Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA)
{"title":"The Role of PTEN in Nasopharyngeal Carcinoma","authors":"Yan Chen, Shuli Xu, Yingchun He, Lan He","doi":"10.31083/j.fbl2905179","DOIUrl":"https://doi.org/10.31083/j.fbl2905179","url":null,"abstract":"Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA)","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":" 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Naso, A. Gandaglia, G. Sturaro, Cesare Galli, Robert J. Melder
Background : Recent studies highlighted the presence of anti-α -Gal antibodies in patients implanted with commercial bioprosthetic heart valves (BHVs). BHVs expose residual α -Gal xenoantigen and their recognition by the circulating anti-Gal antibodies leads to opsonization of the device’s tissue component with the consequent triggering of a deterioration pathway that culminates with calcification. Small animal models such as mice and rats have been broadly involved in the in vivo testing of biomaterials by subcutaneous implantation, especially for the effectiveness of BHVs anti-calcific treatments. However, since models employed for this purpose express α -Gal antigen, the implantation of BHVs’ leaflets does not elicit a proper immunological response, so the calcification propensity may be dramatically underestimated. Methods : An α -Gal knockout (KO) mouse model has been created, using the CRISP/Cas9 approach, and adopted to assess the calcification potential of commercial BHVs leaflets through the surgical implantation in the back subcutis area. Calcium quantification was performed by inductively coupled plasma analysis; immune response against the BHVs leaflets and α -Gal silencing was evaluated through immunological assays. Results : Two months after the implantation of commercial BHV leaflets, the anti-Gal antibody titers in KO mice doubled when compared with those found in wild-type (WT) ones. Leaflets explanted from KO mice, after one month, showed a four-time increased calcium deposition concerning the ones explanted from WT. The degree of silencing of α -Gal varied, depending on the specific organ that was assessed. In any case, the animal model was suitable for evaluating implanted tissue responses. Conclusions : Such mouse model proved to be an accurate tool for the study of the calcific propensity of commercial BHVs leaflets than those hitherto used. Given its reliability, it could also be successfully used to study even other diseases in which the possible involvement of α -Gal has been observed.
{"title":"The α-Gal KO Mouse Animal Model is a Reliable and Predictive Tool for the Immune-Mediated Calcification Assessment of Heart Valve Bioprostheses","authors":"F. Naso, A. Gandaglia, G. Sturaro, Cesare Galli, Robert J. Melder","doi":"10.31083/j.fbl2905181","DOIUrl":"https://doi.org/10.31083/j.fbl2905181","url":null,"abstract":"Background : Recent studies highlighted the presence of anti-α -Gal antibodies in patients implanted with commercial bioprosthetic heart valves (BHVs). BHVs expose residual α -Gal xenoantigen and their recognition by the circulating anti-Gal antibodies leads to opsonization of the device’s tissue component with the consequent triggering of a deterioration pathway that culminates with calcification. Small animal models such as mice and rats have been broadly involved in the in vivo testing of biomaterials by subcutaneous implantation, especially for the effectiveness of BHVs anti-calcific treatments. However, since models employed for this purpose express α -Gal antigen, the implantation of BHVs’ leaflets does not elicit a proper immunological response, so the calcification propensity may be dramatically underestimated. Methods : An α -Gal knockout (KO) mouse model has been created, using the CRISP/Cas9 approach, and adopted to assess the calcification potential of commercial BHVs leaflets through the surgical implantation in the back subcutis area. Calcium quantification was performed by inductively coupled plasma analysis; immune response against the BHVs leaflets and α -Gal silencing was evaluated through immunological assays. Results : Two months after the implantation of commercial BHV leaflets, the anti-Gal antibody titers in KO mice doubled when compared with those found in wild-type (WT) ones. Leaflets explanted from KO mice, after one month, showed a four-time increased calcium deposition concerning the ones explanted from WT. The degree of silencing of α -Gal varied, depending on the specific organ that was assessed. In any case, the animal model was suitable for evaluating implanted tissue responses. Conclusions : Such mouse model proved to be an accurate tool for the study of the calcific propensity of commercial BHVs leaflets than those hitherto used. Given its reliability, it could also be successfully used to study even other diseases in which the possible involvement of α -Gal has been observed.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"F2RL3 Regulates Epithelial-Mesenchymal Transition and Angiogenesis in Gastric Cancer through the Rap1/MAPK Signaling Pathway","authors":"Jun Ma, Yongkang Shi, Qiliang Lu, Dongsheng Huang","doi":"10.31083/j.fbl2905177","DOIUrl":"https://doi.org/10.31083/j.fbl2905177","url":null,"abstract":"","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140994278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tariq Aziz, M. Naveed, M. A. Shabbir, Khizra Jabeen, Ayaz Ali Khan, Ammarah Hasnain, Zhennai Yang, A. Zinedine, João Miguel Rocha, Thamer H Albekairi
Background : Listeria monocytogenes , a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease. Methods : A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against L. monocytogenes . The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response. Results : The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct’s efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells. Conclusions : The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against Listeria , paving the way for future advances in preventive methods and vaccine design.
{"title":"Designing a Multiepitope Vaccine against the Foodborne Pathogenic Bacteria Listeria monocytogenes Using Subtractive Immunoinformatics Approaches","authors":"Tariq Aziz, M. Naveed, M. A. Shabbir, Khizra Jabeen, Ayaz Ali Khan, Ammarah Hasnain, Zhennai Yang, A. Zinedine, João Miguel Rocha, Thamer H Albekairi","doi":"10.31083/j.fbl2905176","DOIUrl":"https://doi.org/10.31083/j.fbl2905176","url":null,"abstract":"Background : Listeria monocytogenes , a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease. Methods : A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against L. monocytogenes . The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response. Results : The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct’s efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells. Conclusions : The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against Listeria , paving the way for future advances in preventive methods and vaccine design.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140994688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanguang Yang, Yuting Gao, Yajun Xiong, Yi Gong, Junlan Lu, Yuman Zhang, Dan Wang, Zhihan Liu, Xinli Shi
The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.
{"title":"Research Progress of Warburg Effect in Hepatocellular Carcinoma","authors":"Yanguang Yang, Yuting Gao, Yajun Xiong, Yi Gong, Junlan Lu, Yuman Zhang, Dan Wang, Zhihan Liu, Xinli Shi","doi":"10.31083/j.fbl2905178","DOIUrl":"https://doi.org/10.31083/j.fbl2905178","url":null,"abstract":"The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuropares-thesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.
{"title":"TRPV1 in Dry Eye Disease","authors":"Qingqing Gou, Zhi Song, Yu Gong, Jiawen Li","doi":"10.31083/j.fbl2905175","DOIUrl":"https://doi.org/10.31083/j.fbl2905175","url":null,"abstract":"Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuropares-thesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"140 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhipeng Li, Hui Chen, Zhongqing Chen, Lihe Xie, D. Pan
Background: Gastric adenocarcinoma (GAC) is a malignant tumor with the highest incidence in the digestive system. Macrophages have been proven to play important roles in tumor microenvironment. Methods: Herein, single-cell RNA sequencing (scRNA-seq) profiles from the Gene Expression Omnibus (GEO) and bulk RNA-seq data from the Cancer Genome Atlas (TCGA) database were utilized to construct a macrophage marker gene signature (MMGS) to predict the prognosis of GAC patients. Subsequently, a risk score model based on the MMGS was built to predict the prognosis of GAC patients; further, this was validated in the GEO cohort. The risk score categorized patients into the high-and low-risk groups. A nomogram model based on the risk score and clinic-pathological characteristics was developed. Results: Seven genes, ABCA1 , CTHRC1 , GADD45B , NPC2 , PLTP , PRSS23 , and RNASE1 , were included in the risk score model. Patients with a low-risk score showed a better prognosis. The MMGS had good sensitivity and specificity for predicting the prognosis inGAC patients. The risk score was an independent prognostic factor. The constructed nomogram exhibited favorable predictability and reliability for predicting GAC prognosis. Conclusion: In conclusion, the risk score model based on the seven MMGSs performed well in the predicting prognosis of GAC patients. Our study may provide new insights into clinical decision-making for the personalized treatment of patients with gastric cancer (GC).
{"title":"Bioinformatics Analysis Reveals Prognostic Significance of the Macrophage Marker Gene Signature in Gastric Adenocarcinoma","authors":"Zhipeng Li, Hui Chen, Zhongqing Chen, Lihe Xie, D. Pan","doi":"10.31083/j.fbl2905172","DOIUrl":"https://doi.org/10.31083/j.fbl2905172","url":null,"abstract":"Background: Gastric adenocarcinoma (GAC) is a malignant tumor with the highest incidence in the digestive system. Macrophages have been proven to play important roles in tumor microenvironment. Methods: Herein, single-cell RNA sequencing (scRNA-seq) profiles from the Gene Expression Omnibus (GEO) and bulk RNA-seq data from the Cancer Genome Atlas (TCGA) database were utilized to construct a macrophage marker gene signature (MMGS) to predict the prognosis of GAC patients. Subsequently, a risk score model based on the MMGS was built to predict the prognosis of GAC patients; further, this was validated in the GEO cohort. The risk score categorized patients into the high-and low-risk groups. A nomogram model based on the risk score and clinic-pathological characteristics was developed. Results: Seven genes, ABCA1 , CTHRC1 , GADD45B , NPC2 , PLTP , PRSS23 , and RNASE1 , were included in the risk score model. Patients with a low-risk score showed a better prognosis. The MMGS had good sensitivity and specificity for predicting the prognosis inGAC patients. The risk score was an independent prognostic factor. The constructed nomogram exhibited favorable predictability and reliability for predicting GAC prognosis. Conclusion: In conclusion, the risk score model based on the seven MMGSs performed well in the predicting prognosis of GAC patients. Our study may provide new insights into clinical decision-making for the personalized treatment of patients with gastric cancer (GC).","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"58 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141008864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyi Long, Xiaojie Liu, Wenjun Xia, Lu Liu, Wei Chen
Background : Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent CRC cell proliferation. Therefore, clarifying the molecular mechanism of brexpipra-zole is vital to developing a novel therapeutic strategy for CRC. Methods : The effect of brexpiprazole on human colorectal cancer cell proliferation was measured with Cell Counting Kit-8 (CCK-8) kits. Cell migration capability was measured using wound healing and transwell. Cell apoptosis was evaluated with a flow cytometer. Western blots and immunohistochemical staining were used to evaluate protein expression. The effects observed in vitro were also confirmed in xenograft models. Results : Brexpiprazole remarkably inhibited the proliferation, suppressed the migration ability, and induced apoptosis of colorectal cancer cells. Mechanism study showed that brex-piprazole exerted these effects by inhibiting the EGFR pathway. Brexpiprazole enhanced HCT116 cells’ sensitivity to cetuximab, and a combination of brexpiprazole and cetuximab inhibited xenograft tumor growth in vivo . Conclusions : Our finding suggested that brex-piprazole inhibits proliferation, promotes apoptosis, and enhances CRC cells’ sensitivity to cetuximab by regulating the EGFR pathway and it might be an efficacious treatment strategy for CRC.
{"title":"Brexpiprazole Prevents the Malignant Progression of Human Colorectal Cancer Cells and Increases Its Sensitivity to EGFR Inhibition","authors":"Xiaoyi Long, Xiaojie Liu, Wenjun Xia, Lu Liu, Wei Chen","doi":"10.31083/j.fbl2905174","DOIUrl":"https://doi.org/10.31083/j.fbl2905174","url":null,"abstract":"Background : Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent CRC cell proliferation. Therefore, clarifying the molecular mechanism of brexpipra-zole is vital to developing a novel therapeutic strategy for CRC. Methods : The effect of brexpiprazole on human colorectal cancer cell proliferation was measured with Cell Counting Kit-8 (CCK-8) kits. Cell migration capability was measured using wound healing and transwell. Cell apoptosis was evaluated with a flow cytometer. Western blots and immunohistochemical staining were used to evaluate protein expression. The effects observed in vitro were also confirmed in xenograft models. Results : Brexpiprazole remarkably inhibited the proliferation, suppressed the migration ability, and induced apoptosis of colorectal cancer cells. Mechanism study showed that brex-piprazole exerted these effects by inhibiting the EGFR pathway. Brexpiprazole enhanced HCT116 cells’ sensitivity to cetuximab, and a combination of brexpiprazole and cetuximab inhibited xenograft tumor growth in vivo . Conclusions : Our finding suggested that brex-piprazole inhibits proliferation, promotes apoptosis, and enhances CRC cells’ sensitivity to cetuximab by regulating the EGFR pathway and it might be an efficacious treatment strategy for CRC.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141009541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background : Neointimal hyperplasia (NIH) is the pathological basis of vascular injury disease. Vascular cells are the dominant cells in the process of NIH, but the extent of heterogeneity amongst them is still unclear. Methods : A mouse model of NIH was constructed by inducing carotid artery ligation. Single-cell sequencing was then used to analyze the transcriptional profile of vascular cells. Cluster features were determined by functional enrichment analysis, gene set scoring, pseudo-time analysis, and cell-cell communication analysis. Additionally, immunofluorescencestainingwasconductedonvasculartissuesfromfibroblastlineage-traced(Pdgfra DreER -tdTomato)mice to validate the presence of Pecam1 + Pdgfra + tdTomato + cells. Results : The left carotid arteries (ligation) were compared to right carotid arteries (sham) from ligation-induced NIH C57BL/6 mice. Integrative analyses revealed a high level of heterogeneity amongst vascular cells, including fourteen clusters and seven cell types. We focused on three dominant cell types: endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and fibroblasts. The major findings were: (1) four subpopulations of ECs, including ECs4, mesenchymal-like ECs (ECs1 and ECs2), and fibro-like ECs (ECs3); (2) four subpopulations of fibroblasts, including pro-inflammatory Fibs-1, Sca1 + Fibs-2, collagen-producing Fibs-3, and mesenchymal-like Fibs-4; (3) four subpopulations of vSMCs, including vSMCs-1, vSMCs-2, vSMCs-3, and vSMCs-3-derived vSMCs; (4) ECs3 express genes related to extracellular matrix (ECM) remodeling and cell migration, and fibro-like vSMCs showed strong chemokine secretion and relatively high levels of proteases; (5) fibro-like vSMCs that secrete Vegfa interact with ECs mainly through vascular endothelial growth factor receptor 2 (Vegfr2). Conclusions : This study presents the dynamic cellular landscape within NIH arteries and reveals potential relationships between several clusters, with a specific focus on ECs3 and fibro-like vSMCs. These two subpopulations may represent potential target cells for the treatment of NIH.
{"title":"Single-Cell Transcriptome Analysis Reveals Dynamic Populations of Vascular Cells in Neointimal Hyperplasia","authors":"Guangzhen Shi, Xinran Tong, Weihong Sun, Zilong Fang, Wendong Chen, Gonghao Jiang, Peili Zhang, Qun Li","doi":"10.31083/j.fbl2905173","DOIUrl":"https://doi.org/10.31083/j.fbl2905173","url":null,"abstract":"Background : Neointimal hyperplasia (NIH) is the pathological basis of vascular injury disease. Vascular cells are the dominant cells in the process of NIH, but the extent of heterogeneity amongst them is still unclear. Methods : A mouse model of NIH was constructed by inducing carotid artery ligation. Single-cell sequencing was then used to analyze the transcriptional profile of vascular cells. Cluster features were determined by functional enrichment analysis, gene set scoring, pseudo-time analysis, and cell-cell communication analysis. Additionally, immunofluorescencestainingwasconductedonvasculartissuesfromfibroblastlineage-traced(Pdgfra DreER -tdTomato)mice to validate the presence of Pecam1 + Pdgfra + tdTomato + cells. Results : The left carotid arteries (ligation) were compared to right carotid arteries (sham) from ligation-induced NIH C57BL/6 mice. Integrative analyses revealed a high level of heterogeneity amongst vascular cells, including fourteen clusters and seven cell types. We focused on three dominant cell types: endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and fibroblasts. The major findings were: (1) four subpopulations of ECs, including ECs4, mesenchymal-like ECs (ECs1 and ECs2), and fibro-like ECs (ECs3); (2) four subpopulations of fibroblasts, including pro-inflammatory Fibs-1, Sca1 + Fibs-2, collagen-producing Fibs-3, and mesenchymal-like Fibs-4; (3) four subpopulations of vSMCs, including vSMCs-1, vSMCs-2, vSMCs-3, and vSMCs-3-derived vSMCs; (4) ECs3 express genes related to extracellular matrix (ECM) remodeling and cell migration, and fibro-like vSMCs showed strong chemokine secretion and relatively high levels of proteases; (5) fibro-like vSMCs that secrete Vegfa interact with ECs mainly through vascular endothelial growth factor receptor 2 (Vegfr2). Conclusions : This study presents the dynamic cellular landscape within NIH arteries and reveals potential relationships between several clusters, with a specific focus on ECs3 and fibro-like vSMCs. These two subpopulations may represent potential target cells for the treatment of NIH.","PeriodicalId":503756,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"42 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141008198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wentao Lin, Yong Xia, Anqi He, Shuang Chen, Jie Zhang
Background : The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. Methods : Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo , including MBM models. Results : Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. Conclusions : These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.
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