Clinical science最新文献_第5页

Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope® Diagnostic System (MMDx). 利用芯片评估基因表达对移植器官进行精确诊断：分子显微镜®诊断系统（MMDx）的概念和技术方法。

IF 6 2区医学

Clinical science Pub Date : 2024-06-05 DOI: 10.1042/CS20220530

Katelynn S Madill-Thomsen, Philip F Halloran

{"title":"Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope® Diagnostic System (MMDx).","authors":"Katelynn S Madill-Thomsen, Philip F Halloran","doi":"10.1042/CS20220530","DOIUrl":"10.1042/CS20220530","url":null,"abstract":"There is a major unmet need for improved accuracy and precision in the assessment of transplant rejection and tissue injury. Diagnoses relying on histologic and visual assessments demonstrate significant variation between expert observers (as represented by low kappa values) and have limited ability to assess many biological processes that produce little histologic changes, for example, acute injury. Consensus rules and guidelines for histologic diagnosis are useful but may have errors. Risks of over- or under-treatment can be serious: many therapies for transplant rejection or primary diseases are expensive and carry risk for significant adverse effects. Improved diagnostic methods could alleviate healthcare costs by reducing treatment errors, increase treatment efficacy, and serve as useful endpoints for clinical trials of new agents that can improve outcomes. Molecular diagnostic assessments using microarrays combined with machine learning algorithms for interpretation have shown promise for increasing diagnostic precision via probabilistic assessments, recalibrating standard of care diagnostic methods, clarifying ambiguous cases, and identifying potentially missed cases of rejection. This review describes the development and application of the Molecular Microscope® Diagnostic System (MMDx), and discusses the history and reasoning behind many common methods, statistical practices, and computational decisions employed to ensure that MMDx scores are as accurate and precise as possible. MMDx provides insights on disease processes and highly reproducible results from a comparatively small amount of tissue and constitutes a general approach that is useful in many areas of medicine, including kidney, heart, lung, and liver transplants, with the possibility of extrapolating lessons for understanding native organ disease states.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 11","pages":"663-685"},"PeriodicalIF":6.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11147747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178807","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

Is endothelin targeting finally ready for prime time? 内皮素靶向疗法终于准备好进入黄金时代了吗？

IF 6 2区医学

Clinical science Pub Date : 2024-06-05 DOI: 10.1042/CS20240607

Francesca Schinzari, Manfredi Tesauro, Carmine Cardillo

{"title":"Is endothelin targeting finally ready for prime time?","authors":"Francesca Schinzari, Manfredi Tesauro, Carmine Cardillo","doi":"10.1042/CS20240607","DOIUrl":"10.1042/CS20240607","url":null,"abstract":"The endothelin family of peptides has long been recognized as a physiological regulator of diverse biological functions and mechanistically involved in various disease states, encompassing, among others, the cardiovascular system, the kidney, and the nervous system. Pharmacological blockade of the endothelin system, however, has encountered strong obstacles in its entry into the clinical mainstream, having obtained only a few proven indications until recently. This translational gap has been attributable predominantly to the relevant side effects associated with endothelin receptor antagonism (ERA), particularly fluid retention. Of recent, however, an expanding understanding of the pathophysiological processes involving endothelin, in conjunction with the development of new antagonists of endothelin receptors or adjustment of their doses, has driven a flourish of new clinical trials. The favorable results of some of them have extended the proven indications for ET targeting to a variety of clinical conditions, including resistant arterial hypertension and glomerulopathies. In addition, on the ground of strong preclinical evidence, other studies are ongoing to test the potential benefits of ERA in combination with other treatments, such as sodium-glucose co-transporter 2 inhibition in fluid retentive states or anti-cancer therapies in solid tumors. Furthermore, antibodies providing long-term blockade of endothelin receptors are under testing to overcome the short half-life of most small molecule endothelin antagonists. These efforts may yet bring new life to the translation of endothelin targeting strategies in clinical practice.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 11","pages":"635-644"},"PeriodicalIF":6.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086914","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

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":" ","pages":"573-597"},"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 6.7 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":" ","pages":"599-614"},"PeriodicalIF":6.7,"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

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

The complement system in neurodegenerative diseases. 神经退行性疾病中的补体系统。

IF 6.7 2区医学

Clinical science Pub Date : 2024-03-20 DOI: 10.1042/CS20230513

Jacqui Nimmo, Robert A J Byrne, Nikoleta Daskoulidou, Lewis M Watkins, Sarah M Carpanini, Wioleta M Zelek, B Paul Morgan

{"title":"The complement system in neurodegenerative diseases.","authors":"Jacqui Nimmo, Robert A J Byrne, Nikoleta Daskoulidou, Lewis M Watkins, Sarah M Carpanini, Wioleta M Zelek, B Paul Morgan","doi":"10.1042/CS20230513","DOIUrl":"10.1042/CS20230513","url":null,"abstract":"Complement is an important component of innate immune defence against pathogens and crucial for efficient immune complex disposal. These core protective activities are dependent in large part on properly regulated complement-mediated inflammation. Dysregulated complement activation, often driven by persistence of activating triggers, is a cause of pathological inflammation in numerous diseases, including neurological diseases. Increasingly, this has become apparent not only in well-recognized neuroinflammatory diseases like multiple sclerosis but also in neurodegenerative and neuropsychiatric diseases where inflammation was previously either ignored or dismissed as a secondary event. There is now a large and rapidly growing body of evidence implicating complement in neurological diseases that cannot be comprehensively addressed in a brief review. Here, we will focus on neurodegenerative diseases, including not only the 'classical' neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, but also two other neurological diseases where neurodegeneration is a neglected feature and complement is implicated, namely, schizophrenia, a neurodevelopmental disorder with many mechanistic features of neurodegeneration, and multiple sclerosis, a demyelinating disorder where neurodegeneration is a major cause of progressive decline. We will discuss the evidence implicating complement as a driver of pathology in these diverse diseases and address briefly the potential and pitfalls of anti-complement drug therapy for neurodegenerative diseases.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 6","pages":"387-412"},"PeriodicalIF":6.7,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173982","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