Journal of Inflammation Research最新文献

{"title":"Analysis of a Familial IgAN Accompanied by COL4A3 Mutation.","authors":"Sen-Qing Lin, Jin-Xiu Deng, Hui Jiang, Shi-Hong Xiang, Wen-Jing Lin, Feng-Qi Qian, Sen-Chao Wu, Fu-Zhen Wang","doi":"10.2147/JIR.S480279","DOIUrl":"10.2147/JIR.S480279","url":null,"abstract":"<p><strong>Objective: </strong>IgA nephropathy (IgAN) is the prevailing primary glomerulonephritis globally and is the key factor contributing to the onset of chronic kidney disease and eventual progression to end-stage renal disease. This study aims to explore the mutated gene in a familial case of IgAN, especially COL4A3.</p><p><strong>Methods: </strong>Family lineages diagnosed with familial IgAN at the Longyan First Hospital of Fujian Medical University were selected for this study, followed by comprehensive whole exome sequencing. After obtaining the sequencing data, bioinformatics analyses were conducted to discern potential mutated genes. These findings within the familial lineages were validated using Sanger sequencing to identify IgAN-associated mutated genes, based on literature references and in accordance with the genetic variation classification criteria determined by the American College of Medical Genetics and Genomics.</p><p><strong>Results: </strong>Whole exome sequencing analysis of familial IgAN family lineages led to the identification of a total of 212,187 single nucleotide variant/insertion-deletion mutation sites, annotated using ANNOVAR. These sites were screened targeting four mutated genes, revealing three mutations of undetermined significance along with a single disease-causing mutation: a heterozygous disease-causing mutation within COL4A3 (p.G1167R). This mutation manifested across seven family members within the group, encompassing both family members diagnosed with kidney disease and those serving as normal carriers. Notably, one additional family member with IgAN within the familial lineage exhibited an absence of the pathogenic mutation.</p><p><strong>Conclusion: </strong>This study identified four mutated genes that may be involved in the onset and progression of IgAN, further revealing the complex multigenic inheritance characteristics of IgAN. The underlying mechanisms of the disease require further investigation. Additionally, we discovered potential mutations associated with known genetic kidney diseases, such as COL4A3 mutations. Therefore, we recommend comprehensive genetic screening in familial cases of IgAN to improve disease diagnosis and facilitate genetic counseling.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9269-9283"},"PeriodicalIF":4.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710517","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}

{"title":"The Impact of Cytomegalovirus Infection on Ulcerative Colitis Relapse: A Multicenter Retrospective Cohort Study.","authors":"Linmei Xiao, Jingjing Ma, Ruidong Chen, Jie Chen, Qiang Wang, Nana Tang, Xiaojing Zhao, Hongjie Zhang, Chunhua Jiao","doi":"10.2147/JIR.S479663","DOIUrl":"10.2147/JIR.S479663","url":null,"abstract":"<p><strong>Purpose: </strong>Cytomegalovirus (CMV) infection exacerbates intestinal inflammation in ulcerative colitis (UC) patients, yet the effect of CMV infection on UC relapse has not been fully elucidated. This study aimed to investigate the impact of CMV infection on UC relapse and identify associated risk factors.</p><p><strong>Patients and methods: </strong>This multicenter retrospective cohort study included UC patients who visited research centers from January 2016 to December 2020. Univariate and multivariate Cox regression analyses were conducted to explore risk factors for UC relapse. Propensity score matching was used to balance the differences in the clinical characteristics between the groups.</p><p><strong>Results: </strong>A total of 298 UC patients participated in this study, including 19 with CMV colitis, 37 with CMV viremia, and 242 CMV-negative patients. The 2-year cumulative recurrence rate was higher in patients with CMV colitis than that in CMV-negative patients (84.21% vs 51.65%, <i>p</i> = 0.01). Univariate and multivariate Cox regression analyses confirmed that fecal calprotectin ≥ 250 µg/g, Montreal classification E3, CMV colitis, duration > 48 months, and serum albumin < 30 g/L were independent risk factors for UC relapse at 2 years, whereas the use of biologics for induction of remission was identified as an independent protective factor.</p><p><strong>Conclusion: </strong>Our study suggests that the risk of relapse increases among UC patients with CMV colitis over two years. Risk factors for UC relapse at 2 years include fecal calprotectin ≥ 250 μg/g, Montreal classification E3, CMV colitis, UC duration > 48 months, and albumin < 30 g/L, whereas the use of biologics during induction is a protective factor.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9059-9070"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709241","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}

{"title":"Early-Life Stress Induced by Neonatal Maternal Separation Leads to Intestinal 5-HT Accumulation and Causes Intestinal Dysfunction.","authors":"Ding Yang, Rulan Bai, Chengzhong Li, Yan Sun, Hongyu Jing, Zixu Wang, Yaoxing Chen, Yulan Dong","doi":"10.2147/JIR.S488290","DOIUrl":"10.2147/JIR.S488290","url":null,"abstract":"<p><strong>Background: </strong>The early childhood period is a critical development stage, and experiencing stress during this time may increase the risk of gastrointestinal disorders, including irritable bowel syndrome (IBS). Neonatal maternal separation (NMS) in rodent models has been shown to cause bowel dysfunctions similar to IBS, and 5-HT is considered to be a key regulator regulating intestinal function, but the precise underlying mechanisms remain unclear.</p><p><strong>Results: </strong>We established a maternal separation stress mouse model to simulate early-life stress, exploring the expression patterns of 5-HT under chronic stress and its mechanisms affecting gut function. We observed a significant increase in 5-HT expression due to NMS, leading to disruptions in intestinal structure and function. However, inhibiting 5-HT reversed these effects, suggesting its potential as a therapeutic target. Furthermore, our research revealed that excess 5-HT in mice with early life stress increased intestinal neural network density and promoted excitatory motor neuron expression. Mechanistically, 5-HT activated the Wnt signaling pathway through the 5-HT₄ receptor, promoting neurogenesis within the intestinal nervous system.</p><p><strong>Conclusion: </strong>These findings shed light on the intricate changes induced by early life stress in the intestines, confirming the regulatory role of 5-HT in the enteric nervous system and providing potential insights for the development of novel therapies for gastrointestinal disorders.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8945-8964"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715822","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}

{"title":"Role of Cellular Senescence Genes and Immune Infiltration in Sepsis and Sepsis-Induced ARDS Based on Bioinformatics Analysis.","authors":"Xiao-Ling Wu, Ya-Nan Guo","doi":"10.2147/JIR.S488463","DOIUrl":"10.2147/JIR.S488463","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is the leading cause of death in critically ill patients; it results in multiorgan dysfunction, including acute respiratory distress syndrome (ARDS). Our study was conducted to determine the role of cellular senescence genes and immune infiltration in sepsis and sepsis-induced ARDS via bioinformatic analyses.</p><p><strong>Experimental procedures: </strong>Datasets GSE66890 and GSE145227 were obtained from the Gene Expression Omnibus (GEO) database and utilized for bioinformatics analyses. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the differentially expressed genes (DEGs) were performed to identify the key functional modules. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were used to screen for characteristic genes in sepsis and sepsis-induced ARDS. ROC curves were generated to evaluate the predictive ability of gene hubs. Differences in immune infiltration levels between the disease and control groups were compared via ssGSEA. The diagnostic value of the hub genes was verified via quantitative PCR (qPCR) in hospitalized patients.</p><p><strong>Results: </strong>Four characteristic genes (ATM, CCNB1, CCNA1, and E2F2) were identified as biomarkers for the progression of sepsis-induced ARDS. E2F2 showed the highest predictive ability for the occurrence of ARDS in patients with sepsis. CD56bright and plasmacytoid dendritic cells exhibited high infiltration in the sepsis-induced ARDS group, whereas eosinophils, MDSCs, macrophages, and neutrophils exhibited low infiltration. In addition, ATM expression was lower in patients with sepsis than in those without sepsis (n = 6).</p><p><strong>Conclusion: </strong>Sepsis-induced ARDS is correlated with circulating immune responses, and the expression of ATM, CCNB1, CCNA1, and E2F2 may serve as potential diagnostic biomarkers and therapeutic targets in sepsis-induced ARDS.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9119-9133"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716116","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}

{"title":"Mesenchymal Stem Extracellular Vesicles in Various Respiratory Diseases: A New Opportunity.","authors":"Zijun Hu, Lujian Zhu, Yanglin Zhu, Yejin Xu","doi":"10.2147/JIR.S480345","DOIUrl":"10.2147/JIR.S480345","url":null,"abstract":"<p><p>Lung diseases are associated with high morbidity and mortality rates, thereby jeopardizing human health and imposing a great burden on society. Currently, lung diseases are mainly treated with medications, oxygen therapy and mechanical ventilation, but these approaches are unable to effectively reduce the mortality rate. Therefore, lung transplantation remains the ultimate treatment for various chronic lung diseases, but this treatment is also hindered by the limited availability of lung sources, immature technology and a low survival rate after transplantation. With constant changes in the environment, pathogens, type and amount of harmful substances and the prevalence of respiratory diseases, there is an urgent need to identify alternative treatment methods. Research on stem cell therapy has been very successful in recent years, and mesenchymal stem cells (MSCs), together with their secretory bodies, play a significant therapeutic role. Extracellular vesicles of MSCs (MSC-EVs) are also major components of the paracrine secretion of MSCs, including exosomes, microvesicles, and apoptotic bodies, among which exosomes are the most typical. MSC-EVs are believed to be present in various tissues of the human body where they can carry proteins, DNA, RNA and biologically active factors, just to name a few. They can also transmit various biological signals to participate in different biological activities, including the maintenance of homeostasis within the tissue. Several studies have further demonstrated that MSCs and their generated extracellular vesicles play an important role in the treatment of diseases. In this paper, the origin, properties and roles of MSCs and MSC-EVs are reviewed, the mechanisms of different lung diseases, the limitations of current therapeutic options and the roles of MSC-EVs in Chronic Obstructive Pulmonary Disease, asthma, infectious lung disease, lung cancer, pulmonary fibrosis, pulmonary arterial hypertension, and acute lung injury/ acute respiratory distress syndrome are also discussed (Figure 1). In addition, the current limitations and possible future research directions are also discussed in view of providing new ideas for the role of MSC-EVs in the treatment of lung diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9041-9058"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710565","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}

{"title":"Prognostic Prediction for Recurrent/Residual CIN in HSIL Patients After Conization: An Updated Retrospective Study Based on Ambulatory Surgery.","authors":"Guanxiang Huang, Wenyu Lin, Hangjing Gao, Yuan Ren, Jun Shen, Shuxia Xu, Dabin Liu, Yuanjun Cai, Chengbin Lin, Xite Lin, Tingting Jiang, Binhua Dong, Pengming Sun","doi":"10.2147/JIR.S494622","DOIUrl":"10.2147/JIR.S494622","url":null,"abstract":"<p><strong>Background: </strong>There are currently few prognostic models for conization in patients with high-grade squamous intraepithelial lesion (HSIL) because it is a rapid procedure that typically collects less case information. The present study aimed to establish a rapid/accurate postoperative prognostic assessment model for these patients.</p><p><strong>Methods: </strong>This study included 631 nonpregnant participants with HSIL confirmed by histopathology from January 2015 to January 2018. The recurrent/residual cervical intraepithelial neoplasia (CIN) were divided into residual CIN, simple recurrent CIN and recurrent CIN accompanied with CIN progression. The recurrence/residual-free survival (RFS) time was defined as the time span from the time of surgery (baseline) until the first lesion of CIN was detected or the 1-/3-/5-year follow-up endpoint was reached.</p><p><strong>Results: </strong>After LASSO regression selection, the higher platelet-to-lymphocyte ratio (PLR) (OR = 1.006, p = 0.002), positive margin status (OR = 2.451, p = 0.021), HPV-16 (OR = 4.414, p < 0.001), -18 (OR = 3.040, p = 0.009), -56 (OR = 10.715, p=0.021), and non-HR-HPV (OR = 2.487, p = 0.028) infection showed significant difference in the Logistic model. And HPV-16 infection (OR = 6.159, p = 0.001) could promote recurrent CIN accompanied with CIN progression. In multivariate Cox regression models, the higher PLR (HR = 1.005/1.005/1.005, p = 0.020/0.002/0.003) and HPV-16 infection (HR = 2.758/2.836/2.674, p < 0.001) showed statistical difference during 1-/3-/5-year follow-up. While gland invasion (p = 0.081), margin status (p = 0.075) and HPV infection genotype (p = 0.150) did not showed statistical difference in multivariate Cox regression models based on LASSO regression. And gland invasion (p = 0.251/0.686) and HPV-58 infection (p = 0.148/0.813) also showed no statistical difference in optimized Logistic regression models.</p><p><strong>Conclusion: </strong>HPV-16, -18, -56 and non-HR-HPV infection status can be considered as indicators for recurrent CIN during the 5-year follow-up, especially for HPV-16 infection, which also lead to a CIN recurrence accompanied with disease progression. And the preoperative PLR level, gland invasion, positive margin may be predictors for recurrent/residual CIN during 1-, 3- and 5-year follow-up.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9087-9102"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710569","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}

{"title":"The Potential Therapeutic Prospect of PANoptosis in Heart Failure.","authors":"Yunfeng Jia, Yayi Liu, Yiming Zuo, Junping Zhang, Yanyang Li, Xuezheng Liu, Shichao Lv","doi":"10.2147/JIR.S485901","DOIUrl":"10.2147/JIR.S485901","url":null,"abstract":"<p><p>Heart failure (HF) represents a serious manifestation or advanced stage of various cardiac diseases. HF continues to impose a significant global disease burden, characterized by high rates of hospitalization and fatality. Furthermore, the pathogenesis and pathophysiological processes underlying HF remain incompletely understood, complicating its prevention and treatment strategies. One significant pathophysiological mechanism associated with HF is the systemic inflammatory response. PANoptosis, a novel mode of inflammatory cell death, has been extensively studied in the context of infectious diseases, neurodegenerative disorders, cancers, and other inflammatory conditions. Recent investigations have revealed that PANoptosis-related genes are markedly dysregulated in HF specimens. Consequently, the PANoptosis-mediated inflammatory response may represent a potential mechanism and therapeutic target for HF. This paper conducts a comprehensive analysis of the molecular pathways that drive PANoptosis. We discuss its role and potential therapeutic targets in HF, thereby providing valuable insights for clinical treatment and the development of novel therapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9147-9168"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709545","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}

{"title":"Interleukin 1β Mediates the Pathogenesis of Nasal Mucosal Epithelial Barrier Dysfunction in Allergic Rhinitis.","authors":"Hanrui Wang, Xiaoyu Song, Yao Wang, Ting Yang, Wanchen Liu, Yakui Mou, Chao Ren, Xicheng Song","doi":"10.2147/JIR.S488340","DOIUrl":"10.2147/JIR.S488340","url":null,"abstract":"<p><strong>Background: </strong>The nasal mucosal epithelial barrier is the primary site of allergic rhinitis (AR). Interleukin-1β (IL-1β), as a crucial factor in immune inflammation, not only plays a crucial role in hypersensitivity reactions but also affects the digestive mucosa and skin epithelial barrier. However, the role of IL-1β in the nasal mucosal epithelial barrier in AR has not been reported, and this study aimed to investigate the effect and possible mechanisms involved.</p><p><strong>Methods: </strong>Dermatophagoides pteronyssinus 1 was used as an allergen to construct an AR mouse model and stimulate human nasal mucosal epithelial cells (HNEpCs) and observe the expression changes of IL-1β and epithelial barrier indicators CLDN1 and OCLN in mouse nasal mucosa and HNEpCs. Then, the possible mechanisms of action were explored via exogenous IL-1β stimulation and pharmacological inhibition of IL-1β or its receptor interleukin-1 receptor type 1 (IL-1R1).</p><p><strong>Results: </strong>The results showed that Dermatophagoides pteronyssinus 1-primed mouse nasal mucosa or human HENpCs had increased expression of IL-1β and decreased CLDN1 and OCLN, and IL-1β could directly lead to reduced expression of epithelial barrier indexes in HNEpCs. In addition, inhibition of IL-1β or IL-1R1 can effectively alleviate the damage to the epithelial barrier.</p><p><strong>Conclusion: </strong>IL-1β has a destructive effect on the nasal mucosal epithelial barrier in AR, and inhibition of IL-1β or its receptor IL-1R1 can effectively protect the nasal mucosal barrier. IL-1β is a potential target for the treatment of AR.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9071-9085"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715947","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}

{"title":"Multi-Omics Exploration of the Role of PTGS2 as a Hub Gene in Ferroptosis Within the Artery of Takayasu Arteritis.","authors":"Qing Gao, Shang Gao, Haiyang Li, Zuoguan Chen, Ran Zhang, Yongjun Li, Hongjia Zhang","doi":"10.2147/JIR.S478413","DOIUrl":"10.2147/JIR.S478413","url":null,"abstract":"<p><strong>Introduction: </strong>Takayasu arteritis (TAK) is an autoimmune disease affecting the aorta and its branches. Despite anti-inflammatory treatments, some patients require surgical vascular reconstruction due to rapid disease progression. The mechanisms behind persistent inflammation are unclear due to a lack of arterial samples. This study explores ferroptosis in TAK using high-throughput and single-cell transcriptomics.</p><p><strong>Methods: </strong>Transcriptomic data were collected from 8 TAK patients (2 for single cell RNA-seq and 6 for bulk RNA-seq) and 8 renal transplant donors, with single-cell data from 3 public carotid artery samples for control. Bioinformatic analysis was performed to identify ferroptosis-related genes in inflamed arteries.</p><p><strong>Results: </strong>We identified 1526 differentially expressed genes and 46 ferroptosis-related genes, with 6 genes including PTGS2 and HIF1A as hub genes. Single-cell analysis of 27,828 cells revealed increased M1-like macrophages, with PTGS2 highly expressed in these cells. Enrichment analysis indicated NF-κB signal pathway involvement.</p><p><strong>Conclusion: </strong>PTGS2 is a core ferroptosis-related gene in TAK vascular inflammation, highly expressed in M1-like macrophages, potentially upregulated via the IL1B-NF-κB pathway.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9135-9146"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716106","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}

{"title":"Comparison of the Cecum Ligation and Puncture Method and the Intraperitoneal Lipopolysaccharide Injection Method for the Construction of a New-Onset Atrial Fibrillation Model of Sepsis.","authors":"Xiuwen Ling, Jun Shen, Junqing Liang, Kai Yang, Jianzhong Yang","doi":"10.2147/JIR.S485142","DOIUrl":"10.2147/JIR.S485142","url":null,"abstract":"<p><strong>Background: </strong>New-onset atrial fibrillation (AF) in sepsis significantly impacted patient morbidity and mortality, yet the optimal animal model for studying this condition remains undetermined. This study aimed to establish a stable animal model for new-onset AF in sepsis and to explore the molecular mechanisms involved.</p><p><strong>Methods: </strong>Forty-seven Sprague-Dawley rats were utilized, with the cecal ligation and puncture (CLP) group divided into 0.6 mm and 1.0 mm needle outer diameter subgroups, and the lipopolysaccharide (LPS) group into 5 mg/kg, 10 mg/kg, 15 mg/kg, and 20 mg/kg dosage subgroups. The incidence of new-onset AF and five-day mortality rates were compared to identify the most stable modeling conditions. Selected subgroups underwent further analysis, including cardiac ultrasound, electrophysiology, and pathological examinations. Inflammation-related molecular levels in the atrium were assessed using ELISA and Western blotting (WB).</p><p><strong>Results: </strong>The intraperitoneal injection of 10 mg/kg LPS was identified as the most stable model for new-onset AF in sepsis, with significant findings including increased left atrial area and fibrosis, left ventricular pump dysfunction, uncoordinated ventricular wall motion, and impaired electrical impulse conduction. The effective atrial refractory period was markedly shorter, and susceptibility to AF was higher in the LPS group compared to the CLP group. Molecular analysis revealed elevated levels of NOD-like receptor protein 3(NLRP3) inflammasomes, apoptosis-associated speck-like protein containing a CARD(ASC), Caspase-1 p20 Elevated levels of three inflammation-related proteins and increased activity of the Sphingosine 1-phosphate/Sphingosine 1-phosphate Receptor 2(S1P/S1P2) signaling axis.</p><p><strong>Conclusion: </strong>Intraperitoneal injection of 10 mg/kg of LPS can successfully construct a new-onset AF model in sepsis, and NLRP3 inflammatory vesicles mediated by the S1P/S1P2 signaling axis may promote new-onset AF in sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"9103-9117"},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710520","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}