Translational Research最新文献

{"title":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(24)00157-9","DOIUrl":"10.1016/S1931-5244(24)00157-9","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148502","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}

{"title":"Information for Readers","authors":"","doi":"10.1016/S1931-5244(24)00158-0","DOIUrl":"10.1016/S1931-5244(24)00158-0","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148503","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}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S1931-5244(24)00156-7","DOIUrl":"10.1016/S1931-5244(24)00156-7","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001567/pdfft?md5=beeb9ea39e3d49bea4bd33c3ae10d3a5&pid=1-s2.0-S1931524424001567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148501","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}

{"title":"DUSP5 deficiency suppresses the progression of acute kidney injury by enhancing autophagy through AMPK/ULK1 pathway","authors":"Fang Bai ,&nbsp;Chunjie Wang ,&nbsp;Sha Wang ,&nbsp;Yuxuan Zhao ,&nbsp;Feng Feng ,&nbsp;Kuipeng Yu ,&nbsp;Lei Liu ,&nbsp;Xiangdong Yang","doi":"10.1016/j.trsl.2024.08.006","DOIUrl":"10.1016/j.trsl.2024.08.006","url":null,"abstract":"<div><p>Acute kidney injury (AKI) represents a critical clinical disease characterized by the rapid decline in renal function, carrying a substantial burden of morbidity and mortality. The treatment of AKI is frequently limited by its variable clinical presentations and intricate pathophysiology, highlighting the urgent need for a deeper understanding of its pathogenesis and potential therapeutic targets. Dual-specific protein phosphatase 5 (DUSP5), a member of the serine-threonine phosphatase family, possesses the capability to dephosphorylate extracellular regulated protein kinases (ERK). DUSP5 has emerged as a pivotal player in modulating metabolic signals, inflammatory responses, and cancer progression, while also being closely associated with various kidney diseases. This study systematically scrutinized the function and mechanism of DUSP5 in AKI for the first time, unveiling a substantial increase in DUSP5 expression during AKI. Moreover, DUSP5 knockdown was observed to attenuate the production of inflammatory factors and apoptotic cells in renal tubular epithelial cells by enhancing AMPK/ULK1-mediated autophagy, thus improving renal function. In a word, DUSP5 knockdown in AKI effectively impede disease progression by activating autophagy. This finding holds promise for introducing fresh perspectives and targets for AKI treatment.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 1-9"},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116718","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}

{"title":"Regulation of monocyte apoptosis and DNA extrusion in monocyte extracellular traps by PSGL-1: Relevance in systemic lupus erythematosus","authors":"Antonio Muñoz-Callejas ,&nbsp;Inés Sánchez-Abad ,&nbsp;Alejandra Ramos-Manzano ,&nbsp;Esther San Antonio ,&nbsp;Elena González-Sánchez ,&nbsp;Javier Silván ,&nbsp;Rafael González-Tajuelo ,&nbsp;Isidoro González-Álvaro ,&nbsp;Javier García-Pérez ,&nbsp;Eva G Tomero ,&nbsp;Rosario García-Vicuña ,&nbsp;Esther F Vicente-Rabaneda ,&nbsp;Santos Castañeda ,&nbsp;Ana Urzainqui","doi":"10.1016/j.trsl.2024.08.005","DOIUrl":"10.1016/j.trsl.2024.08.005","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by severe organ damage and lacking curative treatment. While various immune cell types, especially dysfunctional B and T cells and neutrophils, have been related with disease pathogenesis, limited research has focused on the role of monocytes in SLE. Increased DNA extracellular traps, apoptosis and necrosis have been related to lupus pathogenesis. Our goal is to analyze the contribution of P-selectin glycoprotein ligand 1 (PSGL-1) in SLE monocytes to disease pathogenesis by investigating the control exerted by PSGL-1 on monocyte apoptosis and DNA extrusion in extracellular traps (METs). Monocytes from active disease patients (aSLE) exhibited reduced levels of PSGL-1. Importantly, lower PSGL-1 levels in SLE monocytes associated with several clinical characteristics, including anti-dsDNA autoantibodies, lupus anticoagulant, clinical lung involvement, and anemia. Monocytes from SLE patients showed higher susceptibility to apoptosis than healthy donors (HD) monocytes and PSGL-1/P-selectin interaction decreased secondary necrosis in HD but not in aSLE monocytes. Regarding METs, aSLE monocytes exhibited higher susceptibility to generate METs than HD monocytes. The interaction of HD monocytes with P-selectin induced Syk activation and reduced the levels of DNA extruded in METs. However, in aSLE monocytes, PSGL-1/P-selectin interaction did not activate Syk or reduce the amount of extruded DNA. Our data suggest a dysfunctional PSGL-1/P-selectin axis in aSLE monocytes, unable to reduce secondary necrosis or the amount of DNA released into the extracellular medium in METs, potentially contributing to lupus pathogenesis.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 10-20"},"PeriodicalIF":6.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057752","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}

{"title":"TFEB alleviates periodontitis by activating autophagy and inhibiting inflammation","authors":"Jie Ren ,&nbsp;Jiaxin Li ,&nbsp;Hong Tang ,&nbsp;Liang Hao ,&nbsp;Kai Yang","doi":"10.1016/j.trsl.2024.08.003","DOIUrl":"10.1016/j.trsl.2024.08.003","url":null,"abstract":"<div><p>Periodontitis is a chronic inflammatory oral disease that impaired the tooth-supporting apparatus, including gingival tissue destruction and alveolar bone resorption. The initiation of periodontitis is linked to the presence of oral bacteria, particularly <em>P. gingivalis</em> within pathogenic biofilms. Here, we demonstrated the central role of the autophagy regulator Transcription Factor EB (TFEB) in orchestrating autophagy activation and modulating the host immune response against <em>P. gingivalis</em> in periodontitis. Upregulation of TFEB expression at the protein level and heightened nuclear localization occurred during the progressive stages of periodontitis. Functionally, TFEB overexpression emerges as a potent alleviator of periodontitis-associated phenotypes, operating through the activation of autophagy and the inhibition of the NF-κB pathway in both <em>in vivo</em> and <em>in vitro</em> models. In addition, TFEB knockdown exacerbates the inflammatory response by upregulating pro-inflammatory cytokines. The dual regulatory role of TFEB in governing both autophagy and inflammatory responses unveils novel insights into periodontitis pathogenesis, positioning TFEB as a promising therapeutic target for periodontitis intervention.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 127-136"},"PeriodicalIF":6.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001488/pdfft?md5=479a6c82156e8b09f2226754648a7970&pid=1-s2.0-S1931524424001488-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057753","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}

{"title":"Transcriptome-based classification to predict FOLFIRINOX response in a real-world metastatic pancreatic cancer cohort","authors":"Marjolein F. Lansbergen ,&nbsp;Mark P.G. Dings ,&nbsp;Paul Manoukian ,&nbsp;Arantza Fariña ,&nbsp;Cynthia Waasdorp ,&nbsp;Gerrit K.J. Hooijer ,&nbsp;Joanne Verheij ,&nbsp;Jan Koster ,&nbsp;Danny A. Zwijnenburg ,&nbsp;Johanna W. Wilmink ,&nbsp;Jan Paul Medema ,&nbsp;Frederike Dijk ,&nbsp;Hanneke W.M. van Laarhoven ,&nbsp;Maarten F. Bijlsma","doi":"10.1016/j.trsl.2024.08.002","DOIUrl":"10.1016/j.trsl.2024.08.002","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at metastatic stage and typically treated with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Few patients benefit from this treatment. Molecular subtypes are prognostic in particularly resectable PDAC and might predict treatment response. This study aims to correlate molecular subtypes in metastatic PDAC with FOLFIRINOX responses using real-world data, providing assistance in counselling patients. We collected 131 RNA-sequenced metastatic biopsies and applied a network-based meta-analysis using published PDAC classifiers. Subsequent survival analysis was performed using the most suitable classifier. For validation, we developed an immunohistochemistry (IHC) classifier using GATA6 and keratin-17 (KRT17), and applied it to 86 formalin-fixed paraffin-embedded samples of advanced PDAC. Lastly, GATA6 knockdown models were generated in PDAC organoids and cell lines. We showed that the PurIST classifier was the most suitable classifier. With this classifier, classical tumors had longer PFS and OS than basal-like tumors (PFS: 216 vs. 78 days, p = 0.0002; OS: 251 vs. 195 days, p = 0.049). The validation cohort showed a similar trend. Importantly, IHC GATA6^low patients had significantly shorter survival with FOLFIRINOX (323 vs. 746 days, p = 0.006), but no difference in non-treated patients (61 vs. 54 days, p = 0.925). This suggests that GATA6 H-score predicts therapy response. GATA6 knockdown models did not lead to increased FOLFIRINOX responsiveness. These data suggest a predictive role for subtyping (transcriptomic and GATA6 IHC), though no direct causal relationship was found between GATA6 expression and chemoresistance. GATA6 immunohistochemistry should be seamlessly added to current diagnostics and integrated into upcoming clinical trials.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 137-147"},"PeriodicalIF":6.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001476/pdfft?md5=358badf47c3d1c18405882937a9901bb&pid=1-s2.0-S1931524424001476-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001673","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}

{"title":"Genome-wide characterization of extrachromosomal circular DNA in SLE and functional analysis reveal their association with apoptosis","authors":"Yixi Li ,&nbsp;Fangfang Ge ,&nbsp;Chengxun Liu ,&nbsp;Wenjun Pu ,&nbsp;Wei Lv ,&nbsp;Zhipeng Zeng ,&nbsp;Lianghong Yin ,&nbsp;Dongzhou Liu ,&nbsp;Yasong Li ,&nbsp;Donge Tang ,&nbsp;Peng Han ,&nbsp;Yong Dai","doi":"10.1016/j.trsl.2024.08.004","DOIUrl":"10.1016/j.trsl.2024.08.004","url":null,"abstract":"<div><p>Extrachromosomal circular DNA (eccDNA) derived from linear chromosomes, are showed typical nucleosomal ladder pattern in agarose gel which as a known feature of apoptosis and demonstrated to be immunogenicity. In systemic lupus erythematosus (SLE) patients, elevated levels of cell-free DNA (cfDNA) can be found in either linear forms or circular forms, while circular ones are much less common and harder to detect. The molecular characteristics and function of circular forms in plasma SLE patients remains elusive. Herein, we characterized the hallmarks of plasma eccDNA in SLE patients, including the lower normalized number and GC content of eccDNA in SLE plasma than in the healthy, and SLE eccDNA number positively correlated with C3 and negatively with anti-dsDNA antibodies. The differential eccGenes (eccDNAs carrying the protein coding gene sequence) of SLE was significantly enriched in apoptosis-related pathways. The artificially synthesized eccDNA with sequences of the <em>PRF1</em> exon region could promote transcriptional expression of <em>PRF1, IFNA</em> and <em>IFIT3</em> and inhibit early-stage apoptosis. Plasma eccDNA can serve as a novel autoantigen in the pathogenesis of SLE.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 115-126"},"PeriodicalIF":6.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038150","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}

{"title":"The unveiled mosaic of intra-tumor heterogeneity in ovarian cancer through spatial transcriptomic technologies: A systematic review","authors":"Laura Masatti ,&nbsp;Matteo Marchetti ,&nbsp;Stefania Pirrotta ,&nbsp;Giulia Spagnol ,&nbsp;Anna Corrà ,&nbsp;Jacopo Ferrari ,&nbsp;Marco Noventa ,&nbsp;Carlo Saccardi ,&nbsp;Enrica Calura ,&nbsp;Roberto Tozzi","doi":"10.1016/j.trsl.2024.08.001","DOIUrl":"10.1016/j.trsl.2024.08.001","url":null,"abstract":"<div><p>Epithelial ovarian cancer is a significant global health issue among women. Diagnosis and treatment pose challenges due to difficulties in predicting patient responses to therapy, primarily stemming from gaps in understanding tumor chemoresistance mechanisms. Recent advancements in transcriptomic technologies like single-cell RNA sequencing and spatial transcriptomics have greatly improved our understanding of ovarian cancer intratumor heterogeneity and tumor microenvironment composition. Spatial transcriptomics, in particular, comprises a plethora of technologies that enable the detection of hundreds of transcriptomes and their spatial distribution within a histological section, facilitating the study of cell types, states, and interactions within the tumor and its microenvironment. Studies investigating the spatial distribution of gene expression in ovarian cancer masses have identified specific features that impact prognosis and therapy outcomes. Emerging evidence suggests that specific spatial patterns of tumor cells and their immune and non-immune microenvironment significantly influence therapy response, as well as the behavior and progression of primary tumors and metastatic sites. The importance of spatially contextualizing ovarian cancer transcriptomes is underscored by these findings, which will advance our understanding and therapeutic approaches for this complex disease.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 104-114"},"PeriodicalIF":6.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904114","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}

{"title":"Vericiguat attenuates doxorubicin-induced cardiotoxicity through the PRKG1/PINK1/STING axis","authors":"Xianghui Zeng ,&nbsp;Hao Zhang ,&nbsp;Tianyu Xu ,&nbsp;Xiyuan Mei ,&nbsp;Xiao Wang ,&nbsp;Qiling Yang ,&nbsp;Zhen Luo ,&nbsp;Qingchun Zeng ,&nbsp;Dingli Xu ,&nbsp;Hao Ren","doi":"10.1016/j.trsl.2024.07.005","DOIUrl":"10.1016/j.trsl.2024.07.005","url":null,"abstract":"<div><p>Doxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. However, it is not clear whether vericiguat can improve DIC. In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOX-induced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 90-103"},"PeriodicalIF":6.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001452/pdfft?md5=89bea5d8d1a592d3fd4dc6ca850b3104&pid=1-s2.0-S1931524424001452-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768345","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}