Journal of Advanced Research最新文献

{"title":"ORP5 promotes cardiac hypertrophy by regulating the activation of mTORC1 on lysosome","authors":"Di Zhao ,&nbsp;Ran Xu ,&nbsp;Yufei Zhou ,&nbsp;Jiaying Wu ,&nbsp;Xiaoxue Zhang ,&nbsp;Hong Lin ,&nbsp;Jienan Wang ,&nbsp;Zhiwen Ding ,&nbsp;Yunzeng Zou","doi":"10.1016/j.jare.2024.12.014","DOIUrl":"10.1016/j.jare.2024.12.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Oxysterol binding protein (OSBP)-related protein 5 (ORP5) mainly functions as a lipid transfer protein at membrane contact sites (MCS). ORP5 facilitates cell proliferation through the activation of mTORC1 signaling. While the pro-hypertrophic effects of mTORC1 are well-documented, the specific role of ORP5 in the context of pathological cardiac hypertrophy remains inadequately understood.</div></div><div><h3>Methods</h3><div>To investigate the role of ORP5 in pathological cardiac hypertrophy, AAV9-treated mice and neonatal rat ventricular myocytes (NRVMs) were utilized. Cardiac function, morphology, and mTORC1 signaling alterations induced by pro-hypertrophic stimuli were assessed in both myocardium and NRVMs. Additionally, a range of molecular techniques were employed to elucidate the regulatory mechanisms of ORP5 on mTORC1 in hypertrophied hearts.</div></div><div><h3>Results</h3><div>Increased expression of ORP5 was observed in the hearts of patients with hypertrophic cardiomyopathy (HCM), in mice subjected to transverse aortic constriction (TAC), and in NRVMs treated with angiotensin II (AngII). We found that ORP5 binds to mTOR in cardiomyocytes. Upon exposure to TAC surgery, ORP5-deficient hearts exhibited enhanced cardiac function, reduced cardiomyocyte hypertrophy, and diminished collagen deposition than wild type. Conversely, overexpression of ORP5 significantly aggravated hypertrophic responses in both hearts and NRVMs. Notably, the promotion of cardiac hypertrophy induced by ORP5 overexpression was reversed by rapamycin, an inhibitor of mTORC1. Mechanistically, our study elucidated that the ORD domain of ORP5 interacts with mTORC1, facilitating its translocation to the outer membrane of the lysosome for subsequent activation. This activation triggers the downstream signaling pathways involving S6K1 and 4E-BP1, which initiate protein synthesis, thereby promoting pathological cardiac hypertrophy.</div></div><div><h3>Conclusions</h3><div>Our findings provide the inaugural evidence that ORP5 facilitates pathological ventricular hypertrophy through the translocation of mTORC1 to the lysosome for subsequent activation. Consequently, ORP5 has the potential to serve as a diagnostic biomarker or therapeutic target for pathological cardiac hypertrophy in the future.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 529-541"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797724","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":"Odontogenic exosomes simulating the developmental microenvironment promote complete regeneration of pulp-dentin complex in vivo","authors":"Yifan Wang ,&nbsp;Jing Mao ,&nbsp;Yujie Wang ,&nbsp;Rui Wang ,&nbsp;Nan Jiang ,&nbsp;Xiaohan Hu ,&nbsp;Xin Shi","doi":"10.1016/j.jare.2024.12.048","DOIUrl":"10.1016/j.jare.2024.12.048","url":null,"abstract":"<div><h3>Introduction</h3><div>Establishing an optimized regenerative microenvironment for pulp-dentin complex engineering has become increasingly critical. Recently, exosomes have emerged as favorable biomimetic nanotherapeutic tools to simulate the developmental microenvironment and facilitate tissue regeneration.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate the multifaceted roles of exosomes from human dental pulp stem cells (DPSCs) that initiated odontogenic differentiation while sustaining mesenchymal stem cell (MSC) characteristics in odontogenesis, angiogenesis, and neurogenesis during pulp-dentin complex regeneration.</div></div><div><h3>Methods</h3><div>Differential centrifugation was performed to isolate exosomes from normal DPSCs (DPSC-Exos) and DPSCs that initially triggered odontogenic differentiation (DPSC-Od-Exos). The impact of these exosomes on the biological behavior of DPSCs and human umbilical vein endothelial cells (HUVECs) was examined in vitro through CCK-8 assay and Transwell migration assay, as well as assays dedicated to assessing odontogenic, angiogenic, and neurogenic capabilities. In vivo, Matrigel plugs and human tooth root fragments incorporating either DPSC-Exos or DPSC-Od-Exos were subcutaneously transplanted into mouse models. Subsequent histological, immunohistochemical, and immunofluorescent analyses were conducted to determine the regenerative outcomes.</div></div><div><h3>Results</h3><div>DPSC-Exos and DPSC-Od-Exos revealed no remarkable difference in their characteristics. In vitro analyses indicated that DPSC-Od-Exos significantly facilitated the proliferation, migration, and multilineage differentiation of DPSCs compared with DPSC-Exos. Furthermore, DPSC-Od-Exos elicited a more pronounced effect on the tubular structure formation of HUVECs. Consistently, Matrigel plug assays confirmed that DPSC-Od-Exos exhibited superior performance in promoting endothelial differentiation of DPSCs and stimulating angiogenesis in HUVECs. Notably, DPSC-Od-Exos contributed to complete pulp-dentin complex regeneration in human tooth root fragments, characterized by enriched neurovascular structures and a continuous layer of odontoblast-like cells, which extended cytoplasmic projections into the newly formed dentinal tubules.</div></div><div><h3>Conclusion</h3><div>By simulating the developmental microenvironment, multifunctional DPSC-Od-Exos demonstrated promising potential for reconstructing dentin-like tissue, vascular networks, and neural architectures, thereby enhancing our understanding of the therapeutic implications of DPSC-Od-Exos in regenerative endodontic treatment.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 405-421"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5-Aminolevulinic acid improves strawberry salt tolerance through a NO–H2O2 signaling circuit regulated by FaWRKY70 and FaWRKY40","authors":"Hao Yang,&nbsp;Jianting Zhang,&nbsp;Yan Zhong,&nbsp;Liangju Wang","doi":"10.1016/j.jare.2024.12.031","DOIUrl":"10.1016/j.jare.2024.12.031","url":null,"abstract":"<div><h3>Introduction</h3><div>5-Aminolevulinic acid (ALA) is an essential biosynthetic precursor of tetrapyrrole compounds, naturally occurring in all living organisms. It has also been suggested as a new plant growth regulator. Treatment with ALA promotes strawberry Na⁺ homeostasis under salt stress. Regulation of this process requires the signaling molecules nitric oxide (NO) and hydrogen peroxide (H₂O₂), but the specific signaling cascade and transcriptional regulatory mechanism have not previously been characterized.</div></div><div><h3>Objectives</h3><div>Our work focused on the dissection of the NO and H₂O₂ signaling cascade and transcriptional regulatory mechanism by which FaWRKY70-FaWRKY40 participated in ALA-improved Na⁺ homeostasis and salt tolerance of strawberry.</div></div><div><h3>Methods</h3><div>It was preliminarily confirmed by transcriptome and RT-qPCR that <em>FaWRKY40</em> and <em>FaWRKY70</em> participated in ALA-induced salt tolerance of strawberry. Two WRKY transcription factors overexpressed in woodland strawberry as well as tobacco were used to identify the gene functions in salt tolerance. Yeast one-hybrid (Y1H), β-glucuronidase (GUS), dual luciferase reporter (DLR) and electrophoretic mobility shift assays (EMSA) were used to verify the interaction with the target gene.</div></div><div><h3>Results</h3><div>ALA induced NO and H₂O₂ production, which formed a signaling circuit reciprocally regulated by <em>FaNR1</em> and <em>FaRbohD</em> expression to coordinate Na⁺ homeostasis. FaWRKY40 was shown to act as a positive transcription factor in this pathway: <em>FaWRKY40</em> overexpression improved salt tolerance in woodland strawberry and tobacco, whereas <em>FaWRKY40</em> RNA interference increased plant salt injury. FaWRKY40 bound to the promoters of <em>FaRbohD</em>, <em>FaNHX1</em>, and <em>FaSOS1</em> to promote root H₂O₂ generation and Na⁺ reallocation. Conversely, FaWRKY70, a negative WRKY transcription factor, was found to increase salt sensitivity by inhibiting expression of <em>FvWRKY40</em>, <em>FvNR1</em>, and <em>FvHKT1</em>. ALA inhibited <em>FaWRKY70</em> but increased <em>FaWRKY40</em> expression, coordinating the regulation of NO-H₂O₂ signaling and Na⁺ homeostasis when strawberry was stress by salinity.</div></div><div><h3>Conclusion</h3><div>ALA inhibits NaCl-stimulated <em>FaWRYK70</em> expression, relieving the transcriptional inhibition of its downstream targets. The NO–H₂O₂ signaling circuit can then initiate mechanisms such as Na⁺ exclusion, vacuolar sequestration, and removal of Na⁺ from the xylem sap, limiting Na⁺ accumulation in the leaves and promoting Na⁺ homeostasis and plant salt tolerance.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 91-107"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901929","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":"LTX-315 is a novel broad-spectrum antimicrobial peptide against clinical multidrug-resistant bacteria","authors":"Yang Tang ,&nbsp;Chen Yang ,&nbsp;Jiamin Zhao ,&nbsp;Heng Heng ,&nbsp;Mingxiu Peng ,&nbsp;Liang Sun ,&nbsp;Liang Dai ,&nbsp;Edward Wai-Chi Chan ,&nbsp;Sheng Chen","doi":"10.1016/j.jare.2024.12.044","DOIUrl":"10.1016/j.jare.2024.12.044","url":null,"abstract":"<div><h3>Introduction</h3><div>Infections stemming from multidrug-resistant bacteria present a substantial threat to public health today. Discovering or synthesizing novel compounds is crucial to alleviate this pressing situation.</div></div><div><h3>Objective</h3><div>The main purpose of this study is to verify the antibacterial activity of LTX-315 and explore its primary action mode.</div></div><div><h3>Methods</h3><div>Through antibacterial phenotype assay screening, we obtained a potent compound named LTX-315 from diverse drug libraries, 10,926 compounds in total. Then, the bactericidal effect and its action mode were explored through biochemical and chemistry methods such as a<!--> <!-->time-killing curve, scanning electronic microscopy, isothermal titration calorimetry analysis, and nuclear magnetic resonance. Finally, the efficacy in vivo of LTX-315 against drug-resistant bacteria was proved through a<!--> <!-->mice infection model.</div></div><div><h3>Results</h3><div>In this study, LTX-315, an oncolytic peptide, was discovered to effectively eliminate gram-positive and gram-negative pathogens, even for those multidrug-resistant strains. Through strong electrostatic interactions, LTX-315 can bind to the membrane component phosphatidylglycerol (PG) with extremely high affinity (nanomolar level). Strikingly, in contrast to the typical electrostatic interactions of antibacterial peptides, the indole group of LTX-315, situated near the alkyl chain, exhibits significantly enhanced recognition and interaction with PG due to the hydrophobic effect of the alkyl chain. Furthermore, it exerts various impacts on cell membranes, including damaging integrity, increasing permeability, and decreasing membrane fluidity. Additionally, microscopy revealed significant cell disintegration. The influence, in turn, disrupts several physiological activities inside cells, such as increasing the reactive oxygen species level, ultimately leading to cell death. Finally, the efficacy of LTX-315 in vivo against multidrug-resistant and hypervirulent <em>Klebsiella pneumoniae</em> was demonstrated.</div></div><div><h3>Conclusion</h3><div>The unique mechanism of LTX-315 involves high-affinity binding to PG and subsequent membrane disruption, providing a novel approach against multidrug-resistant bacteria compared to conventional antibiotics. As a potential candidate, it shows promise in effectively treating bacterial infections, particularly those caused by drug-resistant bacteria, thereby addressing the escalating challenge of antibiotic resistance worldwide.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 715-729"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937553","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":"Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus","authors":"Shiqiang Yan ,&nbsp;Yan Lu ,&nbsp;Changming An ,&nbsp;Wanglai Hu ,&nbsp;Yaofeng Chen ,&nbsp;Ziwen Li ,&nbsp;Wenbo Wei ,&nbsp;Zongzheng Chen ,&nbsp;Xianhai Zeng ,&nbsp;Wei Xu ,&nbsp;Zhenghua Lv ,&nbsp;Fan Pan ,&nbsp;Wei Gao ,&nbsp;Yongyan Wu","doi":"10.1016/j.jare.2024.12.024","DOIUrl":"10.1016/j.jare.2024.12.024","url":null,"abstract":"<div><h3>Background</h3><div>Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions.</div></div><div><h3>Aim of Review</h3><div>Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 615-637"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841483","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":"Selective Regulation of ray tissue for achieving ultrastable Zero-Poisson’s-ratio material out of wood","authors":"Xia Yu ,&nbsp;Bo Liu ,&nbsp;Xinyi Zhou ,&nbsp;Tong Wu ,&nbsp;Bohua Ren ,&nbsp;Tao Fang ,&nbsp;Chaonan Cong ,&nbsp;Guofang Wu ,&nbsp;Lihong Yao ,&nbsp;Xiaoding Wei ,&nbsp;Yun Lu","doi":"10.1016/j.jare.2024.12.012","DOIUrl":"10.1016/j.jare.2024.12.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Materials exhibiting a Poisson’s ratio of zero have attracted considerable interest due to their unique properties and potential applications in various fields, including aerospace, athletic footwear, and sporting equipment. However, the high costs associated with their structural fabrication and the dependence on synthetic chemical materials for most zero Poisson’s ratio materials complicate the preparation processes of current elastic materials, resulting in negative environmental impacts.</div></div><div><h3>Objectives</h3><div>This study presents a sustainable treatment strategy that utilizes the inherent cellular structure of wood to achieve a zero Poisson’s ratio, thereby enhancing its elasticity.</div></div><div><h3>Methods</h3><div>By strategically selecting tree species with varying tissue compositions and employing simple chemical and heat treatments, we developed a commercially viable elastic wood material with a zero Poisson’s ratio that meets diverse stress rebound requirements.</div></div><div><h3>Results</h3><div>The unique internal structure of the wood not only provides high fatigue resistance—capable of withstanding 5000 cycles of compression at a strain of 40 %—but also ensures excellent resilience and processability. At a deformation level of 60 %, the elastic modulus reaches 90.9 MPa. Additionally, the material retains its elasticity even at extremely low temperatures of −196 °C and demonstrates the ability to endure elevated temperatures following carbonization at 1200 °C.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that wood-based materials with a zero Poisson’s ratio exhibit remarkable stability after cyclic compression, presenting a viable pathway for developing superelastic materials suitable for both high- and low-temperature applications.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 439-448"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823398","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":"KBTBD8/RRP15 as a potential novel therapeutic target associates with lenvatinib-inhibited progression in hepatocellular carcinoma both in vitro and in vivo","authors":"Saili Zhao ,&nbsp;Xuran Wang ,&nbsp;Rui Wu ,&nbsp;Fenglan Wang ,&nbsp;Xiaoxuan Tang ,&nbsp;Junhui Chen ,&nbsp;Runqiu Jiang ,&nbsp;Wei Kang ,&nbsp;Guifang Xu ,&nbsp;Lei Wang ,&nbsp;Zhangding Wang ,&nbsp;Xiaoping Zou ,&nbsp;Bin Zhang","doi":"10.1016/j.jare.2024.12.017","DOIUrl":"10.1016/j.jare.2024.12.017","url":null,"abstract":"<div><h3>Introduction</h3><div>We have previously demonstrated that RRP15 (Ribosomal RNA Processing 15 Homolog) was significantly elevated in hepatocellular carcinoma (HCC) and correlated directly with poor prognosis. RRP15 suppression curtails HCC progression through induction of cellular senescence and apoptosis. However, the impact of RRP15 on the precise therapeutic potential of lenvatinib has remained underexplored.</div></div><div><h3>Objective</h3><div>To investigate the relationship between RRP15 expression and sensitivity of lenvatinib in HCC treatment, and also explore the potential of targeting RRP15 by lenvatinib to inhibit HCC progression.</div></div><div><h3>Methods</h3><div>RRP15 and KBTBD8 (Kelch Repeat and BTB Domain Containing 8) expression was examined using western blot and immunohistochemistry. Cell viability, proliferation, migration and invasion as well as apoptosis were assessed using CCK-8, clonogenic assays, transwell, TUNEL (Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling) and Annexin V staining assays. The interaction between RRP15 and KBTBD8 was identified through pull-down and mass spectrometry analysis and further validated by immunofluorescence and co-immunoprecipitation assays. RRP15 ubiquitination and degradation were assessed using cycloheximide treatment, plasmid transfection and co-immunoprecipitation, followed by western blot analysis. Tail vein injection lung metastasis model was performed to determine tumor metastasis <em>in vivo</em>.</div></div><div><h3>Results</h3><div>We reveled a correlation between RRP15 downregulation and enhanced sensitivity to lenvatinib, presenting marked suppression of metastasis and invasiveness. Proteomic analyses and subsequent validation disclosed the pivotal role of the E3 ubiquitin ligase KBTBD8 in mediating the ubiquitination and subsequent degradation of RRP15 protein post-lenvatinib treatment in HCC cells. KBTBD8 inhibition stalled RRP15 ubiquitination and degradation, while its overexpression accelerated these processes. Moreover, RRP15 overexpression fosters HCC cell proliferation and metastasis, a pathological effect mitigated by KBTBD8 overexpression. <em>In vivo</em> experiments further validate the role of lenvatinib in promoting RRP15 degradation via KBTBD8 upregulation.</div></div><div><h3>Conclusions</h3><div>Our study elucidated a previously unidentified mechanism of lenvatinib action and identified the RRP15-KBTBD8 axis as a novel therapeutic target in HCC, offering new avenues for treatment strategies in combating HCC.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 569-583"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809723","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":"Maternal fish oil supplementation enhances nutrient transport in the placenta and milk biosynthesis in the mammary gland via the GPR120 signaling pathway","authors":"Qihui Li ,&nbsp;Qianzi Zhang ,&nbsp;Senlin Su ,&nbsp;Siwang Yang ,&nbsp;Jiayuan Shao ,&nbsp;Wutai Guan ,&nbsp;Shihai Zhang","doi":"10.1016/j.jare.2024.12.029","DOIUrl":"10.1016/j.jare.2024.12.029","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal fish oil (FO) supplementation during pregnancy has been shown to improve pregnancy outcomes. FO is recognized as dietary source for n-3 polyunsaturated fatty acids (n-3 PUFAs). While early research has focused on the benefits of n-3 PUFAs for fetal neurodevelopment, retinal maturation and neonatal behavior, their roles in the placenta during late pregnancy and in the mammary gland during lactation still remain unknow.</div></div><div><h3>Objectives</h3><div>Here, we aim to clarify the mechanisms by which maternal supplementation with FO during pregnancy and lactation affects placental and mammary gland function.</div></div><div><h3>Methods</h3><div>We evaluated the effects of FO on maternal placental nutrient transport, mammary gland milk synthesis and offspring growth. We then explored the molecular mechanisms by which docosahexaenoic acid (DHA) affects the biological function of placental trophoblast cells and mammary epithelial cells through <em>in vitro</em> experiments. Finally, a lipopolysaccharide-challenged experiment was performed to access the potential of maternal FO supplementation in alleviating offspring intestinal inflammation.</div></div><div><h3>Results</h3><div>Maternal supplementation with FO during late pregnancy increased offspring birth weight, associated with enhanced maternal placental vascularization and nutrient transporter abundance. Additionally, maternal FO supplementation during lactation improved milk biosynthesis, increasing the fat, protein, and non-fat solids content in both colostrum and mature milk, thereby promoting offspring growth. The stimulatory effects of DHA on nutrient transportation in placental trophoblast cells and nutrient secretion in mammary gland epithelial cells were mediated by GPR120 signaling pathways. Furthermore, maternal FO supplementation strengthened the placental barrier, reduced placental inflammation, oxidative stress and alleviated lipopolysaccharide-induced intestinal inflammation in offspring.</div></div><div><h3>Conclusion</h3><div>Maternal FO supplementation during late pregnancy and lactation enhances offspring growth by increasing placental nutrient transport and milk biosynthesis, mediated by GPR120. Additionally, maternal FO supplementation reduces the susceptibility of offspring to intestinal inflammation.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 73-89"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849349","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 ,&nbsp;Lirong Tian ,&nbsp;Yuru Ma ,&nbsp;Jiahui Xu,&nbsp;Tianyu Bai,&nbsp;Qian Wang,&nbsp;Xigang Liu,&nbsp;Lin Guo","doi":"10.1016/j.jare.2024.12.011","DOIUrl":"10.1016/j.jare.2024.12.011","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim of Review</h3><div>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 are also discussed.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>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.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 173-190"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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":"Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1/PD-L1 signalling","authors":"Guiqin Ye ,&nbsp;Xin Sun ,&nbsp;Jiuzhou Li ,&nbsp;Maomao Pu ,&nbsp;Jianbin Zhang","doi":"10.1016/j.jare.2024.12.045","DOIUrl":"10.1016/j.jare.2024.12.045","url":null,"abstract":"<div><h3>Introduction</h3><div>Parkin-mediated mitophagy is essential for clearing damaged mitochondria, and it inhibits tumour development. The role of mitophagy in modulating tumour immunity is becoming clearer, but the underlying mechanism is still poorly understood.</div></div><div><h3>Objective</h3><div>This study was designed to examine the role of Parkin in the immune microenvironment of liver tumours induced by carbon tetrachloride (CCl₄).</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing analysis, Western blot, immunofluorescence and co-immunoprecipitation were used to verify the mechanism of Parkin affecting the tumour microenvironment by altering the expression of PD-1.</div></div><div><h3>Results</h3><div>Our data revealed that <em>Park2^-/-</em> mice showed severe liver damage and increased malignancy. Single-cell RNA sequencing analysis of T lymphocytes in liver tumours showed that the number of cytotoxic CD8⁺ T cells (Gzmb/Ifng/Fasl) was significantly decreased and the number of exhausted CD8⁺ T cells (Pdcd1/Lag3/Tigit/Havcr2/Ctla4) was significantly increased in <em>Park2^-/-</em> mice, indicating the immune suppressive microenvironment. Single-cell RNA sequencing analysis of myeloid-derived cells also displayed the increase of M2-like macrophages in <em>Park2^-/-</em> mice. Through quantitative proteomic analysis, it was found that the differential protein expression between the two groups mainly localized in the plasma membrane and extracellular, including PD-1, MHC-Ⅰ molecules etc., and was mainly associated with PD-1 and antigen presentation pathways. It could impair the antitumour immune response with Parkin deficiency. Parkin deficiency leads to the decrease of hepatic mitophagy levels and the formation of an immune suppressive microenvironment, which promotes the tumourigenesis of liver cancer.</div></div><div><h3>Conclusion</h3><div>As an E3 ubiquitin ligase, Parkin induces the ubiquitination and degradation of PD-1 in liver cancer and could influence antitumour immunity through the PD-1/PD-L1 signalling pathway. Thus, remodeling the tumour microenvironment through the reintroduction of Parkin or enhancement of mitophagy could activate the anti-tumour immune response and improve the immunotherapy efficacy, which may be a promising strategy for the treatment of HCC.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 731-744"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912032","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}