International Journal of Immunopathology and Pharmacology最新文献

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FGF19 is a biomarker associated with prognosis and immunity in colorectal cancer. FGF19是与结直肠癌预后和免疫相关的生物标志物。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-31 DOI: 10.1177/03946320251324401
Peng Wang, Zhenpeng Zhu, Chenyang Hou, Dandan Xu, Fei Guo, Xuejun Zhi, Weizheng Liang, Jun Xue
{"title":"FGF19 is a biomarker associated with prognosis and immunity in colorectal cancer.","authors":"Peng Wang, Zhenpeng Zhu, Chenyang Hou, Dandan Xu, Fei Guo, Xuejun Zhi, Weizheng Liang, Jun Xue","doi":"10.1177/03946320251324401","DOIUrl":"10.1177/03946320251324401","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between fibroblast growth factor 19 (FGF19) and the prognosis and immune infiltration of colorectal cancer (CRC) and identify the related genes and pathways influencing the onset and progression of CRC.</p><p><strong>Introduction: </strong>The potential of FGF19 to guide the prognosis of CRC and inform immunotherapeutic strategies warrants further investigation.</p><p><strong>Methods: </strong>We performed Quantitative Real-Time PCR to assess the expression of FGF19 and conducted a bioinformatics analysis to evaluate the impact of FGF19 expression on the clinical prognosis of CRC. We also analyzed the association between FGF19 expression and immune cell infiltration in CRC, and explored the related genes and pathways through which FGF19 influences CRC development.</p><p><strong>Results: </strong>CRC patients with higher FGF19 expression exhibited a poorer prognosis. In terms of the Receiver Operating Characteristic (ROC), FGF19 achieved an area under the curve (AUC) of 0.904. FGF19 expression correlated with the N stage, M stage, and pathological stage in patients with CRC. Functional enrichment analysis revealed significant enrichment of FGF19 in pathways associated with tumor development. ssGSEA and Spearman correlation analysis demonstrated that FGF19 expression was linked to tumor immune cells. We discovered that FGF19 is closely related to neutrophil extracellular traps (NETs), which play a significant role in the immune microenvironment.</p><p><strong>Conclusion: </strong>FGF19 is a key gene associated with immunity and prognosis in CRC patients. Our findings suggest that FGF19 may influence CRC progression by promoting NETs expression, which leads to suppression of immune cells.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251324401"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755301","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}
引用次数: 0
Comprehensive Pan-cancer Analysis Revealed CASP10 As a Promising Biomarker For Diverse Tumor Types. 综合泛癌症分析揭示CASP10是多种肿瘤类型的有前途的生物标志物。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-28 DOI: 10.1177/03946320251327620
Qian Wang, Yaping Jiang, Weijia Liao, Pengpeng Zhu
{"title":"Comprehensive Pan-cancer Analysis Revealed CASP10 As a Promising Biomarker For Diverse Tumor Types.","authors":"Qian Wang, Yaping Jiang, Weijia Liao, Pengpeng Zhu","doi":"10.1177/03946320251327620","DOIUrl":"10.1177/03946320251327620","url":null,"abstract":"<p><p>We aimed to explore the comprehensive cancer landscape of Caspase-10 (CASP10). CASP10, a member of the caspase family, is located at the human chromosome locus 2q33-34. Studies have suggested its potential role in the development of certain cancers. To evaluate CASP10 expression in normal and pan-cancer tissues, we integrated data from <i>The Cancer Genome Atlas (TCGA)</i>, GEO, <i>Human Protein Atlas (HPA)</i>, and UALCAN databases. The diagnostic and prognostic significance of CASP10 was analyzed using Receiver Operating Characteristic (ROC), Cox regression, and Kaplan-Meier analysis. Correlations of CASP10 with clinical parameters were assessed via the Wilcoxon test, Kruskal-Wallis test, and logistic regression analysis. Genomic variations were explored with cBioPortal, GSCALite database, and UALCAN databases. LinkedOmics database was used to detect the function of CASP10 in pan-cancer. Interactions between CASP10 and the Tumor Immune Microenvironment (TIME) were investigated using TISIDB, TIMER2, and TISCH databases. The GSCALite database was utilized to assess the sensitivity of CASP10 to small-molecule drugs. In addition, Western Blotting (WB) was employed to detect the expression of the CASP10 in our clinical Liver Hepatocellular Carcinoma (LIHC) and Stomach Adenocarcinoma (STAD) cohorts. The transcription and protein expression of CASP10 significantly differ across cancer types, marking it as a biomarker for diagnosis and prognosis. Its expression correlated with certain clinical characteristics such as histological types and Alpha-Fetoprotein (AFP) levels. CASP10 gene exhibited a 2% alteration frequency across pan-cancer patients, with significant SNV and CNV profiles, and decreased methylation levels. CASP10 was closely related to the Nuclear Factor-κappa B (NF-κB), TNF, cell cycle, and JAK-STAT signal pathways. CASP10 showed correlation with immune components in the tumor microenvironment, including lymphocytes, immune stimulators, immune inhibitors, MHC molecules, chemokines, receptors, and Cancer-Associated Fibroblasts (CAFs). Importantly, CASP10 could predict the sensitivity of diverse anti-cancer drugs. Finally, WB analysis validated the overexpression of CASP10 in LIHC and STAD tissues. Our comprehensive bioinformatic analysis reveal the function of CASP10 on the diagnosis, prognosis, and progression of diverse cancer types.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251327620"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732692","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}
引用次数: 0
Therapeutic drug monitoring and immunogenetic factors associated with the use of adalimumab in Crohn's disease patients. 治疗药物监测和与克罗恩病患者使用阿达木单抗相关的免疫遗传因素
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 DOI: 10.1177/03946320251319379
Livia Moreira Genaro, Juliana Carron, Marina Moreira de Castro, Ana Paula Menezes de Freitas Franceschini, Gustavo Jacob Lourenço, Cristiane Kibune Nagasako Vieira da Cruz, Glaucia Fernanda Soares Rupert Reis, Livia Bitencourt Pascoal, Juliana Delgado Campos Mello, Isabela Machado Pereira, Millene Leal Nascimento, Priscilla De Sene Portel Oliveira, Ligiana Pires Corona, Maria de Lourdes Setsuko Ayrizono, Carmen Silvia Passos Lima, Raquel Franco Leal
{"title":"Therapeutic drug monitoring and immunogenetic factors associated with the use of adalimumab in Crohn's disease patients.","authors":"Livia Moreira Genaro, Juliana Carron, Marina Moreira de Castro, Ana Paula Menezes de Freitas Franceschini, Gustavo Jacob Lourenço, Cristiane Kibune Nagasako Vieira da Cruz, Glaucia Fernanda Soares Rupert Reis, Livia Bitencourt Pascoal, Juliana Delgado Campos Mello, Isabela Machado Pereira, Millene Leal Nascimento, Priscilla De Sene Portel Oliveira, Ligiana Pires Corona, Maria de Lourdes Setsuko Ayrizono, Carmen Silvia Passos Lima, Raquel Franco Leal","doi":"10.1177/03946320251319379","DOIUrl":"10.1177/03946320251319379","url":null,"abstract":"<p><p>Crohn's disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-α). Adalimumab, targeting TNF-α, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA-Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes <i>ATG16L1</i>, <i>CD96</i>, and <i>CD155</i>. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (<i>P</i> = 0.003), with moderate agreement (Lin's correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (<i>P</i> = 0.0125). The genotypic evaluation revealed significant associations for the <i>CD96</i> CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. <i>ATG16L1</i> CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for <i>CD96</i> and <i>ATG16L1</i> with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251319379"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442390","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}
引用次数: 0
Administration of anti-GFAP antibodies increases CGRP expression and increases pain hypersensitivity in spinal cord injured animals. 抗gfap抗体可增加脊髓损伤动物的CGRP表达并增加疼痛超敏反应。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 DOI: 10.1177/03946320251320754
Georgene W Hergenroeder, Samuel T Molina, Juan J Herrera
{"title":"Administration of anti-GFAP antibodies increases CGRP expression and increases pain hypersensitivity in spinal cord injured animals.","authors":"Georgene W Hergenroeder, Samuel T Molina, Juan J Herrera","doi":"10.1177/03946320251320754","DOIUrl":"10.1177/03946320251320754","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.</p><p><strong>Objective: </strong>Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined the effect of exogenous anti-GFAP antibodies on SCI pathology, pain-associated molecular changes, and behavior.</p><p><strong>Methods: </strong>Anti-GFAP or IgG was administered at 7- and 14-days post-injury. Immunohistochemistry was performed to measure the relative levels of calcitonin gene-related peptide (CGRP), and inflammatory proteins in dorsal horn tissue. To assess the development of neuropathic pain, the von Frey test and the Mechanical Conflict-Avoidance Paradigm (MCAP) were performed.</p><p><strong>Results: </strong>CGRP immunoreactivity was significantly higher in the anti-GFAP-treated injured rats compared to control SCI IgG-treated rats. As anticipated, SCI rats had a lower pain threshold at 1- and 2-months post-injury compared to laminectomy-only controls. However, pain withdrawal threshold was not significantly affected by post-injury administration of the anti-GFAP. Operant testing revealed that SCI rats treated with the anti-GFAP had a trending increase in pain sensitivity.</p><p><strong>Conclusion: </strong>Taken together, these data suggest that autoantibodies to GFAP following SCI may contribute to developing pain states following SCI.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251320754"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524865","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}
引用次数: 0
INF-γ/TGF-β1-primed umbilical cord mesenchymal stem cells boost the T-lymphocytes activity: Modulation of CD25 expression and IL-6 secretion. INF-γ/TGF-β1诱导的脐带间充质干细胞提高t淋巴细胞活性:调节CD25表达和IL-6分泌。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 DOI: 10.1177/03946320251315007
Abdulrahman H Almaeen, Heba M Saad-Eldien, Hala Gabr
{"title":"INF-γ/TGF-β1-primed umbilical cord mesenchymal stem cells boost the T-lymphocytes activity: Modulation of CD25 expression and IL-6 secretion.","authors":"Abdulrahman H Almaeen, Heba M Saad-Eldien, Hala Gabr","doi":"10.1177/03946320251315007","DOIUrl":"10.1177/03946320251315007","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory abilities, particularly in a milieu of hyperactive immune system, through secreting a number of cytokines, growth factors, bioactive compounds and peptides, and by cell-cell contact. During viral infection, failure of immuno-neutralization of the viral particles, recruits T-lymphocytes (T-cells) that clear the virally-infected cells. MSCs greatly potentiate T-cells anti-viral activity.</p><p><strong>Objective: </strong>The objective of this study is to assess the ability of the cytokine-primed MSCs to activated T-cells, towards an antiviral application.</p><p><strong>Method: </strong>Human umbilical cord MSCs (UC-MSCs) were isolated from Wharton Jelly of a consented donor. UC-MSCs were primed with interferon (INF)-γ and transforming growth factor (TGF)-β1. Peripheral blood T-cells were isolated using mini-max and CD3+ population was purified using anti-CD3 immuno-magnetic beads. Naïve or primed MSCs were co-cultured with naïve and phytohemagglutinin (PHA)-activated CD3+ T-cells. T-cell activation was evaluated by changes in their rate of proliferation by cell count, flowcytometric immuno-phenotyping for CD25 expression, and IL-6 secretion in the conditioned medium.</p><p><strong>Results: </strong>The findings revealed that CD3+ T-cells count nonsignificant differed comparing the five experimental groups; Naïve MSCs, Naïve T cells, coculture with naïve MSCs, coculture with primed MSCs, and upon phytohemagglutinin-activation, despite a nonsignificant reduction of proliferation in the last two groups' coculture. Only the coculture with the primed MSCs showed significant activation of T-cells assessed as CD25 expression compared to the other groups (<i>p</i> < 0.001 and <i>p</i> = 0.002, respectively). The undetectable levels of IL-6 in the conditioned medium of naïve MSCs, turned markedly high after their cytokine-priming (<i>p</i> < 0.001), reaching nonsignificant difference compared to naïve T-cells. Compared to naïve MSCs, naïve T-cells secreted considerable amounts of IL-6 (<i>p</i> < 0.001). Incubation of naïve MSCs with phytohemagglutinin-activated T-cells further the secretion of IL-6, to a level significantly higher than all of the aforementioned three groups; naïve MSCs, naïve T-cells and primed MSCs (<i>p</i> < 0.001, <i>p</i> = 0.0194, and <i>p</i> < 0.001, respectively). However, coculture of the cytokine-primed MSCs with phytohemagglutinin-activated T-cells dampened IL-6 secretion to a level that was significantly lower than that observed with naïve MSCs-phytohemagglutinin-activated T-cells coculture (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>The cytokine-primed UC-MSCs significantly upregulated CD25+ expression on T-cells, while hindering IL-6, without affecting their proliferation rate. This may point to potentially stronger antiviral effects, while alleviating the viral infection-induced cytokine storm.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251315007"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374196","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}
引用次数: 0
Meta-analysis of EGFR gene polymorphisms and lung cancer risk. EGFR基因多态性与肺癌风险的meta分析。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 DOI: 10.1177/03946320251316731
Meryem Fakhkhari, Ikram Salih, Khaoula Errafii, Salsabil Hamdi, Khalid Sadki
{"title":"Meta-analysis of <i>EGFR</i> gene polymorphisms and lung cancer risk.","authors":"Meryem Fakhkhari, Ikram Salih, Khaoula Errafii, Salsabil Hamdi, Khalid Sadki","doi":"10.1177/03946320251316731","DOIUrl":"10.1177/03946320251316731","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis aims to systematically evaluate the associations of four specific Single Nucleotide Polymorphisms (SNPs)-rs712829, rs712830, rs11568315, and rs884225-located in the promoter, intronic, and 3' untranslated regions (3'UTR) of the EGFR gene, with lung cancer risk.</p><p><strong>Introduction: </strong>The associations between EGFR gene polymorphisms and lung cancer risk is a topic of ongoing debate, which is still deemed controversial. Despite numerous studies, results are inconsistent.</p><p><strong>Methods: </strong>We conducted a comprehensive literature search across the PubMed, Science Direct, and Web of Science databases to identify relevant case-control studies examining the association between EGFR gene polymorphisms and lung cancer risk.</p><p><strong>Results: </strong>From an initial pool of 26,959 articles, 10 case-control studies were included, involving 2471 lung cancer patients and 4489 controls. A significant association between rs712829 and increased lung cancer risk was found across multiple genetic models. Under the allelic contrast model (G vs T), the OR was 1.31 (95% CI = [1.02; 1.68], <i>p</i> < 0.05), the dominant model (GG + GT vs TT) showed an OR of 1.69 (95% CI = [1.07; 2.67], <i>p</i> < 0.05), the homozygote model (GG vs TT) yielded an OR of 1.70 (95% CI = [1.00; 2.88], <i>p</i> < 0.05), and the heterozygote model (GT vs TT) had an OR of 1.64 (95% CI = [1.01; 2.66], <i>p</i> < 0.05). No significant associations were found for rs11568315, rs712830, and rs884225.</p><p><strong>Conclusion: </strong>The findings from the current meta-analysis confirm that rs712829 within the EGFR gene is significantly associated with lung cancer risk according to the allele, dominant, homozygote and heterozygote models.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251316731"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400389","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}
引用次数: 0
Construction of a tumor immune microenvironment-related risk scoring model for prognosis of hepatocellular carcinoma. 肝癌预后肿瘤免疫微环境相关风险评分模型的构建
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-04-23 DOI: 10.1177/03946320251333975
Xinyi Li, Zifan Qin, Haozhi Chen, Daichuan Chen, Nafisa Alimu, Duoduo Li, Xiyu Cheng, Qiong Yan, Lishu Zhang, Xingwei Liu, Zitong Zhou, Jiayi Zhu, Hangqi Ma, Xinyue Pei, Hanli Xu, Jiaqiang Huang
{"title":"Construction of a tumor immune microenvironment-related risk scoring model for prognosis of hepatocellular carcinoma.","authors":"Xinyi Li, Zifan Qin, Haozhi Chen, Daichuan Chen, Nafisa Alimu, Duoduo Li, Xiyu Cheng, Qiong Yan, Lishu Zhang, Xingwei Liu, Zitong Zhou, Jiayi Zhu, Hangqi Ma, Xinyue Pei, Hanli Xu, Jiaqiang Huang","doi":"10.1177/03946320251333975","DOIUrl":"https://doi.org/10.1177/03946320251333975","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to develop a prognostic model for HCC based on TME-related factors.</p><p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is characterized by a poor prognosis, largely due to the complex and heterogeneous interactions between stromal and immune cells within the tumor microenvironment (TME).</p><p><strong>Methods: </strong>Genome and transcriptome data, as well as clinical information of HCC patients, were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The TME score was evaluated using the \"ESTIMATE\" R package. Differentially expressed genes (DEGs) associated with TME phenotype were analyzed using the LIMMA R-package. Survival outcomes were compared using Kaplan-Meier curves with log-rank test and Cox proportional hazards model. Protein-Protein Interaction (PPI) networks integrated with multivariate survival and LASSO analyses were utilized to identify TME-related hub genes for a risk score model. A nomogram predicting prognosis of HCC patients was developed through four independent cohorts.</p><p><strong>Results: </strong>The TME scores showed a negative correlation with tumor progression and survival in HCC patients. We identified 50 core genes with high connectivity in the PPI network, as along with 33 key DEGs associated with survival in HCC. Intersection analysis revealed six hub genes -<i>CXCL8</i>, <i>CXCL1</i>, <i>CCR7</i>, <i>IL7R</i>, <i>MMP9</i>, and <i>CD69</i>. The risk score based on these six TME-related hub genes was significantly associated with overall survival and clinicopathological characteristics of HCC patients. Furthermore, the nomogram demonstrated its ability to discriminate HCC patients from healthy individuals using peripheral blood mononuclear cells.</p><p><strong>Conclusion: </strong>We have developed a TME-related risk scoring model for HCC patients and identified six hub gene panel that serve as a potential biomarker for personalized prognosis of immunotherapy and non-invasive diagnostics of HCC.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251333975"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042658","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}
引用次数: 0
Attenuation of senile pruritus by PAC-14028-mediated downregulation of the NF-κB and MAPK pathways. pac -14028介导的NF-κB和MAPK通路下调对老年性瘙痒的抑制作用。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/03946320251321354
Ji Hye Yoon, Byoung Young Woo, Mi-Yeon Kim, Jae Youl Cho
{"title":"Attenuation of senile pruritus by PAC-14028-mediated downregulation of the NF-κB and MAPK pathways.","authors":"Ji Hye Yoon, Byoung Young Woo, Mi-Yeon Kim, Jae Youl Cho","doi":"10.1177/03946320251321354","DOIUrl":"10.1177/03946320251321354","url":null,"abstract":"<p><strong>Objective: </strong>Senile pruritus is a specific type of itching that occurs in elderly persons. Previously, we assessed antagonism of the nonselective ligand-gated cation channel transient receptor potential vanilloid 1 (TRPV1; capsaicin receptor or vanilloid receptor 1) and attenuation of atopic dermatitis by the non-steroidal TRPV1 antagonist PAC-14028 in clinical studies. The findings led us to postulate that PAC-14028 may also reduce itching in elderly people by antagonizing the TRPV1 pathway. In this study, we evaluated whether PAC-14028 modulates inflammatory markers present in senile pruritus.</p><p><strong>Materials and methods: </strong>HaCaT, RAW264.7, and differentiated THP-1 cells under itching-inducing conditions were treated with zymosan or IL-17A and variety of experimental approaches such as molecular modeling simulations, site-directed mutagenesis, overexpression strategies, confocal microscopy, mRNA analyses, and immunoprecipitation/Western blotting analyses were assessed to check changes in inflammatory markers and explore the underlying mechanisms of PAC-14028 activity.</p><p><strong>Results: </strong>In the bioinformatic analyses, skin inflammation markers were found to be closely related to TRPV1, and the MAPK and NF-κB pathways were upregulated when TRPV1 was activated. In HaCaT cells, PAC-14028 was found to directly bind to TRPV1, inhibiting inflammatory cytokine gene expression and downstream MAPK and NF-κB signaling under various skin inflammatory conditions.</p><p><strong>Conclusions: </strong>By combining the results of multiple assays, we were able to elucidate the molecular mechanism of PAC-14028 to TRPV1. Taken together, the findings indicate that PAC-14028 as a potential therapeutic agent for elderly people with pruritus.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251321354"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606154","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}
引用次数: 0
Pan-cancer multi-omics analysis to identify the potential pro-oncogenic properties of GREM1 as a promising targets for cancer prognosis and therapeutics. 泛癌症多组学分析,以确定GREM1潜在的促癌特性,作为癌症预后和治疗的有希望的靶点。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-04-15 DOI: 10.1177/03946320251331850
Menglu Zhu, Hengli Zhou, Yue Zhuo, Changhua Liu, Jiaxin Li, Peiyao He, Naihua Liu, Ziming Zhao, Pan Huafeng
{"title":"Pan-cancer multi-omics analysis to identify the potential pro-oncogenic properties of GREM1 as a promising targets for cancer prognosis and therapeutics.","authors":"Menglu Zhu, Hengli Zhou, Yue Zhuo, Changhua Liu, Jiaxin Li, Peiyao He, Naihua Liu, Ziming Zhao, Pan Huafeng","doi":"10.1177/03946320251331850","DOIUrl":"https://doi.org/10.1177/03946320251331850","url":null,"abstract":"<p><p>We aimed to investigate the potential pro-oncogenic properties of GREM1 by Pan-cancer multi-omics analysis. Accumulating evidence has highlighted that GREM1 (Gremlin 1), serves as an inhibitor of BMP (Bone Morphogenetic Protein) family, involve in bone related diseases, carcinogenesis, cell stemness, and cell differentiation. However, the effect and underlying mechanism of GREM1 on the cancer biology remain largely elusive. The mRNA expression of GREM1 were extracted from GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) database. Analysis of OS (Overall Survival), PFI (Progression Free Interval), DSS (Disease-Specific Survival), and ROC (Receiver Operating Characteristic) were performed to predicted prognostic value of GREM1 in various cancers. The TIMER (Tumor Immune Estimation Resource) online tool was used to investigate the relationship between GREM1 transcriptional level and infiltration of immune cells. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis and GO (Gene Ontology) analysis were used to investigate the GREM1 related molecular events, and then constructed a PPI (Protein-Protein Interaction) network via the STRING (Search Tool for the Retrieval of Interaction Genes/Proteins) online tool. Western blot was performed to investigate the indicated protein expression. In the present study, our results showed that GREM1 tended to be upregulated in various cancers, which would correlate with the poor prognosis. Mechanistically, our results showed that GREM1 involve in regulating the ECM-receptor interaction pathway, upregulation of MMP activity, angiogenesis, and immune cell infiltration. In vitro studies, our results further showed that BMP agonist significantly decreased the protein level of GREM1 in GES-1 cells and BGC cells, which accompanied by inhibiting migration and proliferation in GES-1 cells and BGC cells. BMP inhibitor significantly promoted GREM1 expression and migration in BGC cells, but not GES-1 cells. GREM1 might serve as a potential and promising prognostic biomarker for drug development and cancer treatment.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251331850"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035565","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}
引用次数: 0
Thanks to Reviewers. 感谢评论者。
IF 3.5 3区 医学
International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-20 DOI: 10.1177/03946320251321083
{"title":"Thanks to Reviewers.","authors":"","doi":"10.1177/03946320251321083","DOIUrl":"10.1177/03946320251321083","url":null,"abstract":"","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251321083"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781652","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}
引用次数: 0
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