Sérgio Lopes Silva, Genilda Castro de Omena Neta, Rodger Marcel Lima Rocha, Ana Kelly da Silva Fernandes Duarte, Carlos Alberto de Carvalho Fraga
Schwann cells in the tumor microenvironment are reportedly involved in the production of several factors that benefit cancer cell growth. During this process, Schwann cells are dedifferentiated and facilitate cancer cellular proliferation. The cells then migrate to the region close to the tumor tissue and assist the development of the neoplastic cells. Accordingly, the present study was designed to evaluate the perineural invasion in prostate cancer, in association with disrupted circadian rhythm-related gene expression in Schwann cells. Initially, we identified a database reporting gene expression in Schwann cells in a neoplastic context from the GEO Datasets platform in the GEO repository. The database contains the expression results from experiments in which two factors produced by tumor cells were added to cell cultures. Comparisons were made between samples from the first and third passages. Then, these data were used in differential gene expression analysis and combined with differential expression data of genes upregulated in perineural invasion-negative and -positive prostate cancers. We observed that the “axon guidance” pathway was upregulated in perineural invasion-negative prostate cancers. Meanwhile, upregulated mRNAs activated the “axon guidance” pathway and, together with ROBO1 and MPZ upregulation, inhibited perineural invasion pathways. Both genes are also associated with inhibition of Schwann cell migration. PER3, NR3C1, PPARGC1A, TIMP3, ID2, PDE6B, and CAVIN1 were upregulated in perineural invasion-negative tumors, while SLC25A10 was upregulated. We also observed upregulated expression in perineural invasion-positive tumors for genes such as PPARGC1A, TIMP3, S100A8, ID2, DEFB1, AQP3, ASS1, PDE6B, NEFH, and CAVIN1. AQP3 and NEFH were upregulated only in perineural invasion-positive tumors and PER3 and NR3C1 were upregulated only in perineural invasion-negative samples. The findings revealed that circadian rhythm and/or melatonin disruption are associated with dedifferentiation of Schwann cells, which consequently produce a set of factors that drive tumor progression. These processes may also be involved in tumor invasion into the perineural tissue in prostate cancer.
{"title":"Perineural invasion in prostate cancer is associated with Schwann cells and disruption of circadian rhythm-related gene expression: A bioinformatics approach","authors":"Sérgio Lopes Silva, Genilda Castro de Omena Neta, Rodger Marcel Lima Rocha, Ana Kelly da Silva Fernandes Duarte, Carlos Alberto de Carvalho Fraga","doi":"10.36922/gpd.3146","DOIUrl":"https://doi.org/10.36922/gpd.3146","url":null,"abstract":"Schwann cells in the tumor microenvironment are reportedly involved in the production of several factors that benefit cancer cell growth. During this process, Schwann cells are dedifferentiated and facilitate cancer cellular proliferation. The cells then migrate to the region close to the tumor tissue and assist the development of the neoplastic cells. Accordingly, the present study was designed to evaluate the perineural invasion in prostate cancer, in association with disrupted circadian rhythm-related gene expression in Schwann cells. Initially, we identified a database reporting gene expression in Schwann cells in a neoplastic context from the GEO Datasets platform in the GEO repository. The database contains the expression results from experiments in which two factors produced by tumor cells were added to cell cultures. Comparisons were made between samples from the first and third passages. Then, these data were used in differential gene expression analysis and combined with differential expression data of genes upregulated in perineural invasion-negative and -positive prostate cancers. We observed that the “axon guidance” pathway was upregulated in perineural invasion-negative prostate cancers. Meanwhile, upregulated mRNAs activated the “axon guidance” pathway and, together with ROBO1 and MPZ upregulation, inhibited perineural invasion pathways. Both genes are also associated with inhibition of Schwann cell migration. PER3, NR3C1, PPARGC1A, TIMP3, ID2, PDE6B, and CAVIN1 were upregulated in perineural invasion-negative tumors, while SLC25A10 was upregulated. We also observed upregulated expression in perineural invasion-positive tumors for genes such as PPARGC1A, TIMP3, S100A8, ID2, DEFB1, AQP3, ASS1, PDE6B, NEFH, and CAVIN1. AQP3 and NEFH were upregulated only in perineural invasion-positive tumors and PER3 and NR3C1 were upregulated only in perineural invasion-negative samples. The findings revealed that circadian rhythm and/or melatonin disruption are associated with dedifferentiation of Schwann cells, which consequently produce a set of factors that drive tumor progression. These processes may also be involved in tumor invasion into the perineural tissue in prostate cancer.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"113 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141665931","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}
Dorra Guermazi, Saira Khan, Asghar Shah, E. Saliba
Exosomes are small extracellular vesicles that play an important role in intercellular communication by transporting proteins, lipids, and nucleic acids between cells. They have emerged as relevant research areas due to their involvement in regulating various physiological and pathological processes. This review explores the potential applications of exosome-based therapies in dermatology and examines the safety aspects of these treatments. Past research has demonstrated that exosomes may effectively treat conditions such as alopecia and accelerate wound healing by stimulating hair follicle growth and enhancing tissue regeneration. Studies have shown that exosomes can promote the proliferation of dermal papilla cells and hair follicle growth in cases of alopecia. They also accelerate wound healing by modulating processes involved in inflammation, cell migration, and tissue remodeling. However, more research is needed to fully characterize the long-term safety profile of exosomes and establish standardized clinical protocols. Both human-derived and plant-derived exosomes appear to have favorable safety profiles based on current evidence, though plant sources may offer advantages in terms of production and biocompatibility. Continued exploration of exosomes’ mechanisms and potential risks will optimize these innovations and offer safe, effective exosome treatments to patients. While further research is warranted, current findings provide valuable insights into the applications of exosome therapy for dermatological conditions and its emerging role in precision medicine.
{"title":"Tiny messengers, big results: A review of exosome-mediated treatments and considerations in dermatology","authors":"Dorra Guermazi, Saira Khan, Asghar Shah, E. Saliba","doi":"10.36922/gpd.3230","DOIUrl":"https://doi.org/10.36922/gpd.3230","url":null,"abstract":"Exosomes are small extracellular vesicles that play an important role in intercellular communication by transporting proteins, lipids, and nucleic acids between cells. They have emerged as relevant research areas due to their involvement in regulating various physiological and pathological processes. This review explores the potential applications of exosome-based therapies in dermatology and examines the safety aspects of these treatments. Past research has demonstrated that exosomes may effectively treat conditions such as alopecia and accelerate wound healing by stimulating hair follicle growth and enhancing tissue regeneration. Studies have shown that exosomes can promote the proliferation of dermal papilla cells and hair follicle growth in cases of alopecia. They also accelerate wound healing by modulating processes involved in inflammation, cell migration, and tissue remodeling. However, more research is needed to fully characterize the long-term safety profile of exosomes and establish standardized clinical protocols. Both human-derived and plant-derived exosomes appear to have favorable safety profiles based on current evidence, though plant sources may offer advantages in terms of production and biocompatibility. Continued exploration of exosomes’ mechanisms and potential risks will optimize these innovations and offer safe, effective exosome treatments to patients. While further research is warranted, current findings provide valuable insights into the applications of exosome therapy for dermatological conditions and its emerging role in precision medicine.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":" 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678818","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}
Jiali Li, Yanbing Pan, Mengjie Tu, Jiayang Han, Binbin Zhao, Jialin Wu, Guangchao Liu, Kaifeng Zhang, Man Yue, Mengwen Hou, Tiantian Sun, Xu Han, Kangxu Chen, Yang An
The zinc finger protein 521 (ZNF521) gene is located on human chromosome 18, specifically in the 18q11.2 region. As a zinc finger DNA-binding protein, ZNF521/Zfp521 acts as a transcription cofactor involved in the regulation of cell differentiation across various cell types, including hematopoietic, neural, and mesenchyme stem cells, B progenitor cells, preadipocytes, and osteoblasts. Its interactions with key proteins such as RUNX2, EBF1, SIAH2, or BMP2 further modulate these processes. In this review, we briefly summarize the current understanding of ZNF521/Zfp521, encompassing its structural, functional, post-translational modification, and cellular signaling pathways, especially its roles in cell differentiation and related diseases. In addition, we explore the process and effects of the interaction between Zfp521 and other proteins and discuss the molecular mechanisms of its roles in adipogenic, osteogenic, chondrogenic, and neural differentiation.
{"title":"Zinc finger protein 521 (ZNF521/Zfp521): Insights into its structure, function, regulation, and significance to cell differentiation","authors":"Jiali Li, Yanbing Pan, Mengjie Tu, Jiayang Han, Binbin Zhao, Jialin Wu, Guangchao Liu, Kaifeng Zhang, Man Yue, Mengwen Hou, Tiantian Sun, Xu Han, Kangxu Chen, Yang An","doi":"10.36922/gpd.3260","DOIUrl":"https://doi.org/10.36922/gpd.3260","url":null,"abstract":"The zinc finger protein 521 (ZNF521) gene is located on human chromosome 18, specifically in the 18q11.2 region. As a zinc finger DNA-binding protein, ZNF521/Zfp521 acts as a transcription cofactor involved in the regulation of cell differentiation across various cell types, including hematopoietic, neural, and mesenchyme stem cells, B progenitor cells, preadipocytes, and osteoblasts. Its interactions with key proteins such as RUNX2, EBF1, SIAH2, or BMP2 further modulate these processes. In this review, we briefly summarize the current understanding of ZNF521/Zfp521, encompassing its structural, functional, post-translational modification, and cellular signaling pathways, especially its roles in cell differentiation and related diseases. In addition, we explore the process and effects of the interaction between Zfp521 and other proteins and discuss the molecular mechanisms of its roles in adipogenic, osteogenic, chondrogenic, and neural differentiation.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"12 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141686009","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}
T-LAK cell-originated protein kinase (TOPK) is a serine/threonine protein kinase that is specifically expressed in actively proliferating cells, such as normal testicular germ cells, lymphocytes, and various tumor cells. It plays a key role in multiple biological processes, such as cell growth, metastasis, drug resistance, angiogenesis, and inflammation, and is a promising therapeutic target for tumors. Aberrant TOPK overexpression or activation has been observed in lung cancer and is related to lung cancer occurrence and development, clinical outcome, and poor prognosis. The inhibition of TOPK has demonstrated significant therapeutic potential for reducing tumor growth and can even be used in combination with chemotherapy or radiotherapy. Thus, targeting TOPK provides a promising avenue for the prevention and treatment of lung cancer. This article reviews the role of TOPK in the occurrence, development, and drug resistance of lung cancer; summarizes the main signaling pathways affected by TOPK in lung cancer; and analyzes its therapeutic value. The role and potential of TOPK in targeted therapy, chemotherapy, radiotherapy, and immunotherapy for lung cancer are also discussed. In addition, the latest progress in the use of TOPK inhibitors for lung cancer treatment is summarized, and their future clinical application is discussed. Overall, TOPK is a valuable target for the treatment of lung cancer, and further development of specific TOPK inhibitors is indispensable for the comprehensive treatment of lung cancer.
{"title":"TOPK: A noteworthy target for lung cancer treatment","authors":"Wenbo Liu, Feng Zhu, Q. Duan, Yafang Li, Shuang Zhao, Juanjuan Xiao, Yijie Zhang","doi":"10.36922/gpd.3062","DOIUrl":"https://doi.org/10.36922/gpd.3062","url":null,"abstract":"T-LAK cell-originated protein kinase (TOPK) is a serine/threonine protein kinase that is specifically expressed in actively proliferating cells, such as normal testicular germ cells, lymphocytes, and various tumor cells. It plays a key role in multiple biological processes, such as cell growth, metastasis, drug resistance, angiogenesis, and inflammation, and is a promising therapeutic target for tumors. Aberrant TOPK overexpression or activation has been observed in lung cancer and is related to lung cancer occurrence and development, clinical outcome, and poor prognosis. The inhibition of TOPK has demonstrated significant therapeutic potential for reducing tumor growth and can even be used in combination with chemotherapy or radiotherapy. Thus, targeting TOPK provides a promising avenue for the prevention and treatment of lung cancer. This article reviews the role of TOPK in the occurrence, development, and drug resistance of lung cancer; summarizes the main signaling pathways affected by TOPK in lung cancer; and analyzes its therapeutic value. The role and potential of TOPK in targeted therapy, chemotherapy, radiotherapy, and immunotherapy for lung cancer are also discussed. In addition, the latest progress in the use of TOPK inhibitors for lung cancer treatment is summarized, and their future clinical application is discussed. Overall, TOPK is a valuable target for the treatment of lung cancer, and further development of specific TOPK inhibitors is indispensable for the comprehensive treatment of lung cancer.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"14 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141355259","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}
M. Mia, Arafat Rahman Oany, T. Pervin, Syeda Sharmin Duza
Cystic fibrosis (CF), a fatal autosomal recessive disorder, is triggered by a genetic alteration of the CF transmembrane conductance regulator (CFTR) gene. On a global scale, around one in 3000 live births are affected with CF annually. While diagnosis and therapy are available for CF patients with non-specific and rare mutations, the current research is dedicated to exploring customized biomarkers, genes, signaling networks, and therapy for improving the management of CF. Although still in the early stages of development and validation, mRNA and gene-based treatment strategies are aimed to target patients who are resistant to CFTR gene restoration therapies. In this study, we utilized the systems biology approaches integrated with gene expression analysis to identify novel biomarkers and pathways for CF treatment. At first, out of 54,676 differentially expressed genes, we identified 104 upregulated and 107 downregulated genes. The upregulated genes were largely concentrated on Glutamatergic synapses, and the downregulated genes were enriched in ubiquitin-mediated proteolysis. Utilizing the enrichment analysis, we explored deeper into the pathways linked to these genes, with emphasis on relevant pathways involving bronchial epithelial cells. Following the enrichment analysis, we identified six essential genes: WWP2, RNASEL, CUL1, CDC42, HDAC4, and UBA2. Furthermore, the discovered genes were evaluated using expression profile analysis. Finally, our data indicate that the WWP2 gene has a critical role in CF management. The current findings provide a coherent theoretical foundation for future experiments to further explore the WWP2 gene as a unique and prognostic target for developing an effective CF therapeutic approach.
{"title":"Deciphering novel molecular gene expression signatures and pathways in cystic fibrosis through integrative bioinformatics strategies","authors":"M. Mia, Arafat Rahman Oany, T. Pervin, Syeda Sharmin Duza","doi":"10.36922/gpd.2937","DOIUrl":"https://doi.org/10.36922/gpd.2937","url":null,"abstract":"Cystic fibrosis (CF), a fatal autosomal recessive disorder, is triggered by a genetic alteration of the CF transmembrane conductance regulator (CFTR) gene. On a global scale, around one in 3000 live births are affected with CF annually. While diagnosis and therapy are available for CF patients with non-specific and rare mutations, the current research is dedicated to exploring customized biomarkers, genes, signaling networks, and therapy for improving the management of CF. Although still in the early stages of development and validation, mRNA and gene-based treatment strategies are aimed to target patients who are resistant to CFTR gene restoration therapies. In this study, we utilized the systems biology approaches integrated with gene expression analysis to identify novel biomarkers and pathways for CF treatment. At first, out of 54,676 differentially expressed genes, we identified 104 upregulated and 107 downregulated genes. The upregulated genes were largely concentrated on Glutamatergic synapses, and the downregulated genes were enriched in ubiquitin-mediated proteolysis. Utilizing the enrichment analysis, we explored deeper into the pathways linked to these genes, with emphasis on relevant pathways involving bronchial epithelial cells. Following the enrichment analysis, we identified six essential genes: WWP2, RNASEL, CUL1, CDC42, HDAC4, and UBA2. Furthermore, the discovered genes were evaluated using expression profile analysis. Finally, our data indicate that the WWP2 gene has a critical role in CF management. The current findings provide a coherent theoretical foundation for future experiments to further explore the WWP2 gene as a unique and prognostic target for developing an effective CF therapeutic approach.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141365453","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}
Stem cell bioengineering addresses regenerative medicine and cellular therapies by applying advanced techniques to stem-cell-derived systems. Despite their promise, stem cell applications are limited by incomplete knowledge. Stem cells and phytochemicals show potential in treating diabetes by halting β-cell degeneration and promoting endogenous islet regeneration. Current diabetes cell therapies include stem cells, mature pancreatic cells, endocrine progenitors, and β-cells, with researchers actively seeking new cell sources for clinically relevant β-cells. Stem cell-derived pancreatic cells are particularly promising for pancreatic islet regeneration. Diabetes mellitus results from cell loss or malfunction: Type 1 diabetes stems from autoimmune damage, whereas Type 2 diabetes is largely attributed to cell malfunction or insulin resistance. The only operative therapy, islet transplantation, necessitates lifelong immune suppression. Significant progress has been made in strategies for therapeutic adult β-cell regeneration. This review assesses studies on cellular signaling pathways linked to β-cell survival and proliferation, exploring regenerative medicine methodologies for pancreatic islet replacement or regeneration. While the “replacement” technique involves cell transplantation, the “regeneration” strategy preserves cell populations through replication. Moreover, artemether and gamma-aminobutyric acid induce pancreatic cells to adopt β-cell-like phenotypes, potentially aiding in the development of new β-cell-like cells for treating severe diabetes in rats. Understanding G-protein-coupled receptor activation pathways is crucial, as new treatment strategies for insulin-dependent diabetic mellitus may emerge from this knowledge.
{"title":"Decoding and understanding molecular mechanisms: Cell signaling pathways, pancreatic β-cell regeneration, and stem cell niche engineering for diabetes","authors":"Rajiv Kumar, Gerardo Caruso","doi":"10.36922/gpd.2996","DOIUrl":"https://doi.org/10.36922/gpd.2996","url":null,"abstract":"Stem cell bioengineering addresses regenerative medicine and cellular therapies by applying advanced techniques to stem-cell-derived systems. Despite their promise, stem cell applications are limited by incomplete knowledge. Stem cells and phytochemicals show potential in treating diabetes by halting β-cell degeneration and promoting endogenous islet regeneration. Current diabetes cell therapies include stem cells, mature pancreatic cells, endocrine progenitors, and β-cells, with researchers actively seeking new cell sources for clinically relevant β-cells. Stem cell-derived pancreatic cells are particularly promising for pancreatic islet regeneration. Diabetes mellitus results from cell loss or malfunction: Type 1 diabetes stems from autoimmune damage, whereas Type 2 diabetes is largely attributed to cell malfunction or insulin resistance. The only operative therapy, islet transplantation, necessitates lifelong immune suppression. Significant progress has been made in strategies for therapeutic adult β-cell regeneration. This review assesses studies on cellular signaling pathways linked to β-cell survival and proliferation, exploring regenerative medicine methodologies for pancreatic islet replacement or regeneration. While the “replacement” technique involves cell transplantation, the “regeneration” strategy preserves cell populations through replication. Moreover, artemether and gamma-aminobutyric acid induce pancreatic cells to adopt β-cell-like phenotypes, potentially aiding in the development of new β-cell-like cells for treating severe diabetes in rats. Understanding G-protein-coupled receptor activation pathways is crucial, as new treatment strategies for insulin-dependent diabetic mellitus may emerge from this knowledge.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141380994","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}
The conventional clinical therapies for autoimmune diseases (ADs) lack specificity, necessitating long-term medication that can lead to serious side effects. In contrast, chimeric antigen receptor (CAR) T cell therapy for ADs, characterized by fewer side effects and longer-lasting therapeutic effects, represents a new direction for the specific treatment of ADs. T cells modified with CAR genes possess the ability to not only secrete perforin, granzymes, and other molecules that target autoreactive immune cells but also to lead effector and regulatory T cells into autoimmune environments, thereby exerting transport, proliferation, and immune regulatory functions. Chimeric autoantibody receptor T cells can recognize and kill autoreactive cells expressing target autoantibodies through their specific antigens. In this article, we comprehensively expound on the application of CAR-T cell therapy in different ADs and summarize the current research progress in this regard. This review aims to enhance the application of CAR-T therapy in AD treatment and facilitate further studies aimed at addressing the existing gaps in CAR-T therapy for ADs.
治疗自身免疫性疾病（ADs）的传统临床疗法缺乏特异性，需要长期服药，可能导致严重的副作用。相比之下，针对自身免疫性疾病的嵌合抗原受体（CAR）T细胞疗法具有副作用小、疗效持久的特点，是特异性治疗自身免疫性疾病的新方向。经 CAR 基因修饰的 T 细胞不仅能分泌穿孔素、颗粒酶和其他靶向自体反应性免疫细胞的分子，还能引导效应和调节性 T 细胞进入自体免疫环境，从而发挥转运、增殖和免疫调节功能。嵌合型自身抗体受体T细胞可通过其特异性抗原识别并杀伤表达靶自身抗体的自身活性细胞。本文全面阐述了CAR-T细胞疗法在不同AD中的应用，并总结了目前这方面的研究进展。本综述旨在加强CAR-T疗法在AD治疗中的应用，并促进进一步的研究，以弥补CAR-T疗法在AD治疗中的现有不足。
{"title":"Application and research progress of CAR-T cell therapy in autoimmune diseases","authors":"Xiaoxiao Yu, Haodong Shang, Xinru Shen, Jing Zhang, Ting Chang, Zhe Ruan, Yongliang Jia, Feng Gao","doi":"10.36922/gpd.2851","DOIUrl":"https://doi.org/10.36922/gpd.2851","url":null,"abstract":"The conventional clinical therapies for autoimmune diseases (ADs) lack specificity, necessitating long-term medication that can lead to serious side effects. In contrast, chimeric antigen receptor (CAR) T cell therapy for ADs, characterized by fewer side effects and longer-lasting therapeutic effects, represents a new direction for the specific treatment of ADs. T cells modified with CAR genes possess the ability to not only secrete perforin, granzymes, and other molecules that target autoreactive immune cells but also to lead effector and regulatory T cells into autoimmune environments, thereby exerting transport, proliferation, and immune regulatory functions. Chimeric autoantibody receptor T cells can recognize and kill autoreactive cells expressing target autoantibodies through their specific antigens. In this article, we comprehensively expound on the application of CAR-T cell therapy in different ADs and summarize the current research progress in this regard. This review aims to enhance the application of CAR-T therapy in AD treatment and facilitate further studies aimed at addressing the existing gaps in CAR-T therapy for ADs.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385059","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}
Shaoting Weng, Kaiqi Lian, Kunpeng Zhang, Shengming Ma, Wenhui Zhang, Zhongyi Luo, Ruifeng Chen, Liqiang Wang, Sen Lin, Xinying Ji, Yao Wang
The strategy of blocking myostatin (MSTN) signal transduction has long been regarded as a promising approach in the treatment of patients with muscle loss. However, individuals taking blocking agents often encounter issues such as lack of strength, fatigue, and poor muscle proliferation due to muscle hypertrophy and the involvement of multiple receptors. To address these challenges, a series of experiments were conducted on a C2C12 cell line in this study. First, the pX601-SaCas9-sgRNA/puro vector carrying a Cas9-encoded gene was constructed and subsequently used to produce Mstn-knockout (Mstn-KO) C2C12 cell lines. The expression level of the MSTN protein and the growth characteristics of the cell lines were verified. Moreover, the expression of muscle growth-related microRNAs in the cell lines was analyzed through real-time polymerase chain reaction (PCR). The results indicate that we have successfully established a method for constructing Mstn-KO cell lines with stable passage. No expression of the MSTN protein and strong cell proliferation were observed in the cell lines. Moreover, real-time PCR experiments showed that the expression levels of miR-1, miR-431, miR-206, and miR-133a were significantly increased (P < 0.01), the expression level of miR-23a was significantly increased (P < 0.05), and the expression level of miR-486 was significantly decreased (P < 0.05). These findings indicate that multiple miRNAs are closely associated with MSTN regulation. This study lays the foundation for further investigation into the effects of the Mstn gene on the physiological function of myoblasts and the development of drugs that block the MSTN signaling pathway.
{"title":"Establishment of a myostatin gene-knockout C2C12 cell line and evaluation of related microRNA expression","authors":"Shaoting Weng, Kaiqi Lian, Kunpeng Zhang, Shengming Ma, Wenhui Zhang, Zhongyi Luo, Ruifeng Chen, Liqiang Wang, Sen Lin, Xinying Ji, Yao Wang","doi":"10.36922/gpd.2991","DOIUrl":"https://doi.org/10.36922/gpd.2991","url":null,"abstract":"The strategy of blocking myostatin (MSTN) signal transduction has long been regarded as a promising approach in the treatment of patients with muscle loss. However, individuals taking blocking agents often encounter issues such as lack of strength, fatigue, and poor muscle proliferation due to muscle hypertrophy and the involvement of multiple receptors. To address these challenges, a series of experiments were conducted on a C2C12 cell line in this study. First, the pX601-SaCas9-sgRNA/puro vector carrying a Cas9-encoded gene was constructed and subsequently used to produce Mstn-knockout (Mstn-KO) C2C12 cell lines. The expression level of the MSTN protein and the growth characteristics of the cell lines were verified. Moreover, the expression of muscle growth-related microRNAs in the cell lines was analyzed through real-time polymerase chain reaction (PCR). The results indicate that we have successfully established a method for constructing Mstn-KO cell lines with stable passage. No expression of the MSTN protein and strong cell proliferation were observed in the cell lines. Moreover, real-time PCR experiments showed that the expression levels of miR-1, miR-431, miR-206, and miR-133a were significantly increased (P < 0.01), the expression level of miR-23a was significantly increased (P < 0.05), and the expression level of miR-486 was significantly decreased (P < 0.05). These findings indicate that multiple miRNAs are closely associated with MSTN regulation. This study lays the foundation for further investigation into the effects of the Mstn gene on the physiological function of myoblasts and the development of drugs that block the MSTN signaling pathway.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385077","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}
Ayodele Sunday Alonge, Toluwase Hezekiah Fatoki, Iseoluwa Isaac Ajayi, Ibrahim Olabayode Saliu, Stanley Chukwuejim, Courage Dele Famusiwa, O. Adetuyi, Ohunene Esther Joseph
Superoxide dismutase 1 (SOD1), a copper-dependent enzyme, facilitates the conversion of superoxide anions into hydrogen peroxide and oxygen, thereby regulating superoxide levels. Dysfunctions in SOD1 have been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis, as well as liver and lung cancers. This study aimed to identify SOD1 modulators using in silico rational virtual enrichment screening, pharmacokinetics, docking, and molecular dynamic simulation (MDS). The findings yielded 38 compounds, predominantly exhibiting high gastrointestinal absorption but mostly non-permeable across the blood–brain barrier, with few exhibiting inhibitory effects on selected cytochrome P450s. Molecular docking revealed that compound 1 (PubChem CID: 36791369) exhibited the highest binding affinity (−6.771 kcal·mol-1), followed by compound 19 (PubChem CID: 30935) with −6.468 kcal·mol-1, and compound 20 (PubChem CID: 135744521) with −5.978 kcal·mol-1. MDS and molecular mechanics/generalized Born surface area analysis indicated that the compound CID 36791369 – SOD1 complex and compound CID 30935 – SOD1 complex remained stable and energetically favorable under simulated physiological conditions at 0 ns and 100 ns. In conclusion, this study identified 38 compounds, among which compounds SN5, SN6, SN7, SN12, and SN25 emerged as potential inhibitors of SOD1 based on overall analyses. Further, research will be necessary to investigate the therapeutic effectiveness of these top five compounds in vitro and in vivo against SOD1.
{"title":"Rational virtual screening, ADME, and molecular simulation studies of potential inhibitors of human superoxide dismutase 1 in a dysfunctional antioxidant system","authors":"Ayodele Sunday Alonge, Toluwase Hezekiah Fatoki, Iseoluwa Isaac Ajayi, Ibrahim Olabayode Saliu, Stanley Chukwuejim, Courage Dele Famusiwa, O. Adetuyi, Ohunene Esther Joseph","doi":"10.36922/gpd.3042","DOIUrl":"https://doi.org/10.36922/gpd.3042","url":null,"abstract":"Superoxide dismutase 1 (SOD1), a copper-dependent enzyme, facilitates the conversion of superoxide anions into hydrogen peroxide and oxygen, thereby regulating superoxide levels. Dysfunctions in SOD1 have been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis, as well as liver and lung cancers. This study aimed to identify SOD1 modulators using in silico rational virtual enrichment screening, pharmacokinetics, docking, and molecular dynamic simulation (MDS). The findings yielded 38 compounds, predominantly exhibiting high gastrointestinal absorption but mostly non-permeable across the blood–brain barrier, with few exhibiting inhibitory effects on selected cytochrome P450s. Molecular docking revealed that compound 1 (PubChem CID: 36791369) exhibited the highest binding affinity (−6.771 kcal·mol-1), followed by compound 19 (PubChem CID: 30935) with −6.468 kcal·mol-1, and compound 20 (PubChem CID: 135744521) with −5.978 kcal·mol-1. MDS and molecular mechanics/generalized Born surface area analysis indicated that the compound CID 36791369 – SOD1 complex and compound CID 30935 – SOD1 complex remained stable and energetically favorable under simulated physiological conditions at 0 ns and 100 ns. In conclusion, this study identified 38 compounds, among which compounds SN5, SN6, SN7, SN12, and SN25 emerged as potential inhibitors of SOD1 based on overall analyses. Further, research will be necessary to investigate the therapeutic effectiveness of these top five compounds in vitro and in vivo against SOD1.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"21 S10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385167","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}
Bikesh Kumar Nirala, G. Shishodia, Praveen Kumar, Ravi Shankar Singh
The conventional understanding of immunological memory within adaptive immunity has faced recent challenges, paving the way for a novel concept known as “trained immunity.” This phenomenon revolves around the epigenetic and metabolic reprogramming of cells as its central components. A growing body of evidence suggests that long non-coding RNAs (lncRNAs) play a crucial role in regulating immune cell development, function, and response to various diseases. Through intricate protein-protein interactions and interactions with DNA and RNA, lncRNAs significantly contribute to the modulation of immune processes. However, our comprehension of the involvement of lncRNAs in trained immunity is still in its early stages. This review delves into the recent advancements in lncRNA research, focusing on their diverse functions in immune cell development, host-pathogen interactions, potential processes, and their biological significance in trained immunity. Special attention is given to the role of lncRNAs in altering chromatin structure, orchestrating chromosomal looping, and driving metabolic reprogramming within cells.
{"title":"Long non-coding RNAs: A trained immunity perspective","authors":"Bikesh Kumar Nirala, G. Shishodia, Praveen Kumar, Ravi Shankar Singh","doi":"10.36922/gpd.2791","DOIUrl":"https://doi.org/10.36922/gpd.2791","url":null,"abstract":"The conventional understanding of immunological memory within adaptive immunity has faced recent challenges, paving the way for a novel concept known as “trained immunity.” This phenomenon revolves around the epigenetic and metabolic reprogramming of cells as its central components. A growing body of evidence suggests that long non-coding RNAs (lncRNAs) play a crucial role in regulating immune cell development, function, and response to various diseases. Through intricate protein-protein interactions and interactions with DNA and RNA, lncRNAs significantly contribute to the modulation of immune processes. However, our comprehension of the involvement of lncRNAs in trained immunity is still in its early stages. This review delves into the recent advancements in lncRNA research, focusing on their diverse functions in immune cell development, host-pathogen interactions, potential processes, and their biological significance in trained immunity. Special attention is given to the role of lncRNAs in altering chromatin structure, orchestrating chromosomal looping, and driving metabolic reprogramming within cells.","PeriodicalId":504889,"journal":{"name":"Gene & Protein in Disease","volume":"8 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265555","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}
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