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Targeting the STAT3/IL-36G signaling pathway can be a promising approach to treat rosacea 靶向 STAT3/IL-36G 信号通路是一种治疗酒渣鼻的有效方法。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.06.013
Xin Meng , Yun Zhong , Xuyuan Kuang , Yiya Zhang , Li Yang , Yisheng Cai , Fan Wang , Fanping He , Hongfu Xie , Ben Wang , Ji Li
{"title":"Targeting the STAT3/IL-36G signaling pathway can be a promising approach to treat rosacea","authors":"Xin Meng ,&nbsp;Yun Zhong ,&nbsp;Xuyuan Kuang ,&nbsp;Yiya Zhang ,&nbsp;Li Yang ,&nbsp;Yisheng Cai ,&nbsp;Fan Wang ,&nbsp;Fanping He ,&nbsp;Hongfu Xie ,&nbsp;Ben Wang ,&nbsp;Ji Li","doi":"10.1016/j.jare.2024.06.013","DOIUrl":"10.1016/j.jare.2024.06.013","url":null,"abstract":"<div><h3>Background</h3><div>Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited.</div></div><div><h3>Objectives</h3><div>To investigate the pathogenesis of rosacea and explore new therapeutic strategies.</div></div><div><h3>Methods</h3><div>Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment.</div></div><div><h3>Results</h3><div>STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocyte-driven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (α-IL36γ) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment.</div></div><div><h3>Conclusions</h3><div>Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 429-440"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443987","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
Nanoparticle-mediated celastrol ER targeting delivery amplify immunogenic cell death in melanoma 纳米颗粒介导的 celastrol ER 靶向递送可扩大黑色素瘤的免疫细胞死亡。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.06.011
Fengling Wang , Wenjing Lai , Dandan Xie, Min Zhou, Jie Wang, Rufu Xu, Rong Zhang, Guobing Li
{"title":"Nanoparticle-mediated celastrol ER targeting delivery amplify immunogenic cell death in melanoma","authors":"Fengling Wang ,&nbsp;Wenjing Lai ,&nbsp;Dandan Xie,&nbsp;Min Zhou,&nbsp;Jie Wang,&nbsp;Rufu Xu,&nbsp;Rong Zhang,&nbsp;Guobing Li","doi":"10.1016/j.jare.2024.06.011","DOIUrl":"10.1016/j.jare.2024.06.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoimmunotherapy, which benefits from the combination of chemotherapy and immunotherapy, has emerged as a promising strategy in cancer treatment. However, effectively inducing a robust immune response remains challenging due to the limited responsiveness across patients. Endoplasmic reticulum (ER) stress is essential for activating intracellular signaling pathways associated with immunogenic cell death (ICD), targeting drugs to ER might enhance ER stress and improve ICD-related immunotherapy.</div></div><div><h3>Objectives</h3><div>To improve the immune response of Chemoimmunotherapy.</div></div><div><h3>Methods</h3><div>ER targeting nanoparticles TSE-CEL/NP were constructed to enhance immunogenic cancer cell death. Flow cytometry, confocal microscope, TEM and immunofluorescence were used to evaluate the ER targeting effect and immunogenic tumor cell death <em>in vitro</em> on B16F10 tumor cells. Unilateral and bilateral tumor models were constructed to investigate the efficacy of anti-tumor and immunotherapy <em>in vivo</em>. Lung metastasis B16F10 melanoma tumor-bearing mice were used to assess the anti-metastasis efficacy.</div></div><div><h3>Results</h3><div>TSE-CEL/NP could specially accumulate in ER, thereby induce ER stress. High ER stress trigger the exposure of CRT, the extracellular release of HMGB1 and ATP. These danger signals subsequently promote the recruitment and maturation of dendritic cells (DCs), which in turn increase the proliferation of cytotoxic T lymphocytes (CD8<sup>+</sup> T cells), ultimately resulted in an improved immunotherapy efficacy against melanoma. <em>In<!--> <!-->vivo</em> experiments showed that TSE-CEL/NP exhibits excellent antitumor efficacy and triggers a strong immune response.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrated that celastrol ER targeting delivery could amplify immunogenic cell death in melanoma, which provide experimental basis for melanoma immunotherapy.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 585-601"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428569","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
Developing a multi-modular assembled prime editing (mPE) system improved precise multi-base insertion efficiency in dicots 开发多模块组装素材编辑(mPE)系统提高了双子叶植物的精确多碱基插入效率。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.06.021
Pengjun Lu, Erwei Zuo, Jianbin Yan
{"title":"Developing a multi-modular assembled prime editing (mPE) system improved precise multi-base insertion efficiency in dicots","authors":"Pengjun Lu,&nbsp;Erwei Zuo,&nbsp;Jianbin Yan","doi":"10.1016/j.jare.2024.06.021","DOIUrl":"10.1016/j.jare.2024.06.021","url":null,"abstract":"<div><h3>Introduction</h3><div>The Prime Editing (PE) system is a precise and versatile genome editing tool with great potential in plant breeding and plant synthetic biology. However, low PE efficiency severely restricts its application, especially in dicots. PE can introduce small tags to trace target protein or <em>cis</em>-element to regulate gene transcription which is an expertise superior to other gene editing tools. Owing to low efficiency, PE adaption in stably transformed <em>Arabidopsis</em> is lacking.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the issue of low PE efficiency in dicots and develop systematic solutions to improve it. Currently, PE in dicots is undetectable and inconsistent, and this study seeks to address it. Split PE into several parts showed better performance in some target sites in mammal cells. We plan to discover the optimal split PE combination in dicot.</div></div><div><h3>Methods</h3><div>We conducted large-scale transformation experiments in dicot model plants <em>Arabidopsis thaliana</em> (<em>At</em>) and <em>Nicotiana benthamiana</em> (<em>Nb</em>) by <em>Agrobacterium</em>-mediated transformation with deep amplicon sequencing (0.2–0.5 million clean total reads).</div></div><div><h3>Results</h3><div>The editing efficiency decreased upon using a fused reverse transcriptase (RT) or an extended pegRNA separately and further decreased dramatically when these were used together. With the help of the pol II strategy to express PE gRNA (pegRNA), we named the most effective split PE combination as a multi-modular assembled prime editing system (mPE). mPE exhibited improved precise editing efficiency on most gene sites with various editing types, ranging from 1.3-fold to 1288.5-fold and achieved PE on some sites that could not be edited by original PE2. Especially, mPE showed superiority for multi-base insertion with an average improvement of 197.9-fold.</div></div><div><h3>Conclusion</h3><div>The original PE architecture strongly inhibited the cleavage activity of Cas9. Split PE improved PE efficiency extensively and was in favor of introducing small insertions in dicot plants, indicating that different PE variants might have their own expertise.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 81-92"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473952","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
Residential greenness and chronic obstructive pulmonary disease in a large cohort in southern China: Potential causal links, risk trajectories, and mediation pathways 中国南方大型队列中的住宅绿化与慢性阻塞性肺病:潜在的因果联系、风险轨迹和中介途径
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.025
Wenjing Wu , Dan Chen , Xingling Ruan , Gonghua Wu , Xinlei Deng , Wayne Lawrence , Xiao Lin , Zhiqiang Li , Ying Wang , Ziqiang Lin , Shuming Zhu , Xueqing Deng , Qiaoxuan Lin , Chun Hao , Zhicheng Du , Jing Wei , Wangjian Zhang , Yuantao Hao
{"title":"Residential greenness and chronic obstructive pulmonary disease in a large cohort in southern China: Potential causal links, risk trajectories, and mediation pathways","authors":"Wenjing Wu ,&nbsp;Dan Chen ,&nbsp;Xingling Ruan ,&nbsp;Gonghua Wu ,&nbsp;Xinlei Deng ,&nbsp;Wayne Lawrence ,&nbsp;Xiao Lin ,&nbsp;Zhiqiang Li ,&nbsp;Ying Wang ,&nbsp;Ziqiang Lin ,&nbsp;Shuming Zhu ,&nbsp;Xueqing Deng ,&nbsp;Qiaoxuan Lin ,&nbsp;Chun Hao ,&nbsp;Zhicheng Du ,&nbsp;Jing Wei ,&nbsp;Wangjian Zhang ,&nbsp;Yuantao Hao","doi":"10.1016/j.jare.2024.05.025","DOIUrl":"10.1016/j.jare.2024.05.025","url":null,"abstract":"<div><h3>Introduction</h3><div>Residential greenness may influence COPD mortality, but the causal links, risk trajectories, and mediation pathways between them remain poorly understood.</div></div><div><h3>Objectives</h3><div>We aim to comprehensively identify the potential causal links, characterize the dynamic progression of hospitalization or posthospital risk, and quantify mediation effects between greenness and COPD.</div></div><div><h3>Methods</h3><div>This study was conducted using a community-based cohort enrolling individuals aged ≥ 18 years in southern China from January 1, 2009 to December 31, 2015. Greenness was characterized by normalized difference vegetation index (NDVI) around participants’ residential addresses. We applied doubly robust Cox proportional hazards model, multi-state model, and multiple mediation method, to investigate the potential causal links, risk trajectories among baseline, COPD hospitalization, first readmission due to COPD or COPD-related complications, and all-cause death, as well as the multiple mediation pathways (particulate matter [PM], temperature, body mass index [BMI] and physical activity) connecting greenness exposure to COPD mortality.</div></div><div><h3>Results</h3><div>Our final analysis included 581,785 participants (52.52% female;</div><div>average age: 48.36 [Standard Deviation (SD): 17.56]). Each interquartile range (IQR: 0.06) increase in NDVI was associated with a reduced COPD mortality risk, yielding a hazard ratio (HR) of 0.88 (95 % CI: 0.81, 0.96). Furthermore, we observed per IQR (0.04) increase in NDVI was inversely associated with the risk of multiple transitions (baseline − COPD hospitalization, baseline − death, and readmission − death risks), especially a declined risk of all-cause death after readmission (HR = 0.66 [95 %CI: 0.44, 0.99]). Within the observed association between greenness and COPD mortality, three mediators were identified, namely PM, temperature, and BMI (HR for the total indirect effect: 0.773 [95 % CI: 0.703, 0.851]), with PM showing the highest mediating effect.</div></div><div><h3>Conclusions</h3><div>Our findings revealed greenness may be a beneficial factor for COPD morbidity, prognosis, and mortality. This protective effect is primarily attributed to the reduction in PM concentration.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 355-367"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141138966","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
Cotton transposon-related variome reveals roles of transposon-related variations in modern cotton cultivation 棉花转座子相关变异组揭示了转座子相关变异在现代棉花种植中的作用。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.019
Shang Liu , Hailiang Cheng , Youping Zhang , Man He , Dongyun Zuo , Qiaolian Wang , Limin Lv , Zhongxv Lin , Ji Liu , Guoli Song
{"title":"Cotton transposon-related variome reveals roles of transposon-related variations in modern cotton cultivation","authors":"Shang Liu ,&nbsp;Hailiang Cheng ,&nbsp;Youping Zhang ,&nbsp;Man He ,&nbsp;Dongyun Zuo ,&nbsp;Qiaolian Wang ,&nbsp;Limin Lv ,&nbsp;Zhongxv Lin ,&nbsp;Ji Liu ,&nbsp;Guoli Song","doi":"10.1016/j.jare.2024.05.019","DOIUrl":"10.1016/j.jare.2024.05.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Transposon plays a vital role in cotton genome evolution, contributing to the expansion and divergence of genomes within <em>the Gossypium</em> genus. However, knowledge of transposon activity in modern cotton cultivation is limited.</div></div><div><h3>Objectives</h3><div>In this study, we aimed to construct transposon-related variome within <em>Gossypium</em> genus and reveal role of transposon-related variations during cotton cultivation. In addition, we try to identify valuable transposon-related variations for cotton breeding.</div></div><div><h3>Methods</h3><div>We utilized graphical genome construction to build up the graphical transposon-related variome. Based on the graphical variome, we integrated <em>t</em>-test, eQTL analysis and Mendelian Randomization (MR) to identify valuable transposon activities and elite genes. In addition, a convolutional neural network (CNN) model was constructed to evaluate epigenomic effects of transposon-related variations.</div></div><div><h3>Results</h3><div>We identified 35,980 transposon activities among 10 cotton genomes, and the diversity of genomic and epigenomic features was observed among 21 transposon categories. The graphical cotton transposon-related variome was constructed, and 9,614 transposon-related variations with plasticity in the modern cotton cohort were used for eQTL, phenotypic <em>t</em>-test and Mendelian Randomization. 128 genes were identified as gene resources improving fiber length and strength simultaneously. 4 genes were selected from 128 genes to construct the elite gene panel whose utility has been validated in a natural cotton cohort and 2 accessions with phenotypic divergence. Based on the eQTL analysis results, we identified transposon-related variations involved in cotton’s environmental adaption and human domestication, providing evidence of their role in cotton’s adaption-domestication cooperation.</div></div><div><h3>Conclusions</h3><div>The cotton transposon-related variome revealed the role of transposon-related variations in modern cotton cultivation, providing genomic resources for cotton molecular breeding.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 17-28"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177143","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 the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects 揭示癌症相关成纤维细胞在肿瘤转移中的关键作用:机制与治疗前景》。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.031
Yingxue Liu , Xiaoyan Zhang , Wenchao Gu , Hui Su , Xin Wang , Xu Wang , Jiayu Zhang , Midie Xu , Weiqi Sheng
{"title":"Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects","authors":"Yingxue Liu ,&nbsp;Xiaoyan Zhang ,&nbsp;Wenchao Gu ,&nbsp;Hui Su ,&nbsp;Xin Wang ,&nbsp;Xu Wang ,&nbsp;Jiayu Zhang ,&nbsp;Midie Xu ,&nbsp;Weiqi Sheng","doi":"10.1016/j.jare.2024.05.031","DOIUrl":"10.1016/j.jare.2024.05.031","url":null,"abstract":"<div><h3>Background</h3><div>Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis.</div></div><div><h3>Aim of review</h3><div>This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy.</div></div><div><h3>Key scientific concepts of review</h3><div>This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 399-413"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201655","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
GYY4137-induced p65 sulfhydration protects synovial macrophages against pyroptosis by improving mitochondrial function in osteoarthritis development 在骨关节炎发展过程中,GYY4137诱导的p65硫酸化作用可通过改善线粒体功能保护滑膜巨噬细胞免受脓毒症的侵袭。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.033
Jun Ma , Peng Yang , Zhibin Zhou , Tengfei Song , Liang Jia , Xiaofei Ye , Wei Yan , Jiuyi Sun , Tianwen Ye , Lei Zhu
{"title":"GYY4137-induced p65 sulfhydration protects synovial macrophages against pyroptosis by improving mitochondrial function in osteoarthritis development","authors":"Jun Ma ,&nbsp;Peng Yang ,&nbsp;Zhibin Zhou ,&nbsp;Tengfei Song ,&nbsp;Liang Jia ,&nbsp;Xiaofei Ye ,&nbsp;Wei Yan ,&nbsp;Jiuyi Sun ,&nbsp;Tianwen Ye ,&nbsp;Lei Zhu","doi":"10.1016/j.jare.2024.05.033","DOIUrl":"10.1016/j.jare.2024.05.033","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoarthritis (OA) is the most common arthritis that is characterized by the progressive synovial inflammation and loss of articular cartilage. Although GYY4137 is a novel and slow-releasing hydrogen sulfide (H<sub>2</sub>S) donor with potent anti-inflammatory properties that may modulate the progression of OA, its underlying mechanism remains unclear.</div></div><div><h3>Objectives</h3><div>In this study, we validated the protective role of GYY4137 against OA pathological courses and elucidated its underlying regulatory mechanisms.</div></div><div><h3>Methods</h3><div>Cell transfection, immunofluorescence staining, EdU assay, transmission electron microscopy, mitochondrial membrane potential measurement, electrophoretic mobility shift assay, sulfhydration assay, qPCR and western blot assays were performed in the primary mouse chondrocytes or the mouse macrophage cell line raw 264.7 for in vitro study. DMM-induced OA mice model and Macrophage-specific p65 knockout (p65<sup>f/f</sup> LysM-CreER<sup>T2</sup>) mice on the C57BL/6 background were used for in vivo study.</div></div><div><h3>Results</h3><div>We found that GYY4137 can alleviate OA progress by suppressing synovium pyroptosis in vivo. Moreover, our in vitro data revealed that GYY4137 attenuates inflammation-induced NLRP3 and caspase-1 activation and results in a decrease of IL-1β production in macrophages. Mechanistically, GYY4137 increased persulfidation of NF-kB p65 in response to inflammatory stimuli that results in a decrease of cellular reactive oxygen species (ROS) accumulation and ameliorates mitochondrial dysfunctions. Using site-directed mutagenesis, we showed that H<sub>2</sub>S persulfidates cysteine38 in p65 protein and hampers p65 transcriptional activity, and p65 mutant impaired macrophage responses to GYY4137.</div></div><div><h3>Conclusion</h3><div>These findings suggest a mechanism by which GYY4137 through redox modification of p65 participates in inhibiting NLRP3 activation by OA to regulate inflammatory responses. Thus, we propose that GYY4137 represents a promising novel therapeutic strategy for the treatment of OA.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 173-188"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285692","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
Fucoidan alleviates high sucrose-induced metabolic disorders and enhances intestinal homeostasis through modulation of Notch signaling 褐藻糖胶通过调节Notch信号传导缓解高蔗糖诱导的代谢紊乱并增强肠道稳态。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.034
Jian Liu , Weiqiang Xia , Qifang Wu , Ya Zhang , Yu Wu , Boyang Li , Fangyu Chen , Xueting Du , Siya Wu , Yue Yang , Yitian Gao , Mingjiang Wu , Laijin Su , Haibin Tong
{"title":"Fucoidan alleviates high sucrose-induced metabolic disorders and enhances intestinal homeostasis through modulation of Notch signaling","authors":"Jian Liu ,&nbsp;Weiqiang Xia ,&nbsp;Qifang Wu ,&nbsp;Ya Zhang ,&nbsp;Yu Wu ,&nbsp;Boyang Li ,&nbsp;Fangyu Chen ,&nbsp;Xueting Du ,&nbsp;Siya Wu ,&nbsp;Yue Yang ,&nbsp;Yitian Gao ,&nbsp;Mingjiang Wu ,&nbsp;Laijin Su ,&nbsp;Haibin Tong","doi":"10.1016/j.jare.2024.05.034","DOIUrl":"10.1016/j.jare.2024.05.034","url":null,"abstract":"<div><h3>Introduction</h3><div>The therapeutic potential of fucoidan (FUC), a natural polysaccharide, in metabolic disorders is recognized, yet its underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>We conducted investigations into the therapeutic mechanisms of FUC sourced from <em>Sargassum fulvellum</em> concerning metabolic disorders induced by a high-sucrose diet (HSD), employing <em>Drosophila melanogaster</em> and mice models. <em>Drosophila</em> larvae were subjected to HSD exposure to monitor growth inhibition, reduced pupation, and developmental delays. Additionally, we examined the impact of FUC on growth- and development-related hormones in <em>Drosophila</em>. Furthermore, we assessed the modulation of larval intestinal homeostasis by FUC, focusing on the regulation of Notch signaling. In mice, we evaluated the effects of FUC on HSD-induced impairments in intestinal epithelial barrier integrity and gut hormone secretion.</div></div><div><h3>Results</h3><div>FUC supplementation significantly enhanced pupal weight in <em>Drosophila</em> larvae and effectively countered HSD-induced elevation of glucose and triglyceride levels. It notably influenced the expression of growth- and development-related hormones, particularly augmenting insulin-like peptides production while mitigating larval growth retardation. FUC also modulated larval intestinal homeostasis by negatively regulating Notch signaling, thereby protecting against HSD-induced metabolic stress. In mice, FUC ameliorated HSD-induced impairments in ileum epithelial barrier integrity and gut hormone secretion.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate the multifaceted therapeutic effects of FUC in mitigating metabolic disorders and maintaining intestinal health. FUC holds promise as a therapeutic agent, with its effects attributed partly to the sulfate group and its ability to regulate Notch signaling, emphasizing its potential for addressing metabolic disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 189-207"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201590","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
Host-virus coevolution drives soil microbial function succession along a millennium land reclamation chronosequence 宿主-病毒共同进化推动土壤微生物功能沿千年土地开垦时序演替。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.06.022
Wenbing Li , Yiling Wang , Kankan Zhao , Linya Xu , Tingfeng Shi , Bin Ma , Xiaofei Lv
{"title":"Host-virus coevolution drives soil microbial function succession along a millennium land reclamation chronosequence","authors":"Wenbing Li ,&nbsp;Yiling Wang ,&nbsp;Kankan Zhao ,&nbsp;Linya Xu ,&nbsp;Tingfeng Shi ,&nbsp;Bin Ma ,&nbsp;Xiaofei Lv","doi":"10.1016/j.jare.2024.06.022","DOIUrl":"10.1016/j.jare.2024.06.022","url":null,"abstract":"<div><h3>Introduction</h3><div>Gene exchange between viruses and hosts plays an important role in driving virus-host coevolution, enabling adaptation of both viruses and hosts to environmental changes. However, the mechanisms and functional significance of virus-host gene exchanges over long-term scales remain largely unexplored.</div></div><div><h3>Objective</h3><div>The present study aimed to gain insights into the role of viruses in virus-host interactions and coevolution by monitoring virome dynamics along a millennium-long land reclamation chronosequence.</div></div><div><h3>Methods</h3><div>We collected 24 soil samples from 8 stages of a millennium-long land reclamation chronosequence, including non-reclamation, and reclamation periods of 10, 50, 100, 300, 500, 700, and 1000 years. We characterized their metagenomes, and identified DNA viruses within these metagenomes.</div></div><div><h3>Results</h3><div>Our findings reveal a significant shift in viral community composition after 50 years of land reclamation, but soil viral diversity reached a stable phase approximately 300 years after the initial reclamation. Analysis of the virus-host network showed a scale-free degree distribution and a reduction in complexity over time, with generalist viruses emerging as key facilitators of horizontal gene transfer.</div></div><div><h3>Conclusion</h3><div>These findings highlight the integral role of viruses, especially generalist types, in mediating gene exchanges between viruses and hosts, thereby influencing the coevolutionary dynamics in soil ecosystems over significant timescales. This study offers novel insights into long-term virus-host interactions, showing how the virome responds to environmental changes, driving shifts in various microbial functions in reclaimed land.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 297-306"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499951","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
Biosynthesis and functions of triterpenoids in cereals 谷物中三萜类化合物的生物合成和功能。
IF 11.4 1区 综合性期刊
Journal of Advanced Research Pub Date : 2025-05-01 DOI: 10.1016/j.jare.2024.05.021
Jiaojiao Lu , Shan Yan , Zheyong Xue
{"title":"Biosynthesis and functions of triterpenoids in cereals","authors":"Jiaojiao Lu ,&nbsp;Shan Yan ,&nbsp;Zheyong Xue","doi":"10.1016/j.jare.2024.05.021","DOIUrl":"10.1016/j.jare.2024.05.021","url":null,"abstract":"<div><h3>Background</h3><div>Triterpenoids are versatile secondary metabolites with a diverse array of physiological activities, possessing valuable pharmacological effects and influencing the growth and development of plants. As more triterpenoids in cereals are unearthed and characterized, their biological roles in plant growth and development are gaining recognition.</div></div><div><h3>Aim of the review</h3><div>This review provides an overview of the structures, biosynthetic pathways, and diverse biological functions of triterpenoids identified in cereals. Our goal is to establish a basis for further exploration of triterpenoids with novel structures and functional activities in cereals, and to facilitate the potential application of triterpenoids in grain breeding, thus accelerating the development of superior grain varieties.</div></div><div><h3>Key scientific concepts of the review</h3><div>This review consolidates information on various triterpenoid skeletons and derivatives found in cereals, and summarizes the pivotal enzyme genes involved, including oxidosqualene cyclase (OSC) and other triterpenoid modifying enzymes like cytochrome P450, glycosyltransferase, and acyltransferase. Triterpenoid-modifying enzymes exhibit specificity towards catalytic sites within triterpenoid skeletons, generating a diverse array of functional triterpenoid derivatives. Furthermore, triterpenoids have been shown to significantly impact the nutritional value, yield, disease resistance, and stress response of cereals.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 ","pages":"Pages 155-171"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094679","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
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