Translational Research最新文献

{"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}

{"title":"Lactate promotes bone healing by regulating the osteogenesis of bone marrow mesenchymal stem cells through activating Olfr1440","authors":"Tai Wei ,&nbsp;Danning Ma ,&nbsp;Lulu Liu ,&nbsp;Ying Huang ,&nbsp;Xuehui Zhang ,&nbsp;Mingming Xu ,&nbsp;Yan Wei ,&nbsp;Jinqi Wei ,&nbsp;Xuliang Deng","doi":"10.1016/j.trsl.2024.07.004","DOIUrl":"10.1016/j.trsl.2024.07.004","url":null,"abstract":"<div><p>Bone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation <em>in vivo</em>. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 78-89"},"PeriodicalIF":6.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001439/pdfft?md5=c5d4a0d60f082c35fa672de2d66a7fa4&pid=1-s2.0-S1931524424001439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750153","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":"Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis","authors":"Francesco Niro ,&nbsp;Soraia Fernandes ,&nbsp;Marco Cassani ,&nbsp;Monica Apostolico ,&nbsp;Jorge Oliver-De La Cruz ,&nbsp;Daniel Pereira-Sousa ,&nbsp;Stefania Pagliari ,&nbsp;Vladimir Vinarsky ,&nbsp;Zbyněk Zdráhal ,&nbsp;David Potesil ,&nbsp;Vaclav Pustka ,&nbsp;Giulio Pompilio ,&nbsp;Elena Sommariva ,&nbsp;Davide Rovina ,&nbsp;Angela Serena Maione ,&nbsp;Luca Bersanini ,&nbsp;Malin Becker ,&nbsp;Marco Rasponi ,&nbsp;Giancarlo Forte","doi":"10.1016/j.trsl.2024.07.003","DOIUrl":"10.1016/j.trsl.2024.07.003","url":null,"abstract":"<div><p>Cardiac fibrosis occurs following insults to the myocardium and is characterized by the abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte contractile activity and eventually leads to heart failure. This phenomenon is driven by the activation of cardiac fibroblasts (cFbs) to myofibroblasts and results in changes in ECM biochemical, structural and mechanical properties. The lack of predictive <em>in vitro</em> models of heart fibrosis has so far hampered the search for innovative treatments, as most of the cellular-based <em>in vitro</em> reductionist models do not take into account the leading role of ECM cues in driving the progression of the pathology. Here, we devised a single-step decellularization protocol to obtain and thoroughly characterize the biochemical and micro-mechanical properties of the ECM secreted by activated cFbs differentiated from human induced pluripotent stem cells (iPSCs). We activated iPSC-derived cFbs to the myofibroblast phenotype by tuning basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF-β1) signalling and confirmed that activated cells acquired key features of myofibroblast phenotype, like SMAD2/3 nuclear shuttling, the formation of aligned alpha-smooth muscle actin (α−SMA)-rich stress fibres and increased focal adhesions (FAs) assembly. Next, we used Mass Spectrometry, nanoindentation, scanning electron and confocal microscopy to unveil the characteristic composition and the visco-elastic properties of the abundant, collagen-rich ECM deposited by cardiac myofibroblasts <em>in vitro</em>. Finally, we demonstrated that the fibrotic ECM activates mechanosensitive pathways in iPSC-derived cardiomyocytes, impacting on their shape, sarcomere assembly, phenotype, and calcium handling properties. We thus propose human bio-inspired decellularized matrices as animal-free, isogenic cardiomyocyte culture substrates recapitulating key pathophysiological changes occurring at the cellular level during cardiac fibrosis.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 58-77"},"PeriodicalIF":6.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001440/pdfft?md5=776bb9b06c146f8fdff2caffc3b1b0d6&pid=1-s2.0-S1931524424001440-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716264","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":"A multi-biomarker panel for predicting Tocilizumab response in Rheumatoid arthritis patients","authors":"Ara Cho ,&nbsp;Jinsung Ahn ,&nbsp;Andrew Kim ,&nbsp;Yun Jong Lee ,&nbsp;Yeong Wook Song ,&nbsp;Yoshiya Tanaka ,&nbsp;Eugene C. Yi","doi":"10.1016/j.trsl.2024.07.001","DOIUrl":"10.1016/j.trsl.2024.07.001","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (<em>N</em> = 70) and a test set (<em>N</em> = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 23-31"},"PeriodicalIF":6.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556370","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":"An optimal promoter regulating cytokine transgene expression is crucial for safe and effective oncolytic virus immunotherapy","authors":"Hirotaka Kawakami ,&nbsp;Nobuhiro Ijichi ,&nbsp;Yuki Obama ,&nbsp;Eriko Matsuda ,&nbsp;Kaoru Mitsui ,&nbsp;Yuya Nishikawaji ,&nbsp;Maki Watanabe ,&nbsp;Satoshi Nagano ,&nbsp;Noboru Taniguchi ,&nbsp;Setsuro Komiya ,&nbsp;Ken-ichiro Kosai","doi":"10.1016/j.trsl.2024.07.002","DOIUrl":"10.1016/j.trsl.2024.07.002","url":null,"abstract":"<div><p>In general, ensuring safety is the top priority of a new modality. Although oncolytic virus armed with an immune stimulatory transgene (OVI) showed some promise, the strategic concept of simultaneously achieving maximum effectiveness and minimizing side effects has not been fully explored. We generated a variety of survivin-responsive “conditionally replicating adenoviruses that can target and treat cancer cells with multiple factors (m-CRAs)” (Surv.m-CRAs) armed with the granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene downstream of various promoters using our m-CRA platform technology. We carefully analyzed both therapeutic and adverse effects of them in the <em>in vivo</em> syngeneic Syrian hamster cancer models. Surprisingly, an intratumor injection of a conventional OVI, which expresses the GM-CSF gene under the constitutively and strongly active “cytomegalovirus enhancer and β-actin promoter”, provoked systemic and lethal GM-CSF circulation and shortened overall survival (OS). In contrast, a new conceptual type of OVI, which expressed GM-CSF under the cancer-predominant and mildly active E2F promoter or the moderately active “Rous sarcoma virus long terminal repeat”, not only abolished lethal adverse events but also prolonged OS and systemic anti-cancer immunity. Our study revealed a novel concept that optimal expression levels of an immune stimulatory transgene regulated by a suitable upstream promoter is crucial for achieving high safety and maximal therapeutic effects simultaneously in OVI therapy. These results pave the way for successful development of the next-generation OVI and alert researchers about possible problems with ongoing clinical trials.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"273 ","pages":"Pages 32-45"},"PeriodicalIF":6.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424001427/pdfft?md5=16232ad1cdac9dc88bbf20b26021ba9b&pid=1-s2.0-S1931524424001427-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141539141","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":"Chronic kidney disease and pulmonary hypertension: Progress in diagnosis and treatment","authors":"Shanshan Yuan ,&nbsp;Shicheng Li ,&nbsp;Jiangwen Ruan ,&nbsp;Hui Liu ,&nbsp;Tongmeng Jiang ,&nbsp;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}

{"title":"IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability","authors":"Yaqin Li ,&nbsp;Congwei Luo ,&nbsp;Yating Cai ,&nbsp;Yan Wu ,&nbsp;Tao Shu ,&nbsp;Jingyan Wei ,&nbsp;Hongsheng Wang ,&nbsp;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 m⁶A modification. Specifically, IGF2BP3 recognizes m⁶A 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}

{"title":"Interplay between pulmonary epithelial stem cells and innate immune cells contribute to the repair and regeneration of ALI/ARDS","authors":"Jiang Wang ,&nbsp;Xinyue Peng ,&nbsp;Nan Yuan ,&nbsp;Bin Wang ,&nbsp;Siyu Chen ,&nbsp;Bo Wang ,&nbsp;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}