Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.025157
Xianglai Jiang, Jin He, Yongfeng Wang, Jiahui Liu, Xiangyang Li, Xiaoniu He, Hui Cai
B and T-lymphocyte attenuator (BTLA) plays an immunosuppressive role by inhibiting Tand B-cell functions. BTLA is associated with a variety of diseases, especially cancer immunity. However, the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed. This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression, its clinical value, immune infiltration, and the correlation with immune-related genes in various cancers. Data regarding mRNA expression, miRNA expression, lncRNA expression, and clinical data of patients of 33 existing cancers were collected from the TCGA database. Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database. Based on bioinformatics analysis methods, the relationship between various types of cancers and BTLA was thoroughly investigated, and a competing endogenous RNA network of BTLA, target miRNA, and interacting lncRNA was constructed. The Kaplan-Meier (KM) prognostic analysis of BTLA and target miRNA (has-miR-137) in various types of cancers was completed using the KM plotter. BTLA expression varied in different cancers, with statistical significance in nine cancer types. KM plotter to analyze the overall survival (OS) and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers; the OS of 8 type of cancers was also statistically different. Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene (CTLA4 and PDCD1) expression. Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways, including immune response regulation, cell surface receptor signaling pathway, antigen binding, antigen receptor-mediated signaling pathway, and leukocyte migration. BTLA has the potential as a prognostic marker for CLL, COAD, NSCLC, and OV and a diagnostic marker for CLL, COAD, and KIRC. BTLA has a close and complex relationship with the occurrence and development of tumors, and cancer immunotherapy for BTLA is worthy of further analysis.
{"title":"A pan-cancer analysis of the biological function and clinical value of BTLA in tumors","authors":"Xianglai Jiang, Jin He, Yongfeng Wang, Jiahui Liu, Xiangyang Li, Xiaoniu He, Hui Cai","doi":"10.32604/biocell.2023.025157","DOIUrl":"https://doi.org/10.32604/biocell.2023.025157","url":null,"abstract":"B and T-lymphocyte attenuator (BTLA) plays an immunosuppressive role by inhibiting Tand B-cell functions. BTLA is associated with a variety of diseases, especially cancer immunity. However, the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed. This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression, its clinical value, immune infiltration, and the correlation with immune-related genes in various cancers. Data regarding mRNA expression, miRNA expression, lncRNA expression, and clinical data of patients of 33 existing cancers were collected from the TCGA database. Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database. Based on bioinformatics analysis methods, the relationship between various types of cancers and BTLA was thoroughly investigated, and a competing endogenous RNA network of BTLA, target miRNA, and interacting lncRNA was constructed. The Kaplan-Meier (KM) prognostic analysis of BTLA and target miRNA (has-miR-137) in various types of cancers was completed using the KM plotter. BTLA expression varied in different cancers, with statistical significance in nine cancer types. KM plotter to analyze the overall survival (OS) and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers; the OS of 8 type of cancers was also statistically different. Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene (CTLA4 and PDCD1) expression. Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways, including immune response regulation, cell surface receptor signaling pathway, antigen binding, antigen receptor-mediated signaling pathway, and leukocyte migration. BTLA has the potential as a prognostic marker for CLL, COAD, NSCLC, and OV and a diagnostic marker for CLL, COAD, and KIRC. BTLA has a close and complex relationship with the occurrence and development of tumors, and cancer immunotherapy for BTLA is worthy of further analysis.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76755198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.028331
Qiao-mei Zhou, Jian Liu, L. Xin, Yanyan Fang, L. Wan, D. Huang, J. Wen
{"title":"Exploration of the oxidative-inflammatory potential targets of Coicis Semen in osteoarthritis: Data mining and systematic pharmacology","authors":"Qiao-mei Zhou, Jian Liu, L. Xin, Yanyan Fang, L. Wan, D. Huang, J. Wen","doi":"10.32604/biocell.2023.028331","DOIUrl":"https://doi.org/10.32604/biocell.2023.028331","url":null,"abstract":"","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86823146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.028567
Carl RANDALL HARREL, Valentin Djonov, A. Volarević, D. Pavlovic, V. Volarevic
{"title":"The role of mesenchymal stem cell-derived exosomes in tumor progression","authors":"Carl RANDALL HARREL, Valentin Djonov, A. Volarević, D. Pavlovic, V. Volarevic","doi":"10.32604/biocell.2023.028567","DOIUrl":"https://doi.org/10.32604/biocell.2023.028567","url":null,"abstract":"","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86444360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.025203
Xiaoxu Zhang, Lin Zhang, Lin Du, Huiyan Sun, Xia Zhao, Yang Sun, Wen Wang, Lisheng Wang
: Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation, differentiation, and immune regulation. However, during in vitro expansion, MSCs are prone to aging, which largely limits their application. Prostaglandin E-2 (PGE-2) is a key effector secreted by MSCs to exert immunomodulatory effects. By screening the compound library for PGE-2 secretion, the antioxidant trolox was veri fi ed as a stimulator of MSCs to secrete PGE-2. The effect of antioxidant trolox on biological characteristics of MSCS, including aging, proliferation, and gene expression, was examined. The results demonstrated that trolox can resist aging, promote proliferation, and enhance PGE-2 secretion of MSCs without affecting their surface marker expression. Furthermore, trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects. Thus, trolox addition might be bene fi cial for MSCs expansion and their application.
{"title":"The antioxidant trolox inhibits aging and enhances prostaglandin E-2 secretion in mesenchymal stem cells","authors":"Xiaoxu Zhang, Lin Zhang, Lin Du, Huiyan Sun, Xia Zhao, Yang Sun, Wen Wang, Lisheng Wang","doi":"10.32604/biocell.2023.025203","DOIUrl":"https://doi.org/10.32604/biocell.2023.025203","url":null,"abstract":": Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation, differentiation, and immune regulation. However, during in vitro expansion, MSCs are prone to aging, which largely limits their application. Prostaglandin E-2 (PGE-2) is a key effector secreted by MSCs to exert immunomodulatory effects. By screening the compound library for PGE-2 secretion, the antioxidant trolox was veri fi ed as a stimulator of MSCs to secrete PGE-2. The effect of antioxidant trolox on biological characteristics of MSCS, including aging, proliferation, and gene expression, was examined. The results demonstrated that trolox can resist aging, promote proliferation, and enhance PGE-2 secretion of MSCs without affecting their surface marker expression. Furthermore, trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects. Thus, trolox addition might be bene fi cial for MSCs expansion and their application.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90402015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The development and prognosis of breast cancer are intricately linked to psychological stress. In addition, depression is the most common psychological comorbidity among breast cancer survivors, and reportedly, Fang-Xia-Dihuang decoction (FXDH) can effectively manage depression in such patients. However, its pharmacological and molecular mechanisms remain obscure. Methods: Public databases were used for obtaining active components and related targets. Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways. Molecule docking was used to understand the interactions between main compounds and hub targets. In addition, an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology. Results: 174 active components of FXDH and 163 intersection targets of FXDH, breast cancer, and depression were identified. Quercetin, methyl ferulate, luteolin, ferulaldehyde, wogonin, and diincarvilone were identified as the principal active components of FXDH. Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression. In addition, in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression. FXDH treatment downregulated the expression of epinephrine, PI3K, AKT, STAT3, and JAK2 compared with the control treatment (p < 0.05). Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT, and STAT3. Conclusion: This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress. The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways. This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
{"title":"Fang-Xia-Dihuang decoction inhibits breast cancer progression induced by psychological stress via down-regulation of PI3K/AKT and JAK2/STAT3 pathways: An in vivo and a network pharmacology assessment","authors":"LINGYAN LV, JING ZHAO, XUAN WANG, LIUYAN XU, YINGYI FAN, CHUNHUI WANG, HONGQIAO FAN, XIAOHUA PEI","doi":"10.32604/biocell.2023.030742","DOIUrl":"https://doi.org/10.32604/biocell.2023.030742","url":null,"abstract":"<b>Background:</b> The development and prognosis of breast cancer are intricately linked to psychological stress. In addition, depression is the most common psychological comorbidity among breast cancer survivors, and reportedly, Fang-Xia-Dihuang decoction (FXDH) can effectively manage depression in such patients. However, its pharmacological and molecular mechanisms remain obscure. <b>Methods:</b> Public databases were used for obtaining active components and related targets. Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways. Molecule docking was used to understand the interactions between main compounds and hub targets. In addition, an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology. <b>Results:</b> 174 active components of FXDH and 163 intersection targets of FXDH, breast cancer, and depression were identified. Quercetin, methyl ferulate, luteolin, ferulaldehyde, wogonin, and diincarvilone were identified as the principal active components of FXDH. Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression. In addition, <i>in vivo</i> experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression. FXDH treatment downregulated the expression of epinephrine, PI3K, AKT, STAT3, and JAK2 compared with the control treatment (<i>p</i> < 0.05). Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT, and STAT3. <b>Conclusion:</b> This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress. The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways. This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135753664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.32604/biocell.2023.029277
CHUNYANG XU, CAIYUN YANG, JINSONG ZHANG, XIAOHUA PAN, JUN WANG, LEI JIANG, HONGWEI YE, BO CHEN
Background: The lung is one of the primary target organs of hydrogen sulfide (H2S), as exposure to H2S can cause acute lung injury (ALI) and pulmonary edema. Dexamethasone (Dex) exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic; however, the underlying mechanisms remain elusive, and the dose is unclear. Methods:In vivo experiments: divided C57BL6 mice into 6 groups at random, 12 in each group. The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure, sacrificed 12 h later. The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated. The wet/dry ratio of lung tissue was measured. Bronchial alveolar lavage fluid (BALF) protein content and lung permeability index were detected. The expression of AQP5 protein was measured by immunohistochemistry and Western Blot (WB). In vitro experiments: divided human lung adenocarcinoma cell line A549 into 4 groups. 1 μmol/L dexamethasone was added to pre-incubation. The WB analyzed the protein of p-ERK1/2, p-JNK, and p-p38 in MAPK pathway after 1 h of NaHS exposure; six hours after NaHS exposure, the AQP5 protein was measured by WB. Results: Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall, increase the wet-to-dry weight ratio and decrease pulmonary permeability index, with high-dose dexamethasone seemingly functioning better. Additionally, our previous studies showed that aquaporin 5 (AQP 5), a critical protein that regulates water flux, decreased both in a mouse and cell model following the exposure to H2S. This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment. Additionally, the mitogen activated protein kinase (MAPK) pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2S-induced MAPK activation could be inhibited by Dex. Conclusion: The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.
{"title":"The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide","authors":"CHUNYANG XU, CAIYUN YANG, JINSONG ZHANG, XIAOHUA PAN, JUN WANG, LEI JIANG, HONGWEI YE, BO CHEN","doi":"10.32604/biocell.2023.029277","DOIUrl":"https://doi.org/10.32604/biocell.2023.029277","url":null,"abstract":"<b>Background:</b> The lung is one of the primary target organs of hydrogen sulfide (H<sub>2</sub>S), as exposure to H<sub>2</sub>S can cause acute lung injury (ALI) and pulmonary edema. Dexamethasone (Dex) exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic; however, the underlying mechanisms remain elusive, and the dose is unclear. <b>Methods:</b> <i>In vivo</i> experiments: divided C57BL6 mice into 6 groups at random, 12 in each group. The mice were exposed to H<sub>2</sub>S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure, sacrificed 12 h later. The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated. The wet/dry ratio of lung tissue was measured. Bronchial alveolar lavage fluid (BALF) protein content and lung permeability index were detected. The expression of AQP5 protein was measured by immunohistochemistry and Western Blot (WB). <i>In vitro</i> experiments: divided human lung adenocarcinoma cell line A549 into 4 groups. 1 μmol/L dexamethasone was added to pre-incubation. The WB analyzed the protein of p-ERK1/2, p-JNK, and p-p38 in MAPK pathway after 1 h of NaHS exposure; six hours after NaHS exposure, the AQP5 protein was measured by WB. <b>Results:</b> Dex treatment could significantly attenuate the H<sub>2</sub>S-induced destruction to the alveolar wall, increase the wet-to-dry weight ratio and decrease pulmonary permeability index, with high-dose dexamethasone seemingly functioning better. Additionally, our previous studies showed that aquaporin 5 (AQP 5), a critical protein that regulates water flux, decreased both in a mouse and cell model following the exposure to H<sub>2</sub>S. This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment. Additionally, the mitogen activated protein kinase (MAPK) pathway may be involved in the protective effects of Dex in ALI caused by exposure to H<sub>2</sub>S since H<sub>2</sub>S-induced MAPK activation could be inhibited by Dex. <b>Conclusion:</b> The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H<sub>2</sub>S or other hazardous gases-induced ALI.","PeriodicalId":55384,"journal":{"name":"Biocell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135755121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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