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Key β1-4 galactosylated glycan receptors of SARS-CoV-2 and its inhibitor from the galactosylated glycoproteins of bovine milk 牛乳半乳糖糖蛋白中SARS-CoV-2的关键β1-4 -半乳糖糖化受体及其抑制剂
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.010
Hanjie Yu , Wentian Chen , Jian Shu , Xin Wu , Jia Quan , Hongwei Cheng , Xiaojuan Bao , Di Wu , Xilong Wang , Zheng Li
{"title":"Key β1-4 galactosylated glycan receptors of SARS-CoV-2 and its inhibitor from the galactosylated glycoproteins of bovine milk","authors":"Hanjie Yu ,&nbsp;Wentian Chen ,&nbsp;Jian Shu ,&nbsp;Xin Wu ,&nbsp;Jia Quan ,&nbsp;Hongwei Cheng ,&nbsp;Xiaojuan Bao ,&nbsp;Di Wu ,&nbsp;Xilong Wang ,&nbsp;Zheng Li","doi":"10.1016/j.jare.2024.12.010","DOIUrl":"10.1016/j.jare.2024.12.010","url":null,"abstract":"<div><h3>Introduction</h3><div>The binding of the spike (S) protein of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) is a critical stage in the process of infection. While previous studies indicated that the S protein and ACE2 are extensively glycosylated, the functions of glycans in their interactions remain uncertain.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the glycan receptors of SARS-CoV-2 and evaluate the inhibitory effects of galactosylated glycoproteins derived from bovine milk on the attachment of SARS-CoV-2 pseudovirus.</div></div><div><h3>Methods</h3><div>An antibody-overlay lectin microarray was used to profile the glycopatterns of the S protein-S1 of SARS-CoV-2 and ACE2. Molecular dynamics simulation was used to mimic the interaction between the S protein and ACE2. The effects of N-glycans and β1-4 galactosylation on the interactions between SARS-CoV-2, its variations (B1.617.2 (Delta) and B1.1.529 (Omicron)), and ACE2 was assessed using molecular docking simulation and protein microarrays. The impact of glycoproteins (specifically sialylated glycoproteins or de-sialylated glycoproteins) derived from bovine milk on the interaction between S1 and ACE2, as well as on pseudoviral attachment and entry, was assessed using protein microarrays and pseudovirus-based microneutralization assays.</div></div><div><h3>Results</h3><div>Our findings indicated that the galactosylated glycoforms were the most prevalent for both S1 and ACE2. Importantly, we demonstrated that the β1-4 galactosylated N-glycans of ACE2 played a crucial role in the binding of S1 of SARS-CoV-2 and its variations to ACE2. The glycoproteins derived from bovine milk had a large amount of galactosylated glycans, which are comparable to the glycoforms of ACE2. The glycoproteins effectively blocked the attachment and entry of the SARS-CoV-2 pseudovirus by competitively blocking the binding of S1 to ACE2.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrated that the β1-4 galactosylated N-glycans of ACE2 play a crucial role as glycan receptors for the binding of S1 of SARS-CoV-2 and its variations. Moreover, the glycoproteins with ’receptor-like’ glycoforms could be an effective inhibitor to prevent SARS-CoV-2 infection.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 159-172"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804649","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}
引用次数: 0
An accurate prediction for respiratory diseases using deep learning on bronchoscopy diagnosis images 在支气管镜诊断图像上使用深度学习准确预测呼吸系统疾病
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.11.023
Weiling Sun , Pengfei Yan , Minglei Li , Xiang Li , Yuchen Jiang , Hao Luo , Yanbin Zhao
{"title":"An accurate prediction for respiratory diseases using deep learning on bronchoscopy diagnosis images","authors":"Weiling Sun ,&nbsp;Pengfei Yan ,&nbsp;Minglei Li ,&nbsp;Xiang Li ,&nbsp;Yuchen Jiang ,&nbsp;Hao Luo ,&nbsp;Yanbin Zhao","doi":"10.1016/j.jare.2024.11.023","DOIUrl":"10.1016/j.jare.2024.11.023","url":null,"abstract":"<div><h3>Introduction</h3><div>Bronchoscopy is of great significance in diagnosing and treating respiratory illness. Using deep learning, a diagnostic system for bronchoscopy images can improve the accuracy of tracheal, bronchial, and pulmonary disease diagnoses for physicians and ensure timely pathological or etiological examinations for patients. Improving the diagnostic accuracy of the algorithms remains the key to this technology.</div></div><div><h3>Objectives</h3><div>To deal with the problem, we proposed a multiscale attention residual network (MARN) for diagnosing lung conditions through bronchoscopic images. The multiscale convolutional block attention module (MCBAM) was designed to enable accurate focus on lesion regions by enhancing spatial and channel features. Gradient-weighted Class Activation Map (Grad-CAM) was provided to increase the interpretability of diagnostic results.</div></div><div><h3>Methods</h3><div>We collected 615 cases from Harbin Medical University Cancer Hospital, including 2900 images. The dataset was partitioned randomly into training sets, validation sets and test sets to update model parameters, evaluate the model’s training performance, select network architecture and parameters, and estimate the final model. In addition, we compared MARN with other algorithms. Furthermore, three physicians with different qualifications were invited to diagnose the same test images, and the results were compared to those of the model.</div></div><div><h3>Results</h3><div>In the dataset of normal and lesion images, our model displayed an accuracy of 97.76% and an AUC of 99.79%. The model recorded 92.26% accuracy and 96.82% AUC for datasets of benign and malignant lesion images, while it achieved 93.10% accuracy and 99.02% AUC for normal, benign, and malignant lesion images.</div></div><div><h3>Conclusion</h3><div> <!-->These results demonstrated that our network outperforms other methods in diagnostic performance. The accuracy of our model is roughly the same as that of experienced physicians and the efficiency is much higher than doctors. MARN has great potential for assisting physicians with assessing the bronchoscopic images precisely.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 423-438"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673784","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}
引用次数: 0
Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects 评价草药网络药理学的现状,重点是确定其机制和治疗效果
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.040
Won-Yung Lee , Kwang-Il Park , Seon-Been Bak , Seungho Lee , Su-Jin Bae , Min-Jin Kim , Sun-Dong Park , Choon Ok Kim , Ji-Hwan Kim , Young Woo Kim , Chang-Eop Kim
{"title":"Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects","authors":"Won-Yung Lee ,&nbsp;Kwang-Il Park ,&nbsp;Seon-Been Bak ,&nbsp;Seungho Lee ,&nbsp;Su-Jin Bae ,&nbsp;Min-Jin Kim ,&nbsp;Sun-Dong Park ,&nbsp;Choon Ok Kim ,&nbsp;Ji-Hwan Kim ,&nbsp;Young Woo Kim ,&nbsp;Chang-Eop Kim","doi":"10.1016/j.jare.2024.12.040","DOIUrl":"10.1016/j.jare.2024.12.040","url":null,"abstract":"<div><h3>Introduction</h3><div>Network pharmacology has gained significant traction as a tool for identifying the mechanisms and therapeutic effects of herbal medicines. However, despite the usefulness of these approaches, their diversity underscores the critical need for a systematic evaluation to ensure consistency and reliability.</div></div><div><h3>Objectives</h3><div>We aimed to evaluate the network pharmacological analyses, focusing on identifying the mechanisms and therapeutic effects of herbal medicines.</div></div><div><h3>Methods</h3><div>We employed a comprehensive approach involving systematic data retrieval, network construction, and analysis. Herbal compounds and their targets were meticulously extracted from five distinct network pharmacology databases to ensure extensive coverage and high data reliability. Advanced network-based methods were used to identify key herbal targets and predict therapeutic effects, thereby enriching the depth and breadth of the analysis. Experimental validation was performed on prostate cancer models to substantiate the computational predictions.</div></div><div><h3>Results</h3><div>The results of the recapitulating task for known herbal ingredient targets revealed distinct patterns in performance and coverage based on network construction and aggregation methods. We performed the same analysis to identify herbal targets and found that network centrality, path counts, and downweighted path counts had their own pros and cons. By comparing network-based methods, we found that considering the impact on the multiscale interactome yielded the highest accuracy in discriminating known therapeutic effects. Using optimal conditions, we successfully identified new indications for herbal medicines and validated these findings through follow-up <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Conclusion</h3><div>This study presents the first comprehensive and critical evaluation of the current network pharmacology analyses in the field of herbal medicine and provides valuable guidance for continued advances in the elucidation of the mechanisms and therapeutic effects.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 799-815"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884682","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}
引用次数: 0
Insulin-like growth factor binding protein 7 identified in aged dental pulp by single-cell RNA sequencing 单细胞RNA测序在老年牙髓中鉴定胰岛素样生长因子结合蛋白7
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.018
Zhongchun Tong , Jie Wu , Qimei Gong , Yifang Yuan , Shengchao Wang , Wenkai Jiang
{"title":"Insulin-like growth factor binding protein 7 identified in aged dental pulp by single-cell RNA sequencing","authors":"Zhongchun Tong ,&nbsp;Jie Wu ,&nbsp;Qimei Gong ,&nbsp;Yifang Yuan ,&nbsp;Shengchao Wang ,&nbsp;Wenkai Jiang","doi":"10.1016/j.jare.2024.12.018","DOIUrl":"10.1016/j.jare.2024.12.018","url":null,"abstract":"<div><h3>Introduction</h3><div>Aging influences the regenerative and reparative functions of dental pulp, and an in-depth and complete understanding of aged dental pulp is highly important.</div></div><div><h3>Objective</h3><div>This study aimed to explore the heterogeneity of young and aged dental pulp tissue via single-cell RNA sequencing (scRNA-seq), search novel markers of aged dental pulp, and further explore their mechanism.</div></div><div><h3>Methods</h3><div>ScRNA-seq was employed to analyze the heterogeneity of young and aged dental pulp tissue, and immunohistochemical staining was used to detect new marker Insulin-like Growth Factor Binding Protein 7 (IGFBP7) in aged dental pulp. Differentially expressed genes (DEGs) between young and aged dental pulp tissue related with senescence-associated secretory phenotype (SASP) were validated in aging model of H<sub>2</sub>O<sub>2</sub>-induced dental pulp fibroblast (DPF). The effect of IGFBP7 on cellular senescence were validated by SA-β-Gal, γ-H2AX, and F-actin cytoskeletal staining. RNA-seq was used to analyze the mechanism of IGFBP7 alleviating senescence of H<sub>2</sub>O<sub>2</sub>-induced DPFs.</div></div><div><h3>Results</h3><div>A total of 32,012 cells were sequenced from 8 dental pulp samples and categorized into 8 main clusters, including fibroblasts (FB), endothelial cells, monocytes, T cells, B cells, mesenchymal stem cells, Schwann cells, and nonmyelinating ScCs. The ratio of fibroblasts was the highest, and FB1 was the largest subcluster of fibroblasts in the young group. In aged dental pulp, the ratio of fibroblasts was relatively low, and fibroblasts had more cellular communication with other cell types in fibroblast growth factor (FGF) and insulin-like growth factor (IGF) signal pathways. IGFBP7 was significantly upregulated in the aged group. Recombinant IGFBP7 reduced the senescence of H<sub>2</sub>O<sub>2</sub>-induced DPFs.</div></div><div><h3>Conclusions</h3><div>These findings offer insights into the mechanisms of dental pulp aging and enhance our understanding of dental pulp at the single-cell level. Further comprehensive studies are required to clarify the exact mechanisms through which IGFBP7 influences dental pulp aging.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 371-385"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816331","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}
引用次数: 0
Ubiquitin proteasome system in cardiac fibrosis 泛素蛋白酶体系统在心脏纤维化中的作用
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.006
Linqi Zeng , Xiaokai Zhang , Zihang Huang , Shuai Song , Mohan Li , Tongyao Wang , Aijun Sun , Junbo Ge
{"title":"Ubiquitin proteasome system in cardiac fibrosis","authors":"Linqi Zeng ,&nbsp;Xiaokai Zhang ,&nbsp;Zihang Huang ,&nbsp;Shuai Song ,&nbsp;Mohan Li ,&nbsp;Tongyao Wang ,&nbsp;Aijun Sun ,&nbsp;Junbo Ge","doi":"10.1016/j.jare.2024.12.006","DOIUrl":"10.1016/j.jare.2024.12.006","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim of review</h3><div>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.</div></div><div><h3>Key scientific concepts of review</h3><div>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 ubiquitin ligases (E3 ligases) and deubiquitinating enzymes (DUBs) across various cardiac fibrotic diseases. Insights into UPS-mediated regulation of cardiac fibrosis provide potential anti-fibrotic therapeutic strategies, emphasizing the importance of targeting UPS components specific to the heart for effective therapy against cardiac fibrosis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 501-510"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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}
引用次数: 0
Unlocking biological insights from differentially expressed genes: Concepts, methods, and future perspectives 从差异表达基因中解锁生物学见解:概念、方法和未来前景
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.004
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
{"title":"Unlocking biological insights from differentially expressed genes: Concepts, methods, and future perspectives","authors":"Huachun Yin ,&nbsp;Hongrui Duo ,&nbsp;Song Li ,&nbsp;Dan Qin ,&nbsp;Lingling Xie ,&nbsp;Yingxue Xiao ,&nbsp;Jing Sun ,&nbsp;Jingxin Tao ,&nbsp;Xiaoxi Zhang ,&nbsp;Yinghong Li ,&nbsp;Yue Zou ,&nbsp;Qingxia Yang ,&nbsp;Xian Yang ,&nbsp;Youjin Hao ,&nbsp;Bo Li","doi":"10.1016/j.jare.2024.12.004","DOIUrl":"10.1016/j.jare.2024.12.004","url":null,"abstract":"<div><h3>Background</h3><div>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 graph, 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.</div></div><div><h3>Aim of review</h3><div>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><path></path></svg></span>), which integrates over 300 easily accessible databases and tools.</div></div><div><h3>Key scientific concepts of review</h3><div>This review offers strong support and guidance for exploring DEGs, and also will accelerate the discovery of hidden biological insights within genomes.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 135-157"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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}
引用次数: 0
Exercise-driven cellular autophagy: A bridge to systematic wellness 运动驱动的细胞自噬:通往系统健康的桥梁
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.036
Xiao-Han Zhou , Ya-Xi Luo , Xiu-Qing Yao
{"title":"Exercise-driven cellular autophagy: A bridge to systematic wellness","authors":"Xiao-Han Zhou ,&nbsp;Ya-Xi Luo ,&nbsp;Xiu-Qing Yao","doi":"10.1016/j.jare.2024.12.036","DOIUrl":"10.1016/j.jare.2024.12.036","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim of Review</h3><div>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.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>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.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 271-291"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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}
引用次数: 0
Risk classification for non-cancer death in middle-aged cancer patients 中年癌症患者非癌性死亡的风险分类
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.039
Tianwang Guan , Yanting Jiang , Peinan Tu , Baokui Ye , Liangjia Zeng , Zehao Luo , Kaiyi Chi , Haowen Liang , Yuting Yang , Jinqi Huang , Binghua Zhang , Rundong Tai , Jujian Ye , Zhilin Deng , Yushen Ke , Huiwan Chen , Zhiling Zhang , Zhigang Liu , Caiwen Ou
{"title":"Risk classification for non-cancer death in middle-aged cancer patients","authors":"Tianwang Guan ,&nbsp;Yanting Jiang ,&nbsp;Peinan Tu ,&nbsp;Baokui Ye ,&nbsp;Liangjia Zeng ,&nbsp;Zehao Luo ,&nbsp;Kaiyi Chi ,&nbsp;Haowen Liang ,&nbsp;Yuting Yang ,&nbsp;Jinqi Huang ,&nbsp;Binghua Zhang ,&nbsp;Rundong Tai ,&nbsp;Jujian Ye ,&nbsp;Zhilin Deng ,&nbsp;Yushen Ke ,&nbsp;Huiwan Chen ,&nbsp;Zhiling Zhang ,&nbsp;Zhigang Liu ,&nbsp;Caiwen Ou","doi":"10.1016/j.jare.2024.12.039","DOIUrl":"10.1016/j.jare.2024.12.039","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-cancer events are important causes of competing mortality among cancer patients. However, the risk of non-cancer death and risk classification in middle-aged cancer patients is not clear. To comprehensively analyze the risk of non-cancer deaths in 24 different cancers among middle-aged patients.</div></div><div><h3>Methods</h3><div>Standardized mortality rate (SMR), absolute excess risk (AER), proportion of deaths, age-adjusted mortality rate (AAMR), and the competing model were used to assess the risk of non-cancer death in middle-aged cancer patients. A non-cancer death risk classification was developed for the 24 cancer types based on the competing risk of non-cancer death and the risk of non-cancer death (hazard ratio).</div></div><div><h3>Results</h3><div>A total of 1,082,030 middle-aged cancer patients of 24 cancer types was identified. The risk of non-cancer death was elevated in middle-aged cancer patients compared to the general middle-aged population (SMR = 3.37, 95 % CI 3.35–3.39, AER = 99.18). The cumulative mortality was higher for non-cancer causes compared to primary cancer in 15 cancer types. The AAMR for non-cancer causes declined from 2.3 % in 1975 to 1.4 % in 2017. A risk classification was developed to classify different cancers into 6 risk categories.</div></div><div><h3>Conclusion</h3><div>The risk of non-cancer death was elevated in middle-aged cancer patients and varied for different cancer types. A new risk classification system was developed to estimate the risk of non-cancer deaths in different cancers, and the 24 cancer types were classified into 6 distinct categories. These results highlight the necessity for risk stratification management for non-cancer death in middle-aged cancer patients.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 669-678"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886717","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}
引用次数: 0
Targeting macrophages in cancer immunotherapy: Frontiers and challenges 靶向巨噬细胞在癌症免疫治疗:前沿和挑战
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.12.043
Yu’e Liu , Huabing Tan , Jingyuan Dai , Jianghua Lin , Kaijun Zhao , Haibo Hu , Chunlong Zhong
{"title":"Targeting macrophages in cancer immunotherapy: Frontiers and challenges","authors":"Yu’e Liu ,&nbsp;Huabing Tan ,&nbsp;Jingyuan Dai ,&nbsp;Jianghua Lin ,&nbsp;Kaijun Zhao ,&nbsp;Haibo Hu ,&nbsp;Chunlong Zhong","doi":"10.1016/j.jare.2024.12.043","DOIUrl":"10.1016/j.jare.2024.12.043","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim of review</h3><div>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.</div></div><div><h3>Key scientific concepts of review</h3><div>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.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 695-713"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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}
引用次数: 0
Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis 均匀乳杆菌通过靶向内质网应激介导的铁蛋白沉积,改善饮食引起的炎症性加剧结肠炎
IF 13 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-10-01 DOI: 10.1016/j.jare.2024.11.025
Caiguang Liu , Linxin Liu , Zhenyi Tian , Shukai Zhan , Yun Qiu , Manying Li , Tong Li , Ren Mao , Shenghong Zhang , Minhu Chen , Zhirong Zeng , Xiaojun Zhuang
{"title":"Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis","authors":"Caiguang Liu ,&nbsp;Linxin Liu ,&nbsp;Zhenyi Tian ,&nbsp;Shukai Zhan ,&nbsp;Yun Qiu ,&nbsp;Manying Li ,&nbsp;Tong Li ,&nbsp;Ren Mao ,&nbsp;Shenghong Zhang ,&nbsp;Minhu Chen ,&nbsp;Zhirong Zeng ,&nbsp;Xiaojun Zhuang","doi":"10.1016/j.jare.2024.11.025","DOIUrl":"10.1016/j.jare.2024.11.025","url":null,"abstract":"<div><h3>Introduction</h3><div>A pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases (IBD). Recently, ferroptosis has been observed in patients with different dietary patterns-associated intestinal inflammation, while the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown.</div></div><div><h3>Objectives</h3><div>This study aims to elucidate the mechanisms underlying pro-inflammatory diet-mediated colitis and explore potential intervention strategies.</div></div><div><h3>Methods</h3><div>Mice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5 % dextran sulfate sodium. The body weight, pathological score, immune response and mucosal barrier function were evaluated to assess intestinal inflammation. Intestine tissue transcriptomics, fecal microbiome analysis and serum metabolomics were applied to identify diet–microbe–host interactions. Additionally, the dietary inflammatory index (DII) scores and intestinal specimens of 32 patients with Crohn’s disease were evaluated. The biological functions of <em>Bacteroides uniformis</em> were observed <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Pro-inflammatory diet induces low-grade intestinal inflammation in mice and exacerbates colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway. These effects are reversed by ferrostatin-1 treatment. Additionally, the pro-inflammatory diet triggers colitis by modulating the gut microbiota and metabolites. Notably, supplementation with <em>B. uniformis</em> improves the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Moreover, <em>B. uniformis</em> is non-enterotoxigenic and non-enteroinvasive in co-cultures with intestinal epithelial cells.</div></div><div><h3>Conclusions</h3><div>Pro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating IBD.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 481-499"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670842","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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