Journal of Advanced Research最新文献

{"title":"Spatiotemporal translation of sperm acrosome associated proteins during early capacitation modulates sperm fertilizing ability","authors":"Yoo-Jin Park, Won-Ki Pang, Do-Yeal Ryu, Md Saidur Rahman, Myung-Geol Pang","doi":"10.1016/j.jare.2025.03.035","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.035","url":null,"abstract":"<h3>Introduction</h3>Despite the lack of essential cytoplasmic organelles in mature spermatozoa, which creates unfavorable conditions for transcription and translation, the presence of various mRNA and proteins during capacitation suggests potential for de novo protein synthesis.<h3>Objectives</h3>We applied a metabolic labeling method using a fluorescent noncanonical amino acid tagging system (FUNCAT) and proximity ligation method (PLA) in normal and reduced fertility spermatozoa to detect different translation phenomena during sperm capacitation according to their fertility.<h3>Methods</h3>We explored different proteome changes in spermatozoa according to the time-sequential capacitation process (0, 20, 40, 60, and 120 min) between normal [average fertility rate (FR) = 77.44 % ± 1.51] and reduced fertility (average FR = 58.57 % ± 1.64) spermatozoa bull spermatozoa, as the representative male fertility models owing to their broad spectrum of fertility phenotypes. Moreover, the FUNCAT/PLA method was used to detect and visualize different translation phenomena during sperm capacitation according to fertility.<h3>Results</h3>We found that sperm-associated protein (SPACA) 1 and SPACA5 were newly synthesized in the head of normal-fertility spermatozoa, whereas a lack of newly synthesized proteins in the head and a relatively earlier loss of SPACA1 and SPACA5 were observed in the reduced-fertility spermatozoa. Moreover, the mitochondrial translation inhibitor, chloramphenicol, partially inhibited sperm translation and delayed translocation, suggesting that mitochondria participate in sperm translation.<h3>Conclusion</h3>Our results unveil time-sequential microenvironmental changes in sperm proteomes during capacitation, which lead to the orchestra of proteins that complete fertilization. Fertile spermatozoa are selected through inter-competition during the journey of fertilization in the female reproductive tract. This study provides an overview of how translation dynamics acts on the sperm selection and influence the evolution of sperm fertility.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"22 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653854","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":"Minichromosome maintenance 4 plays a key role in protecting against acute kidney injury by regulating tubular epithelial cells survival and regeneration","authors":"Jing Huang, Feng Liu, Zhi-Feng Xu, Hui-Ling Xiang, Qian Yuan, Chun Zhang","doi":"10.1016/j.jare.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.032","url":null,"abstract":"<h3>Introduction</h3>Minichromosome maintenance 4 (MCM4), a constituent of the MCM family, playing a pivotal role in DNA replication. Although MCM4 expression has been widely linked to various malignant tumors, its role in kidney diseases is not well-studied. This study primarily investigates the role and underlying mechanism of MCM4 in acute kidney injury (AKI).<h3>Objectives</h3>Characterizing a novel target of MCM4 in patients with AKI.<h3>Methods</h3>We used CRISPR/Cas9 gene editing to delete MCM4 gene in tubular cells from C57BL/6J mice. Adeno-associated virus 9 harboring MCM4 was administered via intraparenchymal injection into the kidney to enhance MCM4 expression <em>in vivo</em>. These mice were used to established cisplatin- and ischemic reperfusion injury (IRI)-induced AKI mouse models, for detecting the functional role of MCM4 in the pathological process of AKI.<h3>Results</h3>MCM4 level was increased in the tubules of cisplatin- and IRI-induced AKI mouse models. Compare to wide-type mice, MCM4 knockout mice demonstrated greater degree of histological damage and a higher ratio of apoptotic tubular cells, as well as kidney dysfunction upon cisplatin- and IRI-induced AKI models. Conversely, MCM4 overexpression ameliorated the severity of kidney injury and promoted regenerative capacity of tubular cells during AKI development. Mechanically, loss of MCM4 induced the expression of p53-binding protein 1, activating the p53/p21 pathway and exacerbating AKI progression. Additional, MAD2B, as an upstream molecule of MCM4, regulates the transcription level of MCM4 by affecting the level of E2F1.<h3>Conclusions</h3>These findings demonstrate that MCM4 upregulation during AKI development is an adaptive response that preserves tubular cell regenerative capacity and limits the severity of renal injury, thus highlighting the potential value of MCM4 as a biomarker or therapeutic target in patients with AKI.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"36 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640874","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":"Adaptive bilirubin nanoscavenger alleviates pulmonary oxidative stress and inflammation for acute lung injury therapy","authors":"Longfa Kou, Yitianhe Xu, Shize Li, Zhinan He, Di Huang, Zhanzheng Ye, Yixuan Zhu, Yunzhi Wang, Xinyu Di, Yuqi Yan, Yinhao Lin, Wanling Zhu, Xianbao Shi, Hailin Zhang, Ruijie Chen","doi":"10.1016/j.jare.2025.03.027","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.027","url":null,"abstract":"<h3>Introduction</h3>Acute lung injury (ALI) is a life-threatening condition characterized by rapidly progressing respiratory distress and hypoxemia. Oxidative stress-induced inflammation in lung tissue plays a crucial role in the progression of ALI. Excessive generation of reactive oxygen species (ROS) in the pulmonary microenvironment activates inflammatory signaling pathways, enhancing the transcription of pro-inflammatory factors and ultimately leading to tissue necrosis.<h3>Objectives</h3>Bilirubin (BR), an exceptional endogenous antioxidant, possesses the ability to counteract elevated levels of reactive oxygen species (ROS) through direct reactions or by inducing antioxidant systems such as Nrf2/HO-1 signaling. However, its limited solubility poses a hindrance to further applications. Hence, it is imperative to develop a suitable bilirubin-based system for biological utilization.<h3>Methods</h3>In this study, we developed a bilirubin-based ROS-sensitive adaptive nanoscavenger (GP@BR) by co-assembling bilirubin-conjugated glycol chitosan (GC-BR) and bilirubin-conjugated polyethylene glycol (PEG-BR), aiming to alleviate oxidative stress for ALI treatment.<h3>Results</h3>The different conjugations endowed the bilirubin derivatives with varying sensitivity towards reacting with ROS, enabling GP@BR to exert antioxidative properties specifically in oxidative environments on demand. Besides its excellent antioxidant properties, GP@BR also demonstrated the ability to absorb excess inflammatory cytokines. Moreover, our optimized nanoscavenger facilitated bilirubin transport across the mucosal layer on pulmonary epithelial cells. In vivo studies confirmed that GP@BR significantly improved ALI symptoms and suppressed pulmonary fibrosis.<h3>Conclusion</h3>This study highlighted the potential of ROS-sensitive adaptive properties and multiple actions of this nanoscavenger in the treatment of ALI.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"43 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640627","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":"Mitochondrial fatty acid oxidation as the target for blocking therapy-resistance and inhibiting tumor recurrence: The proof-of-principle model demonstrated for ovarian cancer cells","authors":"Hui Lin, Lingfang Wang, Hanwen Chen, Yuqing Shen, Conghui Wang, Yite Xue, Zhi Zheng, Yanan Zhang, Dajing Xia, Yihua Wu, Fenfen Wang, Xiao Li, Xiaodong Cheng, Hui Wang, Junfen Xu, Weiguo Lu","doi":"10.1016/j.jare.2025.03.026","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.026","url":null,"abstract":"<h3>Introduction</h3>Cancer patients treated with current chemotherapeutic and targeted therapies frequently achieve partial remission, which ultimately relapse with more aggressive, drug-resistant tumor phenotypes. To a certain extent, drug-tolerant persister (DTP) cells are responsible for residual tumors after systemic anticancer therapy and the onset of acquired drug resistance. Therefore, novel therapies targeting DTP cells to prevent drug resistance and tumor recurrence are urgently needed.<h3>Objectives</h3>We aimed to investigate the traits and key vulnerabilities of drug-tolerant ovarian cancer persister cells and to seek out potential therapeutic strategies.<h3>Methods</h3>We constructed paclitaxel-tolerant ovarian cancer persister cells by exposing ovarian cancer parental cells to a lethal dose of paclitaxel. Proteomics analysis, <em>in vitro</em> and <em>in vivo</em> assays were performed to identify biological processes that could serve as potential vulnerabilities in persister cells.<h3>Results</h3>Paclitaxel-tolerant ovarian cancer persister cells were found to undergo a metabolic reprogramming through the upregulation of fatty acid oxidation (FAO). Treatment with the FAO inhibitor ST1326 suppressed FAO and increased sensitivity to paclitaxel in persister cells. Moreover, combination therapy with paclitaxel and ST1326 prevented ovarian tumor recurrence with satisfactory biosafety in a mouse model of ovarian cancer relapse, indicating that FAO disruption can improve the efficacy of paclitaxel-based therapy in ovarian cancer. Mechanistically, we found that paclitaxel treatment upregulated CEBPB, a transcription factor that induced the expression of the FAO-related enzyme HADHA and contributed to FAO elevation in persister cells.<h3>Conclusions</h3>This study revealed an upregulation of FAO in paclitaxel-tolerant ovarian cancer persister cells and provided a prospective paclitaxel-ST1326 combination therapy targeting persister cells that may prevent the development of acquired drug resistance and achieve superior long-term ovarian cancer control in the future. Our research established a conceptual framework for advancing personalized treatment approaches and enhancing patient outcomes in ovarian cancer therapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"183 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640875","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":"Mitigating life-cycle multiple environmental burdens while increasing ecosystem economic benefit and crop productivity with regional universal nitrogen strategy","authors":"Zhi Yao, Xingbang Wang, Wei Zhang, Dunyi Liu, Wushuai Zhang, Xiaopeng Gao, Xinping Chen","doi":"10.1016/j.jare.2025.03.030","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.030","url":null,"abstract":"<h3>Introduction</h3>Nitrogen fertiliser is critical for increasing crop yields worldwide, but excessive use causes significant N losses in various forms and subsequent environmental issues, such as greenhouse gas (GHG) emissions. Establishing regional universal nitrogen strategy (RUNs) is indispensable for technology adoption, resource conservation, and pollution mitigation in crop production.<h3>Objectives</h3>This study aims to develop a regional universal nitrogen fertilizer strategy to address variations in N application effectiveness, balancing agricultural productivity with environmental and eco-economic benefits.<h3>Methods</h3>We conducted a total of 48 site-year field experiments including no nitrogen application (Control), farmers’ practice (FP), and the implementation of the RUNs with optimized nitrogen recommended formulas and one-off application method.<h3>Results</h3>The RUNs significantly increased yields by 5.9%, 12%, and 11% for grain, sweet, and silage maize, respectively, compared with FP. Further, RUNs reduced life-cycle potentials of global warming, soil acidification, water eutrophication, and energy depletion by 22–45%, 63–76%, 51–73%, and 46–67%, respectively. The RUNs increased economic benefits by 11%–58.2%, and net ecosystem-economic benefits by 11.3–77.5%, particularly through the reduction of nitrogen fertiliser and labour-associated agricultural and ecological costs.<h3>Conclusion</h3>We propose that the RUNs reconciled crop yield, resource efficiency, environmental impacts, and ecosystem economic benefits, demonstrating a regional sustainable N strategy for global food security and resource conservation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"61 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640876","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":"MG53 protects against septic cardiac dysfunction by ubiquitinating ATF2","authors":"Miao Tian, Yu Shi, Xue Gong, Wenjie Tan, Xinyi Guo, Yinghong Chen, Peili Yang, Hongmei Ren, Qi Cai, Jianjie Ma, Chunyu Zeng, Gengze Wu","doi":"10.1016/j.jare.2025.03.031","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.031","url":null,"abstract":"<h3>Introduction</h3>Septic cardiac dysfunction (SCD) is the most common complication of sepsis, which has become the primary cause of death in intensive care units. The muscle-specific protein mitsugumin-53 (MG53) has been identified to protect cell integrity as a “Molecular Band-Aid”.<h3>Objectives</h3>The recombinant human MG53 (rhMG53) pretreatment has been reported to prevent cardiac function damage caused by cecal ligation and puncture (CLP). However, whether or not MG53 protects against SCD remains to be further clarified.<h3>Methods</h3>C57BL/6J mice were intraperitoneally injected with lipopolysaccharide (LPS) to generate the SCD model. MG53 was overexpressed by intravenously injected adeno-associated virus, and the rhMG53 was administrated intraperitoneally. The cardiac function was evaluated by echocardiography, and the cardiac inflammation was assessed through ELISA and Western blot. The mechanisms of MG53 were studied by quantitative real-time PCR (qPCR) and co-immunoprecipitation (co-IP).<h3>Results</h3>Our present study found that MG53 expression was lower in hearts from SCD mice than controls. Overexpression or exogenous MG53 treatment alleviated cardiac dysfunction, improved survival rate in SCD mice, accompanied with improved pathological changes, reduced cardiomyocyte apoptosis, and lowered inflammatory factor levels in serum or hearts. Mechanistically, MG53 inhibited TLR4 transcriptional activity by ubiquitinating ATF2, an essential transcriptional factor for TLR4, which ultimately reduced the expression of TLR4.<h3>Conclusion</h3>MG53 protect the cardiac function against sepsis by down-regulation of TLR4 expression, via ubiquitination of ATF2, a TLR4 transcriptional factor, which might be a promising therapeutic approach for septic cardiac dysfunction.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"49 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640623","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":"Insights into dill (Anethum graveolens) flavor formation via integrative analysis of chromosomal-scale genome, metabolome and transcriptome","authors":"Ya-Hui Wang, Pei-Zhuo Liu, Rong-Rong Zhang, Yu-Jie Sun, Yang-Qin Xie, Fei Fang, Hui Liu, Guo-Fei Tan, Zhi-Feng Chen, Jian Zhang, Ai-Sheng Xiong","doi":"10.1016/j.jare.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.024","url":null,"abstract":"<h3>Introduction</h3>Dill (<em>Anethum graveolens</em>) is a significant medicinal herb belonging to the Apiaceae family. Owing to its high levels of volatile organic compounds (VOCs), dill is commonly utilized for essential oil extraction and medicine purpose. However, the biosynthesis of the crucial VOC in dill remains obscure.<h3>Objectives</h3>Identify the key VOCs related to the flavor formation in dill and dissect the regulatory mechanism of their synthesis.<h3>Methods</h3>The dill chromosomal-level genome was constructed by PacBio HiFi, Hi-C, and BGISEQ second generation sequencing and assembly. The VOCs in dill leaves were identified through GC–MS. The potential mechanism involved in regulating the VOC accumulation in dill flavor formation was analyzed by multi-omics analysis.<h3>Results</h3>A 1.17 Gb chromosome-scale genome of dill with a contig N50 of 10.78 Mb was constructed. A total of 46,538 genes were annotated across 11 assembled chromosomes. Comparative genomics analysis suggested that transposable element insertions, especially LTR-<em>Gypsy</em>, have contributed to the evolution and expansion of the dill genome. The flavor formation of dill was mainly attributed to terpenoids, especially α-phellandrene, β-ocimene, and o-cymene. The contribution of expansion and replication of terpenoid synthesis pathway genes, especially terpene synthase (<em>TPS</em>), to the abundant terpenoid production of dill was identified. Differential gene expression patterns observed at various developmental stages and tissues provided key candidate genes for the regulation of terpenoid synthesis, as well as transcription factors. The difference accumulation of esters and aromatics also affected the flavor formation of dill. The key genes implicated in the synthesis of anethole, namely <em>AIS</em> and <em>AMT</em> were further identified.<h3>Conclusion</h3>This study constructed the chromosome level genome and identified the main VOCs and related key genes in flavor formation of dill, shedding lights on our understanding of terpenoid biosynthesis but also offered guidance for future genetic research on molecular breeding in <em>Anethum graveolens</em>.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631454","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":"Intestinal tissue-resident memory T cells: Characteristics, functions under physiological and pathological conditions and spatial specificity","authors":"Ruochen Yan, Dingjiacheng Jia, Yadong Qi, Qiwen Wang, Shujie Chen","doi":"10.1016/j.jare.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.021","url":null,"abstract":"<h3>Background</h3>Tissue-resident memory T (T_RM) cells are a distinct subset of memory T cells that persist in non-lymphoid tissues, providing localized and rapid immune responses to infection and malignancy. Unlike circulating memory T cells, T_RM cells have unique homing and functional characteristics that are shaped by the tissue microenvironment. In the gut, T_RM cells play a pivotal role in maintaining mucosal immunity, exhibiting phenotypic and functional heterogeneity in different intestinal compartments and in response to aging and pathological conditions.<h3>Aim of review</h3>This review aims to systematically examine the definition, spatial heterogeneity and functional roles of intestinal T_RM (iT_RM) cells. It highlights their contributions to physiological immunity, their involvement in pathological processes such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), and their age-related dynamics. The review also explores emerging therapeutic implications of modulating iT_RM cells for intestinal health and disease management.<h3>Key scientific concepts of review</h3>iT_RM cells are defined by surface markers like CD69 and CD103, transcriptional regulators such as Hobit, Runx3, Blimp-1, as well as cytokine signals including TGF-β, IFN-β, IL-12. They exhibit spatial and functional heterogeneity across intestinal layers (epithelium versus lamina propria) and regions (small intestine versus colon). In IBD, iT_RM cells play a dual role, contributing to both inflammation and tissue repair, whereas in CRC, specific subsets of iT_RM cells (e.g., CD8⁺ CD103⁺ CD39⁺) are associated with enhanced antitumor immunity. Aging impacts iT_RM functionality, with shifts in the CD4⁺/CD8⁺ ratio and reduced cytokine production in elderly individuals. Insights into the metabolic, transcriptional, and environmental regulation of iT_RM cells provide avenues for targeted therapies in intestinal diseases, cancer immunotherapy, and interventions to delay intestinal aging.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"56 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631207","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":"Deficit of neuronal EAAT2 impairs hippocampus CA3 neuron’s activity and may induce depressive like behaviors","authors":"Ke Cheng, Chong Chen, Qinji Zhou, Xiangyu Chen, Peng Xie","doi":"10.1016/j.jare.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.016","url":null,"abstract":"<h3>Introduction</h3>Major depressive disorder (MDD) is a severe neuropsychiatric disease that is accompanied by hippocampal dysfunction. Currently, the complex neuronal types and molecules involved in the various hippocampal subfields in patients with depression remain unclear.<h3>Objectives</h3>We focused on the role of hippocampal excitatory amino acid transporter 2 (EAAT2) in chronic stress.<h3>Methods</h3>We studied two chronic stress models, the chronic unpredictable mild stress (CUMS) and the chronic social defeat stress (CSDS) models, and performed pharmacological inhibition, genetic manipulations to examine overexpression of neuron-specific solute carrier family 1 member 2 (<em>SLC1A2</em>), the gene encoding EAAT2, in the dorsal CA3 and conditional <em>Slc1a2</em> knockout in CA3, whole-cell recording, and behavioral tests.<h3>Results</h3>Our results indicated that decreased EAAT2 expression and specific inhibition were associated with depression-like behavior and enhanced CA3 pyramidal neuron activity. In addition, neuron-specific EAAT2 overexpression in the CA3 yielded antidepressant-like effects and inhibited CA3 pyramidal neuron hyperactivity, whereas conditional CA3 EAAT2 knockout showed opposite effects at both behavioral and functional levels. We also found that the single-nucleotide polymorphism, rs77619780, in the <em>SLCA1A2</em> gene was associated with lower MDD risk.<h3>Conclusion</h3>Our findings revealed that EAAT2 deficit in the CA3 induces depression-like behavior, which offers novel insight into MDD pathophysiology.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis","authors":"Jingjing Fan, Ying Wu, Xing Wang, Habib Ullah, Zhenmin Ling, Pu Liu, Yu Wang, Pengya Feng, Jing Ji, Xiangkai Li","doi":"10.1016/j.jare.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.017","url":null,"abstract":"<h3>Introduction</h3>The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.<h3>Objectives</h3>This study investigated whether pretreatment of donor microbiota with <em>L. plantarum</em> GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.<h3>Methods</h3>Donor mice received <em>L. plantarum</em> GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.<h3>Results</h3>GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, <em>p</em> &lt; 0.0001) enriched butyrogenic <em>Butyricicoccus</em> (73 % butyrate increase, <em>p</em> &lt; 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (<em>Sporobacter</em>, <em>Butyricimonas</em>), while suppressing pathogens (<em>Clostridium papyrosolvens</em>).<h3>Conclusions</h3><em>L. plantarum</em> GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"90 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618857","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}