Inflammation Research最新文献

{"title":"Immune-related genetic single-nucleotide polymorphisms contribute to prognosis and response to chemotherapy in patients with acute lymphoblastic leukemia.","authors":"Amin Zhang, Wancheng Liu, Can Can, Xiaodong Guo, Hexiao Jia, Yihong Wei, Hanyang Wu, Xinyu Yang, Chunyan Ji, Daoxin Ma","doi":"10.1007/s00011-025-02014-7","DOIUrl":"https://doi.org/10.1007/s00011-025-02014-7","url":null,"abstract":"<p><p>The immune system is essential for immuno-surveillance and the generation of anti-tumor immunity. However, the role of immune-related single-nucleotide polymorphisms (SNPs) in the susceptibility and progression of acute lymphoblastic leukemia (ALL) is currently unknown. Here, we selected and analyzed 28 immune-related SNPs in 201 ALL patients and 228 healthy controls. We uncovered five important SNPs related to ALL susceptibility, including in TGFB1(rs1800469), GATA3 (rs3824662), TNFA (rs1800629), PARP1 (rs1805414), and IL6R (rs2228145). PARP1 (rs1805414) and GATA3 (rs3824662) were also associated with the ALL immunophenotype. Additionally, STAT3 (rs744166) and TMPRSS2 (rs12329760) significantly contributed to the susceptibility of Philadelphia chromosome-positive (Ph+) ALL. More importantly, MAVS (rs7269320) and NF-KBIA (rs2233406) were remarkably associated with the overall survival (OS) of ALL patients. Furthermore, ITGAM (rs4597342), PTPN22 (rs2488457), STAT5B (rs6503691), and MAVS (rs7269320) were significantly associated with the progression-free survival (PFS) of ALL patients. In the training cohort, we built a prognostic classifier, which identified five features. The five selected SNPs were related to GATA3, IL-6R, ITGAM, PTPN22, and STAT1. Moreover, the five SNP-based classifiers demonstrated a higher accuracy in predicting the OS and the PFS. In addition, we found that the mRNA expression of GATA3 gene was significantly higher in ALL patients than in healthy controls. GATA3 mRNA expression were also elevated in ALL patients with CA and AA genotypes. Our findings suggest that immune-related genetic polymorphisms contribute to the prognosis and treatment of ALL and could also serve as a valuable disease predictor.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"73"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2 mediated signaling axis in sepsis-induced cardiomyopathy: potential Pharmacological receptor.","authors":"Sumei Wang, Shasha He, Xiao Hu, Fusheng Liu, Xiaolei Fang, Po Huang","doi":"10.1007/s00011-025-02037-0","DOIUrl":"https://doi.org/10.1007/s00011-025-02037-0","url":null,"abstract":"<p><strong>Background: </strong>Sepsis has emerged as the most pressing health concerns globally in emergency and intensive care unit. Sepsis-Induced Cardiomyopathy (SIC) represents an acute cardiac insufficiency syndrome secondary to sepsis, characterized by a high incidence and a significant increase in mortality among sepsis patients. To date, no specific treatment exists for this condition. In recent years, mounting evidence has indicated that Nrf2 plays a critical protective role in SIC and may represent a potential therapeutic target.</p><p><strong>Methods: </strong>Pubmed database literature was searched for studies pertaining to the role of Nrf2 in sepsis, from the inception of the database to October 1, 2024. Biorender software was performed to draw the corresponding mechanism diagram.</p><p><strong>Results: </strong>Using the keywords \"Nrf2 and Sepsis\", we initially identified 454 articles. To refine our search, we employed \"Nrf2 and Sepsis and Cardiac\" as keywords, yielding 63 articles. Upon reviewing the full texts, we selected 26 studies for inclusion in our review. Nrf2 is implicated in various protective aspects against cardiomyocyte injury stemming from sepsis, including its inhibitory effects on inflammation, apoptosis, mitochondrial dysfunction, pyroptosis, and ferroptosis. 23 natural compounds under investigation for this application were identified.</p><p><strong>Conclusion: </strong>The Nrf2-mediated signaling pathway plays a critical role in sepsis-induced myocardial injury. Given the complex, systemic, and multifactorial nature of sepsis, these natural compounds should be regarded as adjunctive therapeutic options for scholarly investigation rather than standalone therapeutic interventions. Substantial future research will still be required to validate their clinical efficacy and mechanistic roles.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"76"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IL-6 autocrine loop promoting IFN-γ-induced fibroblast senescence is involved in psychological stress-mediated exacerbation of vitiligo.","authors":"Cheng Cao, Wen Xu, Jingdi Lei, Yujie Zheng, An Zhang, Aie Xu, Fuquan Lin, Miaoni Zhou","doi":"10.1007/s00011-025-02035-2","DOIUrl":"https://doi.org/10.1007/s00011-025-02035-2","url":null,"abstract":"<p><strong>Background: </strong>Psychological stress is the most common psychological comorbidity and a significant triggering factor of vitiligo. Moderate to severe psychological stress can markedly affect the efficacy of vitiligo treatment. However, the specific mechanisms underlying its involvement remain insufficiently studied.</p><p><strong>Methods: </strong>Chronic unpredictable mild stress (CUMS)-induced major depressive disorder (MDD)-like behavior was modeled in C57BL/6 mice alongside wild-type mice to investigate differences in vitiligo pathogenesis. White spot tissues from mouse tails were subjected to high-throughput transcriptomic sequencing (RNA-seq). In vitro experiments utilized β-galactosidase, P16, and P21 to assess IFN-γ-induced senescence. The effects of exogenous IL-6 on fibroblast senescence were assessed, and the role of blocking the IL-6 autocrine loop with an IL-6R inhibitor in reversing IFN-γ-induced fibroblast senescence was evaluated.</p><p><strong>Results: </strong>CUMS-induced MDD -like mice exhibited significantly lower body mass index and sugar-water preference index compared to wild-type mice, and their vitiligo severity was markedly increased. Transcriptomic sequencing revealed significant upregulation of cellular senescence and JAK-STAT signaling pathways in white spot tissues of depressive-like vitiligo mice. In vitro findings indicated that IFN-γ induced fibroblast senescence via activation of the JAK2-STAT3 signaling pathway, which subsequently promoted melanocyte apoptosis and increased IL-6 secretion and IL-6R expression. Exogenous IL-6 further activated the JAK2-STAT3 signaling pathway, induced fibroblast senescence, and synergistically intensified IFN-γ-induced fibroblast senescence.</p><p><strong>Conclusion: </strong>Excessive activation of the IL-6 autocrine loop, synergizing with IFN-γ to aggravate fibroblast senescence and promote melanocyte apoptosis. Blocking the IL-6 autocrine loop may serve as an effective approach to mitigate the impact of CUMS on vitiligo pathogenesis and treatment efficacy.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"72"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophils but not mast cells exert anti-tumorigenic activity, without being predictive markers of the long-term response to Bacillus Calmette-Guérin (BCG) therapy in patients with bladder carcinoma.","authors":"Ilan Zaffran, Yara Zoabi, Pratibha Gaur, Fidan Rahimli Alekberli, Ekaterini Tiligada, Vladimir Yutkin, Francesca Levi-Schaffer","doi":"10.1007/s00011-025-02028-1","DOIUrl":"https://doi.org/10.1007/s00011-025-02028-1","url":null,"abstract":"<p><strong>Background: </strong>Bacillus Calmette-Guerin (BCG) therapy is an established immunotherapy for non-muscle invasive bladder cancer (NMIBC); however, the response variability of patients remains a challenge, necessitating insight into immune cell function. Previous studies established that a preexisting Th2 immune microenvironment correlates with a positive BCG therapy outcome. Therefore, in this study, we explored the role of mast cells (MCs) and eosinophils in bladder cancer as a potential predicting tool for BCG immunotherapy response.</p><p><strong>Methods: </strong>We investigated the effect of MCs and eosinophils on bladder cancer cell viability together with their chemotactic migration towards cancer cells in vitro. The effect of BCG on these immune cells was also evaluated. Moreover, we performed an orthotopic model of bladder cancer in MC- and eosinophil-deficient mice. Finally, to evaluate whether these immune cells predict the therapy response, 26 patient biopsies pre-BCG treatment were analyzed for MC and eosinophil numbers in the tissue and sequenced for gene expression.</p><p><strong>Results: </strong>Eosinophils, but not MCs, reduced bladder cancer cell viability in vitro and inhibited tumor growth in vivo. However, addition of BCG did not increase these effects in vitro. Patient biopsy analysis and mRNA sequencing showed that neither cell type predicted long-term therapy responsiveness. Gene expression analysis suggested that extracellular matrix and epithelial-to-mesenchymal transition factors could influence BCG therapy outcomes.</p><p><strong>Conclusion: </strong>Even though eosinophils exhibit anti-tumorigenic effects in bladder cancer, neither MCs nor eosinophils were predictive of the long-term BCG therapy response. However, our findings implicate that matrix-related factors may modulate BCG therapy responses.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"68"},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of remote ischemic preconditioning and/or erythropoietin on lung injury induced by skeletal ischemia reperfusion: role of the NLRP3 inflammasome.","authors":"Mennatallah A Ali, Asmaa A Khalifa, Samar S Elblehi, Nahed H Elsokkary, Mahmoud M El-Mas","doi":"10.1007/s00011-025-02033-4","DOIUrl":"https://doi.org/10.1007/s00011-025-02033-4","url":null,"abstract":"<p><strong>Background and objectives: </strong>Remote ischemic preconditioning (RIPC) diminishes multi-organ failure induced by skeletal muscle ischemia and reperfusion (S-I/R). The current study investigated whether skeletal RIPC protection against S-I/R-induced acute lung injury (ALI) could be facilitated following simultaneous exposure to the glycoprotein hormone erythropoietin (EPO) in rats and whether this interaction is modulated by the NLRP3 inflammasome.</p><p><strong>Methods: </strong>S-I/R challenge was performed by 3-h ischemia followed by 3-h reperfusion of the right hindlimb, whereas RIPC involved three 20-min brief consecutive I/R cycles of the contralateral hindlimb.</p><p><strong>Results: </strong>The lung injurious response to S-I/R was verified by: (i) decreases in minute respiratory volume (MRV), forced expiratory volume 1 (FEV1) and functional vital capacity (FVC), (ii) increases in respiratory rate (RR), (iii) falls in lung surfactant protein-D (SP-D) and rises in of lung plasminogen activator inhibitor-1 (PAI-1) and intercellular adhesion molecule-1 (ICAM-1), and (iv) disruption of alveolar architecture. These lung defects were partially amended by RIPC or EPO (500 or 5000 IU/kg). Further, the prior exposure to RIPC plus EPO-500 was more effective than separate interventions in rectifying ALI damages. Molecularly, the dual RIPC/EPO-500 regimen was also more effective in reversing the S-I/R-associated increments in pulmonary expressions of NLRP3 and related inflammatory (TLR4, MyD88, TRAF, NF-κB, TNF-α, IL-1β, and IL-18), apoptotic (ASC, procaspse-1, caspase-1), and microRNA signals (increases in miR-21 and decreases miR-495).</p><p><strong>Conclusion: </strong>These findings suggest a pivotal role for the suppression of NLRP3 inflammasome and interconnected cellular offenses in the augmented therapeutic potential of the RIPC/EPO-500 regimen against S-I/R-induced ALI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"67"},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization.","authors":"Arthid Thim-Uam, Papasara Chantawichitwong, Pornpimol Phuengmaung, Warerat Kaewduangduen, Wilasinee Saisorn, Sarinya Kumpunya, Trairak Pisitkun, Prapaporn Pisitkun, Asada Leelahavanichkul","doi":"10.1007/s00011-025-02036-1","DOIUrl":"https://doi.org/10.1007/s00011-025-02036-1","url":null,"abstract":"<p><strong>Background: </strong>Due to the possible influence of inflammation and gut microbiota in cancers.</p><p><strong>Methods: </strong>Fc gamma receptor IIb deficient (FcGRIIb-/-) and cyclic GMP-AMP synthase deficient (cGAS-/-) mice, the model with hyperinflammation and hypo-inflammation, respectively, were subcutaneously injected with MC38 cells (a murine colon cancer cell line).</p><p><strong>Results: </strong>As such, the tumor burdens were most prominent in cGAS-/- mice, while FcGRIIb-/- mice demonstrated the least tumor sizes compared with wild-type (WT). Intra-tumoral mononuclear cells of FcGRIIb-/- (hematoxylin and eosin staining) were more prominent than other groups with the most dominant CD86-positive cells (mostly M1 proinflammatory macrophages) and the least CD206-positive cells (mostly M2 anti-inflammatory macrophages). While fecal microbiome analysis demonstrated a subtle difference among mouse strains with tumors at 24 days post-cancer injection, serum cytokines (TNF-α, IL-6, IL-1α, IFN-β, IFN-γ, IL-23, IL-12p70, GM-CSF, IL-27, and IL-17A) (fluorescence-encoded bead multiplex assay) and the expansion of immune cells in the spleens of FcGRIIb-/- mice (flow cytometry) were more prominent than others. With bone marrow-derived macrophages, prominent M1 (LPS) and M2 polarization (IL4 and cancer supernatant) in FcGRIIb-/- and cGAS-/- macrophages, respectively, were demonstrated using polymerase chain reaction and flow cytometry. The most prominent tumoricidal activity (percentage of F4/80-negative flexible780 viable dye-positive cells using flow cytometry) of LPS-stimulated FcGRIIb-/- macrophages compared with other groups supported dominant pro-inflammatory characteristics of FcGRIIb-/- macrophages.</p><p><strong>Conclusions: </strong>In conclusion, the protective and promoting effects of FcGRIIb-/- and cGAS-/- mice, respectively, against cancers are partly related to macrophage functions with a subtle correlation to fecal microbiota, and FcGRIIb inhibitors and cGAS enhancers might be helpful for cancer adjuvant treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"69"},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TIPE2 deficiency amplifies inflammation and immune dysregulation in MASH through modulating hepatic lipid metabolism and immune cell function.","authors":"Lawan Rabiu, Pengchao Zhang, Zhongming Liu, Yexiao Tang, Khalid I Gidado, Abdulrahman Ibrahim, Muhammad A Saliu, Hafiza Kashaf Tariq, Xiaochun Wan, Shu Xu, Zhiming Xu, Guizhong Zhang","doi":"10.1007/s00011-025-02031-6","DOIUrl":"https://doi.org/10.1007/s00011-025-02031-6","url":null,"abstract":"<p><strong>Background: </strong>Metabolic Dysfunction-Associated Steatohepatitis (MASH) affects nearly 25% of the global population, yet there are no effective pharmacological treatments. Tumor necrosis factor α-induced protein 8-like 2 (TIPE2) is expressed in various immune cells and is crucial for regulating both innate and adaptive immune responses. However, its role in MASH development and the underlying mechanisms remain unclear.</p><p><strong>Method: </strong>In this study, the role of TIPE2 in MASH was investigated using TIPE2 knockout (KO) mice and human hepatic LO2 cells. Immune cell infiltration, cytokine levels, and gene expression were analyzed. Techniques included flow cytometry for immune cell profiling, cytokine analysis, RNA sequencing, and quantitative PCR (qPCR) for validating gene expression changes.</p><p><strong>Results: </strong>TIPE2 was identified as a key regulator in MASH, influencing immune modulation and metabolic processes. TIPE2 KO mice exhibited increased infiltration and activation of natural killer (NK) cells, M1 macrophages, and myeloid-derived suppressor cells (MDSCs), along with elevated pro-inflammatory cytokines such as IFN-gamma, TNF-alpha, IL- 1 beta, and IL- 6. MDSCs from TIPE2 KO mice demonstrated enhanced PD-L1 expression, contributing to chronic liver inflammation through T cell suppression. RNA sequencing revealed that TIPE2 overexpression in human hepatic LO2 cells upregulated genes associated with amino acid biosynthesis, carbon metabolism, lipid regulation, glycolysis, and gluconeogenesis. These findings were supported by qPCR analyses of liver samples from mice, confirming TIPE2's role in maintaining lipid homeostasis and modulating immune responses.</p><p><strong>Conclusion: </strong>The study highlights the pivotal role of TIPE2 in immune regulation and its influence on immune cell activation and inflammatory responses, which are critical in MASH progression. By exploring TIPE2-mediated immune regulation and its impact on the interplay between immune cell dynamics and liver metabolism, this research underscores TIPE2's central role in linking immune dysfunction to metabolic disturbances in MASH.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"65"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAGE deficiency ameliorates abdominal aortic aneurysm progression.","authors":"Cong Bi, Bingqi Liu, Peixian Gao, Chuanle Wang, Sheng Fang, Zhengkun Huo, Qingpeng Song, Dianning Dong, Xuejun Wu, Gang Li","doi":"10.1007/s00011-025-02027-2","DOIUrl":"https://doi.org/10.1007/s00011-025-02027-2","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysm (AAA) is a vascular disease characterized by inflammation and arterial wall degradation. The receptor for advanced glycation end products (RAGE) plays a pivotal role in regulating inflammatory pathways, but its specific contribution to AAA pathogenesis remains unclear.</p><p><strong>Purpose: </strong>This study aimed to investigate the role of RAGE in AAA development by examining its expression in human and mice AAA tissues and exploring the effects of RAGE deficiency on aneurysm progression, macrophage polarization, and inflammatory responses.</p><p><strong>Methods: </strong>RAGE expression was analyzed in human AAA samples and porcine pancreatic elastase (PPE) induced AAA mouse models using Western blotting, immunohistochemistry, and immunofluorescence. In vivo RAGE-deficient (RAGE^-/-) mice were generated to assess the impact of RAGE knockout on AAA progression. In vitro experiments utilized RAW264.7 transfected with RAGE-targeting siRNA to study macrophage polarization and NF-κB signaling.</p><p><strong>Results: </strong>RAGE expression was elevated in AAA tissues, particularly in macrophages. RAGE^-/- mice exhibited reduced AAA incidence, mortality, and aortic dilation compared to wild-type mice. Histological analysis showed preserved elastic fibers and smooth muscle layers, along with decreased inflammatory cell infiltration and MMP2/MMP9 expression. RAGE deficiency inhibited M1-like macrophage polarization and pro-inflammatory cytokine secretion, mediated through suppression of the NF-κB pathway.</p><p><strong>Conclusions: </strong>RAGE deficiency mitigates AAA progression by modulating macrophage polarization and reducing inflammation via the NF-κB pathway. These findings highlight RAGE as a potential therapeutic target for AAA treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"63"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 nucleocapsid protein induces a Mincle-dependent macrophage inflammatory response in acute kidney injury.","authors":"Rui-Zhi Tan, Wen-Jing Zhao, Jing Gao, Hui-Yao Lan, Jian Liu, Li Wang","doi":"10.1007/s00011-025-02030-7","DOIUrl":"https://doi.org/10.1007/s00011-025-02030-7","url":null,"abstract":"<p><strong>Background: </strong>Although the COVID-19 pandemic has receded, the SARS-CoV-2 virus still poses a significant threat to individuals with pre-existing renal conditions, leading to severe acute kidney injury (AKI). However, the underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>In this study, we used ultrasound microbubble technology to transfect and overexpress the SARS-CoV-2 nucleocapsid (N) protein in the kidneys of IRI (ischemia-reperfusion injury) and Cis (cisplatin) induced AKI mice. Additionally, we generated macrophage-specific Mincle knockout mice to investigate the amplifying effects of the SARS-CoV-2 N protein on AKI renal injury and the critical regulatory role of macrophage inducible C-type lectin (Mincle). Finally, we employed Mincle-neutralizing antibodies to intervene in the SARS-CoV-2 N-induced exacerbation of kidney injury in AKI.</p><p><strong>Results: </strong>We found that the specific overexpression of the SARS-CoV-2 N protein significantly aggravates kidney injury in the context of AKI. Mechanistically, we found that the exacerbation of acute kidney injury by the SARS-CoV-2 N protein is dependent on Mincle, as the SARS-CoV-2 N protein activates Mincle to enhance the Syk/NF-κB signaling pathway, leading to damage and inflammation of renal tubular epithelial cells. This was confirmed in Mincle knockout mice and cells, where Mincle knockout alleviated the renal tubular injury and inflammation caused by SARS-CoV-2 N transfection. Importantly, the use of anti-Mincle neutralizing antibodies could effectively mitigate the acute kidney injury exacerbated by the SARS-CoV-2 N protein.</p><p><strong>Conclusions: </strong>In summary, we identified the SARS-CoV-2 N protein as a key mediator of kidney injury in AKI and demonstrated that it exacerbates the injury through a Mincle-dependent mechanism. Targeting Mincle may represent a novel therapeutic strategy for treating COVID-19-related acute kidney injury.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"64"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell hdWGCNA reveals a novel diagnostic model and signature genes of macrophages associated with chronic obstructive pulmonary disease.","authors":"Xianqiang Zhou, Yufeng Meng, Jie Yang, Hongtao Wang, Yixin Zhang, Zhengjie Jin, Cuiling Feng","doi":"10.1007/s00011-025-02025-4","DOIUrl":"https://doi.org/10.1007/s00011-025-02025-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory system-related mortality worldwide. Although COPD is associated with immune regulation, its underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>Cells from the single-cell RNA sequencing (scRNA-seq) datasets were subjected to clustering analysis and cell type identification to isolate immune cell subgroups specifically expressed in COPD. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify hub genes related to the immune cell subpopulations. Machine learning algorithms were applied to identify diagnostic genes in the immune cell subpopulations and construct clinical diagnostic models for COPD. In bulk RNA sequencing data, AUC curves were used to assess the stability of the diagnostic models in predicting COPD.</p><p><strong>Results: </strong>Through 2 rounds of clustering analysis, the macrophage subgroups 1, 2, 7, 11, and 13 which specifically expressed in COPD (COPD_Mφ) were identified. HdWGCNA analysis revealed a hub set of genes closely related to COPD_Mφ from black, blue, yellow, and brown modules. Nonnegative Matrix Factorization (NMF) analysis separated the COPD samples into 2 clusters, with significant increases in the infiltration of Monocytic_lineage, Myeloid_dendritic_cells, and Neutrophils in cluster 1 (P < 0.001). Univariate logistic regression and LASSO regression analyses identified 11 feature genes associated with COPD_Mφ, including CST3, LGALS3, CSTB, S100A10, CYBA, S100A11, ARPC3, FTH1, PFN1, MAN2B1, and RPL39. The RF and convolutional neural network (CNN) models constructed using these feature genes effectively distinguished between normal and COPD patients. Among them, S100A10, RPL39, and FTH1 exhibited differential expression between COPD patients and normal individuals and could serve as potential clinical diagnostic markers for COPD.</p><p><strong>Conclusions: </strong>The study provides new insights into the immune mechanisms of COPD and lays the theoretical foundation for its future clinical diagnosis and personalized treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"66"},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}