RESUMO
Diseases of the heart and the kidney, including heart failure and chronic kidney disease, can dramatically impair life expectancy and the quality of life of patients. The heart and kidney form a functional axis; therefore, functional impairment of 1 organ will inevitably affect the function of the other. Fibrosis represents the common final pathway of diseases of both organs, regardless of the disease entity. Thus, inhibition of fibrosis represents a promising therapeutic approach to treat diseases of both organs and to resolve functional impairment. However, despite the growing knowledge in this field, the exact pathomechanisms that drive fibrosis remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized the investigation of pathomechanisms at a molecular level and facilitated the discovery of disease-associated cell types and mechanisms. In this review, we give a brief overview over the evolution of RNA-sequencing techniques, summarize most recent insights into the pathogenesis of heart and kidney fibrosis, and discuss how transcriptomic data can be used, to identify new drug targets and to develop novel therapeutic strategies.
Assuntos
RNA , Insuficiência Renal Crônica , Humanos , RNA/metabolismo , Qualidade de Vida , Rim/metabolismo , Insuficiência Renal Crônica/metabolismo , Fibrose , Miofibroblastos/metabolismoRESUMO
With over 90% of deaths following mushroom ingestion, poisoning with Amatoxin is one of the most dangerous food intoxications. Despite numerous case reports, treatment recommendations are based on a moderate level of evidence due to a lack of randomized controlled trials.We present the case of a 32-year-old patient who presented with acute liver failure after Amanita phalloides (green death cap mushroom) ingestion and whose therapeutic success was significantly influenced by the administration of activated charcoal, silibinin, and N-acetylcysteine as well as the determined research of an external mycologist.In various retrospective studies, a relevant reduction of mortality could be shown by the mentioned medicinal measures. Despite the high estimated amount of ingestion, we could confirm the effectiveness of this combination therapy in this case.Here, in addition to the drug therapy, attention should also be paid to the extraordinary cooperation of a mycologist, who was able to confirm the suspected diagnosis by his investigative approach and thus contributed to the success of the therapy. Immediate contact with the competent poison centre and the involvement of an expert is therefore recommended in unclear situations.
Assuntos
Amanita , Intoxicação Alimentar por Cogumelos , Humanos , Adulto , Estudos Retrospectivos , Intoxicação Alimentar por Cogumelos/complicações , Intoxicação Alimentar por Cogumelos/diagnóstico , Intoxicação Alimentar por Cogumelos/terapia , Florestas , Unidades de Terapia IntensivaRESUMO
Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants. Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19. Results: We observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions. Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.