Shanshan Yuan , Shicheng Li , Jiangwen Ruan , Hui Liu , Tongmeng Jiang , Hongyan Dai
{"title":"Chronic kidney disease and pulmonary hypertension: Progress in diagnosis and treatment","authors":"Shanshan Yuan , Shicheng Li , Jiangwen Ruan , Hui Liu , Tongmeng Jiang , Hongyan Dai","doi":"10.1016/j.trsl.2024.06.003","DOIUrl":"10.1016/j.trsl.2024.06.003","url":null,"abstract":"<div><p>Pulmonary hypertension (PH) is a medical condition characterized by elevated pulmonary vascular resistance and pressure, resulting from different diseases. Due to their high occurrence of PH, intricate hemodynamic classification, and frequently multifactorial cause and mechanism, individuals suffering from chronic kidney disease (CKD) are categorized as the fifth primary group of PH. Based on both domestic and international research, this article provides information on the epidemiology, risk factors, pathogenesis, and targeted drug treatment of PH associated with CKD.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 16-22"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500096","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":"Fu's subcutaneous needling promotes axonal regeneration and remyelination by inhibiting inflammation and endoplasmic reticulum stress","authors":"","doi":"10.1016/j.trsl.2024.06.005","DOIUrl":"10.1016/j.trsl.2024.06.005","url":null,"abstract":"<div><p>Fu's subcutaneous needling (FSN) is a traditional Chinese acupuncture procedure used to treat pain-related neurological disorders. Moreover, the regulation of inflammatory cytokines may provide a favorable environment for peripheral nerve regeneration. In light of this, FSN may be an important novel therapeutic strategy to alleviate pain associated with peripheral neuropathy; however, the underlying molecular mechanisms remain unclear. This study revealed that patients who had osteoarthritis with peripheral neuropathic pain significantly recovered after 1 to 2 weeks of FSN treatment according to the visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne index, walking speed, and passive range of motion. Similarly, we demonstrated that FSN treatment in an animal model of chronic constriction injury (CCI) significantly improved sciatic nerve pain using paw withdrawal thresholds, sciatic functional index scores, and compound muscle action potential amplitude tests. In addition, transmission electron microscopy images of sciatic nerve tissue showed that FSN effectively reduced axonal swelling, abnormal myelin sheaths, and the number of organelle vacuoles in CCI-induced animals. Mechanistically, RNA sequencing and gene set enrichment analysis revealed significantly reduced inflammatory pathways, neurotransmitters, and endoplasmic reticulum stress pathways and increased nerve regeneration factors in the FSN+CCI group, compared with that in the CCI group. Finally, immunohistochemistry, immunoblotting and enzyme-linked immunosorbent assay showed similar results in the dorsal root ganglia and sciatic nerve. Our findings suggest that FSN can effectively ameliorate peripheral neuropathic pain by regulate inflammation and endoplasmic reticulum stress, thereby determine its beneficial application in patients with peripheral nerve injuries.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 46-57"},"PeriodicalIF":6.4,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001403/pdfft?md5=2c5061454182dea3971141759123c439&pid=1-s2.0-S1931524424001403-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478321","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}
Yaqin Li , Congwei Luo , Yating Cai , Yan Wu , Tao Shu , Jingyan Wei , Hongsheng Wang , Hongxin Niu
{"title":"IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability","authors":"Yaqin Li , Congwei Luo , Yating Cai , Yan Wu , Tao Shu , Jingyan Wei , Hongsheng Wang , Hongxin Niu","doi":"10.1016/j.trsl.2024.06.004","DOIUrl":"10.1016/j.trsl.2024.06.004","url":null,"abstract":"<div><p>Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852–1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence <em>in vitro</em>. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing m<sup>6</sup>A modification. Specifically, IGF2BP3 recognizes m<sup>6</sup>A motif \"GGACU\" at nucleotides 110–114 in the 5′ untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 1-15"},"PeriodicalIF":6.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001397/pdfft?md5=de1575c53236bca4b9caeb4c665f7a63&pid=1-s2.0-S1931524424001397-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474264","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}
Jiang Wang , Xinyue Peng , Nan Yuan , Bin Wang , Siyu Chen , Bo Wang , Lixin Xie
{"title":"Interplay between pulmonary epithelial stem cells and innate immune cells contribute to the repair and regeneration of ALI/ARDS","authors":"Jiang Wang , Xinyue Peng , Nan Yuan , Bin Wang , Siyu Chen , Bo Wang , Lixin Xie","doi":"10.1016/j.trsl.2024.05.012","DOIUrl":"10.1016/j.trsl.2024.05.012","url":null,"abstract":"<div><p>Mammalian lung is the important organ for ventilation and exchange of air and blood. Fresh air and venous blood are constantly delivered through the airway and vascular tree to the alveolus. Based on this, the airways and alveolis are persistently exposed to the external environment and are easily suffered from toxins, irritants and pathogens. For example, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common cause of respiratory failure in critical patients, whose typical pathological characters are diffuse epithelial and endothelial damage resulting in excessive accumulation of inflammatory fluid in the alveolar cavity. The supportive treatment is the main current treatment for ALI/ARDS with the lack of targeted effective treatment strategies. However, ALI/ARDS needs more targeted treatment measures. Therefore, it is extremely urgent to understand the cellular and molecular mechanisms that maintain alveolar epithelial barrier and airway integrity. Previous researches have shown that the lung epithelial cells with tissue stem cell function have the ability to repair and regenerate after injury. Also, it is able to regulate the phenotype and function of innate immune cells involving in regeneration of tissue repair. Meanwhile, we emphasize that interaction between the lung epithelial cells and innate immune cells is more supportive to repair and regenerate in the lung epithelium following acute lung injury. We reviewed the recent advances in injury and repair of lung epithelial stem cells and innate immune cells in ALI/ARDS, concentrating on alveolar type 2 cells and alveolar macrophages and their contribution to post-injury repair behavior of ALI/ARDS through the latest potential molecular communication mechanisms. This will help to develop new research strategies and therapeutic targets for ALI/ARDS.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Pages 111-125"},"PeriodicalIF":6.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428634","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}
Sara G. Pelaz , Raquel Flores-Hernández , Tatjana Vujic , Domitille Schvartz , Andrea Álvarez-Vázquez , Yuxin Ding , Laura García-Vicente , Aitana Belloso , Rocío Talaverón , Jean-Charles Sánchez , Arantxa Tabernero
{"title":"A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma","authors":"Sara G. Pelaz , Raquel Flores-Hernández , Tatjana Vujic , Domitille Schvartz , Andrea Álvarez-Vázquez , Yuxin Ding , Laura García-Vicente , Aitana Belloso , Rocío Talaverón , Jean-Charles Sánchez , Arantxa Tabernero","doi":"10.1016/j.trsl.2024.06.001","DOIUrl":"10.1016/j.trsl.2024.06.001","url":null,"abstract":"<div><p>Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43<sub>266-283</sub>, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43<sub>266-283</sub>. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43<sub>266-283</sub> and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43<sub>266-283</sub> may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43<sub>266-283</sub> correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43<sub>266-283</sub> correlated with shorter survival, supporting its use in clinical trials.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Pages 95-110"},"PeriodicalIF":6.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001154/pdfft?md5=4420ed4d791a6c241a0b541ae23d1554&pid=1-s2.0-S1931524424001154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141322278","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}