidate the regulatory functions of these proteins during infection and disease, such as influenza infection, cancer and diabetes. Therefore, this review aims to describe and discuss studies detailing our current understanding of SOCS4-7, painting a clearer picture of the biological processes these regulatory proteins maintain. Indeed, our review highlights important evidence proving that all SOCS play a role in biological processes that are essential for normal immunological homeostasis, clearance of infection and avoidance of disease. Understanding how SOCS proteins interact with other proteins or how they are dysregulated in disease is likely to provide valuable insights for advancing therapeutic approaches.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499561","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

Metformin Attenuates Vocal Fold Fibrosis via AMPK Signaling. 二甲双胍通过 AMPK 信号减轻声带皱褶纤维化

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-24 DOI: 10.1007/s10753-024-02165-5

Jie Cai, Lucheng Fang, Peng Zhou, Jianghao Wu, Yuliang Song, Aikebaier Tuohuti, Yuechen Sun, Xiong Chen

{"title":"Metformin Attenuates Vocal Fold Fibrosis via AMPK Signaling.","authors":"Jie Cai, Lucheng Fang, Peng Zhou, Jianghao Wu, Yuliang Song, Aikebaier Tuohuti, Yuechen Sun, Xiong Chen","doi":"10.1007/s10753-024-02165-5","DOIUrl":"https://doi.org/10.1007/s10753-024-02165-5","url":null,"abstract":"Vocal fold fibrosis is a challenging condition with no clear consensus on effective treatment methods. Given the demonstrated efficacy of metformin in treating various fibrotic diseases, we hypothesized that metformin could reduce vocal fold fibrosis via the AMPK signaling pathway. In our study, we induced vocal fold injury in rabbits and administered metformin intraperitoneally at a dose of 250 mg/kg two weeks post-injury. Four weeks after the injury, vocal folds were excised and analyzed for fibrosis using Masson's trichrome staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), and Western blotting. In vitro, vocal fold fibroblasts treated with metformin (10 μM) ± TGF-β1 (10 ng/mL) were utilized to assess metformin's antifibrotic effects, with Compound C (10 μM) employed to inhibit AMPK signaling. Our results demonstrate that metformin significantly improved the structural integrity of the vocal fold lamina, reduced collagen deposition, and decreased the expression levels of COL1A1 and α-SMA. Furthermore, metformin activated the AMPK signaling pathway in vocal fold fibroblasts, resulting in decreased expression of COL1A1, α-SMA, TGF-β, Smad2, and Smad3. These findings suggest that metformin attenuates vocal fold fibrosis by modulating the AMPK signaling pathway, providing a foundation for developing new therapeutic options for vocal fold fibrosis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499559","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

Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway. 奈罗多米司特通过调节 TGF-β1 通路改善博莱霉素诱导的小鼠系统性硬化相关性间质性肺病

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-23 DOI: 10.1007/s10753-024-02153-9

Yuming Liu, Zhigang Liu, Xiaohe Li, Wenqi Li, Zhongyi Yang, Ran Jiao, Qing Wang, Lingxin Meng, Tiantian Zhang, Jing Liu, Dan Chai, Na Zhang, Shouchun Peng, Honggang Zhou, Cheng Yang

{"title":"Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway.","authors":"Yuming Liu, Zhigang Liu, Xiaohe Li, Wenqi Li, Zhongyi Yang, Ran Jiao, Qing Wang, Lingxin Meng, Tiantian Zhang, Jing Liu, Dan Chai, Na Zhang, Shouchun Peng, Honggang Zhou, Cheng Yang","doi":"10.1007/s10753-024-02153-9","DOIUrl":"https://doi.org/10.1007/s10753-024-02153-9","url":null,"abstract":"Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common complication of SSc and a major contributor to SSc-related deaths. Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Previous studies have shown that cyclic adenosine monophosphate (cAMP) plays a crucial role in the pathogenesis of SSc and lung fibrosis. Phosphodiesterases (PDEs) are enzymes that specifically hydrolyze cAMP, making PDE inhibitors promising candidates for SSc-ILD treatment. Nerandomilast, a preferential phosphodiesterase 4B (PDE4B) inhibitor currently undergoing phase III clinical trials for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases (PF-ILD), has good preference for PDE4B but lacks studies for SSc-ILD. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-β1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499560","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

Quorum Sensing Molecule Autoinducer-2 Promotes Macrophage Classical Polarization and Exacerbates Periodontal Inflammation Via Nf-Κb Signalling. 定量感应分子Autoinducer-2通过Nf-Κb信号促进巨噬细胞经典极化并加剧牙周炎症

IF 4.5 2区医学

Inflammation Pub Date : 2024-10-22 DOI: 10.1007/s10753-024-02168-2

Hancheng Zhou, Jiaxin Huang, Zixin Fan, Wen Sun, Yan Xu, Lu Li

{"title":"Quorum Sensing Molecule Autoinducer-2 Promotes Macrophage Classical Polarization and Exacerbates Periodontal Inflammation Via Nf-Κb Signalling.","authors":"Hancheng Zhou, Jiaxin Huang, Zixin Fan, Wen Sun, Yan Xu, Lu Li","doi":"10.1007/s10753-024-02168-2","DOIUrl":"https://doi.org/10.1007/s10753-024-02168-2","url":null,"abstract":"Background: The role of quorum sensing signaling in the immunoinflammatory response during the development of periodontitis is not yet known. This study aimed to explore the effect of Autoinducer-2, a quorum sensing signaling molecule, on macrophage phenotypic remodeling in the immune microenvironment of periodontitis, to further elucidate its mechanism and to discover inhibitors against periodontitis.Methods: Bioluminescence experiments and periodontitis model were used to demonstrate the association between periodontitis progression with AI-2. Next, AI-2 challenged macrophage was introduced to transcriptomic sequence and the immune profile was characterized in combination with flow cytometry, qPCR, and immunofluorescence. Activation of NF-κB signalling by AI-2 was confirmed by fluorescence co-localization and immunoblotting. Finally, morphological methods such as Micro-CT and HE, TRAP staining and immunological methods such as immunohistochemistry/fluorescence staining were used to assess the mechanisms by which AI-2 regulates periodontitis progression.Results: AI-2 level was positively correlated with the progression of periodontitis stages and was significantly higher in periodontitis stage III and IV patients. AI-2 promotes macrophage classical polarization and facilitates the secretion of inflammatory factors in vitro, which is dependent on the activation of the NF-κB signaling pathway. AI-2 promotes alveolar bone resorption, but D-ribose acts as a quorum sensing inhibitor to alleviate macrophage classical polarization and attenuates alveolar bone resorption and inflammatory responses in periodontitis mice.Conclusions: Our study demonstrates that AI-2 promoted classical polarization of macrophage and exacerbated periodontal inflammation which could be reversed by D-ribose.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464287","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