Journal of Advanced Research最新文献

{"title":"Urinary proteins from stone formers promote calcium oxalate crystallization, growth and aggregation via oxidative modifications","authors":"Sudarat Hadpech, Paleerath Peerapen, Sakdithep Chaiyait, Suchai Sritippayawan, Visith Thongboonkerd","doi":"10.1016/j.jare.2025.05.040","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.040","url":null,"abstract":"<h3>Introduction</h3>Various urinary parameters are used for determining kidney stone risk. However, almost all of the widely used lithogenic indices rely on urinary concentrations of small molecules/ions and pH.<h3>Objective</h3>To address whether urinary macromolecules (especially oxidatively modified proteins) also play a critical role in determining the stone risk.<h3>Methods</h3>Complexed urinary proteins (proteome) were purified from healthy individuals and calcium oxalate (CaOx) stone formers and performed various crystal assays and quantitative proteomics to compare them. Bioinformatic analyses were performed to gain additional insights, and the obtained data were verified by ELISA.<h3>Results</h3>While the normal urinary proteome inhibited CaOx stone-forming mechanisms (i.e., crystallization, growth and aggregation), the stone formers’ urinary proteome promoted all these CaOx crystal parameters. Descriptive proteomics by nanoLC-ESI-LTQ-Orbitrap-MS/MS analysis identified 203 and 381 proteins in the urine of healthy individuals and stone formers, respectively. Analyses of physicochemical properties revealed only molecular mass and isoelectric point that slightly increased in the stone formers’ urine, whereas instability index, grand average of hydrophathicity (GRAVY) and amino acid composition were comparable. Interestingly, proportion of oxidatively modified proteins (particularly those with methionine oxidation, methionine dioxidation and cysteine trioxidation) markedly increased (∼2.5-fold) in the stone formers’ urine. Quantitative proteomics revealed 89 increased and 56 decreased proteins in the stone formers’ urine. The oxidized proteins had a greater proportion (&gt;3-fold) in the increased proteins (77 %) compared with the decreased ones (23 %), whereas the non-oxidized proteins showed comparable proportions (54 % and 46 %, respectively). Functional enrichment analyses revealed a correlation between the increased proteins and oxidative stress biological processes and molecular functions. Finally, ELISA confirmed the significantly increased levels of oxidized proteins in the stone formers’ urine compared with that of healthy individuals.<h3>Conclusion</h3>These data implicate that oxidatively modified proteome serves as a key pathogenic factor or risk for CaOx kidney stone formation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122747","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":"Fish oil reduces intestinal fat absorption by promoting lacteal junction zippering via GPR120-VEGFR3-MLCK pathway","authors":"Junfeng Wang, Liling Cai, Jinhao Liu, Fenglin Zhang, Gonghao Zhang, Haoyan Kang, Guo Ren, Lidong Yan, Yue Zhang, Zhe Pan, Shilong Liu, Canjun Zhu, Ruifan Wu, Lina Wang, Gang Shu, Qingyan Jiang, Songbo Wang","doi":"10.1016/j.jare.2025.05.026","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.026","url":null,"abstract":"<h3>Introduction</h3>Diet-induced obesity can be improved by reducing intestinal fat absorption. Fish oil, enriched in n-3 PUFAs such as DHA and EPA, has shown promise in weight reduction. However, the role of fish oil in regulating intestinal fat absorption and the possible underlying mechanism remains largely unknown.<h3>Objectives</h3>The aim of this study was to understand the mechanism underlying the fish oil elicited anti-obesity effects.<h3>Methods</h3>HFD-fed mice were subjected to fish oil and lymphatic endothelial cells (LECs) were treated with DHA or EPA. The intestinal fat absorption, the lacteal zipper-like junctions, and the involvement of GPR120-VEGFR3-MLCK pathway were assessed.<h3>Results</h3>We found that fish oil gavage suppressed intestinal fat absorption associated with elevated proportion of lacteal zipper-like junctions and decreased expression of VEGFR3 in mice jejunum. Meanwhile, inhibition of VEGFR3 signaling in HFD-fed mice enhanced zipper-like junctions in jejunal lacteal to reduce fat absorption and combat obesity. In addition, DHA and EPA increased the proportion of zipper-like junctions via downregulation of VEGFR3 signaling in PA-treated LECs. However, activation of VEGFR3 signaling with VEGFC or inhibition of GPR120 with AH-7614 totally blocked the elevation of zipper-like junctions induced by DHA and EPA. Furthermore, DHA and EPA inhibited MLCK signaling in a GPR120-VEGFR3 dependent manner and inhibition of MLCK mimicked the promotive effects of DHA and EPA on zipper-like junctions. These in vitro results suggested that DHA and EPA increased the proportion of zipper-like junctions in PA-treated LECs through the GPR120-VEGFR3-MLCK signaling pathway. Finally, fish oil supplementation reduced intestinal fat absorption, promoted lacteal zipper-like junctions, enhanced GPR120 expression, inhibited VEGFR3 expression and MLCK signaling.<h3>Conclusion</h3>Overall, these findings showed for the first time that fish oil reduced intestinal fat absorption by promoting lacteal junctions zippering via GPR120-VEGFR3-MLCK pathway.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114320","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 exposure to urban particulate matter induces cardiac developmental toxicity in zebrafish offspring by disrupting mitochondrial homeostasis","authors":"Shiqian Liu, Ruiyang Ding, Linyuan Huang, Jianong Lv, Zhiwei Sun, Xiaoxiao Wang, Junchao Duan","doi":"10.1016/j.jare.2025.05.041","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.041","url":null,"abstract":"<h3>Introduction</h3>Urban particulate matter (UPM) is a major air pollutant affecting public health, with maternal exposure potentially leading to cardiac developmental disorders in offspring. However, the exact mechanisms underlying the intergenerational effects of UPM remain unclear.<h3>Objective</h3>This study aimed to investigate the molecular mechanisms involved in cardiac developmental defects caused by maternal UPM exposure in offspring zebrafish.<h3>Methods and results</h3>Female zebrafish were exposed to UPM for 21 days to examine intergenerational effects. The results indicated that maternal zebrafish in the exposed group exhibited ovarian damage and a reduced number of embryos and fertilization rates. Zebrafish offspring exhibited abnormal cardiac development, including pericardial edema and pathological heart injury. Mechanistically, transcriptomic analysis of the offspring indicated that UPM exposure induced significant modifications in the mitochondrial biogenesis pathway, with altered expression of mitochondrial function-related genes. Maternal UPM exposure impaired respiration in zebrafish embryos and increased angiopoietin-like 4 (ANGPTL4) expression in offspring hearts. <em>In vitro</em>, <em>Angptl4</em> knockdown alleviated UPM-induced mitochondrial membrane potential reduction and mitochondrial reactive oxygen species overproduction in cardiomyocytes, whereas <em>Angptl4</em> overexpression exacerbated UPM-induced mitochondrial toxicity.<h3>Conclusion</h3>These findings show that maternal UPM exposure disrupts mitochondrial homeostasis by upregulating ANGPTL4 expression, leading to abnormal cardiac development in zebrafish offspring.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104194","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":"Dynamic heterogeneity towards drug resistance in AML cells is primarily driven by epigenomic mechanism unveiled by multi-omics analysis","authors":"Yulong Zhang, Yanfang Lu, Liyao Mai, Zebin Wen, Min Dai, Siwen Xu, Xianwei Lin, Yongjian Luo, Yinbin Qiu, Yuting Chen, Zhanying Dong, Caiming Chen, Wei Meng, Xingguang Luo, Guanchuan Lin, Paul K.H. Tam, Xinghua Pan","doi":"10.1016/j.jare.2025.05.038","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.038","url":null,"abstract":"<h3>Introduction</h3>Acute myeloid leukemia (AML) is a hematologic malignancy characterized by aggressive proliferation and chemoresistance, leading to poor patient outcomes. Despite advances in chemotherapy, resistance mechanisms remain inadequately understood, particularly at the cellular and molecular level.<h3>Objectives</h3>This study aims to elucidate the cellular and molecular mechanisms underlying drug resistance in AML cells.<h3>Methods</h3>A multi-omics approach was employed, integrating single-cell RNA sequencing (scRNA-seq), chromatin accessibility profiling (scATAC-seq), DNA methylation analysis, and whole-exome sequencing (WES). AML cell lines (KG-1a, Kasumi-1, and HL-60) were treated with standard chemotherapeutic agents, including cytarabine (Ara-C), daunorubicin (DNR), azacitidine (AZA), and decitabine (DEC). Additionally, we developed a novel multiplexed scRNA-seq strategy, NAMUL-seq, to enhance the efficiency and scalability of single-cell transcriptomic research.<h3>Results</h3>We observed substantial cellular heterogeneity and dynamic transcriptomic trajectories in AML cells subjected to various treatments, uncovering a tendency for reprogramming towards a more stem-like state. Notably, Ara-C-resistant KG-1a cells predominantly originated from G2/M phase subpopulations, suggesting a resistance mechanism linked to specific cell cycle stages. Our findings further indicate that rapid Ara-C resistance is primarily driven by epigenomic changes, including alterations in DNA methylation, chromatin architecture, and transcription factor activity, whereas exonic mutations played a minimal role.<h3>Conclusion</h3>This study demonstrates that AML drug resistance is predominantly driven by epigenomic mechanisms rather than genetic mutations. This study provides a detailed cellular and molecular characterization of AML drug response and resistance, identifying potential therapeutic targets and laying the groundwork for future efforts to overcome chemoresistance.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104193","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":"Aroma compounds with enhanced sweet perception in tea infusions: Screening, characterization, and sweetening mechanism","authors":"Yuming Wei, Ya-Ya Yu, Yuan-Chao Li, Xiao-Yu Zhong, Chun Zou, Jingming Ning, Wen-Jiang Dong, Kegang Wu, Yong-Quan Xu","doi":"10.1016/j.jare.2025.05.044","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.044","url":null,"abstract":"<h3>Introduction</h3>Tea (<em>Camellia sinensis</em>) is globally consumed for its pleasant flavor, with sweetness being a key factor in evaluating tea quality. While taste compounds contribute to this sweetness, aroma also plays a significant role, but its contribution is not well understood in tea infusion.<h3>Objectives</h3>This study aimed to identify aroma compounds that enhance sweetness in tea infusion using a sensomics approach, and explore their synergistic effects through molecular docking.<h3>Results</h3>The aroma increased the sweetness of the tea infusion by more than 24.0 %. Eighteen aroma-active compounds linked to sweetness were identified, among which (<em>E</em>)-<em>β</em>-damascenone (apple-like), linalool (citrus-like), geraniol (citrus-like), dimethyl sulfide (corn-like), (<em>E,E</em>)-2,4-heptadienal (floral), (<em>E,Z</em>)-2,6-nonadienal (cucumber-like), (<em>E</em>)-linalool oxide (furanoid) (floral), dihydroactinidiolide (fruity), <em>γ</em>-nonalactone (coconut-like), and (<em>E</em>)-<em>β</em>-ionone (floral) had higher sweetness similarity and significantly increased the sweet intensity of sucrose (<em>p</em> &lt; 0.05). They likely enhance sweetness by reducing the binding energy of sucrose to sweet taste receptors, forming new hydrogen bonds and hydrophobic interactions.<h3>Conclusion</h3>This study provides new insights into the role of aroma compounds in tea sweetness and suggests a potential mechanism for their sweetening effect. These compounds could be used as flavour enhancers or additives to improve the sweetness of tea beverages.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097349","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":"Aquaporin 4 and its isoforms regulation ameliorate AQP4 Mis-localization-induced glymphatic dysfunction in ischemic stroke","authors":"Hanhong Zhang, Jinjing Wang, Siyuan Zhang, Dingyi Yan, Yiran Dong, Pan Zhang, Wen Sun, Xinfeng Liu","doi":"10.1016/j.jare.2025.05.022","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.022","url":null,"abstract":"<h3>Introduction</h3>The glymphatic system, a brain waste clearance pathway, is impaired during ischemic stroke-induced edema, although the underlying mechanisms remain unclear.<h3>Objectives</h3>This study investigates the temporal dynamics of glymphatic dysfunction post-stroke and the roles of aquaporin 4 (AQP4), its isoforms, and syntrophin alpha 1 (SNTA1) in AQP4 polarization.<h3>Methods</h3>Using a transient middle cerebral artery occlusion (tMCAO) mouse model, glymphatic function was assessed via cisterna magna contrast injection and magnetic resonance imaging. The AQP4 antagonist TGN-020 was administered to elucidate edema’s role in glymphatic dysfunction. AQP4 isoforms viral vectors and SNTA1 modulation were used to study AQP4 polarization and glymphatic function. Techniques included western blotting, q-PCR, immunofluorescence, TEM and behavioral tests. Transcriptomic and metabolomic analyses were performed to assess gene expression and metabolic changes.<h3>Results</h3>Cerebrospinal fluid (CSF) flow decreased during the hyperacute phase, recovering with edema resolution. By administering TGN-020 to reduce edema, distinct alterations in the localization of AQP4 were observed. Specifically, there was a notable increase in AQP4 localization within the astrocyte end-feet. Consequently, CSF inflow and interstitial fluid (ISF) drainage were restored. Transcriptomic sequencing was used to analyze ubiquitination-related channels in tMCAO mice. Metabolic sequencing showed that TGN-020 therapy protected the metabolic stability. Our findings highlight the critical role of AQP4 isoforms in the polarized distribution of AQP4. The upregulation of the AQP4-M1 isoform exacerbated edema and motor dysfunction, whereas the AQP4-M23 isoform corrected the mis-localization of AQP4. Inhibition of AQP4 not only restored the polarized integrity of AQP4 in astrocyte end-feet but also alleviated the metabolic disruptions caused by tMCAO. Furthermore, overexpression of SNTA1 enhanced AQP4 polarity by modulating the expression of AQP4 isoforms.<h3>Conclusion</h3>Cerebral edema disrupts AQP4 localization and glymphatic function following stroke. TGN-020 modulates AQP4 polarization through regulation of AQP4 isoforms and restores glymphatic dysfunction. AQP4-M23 isoform emerges as a key regulator of AQP4 polarization, providing new insights into ischemic stroke pathophysiology.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"12 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097348","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":"Clostridium butyricum and its metabolites regulate macrophage polarization through miR-146a to antagonize gouty arthritis","authors":"Siyue Song, Kaiyue Shi, Moqi Fan, Xianghui Wen, Jiatao Li, Yining Guo, Yu Lou, Fusen Chen, Jialu Wang, Lin Huang, Chengping Wen, Tiejuan Shao","doi":"10.1016/j.jare.2025.05.036","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.036","url":null,"abstract":"<h3>Introduction</h3>Gut microbiota modulation has recently been identified as a prospective avenue for the exploration of novel therapeutic strategies for the management of gout. Nevertheless, the application of a single specific strain or bacterial metabolite for gout intervention has rarely been explored and the underlying regulatory mechanism remains elusive.<h3>Objectives</h3>To ascertain the potential role and the molecular mechanism of <em>Clostridium butyricum</em> and butyrate in the management of gouty arthritis.<h3>Methods</h3>A <em>Uox</em>-KO mouse model of gouty arthritis was developed and the composition of the gut microbiota was analyzed. <em>Clostridium butyricum</em> and butyrate were supplemented to assess functional recovery and intestinal homeostasis. NanoString analysis identified miRNA variations. GC/MS measured butyric acid levels and qPCR detected the abundance of butyrate-producing enzymes and bacteria. Flow cytometry analyzed macrophage polarization and ELISA measured pro-inflammatory cytokine production. Agomir and antagomir were transfected and dual-luciferase reporter assay was adapted for validation of miRNA target binding. siRNA and rescue experiments were performed to validate the role of SOCS7 in macrophage polarization. In addition, a cohort of patients with gouty arthritis were assembled for the purpose of validating the molecular mechanism.<h3>Results</h3>The results of our study demonstrated that a reduction of butyrate levels, resulting from a deficiency of butyrate-producing bacteria, leads to aberrant miR-146a expression. This, in turn, induces an imbalance in macrophage polarization and the onset of gouty arthritis. The administration of <em>Clostridium butyricum</em> and butyrate demonstrated considerable anti-inflammatory efficacy by restoring intestinal homeostasis, modulating miR-146a expression, and skewing macrophage polarization. The SOCS7/JAK2-STAT3 signaling pathway was identified as a pivotal mediator in the skewing of macrophage polarization induced by miR-146a.<h3>Conclusion</h3>Our findings enrich the understanding of the regulatory mechanisms underlying macrophage polarization in gouty arthritis and highlight the potential applications of probiotics and their metabolites in clinical gout treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"36 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097351","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":"JAM-C prevents ocular fibrosis by suppressing the TAZ/KLF6 pathway","authors":"Min Chen, Wanhong Li, Yuxiang Du, Yuanlong Zhao, Ying Guo, Ying Li, Xiaolu Wang, Lijuan Huang, Xiaoling Zeng, Yihan Zhang, Guanqun Huang, Shasha Wang, Haiqing Kuang, Guangli Sun, Qin Jiang, Xuri Li, Weisi Lu","doi":"10.1016/j.jare.2025.05.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.037","url":null,"abstract":"<h3>Introduction</h3>Ocular fibrosis is one of the leading causes of irreversible visual impairment or blindness. Currently, there is no effective drug available for such diseases. Therefore, understanding the underlying mechanisms is a prerequisite for finding better therapeutic strategies.<h3>Objectives</h3>This study aims to investigate the role of the junctional adhesion molecule C (JAM-C) in ocular fibrosis.<h3>Methods</h3>The protein levels of JAM-C were determined in the vitreous humor samples of patients with ocular fibrosis using ELISA. <em>Jam-c</em> genetic deletion mice and ocular fibrosis mouse models were generated to study the role of JAM-C <em>in vivo</em>. EMT, proliferation, migration, and gel contraction capacities in RPE cells were examined after JAM-C knockdown by siRNAs. RNA sequencing, co-IP, ChIP-qPCR, and luciferase reporter assay were performed to investigate the underlying mechanisms. Subretinal injection of adeno-associated virus, immunofluorescence, western blot were performed to evaluate the potential of JAM-C in preventing ocular fibrosis in different mouse models.<h3>Results</h3>Markedly reduced JAM-C expression was found in patients with ocular fibrosis. Genetic deletion of <em>Jam-c</em> in mice exacerbated ocular fibrosis, and JAM-C knockdown triggered the EMT process in RPE cells. Mechanistically, we reveal that JAM-C inhibits ocular fibrosis by suppressing the nuclear localization and function of TAZ, which otherwise binds to KLF6 to promote its expression and activity to initiate the EMT cascade. Importantly, AAV-mediated JAM-C augmentation alleviated ocular fibrosis in different mouse models.<h3>Conclusion</h3>Our findings unveil a novel function of JAM-C in preventing ocular fibrosis by inhibiting the TAZ/KLF6 pathway, and suggest new therapeutic possibilities for the treatment of fibrotic diseases","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"45 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097355","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":"Ketogenic diet and β-hydroxybutyrate inhibit HDAC1 to preserve vascular smooth muscle cell function in thoracic aortic aneurysm","authors":"Xinyu Weng, Lihong Pan, Xiurui Ma, Wei Luo, Hongdong Su, Zhiqiang Pei, Zhen Dong, Liwei Liu, Jing Yang, Pingjin Gao, Aijun Sun","doi":"10.1016/j.jare.2025.05.035","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.035","url":null,"abstract":"<h3>Background</h3>Thoracic aortic aneurysm (TAA) is a serious condition characterized by dilation of the thoracic aorta, often leading to aortic dissection or rupture. Current treatments involve surgical and pharmacological interventions and do not effectively address the underlying molecular mechanisms. This study explores the effects of ketogenic diet (KD) on TAA, focusing on histone deacetylase 1 (HDAC1) and vascular smooth muscle cells (VSMCs) function.<h3>Methods</h3>A β-aminopropionitrile monofumarate (BAPN)-induced TAA mouse model was used. Mice were divided into groups receiving either a standard diet or KD. Additionally, β-hydroxybutyrate (BHB), a KD-derived ketone body, and parthenolide or ITSA-1 were administered. The study measured survival rates, aortic dilation, elastin degradation, VSMC contractile markers, mitochondrial function, and oxidative stress levels.<h3>Results</h3>KD significantly improved survival rates and reduced aortic dilation and elastin degradation in the TAA mouse model. BHB also mitigated TAA development, demonstrating similar protective effects. KD and BHB were particularly effective in preserving mitochondrial function and maintaining VSMC contractile phenotype by restoring contractile marker expression. Additionally, KD and BHB significantly reduced oxidative stress levels. The addition of HDAC1 inhibitor parthenolide or HDAC agonist ITSA-1 further evaluated the protective effects of BHB against vascular damage.<h3>Conclusion</h3>Our study reveals the important roles of KD and BHB in regulating HDAC1, preserving mitochondrial function, maintaining VSMC phenotype, and reducing oxidative stress in TAA. Our findings demonstrate KD and BHB as promising therapeutic strategies for treating TAA by targeting specific molecular pathways involved in its progression. This study highlights the significance and innovation of lifestyle interventions, such as KD, in mitigating TAA by addressing its underlying molecular mechanisms.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"14 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097352","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":"Multi-omics analysis of glycolytic reprogramming and ROS dynamics in host-specific responses to Salmonella Typhi infection in mice","authors":"Yanrui Bai, Wenxiu Liu, Zhiyuan Liu, Dandan Ding, Huiya Jin, Shangyu Xiao, Jiayin Guo, Xiaoe He, Qian Wang, Han Xiao, Yan Wang, Tiansheng Zhang, Yana Li, Jing Yang, Hui Sun","doi":"10.1016/j.jare.2025.05.027","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.027","url":null,"abstract":"<h3>Introduction</h3><em>Salmonella</em> Typhi (<em>S.</em> Typhi), a Gram-negative, serves as the etiological agent of typhoid fever. In contrast to other <em>Salmonella</em> serovars, <em>S.</em> Typhi exclusively infects humans. However, the molecular interactions it engages in with the host immune system remain inadequately characterized. This study adopts a multi-omics strategy to elucidate the immune and metabolic dynamics within the murine spleen during <em>S.</em> Typhi infection.<h3>Objectives</h3>To identify and analyze transcriptomic, proteomic, and metabolomic alterations in the spleens of mice infected with <em>S.</em> Typhi. By comparing these host responses with those elicited by <em>Salmonella</em> Typhimurium (<em>S.</em> Typhimurium), a closely related serovar possessing a broad host range, the study seeks to uncover the unique metabolic reprogramming and immune-modulatory mechanisms specific to <em>S.</em> Typhi infection.<h3>Methods</h3>A multi-omics strategy was adopted, integrating transcriptomic, proteomic, and metabolomic data obtained from the spleen tissues of <em>S.</em> Typhi-infected mice. <em>S.</em> Typhimurium was utilized as a comparative control to distinguish host-specific responses. Additionally, the dynamics of reactive oxygen species (ROS), which play pivotal roles in mediating immune responses during infection, were examined.<h3>Results</h3>Integration of multi-omics datasets demonstrated distinct metabolic and immunological responses orchestrated by <em>S.</em> Typhi infection. Host metabolism was reprogrammed by <em>S.</em> Typhi through the upregulation of glycolysis and the facilitation of glucose-to-pyruvate conversion, while concurrently suppressing the tricarboxylic acid cycle (TCA cycle). These changes culminated in increased lactate accumulation, and augmented ROS production, all of which were associated with intensified immune activation.<h3>Conclusion</h3><em>S.</em> Typhi infection induces metabolic reprogramming in the host, characterized by a redirected glycolytic flux and altered pyruvate metabolism. This metabolic shift enhances ROS production and modulates the immune response. These findings yield novel insights into host-specific strategies employed by <em>S.</em> Typhi and highlight the significance of metabolic remodeling in immune defense, thereby presenting potential therapeutic targets for combating typhoid fever.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"75 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083356","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}