Journal of Inflammation Research最新文献

{"title":"Comprehensive Bioinformatics Analyses and Experimental Validation of the Cell Cycle Related Protein SAPCD2 as a New Biomarker and Potential Therapeutic Target in Pancreatic Cancer.","authors":"Yuting Liu, Bo Li, Lingling Ke, Tingting Luo, Huixian Wu, Jiahui Lin, Yu Deng, Xiuji Huang, Liangliang Xu, Yuchen Liu, Jian Qi","doi":"10.2147/JIR.S501850","DOIUrl":"10.2147/JIR.S501850","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with a poor prognosis, reliable markers are urgently needed for early detection and prognosis evaluation. <i>SAPCD2</i>, a cell cycle related gene, has been implicated in tumorigenesis and proposed as a potential therapeutic target in cancer. However, no comprehensive study has explored its expression and regulation, discussed its role in tumor prognosis and immune modulation, along with therapy response in pan-cancer until now.</p><p><strong>Methods: </strong>SAPCD2 expression was analyzed using data from The Cancer Genome Atlas database (TCGA) and Human Protein Atlas (HPA) database. Genetic and epigenetic alterations of <i>SAPCD2</i> and the immune microenvironment were explored via NCBI, TIMER2 and cBioPortal platforms. Western blot analysis and immunohistochemistry (IHC) were performed to check SAPCD2 protein expression in PAAD cells and tissues. Cell counting kit 8 (CCK8), flow cytometry, and transwell experiments were used to evaluate the role of SAPCD2 in PAAD cell lines.</p><p><strong>Results: </strong>Our study found that SAPCD2 is notably upregulated in various cancers, especially early-stage digestive cancers, and is linked to poor survival in most cancers like PAAD and LIHC. Gene amplification and promoter DNA hypomethylation appear to drive this upregulation. Additionally, SAPCD2 expression correlates with tumor mutation burden, microsatellite instability, and immune scores across several cancers. In PAAD, elevated SAPCD2 levels correlated with reduced immune activity, whereas in stomach cancer (STAD), its prognostic impact appeared immune-independent. In PDAC cell lines, SAPCD2 knockdown reduced proliferation and invasion, and caused reduction of G0/G1 phase. PAAD cells with high SAPCD2 expression showed increased sensitivity to DNA-PK, p38α MAPK, and Bcl-2 inhibitors.</p><p><strong>Conclusion: </strong>SAPCD2 serves as both a prognostic marker and a potential therapeutic target in PAAD, where its low expression may enhance responsiveness to specific drugs. These findings underscore SAPCD2's dual role in cancer progression and therapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2855-2877"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immune Modulatory Role of Surfactants in <i>Mycoplasma pneumoniae</i> Infection.","authors":"Xinru Li, Qianrui Zeng, Chang Liu, Xinchao Yi, Haodang Luo, Qin Tong, Hongliang Chen, Xiaoxing You","doi":"10.2147/JIR.S507526","DOIUrl":"10.2147/JIR.S507526","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i> is a prevalent respiratory microbe that causes acute inflammation in the respiratory system. Surfactant proteins (SP), particularly SP-A and SP-D, are essential for the immunological protection against <i>M. pneumoniae</i> infection. Variant SP-A2 may lead to immune reactions, which could account for the variability in clinical manifestations among individuals. Mechanistically, these surfactant proteins may act as candidate receptors, facilitating both the adhesion of <i>M. pneumoniae</i> and internalization of community-acquired respiratory distress syndrome toxin. They also exhibit a high affinity for lipid ligands on the surface of <i>M. pneumoniae</i> membranes via their carbohydrate recognition domains, which aid in the direct clearing of the bacteria. In addition, SP-A and SP-D demonstrated synergistic effects in augmenting the intake and elimination of <i>M. pneumoniae</i> by alveolar macrophages. Furthermore, these surfactant proteins negatively regulate pulmonary inflammation by influencing lymphocyte and dendritic cell activities, reducing airway eosinophilic infiltration, and managing asthma-related inflammatory responses. A thorough understanding of the immunomodulatory roles of surfactant proteins in <i>M. pneumoniae</i> infection will shed light on how homeostasis is preserved during mycoplasma pneumonia and may guide the development of novel therapeutic strategies against this organism.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2909-2922"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542268","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":"Single-Cell Sequencing and Transcriptome Analysis Explored Changes in Midnolin-Related Immune Microenvironment and Constructed Combined Prognostic Model for Pancreatic Cancer.","authors":"Xiao Guan, Lei Xu, Jinsong Liu, He Fei, Chengfeng Wang","doi":"10.2147/JIR.S503326","DOIUrl":"https://doi.org/10.2147/JIR.S503326","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer has one of the worst prognoses of any malignant tumor. The value of MIDN, midnolin-related genes and midnolin-related immune infiltrating cells (MICs) in the prognosis of pancreatic cancer remains unknown.</p><p><strong>Methods: </strong>Single-cell analysis were used to identify midnolin-related genes. Immune cell infiltration was obtained using CIBERSORT. The prognostic midnolin-related genes were identified through the utilization of Cox regression and the least absolute selection operator (LASSO) approach. The combined prognostic model was created using multifactorial Cox regression analysis. Survival analyses, immune microenvironment assessments, drug sensitivity checks were performed to evaluate the combined model performance. Finally, cellular experiments were carried out to confirm MIDN significance in pancreatic cancer.</p><p><strong>Results: </strong>The combined model was constructed based on MIDN expression, prognostic model of 10 midnolin-related genes and M1 cell infiltration. Most immune checkpoint-related genes were expressed at greater levels in the low-risk group, suggesting a greater chance of immunotherapy's benefits. The most significant model gene, MIDN, was shown to have a function by cellular tests. In pancreatic cancer, MIDN knockdown drastically decreased pancreatic cancer cell lines' activity, proliferation, and invasive potential.</p><p><strong>Conclusion: </strong>The combined model helped assess the prognosis of pancreatic cancer and offered fresh perspectives on immunotherapy in particular.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2975-2990"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542266","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":"Reflections on the Clinical Application and Optimization of the Pneumonia Risk Prediction Model Following Intracerebral Hemorrhage [Letter].","authors":"Hongjian Li, Jiayin Wang","doi":"10.2147/JIR.S522264","DOIUrl":"https://doi.org/10.2147/JIR.S522264","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2923-2924"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542261","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":"Microglial Mechanisms and Therapeutic Potential in Brain Injury Post-Intracerebral Hemorrhage.","authors":"Yuhua Gong, Hui Li, Huanglin Cui, Yuping Gong","doi":"10.2147/JIR.S498809","DOIUrl":"https://doi.org/10.2147/JIR.S498809","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a particularly common public health problem with a high mortality and disability rate and no effective treatments to enhance clinical prognosis. The increased aging population, improved vascular prevention, and augmented use of antithrombotic agents have collectively contributed to the rise in ICH incidence over the past few decades. The exploration and understanding of mechanisms and intervention strategies has great practical significance for expanding treatments and improving prognosis of ICH. Microglia, as resident macrophages of central nervous system, are responsible for the first immune defense post-ICH. After ICH, M1 microglia is firstly activated by primary injury and thrombin; subsequently, reactive microglia can further amplify the immune response and exert secondary injury (eg, oxidative stress, neuronal damage, and brain edema). The pro-inflammatory phenotype transmits to M2 microglia within 7 days post-ICH, which plays a key role in erythrophagocytosis and limiting the inflammatory secondary injury. Microglial M2 polarization has significant implications for improving prognosis, this process can be mediated through crosstalk with other cells, metabolic changes, and microbiota interaction. Clarifying the effect, timing, and potential downstream effects of multiple mechanisms that synergistically trigger anti-inflammatory responses may be necessary for clinical translation. Analyses of such intricate interaction between microglia cells and brain injury/repair mechanisms will contribute to our understanding of the critical microglial responses to microenvironment and facilitating the discovery of appropriate intervention strategies. Here, we present a comprehensive overview of the latest evidences on microglial dynamics following ICH, their role in driving primary/secondary injury mechanisms as well as neurorepair/plasticity, and possible treatment strategies targeting microglia.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2955-2973"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542259","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":"Advanced Combination Therapy with Biologics and Upadacitinib in Refractory Inflammatory Bowel Disease: A Retrospective Study from Taiwan.","authors":"Ming-Jung Meng, Chia-Jung Kuo, Ming-Wei Lai, Cheng-Tang Chiu, Ming-Yao Su, Ming-Ling Chang, Puo-Hsien Le","doi":"10.2147/JIR.S511309","DOIUrl":"https://doi.org/10.2147/JIR.S511309","url":null,"abstract":"<p><strong>Background: </strong>Refractory inflammatory bowel disease (IBD) remains challenging despite the availability of various biologics. Advanced combination therapy (ACT) with biologics and Upadacitinib (UPA), a rapid-onset oral selective Janus kinase inhibitor, has shown promise in managing refractory IBD. However, its use in Asia has not been explored. This study aims to fill that gap by providing data from Taiwan.</p><p><strong>Materials and methods: </strong>This retrospective study included refractory IBD patients who received ACT with biologics and UPA, followed up at the Chang Gung Inflammatory Bowel Disease Center from July 2020 to August 2024. Patients were assessed for clinical response and remission at weeks 4, 12, and 24. Safety profiles were monitored throughout the follow-up period to evaluate the risk of adverse events.</p><p><strong>Results: </strong>Sixteen refractory IBD patients were enrolled. The median disease duration was 4.5 years [IQR 2.25-9.50]. The most common regimen was Ustekinumab plus UPA (63%). Clinical response rates at weeks 4, 12, and 24 were 88%, 83%, and 100%, respectively, while remission rates were 31%, 50%, and 80%. One patient (6.25%) experienced a minor adverse event (acne), with no major events like herpes zoster reactivation or major cardiac complications.</p><p><strong>Conclusion: </strong>This is the first study in Asia to demonstrate that UPA-based ACT is both effective and safe in treating refractory IBD. However, the limitations of this retrospective, single-center study with a relatively small sample size highlight the need for future larger-scale, multi-center prospective studies to confirm these findings, identify predictors of treatment response, and evaluate long-term outcomes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2733-2742"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542241","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":"Inflammation-Induced Nitric Oxide Synthase May Mediate the Acute Hypotensive Effect of ST36 Stimulation.","authors":"Qiu-Lian Lei, Xing Yue, Xiao-Xiang Sun, Li-Juan Zhu, Shuqing Liu, Hao Hong, Zili Tang, Xin Cao","doi":"10.2147/JIR.S494037","DOIUrl":"10.2147/JIR.S494037","url":null,"abstract":"<p><strong>Purpose: </strong>Acupoint Zusanli (ST36) has been shown to reduce blood pressure, but the underlying mechanism remains unknown. This study aimed to characterize the effects of manual acupuncture (MA) at ST36 on BP and its associated mechanisms in anesthetized rats.</p><p><strong>Methods: </strong>The cardiovascular response to MA at ST36 in Sprague-Dawley rats was measured by electrocardiogram, hemodynamic methods, heart rate variability, echocardiography, laser speckle contrast imaging, and Western blotting. RNA sequencing was employed for mechanistic investigation, and validation was performed through blood enzyme-linked immunosorbent assay and pharmacologic inhibition.</p><p><strong>Results: </strong>Stimulation of ST36 increased peripheral blood flow while decreasing the velocity time integral of the femoral artery and cardiac stroke volume. This stimulation induced transient hypotension, accompanied by a decreased heart rate and reduced cardiac contractility, thereby exerting negative chronotropic and inotropic effects on the heart. Furthermore, the increased low-/high-frequency ratio after ST36 stimulation, along with the upregulation of phosphorylated tyrosine hydroxylase, indicated sympathetic activation. RNA sequencing at the local acupoint revealed enrichment of inflammation-related pathways following ST36 stimulation, which was corroborated by elevated tumor necrosis factor-alpha (TNF-α) levels in the serum. Notably, the nitric oxide synthase (NOS) inhibitor L-NG-Nitro arginine methyl ester (L-NAME) effectively suppressed the induced hypotension.</p><p><strong>Conclusion: </strong>These results indicated that MA at ST36 induced inflammation, which activated NOS and resulted in the release of nitric oxide. This led to the vasodilation of peripheral vessels and transient hypotension.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2717-2731"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567394","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":"Exercise and Berberine Intervention Ameliorate High-Fat Diet-Induced MAFLD by Regulating Gut Microbiota and Hepatic Fatty Acid Beta-Oxidation.","authors":"Xiaojian Zhang, Yanbin Cheng, Qingyu Wei, Lixuan Sang, Quansheng Li","doi":"10.2147/JIR.S498782","DOIUrl":"10.2147/JIR.S498782","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global concern. The gut microbiota and hepatic fatty acid beta-oxidation have been shown to be important factors in the development of MAFLD. Independently, exercise and berberine can significantly ameliorate symptoms of MAFLD, although the specific mechanism is not clear; moreover, it is not known whether the combination of exercise and berberine produces a better therapeutic effect.</p><p><strong>Methods: </strong>Over an experimental period of 17 weeks, the effects of exercise, berberine, and a combined (exercise/berberine) intervention on the composition of the gut microbiota and the expression of hepatic fatty acid beta-oxidation related proteins were examined. The mice were divided into five treatment groups: CON (control group, n = 10), HFD (high-fat diet, n = 10), HFE (high-fat diet + exercise, n = 10), HFB (high-fat diet + berberine, n = 10), and HBE (high-fat-diet + exercise + berberine, n = 10). The dose of BBR administered for oral gavage was 300 mg/kg, once per day, for 8 weeks. Mice were subjected to treadmill exercise, 5 days per week for 8 weeks, and the intensity was increased gradually.</p><p><strong>Results: </strong>Serological and histopathological results showed that exercise, berberine and a combined (exercise/berberine) intervention effectively improved liver lipid accumulation caused by a high-fat diet. Analysis of 16S rRNA showed that the three interventions restored the species and number of gut microbiota in MAFLD mice. The functional prediction of gut microbiota revealed significant differences in beta-oxidation-related units among groups. Simultaneously, exercise and berberine intervention regulated the expression of hepatic fatty acid beta-oxidation-related proteins ACOX1, HMGCS2, and CPT-1α, with the combined intervention having a more significant effect than each intervention alone.</p><p><strong>Conclusion: </strong>Our findings indicate that exercise and berberine ameliorate MAFLD by regulating the gut microbiota and hepatic fatty acid beta-oxidation, suggesting that their combination may be a potential therapy for MALFD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2837-2854"},"PeriodicalIF":4.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567390","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":"Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Changes in Primary Angiitis of the Central Nervous System.","authors":"Ping Lu, Lingyun Cui, Lulin Zhang, Huabing Wang, Linlin Yin, Decai Tian, Xinghu Zhang","doi":"10.2147/JIR.S503058","DOIUrl":"https://doi.org/10.2147/JIR.S503058","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic characterization of primary angiitis of the central nervous system (PACNS) is crucial for understanding the disease pathogenesis and progression mechanisms, but it has not been reported in patients. This study aimed to explore changes in the plasma metabolome during the active and remission phases of PACNS and identify potential biomarkers.</p><p><strong>Methods: </strong>We collected plasma samples from 35 patients with PACNS during the active and remission phases and 22 samples from patients with non-inflammatory disease as controls. Liquid and gas chromatography-mass spectrometry were used to analyze 63 plasma samples from 57 patients metabolically. Meanwhile, we cross-validated the metabolomics results with brain tissue transcriptomic data from comprehensive gene expression databases, enhancing the reliability of our conclusions.</p><p><strong>Results: </strong>A total of 3,233 metabolites were identified. Enrichment analysis showed significant changes in lactate/amino acid/glycerol-pyruvic-tricarboxylic acid, glycerophospholipid/sphingolipid-membrane metabolism, lysine/tryptophan-essential amino acid metabolism, and uracil metabolism pathways during the active phase of PACNS. These findings were confirmed in both the remission phase of PACNS patients and the transcriptomic samples. Meanwhile, metabolic abnormalities in patients with PACNS were observed with benzoxazole, sesquiterpenoid, and octyl-phenolic products, and enrichment of environmental pollutants and their estrogen-like effects. Twelve metabolites, including D-Ribose, 13s-HPODE, and C16 Sphinganine, showed potential diagnostic and therapeutic evaluation value.</p><p><strong>Conclusion: </strong>Our study identified potential biomarkers and metabolic characteristics of PACNS using integrated metabolomics and transcriptomics approaches. These findings highlight the importance of understanding PACNS from a metabolic perspective and guide future diagnostic and therapeutic strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2767-2780"},"PeriodicalIF":4.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542255","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":"Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis.","authors":"Jiaxuan Fan, Yaohui Xie, Desun Liu, Rui Cui, Wei Zhang, Mengying Shen, Linzhong Cao","doi":"10.2147/JIR.S502604","DOIUrl":"https://doi.org/10.2147/JIR.S502604","url":null,"abstract":"<p><p>The crosstalk between H-type endothelial cells (ECs) and macrophages is critical for maintaining angiogenesis and osteogenesis in bone homeostasis. As core components of type H vessels, ECs respond to various pro-angiogenic signals, forming specialized vascular structures characterized by high expression of platelet-endothelial cell adhesion molecule-1 (CD31) and endothelial mucin (EMCN), thereby facilitating angiogenesis-osteogenesis coupling during bone formation. Macrophages, as key immune cells in the perivascular region, are primarily classified into the classically activated pro-inflammatory M1 phenotype and the selectively activated anti-inflammatory M2 phenotype, thereby performing dual functions in regulating local tissue homeostasis and innate immunity. In recent years, the complex crosstalk between type H vessel ECs and macrophages has garnered significant interest in the context of bone-related diseases. Orderly regulation of angiogenesis and bone immunity provides a new direction for preventing bone metabolic disorders such as osteoporosis and osteoarthritis. However, their interactions in bone homeostasis remain insufficiently understood, with limited clinical data available. This review comprehensively examines the intricate interactions between type H vessel ECs and macrophages with diverse phenotypes, and Insights into the signaling pathways that regulate their crosstalk, focusing on their roles in angiogenesis and osteogenesis. Furthermore, the review discusses recent interventions targeting this crosstalk and the challenges that remain. These insights may offer new perspectives on bone homeostasis and provide a theoretical foundation for developing novel therapeutic strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"2743-2765"},"PeriodicalIF":4.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542245","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}