Mediators of Inflammation最新文献

{"title":"Cross Talk Between Macrophages and Podocytes in Diabetic Nephropathy: Potential Mechanisms and Novel Therapeutics.","authors":"Siming Yu, Zehui Han, Chunsheng Li, Xinxin Lu, Yue Li, Xingxing Yuan, Dandan Guo","doi":"10.1155/mi/8140479","DOIUrl":"https://doi.org/10.1155/mi/8140479","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal failure worldwide. Podocytes, essential components of the glomerular filtration barrier (GFB), are profoundly affected in the diabetic milieu, resulting in structural and functional alterations. Concurrently, macrophages, pivotal innate immune cells, infiltrate the diabetic kidney and exhibit diverse activation states influenced by the local environment, playing a crucial role in kidney physiology and pathology. This review synthesizes current insights into how the dynamic cross talk between these two cell types contributes to the progression of DN, exploring the molecular and cellular mechanisms underlying this interaction, with a particular focus on how macrophages influence podocyte survival through various forms of cell death, including apoptosis, pyroptosis, and autophagy. The review also discusses the potential of targeting macrophages to develop more effective treatments for DN.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8140479"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Pogostemon cablin</i> Acts as a Key Regulator of NF-<i>κ</i>B Signaling and Has a Potent Therapeutic Effect on Intestinal Mucosal Inflammation.","authors":"Yuqing Deng, Xin Liang, Long Zhao, Xin Zhou, Jianqin Liu, Zhi Li, Shanshan Chen, Guohui Xiao","doi":"10.1155/mi/9000672","DOIUrl":"https://doi.org/10.1155/mi/9000672","url":null,"abstract":"<p><p>Persistent intestinal inflammation is a major contributor to various diseases, including digestive disorders, immune dysregulation, and cancer. The NF-<i>κ</i>B signaling pathway is pivotal in the inflammatory response of intestinal cells, regulating the secretion of inflammatory factors, mediating signal transduction, and activating receptors. In colitis, NF-<i>κ</i>B signaling and its effector molecules are excessively activated by various stimuli, leading to overexpression of inflammatory mediators and immune regulators. Colitis, an inflammation of the intestinal mucosa, underlies many intestinal diseases, with increasing incidence. Traditional treatments such as glucocorticoids and nonsteroidal antiinflammatory drugs have significant limitations and side effects. <i>Pogostemon cablin</i>, a traditional Chinese medicine and food, is widely used in food, spices, and pharmaceuticals. Studies have demonstrated its positive therapeutic effects on intestinal inflammation, primarily through regulation of the NF-<i>κ</i>B signaling pathway. Moreover, <i>P. cablin</i> and its active components exhibit pharmacological activities such as antiapoptotic, antioxidant, and antitumor effects. This review summarizes the original research on treating intestinal mucosal inflammation via NF-<i>κ</i>B signaling regulation using <i>P. cablin</i> and its active components, providing new insights for colitis treatment.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9000672"},"PeriodicalIF":4.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liangxue Qushi Zhiyang Decoction Inhibits Atopic Dermatitis in Mice via Fc<i>γ</i>R-Mediated Phagocytosis.","authors":"Lili Zhang, Linxian Li, Zhanxue Sun","doi":"10.1155/mi/7068964","DOIUrl":"https://doi.org/10.1155/mi/7068964","url":null,"abstract":"<p><p><b>Background:</b> Liangxue Qushi Zhiyang Decoction (LQZ) is a traditional formula known for its efficacy in treating Atopic Dermatitis (AD). However, the specific mechanisms through which LQZ alleviates AD symptoms remain largely unknown. The objective of this study is to investigate the protective effects of LQZ on AD and to uncover its potential mechanisms of action. <b>Methods:</b> An AD model was established in mice using 2,4-dinitrochlorobenzene (DNCB). Mice were then orally administered LQZ or prednisolone (PDN). Throughout the treatment period, dermatitis scores and scratching frequencies of the mice were regularly monitored. Histopathological analyses were conducted using hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining. Serum levels of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Further, tandem mass tag (TMT) labeling quantitative proteomics was employed to identify differentially expressed proteins (DEPs). Enrichment analysis was conducted to pinpoint potential targets and pathways involved in LQZ's therapeutic action. Finally, validation experiments were performed to further explore the specific pathways and core targets of LQZ in AD treatment.. <b>Results:</b> LQZ treatment notably mitigated the skin barrier damage and inflammatory response induced by DNCB in AD mice, and reduced the serum levels of IgE, IL-4, and IL-1<i>β</i>. Proteomic analysis identified 248 proteins with differential expression, implicating multiple pathways in LQZ' therapeutic action. Among these, the Fc gamma R(Fc<i>γ</i>R)-mediated phagocytosis pathway emerged as a crucial factor in AD's inflammatory and immune responses. Key proteins associated with this pathway, including Fc-gamma RIII (Fcgr3), V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), Tyrosine-protein kinase (Syk), Phosphoinositide phospholipase C-gamma-2 (Plcg2), Neutrophil cytosol factor 1 (Ncf1), Ras-related C3 botulinum toxin substrate 2 (Rac2) and Actin-related protein 2/3 complex subunit 3 (Arpc3), exhibited significantly reduced expression levels following LQZ treatment. <b>Conclusion:</b> LQZ is effective in treating AD by alleviating skin barrier damage and inflammatory reactions. Its anti-AD properties of LQZ may be attributed to the inhibition of the Fc<i>γ</i>R-mediated phagocytic pathway.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7068964"},"PeriodicalIF":4.4,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Relationship Between 91 Inflammatory Cytokines and IgA Nephropathy Using a Two-Sample Mendelian Randomization Study and the Gene Expression Omnibus Database.","authors":"Manyi Wu, Xingxin Yang, Mengxiao Zou, Xiaojing Cai, Chunyu Pan, Junhua Li, Shuwang Ge","doi":"10.1155/mi/5142090","DOIUrl":"https://doi.org/10.1155/mi/5142090","url":null,"abstract":"<p><p><b>Objectives:</b> Previous research has demonstrated associations between various inflammatory cytokines and IgA nephropathy (IgAN). However, the causal relationships between them remain unclear. The purpose of this study is to extensively analyze the causal links between 91 circulating cytokines and IgAN. <b>Methods:</b> This study commenced with a two-sample bidirectional Mendelian randomization analysis. Genetic variations associated with 91 circulating inflammatory cytokines were extracted from genome-wide association study (GWAS) data involving individuals of European ancestry (<i>n</i> = 14824). In the corresponding GWAS dataset, the genetic variations for IgAN were obtained from a Finnish cohort of European ancestry, consisting of a case group (<i>n</i> = 653) and a control group (<i>n</i> = 411528). The findings from the Mendelian randomization analysis were subsequently subjected to preliminary validation using the GSE116626 dataset from the GEO database. <b>Results:</b> Our MR analysis indicates that transforming growth factor-alpha (TGF-alpha), leukemia inhibitory factor (LIF), and C-C motif chemokine 19 (CCL19) are linked to an increased risk of IgAN. There were no causal connections found when IgAN was used as an exposure and the 91 circulating inflammatory cytokines as outcomes. In addition, the GSE116626 dataset from the GEO database revealed significant upregulation of CCL19 in renal tissues from patients diagnosed with IgAN. <b>Conclusions:</b> This study shows a causal link between inflammatory cytokines and IgAN, suggesting that TGF-alpha, LIF, and CCL19 may act as upstream mediators in the pathogenic pathways of IgAN. The critical role of CCL19 in the pathogenesis of IgAN was further validated using data from the GEO database. However, whether these cytokines can be used to predict or ameliorate the progression of IgAN requires further investigation.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5142090"},"PeriodicalIF":4.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights Into GDFMD-Mediated Inhibition of Liver Fibrosis via miRNA-29b-3p Upregulation in Wilson's Disease.","authors":"Peng Huang, Yuzhe Huang, Ting Dong, Han Wang, Meixia Wang, Xiang Li, Wei Dong, Yulong Yang, Wei He, Wenming Yang","doi":"10.1155/mi/2776808","DOIUrl":"https://doi.org/10.1155/mi/2776808","url":null,"abstract":"<p><p><b>Background:</b> Wilson's disease (WD) is an abnormal copper metabolism disease. GanDouFuMu decoction (GDFMD) is a traditional Chinese medicine, whicn has shown good therapeutic effects in clinical treatment of WD liver fibrosis;but its regulatory mechanism is still unclear. <b>Methods:</b> The serum of WD patients before and after GDFMD treatment were collected, the four items of liver fibrosis were detected by ELISA. The hepatic stellate cell (HSC) activities were assesed via CCK8 assay. The mRNA levels were evaluated by qPCR. The protein levels were checked by western blot. The autophygosomes were observed by transmission electron microscope (TEM). The transdifferentiation ability of HSCs into myofibroblasts was evaluated with anti-α-SMA antibody by immunofluorescence (IF). In copper-laden rats with WD, the autophagy levels, and fibrosis level were observed by IF. <b>Results:</b> The four items of liver fibrosis levels were decreased. GDFMD could increase the HSCs cell activity. GDFMD could increase miRNA-29b-3p levels, which was decreased by TGF-β1. miRNA-29b-3p inhibitors could reversed the suppression response of GDFMD on the the protein expression of ULK1, beclin1, LC3, α-SMA, and Col1. GDFMD blocked the transdifferentiation of HSCs into myofibroblasts, inhibited liver fibrosis. <b>Conclusion:</b> GDFMD blocked the transdifferentiation of HSCs into myofibroblasts by upregulating miRNA-29b-3p, and then inhibited liver fibrosis in WD.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2776808"},"PeriodicalIF":4.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Altered Immune-Inflammatory Axis on the Risk of Osteomyelitis and Its Network Interaction Effect in European Population.","authors":"Yangguang Lu, Siyao Chen, Ruotong Yao, Feng Chen, Yukai Wang, Zihui Yuan, Di Lu, Haiyong Ren, Xiang Wang, Bingyuan Lin, Qiaofeng Guo, Kai Huang","doi":"10.1155/mi/5707884","DOIUrl":"https://doi.org/10.1155/mi/5707884","url":null,"abstract":"<p><p><b>Background:</b> Osteomyelitis (OM) is a severe bone infection with rising incidence rates, particularly among elderly and diabetic patients. The immune-inflammatory axis is implicated in OM pathogenesis, but its complex interplay remains poorly defined. This study aims to explore the causal relationships between immunophenotypes, plasma inflammatory proteins, and OM using Mendelian randomization (MR) and bioinformatics. <b>Methods:</b> Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted MR using inverse variance weighting to explore the causal relationships between immunophenotypes, plasma inflammatory proteins, and OM. Bioinformatics tools were applied to explore the functional enrichment and protein-protein interaction networks of the implicated genes. <b>Results:</b> The MR analysis identified 13 immune cell phenotypes and 2 plasma inflammatory proteins associated with risk of OM. Notably, higher levels of HLA DR on plasmacytoid dendritic cells, memory B cell absolute counts, and CD8dim T cell percentages were associated with increased OM risk. Additionally, elevated levels of CD6 and IL-12 subunit B were correlated with OM risk. Bioinformatics analysis revealed the enrichment of related genes in immune-related pathways and highlighted the complex interaction networks of the implicated proteins. <b>Conclusions:</b> This study provides novel insights into the immune-inflammatory axis in OM and identifies potential biomarkers for risk assessment. The findings warrant further validation in diverse populations and pave the way for developing targeted preventive and therapeutic strategies for OM.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5707884"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Infection and Poststroke Fatigue Affecting Long-Term Neurological Outcomes in Stroke Patients.","authors":"Lei Zuo, Leiyu Geng, Yujia Cao, Xin-Yu Zhou, Wu Di, Yun Liu, Zhe Zhong, Dandan Liu, Zhengsheng Zhang, Fuling Yan","doi":"10.1155/mi/5202480","DOIUrl":"https://doi.org/10.1155/mi/5202480","url":null,"abstract":"<p><p><b>Background:</b> Since peripheral leukocytes may contribute to the pathophysiology of stroke, the aim of this study was to elucidate the relationship between leukocytes and stroke outcomes and identify which leukocyte subtypes most accurately predict functional outcomes and poststroke fatigue (PSF) in stroke patients. <b>Methods:</b> A total of 788 ischemic stroke patients within 72 h of onset of disease were admitted in our study. Stroke-associated infection (SAI) and PSF were evaluated according to diagnosis standards by a special neurologist. Analyses were performed using SPSS 23.0 and GraphPad Prism 10.0. <b>Results:</b> Neutrophil-to-lymphocyte ratio (NLR) has discriminative power in predicting stroke outcome, and the area under the curve (AUC) of NLR to distinguish stroke outcomes was 0.689 (95% confidence interval, 0.646-0.732). Positive correlation was found between NLR levels and NIHSS score on admission (<i>r</i> = 0.2786, <i>p</i> < 0.001). Risk model for predicting stroke outcome was constructed using age, NIHSS, previous stroke history, triglycerides, glucose and hemoglobin levels, thrombolysis treatment, and NLR, with an AUC of 0.865. Patients who developed SAI and PSF both had significantly higher NLR levels at admission than those patients not diagnosed with SAI and PSF (<i>p</i> < 0.0001). A risk model was constructed to predict PSF based on parameters including age, NIHSS score, lipoprotein(a) and NLR, and an AUC of 0.751. <b>Conclusions:</b> Higher NLR levels in the acute phase of stroke might indicate a higher incidence of SAI and PSF. Therefore, higher NLR is associated with a poor stroke prognosis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5202480"},"PeriodicalIF":4.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac and Digestive Forms of Chagas Disease: An Update on Pathogenesis, Genetics, and Therapeutic Targets.","authors":"Amanda Farage Frade, Hélléa Guérin, Joao Paulo Silva Nunes, Luiz Felipe Souza E Silva, Vinicius Moraes de Paiva Roda, Rafael Pedro Madeira, Pauline Brochet, Pauline Andrieux, Jorge Kalil, Christophe Chevillard, Edecio Cunha-Neto","doi":"10.1155/mi/8862004","DOIUrl":"https://doi.org/10.1155/mi/8862004","url":null,"abstract":"<p><p>Chagas disease, caused by the protozoan parasite <i>Trypanosoma cruzi</i> (<i>T. cruzi</i>), is a neglected disease affecting around 6 million people, with no effective antiparasitic drugs or vaccines. About 40% of Chagas disease patients develop symptomatic forms in the chronic phase of infection, chronic Chagas cardiomyopathy (CCC) or digestive forms like megaoesophagus and megacolon, while most infected patients (60%) remain asymptomatic (ASY) in the so-called indeterminate form (IF). CCC is an inflammatory cardiomyopathy that occurs decades after the initial infection. Death results from heart failure or arrhythmia in a subset of CCC patients. Myocardial fibrosis, inflammation, and mitochondrial dysfunction are involved in heart failure and arrhythmia. Survival in CCC is worse than in other cardiomyopathies. Distinct from other cardiomyopathies, CCC displays a helper T-cell type 1 (Th1-T) cell-rich myocarditis with abundant interferon-gamma (IFN-<i>γ</i>) and tumor necrosis factor-alpha (TNF-<i>α</i>) and selectively lower levels of mitochondrial energy metabolism enzymes and high-energy phosphates in the heart. A CD8+ T cell-rich inflammatory infiltrate has also been found in the Chagasic megaesophagus, which is associated with denervation of myoenteric plexi. IFN-<i>γ</i> and TNF-<i>α</i> signaling, which are constitutively upregulated in Chagas disease patients, negatively affect mitochondrial function and adenosine 5'-triphosphate (ATP) production-cytokine-induced mitochondrial dysfunction. In addition, the differential susceptibility to developing CCC has prompted many studies over the past 25 years on the association of genetic polymorphisms with disease outcomes. A comprehensive understanding of Chagas disease pathogenesis is crucial for identifying potential therapeutic targets. Genetic studies may offer valuable insights into factors with prognostic significance. In this review, we present an updated perspective on the pathogenesis and genetic factors associated with Chagas disease, emphasizing key studies that elucidate the differential progression of patients to CCC and other symptomatic forms. Furthermore, we explore the interplay between genetic susceptibility, inflammatory cytokines, mitochondrial dysfunction and discuss emerging therapeutic targets.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8862004"},"PeriodicalIF":4.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the Notch Pathway Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain in Rats by Suppressing HMGB1/Caveolin-1 Signaling in the Spinal Cord.","authors":"Xing Wei, Yaqing Zhou, Li Ma, Weimiao Li, Changyou Shan, Shuqun Zhang, Yonglin Zhao","doi":"10.1155/mi/4638804","DOIUrl":"https://doi.org/10.1155/mi/4638804","url":null,"abstract":"<p><p><b>Background:</b> Paclitaxel (PTX) is widely used in the clinical treatment of cancer, and peripheral neuropathy is a common adverse side effect of PTX. Diverse mechanisms contribute to the development and maintenance of PTX-induced peripheral neuropathy. However, the role of the spinal Notch pathway in PTX-induced peripheral neuropathy is not completely understood. <b>Methods:</b> A Sprague-Dawley male rat model of PTX-induced peripheral neuropathy was established by nab-PTX. A total 120 rats were randomly divided into a control group (<i>n</i> = 36), PTX d8 group (<i>n</i> = 6), PTX d15 group (PTX group, <i>n</i> = 36), PTX d21 group (<i>n</i> = 6), and PTX+N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) (Notch pathway inhibitor) group (<i>n</i> = 36). The expression of Notch downstream signaling molecules, including NICD, JAG1, and Hes1 was examined in the control group, PTX d8 group, PTX d15 group, and PTX d21 group. The effects of the DAPT on behavioral assays, apoptosis, neuronal and axonal injury, glial responses, and vascular permeability were detected. The monolayer of mouse brain microvascular endothelial cells was used to simulate vascular permeability in vitro. Cells were divided into the following groups: control group, nab-PTX group, PTX+DAPT group, PTX+DAPT+recombinant mouse high mobility group Box 1 (rmHMGB1) group, and PTX+rmHMGB1+methyl-<i>β</i>-cyclodextrin (M<i>β</i>CD) group. The underlying mechanisms were explored by examining the expression and translocation of the HMGB1/caveolin-1 signaling pathways, inflammatory cytokines, and oxidative stress in vivo and in vitro. <b>Results:</b> The levels of Notch downstream signaling molecules were elevated and peaked at d15 after nab-PTX treatment. The mechanical and thermal pain thresholds of rats were decreased with nab-PTX treatment, accompanied by enhanced apoptosis, neuronal and axonal injury, glial responses, and vascular permeability. DAPT could restore the mechanical and thermal thresholds and decrease apoptosis, neuronal and axonal injury, and glial responses induced by nab-PTX. DAPT also protected vascular permeability by increasing the expression of tight junction proteins in vivo. RmHMGB1 could abrogate the protective effect of DAPT on vascular permeability, while the inhibitor of caveolin-1, M<i>β</i>CD, could further abrogate the effect of rmHMGB1 in vitro. DAPT relieved nab-PTX-induced peripheral neuropathy by inhibiting the activation of the HMGB1/caveolin-1 signaling pathways and decreasing the levels of inflammatory cytokines and oxidative stress in vivo and in vitro. <b>Conclusion:</b> Taken together, the results of this study demonstrated that the Notch pathway may serve as a potential target for PTX-induced peripheral neuropathy intervention.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4638804"},"PeriodicalIF":4.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic and Static Effects of the Systemic Inflammatory Response Index on All-Cause Mortality in Individuals With Atherosclerotic Cardiovascular Disease: Evidence From National Health and Nutrition Examination Survey.","authors":"Chenglin Duan, Yihang Du, Jiafan Chen, Shuqing Shi, Xiaohan Zhang, Yuanhui Hu","doi":"10.1155/mi/5343213","DOIUrl":"https://doi.org/10.1155/mi/5343213","url":null,"abstract":"<p><p><b>Objective:</b> This research focuses on analyzing the link between the systemic inflammatory response index (SIRI) and all-cause mortality in individuals with atherosclerotic cardiovascular disease (ASCVD) . <b>Methods:</b> This research analyzed data from 4693 patients using nine cycles of the National Health and Nutrition Examination Survey (NHANES). The connection between SIRI and mortality was determined by employing survey-weighted Cox models, with hazard ratios (HRs) and 95% confidence intervals (CIs) being computed. Kaplan-Meier method illustrated survival differences across SIRI levels. Sensitivity analyses involved restricted cubic splines (RCS), stratified analysis, and <i>E</i>-value calculations. Landmark analysis assessed survival differences at multiple follow-up intervals, while time-dependent receiver operating characteristic curves evaluated SIRI's prognostic value. Mediation analysis identified potential intermediaries impacting the SIRI-mortality relationship. <b>Results:</b> Over 406,564 person-months, 1933 deaths occurred. Adjusted Cox models discovered that higher SIRI was connected with elevated overall mortality [HR 1.192, (95% CI 1.131-1.256), <i>p</i> < 0.001]. Higher SIRI consistently showed lower survival probabilities. RCS and stratified analysis confirmed the robustness of these findings. Survival probability at different follow-up periods was considerably lower in those with higher SIRI. Additionally, SIRI demonstrated a prognostic value of 0.66 for all-cause mortality at 1 year and 3 years, and 0.65 at 5 years. Notably, serum uric acid (6.2%) partially mediated the connection between SIRI and mortality from all causes. <b>Conclusion:</b> In ASCVD patients, SIRI was robustly correlated with all-cause mortality, partially mediated by serum uric acid.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5343213"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}