{"title":"Serum L C3-II levels in type 2 diabetic patients with impaired renal functions","authors":"Shahab Ahmed Salıh Gezh , Koksal Deveci , Hakan Sivgin , Figen Guzelgul","doi":"10.1016/j.cyto.2024.156683","DOIUrl":"10.1016/j.cyto.2024.156683","url":null,"abstract":"<div><p>This study was designed to evaluate serum LC3-II, BCL-2, IL-1β, TGF-β1, and podocin levels in.</p><p>type 2 diabetes (T2DM) patients with renal dysfunction.</p></div><div><h3>Materials</h3><p>176 Turkish subjects were enrolled, of whom 26 were healthy, and 150 had T2DM. Patients.</p><p>were classified according to albumin urea ratio: 88 patients had macroalbuminuria, 20.</p><p>patients had microalbuminuria, and 42 had normoalbuminuria. T2DM patients were also.</p><p>classified into three groups according to proteinuria and eGFR stages.</p></div><div><h3>Results</h3><p>Increased serum LC3-II levels in patients with T2DM with increased urinary albumin.</p><p>extraction and impaired renal functions. There was a strong relationship between serum.</p><p>LC3-II levels and serum BCL-2, IL-1β, TGF-β1, and Podocin levels. The efficiency of LC3-</p><p>II as a diagnostic biomarker in the differential diagnosis of DM patients with.</p><p>macroproteinuria from DM patients with normoproteinuria was 75.4%.</p></div><div><h3>Conclusions</h3><p>It was thought that increased serum LC3-II levels in T2DM patients with impaired renal.</p><p>functions may cause renal podocyte damage. In these patients, serum LC3-II levels can be.</p><p>evaluated as a new biomarker to follow the development of renal damage.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464809","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}
Pub Date : 2024-06-28DOI: 10.1016/j.cyto.2024.156671
Meimin Pan , Chunlin Cai , Wenjuan Li , Tianran Cao , Yu Liu , Lihui Yang , Qing Xie , Xuehong Zhang
Nonalcoholic fatty liver disease (NAFLD), a metabolic disease associated with obesity and type 2 diabetes. Due to its complex pathogenesis, there are still limitations in the knowledge of the disease. To date, no drug has been approved to treat NAFLD. This study aims to explore the role and mechanism of Ebselen (EbSe) in NAFLD. A high-fat diet-induced mouse model of NAFLD was employed to investigate EbSe function in NAFLD mice by EbSe gavage and to regularly monitor the mouse body weight. HE and oil red O staining were performed, respectively, to detect the pathological damage and lipid accumulation in mouse liver tissues. The biochemical and ELISA kits were employed to measure the levels of ALT, AST, TG, TC, LDL-C, HDL-C and pro-inflammatory cytokines within mouse serum or liver tissue. The expression of key proteins of PPARα, fatty acid β oxidation-related protein, PI3K/Akt and TLR4/JNK signaling pathway was detected by western blot. EbSe significantly downregulated body weight, liver weight and liver lipid accumulation in NAFLD mice and downregulated ALT, AST, TG, TC, LDL-C and increased HDL-C serum levels. EbSe upregulated the expression levels of PPARα and fatty acid β oxidation-associated proteins CPT1α, ACOX1, UCP2 and PGC1α. EbSe promoted Akt and PI3K phosphorylation, and inhibited TLR4 expression and JNK phosphorylation. EbSe can upregulate PPARα to promote fatty acid β-oxidation and improve hepatic lipid metabolism. Meanwhile, EbSe also activated PI3K/Akt and inhibited TLR4/JNK signaling pathway. EbSe is predicted to be an effective therapeutic drug for treating NAFLD.
{"title":"Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver","authors":"Meimin Pan , Chunlin Cai , Wenjuan Li , Tianran Cao , Yu Liu , Lihui Yang , Qing Xie , Xuehong Zhang","doi":"10.1016/j.cyto.2024.156671","DOIUrl":"10.1016/j.cyto.2024.156671","url":null,"abstract":"<div><p>Nonalcoholic fatty liver disease (NAFLD), a metabolic disease associated with obesity and type 2 diabetes. Due to its complex pathogenesis, there are still limitations in the knowledge of the disease. To date, no drug has been approved to treat NAFLD. This study aims to explore the role and mechanism of Ebselen (EbSe) in NAFLD. A high-fat diet-induced mouse model of NAFLD was employed to investigate EbSe function in NAFLD mice by EbSe gavage and to regularly monitor the mouse body weight. HE and oil red O staining were performed, respectively, to detect the pathological damage and lipid accumulation in mouse liver tissues. The biochemical and ELISA kits were employed to measure the levels of ALT, AST, TG, TC, LDL-C, HDL-C and pro-inflammatory cytokines within mouse serum or liver tissue. The expression of key proteins of PPARα, fatty acid β oxidation-related protein, PI3K/Akt and TLR4/JNK signaling pathway was detected by western blot. EbSe significantly downregulated body weight, liver weight and liver lipid accumulation in NAFLD mice and downregulated ALT, AST, TG, TC, LDL-C and increased HDL-C serum levels. EbSe upregulated the expression levels of PPARα and fatty acid β oxidation-associated proteins CPT1α, ACOX1, UCP2 and PGC1α. EbSe promoted Akt and PI3K phosphorylation, and inhibited TLR4 expression and JNK phosphorylation. EbSe can upregulate PPARα to promote fatty acid β-oxidation and improve hepatic lipid metabolism. Meanwhile, EbSe also activated PI3K/Akt and inhibited TLR4/JNK signaling pathway. EbSe is predicted to be an effective therapeutic drug for treating NAFLD.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464807","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}
Pub Date : 2024-06-26DOI: 10.1016/j.cyto.2024.156684
Yan Lv , Ziyin Yang , Lei Hai , Xiaoyu Chen , Jiayuan Wang , Shaohua Hu , Yuhong Zhao , Huiming Yuan , Zhengjun Hu , Dawei Cui , Jue Xie
As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9–11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman’s correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.
{"title":"Differential alterations of CXCR3, CXCR5 and CX3CR1 in patients with immune thrombocytopenia","authors":"Yan Lv , Ziyin Yang , Lei Hai , Xiaoyu Chen , Jiayuan Wang , Shaohua Hu , Yuhong Zhao , Huiming Yuan , Zhengjun Hu , Dawei Cui , Jue Xie","doi":"10.1016/j.cyto.2024.156684","DOIUrl":"10.1016/j.cyto.2024.156684","url":null,"abstract":"<div><p>As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9–11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman’s correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5<sup>+</sup> Tc cells and CX3CR1<sup>+</sup> T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464806","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}
Pub Date : 2024-06-22DOI: 10.1016/j.cyto.2024.156682
Ling Zhang, Jing Qin, Peiwu Li
Background
A growing body of research has shown that patients with coronavirus disease 2019 (COVID-19) have significantly higher rates of venous thromboembolism (VTE) than healthy. However, the mechanism remains incompletely elucidated. This study aimed to further investigate the molecular mechanisms underlying the development of this complication.
Methods
The gene expression profiles of COVID-19 and VTE were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for COVID-19 and VTE, functional annotation, a protein–protein interactions (PPI) network, module construction, and hub gene identification were performed. Finally, we constructed a transcription factor (TF)-gene regulatory network and a TF-miRNA regulatory network for hub genes.
Results
A total of 42 common DEGs were selected for subsequent analyses. Functional analyses showed that biological function and signaling pathways collectively participated in the development and progression of VTE and COVID-19. Finally, 8 significant hub genes were identified using the cytoHubba plugin, including RSL24D1, RPS17, RPS27, HINT1, COX7C, RPL35, RPL34, and NDUFA4, which had preferable values as diagnostic markers for COVID-19 and VTE.
Conclusions
Our study revealed the common pathogenesis of COVID-19 and VTE. These common pathways and pivotal genes may provide new ideas for further mechanistic studies.
{"title":"Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 and venous thromboembolism","authors":"Ling Zhang, Jing Qin, Peiwu Li","doi":"10.1016/j.cyto.2024.156682","DOIUrl":"10.1016/j.cyto.2024.156682","url":null,"abstract":"<div><h3>Background</h3><p>A growing body of research has shown that patients with coronavirus disease 2019 (COVID-19) have significantly higher rates of venous thromboembolism (VTE) than healthy. However, the mechanism remains incompletely elucidated. This study aimed to further investigate the molecular mechanisms underlying the development of this complication.</p></div><div><h3>Methods</h3><p>The gene expression profiles of COVID-19 and VTE were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for COVID-19 and VTE, functional annotation, a protein–protein interactions (PPI) network, module construction, and hub gene identification were performed. Finally, we constructed a transcription factor (TF)-gene regulatory network and a TF-miRNA regulatory network for hub genes.</p></div><div><h3>Results</h3><p>A total of 42 common DEGs were selected for subsequent analyses. Functional analyses showed that biological function and signaling pathways collectively participated in the development and progression of VTE and COVID-19. Finally, 8 significant hub genes were identified using the cytoHubba plugin, including RSL24D1, RPS17, RPS27, HINT1, COX7C, RPL35, RPL34, and NDUFA4, which had preferable values as diagnostic markers for COVID-19 and VTE.</p></div><div><h3>Conclusions</h3><p>Our study revealed the common pathogenesis of COVID-19 and VTE. These common pathways and pivotal genes may provide new ideas for further mechanistic studies.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441870","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}
Pub Date : 2024-06-20DOI: 10.1016/j.cyto.2024.156666
Zahra Bagheri-Hosseinabadi , Seyed Mohammad Sadat Eshkevari , Solmaz Khalighfard , Ali Mohammad Alizadeh , Vahid Khori , Taghi Amiriani , Amirhoushang Poorkhani , Somayeh Sadani , Ebrahim Esmati , Marzih Lashgari , Mehdi Mahmoodi , Mohammad Reza Hajizadeh
Background
This study aims to investigate cell-free DNA (cfDNA) methylation of genes involved in some immune system targets as biomarkers of radioresistance in patients with non-metastatic rectal cancer.
Methods
Gene expression (GSE68204, GPL6480, and GSE15781) and DNA methylation profiles (GSE75548 and GSE139404) of rectal cancer patients were obtained from the Gene Expression Omnibus (GEO) database. GEO2R and FunRich software were first used to identify genes with significant expression differences. Enricher softwer was then used to analyze Gene Ontology and detect pathway enrichment of hub genes. Blood samples were then taken from 43 rectal cancer patients. After cfDNA extraction from samples, it was treated with bisulfite and analyzed by methylation-specific PCR.
Results
1088 genes with high and 629 with low expression were identified by GEO2R and FunRich software. A total of five high-expression hub genes, including CDH24, FGF18, CCND1, IFITM1, UBE2V1, and three low-expression hub genes, including CBLN2, VIPR2, and IRF4, were identified from UALCAN and DNMIVD databases. Methylation-specific PCR indicated a significant difference in hub gene methylation between cancerous and non-cancerous individuals. Radiochemotherapy significantly affected hub gene methylation. There was a considerable difference in the methylation rate of hub genes between patients who responded to radiochemotherapy and those who did not.
Conclusions
Evaluating gene methylation patterns might be an appropriate diagnostic tool to predict radiochemotherapy response and develop targeted therapeutic agents.
{"title":"A systematic approach introduced some immune system targets in rectal cancer by considering cell-free DNA methylation in response to radiochemotherapy","authors":"Zahra Bagheri-Hosseinabadi , Seyed Mohammad Sadat Eshkevari , Solmaz Khalighfard , Ali Mohammad Alizadeh , Vahid Khori , Taghi Amiriani , Amirhoushang Poorkhani , Somayeh Sadani , Ebrahim Esmati , Marzih Lashgari , Mehdi Mahmoodi , Mohammad Reza Hajizadeh","doi":"10.1016/j.cyto.2024.156666","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156666","url":null,"abstract":"<div><h3>Background</h3><p>This study aims to investigate cell-free DNA (cfDNA) methylation of genes involved in some immune system targets as biomarkers of radioresistance in patients with non-metastatic rectal cancer.</p></div><div><h3>Methods</h3><p>Gene expression (GSE68204, GPL6480, and GSE15781) and DNA methylation profiles (GSE75548 and GSE139404) of rectal cancer patients were obtained from the Gene Expression Omnibus (GEO) database. GEO2R and FunRich software were first used to identify genes with significant expression differences. Enricher softwer was then used to analyze Gene Ontology and detect pathway enrichment of hub genes. Blood samples were then taken from 43 rectal cancer patients. After cfDNA extraction from samples, it was treated with bisulfite and analyzed by methylation-specific PCR.</p></div><div><h3>Results</h3><p>1088 genes with high and 629 with low expression were identified by GEO2R and FunRich software. A total of five high-expression hub genes, including CDH24, FGF18, CCND1, IFITM1, UBE2V1, and three low-expression hub genes, including CBLN2, VIPR2, and IRF4, were identified from UALCAN and DNMIVD databases. Methylation-specific PCR indicated a significant difference in hub gene methylation between cancerous and non-cancerous individuals. Radiochemotherapy significantly affected hub gene methylation. There was a considerable difference in the methylation rate of hub genes between patients who responded to radiochemotherapy and those who did not.</p></div><div><h3>Conclusions</h3><p>Evaluating gene methylation patterns might be an appropriate diagnostic tool to predict radiochemotherapy response and develop targeted therapeutic agents.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434225","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}
Pub Date : 2024-06-18DOI: 10.1016/j.cyto.2024.156677
Qianlei Zhao , Guanhao Liu , Qiang Ding , Feixia Zheng , Xulai Shi , Zhongdong Lin , Yafeng Liang
Background
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction activated by microglia. The potential pathological changes of SAE are complex, and the cellular pathophysiological characteristics remains unclear. This study aims to explore the ROS/TXNIP/NLRP3 pathway mediated lipopolysaccharide (LPS)-induced inflammatory response in microglia.
Methods
BV-2 cells were pre-incubated with 10 μM N-acetyl-L-cysteine (NAC) for 2 h, which were then reacted with 1 μg/mL LPS for 24 h. Western blot assay examined the protein levels of IBA1, CD68, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. The contents of inflammatory factor were detected by ELISA assay. The co-immunoprecipitation assay examined the interaction between TXNIP and NLRP3.
Results
LPS was confirmed to promote the positive expressions of IBA1 and CD68 in BV-2 cells. The further experiments indicated that LPS enhanced ROS production and NLRP3 inflammasome activation in BV-2 cells. Moreover, we also found that NAC partially reversed the facilitation of LPS on the levels of ROS, IL-1β, IL-18, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. NAC treatment also notably alleviated the interaction between TXNIP and NLRP3 in BV-2 cells.
Conclusion
ROS inhibition mediated NLRP3 signaling inactivation by decreasing TXNIP expression.
{"title":"The ROS/TXNIP/NLRP3 pathway mediates LPS-induced microglial inflammatory response","authors":"Qianlei Zhao , Guanhao Liu , Qiang Ding , Feixia Zheng , Xulai Shi , Zhongdong Lin , Yafeng Liang","doi":"10.1016/j.cyto.2024.156677","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156677","url":null,"abstract":"<div><h3>Background</h3><p>Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction activated by microglia. The potential pathological changes of SAE are complex, and the cellular pathophysiological characteristics remains unclear. This study aims to explore the ROS/TXNIP/NLRP3 pathway mediated lipopolysaccharide (LPS)-induced inflammatory response in microglia.</p></div><div><h3>Methods</h3><p>BV-2 cells were pre-incubated with 10 μM N-acetyl-L-cysteine (NAC) for 2 h, which were then reacted with 1 μg/mL LPS for 24 h. Western blot assay examined the protein levels of IBA1, CD68, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. The contents of inflammatory factor were detected by ELISA assay. The co-immunoprecipitation assay examined the interaction between TXNIP and NLRP3.</p></div><div><h3>Results</h3><p>LPS was confirmed to promote the positive expressions of IBA1 and CD68 in BV-2 cells. The further experiments indicated that LPS enhanced ROS production and NLRP3 inflammasome activation in BV-2 cells. Moreover, we also found that NAC partially reversed the facilitation of LPS on the levels of ROS, IL-1β, IL-18, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. NAC treatment also notably alleviated the interaction between TXNIP and NLRP3 in BV-2 cells.</p></div><div><h3>Conclusion</h3><p>ROS inhibition mediated NLRP3 signaling inactivation by decreasing TXNIP expression.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424615","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}
Pub Date : 2024-06-18DOI: 10.1016/j.cyto.2024.156675
Wenyan Kang , Chengkun Wang , Minhui Wang, Meiqi Liu, Wei Hu, Xiaoqiu Liang, Yang Zhang
Gastric cancer (GC) is one of the most common malignant tumors in the world, and current treatments are still based on surgery and drug therapy. However, due to the complexity of immunosuppression and drug resistance, the treatment of gastric cancer still faces great challenges. Chemokine receptor 2 (CXCR2) is one of the most common therapeutic targets in targeted therapy. As a G protein-coupled receptor, CXCR2 and its ligands play important roles in tumorigenesis and progression. The abnormal expression of these genes in cancer plays a decisive role in the recruitment and activation of white blood cells, angiogenesis, and cancer cell proliferation, and CXCR2 is involved in various stages of tumor development. Therefore, interfering with the interaction between CXCR2 and its ligands is considered a possible target for the treatment of various tumors, including gastric cancer.
胃癌(GC)是世界上最常见的恶性肿瘤之一,目前的治疗方法仍以手术和药物治疗为主。然而,由于免疫抑制和耐药性的复杂性,胃癌的治疗仍面临巨大挑战。趋化因子受体 2(CXCR2)是靶向治疗中最常见的治疗靶点之一。作为一种 G 蛋白偶联受体,CXCR2 及其配体在肿瘤发生和发展过程中发挥着重要作用。这些基因在癌症中的异常表达对白细胞的募集和激活、血管生成和癌细胞增殖起着决定性作用,而 CXCR2 则参与了肿瘤发生发展的各个阶段。因此,干扰 CXCR2 与其配体之间的相互作用被认为是治疗包括胃癌在内的各种肿瘤的可能靶点。
{"title":"The CXCR2 chemokine receptor: A new target for gastric cancer therapy","authors":"Wenyan Kang , Chengkun Wang , Minhui Wang, Meiqi Liu, Wei Hu, Xiaoqiu Liang, Yang Zhang","doi":"10.1016/j.cyto.2024.156675","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156675","url":null,"abstract":"<div><p>Gastric cancer (GC) is one of the most common malignant tumors in the world, and current treatments are still based on surgery and drug therapy. However, due to the complexity of immunosuppression and drug resistance, the treatment of gastric cancer still faces great challenges. Chemokine receptor 2 (CXCR2) is one of the most common therapeutic targets in targeted therapy. As a G protein-coupled receptor, CXCR2 and its ligands play important roles in tumorigenesis and progression. The abnormal expression of these genes in cancer plays a decisive role in the recruitment and activation of white blood cells, angiogenesis, and cancer cell proliferation, and CXCR2 is involved in various stages of tumor development. Therefore, interfering with the interaction between CXCR2 and its ligands is considered a possible target for the treatment of various tumors, including gastric cancer.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424614","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}
Pub Date : 2024-06-18DOI: 10.1016/j.cyto.2024.156670
Xiaojie Yuan , Yuzhang Shao , Rui Huang , Samuel Seery , Hairong Wang , Ni Hu , Leji Wen , Xin Lin , Lei Zhang
Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(−) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05–1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00–1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06–1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00–1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.
{"title":"Understanding the influence of cytokines in intrauterine hepatitis B transmission: A cross-sectional study in China","authors":"Xiaojie Yuan , Yuzhang Shao , Rui Huang , Samuel Seery , Hairong Wang , Ni Hu , Leji Wen , Xin Lin , Lei Zhang","doi":"10.1016/j.cyto.2024.156670","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156670","url":null,"abstract":"<div><p>Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(−) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05–1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00–1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06–1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00–1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424616","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}
Pub Date : 2024-06-16DOI: 10.1016/j.cyto.2024.156680
Zishen Liu, Yingying Zheng, Mengqi Yuan, Ganlin Zhang, Guowang Yang
Background
In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations.
Methods
We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13.
Results
By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001–1.204, P = 0.047; IL-2, OR = 1.112, 95 % CI 1.009–1.225, P = 0.032; IL-13, OR = 1.068, 95 % CI 1.007–1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010–1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer.
Conclusion
The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.
背景近年来,有相关研究报告称,炎性细胞因子与癌症的发生有关。然而,与肺癌的相关性尚不明确。方法我们通过开放数据库获得了炎性细胞因子的单核苷酸多态性(SNPs),并通过 IEU OpenGWAS 项目获得了肺癌(欧洲和东亚)的 SNPs。反方差加权(IVW)磁共振分析用于确定暴露和结果的因果关系。此外,还使用加权中位数和 MR-Egger 回归进行了补充分析。之后,还进行了敏感性分析以检验稳健性。结果通过 IVW 方法,我们发现 CTACK、IL-2 和 IL-13 与欧洲人群肺癌风险增加有关(CTACK,OR = 1.098,95 % CI 1.001-1.204,P = 0.047;IL-2,OR = 1.112,95 % CI 1.009-1.225,P = 0.032;IL-13,OR = 1.068,95 % CI 1.007-1.132,P = 0.029),而在东亚人群中,只有 IL-13 与肺癌风险增加有关(IL-13,OR = 1.110,95 % CI 1.010-1.220,P = 0.030)。加权中位数和MR-Egger回归方法与IVW效应大小方向相同。此外,使用 MR-Egger 截距作为敏感性分析,也没有发现多向性的证据。结论研究结果表明,炎性细胞因子 CTACK、IL-2 和 IL-13 会增加罹患肺癌的风险。目前缺乏针对这三个靶点的药物适应症。我们探讨了炎性细胞因子与肺癌之间的因果关系,为未来的癌症预测模型和抗肿瘤治疗靶点提供了依据。
{"title":"Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study","authors":"Zishen Liu, Yingying Zheng, Mengqi Yuan, Ganlin Zhang, Guowang Yang","doi":"10.1016/j.cyto.2024.156680","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156680","url":null,"abstract":"<div><h3>Background</h3><p>In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations.</p></div><div><h3>Methods</h3><p>We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13.</p></div><div><h3>Results</h3><p>By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001–1.204, <em>P</em> = 0.047; IL-2, OR = 1.112, 95 % CI 1.009–1.225, <em>P</em> = 0.032; IL-13, OR = 1.068, 95 % CI 1.007–1.132, <em>P</em> = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010–1.220, <em>P</em> = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer.</p></div><div><h3>Conclusion</h3><p>The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333152","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}
Pub Date : 2024-06-14DOI: 10.1016/j.cyto.2024.156669
Jiahui Chen , Yuyu Ma , Yumei Liu , Hui Zhao , Xinwei Qi , Yuqin Sun , Xuan Zhou , Jinping Zhou , Xiumin Ma , Liang Wang
Objectives
Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality.
Methods
This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses.
Results
The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80.
Conclusion
CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.
{"title":"CCL17 and CCL19 are markers of disease progression in alveolar echinococcosis","authors":"Jiahui Chen , Yuyu Ma , Yumei Liu , Hui Zhao , Xinwei Qi , Yuqin Sun , Xuan Zhou , Jinping Zhou , Xiumin Ma , Liang Wang","doi":"10.1016/j.cyto.2024.156669","DOIUrl":"10.1016/j.cyto.2024.156669","url":null,"abstract":"<div><h3>Objectives</h3><p>Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality.</p></div><div><h3>Methods</h3><p>This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses.</p></div><div><h3>Results</h3><p>The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80.</p></div><div><h3>Conclusion</h3><p>CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320212","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}