Translational Research最新文献

{"title":"Dihydrolipoamide S-acetyltransferase activation alleviates diabetic kidney disease via AMPK-autophagy axis and mitochondrial protection","authors":"Peihui Zhou,&nbsp;Ning Wang,&nbsp;Sijia Lu,&nbsp;Jie Xiong,&nbsp;Yao Zhang,&nbsp;Quanxin Jiang,&nbsp;Qiqi Qian,&nbsp;Qian Zhou,&nbsp;Junli Liu,&nbsp;Suzhen Chen","doi":"10.1016/j.trsl.2024.09.005","DOIUrl":"10.1016/j.trsl.2024.09.005","url":null,"abstract":"<div><div>Diabetic kidney disease (DKD), a severe complication of diabetes marked by deregulated glucose metabolism, remains enigmatic in its pathogenesis. Herein, we delved into the functional role of Dihydrolipoamide S-acetyltransferase (DLAT), a pivotal E2 component of the pyruvate dehydrogenase complex (PDC), in the context of DKD. Our findings revealed a downregulation of DLAT in the kidneys of diabetic patients, correlating inversely with kidney function. Parallel downregulation was observed in both high-fat diet/streptozotocin (HFD/STZ) and <em>db/db</em> mouse models, as well as in human proximal tubular epithelial cells (HK-2) cultured under hyperglycemic conditions. To further elucidate the role of endogenous DLAT in DKD, we employed genetic ablation of Dlat in mouse models. Dlat haploinsufficient mice exhibited exacerbated renal dysfunction, structural damage, fibrosis, and mitochondrial dysfunction under DKD conditions. Consistent with these findings, modulation of DLAT expression in HK-2 cells highlighted its influence on fibrosis, with overexpression attenuating Fibronectin and Collagen I levels, while downregulation exacerbated fibrosis. Mechanistically, we discovered that DLAT activates mitochondria autophagy through the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, thereby mitigating mitochondrial dysfunction associated with DKD progression. Inhibition of AMPK abrogated the protective effects of DLAT against mitochondrial dysfunction and DKD. Notably, we identified Hyperforin (HPF), a phytochemical, as a potential therapeutic agent. HPF activates DLAT and AMPK, subsequently ameliorating renal dysfunction, injuries, and fibrosis in both <em>in vivo</em> and <em>in vitro</em> models. In summary, our study underscores the pivotal role of DLAT and AMPK in kidney health and highlights the therapeutic potential of HPF in treating DKD.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 81-100"},"PeriodicalIF":6.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402609","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":"Spatial proteomics and transcriptomics of the maternal-fetal interface in placenta accreta spectrum","authors":"Helena C Bartels ,&nbsp;Sodiq Hameed ,&nbsp;Constance Young ,&nbsp;Myriam Nabhan ,&nbsp;Paul Downey ,&nbsp;Kathleen M Curran ,&nbsp;Janet McCormack ,&nbsp;Aurelie Fabre ,&nbsp;Walter Kolch ,&nbsp;Vadim Zhernovkov ,&nbsp;Donal J Brennan","doi":"10.1016/j.trsl.2024.09.004","DOIUrl":"10.1016/j.trsl.2024.09.004","url":null,"abstract":"<div><div>In severe Placenta Accreta Spectrum (PAS), trophoblasts gain deep access in the myometrium (placenta increta). This study investigated alterations at the fetal-maternal interface in PAS cases using a systems biology approach consisting of immunohistochemistry, spatial transcriptomics and proteomics. We identified spatial variation in the distribution of CD4⁺, CD3⁺ and CD8⁺ T-cells at the maternal-interface in placenta increta cases. Spatial transcriptomics identified transcription factors involved in promotion of trophoblast invasion such as AP-1 subunits ATF-3 and JUN, and NFKB were upregulated in regions with deep myometrial invasion. Pathway analysis of differentially expressed genes demonstrated that degradation of extracellular matrix (ECM) and class 1 MHC protein were increased in increta regions, suggesting local tissue injury and immune suppression. Spatial proteomics demonstrated that increta regions were characterised by excessive trophoblastic proliferation in an immunosuppressive environment. Expression of inhibitors of apoptosis such as BCL-2 and fibronectin were increased, while CTLA-4 was decreased and increased expression of PD-L1, PD-L2 and CD14 macrophages. Additionally, CD44, which is a ligand of fibronectin that promotes trophoblast invasion and cell adhesion was also increased in increta regions. We subsequently examined ligand receptor interactions enriched in increta regions, with interactions with ITGβ1, including with fibronectin and ADAMS, emerging as central in increta. These ITGβ1 ligand interactions are involved in activation of epithelial–mesenchymal transition and remodelling of ECM suggesting a more invasive trophoblast phenotype. In PAS, we suggest this is driven by fibronectin via AP-1 signalling, likely as a secondary response to myometrial scarring.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 67-80"},"PeriodicalIF":6.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335635","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":"Siglec-5 as a novel receptor mediates endothelial cells oxLDL transcytosis to promote atherosclerosis","authors":"Xiong Jia ,&nbsp;Xiangli Bai ,&nbsp;Zhiqiang Yin ,&nbsp;Qijun Zheng ,&nbsp;Yin Zhao ,&nbsp;Yajing Lu ,&nbsp;Yan Shu ,&nbsp;Yayu Wang ,&nbsp;Yifei Zhang ,&nbsp;Si Jin","doi":"10.1016/j.trsl.2024.09.003","DOIUrl":"10.1016/j.trsl.2024.09.003","url":null,"abstract":"<div><h3>Background</h3><div>Excessive subendothelial retention of oxidized low-density lipoprotein (oxLDL) and subsequent oxLDL engulfment by macrophages leads to the formation of foam cells and the development of atherosclerosis. Our previous study showed that the plasma level of sialic acid-binding immunoglobulin-like lectin 5 (Siglec-5) was a novel biomarker for the prognosis of atherosclerosis in diabetic patients. However, the role and underlying mechanisms of Siglec-5 in atherosclerosis have not been elucidated.</div></div><div><h3>Methods</h3><div>The interaction between oxLDL and Siglec-5 was detected by fluorescence colocalization and coimmunoprecipitation. The effect of oxLDL on Siglec-5 expression was detected in endothelial cells and macrophages, and the effect of Siglec-5 on oxLDL transcytosis and uptake was investigated. Siglec-5 was overexpressed in mice using recombinant adeno-associated virus vector serotype 9 (rAAV9-Siglec-5) to evaluate the effect of Siglec-5 on oxLDL uptake and atherogenesis <em>in vivo</em>. In addition, the effects of Siglec-5 antibodies and soluble Siglec-5 proteins on oxLDL transcytosis and uptake and their role in atherogenesis were investigated <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>We found that oxLDL interacted with Siglec-5 and that oxLDL stimulated the expression of Siglec-5. Siglec-5 promotes the transcytosis and uptake of oxLDL, while both anti-Siglec-5 antibodies and soluble Siglec-5 protein attenuated oxLDL transcytosis and uptake. Interestingly, overexpression of Siglec-5 by recombinant adeno-associated viral vector serotype 9 (rAAV9-Siglec-5) promoted the retention of oxLDL in the aorta of C57BL/6 mice. Moreover, overexpression of Siglec-5 significantly accelerated the formation of atherosclerotic lesions in Apoe^−/− mice. Moreover, both anti-Siglec-5 antibodies and soluble Siglec-5 protein significantly alleviated the retention of oxLDL in the aorta of rAAV9-Siglec-5-transfected C57BL/6 mice and the formation of atherosclerotic plaques in rAAV9-Siglec-5-transfected Apoe^−/− mice.</div></div><div><h3>Conclusion</h3><div>Our results suggested that Siglec-5 was a novel receptor that mediated oxLDL transcytosis and promoted the formation of foam cells. Interventions that inhibit the interaction between oxLDL and Siglec-5, including anti-Siglec-5 antibody or soluble Siglec-5 protein treatment, may provide novel therapeutic strategies in treating atherosclerosis.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 49-66"},"PeriodicalIF":6.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335634","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":"Diagnostic, prognostic, and predictive biomarkers in gastric cancer: from conventional to novel biomarkers","authors":"Ghazaleh Khalili-Tanha ,&nbsp;Nima Khalili-Tanha ,&nbsp;Arian Karimi Rouzbahani ,&nbsp;Ramisa Mahdieh ,&nbsp;Kimia Jasemi ,&nbsp;Rosa Ghaderi ,&nbsp;Fatemeh Khojasteh Leylakoohi ,&nbsp;Elnaz Ghorbani ,&nbsp;Majid Khazaei ,&nbsp;Seyed Mahdi Hassanian ,&nbsp;Ibrahim Saeed Gataa ,&nbsp;Gordon A Ferns ,&nbsp;Elham Nazari ,&nbsp;Amir Avan","doi":"10.1016/j.trsl.2024.09.001","DOIUrl":"10.1016/j.trsl.2024.09.001","url":null,"abstract":"<div><div>Gastric cancer is a major health concern worldwide. The survival rate of Gastric cancer greatly depends on the stage at which it is diagnosed. Early diagnosis is critical for improving survival outcomes. To improve the chances of early diagnosis, regular screening tests, such as an upper endoscopy or barium swallow, are recommended for individuals at a higher risk due to factors like family history or a previous diagnosis of gastric conditions. Biomarkers can be detected and measured using non-invasive methods such as blood tests, urine tests, breath analysis, or imaging techniques. These non-invasive approaches offer many advantages, including convenience, safety, and cost-effectiveness, making them valuable tools for disease diagnosis, monitoring, and research. Biomarker-based tests have emerged as a useful tool for identifying gastric cancer early, monitoring treatment response, assessing the recurrence risk, and personalizing treatment plans. In this current review, we have explored both classical and novel biomarkers for gastric cancer. We have centralized their potential clinical application and discussed the challenges in Gastric cancer research.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 35-48"},"PeriodicalIF":6.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305344","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)00165-8","DOIUrl":"10.1016/S1931-5244(24)00165-8","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Page IBC"},"PeriodicalIF":6.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157823","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)00164-6","DOIUrl":"10.1016/S1931-5244(24)00164-6","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages iii-iv"},"PeriodicalIF":6.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157822","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)00163-4","DOIUrl":"10.1016/S1931-5244(24)00163-4","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Page ii"},"PeriodicalIF":6.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001634/pdfft?md5=a76ad259a7dd427d26d8447389f22bc1&pid=1-s2.0-S1931524424001634-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157821","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":"J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway","authors":"Rong Jin ,&nbsp;Min Wang ,&nbsp;Manish Shukla ,&nbsp;Yuguo Lei ,&nbsp;Dong An ,&nbsp;Jiwen Du ,&nbsp;Guohong Li","doi":"10.1016/j.trsl.2024.08.007","DOIUrl":"10.1016/j.trsl.2024.08.007","url":null,"abstract":"<div><p>Endoplasmic reticulum (ER) stress is recognized as a crucial contributor to the progression of traumatic brain injury (TBI) and represents a potential target for therapeutic intervention. This study aimed to assess the potential of J147, a novel neurotrophic compound, in alleviating ER stress by modulating related signaling pathways, thereby promoting functional recovery in TBI. To this end, adult mice underwent controlled cortical impact (CCI) injury to induce TBI, followed by oral administration of J147 one-hour post-injury, with daily dosing for 3 to 7 days. Multiple behavioral assessments were conducted over 35 days, revealing a significant, dose-dependent improvement in neurofunctional recovery with J147 treatment. The neuropathological analysis demonstrated reduced acute neurodegeneration (observed at three days through FJC staining), enhanced long-term neuron survival (H&amp;E and Nissl staining), and improved neuroplasticity (Golgi staining) at 35 days post-TBI. At the molecular level, TBIinduced AMP-activated protein kinase (AMPK) dephosphorylation, sterol regulatory element binding protein-1 (SREBP-1) activation, and upregulation of ER stress marker proteins, including phosphorylated eukaryotic initiation factor-2α (p-eIF2a), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in perilesional cortex neurons at three days post-injury. Notably, the J147 treatment significantly attenuated AMPK dephosphorylation, SERBP-1 activation, and expression of the ER stress markers. In summary, this study reveals the therapeutic promise of J147 in mitigating secondary brain damage associated with TBI and improving long-term functional recovery by modulating ER stress pathways.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"274 ","pages":"Pages 21-34"},"PeriodicalIF":6.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157085","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)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}