Inflammation最新文献

Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3β/Snail Signaling Axis 二甲双胍通过 PI3K/Akt/GSK3β/Snail 信号轴减轻唾液腺炎症中的部分上皮-间充质转化

IF 5.1 2区医学

Inflammation Pub Date : 2024-09-13 DOI: 10.1007/s10753-024-02142-y

Boyuan Peng, Lianhao Wang, Shijiao Pan, Jialing Kang, Lili Wei, Bo Li, Yong Cheng

{"title":"Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3β/Snail Signaling Axis","authors":"Boyuan Peng, Lianhao Wang, Shijiao Pan, Jialing Kang, Lili Wei, Bo Li, Yong Cheng","doi":"10.1007/s10753-024-02142-y","DOIUrl":"https://doi.org/10.1007/s10753-024-02142-y","url":null,"abstract":"Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3β/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton’s duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100 mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24 h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3β/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3β/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation.<h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142210836","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

Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation TRPM3 通道的功能性上调是急性胰腺炎相关疼痛和炎症的原因之一

IF 5.1 2区医学

Inflammation Pub Date : 2024-09-11 DOI: 10.1007/s10753-024-02138-8

Lei Liu, Hanwen Liu, Mengmeng Zhao, Jiliang Wen, Jiaxin Liu, Guangda Lv, Zhiying Xiao, Wenzhen Wang, Shulu Zu, Wendong Sun, Xiulin Zhang, Liping Gong

{"title":"Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation","authors":"Lei Liu, Hanwen Liu, Mengmeng Zhao, Jiliang Wen, Jiaxin Liu, Guangda Lv, Zhiying Xiao, Wenzhen Wang, Shulu Zu, Wendong Sun, Xiulin Zhang, Liping Gong","doi":"10.1007/s10753-024-02138-8","DOIUrl":"https://doi.org/10.1007/s10753-024-02138-8","url":null,"abstract":"Transient receptor potential melastatin M3 (TRPM3) channels have been recognized as a pain transducer in dorsal root ganglion (DRG) neurons in recent years. TRPM3 activation initiates neurogenic inflammation and is required for the development of inflammatory hyperalgesia. We aimed to evaluate the role of TRPM3 in pancreas sensory afferents in pancreatic nociception, neurogenic inflammation, and acute pancreatitis (AP)-associated pain. AP was induced by intraperitoneal (i.p.) injection of L-arginine in rats. TRPM3 expression in pancreatic DRG neurons, spontaneous or mechanical-stimulation-evoked pain behaviors, and the extent of inflammation were evaluated. We found that TRPM3 channels were expressed on pancreatic primary afferent nerve terminals containing calcitonin gene-related peptide (CGRP). Activation of TRPM3 in the pancreas by injection of its specific agonist CIM0216 (10 μM) induced pain, CGRP and substance P release, and neurogenic inflammation, as evidenced by edema, plasma extravasation, and inflammatory cell accumulation in the pancreas. Increased TRPM3 functional expression was detected in pancreatic DRG neurons from AP rats, and blocking TRPM3 activity with its antagonist (Primidone, 5 mg/kg, i.p.) attenuated AP-associated pain behaviors and pancreatic inflammation. Pre-incubation of pancreatic DRG neurons with nerve growth factor (NGF) enhanced the increase in intracellular Ca2+ induced by the TRPM3 agonist (CIM0216, 1 μM). Our findings indicate that, in addition to TRPV1 and TRPA1 channels, TRPM3 is another pain channel that has a critical role in pancreatic nociception, neurogenic inflammation, and AP-associated pain behaviors. TRPM3 may be a promising pharmaceutical target for AP pain treatment.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142210853","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

Comparative Analysis of Canonical Inflammasome Activation by Flow Cytometry, Imaging Flow Cytometry and High-Content Imaging 通过流式细胞术、成像流式细胞术和高内涵成像技术对典型炎症小体激活进行比较分析

IF 5.1 2区医学

Inflammation Pub Date : 2024-09-10 DOI: 10.1007/s10753-024-02141-z

Nico Wittmann, Sander Bekeschus, Doreen Biedenweg, Daniela Kuthning, Christopher Pohl, Jana Gramenz, Oliver Otto, Lukas Bossaller, Almut Meyer-Bahlburg

{"title":"Comparative Analysis of Canonical Inflammasome Activation by Flow Cytometry, Imaging Flow Cytometry and High-Content Imaging","authors":"Nico Wittmann, Sander Bekeschus, Doreen Biedenweg, Daniela Kuthning, Christopher Pohl, Jana Gramenz, Oliver Otto, Lukas Bossaller, Almut Meyer-Bahlburg","doi":"10.1007/s10753-024-02141-z","DOIUrl":"https://doi.org/10.1007/s10753-024-02141-z","url":null,"abstract":"Inflammasome activation occurs in various diseases, including rare diseases that require multicenter studies for investigation. Flow cytometric analysis of ASC speck+ cells in patient samples can be used to detect cell type-specific inflammasome activation. However, this requires standardized sample processing and the ability to compare data from different flow cytometers. To address this issue, we analyzed stimulated and unstimulated PBMCs from healthy donors using seven different flow cytometers. Additionally, human PBMCs were analyzed by fluorescence microscopy, imaging flow cytometry and high-content imaging (HCI). Flow cytometers differed significantly in their ability to detect ASC speck+ cells. Aria III, Astrios EQ, and Canto II performed best in separating ASC speck+ from diffuse ASC cells. Imaging flow cytometry and HCI provided additional insight into ASC speck formation based on image-based parameters. For optimal results, the ability to separate cells with diffuse ASC from ASC speck+ cells is decisive. Image-based parameters can also differentiate cells with diffuse ASC from ASC speck+ cells. For the first time, we analyzed ASC speck detection by HCI in PBMCs and demonstrated advantages of this technique, such as high-throughput, algorithm-driven image quantification and 3D-rendering. Thus, inflammasome activation by ASC speck formation can be detected by various technical methods. However, the results may vary depending on the device used.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226772","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 Kynurenine Pathway in Gut Permeability and Inflammation 犬尿氨酸通路在肠道渗透性和炎症中的作用

IF 5.1 2区医学

Inflammation Pub Date : 2024-09-10 DOI: 10.1007/s10753-024-02135-x

Rowan Kearns

{"title":"The Kynurenine Pathway in Gut Permeability and Inflammation","authors":"Rowan Kearns","doi":"10.1007/s10753-024-02135-x","DOIUrl":"https://doi.org/10.1007/s10753-024-02135-x","url":null,"abstract":"The gut-brain axis (GBA) is a crucial communication network linking the gastrointestinal (GI) tract and the central nervous system (CNS). The gut microbiota significantly influences metabolic, immune, and neural functions by generating a diverse array of bioactive compounds that modulate brain function and maintain homeostasis. A pivotal mechanism in this communication is the kynurenine pathway, which metabolises tryptophan into various derivatives, including neuroactive and neurotoxic compounds. Alterations in gut microbiota composition can increase gut permeability, triggering inflammation and neuroinflammation, and contributing to neuropsychiatric disorders. This review elucidates the mechanisms by which changes in gut permeability may lead to systemic inflammation and neuroinflammation, with a focus on the kynurenine pathway. We explore how probiotics can modulate the kynurenine pathway and reduce neuroinflammation, highlighting their potential as therapeutic interventions for neuropsychiatric disorders. The review integrates experimental data, discusses the balance between neurotoxic and neuroprotective kynurenine metabolites, and examines the role of probiotics in regulating inflammation, cognitive development, and gut-brain axis functions. The insights provided aim to guide future research and therapeutic strategies for mitigating GI complaints and their neurological consequences.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227670","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

Phosphorylation of Serine 536 of p65(RelA) Downregulates Inflammatory Responses. p65（RelA）丝氨酸 536 的磷酸化可降低炎症反应。

IF 4.5 2区医学

Inflammation Pub Date : 2024-09-08 DOI: 10.1007/s10753-024-02140-0

Tsukasa Aoki, Jing Gao, Aonan Li, Fei Huang, Yiran Tu, Wei Wu, Miho Matsuda, Tamotsu Kiyoshima, Fusanori Nishimura, Eijiro Jimi

{"title":"Phosphorylation of Serine 536 of p65(RelA) Downregulates Inflammatory Responses.","authors":"Tsukasa Aoki, Jing Gao, Aonan Li, Fei Huang, Yiran Tu, Wei Wu, Miho Matsuda, Tamotsu Kiyoshima, Fusanori Nishimura, Eijiro Jimi","doi":"10.1007/s10753-024-02140-0","DOIUrl":"https://doi.org/10.1007/s10753-024-02140-0","url":null,"abstract":"Nuclear factor-κB (NF-κB) is a transcription factor that regulates the expression of various genes involved in inflammatory diseases and immune responses. Recently, a novel transcriptional regulatory mechanism of NF-κB involving the phosphorylation of serine 536 (534 in mice; S534) of its p65 subunit was reported; however, further research is required to elucidate the physiological role of S534 phosphorylation. Therefore, we generated S534A knock-in (KI) mice, in which the S534 of p65 was substituted with alanine. Similar to the wild-type (WT) mice, S534A KI mice developed normally. After stimulation with tumor necrosis factor α (TNFα), mouse embryonic fibroblasts (MEFs) derived from S534A KI mice exhibited increased target gene expression compared with that in the WT MEFs, which was induced by long-term binding of p65 to DNA. According to comprehensive gene expression analysis after stimulation with TNFα, the expression of genes p65ted to inflammatory and immune responses was increased, and the expression of genes p65ted to lipolysis was decreased in S534A KI MEFs. Analyses of a periodontal disease model established using WT and S534A KI mice revealed that alveolar bone resorption was enhanced in S534A KI mice owing to an increase in the number of osteoclasts, which was not attributed to the differentiation of osteoclast precursor cells but to an increased expression of interleukin-1β and receptor activator of NF-κB ligand in the periodontal tissue. Hence, phosphorylation of S536 negatively regulates inflammatory responses in vitro and in vivo.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145591","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

Correction: The Neuroprotective Effect of Syringic Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats. 更正：丁香酸对大鼠脊髓缺血再灌注损伤的神经保护作用

IF 4.5 2区医学

Inflammation Pub Date : 2024-09-03 DOI: 10.1007/s10753-024-02122-2

Mehmet Tokmak, Yasemin Yuksel, Muserref Hilal Sehitoglu, Mustafa Guven, Tarik Akman, Adem Bozkurt Aras, Murat Cosar, Khalid M Abbed

引用次数: 0

The Neuroprotective Effects of Agmatine on Parkinson's Disease: Focus on Oxidative Stress, Inflammation and Molecular Mechanisms. 阿格马丁对帕金森病的神经保护作用：关注氧化应激、炎症和分子机制。

IF 4.5 2区医学

Inflammation Pub Date : 2024-09-03 DOI: 10.1007/s10753-024-02139-7

Mohammad Yasin Zamanian, Mozhgan Nazifi, Lusine G Khachatryan, Niloofar Taheri, Mehraveh Sadeghi Ivraghi, Soumya V Menon, Beneen Husseen, K D V Prasad, Iliya Petkov, Nikta Nikbakht

{"title":"The Neuroprotective Effects of Agmatine on Parkinson's Disease: Focus on Oxidative Stress, Inflammation and Molecular Mechanisms.","authors":"Mohammad Yasin Zamanian, Mozhgan Nazifi, Lusine G Khachatryan, Niloofar Taheri, Mehraveh Sadeghi Ivraghi, Soumya V Menon, Beneen Husseen, K D V Prasad, Iliya Petkov, Nikta Nikbakht","doi":"10.1007/s10753-024-02139-7","DOIUrl":"https://doi.org/10.1007/s10753-024-02139-7","url":null,"abstract":"Agmatine (AGM), a naturally occurring polyamine derived from L-arginine, has shown significant potential for neuroprotection in Parkinson's Disease (PD) due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. This review explores the therapeutic potential of AGM in treating PD, focusing on its neuroprotective mechanisms and evidence from preclinical studies. AGM has been demonstrated to mitigate the neurotoxic effects of rotenone (ROT) by improving motor function, reducing oxidative stress markers, and decreasing levels of pro-inflammatory cytokines in animal models. Additionally, AGM protects against the loss of TH + neurons, crucial for dopamine synthesis. The neuroprotective properties of AGM are attributed to its ability to modulate several key pathways implicated in PD pathogenesis, such as inhibition of NMDA receptors, activation of Nrf2, and suppression of the HMGB1/ RAGE/ TLR4/ MyD88/ NF-κB signaling cascade. Furthermore, the potential of agmatine to promote neurorestoration is highlighted by its role in enhancing neuroplasticity elements such as CREB, BDNF, and ERK1/2. This review highlights agmatine's promising therapeutic potential in PD management, suggesting that it could offer both symptomatic relief and neuroprotective benefits, thereby modifying the disease course and improving the quality of life for patients. Further research is warranted to translate these preclinical findings into clinical applications.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119728","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 C/EBPβ-SESN2 Axis Promotes M2b Macrophage Polarization Induced by T.cp-MIF to Suppress Inflammation in Thelazia Callipaeda Infection. C/EBPβ-SESN2轴促进T.cp-MIF诱导的M2b巨噬细胞极化，从而抑制卡里巴蝇感染中的炎症。

IF 4.5 2区医学

Inflammation Pub Date : 2024-08-31 DOI: 10.1007/s10753-024-02114-2

Bo Luo, Yan-Ting Gou, Hong-Le Cui, Chang-Zhu Yin, Da Sun, Di Li, Ling-Jun Wang, Rong Yan, Hui Liu

{"title":"The C/EBPβ-SESN2 Axis Promotes M2b Macrophage Polarization Induced by T.cp-MIF to Suppress Inflammation in Thelazia Callipaeda Infection.","authors":"Bo Luo, Yan-Ting Gou, Hong-Le Cui, Chang-Zhu Yin, Da Sun, Di Li, Ling-Jun Wang, Rong Yan, Hui Liu","doi":"10.1007/s10753-024-02114-2","DOIUrl":"https://doi.org/10.1007/s10753-024-02114-2","url":null,"abstract":"Infection by the conjunctival sucking nematode Thelazia callipaeda results in ocular inflammation and immune impairment. T.cp-MIF, a macrophage migration inhibitor factor of T. callipaeda, can induce macrophage polarization and is involved in the host innate immune response, but little is known about the regulatory mechanisms and the actual immune effect. Understanding the immunoregulatory mechanisms carries significant clinical relevance for the development of novel preventative and therapeutic strategies. The macrophages were induced by T.cp-MIF in vitro, and the polarization direction at different times and the expression of inflammatory factors were detected by flow cytometry analysis, qPCR and western blotting. The key transcription factors and target genes were screened through transcriptome data, and the functions of transcription factors were verified by inhibition experiments in vitro. T.cp-MIF and T. callipaeda adult worms can cause inflammation of the ocular conjunctiva and macrophage infiltration. T.cp-MIF activated macrophages presenting M2b polarization after 48 h and played a role in inhibiting inflammation. Furthermore, based on the results of transcriptome data analysis and inhibition experiments, we demonstrate that this polarization is dependent on the involvement of the transcription factor C/EBPβ and its target gene SESN2. Our results demonstrated that the C/EBPβ-SESN2 axis plays an important regulatory role in T.cp-MIF-induced macrophage M2b polarization and it provides a new perspective for understanding the immune escape of ocular parasite infection.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107025","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

Metabolomics Reveals Disturbed Amino Acid Metabolism During Different Stages of RA in Collagen-Induced Arthritis Mice. 代谢组学揭示胶原诱导的关节炎小鼠不同阶段的氨基酸代谢紊乱

IF 4.5 2区医学

Inflammation Pub Date : 2024-08-30 DOI: 10.1007/s10753-024-02123-1

Xiafeng Zhang, Mengdi Yin, Dingyi Zhang, Dandan Cao, Xiaoxiao Hou, Zhenghao Xu, Chengping Wen, Jia Zhou

{"title":"Metabolomics Reveals Disturbed Amino Acid Metabolism During Different Stages of RA in Collagen-Induced Arthritis Mice.","authors":"Xiafeng Zhang, Mengdi Yin, Dingyi Zhang, Dandan Cao, Xiaoxiao Hou, Zhenghao Xu, Chengping Wen, Jia Zhou","doi":"10.1007/s10753-024-02123-1","DOIUrl":"https://doi.org/10.1007/s10753-024-02123-1","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography-mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107023","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

Modeling "Two-Hit" Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies. 小鼠 "两击 "重症肺炎模型：病理特征和机理研究

IF 4.5 2区医学

Inflammation Pub Date : 2024-08-30 DOI: 10.1007/s10753-024-02136-w

Mengjia Zhao, Bixu Wang, Fangmei Zhou, Chengnan Fang, Bingqi Zhu, Mingyuan Zhou, Xiaoqing Ye, Yuchi Chen, Zhishan Ding

{"title":"Modeling \"Two-Hit\" Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies.","authors":"Mengjia Zhao, Bixu Wang, Fangmei Zhou, Chengnan Fang, Bingqi Zhu, Mingyuan Zhou, Xiaoqing Ye, Yuchi Chen, Zhishan Ding","doi":"10.1007/s10753-024-02136-w","DOIUrl":"https://doi.org/10.1007/s10753-024-02136-w","url":null,"abstract":"Severe pneumonia is one of the most common critical diseases in clinical practice. Existing models for severe pneumonia have limitations, leading to limited clinical translation. In this study, a two-hit severe pneumonia mouse model was established by inducing primary pneumonia through intratracheal instillation of 800 μg lipopolysaccharide (LPS), followed by intraperitoneal injection of 10 mg/kg LPS. The effectiveness of various inflammatory indicators and the lung tissue damage during the time course of this model were confirmed and evaluated. At 3 h post two-hit, the IL-6, TNF-α levels in peripheral blood and bronchoalveolar lavage fluid (BALF), and the white blood cells, neutrophils, and lymphocytes in BALF notably exhibited the most pronounced elevation. At 12 h post two-hit, the white blood cells and neutrophils in peripheral blood significantly increased, accompanied by notable alterations in splenic immune cells and worsened pulmonary histopathological damage. Transcriptomics of lung tissue, microbiota analysis of lung and gut, as well as plasma metabolomics analyses further indicated changes in transcriptional profiles, microbial composition, and metabolites due to the two-hit modeling. These results validate that the two-hit model mimics the clinical presentation of severe pneumonia and serves as a robust experimental tool for studying the pathogenesis of severe pneumonia and developing and assessing treatment strategies.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107024","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