Journal of Inflammation Research最新文献

{"title":"Inflammatory Risk Factors for Chronic Subdural Hematoma in a Nationwide Cohort.","authors":"Thorbjørn Søren Rønn Jensen, Emilia Myrup Thiesson, Kåre Fugleholm, Jan Wohlfahrt, Tina Nørgaard Munch","doi":"10.2147/JIR.S472849","DOIUrl":"https://doi.org/10.2147/JIR.S472849","url":null,"abstract":"<p><strong>Background: </strong>The discovery of biomarkers in chronic subdural haematomas (CSDH) suggests that inflammation is part of CSDH pathophysiology. It is unknown whether inflammation reflects an independent CSDH driver or haematoma degeneration. This knowledge holds a potential target for anti-inflammatory treatment in patients at risk of CSDH. This study investigated the association of pro- and anti-inflammatory factors with CSDH development.</p><p><strong>Methods: </strong>This cohort study included all individuals in Denmark over 50 years between 2007-2018. The outcome was first-time CSDH surgery. Hazard ratios (HR) according to potential risk factors were estimated using Cox regression, with age as underlying time scale.</p><p><strong>Results: </strong>Among the 2,391,853 individuals, head trauma was registered in 427,612 individuals (17%), and among these, only 812 were operated for CSDH (0.18%). Among individuals without registered head trauma, the pro-inflammatory conditions of alcohol addiction, diabetes, anti-hypertensive treatment, and chronic hepatic disease were significantly associated with CSDH among individuals (50-74 years). The use of glucocorticoids displayed a decreased risk in cohort members aged 75 and older. Non-steroid anti-inflammatory drugs and statins appeared to be risk factors for CSDH in individuals between the ages of 50-64 and 65-74.</p><p><strong>Conclusion: </strong>Although head trauma was a risk factor for CSDH, the absolute risk was low (0.18%), which does not support preventive measures after emergency room contacts for head trauma. Interestingly, pro-and anti-inflammatory factors were significantly associated with CSDH in patients without registered head trauma, and the pronounced age-dependency of the associations suggests that the pathophysiological mechanisms vary with age.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8261-8270"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622113","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":"Circulating Protectin D1 and Neutrophils Extracellular Traps in the Diagnosis and Progression of Acute Pancreatitis.","authors":"Zhiyang Wu, Wenjun Lu, Xin Zhang, Qiaoying Xia, Han Zuo, Xi Guo, Yu Liu, Fan Zhang, Xin Zhang, Luyao Zhang","doi":"10.2147/JIR.S494649","DOIUrl":"https://doi.org/10.2147/JIR.S494649","url":null,"abstract":"<p><strong>Purpose: </strong>Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body's endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).</p><p><strong>Patients and methods: </strong>Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.</p><p><strong>Results: </strong>AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.</p><p><strong>Conclusion: </strong>PD1 is associated with both the presence of AP and the severity of pancreatitis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8215-8225"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622072","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":"Unveiling the Gut-Disc Axis: How Microbiome Dysbiosis Accelerates Intervertebral Disc Degeneration.","authors":"Yu Sun, Zhaoyong Li, Jiahao Duan, Enxu Liu, Fei Sun, Lei Yang, Long Chen, Shaofeng Yang","doi":"10.2147/JIR.S487936","DOIUrl":"https://doi.org/10.2147/JIR.S487936","url":null,"abstract":"<p><p>The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8271-8280"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621852","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":"GSDMD Mediates Ang II-Induced Hypertensive Nephropathy by Regulating the GATA2/AQP4 Signaling Pathway.","authors":"Xiaoxi Fan, Wenli Zhang, Ruihan Zheng, Yucong Zhang, Xianhui Lai, Jibo Han, Zimin Fang, Bingjiang Han, Weijian Huang, Bozhi Ye, Shanshan Dai","doi":"10.2147/JIR.S488553","DOIUrl":"https://doi.org/10.2147/JIR.S488553","url":null,"abstract":"<p><strong>Aim: </strong>Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy.</p><p><strong>Methods: </strong>C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd^-/-) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy.</p><p><strong>Results: </strong>GSDMD was activated in the kidneys of mice induced by Ang II (<i>P</i> < 0.001). This activation was primarily observed in the renal tubular epithelial cells (<i>P</i> < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (<i>P</i> < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (<i>P</i> < 0.01). Mechanistically, GSDMD increased Ang II-induced GATA binding protein 2 (GATA2) transcription factor expression (<i>P</i> < 0.01). GATA2 also bound to the aquaporin 4 (<i>Aqp4</i>) promoter sequence and facilitated <i>Aqp4</i> transcription (<i>P</i> < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II-induced renal injury and fibrosis (<i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8241-8259"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622096","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":"Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.","authors":"Jie Ding, Fu-Ping Chen, Ya-Ying Song, Hong-Yan Li, Xi-Wen Ai, Yi Chen, Lu Han, Xia-Jun Zhou, De-Sheng Zhu, Yang-Tai Guan","doi":"10.2147/JIR.S489723","DOIUrl":"https://doi.org/10.2147/JIR.S489723","url":null,"abstract":"<p><strong>Background: </strong>The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients.</p><p><strong>Methods: </strong>We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184 hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot.</p><p><strong>Results: </strong>Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (<i>p</i><0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (<i>p</i>< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, <i>p</i><0.001), and 2.38 (1.48-3.83, <i>p</i><0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795 mmol/L with potential benefits to prevent relapse in NMOSD.</p><p><strong>Conclusion: </strong>In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8227-8240"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620583","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":"Study on the Anti-Atherosclerotic Mechanisms of Xin-Tong-Tai Granule Through Network Pharmacology, Molecular Docking, and Experimental Validation.","authors":"Junping Zhu, Ziyan Wang, Chengxin Liu, Min Shi, Zhihua Guo, Ya Li, Rong Yu, Jiaming Wei","doi":"10.2147/JIR.S490815","DOIUrl":"https://doi.org/10.2147/JIR.S490815","url":null,"abstract":"<p><strong>Background: </strong>Xin-Tong-Tai Granule (XTTG), a Chinese medicine (CM) formula, has demonstrated significant therapeutic effects on atherosclerosis (AS) in both clinical and experimental settings. Nonetheless, the mechanisms underlying XTTG's efficacy remain largely unexplored. This study aimed to elucidate the mechanisms through which XTTG acts against AS, employing network pharmacology, molecular docking, and experimental validation techniques.</p><p><strong>Methods: </strong>Initially, target identification for the main chemical components of XTTG was conducted using database, followed by determining the intersection targets between these compounds and disease. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were subsequently utilized to investigate the potential pathways through which XTTG exerts its effects on AS. Molecular docking was done to confirm the binding efficacy of XTTG's active components. Additionally, the effects of XTTG were evaluated in vitro using oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HAVSMCs) and in vivo in apolipoprotein E gene knockout (ApoE^-/-) mice fed a high-fat diet (HFD).</p><p><strong>Results: </strong>229 therapeutic targets were screened for PPI network and enrichment analysis. Notably, the nuclear factor kappa-B (NF-κB) signaling pathway, along with processes related to inflammation and autophagy, were significantly enriched, highlighting their importance. In vitro studies showed that XTTG repressed cell proliferation and lipid droplet aggregation in ox-LDL-induced HAVSMCs. It also decreased the ratio of phosphorylated NF-κB p65/ NF-κB p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, and elevated microtubule-associated protein light chain 3 (LC3) and decreased p62 protein expression. In vivo, XTTG ameliorated blood lipid profiles and aortic pathology in HFD-fed ApoE^-/- mice, reduced NF-κB p65 expression and serum levels of TNF-α and IL-6, increased the ratio of LC3II/LC3I while decreasing p62 protein expression.</p><p><strong>Conclusion: </strong>XTTG mitigates AS primarily through anti-inflammatory and autophagy-modulating mechanisms, particularly via inhibition of NF-κB p65 expression. These findings underscore the potential of CM in treating AS and support its further clinical exploration.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8147-8164"},"PeriodicalIF":4.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621206","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":"Successful Treatment of Pediatric Generalized Pustular Psoriasis (GPP) with Spesolimab: 5 Case Reports and Evaluations of Circulating IL-36 Levels.","authors":"Yunliu Chen, Zhaoyang Wang, Yuan Liang, Chunping Shen, Lei Jiao, Xin Xiang, Chaoyang Miao, Zigang Xu","doi":"10.2147/JIR.S485077","DOIUrl":"https://doi.org/10.2147/JIR.S485077","url":null,"abstract":"<p><strong>Background: </strong>Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce.</p><p><strong>Methods: </strong>We treated patients aged 4-12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology.</p><p><strong>Results: </strong>We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months-10 years and 5 months). After 1 week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week.</p><p><strong>Conclusion: </strong>Spesolimab might be a prospective option for children aged 4 to 12 years.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8199-8206"},"PeriodicalIF":4.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621208","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":"A Nomogram Incorporating Inflammation and Nutrition Indexes for Predicting Outcomes in Patients with Acute Coronary Syndrome and Chronic Kidney Disease.","authors":"Weicheng Ni, Zhen-Ze Pan, Hao Zhou","doi":"10.2147/JIR.S488674","DOIUrl":"https://doi.org/10.2147/JIR.S488674","url":null,"abstract":"<p><strong>Background: </strong>Inflammation, immunity, and nutriture are associated with prognosis in cardiovascular disease. We aimed to devise a novel nomogram model based on inflammation and nutrition indexes that accurately predicts Major adverse renal and cardiovascular events (MARCE) in patients diagnosed with acute coronary syndrome (ACS) and coexisting chronic kidney disease (CKD).</p><p><strong>Methods: </strong>We enrolled 685 individuals with ACS and CKD between January 2013 and August 2021. All patients were randomized into the training (70%) and validation (30%) cohorts. Univariable and multivariable Cox regression analyses were used to identify independent predictors for MARCE. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). The performance of the nomogram and GRACE score were compared.</p><p><strong>Results: </strong>The nomogram included six variables: age, left ventricular ejection fraction, systemic immune-inflammatory index (SII), controlling nutritional status (CONUT) score, use of beta-blockers, and use of statins. The constructed nomogram demonstrated robust predictive performance, achieving ROC ranging from 0.830 to 0.935 in the training set and 0.793 to 0.889 in the validation set, respectively. Furthermore, the calibration curves exhibited excellent agreement between the predicted probabilities and the observed outcomes, indicating the reliability of the nomogram's predictions. Finally, the DCA confirmed the clinical value of the nomogram by demonstrating its potential to improve decision-making processes in the context of managing the condition under study. Compared with the GRACE score, the nomogram was superior in terms of both discrimination and reclassification ability.</p><p><strong>Conclusion: </strong>Our novel nomogram, which incorporates the CONUT score and SII, shows promising utility for predicting MARCE in patients with ACS and CKD. The identification of patients at heightened risk through our nomogram model is paramount as it serves as a cornerstone for the implementation of targeted interventions aimed at modifiable variables.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8181-8198"},"PeriodicalIF":4.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622061","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":"RNA Sequencing Reveals That the Genes Related to Cell Cycle and Glycolysis Play an Essential Role in IL-27-Induced Keratinocyte Hyperproliferation.","authors":"Zijun Wu, Ruijing Wang, Yuanjun Liu, Bin Yang, Huiping Wang","doi":"10.2147/JIR.S481835","DOIUrl":"https://doi.org/10.2147/JIR.S481835","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis.</p><p><strong>Methods: </strong>The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein-protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively.</p><p><strong>Results: </strong>We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in \"Mitotic sister chromatid segregation\" and \"Spindle\". Cluster 2 was mainly enriched in the \"Pyruvate metabolic process\" and \"Oxidoreductase complex\". KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in \"Cell cycle\" and \"Glycolysis/Gluconeogenesis\", respectively. We then identified 6 hub genes enriched in the two pathways, including <i>CCNB1, PTTG1, CDC20, PLK1, PKM</i>, and <i>LDHA</i>. GSEA complemented the role of the mitochondrial \"Oxidative phosphorylation\" pathway. Moreover, we found that 6 hub genes were upregulated in psoriasis skin lesions and IL-27 elevated the hub genes expression in M5-induced psoriasiform keratinocytes.</p><p><strong>Conclusion: </strong>IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified <i>CCNB1, PTTG1, CDC20, PLK1, PKM</i>, and <i>LDHA</i> as hub genes that may be involved in the mechanism of IL-27 facilitating keratinocyte proliferation in psoriasis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8165-8180"},"PeriodicalIF":4.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622084","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":"ZLN005 Reduces Neuroinflammation and Improves Mitochondrial Function in Mice with Perioperative Neurocognitive Disorders.","authors":"Xiaofan Wu, Sheng Ding, Guizhi Wang, Wei Zhang, Keqiang He","doi":"10.2147/JIR.S482051","DOIUrl":"https://doi.org/10.2147/JIR.S482051","url":null,"abstract":"<p><strong>Background: </strong>The decrease expression of PGC-1α contributes to perioperative neurocognitive disorders (PND). This study aimed to investigate the effects of the PGC-1α agonist ZLN005 in preventing PND and to explore the potential mechanism.</p><p><strong>Methods: </strong>C57BL/6 mice were randomly divided into four groups: the control group (Group C), the surgery group (Group S), the surgery and ZLN005 (5 mg/(kg⋅d)) group (Group L), and the surgery and ZLN005 (7.5 mg/(kg⋅d)) group (Group H). Except for Group C, the other three groups received intraperitoneal injections of vehicle or ZLN005 once a day from 3 days before surgery to 3 days after surgery. The open field test, novel object recognition test and fear conditioning test were performed to measure anxiety behaviors, locomotor activity and memory. The levels of IL-6 and IL-1β were measured at 24 hours after surgery. ATP and ROS levels were measured at 3 days post-surgery. PGC-1α, NRF-1, Atp5d, Atp5k and Cox5a were measured at one day or three days post-surgery.</p><p><strong>Results: </strong>ZLN005 treatment improved the cognitive function of mice in Group L and Group H compared with Group S. The expression of IL-6 and IL-1β in the hippocampus of the S group was increased after surgery, and ZLN005 reduced the expression of IL-6 and IL-1β in the hippocampus of mice one day after surgery. There were parallel decreases in the expression of PGC-1α/NRF-1 and mitochondrial function in the hippocampus of the Group S mice compared with the Group C mice. The expression of PGC-1α/NRF-1 and mitochondrial function were upregulated after ZLN005 treatment.</p><p><strong>Conclusion: </strong>Neuroinflammation and mitochondrial damage are involved in the occurrence of PND. ZLN005 activates PGC-1α to increase the expression of mitochondrial proteins, improve mitochondrial function, and ultimately ameliorate the cognitive status of mice after surgery.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8135-8146"},"PeriodicalIF":4.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621854","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}