Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and immune checkpoint blockade. Nevertheless, the manipulation of T cells encounters formidable hurdles. Macrophages, serving as the pivotal link between innate and adaptive immunity, play crucial roles in phagocytosis, cytokine secretion, and antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention.
Aim of review
We aim to provide the most cutting-edge insights and future perspectives for macrophage-targeted therapies, fostering the development of novel and effective cancer treatments.
Key scientific concepts of review
To date, the forefront strategies for macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, and targeting phagocytosis checkpoints. Macrophages are characterized by their remarkable diversity and plasticity, offering a unique therapeutic target. In this context, we critically analyze the innovative strategies aimed at transforming macrophages from their M2 (tumor-promoting) to M1 (tumor-suppressing) phenotype. Furthermore, we delve into the design principles, developmental progress, and advantages of CAR-macrophages. Additionally, we illuminate the challenges encountered in targeting phagocytosis checkpoints on macrophages and propose potential strategies to overcome these obstacles.
{"title":"Targeting macrophages in cancer immunotherapy: Frontiers and challenges","authors":"Yu’e Liu, Huabing Tan, Jingyuan Dai, Jianghua Lin, Kaijun Zhao, Haibo Hu, Chunlong Zhong","doi":"10.1016/j.jare.2024.12.043","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.043","url":null,"abstract":"<h3>Background</h3>Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and immune checkpoint blockade. Nevertheless, the manipulation of T cells encounters formidable hurdles. Macrophages, serving as the pivotal link between innate and adaptive immunity, play crucial roles in phagocytosis, cytokine secretion, and antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention.<h3>Aim of review</h3>We aim to provide the most cutting-edge insights and future perspectives for macrophage-targeted therapies, fostering the development of novel and effective cancer treatments.<h3>Key scientific concepts of review</h3>To date, the forefront strategies for macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, and targeting phagocytosis checkpoints. Macrophages are characterized by their remarkable diversity and plasticity, offering a unique therapeutic target. In this context, we critically analyze the innovative strategies aimed at transforming macrophages from their M2 (tumor-promoting) to M1 (tumor-suppressing) phenotype. Furthermore, we delve into the design principles, developmental progress, and advantages of CAR-macrophages. Additionally, we illuminate the challenges encountered in targeting phagocytosis checkpoints on macrophages and propose potential strategies to overcome these obstacles.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.jare.2025.01.010
Xuchang Zhou, Yajing Yang, Xu Qiu, Huili Deng, Hong Cao, Tao Liao, Xier Chen, Caihua Huang, Donghai Lin, Guoxin Ni
Objective
The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration.
Methods
The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were used to explore potential mechanisms by which the small molecule metabolite taurine protects against inflammatory chondrocyte damage. Cell transfection and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects inflammatory chondrocytes in vitro. Finally, adeno-associated virus and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects against cartilage degeneration in vivo.
Results
Metabolomic assays identified taurine as a possible key metabolic molecule in the progression of OA. Transcriptomics and metabolomics revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation and Gpx4-dependent ferroptosis may mediate the inflammatory protective effects of taurine on chondrocytes, which was further confirmed by gain and loss of function in vitro. Subsequently, further experiments indicated that the possible existence of a direct binding site for Gpx4 and OGT proteins, which provides evidence for the presence of O-GlcNAc modification of Gpx4 protein. Finnaly, we demonstrated that Gpx4-dependent ferroptosis and OGT-dependent O-GlcNAcylation may be potential mechanisms by which taurine protects against cartilage degeneration in vivo.
Conclusion
Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling. Supplementation with taurine, a safe nonessential amino acid, may be a potential therapeutic strategy for OA.
{"title":"Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection","authors":"Xuchang Zhou, Yajing Yang, Xu Qiu, Huili Deng, Hong Cao, Tao Liao, Xier Chen, Caihua Huang, Donghai Lin, Guoxin Ni","doi":"10.1016/j.jare.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.010","url":null,"abstract":"<h3>Objective</h3>The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration.<h3>Methods</h3>The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were used to explore potential mechanisms by which the small molecule metabolite taurine protects against inflammatory chondrocyte damage. Cell transfection and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects inflammatory chondrocytes <em>in vitro</em>. Finally, adeno-associated virus and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects against cartilage degeneration <em>in vivo</em>.<h3>Results</h3>Metabolomic assays identified taurine as a possible key metabolic molecule in the progression of OA. Transcriptomics and metabolomics revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation and Gpx4-dependent ferroptosis may mediate the inflammatory protective effects of taurine on chondrocytes, which was further confirmed by gain and loss of function <em>in vitro</em>. Subsequently, further experiments indicated that the possible existence of a direct binding site for Gpx4 and OGT proteins, which provides evidence for the presence of O-GlcNAc modification of Gpx4 protein. Finnaly, we demonstrated that Gpx4-dependent ferroptosis and OGT-dependent O-GlcNAcylation may be potential mechanisms by which taurine protects against cartilage degeneration <em>in vivo</em>.<h3>Conclusion</h3>Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling. Supplementation with taurine, a safe nonessential amino acid, may be a potential therapeutic strategy for OA.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"83 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-05DOI: 10.1016/j.jare.2025.01.008
Lu Liu, Yu-jia Zhao, Feng Zhang
Background
Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate and multifactorial. Recently, post-transcriptional modifications (PTMs) of RNA, with a particular focus on mRNA methylation, have been gaining increasing attention. At present, several regulatory genes associated with mRNA methylation have been identified and closely associated with neurodegenerative disorders.
Aim of review
This review aimed to summarize the mRNA methylation enzymes system, including the writer, reader, and eraser proteins and delve into their functions in the central nervous system (CNS), hoping to open new avenues for exploring the mechanisms and therapeutic strategies for NDs.
Key scientific concepts of review
Recently, studies have highlighted the critical role of mRNA methylation in the development and function of the CNS, and abnormalities in this process may contribute to brain damage and NDs, aberrant expression of enzymes involved in mRNA methylation has been implicated in the onset and development of NDs.
{"title":"RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system","authors":"Lu Liu, Yu-jia Zhao, Feng Zhang","doi":"10.1016/j.jare.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.008","url":null,"abstract":"<h3>Background</h3>Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate and multifactorial. Recently, post-transcriptional modifications (PTMs) of RNA, with a particular focus on mRNA methylation, have been gaining increasing attention. At present, several regulatory genes associated with mRNA methylation have been identified and closely associated with neurodegenerative disorders.<h3>Aim of review</h3>This review aimed to summarize the mRNA methylation enzymes system, including the writer, reader, and eraser proteins and delve into their functions in the central nervous system (CNS), hoping to open new avenues for exploring the mechanisms and therapeutic strategies for NDs.<h3>Key scientific concepts of review</h3>Recently, studies have highlighted the critical role of mRNA methylation in the development and function of the CNS, and abnormalities in this process may contribute to brain damage and NDs, aberrant expression of enzymes involved in mRNA methylation has been implicated in the onset and development of NDs.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"15 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-05DOI: 10.1016/j.jare.2024.12.048
Yifan Wang, Jing Mao, Yujie Wang, Rui Wang, Nan Jiang, Xiaohan Hu, Xin Shi
Introduction
Establishing an optimized regenerative microenvironment for pulp-dentin complex engineering has become increasingly critical. Recently, exosomes have emerged as favorable biomimetic nanotherapeutic tools to simulate the developmental microenvironment and facilitate tissue regeneration.
Objectives
This study aimed to elucidate the multifaceted roles of exosomes from human dental pulp stem cells (DPSCs) that initiated odontogenic differentiation while sustaining mesenchymal stem cell (MSC) characteristics in odontogenesis, angiogenesis, and neurogenesis during pulp-dentin complex regeneration.
Methods
Differential centrifugation was performed to isolate exosomes from normal DPSCs (DPSC-Exos) and DPSCs that initially triggered odontogenic differentiation (DPSC-Od-Exos). The impact of these exosomes on the biological behavior of DPSCs and human umbilical vein endothelial cells (HUVECs) was examined in vitro through CCK-8 assay and Transwell migration assay, as well as assays dedicated to assessing odontogenic, angiogenic, and neurogenic capabilities. In vivo, Matrigel plugs and human tooth root fragments incorporating either DPSC-Exos or DPSC-Od-Exos were subcutaneously transplanted into mouse models. Subsequent histological, immunohistochemical, and immunofluorescent analyses were conducted to determine the regenerative outcomes.
Results
DPSC-Exos and DPSC-Od-Exos revealed no remarkable difference in their characteristics. In vitro analyses indicated that DPSC-Od-Exos significantly facilitated the proliferation, migration, and multilineage differentiation of DPSCs compared with DPSC-Exos. Furthermore, DPSC-Od-Exos elicited a more pronounced effect on the tubular structure formation of HUVECs. Consistently, Matrigel plug assays confirmed that DPSC-Od-Exos exhibited superior performance in promoting endothelial differentiation of DPSCs and stimulating angiogenesis in HUVECs. Notably, DPSC-Od-Exos contributed to complete pulp-dentin complex regeneration in human tooth root fragments, characterized by enriched neurovascular structures and a continuous layer of odontoblast-like cells, which extended cytoplasmic projections into the newly formed dentinal tubules.
Conclusion
By simulating the developmental microenvironment, multifunctional DPSC-Od-Exos demonstrated promising potential for reconstructing dentin-like tissue, vascular networks, and neural architectures, thereby enhancing our understanding of the therapeutic implications of DPSC-Od-Exos in regenerative endodontic treatment.
{"title":"Odontogenic exosomes simulating the developmental microenvironment promote complete regeneration of pulp-dentin complex in vivo","authors":"Yifan Wang, Jing Mao, Yujie Wang, Rui Wang, Nan Jiang, Xiaohan Hu, Xin Shi","doi":"10.1016/j.jare.2024.12.048","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.048","url":null,"abstract":"<h3>Introduction</h3>Establishing an optimized regenerative microenvironment for pulp-dentin complex engineering has become increasingly critical. Recently, exosomes have emerged as favorable biomimetic nanotherapeutic tools to simulate the developmental microenvironment and facilitate tissue regeneration.<h3>Objectives</h3>This study aimed to elucidate the multifaceted roles of exosomes from human dental pulp stem cells (DPSCs) that initiated odontogenic differentiation while sustaining mesenchymal stem cell (MSC) characteristics in odontogenesis, angiogenesis, and neurogenesis during pulp-dentin complex regeneration.<h3>Methods</h3>Differential centrifugation was performed to isolate exosomes from normal DPSCs (DPSC-Exos) and DPSCs that initially triggered odontogenic differentiation (DPSC-Od-Exos). The impact of these exosomes on the biological behavior of DPSCs and human umbilical vein endothelial cells (HUVECs) was examined in vitro through CCK-8 assay and Transwell migration assay, as well as assays dedicated to assessing odontogenic, angiogenic, and neurogenic capabilities. In vivo, Matrigel plugs and human tooth root fragments incorporating either DPSC-Exos or DPSC-Od-Exos were subcutaneously transplanted into mouse models. Subsequent histological, immunohistochemical, and immunofluorescent analyses were conducted to determine the regenerative outcomes.<h3>Results</h3>DPSC-Exos and DPSC-Od-Exos revealed no remarkable difference in their characteristics. In vitro analyses indicated that DPSC-Od-Exos significantly facilitated the proliferation, migration, and multilineage differentiation of DPSCs compared with DPSC-Exos. Furthermore, DPSC-Od-Exos elicited a more pronounced effect on the tubular structure formation of HUVECs. Consistently, Matrigel plug assays confirmed that DPSC-Od-Exos exhibited superior performance in promoting endothelial differentiation of DPSCs and stimulating angiogenesis in HUVECs. Notably, DPSC-Od-Exos contributed to complete pulp-dentin complex regeneration in human tooth root fragments, characterized by enriched neurovascular structures and a continuous layer of odontoblast-like cells, which extended cytoplasmic projections into the newly formed dentinal tubules.<h3>Conclusion</h3>By simulating the developmental microenvironment, multifunctional DPSC-Od-Exos demonstrated promising potential for reconstructing dentin-like tissue, vascular networks, and neural architectures, thereby enhancing our understanding of the therapeutic implications of DPSC-Od-Exos in regenerative endodontic treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"51 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High-density Wheat 660 K and 90 K SNP arrays are powerful tools for understanding the genetic basis of wheat traits. However, their inconsistantly physical positions that were caused by different versions of Chinese Spring genome during developing arrays are confused and inconvenient for further application.
Objective
With the repid development of wheat geonome sequencing, we aim to reconciliate Wheat 660 K and 90 K SNP arrays in modern cultivar and reveal the genetic basis of dough rheological properties in bread wheat.
Methods
We refined physical positions of Wheat 660 K and 90 K SNP arrays in the currently popular wheat cultivar AK58 genome that was released more recently. We next performed genome-wide association studies (GWAS) and linkage analysis to identify important genetic loci related to quality traits using updated and un-updated arrays, respectively.
Results
Refining results showed that 92.3 % and 83 % of SNPs in the Wheat 660 K and 90 K SNP arrays were precisely mapped to the AK58 genome, respective. GWAS results by the updated 660 K and 90 K arrays indicated that 26 intervals composed of 1032 significant SNPs were associated with 9 quality traits in multiple environments. The significant interval for stability time on 1D was narrowed into an 8.4-Mb region using the updated arrays, whereas the interval is 405 Mb using the un-updated arrays. Linkage analysis revealed an important QTL QST.henau-1D.2 for stability time with 1.64 Mb. Integration of GWAS and QTL results narrowed the significant interval into 6.46 Mb containing 35 annotation genes by collinearity analysis. After T-test, gene expression analysis, seven of them are potential candidate genes and thus favorable haplotypes are identified to benefit marker-assisted selection.
Conclusion
A reconciliation of Wheat 660 K and 90 K arrays promote their efficient applications. Important genetic loci and favorable haplotypes identified in this study provided valuable information for wheat quality breeding.
高密度小麦660 K和90 K SNP阵列是了解小麦性状遗传基础的有力工具。然而，由于不同版本的中国春季基因组在构建阵列过程中导致了它们的物理位置不一致，这给进一步的应用带来了混乱和不便。目的随着小麦基因组测序的快速发展，对小麦660 K和90 K SNP序列进行比对，揭示面包小麦面团流变学特性的遗传基础。方法在最近发布的小麦品种AK58基因组中，对小麦660 K和90 K SNP阵列进行物理定位。接下来，我们分别使用更新和未更新的阵列进行了全基因组关联研究（GWAS）和连锁分析，以确定与质量性状相关的重要遗传位点。结果精化结果显示，小麦660 K和90 K SNP阵列中分别有92.3 %和83 %的SNP被精确定位到AK58基因组。更新后的660个 K和90个 K阵列的GWAS结果表明，在多个环境中，由1032个显著snp组成的26个区间与9个品质性状相关。使用更新的阵列时，1D上稳定时间的显著间隔缩小到8.4 Mb，而使用未更新的阵列时，该间隔为405 Mb。连锁分析发现一个重要的QTL QST.henau-1D。2稳定时间为1.64 Mb。通过共线性分析，GWAS和QTL的整合结果将显著区间缩小至6.46 Mb，共包含35个注释基因。经过t检验和基因表达分析，其中7个是潜在的候选基因，从而确定了有利的单倍型，有利于标记辅助选择。结论小麦660 K和90 K阵列的调合促进了它们的高效应用。本研究发现的重要遗传位点和有利单倍型为小麦品质育种提供了有价值的信息。
{"title":"Reconciliation of wheat 660 K and 90 K SNP arrays and their utilization in dough rheological properties of bread wheat","authors":"Congwei Sun, Zhenhai Jing, Xiaoqian Chen, Jiahui Chen, Qiaoqiao Shang, Hui Jin, Jizeng Jia, Yan Ren, Lei Zhao, Lifeng Gao, Zhonghu He, Feng Chen","doi":"10.1016/j.jare.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.011","url":null,"abstract":"<h3>Introduction</h3>High-density Wheat 660 K and 90 K SNP arrays are powerful tools for understanding the genetic basis of wheat traits. However, their inconsistantly physical positions that were caused by different versions of Chinese Spring genome during developing arrays are confused and inconvenient for further application.<h3>Objective</h3>With the repid development of wheat geonome sequencing, we aim to reconciliate Wheat 660 K and 90 K SNP arrays in modern cultivar and reveal the genetic basis of dough rheological properties in bread wheat.<h3>Methods</h3>We refined physical positions of Wheat 660 K and 90 K SNP arrays in the currently popular wheat cultivar AK58 genome that was released more recently. We next performed genome-wide association studies (GWAS) and linkage analysis to identify important genetic loci related to quality traits using updated and un-updated arrays, respectively.<h3>Results</h3>Refining results showed that 92.3 % and 83 % of SNPs in the Wheat 660 K and 90 K SNP arrays were precisely mapped to the AK58 genome, respective. GWAS results by the updated 660 K and 90 K arrays indicated that 26 intervals composed of 1032 significant SNPs were associated with 9 quality traits in multiple environments. The significant interval for stability time on 1D was narrowed into an 8.4-Mb region using the updated arrays, whereas the interval is 405 Mb using the un-updated arrays. Linkage analysis revealed an important QTL <em>QST.henau-1D.2</em> for stability time with 1.64 Mb. Integration of GWAS and QTL results narrowed the significant interval into 6.46 Mb containing 35 annotation genes by collinearity analysis. After <em>T</em>-test, gene expression analysis, seven of them are potential candidate genes and thus favorable haplotypes are identified to benefit marker-assisted selection.<h3>Conclusion</h3>A reconciliation of Wheat 660 K and 90 K arrays promote their efficient applications. Important genetic loci and favorable haplotypes identified in this study provided valuable information for wheat quality breeding.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-04DOI: 10.1016/j.jare.2025.01.009
Mingyu Li, Yiming Shao, Baiwei Pan, Chang Liu, Hexin Tan
Background
Plants produce abundant natural products, among which are species-specific and diversified secondary metabolites that are essential for growth and development, as well as adaptation to adversity and ecology. Moreover, these secondary metabolites are extensively utilized in pharmaceuticals, fragrances, industrial materials, and more. WRKY transcription factors (TFs), as a family of TFs unique to plants, have significant functions in many plant life activities. Especially in recent years, their role in the field of secondary metabolite biosynthesis regulation has received much attention. However, very little comprehensive summarization has been done to review their research progress.
Aim of Review
The purpose of this work is not only to provide valuable insights into the regulation of WRKY TFs over metabolic pathways through compiling the WRKY TFs involved in these processes, but also to offer research directions for WRKY TFs by summarizing the regulatory modes of WRKY TFs in the biosynthesis of secondary metabolites, thereby increasing the yield of valuable natural products in the future.
Key Scientific Concepts of Review
Secondary metabolites can be categorized into three major classes—terpenoids, phenolic compounds, and nitrogen-containing compounds—based on their structural characteristics and biosynthetic pathways, and further subdivided into numerous subclasses. We review in detail the research progress regarding the regulatory roles of WRKY TFs in plant secondary metabolite biosynthesis and summarize more than 40 major related species. Additionally, we have presented the concepts of action modes of WRKY TFs involved in metabolic pathways, including direct regulation, indirect regulation, co-regulation, and self-regulation. It is helpful for others to investigate the molecular mechanisms of TF-mediated regulation. Furthermore, regarding future research prospects, we believe that research in this area lays the foundation for increasing the yield of important plant-derived natural products by molecular breeding, generating significant economic and social benefits.
{"title":"Regulation of important natural products biosynthesis by WRKY transcription factors in plants","authors":"Mingyu Li, Yiming Shao, Baiwei Pan, Chang Liu, Hexin Tan","doi":"10.1016/j.jare.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.009","url":null,"abstract":"<h3>Background</h3>Plants produce abundant natural products, among which are species-specific and diversified secondary metabolites that are essential for growth and development, as well as adaptation to adversity and ecology. Moreover, these secondary metabolites are extensively utilized in pharmaceuticals, fragrances, industrial materials, and more. WRKY transcription factors (TFs), as a family of TFs unique to plants, have significant functions in many plant life activities. Especially in recent years, their role in the field of secondary metabolite biosynthesis regulation has received much attention. However, very little comprehensive summarization has been done to review their research progress.<h3>Aim of Review</h3>The purpose of this work is not only to provide valuable insights into the regulation of WRKY TFs over metabolic pathways through compiling the WRKY TFs involved in these processes, but also to offer research directions for WRKY TFs by summarizing the regulatory modes of WRKY TFs in the biosynthesis of secondary metabolites, thereby increasing the yield of valuable natural products in the future.<h3>Key Scientific Concepts of Review</h3>Secondary metabolites can be categorized into three major classes—terpenoids, phenolic compounds, and nitrogen-containing compounds—based on their structural characteristics and biosynthetic pathways, and further subdivided into numerous subclasses. We review in detail the research progress<!-- --> <!-- -->regarding<!-- --> <!-- -->the regulatory roles of WRKY TFs in plant secondary metabolite<!-- --> <!-- -->biosynthesis and summarize more than 40 major related species. Additionally, we have presented the concepts of action modes of WRKY TFs involved in metabolic pathways, including direct regulation, indirect regulation, co-regulation, and self-regulation. It is helpful for others to investigate the molecular mechanisms of TF-mediated regulation. Furthermore, regarding future research prospects, we believe that research in this area lays the foundation for increasing the yield of important plant-derived natural products by molecular breeding, generating significant economic and social benefits.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-04DOI: 10.1016/j.jare.2025.01.003
Meng-han Qi, Hai-yan Zhang, Yun-yi Hou, Ivan Steve Nguepi Tsopmejio, Wei Liu, Wen-guang Chang, Chen Chen, Zi Wang, Wei Li
Introduction
Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear.
Objectives
To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment.
Methods
The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics.
Results
GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia.
Conclusion
This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.
{"title":"GABAFG isolated fom ginseng ameliorates type 2 diabetes mellitus by modulating gut microbiota and autophagy-lysosome pathway","authors":"Meng-han Qi, Hai-yan Zhang, Yun-yi Hou, Ivan Steve Nguepi Tsopmejio, Wei Liu, Wen-guang Chang, Chen Chen, Zi Wang, Wei Li","doi":"10.1016/j.jare.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.003","url":null,"abstract":"<h3>Introduction</h3>Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of <em>Panax ginseng</em> C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear.<h3>Objectives</h3>To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment.<h3>Methods</h3>The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells <em>(in vivo</em> and <em>in vitro)</em> were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics.<h3>Results</h3>GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells <em>in vitro</em>. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased <em>Akkermansia,</em> decreased <em>Romboutsia</em> abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia.<h3>Conclusion</h3>This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"128 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1016/j.jare.2024.12.036
Xiao-Han Zhou, Ya-Xi Luo, Xiu-Qing Yao
Background
Exercise enhances health by supporting homeostasis, bolstering defenses, and aiding disease recovery. It activates autophagy, a conserved cellular process essential for maintaining balance, while dysregulated autophagy contributes to disease progression. Despite extensive research on exercise and autophagy independently, their interplay remains insufficiently understood.
Aim of Review
This review explores the molecular mechanisms of exercise-induced autophagy in various tissues, focusing on key transduction pathways. It examines how different types of exercise trigger specific autophagic responses, supporting cellular balance and addressing systemic dysfunctions. The review also highlights the signaling pathways involved, their roles in protecting organ function, reducing disease risk, and promoting longevity, offering a clear understanding of the link between exercise and autophagy.
Key Scientific Concepts of Review
Exercise-induced autophagy is governed by highly coordinated and dynamic pathways integrating direct and indirect mechanical forces and biochemical signals, linking physical activity to cellular and systemic health across multiple organ systems. Its activation is influenced by exercise modality, intensity, duration, and individual biological characteristics, including age, sex, and muscle fiber composition. Aerobic exercises primarily engage AMPK and mTOR pathways, supporting mitochondrial quality and cellular homeostasis. Anaerobic training activates PI3K/Akt signaling, modulating molecules like FOXO3a and Beclin1 to drive muscle autophagy and repair. In pathological contexts, exercise-induced autophagy enhances mitochondrial function, proteostasis, and tissue regeneration, benefiting conditions like sarcopenia, neurodegeneration, myocardial ischemia, metabolic disorders, and cancer. However, excessive exercise may lead to autophagic overactivation, leading to muscle atrophy or pathological cardiac remodeling. This underscores the critical need for balanced exercise regimens to maximize therapeutic efficacy while minimizing risks. Future research should prioritize identifying reliable biomarkers, optimizing exercise protocols, and integrating exercise with pharmacological strategies to enhance therapeutic outcomes.
{"title":"Exercise-driven cellular autophagy: A bridge to systematic wellness","authors":"Xiao-Han Zhou, Ya-Xi Luo, Xiu-Qing Yao","doi":"10.1016/j.jare.2024.12.036","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.036","url":null,"abstract":"<h3>Background</h3>Exercise enhances health by supporting homeostasis, bolstering defenses, and aiding disease recovery. It activates autophagy, a conserved cellular process essential for maintaining balance, while dysregulated autophagy contributes to disease progression. <strong>Despite extensive research on exercise and autophagy independently, their interplay remains insufficiently understood.</strong><h3>Aim of Review</h3>This review explores the molecular mechanisms of exercise-induced autophagy in various tissues, focusing on key transduction pathways. It examines how different types of exercise trigger specific autophagic responses, supporting cellular balance and addressing systemic dysfunctions. The review also highlights the signaling pathways involved, their roles in protecting organ function, reducing disease risk, and promoting longevity, offering a clear understanding of the link between exercise and autophagy.<h3>Key Scientific Concepts of Review</h3>Exercise-induced autophagy is governed by highly coordinated and dynamic pathways integrating direct and indirect mechanical forces and biochemical signals, linking physical activity to cellular and systemic health across multiple organ systems. Its activation is influenced by exercise modality, intensity, duration, and individual biological characteristics, including age, sex, and muscle fiber composition. Aerobic exercises primarily engage AMPK and mTOR pathways, supporting mitochondrial quality and cellular homeostasis. Anaerobic training activates PI3K/Akt signaling, modulating molecules like FOXO3a and Beclin1 to drive muscle autophagy and repair. In pathological contexts, exercise-induced autophagy enhances mitochondrial function, proteostasis, and tissue regeneration, benefiting conditions like sarcopenia, neurodegeneration, myocardial ischemia, metabolic disorders, and cancer. However, excessive exercise may lead to autophagic overactivation, leading to muscle atrophy or pathological cardiac remodeling. This underscores the critical need for balanced exercise regimens to maximize therapeutic efficacy while minimizing risks. Future research should prioritize identifying reliable biomarkers, optimizing exercise protocols, and integrating exercise with pharmacological strategies to enhance therapeutic outcomes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"34 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1016/j.jare.2025.01.004
Yizhao Chen, Qianling Xin, Mengjuan Zhu, Jiaqi Qiu, Yan Luo, Ruilin Li, Wei Wei, Jiajie Tu
Background
After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, the first approved CAR cell therapy product, has demonstrated therapeutic potential in treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach in CAR immune cell therapy, particularly for solid tumor treatment, highlighting the feasibility of using macrophages to eliminate pathogens and abnormal cells.
Aim of Review
This review summarizes the progress of CAR-M therapy in non-tumor diseases and discusses various CAR intracellular activation domain designs and their potential to optimize therapeutic effects by modulating interactions between cellular components in the tissue microenvironment and CAR-M. Additionally, we discuss the characteristics and advantages of CAR-M therapy compared to traditional medicine and CAR-T/NK therapy, as well as the challenges and prospects for the clinical translation of CAR-M.
Key scientific concepts of review
This review provides a comprehensive understanding of CAR-M for the treatment of non-tumor diseases, analyzes the advantages and characteristics of CAR-M therapy, and highlights the important impact of CAR intracellular domain design on therapeutic efficacy. In addition, the challenges and clinical translation prospects of developing CAR-M as a new cell therapy are discussed.
{"title":"Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer","authors":"Yizhao Chen, Qianling Xin, Mengjuan Zhu, Jiaqi Qiu, Yan Luo, Ruilin Li, Wei Wei, Jiajie Tu","doi":"10.1016/j.jare.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.jare.2025.01.004","url":null,"abstract":"<h3>Background</h3>After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, the first approved CAR cell therapy product, has demonstrated therapeutic potential in treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach in CAR immune cell therapy, particularly for solid tumor treatment, highlighting the feasibility of using macrophages to eliminate pathogens and abnormal cells.<h3>Aim of Review</h3>This review summarizes the progress of CAR-M therapy in non-tumor diseases and discusses various CAR intracellular activation domain designs and their potential to optimize therapeutic effects by modulating interactions between cellular components in the tissue microenvironment and CAR-M. Additionally, we discuss the characteristics and advantages of CAR-M therapy compared to traditional medicine and CAR-T/NK therapy, as well as the challenges and prospects for the clinical translation of CAR-M.<h3>Key scientific concepts of review</h3>This review provides a comprehensive understanding of CAR-M for the treatment of non-tumor diseases, analyzes the advantages and characteristics of CAR-M therapy, and highlights the important impact of CAR intracellular domain design on therapeutic efficacy. In addition, the challenges and clinical translation prospects of developing CAR-M as a new cell therapy are discussed.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"18 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1016/j.jare.2024.12.049
Nanlin You, Guohao Liu, Mengchen Yu, Wenbo Chen, Xiaoyao Fei, Tao Sun, Mengtao Han, Zhen Qin, Zhaosheng Wei, Donghai Wang
Background
The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression of mesenchymal stromal cells (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow in progression, atherosclerosis (AS) is a potential contributor to various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, the “initiator” of AS, induces the progression of ASCVD such as coronary atherosclerotic heart disease (CHD) and ischemic cerebrovascular disease (ICD), with serious clinical complications such as myocardial infarction (MI) and stroke. In-depth research of the pathomechanisms of EndMT and identification of potential targeted therapeutic strategies hold considerable research value for the prevention and treatment of ASCVD-associated with delayed EndMT. Although previous studies have progressively unraveled the complexity of EndMT and its pathogenicity triggered by alterations in vascular microenvironmental factors, systematic descriptions of the most recent pathogenic roles of EndMT in the progression of AS, targeted therapeutic strategies, and their future research directions are scarce.
Aim of review
We aim to provide new researchers with comprehensive knowledge of EndMT in AS. We exhaustively review the latest research advancements in the field and provide a theoretical basis for investigating EndMT, a biological process with sophisticated mechanisms.
Key scientific concepts of review
This review summarized that altered hemodynamics with microenvironmental crosstalk consisting of inflammatory responses or glycolysis, oxidative stress, lactate or acetyl-CoA (Ac-CoA), fatty acid oxidation (FAO), intracellular iron overload, and transcription factors, including ELK1 and STAT3, modulate the EndMT and affect AS progression. In addition, we provide new paradigms for the development of promising therapeutic agents against these disease-causing processes and indicate promising directions and challenges that need to be addressed to elucidate the EndMT process.
{"title":"Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies","authors":"Nanlin You, Guohao Liu, Mengchen Yu, Wenbo Chen, Xiaoyao Fei, Tao Sun, Mengtao Han, Zhen Qin, Zhaosheng Wei, Donghai Wang","doi":"10.1016/j.jare.2024.12.049","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.049","url":null,"abstract":"<h3>Background</h3>The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression of mesenchymal stromal cells (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow in progression, atherosclerosis (AS) is a potential contributor to various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, the “initiator” of AS, induces the progression of ASCVD such as coronary atherosclerotic heart disease (CHD) and ischemic cerebrovascular disease (ICD), with serious clinical complications such as myocardial infarction (MI) and stroke. In-depth research of the pathomechanisms of EndMT and identification of potential targeted therapeutic strategies hold considerable research value for the prevention and treatment of ASCVD-associated with delayed EndMT. Although previous studies have progressively unraveled the complexity of EndMT and its pathogenicity triggered by alterations in vascular microenvironmental factors, systematic descriptions of the most recent pathogenic roles of EndMT in the progression of AS, targeted therapeutic strategies, and their future research directions are scarce.<h3>Aim of review</h3>We aim to provide new researchers with comprehensive knowledge of EndMT in AS. We exhaustively review the latest research advancements in the field and provide a theoretical basis for investigating EndMT, a biological process with sophisticated mechanisms.<h3>Key scientific concepts of review</h3>This review summarized that altered hemodynamics with microenvironmental crosstalk consisting of inflammatory responses or glycolysis, oxidative stress, lactate or acetyl-CoA (Ac-CoA), fatty acid oxidation (FAO), intracellular iron overload, and transcription factors, including ELK1 and STAT3, modulate the EndMT and affect AS progression. In addition, we provide new paradigms for the development of promising therapeutic agents against these disease-causing processes and indicate promising directions and challenges that need to be addressed to elucidate the EndMT process.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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