Translational Research最新文献

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S1931-5244(24)00099-9","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00099-9","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Page ii"},"PeriodicalIF":7.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000999/pdfft?md5=48f260bb407e4d020be12bc4867001d1&pid=1-s2.0-S1931524424000999-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140902330","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":"Information for Readers","authors":"","doi":"10.1016/S1931-5244(24)00101-4","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00101-4","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Page IBC"},"PeriodicalIF":7.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140902132","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":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(24)00100-2","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00100-2","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages iii-iv"},"PeriodicalIF":7.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140902131","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":"Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway","authors":"Shan-Shan Li,&nbsp;Qiao-Juan Liu,&nbsp;Jia-Xin Bao,&nbsp;Meng-ting Lu,&nbsp;Bing-Quan Deng,&nbsp;Wen-Wen Li,&nbsp;Chang-Chun Cao","doi":"10.1016/j.trsl.2024.05.006","DOIUrl":"10.1016/j.trsl.2024.05.006","url":null,"abstract":"<div><p>Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence ‘YEVEDYR’) from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to β-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown <em>in vivo</em> increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. <em>In vitro</em>, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 26-39"},"PeriodicalIF":7.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909677","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":"Immune cell distribution and DNA methylation signatures differ between tumor and stroma enriched compartment in pancreatic ductal adenocarcinoma","authors":"Erwin Tomasich ,&nbsp;Jakob Mühlbacher ,&nbsp;Katharina Wöran ,&nbsp;Teresa Hatziioannou ,&nbsp;Merima Herac ,&nbsp;Markus Kleinberger ,&nbsp;Julia Maria Berger ,&nbsp;Lea Katharina Dibon ,&nbsp;Luzia Berchtold ,&nbsp;Gerwin Heller ,&nbsp;Elisabeth Sophie Bergen ,&nbsp;Andrea Macher-Beer ,&nbsp;Gerald Prager ,&nbsp;Martin Schindl ,&nbsp;Matthias Preusser ,&nbsp;Anna Sophie Berghoff","doi":"10.1016/j.trsl.2024.05.005","DOIUrl":"10.1016/j.trsl.2024.05.005","url":null,"abstract":"<div><p>The presence of abundant tumor stroma is a prominent characteristic of pancreatic ductal adenocarcinomas (PDAC) that potentially influences disease progression and therapy response. This study aims to investigate immune cell infiltration and epigenetic profiles in tumor cell enriched (“Tumor”) and stroma cell enriched (“Stroma”) regions within human PDAC tissue samples. By comparing those regions, we identified 25,410 differentially methylated positions (DMPs) distributed across 6,963 unique genes. Pathway enrichment analysis using the top 2,000 DMPs that were either hyper- or hypomethylated indicated that immune response pathways and the estrogen receptor pathway are epigenetically dysregulated in Tumor and Stroma regions, respectively. In terms of immune cell infiltration, we observed overall low levels of T cells in both regions. In Tumor regions however, occurrence of tumor-associated macrophages (TAMs) was higher than in Stroma regions (<em>p</em> = 0.02) concomitant with a dualistic distribution that stratifies PDAC patients into those with high and low TAM infiltration. By categorizing TAM levels into quartiles, our analysis revealed that PDAC patients with more than 1,515 TAMs per mm² exhibited significantly shorter overall survival (<em>p</em> = 0.036). Our data suggest that variations in inflammatory characteristics between the Tumor and Stroma defined compartments of PDAC may primarily stem from the presence of macrophages rather than lymphocytes. The abundance of TAMs within regions enriched with tumor cells correlates with patient survival, underscoring the potential significance of exploring therapeutic interventions targeting TAMs. Furthermore, directing attention towards the estrogen receptor pathway may represent a promising strategy to address the stroma cell component within the PDAC tumor microenvironment.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 40-51"},"PeriodicalIF":7.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001038/pdfft?md5=54cb0ec9997866301a308854efd67de6&pid=1-s2.0-S1931524424001038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909696","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":"Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells","authors":"Yuting Zhang ,&nbsp;Xue Mi ,&nbsp;Yunchao Zhang ,&nbsp;Jipeng Li ,&nbsp;Yunlong Qin ,&nbsp;Peng He ,&nbsp;Ya Zhao ,&nbsp;Binxiao Su ,&nbsp;Lijie He","doi":"10.1016/j.trsl.2024.05.004","DOIUrl":"10.1016/j.trsl.2024.05.004","url":null,"abstract":"<div><p>Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 52-67"},"PeriodicalIF":7.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000951/pdfft?md5=3edab8408ba1a3f8c26668d2e4f47c24&pid=1-s2.0-S1931524424000951-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900570","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":"Information for Readers","authors":"","doi":"10.1016/S1931-5244(24)00088-4","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00088-4","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"268 ","pages":"Page IBC"},"PeriodicalIF":7.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843694","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)00086-0","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00086-0","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"268 ","pages":"Page ii"},"PeriodicalIF":7.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000860/pdfft?md5=18e6601eac94f491e20cf5c80fa5239a&pid=1-s2.0-S1931524424000860-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843692","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":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(24)00087-2","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00087-2","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"268 ","pages":"Pages iii-iv"},"PeriodicalIF":7.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843693","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":"Early growth response protein 2 promotes partial epithelial-mesenchymal transition by phosphorylating Smad3 during renal fibrosis","authors":"Anni Song ,&nbsp;Ruiwei Yan ,&nbsp;Wei Xiong,&nbsp;Huiling Xiang,&nbsp;Jing Huang,&nbsp;Anni Jiang,&nbsp;Chun Zhang","doi":"10.1016/j.trsl.2024.04.005","DOIUrl":"10.1016/j.trsl.2024.04.005","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) is a serious health problem worldwide, which ultimately leads to end-stage renal disease (ESRD). Renal fibrosis is the common pathway and major pathological manifestation for various CKD proceeding to ESRD. However, the underlying mechanisms and effective therapies are still ambiguous. Early growth response 2 (EGR2) is reportedly involved in organ formation and cell differentiation. To determine the role of EGR2 in renal fibrosis, we respectively confirmed the increased expression of EGR2 in kidney specimens from both CKD patients and mice with location in proximal tubules. Genetic deletion of EGR2 attenuated obstructive nephropathy while EGR2 overexpression further promoted renal fibrosis in mice subjected to unilateral ureteral obstruction (UUO) due to extracellular matrix (ECM) deposition mediating by partial epithelial-mesenchymal transition (EMT) as well as imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs). We found that EGR2 played a critical role in Smad3 phosphorylation, and inhibition of EGR2 reduced partial EMT leading to blockade of ECM accumulation in cultured human kidney 2 cells (HK2) treated with transforming growth factor β1 (TGF-β1). In addition, the transcription co-stimulator signal transducer and activator of transcription 3 (STAT3) phosphorylation was confirmed to regulate the transcription level of EGR2 in TGF-β1-induced HK2 cells. In conclusion, this study demonstrated that EGR2 played a pathogenic role in renal fibrosis by a p-STAT3-EGR2-p-Smad3 axis. Thus, targeting EGR2 could be a promising strategy for CKD treatment.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 13-25"},"PeriodicalIF":7.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871020","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}