Clinical science最新文献_第3页

Endothelin and the tumor microenvironment: a finger in every pie. 内皮素与肿瘤微环境：各取所需

IF 6 2区医学

Clinical science Pub Date : 2024-06-05 DOI: 10.1042/CS20240426

Philipp F Arndt, Kati Turkowski, Michael J Cekay, Bastian Eul, Friedrich Grimminger, Rajkumar Savai

引用次数: 0

Speaker's Abstract Lectures. 演讲者的演讲摘要。

IF 6 2区医学

Clinical science Pub Date : 2024-05-28 DOI: 10.1042/CS2023ET18

引用次数: 0

Report on the 18th International Conference on Endothelin, October 11th - 14th 2023. 第 18 届内皮素国际会议报告，2023 年 10 月 11 - 14 日。

IF 6.7 2区医学

Clinical science Pub Date : 2024-05-28 DOI: 10.1042/CS2023ET18-MR

Carmine Cardillo

引用次数: 0

Retraction: Prader-Willi region non-protein coding RNA 1 suppressed gastric cancer growth as a competing endogenous RNA of miR-425-5p. 撤回：Prader-Willi区域非蛋白编码RNA 1作为miR-425-5p的竞争内源RNA抑制胃癌生长

IF 6 2区医学

Clinical science Pub Date : 2024-05-22 DOI: 10.1042/CS-2017-1588_RET

引用次数: 0

Striatin plays a major role in angiotensin II-induced cardiomyocyte and cardiac hypertrophy in mice in vivo. 纹蛋白在血管紧张素 II 诱导的小鼠体内心肌细胞和心脏肥大中发挥着重要作用。

IF 6 2区医学

Clinical science Pub Date : 2024-05-22 DOI: 10.1042/CS20240496

Joshua J Cull, Susanna T E Cooper, Hajed O Alharbi, Sonia P Chothani, Owen J L Rackham, Daniel N Meijles, Philip R Dash, Risto Kerkelä, Neil Ruparelia, Peter H Sugden, Angela Clerk

{"title":"Striatin plays a major role in angiotensin II-induced cardiomyocyte and cardiac hypertrophy in mice in vivo.","authors":"Joshua J Cull, Susanna T E Cooper, Hajed O Alharbi, Sonia P Chothani, Owen J L Rackham, Daniel N Meijles, Philip R Dash, Risto Kerkelä, Neil Ruparelia, Peter H Sugden, Angela Clerk","doi":"10.1042/CS20240496","DOIUrl":"10.1042/CS20240496","url":null,"abstract":"The three striatins (STRN, STRN3, STRN4) form the core of STRiatin-Interacting Phosphatase and Kinase (STRIPAK) complexes. These place protein phosphatase 2A (PP2A) in proximity to protein kinases thereby restraining kinase activity and regulating key cellular processes. Our aim was to establish if striatins play a significant role in cardiac remodelling associated with cardiac hypertrophy and heart failure. All striatins were expressed in control human hearts, with up-regulation of STRN and STRN3 in failing hearts. We used mice with global heterozygote gene deletion to assess the roles of STRN and STRN3 in cardiac remodelling induced by angiotensin II (AngII; 7 days). Using echocardiography, we detected no differences in baseline cardiac function or dimensions in STRN+/- or STRN3+/- male mice (8 weeks) compared with wild-type littermates. Heterozygous gene deletion did not affect cardiac function in mice treated with AngII, but the increase in left ventricle mass induced by AngII was inhibited in STRN+/- (but not STRN3+/-) mice. Histological staining indicated that cardiomyocyte hypertrophy was inhibited. To assess the role of STRN in cardiomyocytes, we converted the STRN knockout line for inducible cardiomyocyte-specific gene deletion. There was no effect of cardiomyocyte STRN knockout on cardiac function or dimensions, but the increase in left ventricle mass induced by AngII was inhibited. This resulted from inhibition of cardiomyocyte hypertrophy and cardiac fibrosis. The data indicate that cardiomyocyte striatin is required for early remodelling of the heart by AngII and identify the striatin-based STRIPAK system as a signalling paradigm in the development of pathological cardiac hypertrophy.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891636","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}

引用次数: 0

miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction. miR-486-5p 可保护大鼠缺血性肾损伤，防止向慢性肾病和血管功能障碍过渡。

IF 6 2区医学

Clinical science Pub Date : 2024-05-22 DOI: 10.1042/CS20231752

Adrianna Douvris, Jose L Viñas, Alexey Gutsol, Joseph Zimpelmann, Dylan Burger, Kevin D Burns

{"title":"miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.","authors":"Adrianna Douvris, Jose L Viñas, Alexey Gutsol, Joseph Zimpelmann, Dylan Burger, Kevin D Burns","doi":"10.1042/CS20231752","DOIUrl":"10.1042/CS20231752","url":null,"abstract":"Aim: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia-reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function.Methods: Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography.Results: In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (P<0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (P<0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (P<0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (P<0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function.Conclusion: In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915919","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}

引用次数: 0

Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: Implications for epileptogenesis and epilepsy. 脾脏参与皮质激素诱发癫痫状态后的神经炎症：对癫痫发生和癫痫的影响。

IF 6 2区医学

Clinical science Pub Date : 2024-04-11 DOI: 10.1042/CS20231621

Paula V Sarchi, Dante D Gomez Cuautle, Alicia Rossi, Alberto Javier Ramos

{"title":"Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: Implications for epileptogenesis and epilepsy.","authors":"Paula V Sarchi, Dante D Gomez Cuautle, Alicia Rossi, Alberto Javier Ramos","doi":"10.1042/CS20231621","DOIUrl":"https://doi.org/10.1042/CS20231621","url":null,"abstract":"Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions of individuals worldwide. Despite extensive research, the underlying mechanisms leading to epileptogenesis, the process by which a normal brain develops epilepsy, remain elusive. We here explored the immune system and spleen responses triggered by pilocarpine-induced status epilepticus (SE) focusing on their role in the epileptogenesis that follows SE . Initial examination of spleen histopathology revealed transient disorganization of white pulp, in animals subjected to SE. This disorganization, attributed to immune activation, peaked at 1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheral blood lymphocyte populations, demonstrated a decrease following SE, accompanied by a reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundance of T-lymphocytes in the pyriform cortex and choroid plexus at 3DPSE, suggesting a specific mobilization towards the Central Nervous System. Notably, splenectomy mitigated brain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularly in the hippocampus and piriform cortex. Additionally, splenectomized animals exhibited reduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomy correlated with improved neuronal survival, substantiated by decreased neuronal loss and reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE. Overall, these findings underscore the pivotal role of the spleen in orchestrating immune responses and neuroinflammation following pilocarpine-induced SE, implicating the peripheral immune system as a potential therapeutic target for mitigating neuronal degeneration in epilepsy.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140715346","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}

引用次数: 0

Correction: The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. 更正：SARS-CoV-2 Spike 蛋白通过 CD147 受体介导的信号干扰人类心脏周细胞功能：COVID-19 微血管疾病的潜在非感染机制。

IF 6 2区医学

Clinical science Pub Date : 2024-04-10 DOI: 10.1042/CS-2021-0735_COR

引用次数: 0

Alveolar epithelial cells of lung fibrosis patients are susceptible to severe virus-induced injury. 肺纤维化患者的肺泡上皮细胞易受病毒引起的严重损伤。

IF 6 2区医学

Clinical science Pub Date : 2024-04-05 DOI: 10.1042/CS20240220

Jane Read, Andrew Reid, Claire Thomson, Marshall Plit, Ross Mejia, Darryl A. Knight, Muriel Lize, K. E. Kasmi, C. Grainge, Heiko Stahl, Michael Schuliga

{"title":"Alveolar epithelial cells of lung fibrosis patients are susceptible to severe virus-induced injury.","authors":"Jane Read, Andrew Reid, Claire Thomson, Marshall Plit, Ross Mejia, Darryl A. Knight, Muriel Lize, K. E. Kasmi, C. Grainge, Heiko Stahl, Michael Schuliga","doi":"10.1042/CS20240220","DOIUrl":"https://doi.org/10.1042/CS20240220","url":null,"abstract":"Patients with pulmonary fibrosis (PF) often experience exacerbations of their disease, characterised by a rapid, severe deterioration in lung function that is associated with high mortality. Whilst the pathobiology of such exacerbations is poorly understood, virus infection is a trigger. This study investigated virus-induced injury responses of alveolar and bronchial epithelial cells (AECs and BECs respectively) from patients with PF and age-matched controls (Ctrls). Air liquid interface (ALI) cultures of AECs, comprising type I and II pneumocytes or BECs were inoculated with influenza A virus (H1N1) at 0.1 multiplicity of infection (MOI). Levels of interleukin-6 (IL-6), IL-36γ and IL-1β were elevated in cultures of AECs from PF patients (PF-AECs, n=8-11), being markedly higher than Ctrl-AECs (n=5-6), 48 h post inoculation (pi) (P<0.05); despite no difference in H1N1 RNA copy numbers 24 h pi. Furthermore, the virus-induced inflammatory responses of PF-AECs were greater than BECs (from either PF patients or controls), even though viral loads in the BECs were overall 2 to 3-fold higher than AECs. Baseline levels of the senescence and DNA damage markers, nuclear p21, p16 and H2AXγ were also significantly higher in PF-AECs than Ctrl-AECs and further elevated post-infection. Senescence induction using etoposide augmented virus-induced injuries in AECs (but not viral load), whereas selected senotherapeutics (rapamycin and mitoTEMPO) were protective. This study provides evidence that senescence increases the susceptibility of AECs from PF patients to severe virus-induced injury and suggests targeting senescence may provide an alternative option to prevent or treat the exacerbations that worsen the underlying disease.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738630","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}

引用次数: 0

Inflammatory liver diseases and susceptibility to sepsis. 炎症性肝病与败血症的易感性。

IF 6 2区医学

Clinical science Pub Date : 2024-04-01 DOI: 10.1042/CS20230522

Hong Lu

{"title":"Inflammatory liver diseases and susceptibility to sepsis.","authors":"Hong Lu","doi":"10.1042/CS20230522","DOIUrl":"https://doi.org/10.1042/CS20230522","url":null,"abstract":"Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140773269","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}

引用次数: 0