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1.
Hepatology ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662438

RESUMO

BACKGROUND & AIMS: Ischemia reperfusion (I/R) injury is an inevitable complication of liver transplantation and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain largely unknown in hepatic I/R injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-Acetylgalactosaminyltransferase-4 (GALNT4), in hepatic I/R injury. APPROACH & RESULTS: Via an RNA-seq data-based correlation analysis, we found a close correlation between GALNT4 expression and hepatic I/R-related molecular events in murine model. The mRNA and protein expression of GALNT4 were markedly upregulated upon reperfusion surgery in both clinical samples from subjects underwent liver transplantation and mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to the apoptosis signal-regulating kinase1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of the downstream c-Jun N-terminal kinase (JNK) / p38 and nuclear factor kappa B (NF-κB) signalling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improve liver surgery prognosis by inactivating ASK1-JNK/p38 signalling pathway.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34299810

RESUMO

When facing an infectious disease disaster, nurses' willingness to work is critical. Nurses' lack of willingness to work during a pandemic may worsen the shortage of health care personnel. The purpose of this study is to assess the willingness of nurses to participate in the fight against COVID-19 in China and to identify factors associated therewith. This cross-sectional study examines nurses working in 11 Chinese cities including Macau, Hong Kong, Shenzhen, Dongguan, Huizhou, Guangzhou, Zhaoqing, Foshan, Jiangmen, Zhongshan, and Zhuhai. Questionnaires were collected from 19 May to 7 August 2020. A total of 8065 questionnaires were received, of which 8030 valid questionnaires were included for analysis. A total of 53.4% of participants reported that they had signed up to support the COVID-19 pandemic response. Multivariate logistic regression analysis revealed that being single (OR = 0.72, 95% CI: 0.60-0.87), having no children (OR = 0.81, 95% CI: 0.68-0.97), possessing higher professional qualifications (OR = 1.25, 95% CI: 1.14-1.37), having a more prestigious professional title (OR = 1.68, 95%CI: 1.50-1.90), being an administrative supervisor (OR = 0.53, 95% CI: 0.45-0.63), having a higher caring dimensions inventory score (OR = 1.01, 95% CI: 1.01-1.01), working in a hospital (OR = 0.53, 95% CI: 0.39-0.72), and receiving employer-provided care training (OR = 0.77, 95% CI: 0.68-0.87) were predictive of nurses' willingness to participate in the fight against COVID-19. We suggest that unmarried nurses should be given priority when recruiting to fight an epidemic and, for married nurses with children who are recruited to fight an epidemic, supporting measures should be provided for childcare. We suggest strengthening workplace training of caring for nurses in order to better retain and recruit qualified support for an epidemic outbreak of infectious diseases.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Criança , China , Estudos Transversais , Hong Kong , Humanos , Macau , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
3.
Artigo em Inglês | MEDLINE | ID: mdl-34202158

RESUMO

Caring is central to nursing practice. Chinese nurses take care for the health of about 20% of the world's population and their perception of caring is critical. However, until recently, instrument specifically designed to measure the caring of nurses in China was not found. Caring dimensions inventory (CDI) is one of the most frequently used instrument when measuring caring and is applicable to nurses from different cultures. The aim of this study is to test the validity and reliability of the Chinese version of the 25-item CDI. The English version of CDI was translated into Chinese according to the guidelines of the World Health Organization. Content validity was conducted among seven senior nurses from different institutions in different cities in China. A convenience sample of nurses from 11 cities in China was employed. Exploratory factor analysis and confirmatory factor analysis of the CDI was carried out using a sample of 880 nurses. The overall content validity index was 0.98. Three factors (Nurturance, Collaboration, Skill) were identified in exploratory factor analysis and were confirmed by confirmatory factor analysis. The three-factor solution explains 70.15% of the total variance. The Cronbach alpha for overall the CDI was 0.97. This study demonstrated that the Chinese version of the CDI showed satisfactory reliability and validity, indicating that it could be a useful measurement to assess nurses' perception of caring in China.


Assuntos
Reprodutibilidade dos Testes , China , Análise Fatorial , Humanos , Psicometria , Inquéritos e Questionários
4.
Hepatology ; 74(3): 1319-1338, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33894019

RESUMO

BACKGROUND AND AIMS: NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms. METHODS AND RESULTS: In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition. CONCLUSION: SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

5.
Appl Microbiol Biotechnol ; 101(14): 5913-5923, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28523397

RESUMO

To investigate the differences in the microbial community composition and assembly process in two lake zones (Meiliang Bay (MLB) and Xukou Bay (XKB) in Taihu Lake, China) with different nutrient loadings, water samples were collected. Both the 16S ribosomal RNA (rRNA) gene for the bacterial community and the 18S rRNA gene for the microeukaryote community were investigated using the Illumina second-generation sequencing platform (2 × 250 paired-end). The results indicated that both the bacterioplankton and microeukaryote community composition derived from the two lake zones were significantly different. Significantly higher operational taxonomic unit (OTU) richness (P < 0.01) and phylogenetic diversity (P < 0.05) were found for the bacterioplankton community of MLB. However, a comparable alpha diversity was found between the microeukaryote communities of MLB and XKB (P > 0.05). Environmental factors significantly affected the community compositions in XKB for both the bacterioplankton and microeukaryotes. However, they did not significantly influence the microbial community composition in MLB, except for a weak correlation between dissolved organic carbon (DOC) and the microeukaryote community. The microbial communities tended to be more phylogenetically clustered than expected by chance in the two lake zones. Moreover, the results of the phylogenetic structure suggest that deterministic processes played overwhelming roles in driving the assembly of both the bacterioplankton and microeukaryote community in XKB.


Assuntos
Bactérias/classificação , Lagos/microbiologia , Consórcios Microbianos , Microbiologia da Água , Bactérias/genética , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , Biodiversidade , China , Ecossistema , Eucariotos/classificação , Eucariotos/genética , Eucariotos/isolamento & purificação , Filogenia , Plâncton , RNA Ribossômico 16S/genética , RNA Ribossômico 18S
6.
Acta Pharmacol Sin ; 38(1): 146-155, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27917874

RESUMO

The homomeric α7 nicotinic receptor (α7 nAChR) is widely expressed in the human brain that could be activated to suppress neuroinflammation, oxidative stress and neuropathic pain. Consequently, a number of α7 nAChR agonists have entered clinical trials as anti-Alzheimer's or anti-psychotic therapies. However, high-resolution crystal structure of the full-length α7 receptor is thus far unavailable. Since acetylcholine-binding protein (AChBP) from Lymnaea stagnalis is most closely related to the α-subunit of nAChRs, it has been used as a template for the N-terminal domain of α-subunit of nAChR to study the molecular recognition process of nAChR-ligand interactions, and to identify ligands with potential nAChR-like activities.Here we report the discovery and optimization of novel acetylcholine-binding protein ligands through screening, structure-activity relationships and structure-based design. We manually screened in-house CNS-biased compound library in vitro and identified compound 1, a piperidine derivative, as an initial hit with moderate binding affinity against AChBP (17.2% inhibition at 100 nmol/L). During the 1st round of optimization, with compound 2 (21.5% inhibition at 100 nmol/L) as the starting point, 13 piperidine derivatives with different aryl substitutions were synthesized and assayed in vitro. No apparent correlation was demonstrated between the binding affinities and the steric or electrostatic effects of aryl substitutions for most compounds, but compound 14 showed a higher affinity (Ki=105.6 nmol/L) than nicotine (Ki=777 nmol/L). During the 2nd round of optimization, we performed molecular modeling of the putative complex of compound 14 with AChBP, and compared it with the epibatidine-AChBP complex. The results suggested that a different piperidinyl substitution might confer a better fit for epibatidine as the reference compound. Thus, compound 15 was designed and identified as a highly affinitive acetylcholine-binding protein ligand. In this study, through two rounds of optimization, compound 15 (Ki=2.8 nmol/L) has been identified as a novel, piperidine-based acetylcholine-binding protein ligand with a high affinity.


Assuntos
Proteínas de Transporte/química , Ligantes , Piperidinas/química , Piperidinas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteínas de Transporte/metabolismo , Desenho de Fármacos , Modelos Moleculares , Simulação de Acoplamento Molecular , Nicotina/farmacologia , Piperidinas/síntese química , Piridinas/farmacologia , Ensaio Radioligante , Relação Estrutura-Atividade
7.
Di Yi Jun Yi Da Xue Xue Bao ; 23(8): 856-8, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12919920

RESUMO

OBJECTIVE: To investigate the understanding of the nurses of different levels concerning Total Quality Control (TQC). METHODS: A total of 198 nurses using stratified random sampling in proportion to the ratio of different levels of the nurses. A questionnaire with approved validity was used in the survey, and the results were statistically analyzed. RESULTS: In terms of basic knowledge of TQC, the scores of assistant nurses the lowest (P<0.05), and the responsible nurses had lower scores than head nurses and nursing officers (P<0.05), while the scores of the nurses whose length of service ranged from 3 to 10 years were lower than those of nurses who had been in service for above 10 years. In terms of TQC common methods, both assistant nurses and responsibility nurses had lower scores than nurses-in-charge, head nurses and nursing officers (P<0.05). The scores of nurses in service for less than 15 years did not significantly differ, but were obviously lower than those of nurses in service for over 15 years. There was no significant difference between the scores of nurses with different academic degrees. CONCLUSION: The TQC knowledge of the nurses are different based on their working levels and length of service.


Assuntos
Conhecimento , Enfermeiras e Enfermeiros , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Controle de Qualidade
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