Journal of Inflammation Research最新文献

{"title":"Osteoimmunology in Osteoarthritis: Unraveling the Interplay of Immunity, Inflammation, and Joint Degeneration.","authors":"Kangyi Hu, Min Song, Ting Song, Xiao Jia, Yongjia Song","doi":"10.2147/JIR.S514002","DOIUrl":"10.2147/JIR.S514002","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a degenerative joint disease influenced by multiple factors, with its etiology arising from intricate interactions among mechanical stress, inflammatory processes, and disruptions in bone metabolism. Recent research in bone immunology indicates that immune-mediated mechanisms significantly contribute to the progression of OA, highlighting the interactions among immune cells, cytokine networks, and bone components. Immune cells interact with osteoclasts, osteoblasts, and chondrocytes in a variety of ways. These interactions foster a pro-inflammatory microenvironment, contributing to cartilage breakdown, synovial inflammation, and the sclerosis of subchondral bone. In this article, we present a comprehensive review of bone immunology in OA, focusing on the critical role of immune cells and their cytokine-mediated feedback loops in the pathophysiology of OA. In addition, we are exploring novel therapeutic strategies targeting bone immune pathways, including macrophage polarization, T-cell differentiation, and stem cell therapy to restore the metabolic balance between immunity and bone. By integrating cutting-edge research in bone immunology, this review integrates the latest advancements in bone immunology to construct a comprehensive framework for unraveling the pathogenesis of OA, laying a theoretical foundation for the development of innovative precision therapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4121-4142"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692570","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":"Combining Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation to Uncover the Efficacy and Mechanisms of Si-Miao-Yong-An Decoction in Diabetic Wound Healing.","authors":"Shujuan Zhang, Yiming Shao, Ranran Jin, Baodong Ma","doi":"10.2147/JIR.S506739","DOIUrl":"10.2147/JIR.S506739","url":null,"abstract":"<p><strong>Purpose: </strong>Si-Miao-Yong-An (SMYA) Decoction, a traditional Chinese herbal mixture, shows promise for managing diabetic complications. Up to this point, no reports have explored the effects of SMYA on diabetic wounds or the underlying mechanisms. This study aimed to investigate the therapeutic potential of SMYA in promoting diabetic wound healing and to elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The wound healing effects of SMYA were evaluated in db/db diabetic mice by measuring wound closure rates and histological characteristics, including epidermal thickness and collagen deposition. Network pharmacology was utilized to identify active ingredients and corresponding therapeutic targets of SMYA, followed by validation through molecular docking and molecular dynamics simulations. KEGG and GO enrichment analyses were conducted to elucidate the relevant biological processes and pathways. In vitro studies involving high-glucose-treated HUVECs assessed the effects of SMYA-containing serum on cellular migration and angiogenesis. Finally, the expression of inflammatory factors and RAGE in the wound tissue was detected by qRT-PCR.</p><p><strong>Results: </strong>SMYA significantly accelerated wound closure in db/db mice, as evidenced by improved epidermal thickness, tissue morphology, and collagen deposition. Network pharmacology identified 140 overlapping genes involved in angiogenesis and inflammation, with the AGE-RAGE signaling pathway playing a central role. Molecular docking and dynamics simulations revealed strong binding stability of quercetin and kaempferol to inflammation-related hub targets, including IL-6, TNF, and IL-1β. In vitro, SMYA-containing serum alleviated high-glucose-induced impairments in HUVEC migration and angiogenesis. Furthermore, qRT-PCR analysis showed that SMYA significantly downregulated Tnf, Il1b, Il6, and Rage expression in wound tissues, supporting its anti-inflammatory effect.</p><p><strong>Conclusion: </strong>SMYA promotes diabetic wound healing by modulating the inflammatory microenvironment and inhibiting the AGE-RAGE signaling pathway. These findings provide robust evidence for SMYA's therapeutic potential and lay a foundation for its future clinical application in treating diabetic wounds.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4087-4101"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700510","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":"DNA-PKcs Dysfunction Enhances the Antitumor Activity of Radioimmunotherapy by Activating the cGAS-STING Pathway in HNSCC.","authors":"Lizhu Chen, Jing Lin, Yaoming Wen, Zeng-Qing Guo, Bin Lan, Jiani Xiong, Chuan-Ben Chen, Yu Chen","doi":"10.2147/JIR.S497295","DOIUrl":"10.2147/JIR.S497295","url":null,"abstract":"<p><strong>Introduction: </strong>Combining radiotherapy (RT) with immunotherapy for head and neck squamous cell carcinoma (HNSCC) has limited effectiveness due to the DNA damage repair (DDR) pathway activated by ionizing radiation. DNA-PK, encoded by the <i>PRKDC</i> gene, plays a key role in this repair. The potential improvement of radioimmunotherapy by inhibiting the DDR pathway is still unclear.</p><p><strong>Methods: </strong>The effectiveness of different treatments on tumor growth and survival was tested using the C3H/HeN mouse tumor model. Flow cytometry analyzed treatment-induced immunophenotypic changes. In vitro, Western blot and PCR confirmed the impact of combining immunotherapy with RT on the cGAS-STING pathway after DNA-PKcs dysfunction.</p><p><strong>Results: </strong>The combination of a DNA-PK inhibitor (NU7441), radiation therapy, and a PD-1 checkpoint inhibitor showed improved antitumor effects and extended survival in mice. Adding NU7441 into the RT and immunotherapy regimen increased CD8+ T cell infiltration. <i>PRKDC</i> alterations or DNA-PKcs dysfunction increased IR-induced DNA breaks, activating the cGAS-STING pathway and boosting the anti-tumor immune response.</p><p><strong>Conclusion: </strong>These findings suggest that targeting the DDR pathway may represent a promising therapeutic strategy and biomarker to improve the efficacy of radioimmunotherapy in HNSCC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4177-4193"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700515","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":"Cordyceps Sinensis Reduces Inflammation and Protects BEAS-2B Cells From LPS-Induced THP-1 Cell Injury.","authors":"Xiaqing Wu, Xin Li, Ying Chai, Yushan Tian, Hongjuan Wang, Xiao Li, Jingzheng Zhang, Chunmei Guang, Enliang Hong, Haoping Cheng, Qingyuan Hu, Huan Chen, Hongwei Hou","doi":"10.2147/JIR.S508098","DOIUrl":"10.2147/JIR.S508098","url":null,"abstract":"<p><strong>Introduction: </strong>Cordyceps sinensis, an entomogenous fungus with unique biological properties, has demonstrated significant anti-inflammatory potential. However, its effects on inflammation regulation need to be further investigated in detail.</p><p><strong>Methods: </strong>In this study, we aimed to analyze the Cordyceps sinensis extract (CSE) obtained via ethanol extraction and to assess its effects on inflammation regulation. The secretion of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β) and the level of MMP9, Nrf2/HO-1 and ROS were evaluated. A transwell system with THP-1 and BEAS-2B cells was used to explore the inflammatory damage. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted on the differentially expressed genes.</p><p><strong>Results: </strong>CSE exhibited no cytotoxicity to THP-1 cells at concentrations ≤ 1.6 mg/mL. Treatment of LPS-induced THP-1 cells with CSE significantly inhibited the secretion of pro-inflammatory cytokines. CSE reduced inflammation-related protein MMP9, while upregulating the anti-inflammatory Nrf2/HO-1 signaling pathway. Fluorescence assays using DCF and JC-1 further confirmed that CSE help mitigate oxidative stress-induced inflammation. CSE treatment protected BEAS-2B cells from inflammatory damage. Moreover, the immune system process was a shared GO term between LPS-only treatment and combined LPS and CSE treatment. KEGG enrichment analysis showed that CSE is capable of regulating genes associated with inflammatory and anti-inflammatory responses.</p><p><strong>Conclusion: </strong>These findings highlight the potential of CSE as an immune-regulating agent in functional foods and health products.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4143-4156"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692532","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":"Causal Correlations Between Plasma Metabolites, Inflammatory Proteins, and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization and Bioinformatics-Based Investigation.","authors":"Shurui Cao, Yongqi Gu, Guye Lu, Lizhen Zhu, Shumin Feng, Tao Bian","doi":"10.2147/JIR.S513526","DOIUrl":"10.2147/JIR.S513526","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of studies have demonstrated a strong correlation between metabolism, inflammation, and chronic obstructive pulmonary disease (COPD). However, it remains unclear if there is a causal relationship between these factors. This study employed the Mendelian randomization (MR) approach to investigate the associations between these factors and explore the mediating roles of key inflammatory proteins.</p><p><strong>Methods: </strong>MR was used to assess the causal associations between plasma metabolites, inflammatory proteins, and COPD. Sensitivity analyses were performed to verify the robustness of the findings. Mediation analysis was conducted to explore the roles of inflammatory proteins in the metabolism-COPD pathway. We constructed protein-protein interaction (PPI) network and explored the potential mechanism through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Single-cell sequencing and transcriptome datasets were used for auxiliary validation. Finally, experimental validation was performed using human lung tissue.</p><p><strong>Results: </strong>This study identified 63 metabolites, 10 metabolite ratios, and 48 inflammatory proteins that were associated with COPD, all of which exhibited potential causal relationships. Furthermore, three proteins were identified as mediators in the metabolite-to-COPD pathway. PPI network, GO and KEGG enrichment analysis revealed the biological pathways in which they were involved. Validation of the expression of these three intermediary proteins in lung tissue demonstrated that NRXN3 was expressed in pulmonary endothelial cells and exerted a protective effect against COPD development.</p><p><strong>Conclusion: </strong>The MR analysis revealed causal associations among metabolism, inflammation, and COPD. These findings offer novel insights into metabolism-inflammation-COPD mechanisms, suggesting that interventions targeting metabolic processes may represent a promising strategy for preventing the onset or progression of COPD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4057-4073"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692531","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":"Delirium is a Potential Predictor of Unfavorable Long-term Functional Outcomes in Patients with Acute Ischemic Stroke: A Prospective Observational Study.","authors":"Chenhui Lin, Heyu Zhang, Fangyi Xiao, Yujie Tu, Yaoyao Lin, Luqian Zhan, Yisi Lin, Yanwei Li, Chenglong Xie, Yanyan Chen","doi":"10.2147/JIR.S505038","DOIUrl":"10.2147/JIR.S505038","url":null,"abstract":"<p><strong>Purpose: </strong>Delirium is an acute fluctuating impairment of attention and awareness, common in acute ischemic stroke (AIS). This study aimed to evaluate the prognostic significance of delirium for neurological function at 3 months post-stroke, and develop a predictive model integrating delirium and biomarkers to enhance prognostic accuracy.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of patients admitted to the stroke unit (n=722). All patients were screened for daily delirium during clinical care. Plasma biomarkers were measured within 24 hours after admission. The main outcomes were evaluated with the 3-months modified Rankin Scale (mRS).</p><p><strong>Results: </strong>Delirium developed in 10.2% of patients during the acute phase of stroke. Patients with post-stroke delirium (PSD) was significantly older (median age 74 vs 68 years, <i>P</i><0.001), more likely to have pre-stroke cognitive impairment (14.9% vs 4.8%, <i>P</i>=0.001), a higher prevalence of cardiovascular history (35.1% vs 16.2%, <i>P</i><0.001). PSD was also associated with higher scores of NIHSS (14.3 vs 9.1, <i>P</i><0.001) and greater scores of mRS (3.0 vs 1.5, <i>P</i><0.001) at admission. PSD patients showed worse outcomes, with elevated NIHSS and mRS scores at discharge and 3-month follow-up, as well as higher mortality rates (5.4% vs 1.4%, <i>P</i>=0.025). Biomarker analysis revealed increased plasma levels of inflammatory (white blood cells, neutrophils, C-reactive protein) and coagulation biomarkers (fibrinogen, D-dimer) in PSD patients, particularly those with poorer outcomes (<i>P</i><0.01). Our model, which incorporated delirium and biomarkers of inflammation and coagulation dysfunction, demonstrated strong predictive accuracy for adverse outcomes at 3 months with an AUC of 0.779 (95% CI=0.736-0.822), with clinical utility confirmed by decision curve analysis.</p><p><strong>Conclusion: </strong>PSD is a strong independent predictor of poor 3-month outcomes in AIS, including higher mortality and disability. Our findings highlight the critical role of inflammation and coagulation dysfunction in the pathogenesis of PSD. Furthermore, we present the clinical utility of a predictive model integrating delirium and relevant biomarkers to assess the risk of adverse outcomes at 3 months, suggesting potential targets for intervention.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4019-4035"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692479","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":"Distinct Immunological Features Compared to Lichen Planus and Oral Lichen Planus.","authors":"Dong Min Lim, DoYeon Kim, Hye-Min Ju, Sung-Hee Jeong, Yun Hak Kim, Soo-Min Ok, Hae Ryoun Park","doi":"10.2147/JIR.S506313","DOIUrl":"10.2147/JIR.S506313","url":null,"abstract":"<p><strong>Purpose: </strong>Lichen planus (LP) and oral lichen planus (OLP) share clinical and histological similarities, yet their distinct immunopathological mechanisms make differentiation and management challenging. Clarifying these differences is essential for accurate diagnosis and treatment. This study aimed to investigate the systemic immune profile of OLP using single-cell transcriptomics, identifying distinct immune cell subsets and signaling pathways contributing to its chronic inflammatory state. Additionally, it sought to compare the inflammatory lesion microenvironments of OLP and LP by analyzing key immune pathways and cellular interactions.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) were obtained from 16 OLP patients and 5 healthy controls. Single-cell transcriptomic data from PBMCs and lesion tissues of OLP and LP were analyzed to profile immune and inflammatory signatures. Key molecular findings were validated using independent datasets and enzyme-linked immunosorbent assays (ELISA).</p><p><strong>Results: </strong>Prostaglandin D2 synthase (<i>PTGDS</i>), a pivotal enzyme in prostaglandin metabolism, emerged as a diagnostic marker with elevated expression in NK cells from OLP patients. Additionally, a novel <i>CXCR4</i> ^high-<i>TSC22D3</i> ^high CD4 cytotoxic T cell subset with enhanced cytotoxicity was identified, potentially contributing to OLP pathogenesis. OLP blood samples also demonstrated significant upregulation of TNF and TLR signaling in NK cells, indicating a heightened chronic inflammatory state. Comparative tissue analysis revealed intensified TNF-driven inflammation and a disrupted <i>HIF1A</i>- vascular endothelial growth factor (VEGF) interactions in OLP, contrasting with LP's robust VEGF-mediated angiogenesis.</p><p><strong>Discussion: </strong>These findings highlight distinct immunopathogenic mechanisms between OLP and LP. The upregulation of <i>PTGDS</i> in NK cells and <i>CXCR4</i> ^high-<i>TSC22D3</i> ^high CD4 cytotoxic T cells in PBMCs indicates systemic immune dysregulation in OLP, while tissue-level differences suggest impaired vascular remodeling and chronic inflammation. These insights underscore the need for targeted immunomodulatory therapies.</p><p><strong>Conclusion: </strong>This study identifies distinct immune signatures that differentiate OLP from LP, highlighting potential therapeutic targets that require further validation for personalized treatment strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4037-4056"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692455","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":"Astragaloside IV Attenuates Angiotensin II-Induced Inflammatory Responses in Endothelial Cells: Involvement of Mitochondria.","authors":"Shiyu Zhang, Shijie Li, Lin Cui, Shiyang Xie, Youping Wang","doi":"10.2147/JIR.S504427","DOIUrl":"10.2147/JIR.S504427","url":null,"abstract":"<p><strong>Background: </strong>Angiotensin II (Ang II)-triggered endothelial inflammation is a critical mechanism contributing to Ang II-related cardiovascular diseases. The inflammation is highly correlated with mitochondrial function. Although astragaloside IV (AS-IV), a primary bioactive ingredient extracted from the traditional Chinese medicine <i>Astragalus membranaceus</i> Bunge that can effectively treat numerous cardiovascular diseases, posses the actions of antiinflammation and antioxidation in vivo, limited data are made available on the impacts of AS-IV on mitochondrial function in endothelial inflammation triggered by Ang II. This study was performed to evaluate the in vitro actions of AS-IV on Ang II-triggered inflammatory responses in endothelial cells, and to further clarify the potential role of mitochondria in the actions.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were preincubated with AS-IV and then exposed to Ang II for 12 h.</p><p><strong>Results: </strong>The exposure of HUVECs to Ang II triggered cytokine and chemokine production, the upregulation of adhesive molecules, monocyte attachment, and nuclear factor-kappa B activation. Additionally, our results showed that the inflammatory responses triggered by Ang II were associated with the impairment of mitochondrial function, as evidenced by the reductions of mitochondrial membrane potential, ATP synthesis, and mitochondrial complexes I and III activities. Moreover, the concentrations of malondialdehyde, cellular reactive oxygen species, and mitochondrial superoxide enhanced after HUVECs challenged with Ang II, which were concurrent with the decreases in total superoxide dismutase (SOD) and its isoenzyme activities such as Mn-SOD. These Ang II-induced alterations were reversed by preincubation with AS-IV.</p><p><strong>Conclusion: </strong>Our data indicate that AS-IV attenuates Ang II-triggered endothelial inflammation possibly via ameliorating mitochondrial function.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3951-3967"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692518","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":"Elucidating Molecule-Crosstalk of Neutrophil Extracellular Traps Between Cardiovascular Disease and Psoriasis: Insights Into Mendelian Randomization, Single-Cell RNA Analysis, Shared Targets and the Role of Resveratrol.","authors":"Xiaojun Jin, Yun Zhang, Gaofeng Qin, Xinyan Fang, Xinnan Zhang, Jialin Sun, Min Zhou, Xuecheng Tong, Yuan Xue, Hui Yang, Weihong Tian","doi":"10.2147/JIR.S493416","DOIUrl":"10.2147/JIR.S493416","url":null,"abstract":"<p><strong>Background: </strong>Left ventricular hypertrophy (LVH) associated with hypertension and psoriasis (PSO) are linked by poor prognosis. Neutrophil extracellular traps (NETs) are implicated in both conditions, but the mechanisms remain unclear.</p><p><strong>Methods: </strong>We integrated bulk and single-cell RNA sequencing, mendelian randomization, immune microenvironment analysis, and molecular docking to explore the molecular interactions between LVH and PSO, focusing on NET-related pathways. Prediction models were also developed, and gene function was validated through in vivo and in vitro experiments.</p><p><strong>Results: </strong>Our findings identified NETs-associated genes, AKT serine/threonine kinase 1 (<i>AKT1</i>), and receptor-interacting protein kinase 1 (<i>RIPK1</i>), regulating inflammation, fibroblast activation, and apoptosis in LVH and PSO. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive inflammation as the most prominent shared features of LVH and PSO diseases. Additionally, resveratrol exhibited a high binding affinity to the AKT1 and RIPK1 proteins. Functional validation showed that knockdown of AKT1 reduced LVH cell hypertrophy and PSO cell apoptosis.</p><p><strong>Conclusion: </strong>This study highlights molecular pathways linking LVH and PSO, suggesting novel targets for treating cardiac involvement in PSO patients with LVH.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3913-3935"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692581","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":"Zhike Erfang Alleviates MRSA-Induced Pneumonia by Inhibiting TRAF6 and Activating NLRP3 Inflammatory Body.","authors":"Lian-Qing Zhang, Wen-Can Zheng, Wen-Yan Li","doi":"10.2147/JIR.S466737","DOIUrl":"10.2147/JIR.S466737","url":null,"abstract":"<p><strong>Purpose: </strong>The therapeutic effects of Zhike Erfang in modulating the cellular responses and immune microenvironment associated with MRSA-induced acute lung injury remain unclear. This study aims to elucidate the potential mechanisms by which Zhike Erfang mitigate the cellular and molecular effects of MRSA in a laboratory model.</p><p><strong>Patients and methods: </strong>A mouse model of acute lung injury was established using heat-inactivated MRSA. Lung tissue and bronchoalveolar lavage fluid were collected for analysis. Macrophages were pretreated with Zhike Erfang for 30 minutes before exposure to heat-inactivated MRSA for 24 hours. Protein expressions of TRAF6, iNOS, TNF-α, IL-1β, NLRP3, and caspase-1 in lung tissues were quantified using Western blot. The content of LDH was detected by the lactate dehydrogenase cytotoxicity test kit.</p><p><strong>Results: </strong>Zhike Erfang significantly reduced the expression of iNOS, LDH, TNF-α, IL-1β, NLRP3, and caspase-1 in a dose-dependent manner in lung tissues from the MRSA model. Zhike Erfang inhibited the expression of TRAF6.</p><p><strong>Conclusion: </strong>Zhike Erfang can alleviate pneumonia caused by MRSA by inhibiting TRAF6 and inducing NLRP3 inflammatory body activation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3901-3911"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692647","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}