Inflammation最新文献_第7页

Characteristics of Neutrophil Migration and Function in Acute Inflammation Induced by Zymosan and Carrageenan in the Mice Air Pouch Model. 小鼠气囊模型中由Zymosan和卡拉胶诱发的急性炎症中的中性粒细胞迁移和功能特征

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-06-21 DOI: 10.1007/s10753-024-02064-9

Qi Liu, Yubo Zhao, Shuai Dong, Xingyuan Bai, Bin Chen, Xijuan Liu, Jing Shen, Dan Zhu

{"title":"Characteristics of Neutrophil Migration and Function in Acute Inflammation Induced by Zymosan and Carrageenan in the Mice Air Pouch Model.","authors":"Qi Liu, Yubo Zhao, Shuai Dong, Xingyuan Bai, Bin Chen, Xijuan Liu, Jing Shen, Dan Zhu","doi":"10.1007/s10753-024-02064-9","DOIUrl":"10.1007/s10753-024-02064-9","url":null,"abstract":"Deciphering the complex and redundant process of acute inflammation remains challenging. The failure of numerous clinical trials assessing anti-inflammation agents which had promising preclinical effects inevitably questions the validity of current animal models of inflammation. This study aimed to better understand the process of immune inflammatory response and to select more suitable models to evaluate the effect of potential anti-inflammatory drugs. Zymosan and λ-carrageenan are the most used representatives of particulate and soluble irritants that trigger acute inflammation in the air pouch inflammation model. When zymosan was used, the number of exudate cells first increased at 4 h-8 h, followed by a drop at 12 h-24 h. While, the changes in number of leukocytes in peripheral blood and proportion of neutrophils in bone marrow have the opposite trend. Meanwhile, neutrophils released neutrophil extracellular traps (NETs) to clean zymosan particles. In contrast, the cell migration response to carrageenan increased during 4 h to 24 h, no obvious NETs were observed, and the number of leukocytes in peripheral blood increased and the proportion of neutrophils in bone marrow decreased slightly. This study indicated that although both zymosan and carrageenan are sterile irritants, the characteristics of the inflammatory response induced by each other were different. In the acute phase of inflammation, zymosan-stimulated neutrophils were mobilized, recruited, and engulfed, and then died by NETs. Carrageenan stimulated the production of cytokines/chemokines by neutrophils or macrophages, but did not lead to an obvious death by releasing NETs.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"607-620"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431861","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

Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease. 过氧化物歧化酶 6 保护肺上皮细胞免受慢性阻塞性肺病中与香烟有关的铁氧化作用的影响

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-07-02 DOI: 10.1007/s10753-024-02077-4

Tingting Wei, Xiaocen Wang, Ke Lang, Yansha Song, Jinlong Luo, Zhaolin Gu, Dong Yang, Yuanlin Song

{"title":"Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease.","authors":"Tingting Wei, Xiaocen Wang, Ke Lang, Yansha Song, Jinlong Luo, Zhaolin Gu, Dong Yang, Yuanlin Song","doi":"10.1007/s10753-024-02077-4","DOIUrl":"10.1007/s10753-024-02077-4","url":null,"abstract":"Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"662-675"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491825","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

Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1β/IL-18 Signaling Cascade. 阿洛芬通过抑制 NLRP3/CASP1/IL-1β/IL-18 信号级联缓解 LPS 诱导的子宫内膜炎

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-06-24 DOI: 10.1007/s10753-024-02083-6

Shitian Chen, Lin Zhu, Xinyu Fang, Clara Appiah, Yuanbo Ji, Ziyi Chen, Shuai Qiao, Chen Gong, Jian Li, Ye Zhao

{"title":"Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1β/IL-18 Signaling Cascade.","authors":"Shitian Chen, Lin Zhu, Xinyu Fang, Clara Appiah, Yuanbo Ji, Ziyi Chen, Shuai Qiao, Chen Gong, Jian Li, Ye Zhao","doi":"10.1007/s10753-024-02083-6","DOIUrl":"10.1007/s10753-024-02083-6","url":null,"abstract":"Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1β (IL-1β), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1β/IL-18 signaling cascade.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"730-746"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442499","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

Plasma H3Cit-DNA Discriminates Between Cancer and Inflammation in a Cohort of Patients with Unspecific Cancer Symptoms. 血浆 H3Cit-DNA 可区分无特异性癌症症状患者群中的癌症与炎症

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-06-28 DOI: 10.1007/s10753-024-02085-4

Fredrika Wannberg, Viktoria Hjalmar, Henry Ng, Caroline Johansson, Fay Probert, Mia Phillipson, Mikael Åberg, Max Gordon, Nigel Mackman, Axel Rosell, Charlotte Thålin

{"title":"Plasma H3Cit-DNA Discriminates Between Cancer and Inflammation in a Cohort of Patients with Unspecific Cancer Symptoms.","authors":"Fredrika Wannberg, Viktoria Hjalmar, Henry Ng, Caroline Johansson, Fay Probert, Mia Phillipson, Mikael Åberg, Max Gordon, Nigel Mackman, Axel Rosell, Charlotte Thålin","doi":"10.1007/s10753-024-02085-4","DOIUrl":"10.1007/s10753-024-02085-4","url":null,"abstract":"Cancer detection is challenging, especially in patients with unspecific cancer symptoms. Biomarkers could identify patients at high risk of cancer. Prior studies indicate that neutrophil extracellular traps (NETs) are associated with cancer, but also with autoimmune and infectious diseases. The objective of this prospective study was to investigate markers associated with NET formation (nucleosomal citrullinated histone 3 [H3Cit-DNA], cell free DNA [cfDNA] and neutrophil elastase [NE]), and c-reactive protein (CRP) in patients with unspecific cancer symptoms, such as fatigue, weight loss or radiological sign of malignancy without an apparent primary tumor, referred to the Diagnostic Center at Danderyd Hospital in Sweden. Blood samples were drawn on admission, before cancer diagnosis. Out of 475 patients, 160 (34%) were diagnosed with cancer, 56 (12%) with autoimmune disease, 32 (7%) with infectious disease, 71 (15%) with other diseases and 156 (33%) received no diagnosis. H3Cit-DNA, cfDNA, NE and CRP were significantly higher in patients with cancer compared to patients without cancer (p < 0.0001, p < 0.0001, p = 0.004, and p = 0.0002 respectively). H3Cit-DNA, but not cfDNA, NE or CRP, was significantly elevated in patients with cancer compared to patients with autoimmune disease (p = 0.0001). H3Cit-DNA, cfDNA, NE or CRP did not differ between cancer and infectious disease. In conclusion, H3Cit-DNA is elevated in patients diagnosed with cancer compared to non-cancer patients with the same symptomatology. Further studies should evaluate if H3Cit-DNA could aid in selecting patients that would benefit the most from a rapid cancer diagnostic work-up.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"760-769"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467712","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

Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice. 缺乏分泌型磷蛋白 1 可缓解高氧诱导的新生小鼠支气管肺发育不良症

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-06-29 DOI: 10.1007/s10753-024-02088-1

Juan Liu, Tianping Bao, Yajuan Zhou, Mengmeng Ma, Zhaofang Tian

{"title":"Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice.","authors":"Juan Liu, Tianping Bao, Yajuan Zhou, Mengmeng Ma, Zhaofang Tian","doi":"10.1007/s10753-024-02088-1","DOIUrl":"10.1007/s10753-024-02088-1","url":null,"abstract":"Bronchopulmonary dysplasia (BPD) is a common chronic lung disorder characterized by impaired proximal airway and bronchoalveolar development in premature births. Secreted phosphoprotein 1 (SPP1) is involved in lung development and lung injury events, while its role was not explored in BPD. For establishing the in vivo models of BPD, a mouse model of hyperoxia-induced lung injury was generated by exposing neonatal mice to hyperoxia for 7 days after birth. Alveolar myofibroblasts (AMYFs) were treated with hyperoxia to establish the in vitro models of BPD. Based on the scRNA-seq analysis of lungs of mice housed under normoxia or hyperoxia conditions, mouse macrophages and fibroblasts were main different cell clusters between the two groups, and differentially expressed genes in fibroblasts were screened. Further GO and KEGG enrichment analysis revealed that these differentially expressed genes were mainly enriched in the pathways related to cell proliferation, apoptosis as well as the PI3K-AKT and ERK/MAPK pathways. SPP1 was found up-regulated in the lung tissues of hyperoxia mice. We also demonstrated the up-regulation of SPP1 in the BPD patients, the mouse model of hyperoxia-induced lung injury, and hyperoxia-induced cells. SPP1 deficiency was revealed to reduce the hyperoxia-induced apoptosis, oxidative stress and inflammation and increase the viability of AMYFs. In the mouse model of hyperoxia induced lung injury, SPP1 deficiency was demonstrated to reverse the hyperoxia-induced alveolar growth disruption, oxidative stress and inflammation. Overall, SPP1 exacerbates BPD progression in vitro and in vivo by regulating oxidative stress and inflammatory response via the PI3K-AKT and ERK/MAPK pathways, which might provide novel therapeutic target for BPD therapy.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"783-795"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476545","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

Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice. 新型查耳酮衍生物化合物 27 通过 PI3K/AKT/Nrf2-Keap1 信号通路作用于上皮细胞，减轻 LPS 诱导的小鼠急性肺损伤的证据

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-05-24 DOI: 10.1007/s10753-024-02051-0

Liqin Zhou, Yuting Lin, Tengfei Zhou, Yincong Xue, Saverio Bellusci, Mengya Shen, Chengshui Chen, Chaolei Chen

{"title":"Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice.","authors":"Liqin Zhou, Yuting Lin, Tengfei Zhou, Yincong Xue, Saverio Bellusci, Mengya Shen, Chengshui Chen, Chaolei Chen","doi":"10.1007/s10753-024-02051-0","DOIUrl":"10.1007/s10753-024-02051-0","url":null,"abstract":"Acute lung injury (ALI) is a highly heterogeneous clinical syndrome and an important cause of mortality in critically ill patients, with limited treatment options currently available. Chalcone, an essential secondary metabolite found in edible or medicinal plants, exhibits good antioxidant activity and simple structure for easy synthesis. In our study, we synthesized a novel chalcone derivative, compound 27 (C27). We hypothesized that C27 could be a potential treatment for acute respiratory distress syndrome (ARDS). Therefore, the protective effects of C27 on lung epithelial cells during ALI and the underlying molecular mechanisms were investigated. In vivo, Intratracheal instillation of LPS (10 mg/kg) was used to induce acute lung injury in mice. In vitro, the bronchial epithelial cell line (Beas-2b) was treated with 30 μM tert-butyl hydroperoxide (t-BHP) to simulate oxidative stress. Our findings demonstrate that pretreatment with C27 reduces LPS-induced oxidative destruction and cellular apoptosis in lung tissues of mice. Furthermore, it significantly attenuates t-BHP-induced cellular reactive oxygen species (ROS) generation, mitochondrial damage, and apoptosis in vitro. Mechanistically, the signaling pathway involving Nrf2-Keap1 and the downstream antioxidative proteins were activated by C27 in vivo. Additionally, PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 abolished the effect of C27 in vitro, indicating that the protective effect of C27 is mediated via the PI3K/AKT/Nrf2-Keap1 pathway. Our study provides evidence that C27 protects against LPS-induced ALI by mitigating oxidative stress via activation of the PI3K/AKT/Nrf2-Keap1 signaling pathway. Therefore, we hypothesize that C27 represents a viable alternative for ALI therapy.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"590-606"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093115","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

Platr3/NUDT21/NF-κB Axis Mediates P. gingivalis-Suppressed Cementoblast Mineralization. Platr3/NUDT21/NF-κB轴介导牙龈脓疱抑制的骨水泥母细胞矿化。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-07-03 DOI: 10.1007/s10753-024-02069-4

Hantao Huang, Li Ma, Xiaoxuan Wang, Xin Huang, Huiyi Wang, Yan Peng, Junhong Xiao, Heyu Liu, Zhengkun Yang, Zhengguo Cao

{"title":"Platr3/NUDT21/NF-κB Axis Mediates P. gingivalis-Suppressed Cementoblast Mineralization.","authors":"Hantao Huang, Li Ma, Xiaoxuan Wang, Xin Huang, Huiyi Wang, Yan Peng, Junhong Xiao, Heyu Liu, Zhengkun Yang, Zhengguo Cao","doi":"10.1007/s10753-024-02069-4","DOIUrl":"10.1007/s10753-024-02069-4","url":null,"abstract":"Porphyromonas gingivalis (P. gingivalis) is one of the major pathogens causing periodontitis and apical periodontitis (AP). Long noncoding RNA (lncRNA) can regulate cellular mineralization and inflammatory diseases. The aim of this study was to investigate the role and mechanism of lncRNA in P. gingivalis-stimulated cementoblast mineralization. In vivo, C57BL/6 mice were divided into the healthy, the AP, and AP + P. gingivalis groups (n = six mice per group). Micro computed tomography, immunohistochemistry staining, and fluorescence in situ hybridization were used to observe periapical tissue. In vitro, cementoblasts were treated with osteogenic medium or P. gingivalis. Pluripotency associated transcript 3 (Platr3), interleukin 1 beta (IL1B), and osteogenic markers were analyzed by quantitative real-time polymerase chain reaction and western blot. RNA pull-down and RNA immunoprecipitation assays were used to detect proteins that bind to Platr3. RNA sequencing was performed in Platr3-silenced cementoblasts. In vivo, P. gingivalis promoted periapical tissue destruction and IL1B expression, but inhibited Platr3 expression. In vitro, P. gingivalis facilitated IL1B expression (P < 0.001), whereas suppressed the expression of Platr3 (P < 0.001) and osteogenic markers (P < 0.01 or 0.001). In contrast, Platr3 overexpression alleviated the repressive effect of P. gingivalis on cementoblast mineralization (P < 0.01 or 0.001). Furthermore, Platr3 bound to nudix hydrolase 21 (NUDT21) and regulated the nuclear factor-κB (NF-κB) signaling pathway. Knocking down NUDT21 suppressed osteogenic marker expression and activated the above signaling pathway. Collectively, the results elucidated that Platr3 mediated P. gingivalis-suppressed cementoblast mineralization through the NF-κB signaling pathway by binding to NUDT21.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"621-632"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497878","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

Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation. AER-271 在 tMCAO 小鼠模型中的神经保护作用：自噬、细胞凋亡和炎症的调节作用

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-08-09 DOI: 10.1007/s10753-024-02082-7

Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang

{"title":"Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.","authors":"Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang","doi":"10.1007/s10753-024-02082-7","DOIUrl":"10.1007/s10753-024-02082-7","url":null,"abstract":"Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"713-729"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906516","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

Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis? 肠道微生物群与自闭症谱系障碍：神经炎症介导的发病机制？

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-08-02 DOI: 10.1007/s10753-024-02061-y

Fatemeh Zarimeidani, Rahem Rahmati, Mehrnaz Mostafavi, Mohammad Darvishi, Sanaz Khodadadi, Mahya Mohammadi, Farid Shamlou, Salar Bakhtiyari, Iraj Alipourfard

{"title":"Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?","authors":"Fatemeh Zarimeidani, Rahem Rahmati, Mehrnaz Mostafavi, Mohammad Darvishi, Sanaz Khodadadi, Mahya Mohammadi, Farid Shamlou, Salar Bakhtiyari, Iraj Alipourfard","doi":"10.1007/s10753-024-02061-y","DOIUrl":"10.1007/s10753-024-02061-y","url":null,"abstract":"Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"501-519"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874717","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

Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination. 异荭草素通过降低KDM4A水平和促进SKP1-Cullin1-F-box E3连接酶介导的NLRP3泛素化，改善巨噬细胞焦亡和动脉粥样硬化。

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-25 DOI: 10.1007/s10753-025-02289-2

Xiaoshan Wang, Nuli Xie, Hanyong Zhang, Wenhu Zhou, Jiandu Lei

{"title":"Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination.","authors":"Xiaoshan Wang, Nuli Xie, Hanyong Zhang, Wenhu Zhou, Jiandu Lei","doi":"10.1007/s10753-025-02289-2","DOIUrl":"https://doi.org/10.1007/s10753-025-02289-2","url":null,"abstract":"Isoorientin (ISO) is a flavonoid compound with potential antioxidant and antiatherosclerotic properties. This investigation delves into the impact of ISO on macrophage pyroptosis in atherosclerosis (AS) progression and probes its functional mechanism. ApoE-/- mice were fed a high-fat diet for AS modeling. ISO treatment significantly alleviated atherosclerotic lesions, lipid accumulation, the necrotic core area, and macrophage pyroptosis in model mice. In vitro, ISO reduced oxidized low-density lipoprotein-induced pyroptosis in mouse bone marrow-derived macrophages. The mechanism underlying these effects is linked to a reduction in lysine demethylase 4A (KDM4A) levels in macrophages. Artificial restoration of KDM4A levels reversed the protective effects of ISO and promoted atherogenesis. KDM4A was found to inhibit the transcription of S-phase kinase-associated protein 1 (SKP1), leading to impaired SKP1-Cullin1-F-box (SCF) E3 ligase-mediated ubiquitination of NLR family pyrin domain containing 3 (NLRP3). This disruption promoted NLRP3 inflammasome assembly and activation. Artificial SKP1 overexpression reduced NLRP3 levels and reversed the protective effects of ISO. In conclusion, this study demonstrated that ISO inhibits macrophage pyroptosis and atherogenesis by reducing KDM4A levels and restoring SCF complex-mediated ubiquitination of NLRP3.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709759","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}

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