RESUMO
IGFBP7 has been found to play an important role in inflammatory diseases, such as acute lung injury (ALI). However, the role of IGFBP7 in different stages of inflammation remains unclear. Transcriptome sequencing was used to identify the regulatory genes of IGFBP7, and endothelial IGFBP7 expression was knocked down using Aplnr-Dre mice to evaluate the endothelial proliferation capacity. The expression of proliferation-related genes was detected by Western blotting and RT-PCR assays. In the present study, we found that knockdown of IGFBP7 in endothelial cells significantly decreases the expression of endothelial cell proliferation-related genes and cell number in the recovery phase but not in the acute phase of ALI. Mechanistically, using bulk-RNA sequencing and CO-IP, we found that IGFBP7 promotes phosphorylation of FOS and subsequently up-regulates YAP1 molecules, thereby promoting endothelial cell proliferation. This study indicated that IGFBP7 has diverse roles in different stages of ALI, which extends the understanding of IGFBP7 in different stages of ALI and suggests that IGFBP7 as a potential therapeutic target in ALI needs to take into account the period specificity of ALI.
Assuntos
Lesão Pulmonar Aguda , Proliferação de Células , Células Endoteliais , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Animais , Humanos , Camundongos , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de Sinais , Proteínas de Sinalização YAP/metabolismoRESUMO
Chlamydia psittaci infection in humans, also known as psittacosis, is usually believed to be an uncommon disease which mainly presents as community-acquired pneumonia (CAP). It is usually sporadic, but outbreaks of infection may occasionally occur. In outbreaks, diagnosis and investigations were usually hampered by the non-specificity of laboratory testing methods to identify C. psittaci. In this study, we use metagenomic next-generation sequencing (mNGS) in the diagnosis of a family outbreak of psittacosis under COVID-19. Three members of an extended family of 6 persons developed psittacosis with pneumonia and hepatic involvement with common symptoms of fever and weakness. Two newly purchased pet parrots, which had died successively, were probably the primary source of infection. Imagings show lung consolidations and infiltrates, which are difficult to be differentiated from CAP caused by other common pathogens. mNGS rapidly identified the infecting agent as C. psittaci within 48â h. The results of this work suggest that there are not characteristic clinical manifestations and imagings of psittacosis pneumonia which can differentiate from CAP caused by other pathogens. The use of mNGS can improve accuracy and reduce the delay in the diagnosis of psittacosis especially during the outbreak, which can shorten the course of the disease control. Family outbreak under COVID-19 may be related to the familial aggregation due to the epidemic. To our knowledge, this is the first reported family outbreak of psittacosis in China, and the first reported psittacosis outbreak identified by the method of mNGS in the world.
Assuntos
Chlamydophila psittaci/genética , Família , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Pneumonia/microbiologia , Psitacose/diagnóstico por imagem , Adulto , Idoso , Animais , COVID-19/epidemiologia , China/epidemiologia , Chlamydophila psittaci/isolamento & purificação , Surtos de Doenças , Feminino , Humanos , Masculino , Metagenoma , Pessoa de Meia-Idade , Papagaios/microbiologia , Pneumonia/diagnóstico por imagem , Psitacose/microbiologia , Psitacose/transmissão , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Reliable brain protection during aortic arch surgery remains a formidable surgical challenge. Various cerebral protection techniques have been used in the clinic; however, there is no consensus regarding which strategy is best. We will perform a network meta-analysis (NMA) focusing on the permanent neurological deficits (PND) and perioperative mortality associated with 4 major brain protection strategies used during aortic arch surgery. METHODS: We will perform a literature search of MEDLINE, EMBASE, Cochrane Library, and PubMed databases. The primary outcomes of interest in this analysis will be PND and perioperative mortality. Inconsistencies in the NMA will be evaluated with global and local approaches. Network rank and surface under the cumulative ranking curve (SUCRA) analyses will be performed to evaluate and identify the superiority of different brain protection techniques. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for consideration of publication. CONCLUSIONS: Our study will increase understanding of 4 major brain protection strategies during aortic arch surgery and be helpful to clinicians using NMA in their studies.