International immunopharmacology最新文献

{"title":"Genetic association of tertiary lymphoid structure-related gene signatures with HCC based on Mendelian randomization and machine learning and construction of prognosis model.","authors":"Lei Pu, Xiaoyan Zhang, Cheng Pu, Jiacheng Zhou, Jianyue Li, Xiaorong Wang, Chenpeng Xi, Chunyuan Zhang","doi":"10.1016/j.intimp.2024.113594","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113594","url":null,"abstract":"<p><strong>Background: </strong>Tertiary lymphoid structures (TLS) are formed in numerous cancer types. However, their value and significance in hepatocellular carcinoma (HCC) is unclear.</p><p><strong>Methods: </strong>We performed differential genes expression analysis of TLS-related Genes (TLSG) based on The Cancer Genome Atlas (TCGA) database, and performed Mendelian randomization (MR) analysis using expression quantitative trait loci, and then took their intersecting genes. A TLSG prognostic signature (TLSGPS)-based risk score was constructed using Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate COX regression analysis, and survival analysis was then performed. We used the International Cancer Genome Consortium for outside validation. We also performed biological function, tumor mutational burden, immune infiltration, single-cell analysis, CeRNA and drug sensitivity analysis based on TLSGPS.</p><p><strong>Results: </strong>Three TLSGs (HM13, CSTB, CDCA7L) were identified to construct the TLSGPS, which showed good predictive ability and outperformed most prognostic signatures. MR suggested that HM13 (OR = 0.9997, 95 %CI: 0.9994-0.9999, P = 0.014) and CSTB (OR = 0.9997, 95 %CI: 0.9995-0.9999, P = 0.048) were negatively correlated with the risk of HCC onset, while CDCA7L (OR = 1.0004, 1.0001-1.0007, P = 0.0161) was the opposite. The differences in biological functions between the TLSGPS-based high-risk group (HRG) and low-risk group (LRG) involved cell proliferation, differentiation, and drug metabolism. HRG plus high mutations exhibited extremely poor survival. HRG had higher abundance of immune cell-oncogenic phenotypes, higher immune escape ability, and greater sensitivity to Afatinib, Dasatinib, and Gefitinib.</p><p><strong>Conclusion: </strong>3 TLSGs identified by machine learning and MR can predict the onset, prognosis and clinical treatment of HCC patients, and had significant genetic association with HCC.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113594"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liushen Wan alleviates the virulence and inflammation of Staphylococcus aureus via NLRP3 inflammasome and TLR2-NF-κB/p38 MAPK signaling pathways.","authors":"Yudi Song, Qinhai Ma, Jincan Luo, Zifeng Yang, Jiqiang Li, Jin Zhao","doi":"10.1016/j.intimp.2024.113633","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113633","url":null,"abstract":"<p><p>Infectious diseases have been a major threat to health worldwide, with bacterial infections being particularly prominent. Staphylococcus aureus (S. aureus) infections are associated with the most deaths. Inhibition of virulence factor and excessive inflammation induced by S. aureus has become a potential antibiotic alternative/synergistic therapy without causing greater survival pressure to prevent the emergence of \"superbugs\" in the future. Liushen Wan (LSW), a traditional Chinese medicine, used for multiple bacterial infectious diseases. In this work, we researched its therapeutic effect and explored the potential mechanism of LSW aiming at S. aureus in vivo and in vitro. Minimal inhibitory concentration (MIC) assay, hemolysis assay, invasion assay, staphyloxanthin assay and evolution of resistance assay were performed to show that LSW alleviated the virulence of S. aureus without suppressing S. aureus activity, and short-term use of LSW did not make bacteria resistant to it. Biofilm inhibition assay demonstrated that LSW inhibited the formation of biofilm and destroyed mature biofilm of S. aureus. In vitro experiments using RT-qPCR, ELISA and western blot analysis indicated LSW inhibited the inflammatory reaction triggered by HK-S. aureus and S. aureus through NLRP3 inflammasome and TLR2-NF-κB/p38 MAPK pathway. Moreover, LSW alleviated lung damage induced by S. aureus. Taken together, LSW is a promising antibacterial, anti-virulence and anti-inflammatory drug, which could provide the pharmacological basis on the traditional application of LSW for diseases associated with S. aureus infection in clinical.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113633"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion channels in macrophages: Implications for disease progression.","authors":"Xu Li, Yan-Xi Du, Chun-Lei Yu, Na Niu","doi":"10.1016/j.intimp.2024.113628","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113628","url":null,"abstract":"<p><strong>Rationale: </strong>Macrophages are immune cells found throughout the body and exhibit morphological and functional diversity. Macrophages have been implicated in a wide range of diseases, including autoimmune diseases, acute liver injury, cardiovascular diseases, lung diseases and tumours. Ion channels are transmembrane glycoproteins with important functions in maintaining homeostasis in the intra- and extracellular environment and mediating signal transduction. Many studies have shown that different types of ion channels influence the role of macrophages in the development of various diseases. In recent years, studies on the role of ion channels in macrophages in immune regulation and inflammatory responses have attracted much attention.</p><p><strong>Objective and findings: </strong>In order to gain a deeper understanding of the role of macrophage ion channels, this paper reviews the recent research progress on the role of macrophage ion channels in recent years. The aim is to explore the role of different ion channels in the regulation of macrophage function and their impact on a variety of disease processes. The most studied channels are calcium, sodium and potassium channels, most of which are located in the cell membrane. Among these, TRP channels have a more complex role in M1 and M2 macrophage types.</p><p><strong>Conclusion: </strong>Ion channels are critical for the functional regulation of macrophages. Targeting ion channels provides new avenues for disease prevention and treatment. This review provides researchers with new ideas and introduces readers to the current state of research on ion channels in macrophages.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"113628"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the role of PANoptosis in intervertebral disk degeneration via integrated bioinformatics analysis and experimental validation.","authors":"Daqian Zhou, Jiale Lv, Yongliang Mei, Chao Song, Tao Liu, Kang Cheng, Weiye Cai, Siling Gao, Yang Zhou, Zhongwei Xiong, Zongchao Liu","doi":"10.1016/j.intimp.2024.113528","DOIUrl":"10.1016/j.intimp.2024.113528","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, and death of nucleus pulposus cells (NPCs) has been identified as a key factor in the pathophysiological process of IVDD episodes. Recent studies have shown that \" PANapoptosis \", a newly characterized form of cell death, has emerged as an important factor contributing to the development of several diseases. However, studies on the specific mechanisms of its role in the development of IVDD are lacking. The aim of this study was to explore the characterization of PANoptosis in IVDD and to identify potential biomarkers and therapeutic targets as well as therapeutic agents. We constructed a PANoptosis gene set, based on the GEO database, and used weighted gene co-expression network analysis (WGCNA) and differential expression analysis to identify PANoptosis genes associated with the pathophysiological process of IVDD episodes by Gene Set Enrichment Analysis (GSEA), immune infiltration, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to explore the underlying biological mechanisms of PANoptosis and its role in IVDD. Comprehensive bioinformatics analysis showed that seven key genes (APAF1, MEFV, NLRP3, TNF, GSDMD, AIM2, and IRF1) of PANoptosis have good diagnostic value. In addition, we predicted potential therapeutic agents, among which Andrographolide (AG) had the highest correlation and binding affinity to the target. Finally, we performed Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays, molecular docking, and cell flow to validate the expression of PANoptosis-related genes and the therapeutic effect of AG. We further divided SD rats into sham-operated, IVDD model, and Andrographolide-treated groups, administered AG at 50 mg/kg via gavage for one month, and observed significant therapeutic effects through HE staining. This study identifies key PANoptosis genes and demonstrates the potential of AG as a therapeutic agent for IVDD.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113528"},"PeriodicalIF":4.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning identifies immune-based biomarkers that predict efficacy of anti-angiogenesis-based therapies in advanced lung cancer.","authors":"Peixin Chen, Lei Cheng, Chao Zhao, Zhuoran Tang, Haowei Wang, Jinpeng Shi, Xuefei Li, Caicun Zhou","doi":"10.1016/j.intimp.2024.113588","DOIUrl":"10.1016/j.intimp.2024.113588","url":null,"abstract":"<p><strong>Background: </strong>The anti-angiogenic drugs showed remarkable efficacy in the treatment of lung cancer. Nonetheless, the potential roles of the intra-tumoral immune cell abundances and peripheral blood immunological features in prognosis prediction of patients with advanced lung cancer receiving anti-angiogenesis-based therapies remain unknown. In this study, we aimed to develop an immune-based model for early identification of patients with advanced lung cancer who would benefit from anti-angiogenesis-based therapies.</p><p><strong>Methods: </strong>We assembled the real-world cohort of 1058 stage III-IV lung cancer patients receiving the anti-angiogenesis-based therapies. We comprehensively evaluated the tumor immune microenvironment characterizations (CD4, CD8, CD68, FOXP3, and PD-L1) by multiplex immunofluorescence (mIF), as well as calculated the systemic inflammatory index by flow cytometry and medical record review. Based on the light gradient boosting machine (LightGBM) algorithm, a machine-learning model with meaningful parameters was developed and validated in real-world populations.</p><p><strong>Results: </strong>In the first-line anti-angiogenic therapy plus chemotherapy cohort (n = 385), the intra-tumoral proportion of CD68 + Macrophages and several circulating inflammatory indexes were significantly related to drug response (p < 0.05). Further, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), the systemic inflammation response index (SIRI), and myeloid to lymphoid ratio (M:L) were identified to construct the non-invasive prediction model with high predictive performance (AUC: 0.799 for treatment response and 0.7006-0.915 for progression-free survival (PFS)). Additionally, based on the unsupervised hierarchical clustering results, the circulating cluster 3 with the highest levels of NLR, MLR, SIRI, and M: L had the worst PFS with the first-line anti-angiogenic therapy plus chemotherapy compared to other circulating clusters (2.5 months, 95 % confidence interval 2.3-2.7 vs. 6.0-9.7 months, 95 % confidence interval 4.9-11.1, p < 0.01). The predictive power of the machine-learning model in PFS was also validated in the anti-angiogenic therapy plus immunotherapy cohort (n = 103), the anti-angiogenic monotherapy cohort (n = 284), and the second-line anti-angiogenic therapy plus chemotherapy cohort (n = 286).</p><p><strong>Conclusions: </strong>Integrating pre-treatment circulating inflammatory biomarkers could non-invasively and early forecast clinical outcomes for anti-angiogenic response in lung cancer. The immune-based prognostic model is a promising tool to reflect systemic inflammatory status and predict clinical prognosis for anti-angiogenic treatment in patients with stage III-IV lung cancer.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113588"},"PeriodicalIF":4.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages.","authors":"Jing Zuo, Die Wu, Ying Zhang, Huan Luo, Guoqing Jing, Min Yuan, Qing Fang, Cheng Yang, Xing Wang, Xiaojing Wu, Xuemin Song","doi":"10.1016/j.intimp.2024.113622","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113622","url":null,"abstract":"<p><p>Macrophages are present in all tissues and body compartments under homeostatic physiological conditions. Importantly, they play a key role in pathological inflammatory processes when disturbed. They can quickly produce large amounts of inflammatory cytokines in response to danger signals. Macrophages can recognize muramyl dipeptide (MDP) through nucleotide-binding oligomerization domain (NOD)-like receptors, subsequently activating the NF-κB signaling pathway and producing proinflammatory cytokines. Erbin can bind to NOD2 and inhibit MDP-induced NF-κB activation, thus participating in the regulation of inflammatory response. Stabilizing or enhancing Erbin expression is essential for suppressing inflammatory responses. In this study, we used a deubiquitination enzyme plasmid library to screen for a key deubiquitinase, VCPIP1, which interacts with Erbin and influences its stability through deubiquitination modification. We investigated whether VCPIP1 affects inflammation using MDP-stimulated RAW 264.7 and BMDMs cells. The results showed that VCPIP1 deficiency reduced Erbin expression and increased NF-κB phosphorylation. Additionally, VCPIP1 deficiency promoted the release of inflammatory factors (IL-1β, IL-6, and TNF-α) in RAW 264.7 cells and BMDMs. This study further expands the role of deubiquitinases (DUBs) in inflammation, providing new insights for the prevention and treatment of sepsis, tumors, immune diseases, and other inflammatory reactions.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113622"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of hepatic PCSK9 as a novel therapeutic target ameliorates metabolic steatohepatitis in mice","authors":"Tuoluonayi Mijiti ,&nbsp;Xiaocui Chen ,&nbsp;Xiang Ma ,&nbsp;Yitong Ma ,&nbsp;Xiumin Ma ,&nbsp;Bangdang Chen","doi":"10.1016/j.intimp.2024.113621","DOIUrl":"10.1016/j.intimp.2024.113621","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Metabolic steatohepatitis (MASH) is closely related to metabolic disorders, and the main characteristics of MASH are hepatocyte steatosis with hepatocyte injury and inflammation. In severe cases, MASH can develop into liver cirrhosis. At present, there is no effective treatment for MASH. Proprotein convertase subtilisin/kexin 9 (PCSK9) is a popular target for the development of cholesterol-lowering drugs and therapeutic interventions for cardiovascular disease. The present study aimed to explore the role of PCSK9 in methionine- and choline-deficient (MCD) diet-induced MASH progression and its targeted intervention.</div></div><div><h3>Methods</h3><div>PCSK9 expression was determined in a MASH mouse model, and the role of PCSK9 in the regulation of lipid metabolism, inflammation, and fibrosis was investigated using PCSK9 knockout (PCSK9^−/−) mice fed a MCD diet. An adeno-associated virus was used to alter PCSK9 expression in MASH mice.</div></div><div><h3>Results</h3><div>Following the MCD diet, C57BL/6J wild-type (WT) mice developed marked steatohepatitis and elevated hepatic PCSK9 expression, and circulating PCSK9 expression. PCSK9^−/− mice showed significantly alleviated MCD-induced hepatic steatosis, with lower serum ALT levels, lower serum AST levels, smaller hepatic vacuoles, and less hepatic lipid deposition. PCSK9^−/− mice on the MCD diet showed a significantly reduced levels of inflammation and fibrogenesis. Moreover, adeno-associated virus (AAV)–mediated PCSK9 silencing in mouse livers significantly relieved liver steatosis, inflammation, and fibrosis.</div></div><div><h3>Conclusions</h3><div>The present study demonstrated an important role of PCSK9 in MASH, suggesting that inhibition of PCSK9 may represent a novel and effective therapeutic strategy for MASH treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 ","pages":"Article 113621"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-derived exosomal miR-2137 regulates pyroptosis in LPS-induced acute lung injury.","authors":"Cong Ye, Xiaodong Yang, Lin Zhu, Guilin Chang, Yu Hu, Weixi Wang","doi":"10.1016/j.intimp.2024.113549","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113549","url":null,"abstract":"<p><strong>Background: </strong>Alveolar macrophages (AMs) play a predominant role in acute lung injury (ALI). However, the role of macrophage-derived exosomal miRNAs in lipopolysaccharide (LPS)-induced ALI has not been determined.</p><p><strong>Methods: </strong>We previously reported that exosomes in the bronchoalveolar lavage fluid (BALF) of mice with ALI were derived predominantly from macrophages. Exosomal small RNA sequencing was conducted to identify the miRNA profiles. Exosomes derived from LPS-induced macrophages (LPS-exos) were intravenously administered to C57BL/6J mice, after which lung injury and pyroptosis were assessed. LPS-exos were cultured with alveolar epithelial cells (AECs) to further validate the results of the animal studies.</p><p><strong>Results: </strong>LPS-exos promoted lung inflammation and pyroptosis in vivo and in vitro. MiR-2137 was significantly upregulated in both LPS-exos and in MLE-12 cells. LPS-exos reduced cell viability, promoted the expression of LDH and inflammatory cytokines, and exacerbated vacuolization in MLE-12 cells. The administration of miR-2137 mimics and LPS-treated exosomes further strengthened these effects and enhanced pyroptosis mediated by NLRP3, Caspase1, ASC, and GSDMD. MiR-2137 mediated the effects of LPS-exos by targeting Wnt9a in AECs. In addition, the miR-2137 inhibitor markedly decreased the severity of LPS-exo-induced histological lesions, inflammation and pyroptosis in the lung.</p><p><strong>Conclusion: </strong>Exosomal miR-2137 derived from AMs contributes to LPS-induced ALI by inducing AEC pyroptosis through the targeting of Wnt9a to activate the Wnt signaling pathway. This study revealed that AMs and AECs interact in ALI, providing novel strategies for ALI treatment.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113549"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathophysiological functions and therapeutic potential of GPR39: Focus on agonists and antagonists","authors":"Yuhui Cheng ,&nbsp;Chang Zhao ,&nbsp;Yan Bin ,&nbsp;Yuan Liu ,&nbsp;Lin Cheng ,&nbsp;Fan Xia ,&nbsp;Xiaowen Tian ,&nbsp;Xinlei Liu ,&nbsp;Sicen Liu ,&nbsp;Binwu Ying ,&nbsp;Zhenhua Shao ,&nbsp;Wei Yan","doi":"10.1016/j.intimp.2024.113491","DOIUrl":"10.1016/j.intimp.2024.113491","url":null,"abstract":"<div><div>G protein-coupled receptor 39 (GPR39), a member of the growth hormone-releasing peptide family, exhibits widespread expression across various tissues and demonstrates high constitutive activity, primarily activated by zinc ions. It plays critical roles in cell proliferation, differentiation, survival, apoptosis, and ion transport through the recruitment of Gq/11, Gs, G12/13, and β-arrestin proteins. GPR39 is involved in anti-inflammatory and antioxidant responses, highlighting its diverse pathophysiological functions. Recent discoveries of endogenous ligands have enhanced our understanding of GPR39′s physiological roles. Aberrant expression and reactivation of GPR39 have been implicated in a range of diseases, particularly central nervous system disorders, endocrine disruptions, cardiovascular diseases, cancers, and liver conditions. These findings position GPR39 as a promising therapeutic target, with the efficacy of synthetic ligands validated in various <em>in vivo</em> models. Nonetheless, their clinical applicability remains uncertain, necessitating further exploration of novel agonists—especially biased agonists—and antagonists. This review examines the unique residues contributing to the high constitutive activity of GPR39, its endogenous and synthetic ligands, and its pathophysiological implications, aiming to elucidate its pharmacological potential for clinical application in disease treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 ","pages":"Article 113491"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of rhG-CSF on risk of recurrence after postoperative chemotherapy in NSCLC Patients: A retrospective cohort study.","authors":"Tong Wang, Weiwei Hong, Xinyuan Yao, Chen Fang, Xiaoying Qian, Biao Yu, Bingbiao Zhou, Xin Ye, Yong Wang, Yong Li","doi":"10.1016/j.intimp.2024.113519","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113519","url":null,"abstract":"<p><strong>Purpose: </strong>Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widespread in the prevention and treatment of blood-related toxic effects associated with chemotherapy. This study aimed to explore the correlation between rhG-CSF and the recurrence of non-small cell lung cancer (NSCLC) in patients who have undergone postoperative chemotherapy.</p><p><strong>Methods: </strong>Our study encompassed 517 NSCLC patients at pathological stage I-III, who underwent surgical removal and subsequent chemotherapy from January 2012 to December 2019 at the First Affiliated Hospital of Nanchang University. The research focused on evaluating the separate impact of rhG-CSF on the likelihood of postoperative recurrence. The analysis employed both univariate and multivariate Cox regression models.</p><p><strong>Results: </strong>Of 517 NSCLC patients, 123 patients did not receive rhG-CSF, while 394 patients received rhG-CSF. Unexpectedly, it was discovered that rhG-CSF usage correlated with the emergence of distant metastasis (HR: 1.8, 95 %CI 1.2-2.7, p = 0.005), though not with local recurrence (HR: 1.4, 95 %CI 0.9-2.3, p = 0.142). By multifactorial Cox analysis, rhG-CSF was an independent risk factor for distant metastasis (adjusted HR: 1.7, 95 %CI 1.0-2.6, p = 0.033). We additionally discovered that rhG-CSF could increase the risk of brain metastasis (adjusted HR: 3.9, 95 %CI 1.5-9.8, p = 0.005) and bone metastasis (adjusted HR: 3.1, 95 %CI 1.2-8.2, p = 0.02).</p><p><strong>Conclusion: </strong>Our findings indicate that rhG-CSF independently contributes to the risk of distant metastasis, yet it shows no correlation with local recurrence. Furthermore, employing rhG-CSF played a crucial role in predicting brain metastasis and bone metastasis after postoperative chemotherapy in NSCLC patients.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"143 Pt 3","pages":"113519"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}