Journal of Advanced Research最新文献

{"title":"Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment","authors":"Lihua Tan, Zhimin Miao, Yuxin Zhao, Yongkai Liang, Nan Xu, Xin Chen, Yanbei Tu, Chengwei He","doi":"10.1016/j.jare.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.009","url":null,"abstract":"<h3>Introduction</h3>Osteoporosis is an osteolytic disorder resulting from an inequilibrium between osteoblast-mediated osteogenesis and osteoclast-driven bone absorption. Safe and effective approaches for osteoporosis management are still highly demanded.<h3>Purpose</h3>This study aimed to examine the osteoprotective effect and the mechanisms of phaseol (PHA) <em>in vitro</em> and <em>in vivo</em>.<h3>Methods</h3>Virtual screening identified the potential inhibitors of transforming growth factor-beta-activated kinase 1 (TAK1) from coumestans. The interaction between PHA and TAK1 was investigated by molecular simulation, pronase and thermal resistance assays. The maturation and function of osteoclasts were determined using tartrate-resistant acid phosphatase staining, bone absorption and F-actin ring formation assays. The differentiation and calcification of osteoblasts were assessed by alkaline phosphatase staining and Alizarin Red S staining. The activity of related targets and pathways were detected using immunoblotting, immunofluorescence and co-immunoprecipitation assays. The <em>in vivo</em> osteoprotective effect of PHA was evaluated using a lipopolysaccharide (LPS)-induced mouse osteoporosis model.<h3>Results</h3>Firstly, we confirmed that TAK1 was essential in controlling bone remodeling by regulating osteogenesis and osteoclastogenesis. Moreover, PHA, a coumestan compound predominantly present in leguminous plants, was identified as a potent TAK1 inhibitor through virtual and real experiments. Subsequently, PHA was observed to enhance osteoblast differentiation and calcification, while suppress osteoclast maturation and bone resorptive function <em>in vitro</em>. Mechanistically, PHA remarkably inhibited the TRAF6-TAK1 complex formation, and inhibited the activation of TAK1, MAPK and NF-κB pathways by targeting TAK1. In the <em>in vivo</em> study, PHA strongly attenuated bone loss, inflammatory responses, and osteoclast over-activation in lipopolysaccharide-induced osteoporosis mice.<h3>Conclusion</h3>PHA had a dual-functional regulatory impact on osteogenesis and osteoclastogenesis by targeting TAK1, suppressing TRAF6-TAK1 complex generation, and modulating its associated signaling pathways, ultimately leading to mitigating osteoporosis. This study offered compelling evidence in favor of using PHA for preventing and managing osteoporosis as both a bone anabolic and anti-resorptive agent.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"4 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793741","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}

{"title":"Not only the top: Type I topoisomerases function in multiple tissues and organs development in plants","authors":"Hao Zhang, Lirong Tian, Yuru Ma, Jiahui Xu, Tianyu Bai, Qian Wang, Xigang Liu, Lin Guo","doi":"10.1016/j.jare.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.011","url":null,"abstract":"<h3>Background</h3>DNA topoisomerases (TOPs) are essential components in a diverse range of biological processes including DNA replication, transcription and genome integrity. Although the functions and mechanisms of TOPs, particularly type I TOP (TOP1s), have been extensively studied in bacteria, yeast and animals, researches on these proteins in plants have only recently commenced.<h3>Aim of Review</h3>In this review, the function and mechanism studies of TOP1s in plants and the structural biology of plant TOP1 are presented, providing readers with a comprehensive understanding of the current research status of this essential enzyme.The future research directions for exploring the working mechanism of plant TOP1s is also discussed.<h3>Key Scientific Concepts of Review</h3>Over the past decade, it has been discovered TOP1s play a vital role in multiphasic processes of plant development, such as maintaining meristem activity, gametogenesis, flowering time, gravitropic response and so on. Plant TOP1s affects gene transcription by modulating chromatin status, including chromatin accessibility, DNA/RNA structure, and nucleosome positioning. However, the function and mechanism of this vital enzyme is poorly summarized although it has been systematically summarized in other species. This review summarized the research progresses of plant TOP1s according to the diverse functions and working mechanism in different tissues.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"58 20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793738","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}

{"title":"Ubiquitin proteasome system in cardiac fibrosis","authors":"Linqi Zeng, Xiaokai Zhang, Zihang Huang, Shuai Song, Mohan Li, Tongyao Wang, Aijun Sun, Junbo Ge","doi":"10.1016/j.jare.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.006","url":null,"abstract":"<h3>Background</h3>Cardiac fibrosis, including reactive fibrosis and replacement fibrosis, is a common pathological process in most cardiovascular diseases. The ubiquitin proteasome system (UPS) plays an important role in the development of fibrosis by mediating the degradation and synthesis of proteins involved in transforming growth factor-β (TGF-β)-dependent and TGF-β-independent fibrous pathways.<h3>Aim of review</h3>This review aims to provide an overview of ubiquitinated and deubiquitinated molecules that participating in cardiac fibrosis, with the ultimate purpose to identify promising targets for therapeutic strategies.<h3>Key scientific concepts of review</h3>The UPS primarily impacts cardiac fibrosis through modulation of the TGF-β signaling pathway targeting key molecules involved, including the TGF-β receptors, Smad2/3/4 complexes, and inhibitory Smad7, thereby influencing fibrotic processes. In addition to its effect on TGF-β signaling, UPS also regulates pro-fibrotic pathways independent of TGF-β, including p53, AKT1-p38, and JNK1/2. Understanding these pathways is critical due to their involvement in diverse fibrotic mechanisms. The interplay between ubiquitination and deubiquitination of crucial pathways and molecules is pivotal in cardiac fibrosis and represents a promising area for identifying novel therapeutic targets. Different types of cardiac fibrosis involve distinct fibrotic pathways, leading to differential effects of E3 ligases and DUBs across various cardiac fibrotic diseases. Insights into UPS-mediated regulation of cardiac fibrosis provides potential anti-fibrotic therapeutic strategies, emphasizing the importance of targeting UPS components specific to the heart for effective therapy against cardiac fibrosis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"47 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789837","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}

{"title":"Asperosaponin VI inhibition of DNMT alleviates GPX4 suppression-mediated osteoblast ferroptosis and diabetic osteoporosis","authors":"Fanhao Wei, Binjia Ruan, Jian Dong, Bin Yang, Guofu Zhang, Wai Kwok Kelvin Yeung, Hongwei Wang, Wangsen Cao, Yongxiang Wang","doi":"10.1016/j.jare.2024.11.036","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.036","url":null,"abstract":"<h3>Introduction</h3>Diabetic osteoporosis (DOP) is an insidious complication of diabetes with limited therapeutic options. DOP is pathologically associated with various types of regulated cell death, but the precise role of ferroptosis in the process remains poorly understood. Asperosaponin VI (AVI), known for its clinical efficacy in treating bone fractures and osteoporosis, may exert its osteoprotective effects through mechanisms involving ferroptosis, however this has not been established.<h3>Objectives</h3>This study aimed to investigate the role of AVI in modulating ferroptosis in a mouse model of DOP and to explore the underlying mechanisms.<h3>Methods</h3>We assessed OP alterations in femurs of DOP-conditioned mice and primary bone cells. We generated a strain of osteoblast-specific <em>Gpx4</em>-deficient mice. A combination of micro-CT, immunohistochemistry, immunofluorescence, methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), western blotting (WB), and AVI pull-down assays were employed to elucidate the mechanism and therapeutic target of AVI in DOP.<h3>Results</h3>Our findings revealed that femurs from DOP-conditioned mice exhibited significant ferroptosis and suppression of the core anti-ferroptosis factor GPX4, mainly due to hypermethylation of the <em>Gpx4</em> promoter mediated by DNA methyltransferases DNMT1and DNMT3a. Notably, treatment with AVI effectively reversed the hypermethylation, restored GPX4 expression, and reduced ferroptotic pathologies associated with DOP by inhibiting DNMT1/3a. In primary osteoblasts, AVI alleviated GPX4 suppression and reduced ferroptosis in DOP-conditioned primary osteoblasts through a mechanism dependent on DNMT inhibition and GPX4 restoration. Importantly, the anti-ferroptotic and osteoprotective effects of AVI were abolished in osteoblastic Gpx4 haplo-deficient mice (<em>Gpx4^Ob-/+</em>) or when GPX4 was pharmacologically inactivated with RSL3.<h3>Conclusions</h3>Our study identifies a pivotal epigenetic ferroptotic pathway that contributes significantly to DOP and uncovers a crucial pharmacological property of AVI that is potentially effective in treating patients with DOP and related osteoporotic disorders.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"216 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783091","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}

{"title":"Unlocking biological insights from differentially expressed Genes: Concepts, methods, and future perspectives","authors":"Huachun Yin, Hongrui Duo, Song Li, Dan Qin, Lingling Xie, Yingxue Xiao, Jing Sun, Jingxin Tao, Xiaoxi Zhang, Yinghong Li, Yue Zou, Qingxia Yang, Xian Yang, Youjin Hao, Bo Li","doi":"10.1016/j.jare.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.004","url":null,"abstract":"<h3>Background</h3>Identifying differentially expressed genes (DEGs) is a core task of transcriptome analysis, as DEGs can reveal the molecular mechanisms underlying biological processes. However, interpreting the biological significance of large DEG lists is challenging. Currently, gene ontology, pathway enrichment and protein–protein interaction analysis are common strategies employed by biologists. Additionally, emerging analytical strategies/approaches (such as network module analysis, knowledge graphs, drug repurposing, cell marker discovery, trajectory analysis, and cell communication analysis) have been proposed. Despite these advances, comprehensive guidelines for systematically and thoroughly mining the biological information within DEGs remain lacking.<h3>Aim</h3><em>of review:</em> This review aims to provide an overview of essential concepts and methodologies for the biological interpretation of DEGs, enhancing the contextual understanding. It also addresses the current limitations and future perspectives of these approaches, highlighting their broad applications in deciphering the molecular mechanism of complex diseases and phenotypes. To assist users in extracting insights from extensive datasets, especially various DEG lists, we developed DEGMiner (<span><span>https://www.ciblab.net/DEGMiner/</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>), which integrates over 300 easily accessible databases and tools.<h3>Key scientific concepts of review</h3>This review offers strong support and guidance for exploring DEGs, and also will accelerate the discovery of hidden biological insights within genomes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"27 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783094","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}

{"title":"Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer","authors":"Zhi Xiong, Rui-Lin Zhuang, Shun-Li Yu, Zhao-Xiang Xie, Shi-Rong Peng, Ze-An Li, Bing-Heng Li, Jun-Jia Xie, Yi-Ning Li, Kai-Wen Li, Hai Huang","doi":"10.1016/j.jare.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.003","url":null,"abstract":"<h3>Introduction</h3>Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment, being implicated in enhancing tumor growth and fostering drug resistance. Nonetheless, the mechanisms underlying their function in prostate cancer (PCa) remain incompletely understood, which is essential for devising effective therapeutic strategies.<h3>Objectives</h3>The main objective of this study was to explore the mechanisms by which CAFs mediate PCa growth and chemoresistance.<h3>Methods</h3>We validated through data analysis and experimentation that CAFs significantly impact PCa cell proliferation and chemoresistance. Subsequently, we conducted a comprehensive proteomic analysis of the conditioned media from CAFs and PCa cells and identified angiopoietin-like protein 4 (ANGPTL4) as a key factor. We employed ELISA and multiplex immunofluorescence assays, all of which indicated that ANGPTL4 was primarily secreted by CAFs.Next, we conducted metabolomics analysis, GST pull-down assays, Co-IP, and other experiments to explore the specific molecular mechanisms of ANGPTL4 and its precise effects on PCa cells. Through drug screening, we identified Quercetin 3-O-(6′-galactopyranosyl)-β-D-galactopyranoside (QGGP) as an effective inhibitor of CAFs function. Finally, we thoroughly assessed the therapeutic potential of QGGP both as a monotherapy and in combination with docetaxel in PCa cells<h3>Results</h3>We discovered that the extracrine factor ANGPTL4 is primarily expressed in CAFs in PCa. When ANGPTL4 binds to IQ motif-containing GTPase-activating protein 1 (IQGAP1) on the PCa cell membrane, it activates the Raf-MEK-ERK-PGC1α axis, promoting mitochondrial biogenesis and OXPHOS metabolism, and thereby facilitating PCa growth and chemoresistance. Furthermore, virtual and functional screening strategies identified QGGP as a specific inhibitor of IQGAP1 that promotes its degradation. Combined with docetaxel treatment, QGGP can reverse the effects of CAFs and improve the responsiveness of PCa to chemotherapy.<h3>Conclusions</h3>This study uncovers a paracrine mechanism of chemoresistance in PCa and proposes that targeting the stroma could be a therapeutic choice.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788674","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}

{"title":"Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility","authors":"Renhong Lu, Bowen Lin, Zheyi Lin, Hui Xiong, Junyang Liu, Li Li, Zheng Gong, Siyu Wang, Mingshuai Zhang, Jie Ding, Chengwen Hang, Huixin Guo, Duanyang Xie, Yi Liu, Dan Shi, Dandan Liang, Zhen Liu, Jian Yang, Yi-Han Chen","doi":"10.1016/j.jare.2024.11.037","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.037","url":null,"abstract":"<h3>Introduction</h3>Cell fate determination and transition are of paramount importance in biology and medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear. Osmolarity is an essential physical factor that acts on living cells, especially for pluripotent cells, but its significance in cell fate transition remains unexplored.<h3>Objectives</h3>To investigate the role of osmolarity in cell fate transition and its underlying mechanism.<h3>Methods</h3>Flow cytometry, quantitative PCR, teratoma and chimeric mice assays were performed to assess reprogramming efficiency and characterize iPSCs. TEM, immunofluorescence staining, western blot, chemical treatment and genetic modification were utilized to evaluate cell morphology, signaling pathways, cytoskeleton and nuclear structure. Multiomic sequencings were applied to unveil the transcriptome, histone markers and chromatin accessibility of EpiSCs in hypo-osmotic condition.<h3>Result</h3>In hypo-osmotic condition, the reprogramming efficiency of hypo-osmotic EpiSCs increased over 60-fold than that of <em>iso</em>-osmotic cells (1100 <em>vs</em> 18 colonies per 3 × 10⁵ cells), whereas no colony formed in hyper-osmotic cells. The converted cells displayed naive pluripotency. The hypo-osmotic EpiSCs exhibited larger cell size, nuclear area and less heterochromatin; ATAC-seq and ChIP-seq confirmed the increased accessibility of naive pluripotent gene loci with more H3K27ac. Mechanistically, hypo-osmolarity activated PI3K-AKT-SP1 signaling in EpiSCs, which reshaped cytoskeleton and nucleoskeleton, resulting in genome reorganization and pluripotent gene expression. In contrast, hypo-osmolarity delayed the ESCs’ exit from naive pluripotency. Moreover, in MEFs reprograming, hypo-osmolarity promoted the conversion to naive pluripotency.<h3>Conclusion</h3>Hypo-osmolarity promotes cell fate transition by remodeling cytoskeleton, nucleoskeleton and genome via PI3K-AKT-SP1 pathway.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"27 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776783","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}

{"title":"Targeting Dlat-Trpv3 pathway by hyperforin elicits non-canonical promotion of adipose thermogenesis as an effective anti-obesity strategy","authors":"Sijia Lu, Quanxin Jiang, Peihui Zhou, Limin Yin, Ning Wang, Junting Xu, Qiqi Qian, Mijia Tao, Hanrui Yin, Liu Han, Yunqing Gu, Fei Gao, Junli Liu, Suzhen Chen","doi":"10.1016/j.jare.2024.11.035","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.035","url":null,"abstract":"<h3>Introduction</h3>Promoting adipose thermogenesis is considered as a promising therapeutic intervention in obesity. However, endeavors to develop anti-obesity medications by targeting the canonical thermogenesis regulatory pathway, particularly β3-adrenergic receptor (β3-AR)-dependent mechanism, have failed due to the off-target effects of β3-AR agonists, exacerbating the risk of cardiovascular disease. Hyperforin (HPF), a natural compound extracted from the traditional herbal St. John’s Wort, binds to Dihydrolipoamide s-acetyltransferase (Dlat) and exerts effective anti-obesity properties through promoting adipose thermogenesis.<h3>Objectives</h3>The objective of this study was to investigate the oral efficacy and pharmacokinetics profile of HPF, and explore the detailed mechanism by which Dlat modulates HPF-mediated adipose thermogenesis.<h3>Methods</h3>To assess the anti-obesity efficacy of orally administered HPF <em>in vivo</em>, Dlat heterozygous knockout (Dlat^+/-) mice and wild-type (WT) mice, both fed a high-fat diet (HFD), underwent a validation process that involved the use of metabolic cages, NMR analysis, and infrared imaging. Sprague Dawley rats were employed to determine the pharmacokinetic parameters of HPF. Seahorse assays, JC-1 staining, qPCR, and immunoblotting were performed to evaluate cellular thermogenic efficacy of HPF and Dlat <em>in vitro</em>.<h3>Results</h3>Our study uncovered a non-canonical thermogenesis pathway involving Dlat, transient receptor potential vanilloid 3 (Trpv3, a calcium channel) and AMPK. Dlat interacted with Trpv3 to activate it, resulting in an increase in intracellular calcium (Ca²⁺) and the activation of Camkkβ. Camkkβ then stimulated AMPK, leading to elevated Ucp1 expression and initiating adipose thermogenesis. HPF promoted thermogenesis in adipose tissues through enhancing the Dlat-Trpv3 interaction independently of β3­AR, causing minimal cardiac side effects. Notably, HPF’s thermogenic effects were reduced in Dlat^+/- mice. Moreover, HPF exerted favorable oral bioavailability, a relatively long half-life, and extensive distribution within adipose tissues.<h3>Conclusion</h3>In summary, our study demonstrates that HPF targets a novel mechanism for promoting adipose thermogenesis and exhibits potent and safe anti-obesity efficacy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758548","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}

{"title":"The potential of circular RNAs as biomarkers and therapeutic targets for gastric cancer: A comprehensive review","authors":"Junlin Pu, Xiuli Yan, Hui Zhang","doi":"10.1016/j.jare.2024.11.032","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.032","url":null,"abstract":"<h3>Background</h3>Gastric cancer (GC) is a global health concern, contributing significantly to cancer-related mortality rates. Early detection is vital for improving patient outcomes. Recently, circular RNAs (circRNAs) have emerged as crucial players in the development and progression of various cancers, including GC.<h3>Aim</h3><em>of Review</em>: This comprehensive review underscores the promising potential of circRNAs as innovative biomarkers for the early diagnosis of GC, as well as their possible utility as therapeutic targets for this life-threatening disease. Specifically, the review focuses on recent findings, mechanistic insights, and clinical applications of circRNAs in GC.<em>Key Scientific Concepts of Review</em>: Dysregulation of circRNAs has been consistently observed in GC tissues, offering potential diagnostic value due to their stability in bodily fluids such as blood and urine. For instance, circPTPN22 and hsa_circ_000200. Furthermore, the expression levels of circRNAs such as circCUL2, hsa_circ_0000705 and circSHKBP1 have shown strong associations with critical clinical features of GC, including diagnosis, prognosis, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) stage, and treatment response. Additionally, circRNAs such as circBGN, circLMO7, and circMAP7D1 have shown interactions with specific microRNAs (miRNAs), proteins, and other molecules that play key roles in development and progression of GC. This further highlighting their potential as therapeutic targets. Despite their potential, several challenges need to be addressed to effectively apply circRNAs as GC biomarkers. These include standardizing detection methods, establishing cutoff values for diagnostic accuracy, and validating findings in larger patient cohorts. Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"5 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742449","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}

{"title":"Full dimensional dynamic 3D convolution and point cloud in pulmonary nodule detection","authors":"Yun Tie, Ying Wang, Dalong Zhang, Zepeng Zhang, Fenghui Liu, Lin Qi","doi":"10.1016/j.jare.2024.11.033","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.033","url":null,"abstract":"Lung cancer is a leading cause of death worldwide, making early and accurate diagnosis essential for improving patient outcomes. Recently, deep learning (DL) has proven to be a powerful tool, significantly enhancing the accuracy of computer-aided pulmonary nodule detection (PND). In this study, we introduce a novel approach called the Omni-dimension Dynamic Residual 3D Net (ODR3DNet) for PND, which utilizes full-dimensional dynamic 3D convolution, along with a specialized machine learning algorithm for detecting lung nodules in 3D point clouds. The primary goal of ODR3DNet is to overcome the limitations of conventional 3D Convolutional Neural Networks (CNNs), which often struggle with adaptability and have limited feature extraction capabilities. Our ODR3DNet algorithm achieves a high CPM (Competition Performance Metric) score of 0.885, outperforming existing mainstream PND algorithms and demonstrating its effectiveness. Through detailed ablation experiments, we confirm that the OD3D module plays a crucial role in this performance boost and identify the optimal configuration for the algorithm. Moreover, we developed a dedicated machine learning detection algorithm tailored for lung 3D point cloud data. We outline the key steps for reconstructing the lungs in 3D and establish a comprehensive process for building a lung point cloud dataset, including data preprocessing, 3D point cloud conversion, and 3D volumetric box annotation. Experimental results validate the feasibility and effectiveness of our proposed approach.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"62 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742450","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}