Translational Research最新文献_第3页

Breaking new ground: Unraveling the USP1/ID3/E12/P21 axis in vascular calcification 开辟新天地：揭示血管钙化中的 USP1/ID3/E12/P21 轴。

IF 6.4 2区医学

Translational Research Pub Date : 2025-02-01 DOI: 10.1016/j.trsl.2024.09.002

Aoran Huang , Jianyun Rao , Xin Feng , Xingru Li , Tianhua Xu , Li Yao

{"title":"Breaking new ground: Unraveling the USP1/ID3/E12/P21 axis in vascular calcification","authors":"Aoran Huang , Jianyun Rao , Xin Feng , Xingru Li , Tianhua Xu , Li Yao","doi":"10.1016/j.trsl.2024.09.002","DOIUrl":"10.1016/j.trsl.2024.09.002","url":null,"abstract":"<div><div>Vascular calcification (VC) poses significant challenges in cardiovascular health. This study employs single-cell transcriptome sequencing to dissect cellular dynamics in this process. We identify distinct cell subgroups, notably in vascular smooth muscle cells (VSMCs), and observe differences between calcified atherosclerotic cores and adjacent regions. Further exploration reveals ID3 as a key gene regulating VSMC function. In vitro experiments demonstrate ID3′s interaction with USP1 and E12, modulating cell proliferation and osteogenic differentiation. Animal models confirm the critical role of the USP1/ID3/E12/P21 axis in VC. This study sheds light on a novel regulatory mechanism, offering potential therapeutic targets.<ul><li><span>1.</span><span><div>This study uses single-cell transcriptome to investigate vascular calcification in depth.</div></span></li><li><span>2.</span><span><div>This study successfully identifies cellular heterogeneity related to vascular calcification.</div></span></li><li><span>3.</span><span><div>This study reveals the crucial role of ID3 in vascular smooth muscle cell osteogenic differentiation.</div></span></li><li><span>4.</span><span><div><em>In vivo</em> and <em>in vitro</em> experiments of this study demonstrate the regulatory role of the USP1/ID3/E12/P21 axis in calcification.</div></span></li><li><span>5.</span><span><div>This study provides potential molecular targets for the treatment of calcification-related diseases.</div></span></li></ul></div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"276 ","pages":"Pages 1-20"},"PeriodicalIF":6.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine 在儿科猪中，体外循环与深度低温循环停止导致器官特异性转录组反应。

IF 6.4 2区医学

Translational Research Pub Date : 2025-01-17 DOI: 10.1016/j.trsl.2025.01.002

Jesse A. Davidson , John Iguidbashian , Ludmila Khailova , Tanner Lehmann , Alejandro Suarez-Pierre , Lindsay M. Thomson , Jack Zakrzewski , Eiman Ali , Schuyler Lee , Benjamin S. Frank , Richard J. Ing , Matthew L. Stone , Suzanne Osorio Lujan , Sierra Niemiec , Christopher A. Mancuso

{"title":"Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine","authors":"Jesse A. Davidson , John Iguidbashian , Ludmila Khailova , Tanner Lehmann , Alejandro Suarez-Pierre , Lindsay M. Thomson , Jack Zakrzewski , Eiman Ali , Schuyler Lee , Benjamin S. Frank , Richard J. Ing , Matthew L. Stone , Suzanne Osorio Lujan , Sierra Niemiec , Christopher A. Mancuso","doi":"10.1016/j.trsl.2025.01.002","DOIUrl":"10.1016/j.trsl.2025.01.002","url":null,"abstract":"<div><div>The organ-level molecular response to cardiac surgery with cardiopulmonary bypass (CPB) remains inadequately understood and may be heterogeneous. Here, we measured organ-specific gene expression in a piglet model of CPB with deep hypothermic circulatory arrest (DHCA). Infant piglets underwent peripheral CPB with 75 min of DHCA and 6 h of critical care after separation from CPB. Mechanically ventilated animals served as controls. Tissue was obtained from the lung, kidney, liver, heart, and ileum. RNA sequencing was performed using NovaSeq 6000 and evaluated via differentially expressed gene (DEG) and pathway/network analyses. CPB/DHCA induced significant transcriptomic alterations, with greater changes seen in liver (2,166 DEGs), heart (775 DEGs), and kidney (1,759 DEGs) compared to lung (401 DEGs) and ileum (11 DEGs), and little overlap across organs (<20 % differentially expressed in >1 organ). Key upregulated systems included ribosomal proliferation and mitochondrial assembly in the liver, oxidative stress response and proximal tubular repair in the kidney, myofilament structural genes and pro-hypertrophy pathways in the heart, and solute channels and arginine metabolism in the lung. Downregulation of adaptive immunity genes occurred in multiple organs. Transcriptomics could inform the investigation of targeted therapies and adverse event screening after cardiac surgery.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 64-74"},"PeriodicalIF":6.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the impact of e-cigarettes on human barrier systems: A systematic review 评估电子烟对人体屏障系统的影响：一项系统综述。

IF 6.4 2区医学

Translational Research Pub Date : 2025-01-14 DOI: 10.1016/j.trsl.2025.01.001

Gabriella Lupo , Carmelina Daniela Anfuso , Giuseppe Smecca , Alessia Cosentino , Aleksandra Agafonova , Chiara Prinzi , Rosario Junior Ferrauto , Stefano Turzo , Venerando Rapisarda , Caterina Ledda

{"title":"Assessing the impact of e-cigarettes on human barrier systems: A systematic review","authors":"Gabriella Lupo , Carmelina Daniela Anfuso , Giuseppe Smecca , Alessia Cosentino , Aleksandra Agafonova , Chiara Prinzi , Rosario Junior Ferrauto , Stefano Turzo , Venerando Rapisarda , Caterina Ledda","doi":"10.1016/j.trsl.2025.01.001","DOIUrl":"10.1016/j.trsl.2025.01.001","url":null,"abstract":"<div><div>The use of e-cigarettes has grown rapidly in recent years, raising concerns about their impact on human health, particularly on critical physiological barriers such as the blood-brain barrier (BBB), alveolar-capillary barrier, and vascular systems. This systematic review evaluates the current literature on the effects of e-cigarette exposure on these barrier systems. E-cigarettes, regardless of nicotine content, have been shown to induce oxidative stress, inflammation, and disruption of tight junction proteins, leading to impaired barrier function. Key findings include compromised pulmonary function, increased vascular stiffness, and neuroinflammation. The review highlights potential long-term health risks associated with e-cigarette use, such as cardiovascular disease, neurodevelopmental disorders, and multi-organ fibrosis, and emphasizes the need for public health interventions to regulate e-cigarette use, especially in vulnerable populations like pregnant women and adolescents.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 39-63"},"PeriodicalIF":6.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors ameliorate renal ischemia-reperfusion injury (IRI) by modulating autophagic processes 钠-葡萄糖共转运蛋白2 （SGLT-2）抑制剂通过调节自噬过程改善肾缺血再灌注损伤（IRI）。

IF 6.4 2区医学

Translational Research Pub Date : 2025-01-04 DOI: 10.1016/j.trsl.2024.12.006

Mengmeng Liu , Yuanqing Yao , Fangyan Tan , Jing Wang , Rong Hu , Jianlin Du , Yonghong Jiang , Xin Yuan

{"title":"Sodium-glucose co-transporter 2 (SGLT-2) inhibitors ameliorate renal ischemia-reperfusion injury (IRI) by modulating autophagic processes","authors":"Mengmeng Liu , Yuanqing Yao , Fangyan Tan , Jing Wang , Rong Hu , Jianlin Du , Yonghong Jiang , Xin Yuan","doi":"10.1016/j.trsl.2024.12.006","DOIUrl":"10.1016/j.trsl.2024.12.006","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury (IRI) is a common clinical condition that currently lacks effective treatment options. Inhibitors targeting the sodium-glucose co-transporter-2 (SGLT-2), recognized for their role in managing hyperglycemia, have demonstrated efficacy in enhancing the health outcomes for diabetic patients grappling with chronic kidney disease. Nevertheless, the precise impact of SGLT-2 inhibitors on renal ischemia-reperfusion injury (IRI) and the corresponding transcriptomic alterations remain to be elucidated. In our research, we developed a model of IRI using male C57BL/6 mice by clamping the unilateral renal artery and administering empagliflozin Transcriptomic alterations were analyzed using RNA sequencing (RNA-Seq), complemented by proteomic analysis to investigate the effects of empagliflozin. Histological assessments revealed increased renal inflammatory cell infiltration, widespread renal tubular injury, and elevated autophagosomes formation in the IRI group compared to controls. These pathological changes were significantly attenuated following empagliflozin treatment. Besides, renal function impairment can be alleviated in empagliflozin-treated group. RNA-Seq analysis identified lysosomal autophagy as a key biological process in IRI mice. Empagliflozin exerted a renoprotective effect by downregulating lysosome-associated membrane proteins, primarily LAMP1, LAMP2, and LAMP4 (CD68), through the PI3K-Akt, MAPK, and mTOR signaling pathways, thereby inhibiting autophagic processes. In conclusion, this study highlights enhanced inflammation and disrupted metabolism as hallmark transcriptomic signatures of renal. Furthermore, it demonstrates the renoprotective effects of empagliflozin in alleviating renal IRI by modulating autophagic processes.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 27-38"},"PeriodicalIF":6.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Canagliflozin inhibits hedgehog interacting protein (Hhip) induction of tubulopathy in diabetic Akita mice 卡格列净抑制刺猬相互作用蛋白（hip）诱导糖尿病秋田小鼠小管病变。

IF 6.4 2区医学

Translational Research Pub Date : 2025-01-03 DOI: 10.1016/j.trsl.2024.12.005

Shiao-Ying Chang , Min-Chun Liao , Kana N. Miyata , Yuchao Pang , Xin-Ping Zhao , Junzheng Peng , Alain Rivard , Julie R. Ingelfinger , John S.D. Chan , Shao-Ling Zhang

{"title":"Canagliflozin inhibits hedgehog interacting protein (Hhip) induction of tubulopathy in diabetic Akita mice","authors":"Shiao-Ying Chang , Min-Chun Liao , Kana N. Miyata , Yuchao Pang , Xin-Ping Zhao , Junzheng Peng , Alain Rivard , Julie R. Ingelfinger , John S.D. Chan , Shao-Ling Zhang","doi":"10.1016/j.trsl.2024.12.005","DOIUrl":"10.1016/j.trsl.2024.12.005","url":null,"abstract":"<div><div>Renal hedgehog interacting protein (Hhip) activates sodium-glucose cotransporter 2 (Sglt2) expression and promotes tubular senescence in murine diabetic kidney disease (DKD), yet its underlying mechanism(s) are poorly understood. Here we study the effect of the SGLT2 inhibitor, canagliflozin on tubulopathy (fibrosis and apoptosis) in Akita/<em>Hhip</em><sup>RPTC</sup>-transgenic (Tg) mice with overexpression of Hhip in their renal proximal tubular cells (RPTCs) and its relevant mechanisms. The DKD-tubulopathy with pronounced Sglt2 expression was aggravated in the kidney of Akita/<em>Hhip</em><sup>RPTC</sup>-Tg cf. Akita/non-Tg mice. A strong association was observed between Hhip and tubular senescence in Nephroseq from the Nakagawa chronic kidney disease study. Both <em>in vivo</em> and <em>in vitro</em>, excessive Hhip in RPTCs triggered RPTC senescence (polyploidization and cytoskeleton destabilization) and released extracellular vesicles (EVs) carrying Hhip (EVs<sup>Hhip</sup>), most of which were apoptotic bodies (ABs<sup>Hhip</sup>) or microvesicles (MVs<sup>Hhip</sup>) and little exosomes (EXOs<sup>Hhip</sup>). Further, Hhip stimulated β2-microglobulin, which further interacts with EVs<sup>Hhip</sup>, together facilitating RPTC turn-over from cellular senescence to fibrosis and/or apoptosis, ultimately leading to advanced tubulopathy. In contrast, canagliflozin administration offset the action of Hhip in RPTCs, thereby preventing DKD progression. In conclusion, canagliflozin prevented excessive Hhip-mediated tubulopathy, possibly via the inhibition of excessive Hhip carried by extracellular vehicles in DKD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 13-26"},"PeriodicalIF":6.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Corrigendum to “Characterization of upregulated adhesion GPCRs in acute myeloid leukemia” [Transl Res. 2019 Oct:212:26-35. doi: 10.1016/j.trsl.2019.05.004. Epub 2019 May 17.] “急性髓性白血病中粘附性gpcr上调的表征”的更正[翻译]. 2019年10月：22 -35。doi: 10.1016 / j.trsl.2019.05.004。[Epub 2019年5月17日]。

IF 6.4 2区医学

Translational Research Pub Date : 2025-01-01 DOI: 10.1016/j.trsl.2024.11.003

Jiawen Yang, Sharon Wu, Houda Alachkar

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IF 6.4 2区医学

Translational Research Pub Date : 2025-01-01 DOI: 10.1016/S1931-5244(24)00191-9

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IF 6.4 2区医学

Translational Research Pub Date : 2025-01-01 DOI: 10.1016/S1931-5244(24)00193-2

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IF 6.4 2区医学

Translational Research Pub Date : 2025-01-01 DOI: 10.1016/S1931-5244(24)00192-0

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Aldehyde dehydrogenase 2 attenuates renal injury through inhibiting CYP4A expression 醛脱氢酶2通过抑制CYP4A表达减轻肾损伤。

IF 6.4 2区医学

Translational Research Pub Date : 2024-12-31 DOI: 10.1016/j.trsl.2024.12.007

Hao Chen , Qianchao Hu , Zhongshan Lu , Jie Zhao , Anxiong Liu , Zhongzhong Liu , Jun Luo , Qifa Ye , Zibiao Zhong

{"title":"Aldehyde dehydrogenase 2 attenuates renal injury through inhibiting CYP4A expression","authors":"Hao Chen , Qianchao Hu , Zhongshan Lu , Jie Zhao , Anxiong Liu , Zhongzhong Liu , Jun Luo , Qifa Ye , Zibiao Zhong","doi":"10.1016/j.trsl.2024.12.007","DOIUrl":"10.1016/j.trsl.2024.12.007","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury (IRI) is a prevalent clinical syndrome, yet its underlying pathogenesis remains largely unknown. Aldehyde dehydrogenase 2 (ALDH2), an enzyme responsible for detoxifying lipid aldehydes, has been suggested to play a protective role against IRI. In our study, we observed that Aldh2 knock-out C57BL/6 mice experienced more severe renal functional impairment following IRI. This was characterized by elevated levels of creatinine and blood urea nitrogen, as well as increased apoptosis. Proteomic analysis further revealed that ALDH2 deficiency significantly disrupted lipid metabolism, resulting in higher levels of the proinflammatory protein CYP4A and its metabolic byproduct, 20-HETE. This metabolic disruption exacerbated renal inflammation and triggered endoplasmic reticulum stress. However, we found that administration of the CYP4A inhibitor, HET0016, could ameliorate these effects. Mechanistically, we discovered that after IRI, ALDH2 translocates to the nucleus and interacts with nuclear receptor corepressor 1 (NCOR1) to repress <em>Cyp4a</em> transcription. ALDH2 specifically interacts with the N-terminal domain of NCOR1, which is responsible for its interaction with its E3 ligase SIAH2. This interaction inhibits the proteasome degradation of NCOR1, ultimately stabilizing the NCOR1 transcriptional repression complex. In summary, our research uncovers the role of ALDH2 in mitigating renal IRI by inhibiting 20-HETE synthesis through the transcriptional repression of <em>Cyp4a</em>.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"277 ","pages":"Pages 1-12"},"PeriodicalIF":6.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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