Mediators of Inflammation最新文献

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Mechanistic Insights Into GDFMD-Mediated Inhibition of Liver Fibrosis via miRNA-29b-3p Upregulation in Wilson's Disease. 威尔森病中gdfmd介导的miRNA-29b-3p上调抑制肝纤维化的机制
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-26 eCollection Date: 2025-01-01 DOI: 10.1155/mi/2776808
Peng Huang, Yuzhe Huang, Ting Dong, Han Wang, Meixia Wang, Xiang Li, Wei Dong, Yulong Yang, Wei He, Wenming Yang
{"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}
引用次数: 0
Influence of Altered Immune-Inflammatory Axis on the Risk of Osteomyelitis and Its Network Interaction Effect in European Population. 免疫-炎症轴改变对欧洲人群骨髓炎风险的影响及其网络相互作用效应。
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-23 eCollection Date: 2025-01-01 DOI: 10.1155/mi/5707884
Yangguang Lu, Siyao Chen, Ruotong Yao, Feng Chen, Yukai Wang, Zihui Yuan, Di Lu, Haiyong Ren, Xiang Wang, Bingyuan Lin, Qiaofeng Guo, Kai Huang
{"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}
引用次数: 0
Circulating Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Infection and Poststroke Fatigue Affecting Long-Term Neurological Outcomes in Stroke Patients. 循环中性粒细胞与淋巴细胞比值预测卒中相关感染和卒中后疲劳影响卒中患者的长期神经预后。
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-22 eCollection Date: 2025-01-01 DOI: 10.1155/mi/5202480
Lei Zuo, Leiyu Geng, Yujia Cao, Xin-Yu Zhou, Wu Di, Yun Liu, Zhe Zhong, Dandan Liu, Zhengsheng Zhang, Fuling Yan
{"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}
引用次数: 0
Cardiac and Digestive Forms of Chagas Disease: An Update on Pathogenesis, Genetics, and Therapeutic Targets. 恰加斯病的心脏和消化形式:发病机制、遗传学和治疗靶点的最新进展
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-21 eCollection Date: 2025-01-01 DOI: 10.1155/mi/8862004
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
{"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}
引用次数: 0
Inhibition of the Notch Pathway Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain in Rats by Suppressing HMGB1/Caveolin-1 Signaling in the Spinal Cord. Notch通路抑制通过抑制脊髓HMGB1/Caveolin-1信号通路减轻nab -紫杉醇诱导的大鼠周围神经性疼痛
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-18 eCollection Date: 2025-01-01 DOI: 10.1155/mi/4638804
Xing Wei, Yaqing Zhou, Li Ma, Weimiao Li, Changyou Shan, Shuqun Zhang, Yonglin Zhao
{"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}
引用次数: 0
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. 全身炎症反应指数对动脉粥样硬化性心血管疾病患者全因死亡率的动态和静态影响:来自全国健康和营养检查调查的证据
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1155/mi/5343213
Chenglin Duan, Yihang Du, Jiafan Chen, Shuqing Shi, Xiaohan Zhang, Yuanhui Hu
{"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}
引用次数: 0
Correlation of the Expression Profile of Peripheral Leukocyte and Liver Tissue Immune Markers With Serum Liver Injury Indices in Children With Biliary Atresia. 胆道闭锁患儿外周血白细胞及肝组织免疫标志物表达谱与血清肝损伤指标的相关性
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1155/mi/9889239
Anna Helmin-Basa, Izabela Kubiszewska, Joanna B Trojanek, Małgorzata Wiese-Szadkowska, Maria Janowska, Zbigniew Kułaga, Joanna Pawłowska, Jacek Michałkiewicz
{"title":"Correlation of the Expression Profile of Peripheral Leukocyte and Liver Tissue Immune Markers With Serum Liver Injury Indices in Children With Biliary Atresia.","authors":"Anna Helmin-Basa, Izabela Kubiszewska, Joanna B Trojanek, Małgorzata Wiese-Szadkowska, Maria Janowska, Zbigniew Kułaga, Joanna Pawłowska, Jacek Michałkiewicz","doi":"10.1155/mi/9889239","DOIUrl":"https://doi.org/10.1155/mi/9889239","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The aim of the study was to find associations between the levels of liver injury serum markers and the selected liver, peripheral leukocytes, and plasma immune characteristics in biliary atresia (BA) children. Twenty-five newly diagnosed BA children aged 4-30 weeks and 12 age-matched controls were included (for leukocytes characteristics) and 19 BA children and 11 controls (for liver studies). The frequencies of T helper 1 (Th1), Th2, Th17, Th17.1 cells as well as numbers of regulatory T (Treg), B cell subsets, and matrix metalloproteinase -2 and -9 (MMP-2 and MMP-9) expressing leukocytes in the whole blood were evaluated by flow cytometry. Plasma concentrations of tissue inhibitors of metalloproteinase (TIMP)-1, -2, MMP-9, interleukin-17A (IL-17A) and IL-6 were assessed by enzyme-linked immunosorbent assay (ELISA). The leukocyte and liver expression of the retinoic acid receptor-related orphan nuclear receptor gamma (&lt;i&gt;RORγT&lt;/i&gt;), fork-head winged helix transcription factor P3 (&lt;i&gt;FoxP3&lt;/i&gt;), transforming growth factor beta (&lt;i&gt;TGF-β&lt;/i&gt;), interleukin-17A (&lt;i&gt;IL-17A&lt;/i&gt;), &lt;i&gt;IL-6&lt;/i&gt;, &lt;i&gt;IL-1β&lt;/i&gt;, &lt;i&gt;IL-21&lt;/i&gt;, interleukin 1 receptor antagonist (&lt;i&gt;IL-1Ra)&lt;/i&gt;, &lt;i&gt;MMP-2&lt;/i&gt;, &lt;i&gt;MMP-9&lt;/i&gt;, &lt;i&gt;MMP-12&lt;/i&gt; (liver only), &lt;i&gt;TIMP-1&lt;/i&gt;, &lt;i&gt;TIMP-2&lt;/i&gt;, T-box transcription factor expressed in T cells, also called TBX21 (&lt;i&gt;T-bet&lt;/i&gt;), GATA-binding protein 3 (&lt;i&gt;GATA3&lt;/i&gt;), and C-type lectin (&lt;i&gt;CD161&lt;/i&gt;) mRNA were determined by real time RT-PCR (reverse-transcription polymerase chain reaction). The BA patients were characterized by increased frequencies of peripheral \"suppressor\" glycoprotein-A repetitions predominant protein (GARP)&lt;sup&gt;+&lt;/sup&gt;latency-associated peptide (LAP)&lt;sup&gt;+&lt;/sup&gt;Treg and activated Treg cells as well as MMP-2 and MMP-9 bearing lymphocytes, elevated plasma TIMP-1 levels, increased leukocyte expression of &lt;i&gt;MMP-9&lt;/i&gt;, &lt;i&gt;TIMP-1&lt;/i&gt;, &lt;i&gt;TIMP-2&lt;/i&gt;, &lt;i&gt;IL-6&lt;/i&gt;, and &lt;i&gt;TGF-β&lt;/i&gt;, and decreased leukocyte expression of IL-21 and T-bet, increased liver expression of &lt;i&gt;FoxP3&lt;/i&gt;, &lt;i&gt;TIMP-1&lt;/i&gt;, and decreased liver expression of &lt;i&gt;IL-1β&lt;/i&gt; and &lt;i&gt;MMP-2&lt;/i&gt;. The following correlations were found between serum markers of liver injury and leukocyte and liver immune characteristics: (a) hemoglobin (Hb) levels correlated negatively with frequency of peripheral \"suppressor\" GARP&lt;sup&gt;+&lt;/sup&gt;LAP&lt;sup&gt;+&lt;/sup&gt; Tregs; (b) aspartate aminotransferase (AST) levels correlated positively with frequency of the peripheral Th17.1 subset and expression of leukocyte &lt;i&gt;FoxP3&lt;/i&gt;, (c) gamma glutamyltransferase (GGT) levels correlated positively with the peripheral memory B cells frequencies, the leukocyte &lt;i&gt;IL-6&lt;/i&gt; and &lt;i&gt;TIMP-1&lt;/i&gt; gene expression, (d) alanine aminotransferase (ALT) serum levels correlated positively with the naïve B cell frequency and liver &lt;i&gt;TIMP-2&lt;/i&gt; expression, (e) total bilirubin (Bil) levels correlated positively with the leukocyte &lt;i&gt;MMP-9&lt;/i&gt;, the plasma IL-6 levels, and the liver &lt;i&gt;TIMP-2&lt;/i&gt; gene expression, (f) dir","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9889239"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004346","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}
引用次数: 0
The Association Between Sleep Disorder and Female Infertility: A Mediation Analysis of Inflammatory and Oxidative Markers. 睡眠障碍与女性不孕之间的关系:炎症和氧化标志物的中介分析。
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1155/mi/4572392
Qiaorui Yang, Jinfu Zhang, Zhenliang Fan
{"title":"The Association Between Sleep Disorder and Female Infertility: A Mediation Analysis of Inflammatory and Oxidative Markers.","authors":"Qiaorui Yang, Jinfu Zhang, Zhenliang Fan","doi":"10.1155/mi/4572392","DOIUrl":"https://doi.org/10.1155/mi/4572392","url":null,"abstract":"<p><p><b>Background:</b> Sleep disorder in women of reproductive age may contribute to infertility development, but there is a lack of substantial evidence linking sleep disorder to inflammation and oxidative stress, and the subsequent risk of infertility. <b>Methods:</b> A total of 2365 women aged 18-45 years from the National Health and Nutrition Examination Survey (NHANES) were included in this analysis. Sleep disorder and infertility were assessed according to NHANES questionnaire data module. Inflammatory and oxidative biomarkers such as high-sensitivity C-reactive protein (hs-CRP), white blood cell (WBC), gamma-glutamyl transpeptidase (GGT), albumin, ferritin, and total bilirubin were derived from the laboratory data module, and systemic immune inflammation index (SII), and system inflammation response index (SIRI) were calculated based on complete blood cell counts. A sophisticated multistage sampling design and weighted multivariable adjusted regression models were employed to conduct comprehensive analysis. Mediation models were applied to explicate the mediating role of biomarkers of inflammation and oxidative stress. <b>Results:</b> Compared to the noninfertility group, the infertile participants had a higher incidence of sleep disorder (34% vs. 25%, <i>p</i> < 0.05). In models with fully adjusted covariates, sleep disorder was positively associated with infertility risk (OR: 1.58; 95%CI: 1.01-2.50, <i>p</i> < 0.05), particularly in subgroups of individuals aged over 30 years old (OR: 1.75; 95%CI: 1.00-3.04, <i>p</i> < 0.05) or with a body mass index (BMI) ≥ 30 kg/m<sup>2</sup> (OR:2.05; 95%CI: 1.00-4.22, <i>p</i> < 0.05). In terms of mechanisms, there were significant correlations between inflammatory and oxidative markers and both sleep disorder and infertility. Mediation analysis indicated that hs-CRP, SII, SIRI, GGT, and total bilirubin played a significant mediating role in the relationship between sleep disorder and infertility, accounting for 0.4822%, 6.0515%, 1.2485%, 5.1584%, and 0.4738%, respectively. <b>Conclusions:</b> Sleep disorder is a significant risk factor for infertility, particularly in women aged >30 years or with obesity. Furthermore, the presence of inflammation and oxidative stress status in the body, which also significantly mediate the association between sleep disorder and infertility, can be swiftly and repeatedly identified through blood tests. Sleep, as a modifiable behavioral pattern, can be regarded as a new strategy to cope with infertility.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4572392"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001466","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}
引用次数: 0
A Predictive Model for Acute Kidney Injury Based on Leukocyte-Related Indicators in Hepatocellular Carcinoma Patients Admitted to the Intensive Care Unit. 基于白细胞相关指标的重症监护室肝癌患者急性肾损伤预测模型
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1155/mi/7110012
Xiulan Peng, Yahong Cai, Huan Huang, Haifeng Fu, Wei Wu, Lifeng Hong
{"title":"A Predictive Model for Acute Kidney Injury Based on Leukocyte-Related Indicators in Hepatocellular Carcinoma Patients Admitted to the Intensive Care Unit.","authors":"Xiulan Peng, Yahong Cai, Huan Huang, Haifeng Fu, Wei Wu, Lifeng Hong","doi":"10.1155/mi/7110012","DOIUrl":"https://doi.org/10.1155/mi/7110012","url":null,"abstract":"<p><p><b>Background:</b> This study aimed to develop and validate a straightforward clinical risk model utilizing white blood cell (WBC) counts to predict acute kidney injury (AKI) in critically sick patients with hepatocellular carcinoma (HCC). <b>Methods:</b> Data were taken from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for the training cohort. Data for an internal validation cohort were obtained from the eICU Collaborative Research Database (eICU-CRD), while patients from our hospital were utilized for external validation. A risk model was created utilizing significant indicators identified through multivariate logistic regression, following logistic regression analysis to determine the primary predictors of WBC-related biomarkers for AKI prediction. The Kaplan-Meier curve was employed to evaluate the prognostic efficacy of the new risk model. <b>Results:</b> A total of 1628 critically sick HCC patients were enrolled. Among these, 23 (23.2%) patients at our hospital, 84 (17.9%) patients in the eICU-CRD database, and 379 (35.8%) patients in the MIMIC-IV database developed AKI. A unique risk model was developed based on leukocyte-related indicators following the multivariate logistic regression analysis, incorporating white blood cell to neutrophil ratio (WNR), white blood cell to monocyte ratio (WMR), white blood cell to hemoglobin ratio (WHR), and platelet to lymphocyte ratio (PLR). This risk model exhibited robust predictive capability for AKI, in-hospital mortality, and ICU mortality across the training set, internal validation set, and external validation set. <b>Conclusion:</b> This risk model seems to have practical consequences as an innovative and accessible tool for forecasting the prognosis of critically ill HCC patients, which may, to some degree, aid in identifying equitable risk assessments and treatment strategies.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7110012"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033539","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}
引用次数: 0
Exploring the Relationship Between Immune Cells and Chronic Kidney Disease by Mendelian Randomization, Colocalization Analysis, and SMR. 通过孟德尔随机化、共定位分析和SMR研究免疫细胞与慢性肾脏疾病的关系。
IF 4.4 3区 医学
Mediators of Inflammation Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1155/mi/4279158
Huiling Zhu, Chaofan Qin, Si Cheng, Xi Zhang
{"title":"Exploring the Relationship Between Immune Cells and Chronic Kidney Disease by Mendelian Randomization, Colocalization Analysis, and SMR.","authors":"Huiling Zhu, Chaofan Qin, Si Cheng, Xi Zhang","doi":"10.1155/mi/4279158","DOIUrl":"https://doi.org/10.1155/mi/4279158","url":null,"abstract":"<p><p><b>Background:</b> Chronic kidney disease (CKD) impacts millions of individuals annually. Current research suggests that immune factors played a significant role in CKD. However, the potential causal relationship between them remains unclear. <b>Methods:</b> We conducted a comprehensive Mendelian randomization (MR) analysis to assess the potential causal association between 731 immune cells and CKD. Sensitivity analysis was performed to test for heterogeneity and horizontal pleiotropy, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis, and MR-PRESSO test. The bidirectional MR was utilized to investigate the bidirectional relationship between the immune cells and CKD. Multivariable MR was also conducted to mitigate confounding among immune cells. The colocalization analysis was performed to find the key genes of immune cells. We used the Summary data-based MR (SMR) analysis to generate effect estimates between the cis-eQTL and immune cells. The heterogeneity in dependent instruments (HEIDIs) test was used to test the heterogeneity between dependent instrumental variables. <b>Results:</b> We identified 14 potential pathogenic factors and six potential protective factors through the univariable MR. Moreover, we did not find reverse causation by using the bidirectional MR. We finally identified one risk factor and two protective factors after multivariate MR adjustment for effects between immune cells. CD28 on CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cell could increase the risk of CKD (Pval: 0.033, OR: 1.112, 95% CI: 1.009-1.227). CD11c on myeloid dendritic cell (DC) could decrease the risk of CKD (Pval: 0.02, OR: 0.854, 95% CI: 0.748-0.975). CD45RA on naive CD4<sup>+</sup> T cell could decrease the risk of CKD (Pval: 0.026, OR: 0.918, 95% CI: 0.852-0.990). Importantly, we observed no evidence of heterogeneity and pleiotropy, signifying the robustness of our results. <i>BACH2</i> (PPH4.abf = 0.999, P_SMR: <0.001, P_HIEDI: 0.132) and <i>HLA-G</i> (PPH4.abf = 0.990, P_SMR: <0.001, P_HIEDI: 0.141) shared the same variant with CD28 on CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cell. <i>PAQR9</i> (PPH4.abf = 0.992, P_SMR: <0.001, P_HIEDI: 0.215) shared the same variant with CD11c on myeloid DC. <b>Conclusion:</b> MR identified a potential correlation between CKD and immune cells. Colocalization and SMR found the key genes of immune cells. Our findings offer insights into the prevention and management of CKD. However, further investigation is required to elucidate the precise mechanisms underlying this relationship.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4279158"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017607","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}
引用次数: 0
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