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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989610

RESUMO

Objective:To study the evolution of Traditional Chinese Medicine (TCM) syndromes of 171 cases of Kawasaki disease (KD) under the intervention of gamma globulin therapy based on factor analysis.Methods:A cross-sectional study. 171 cases of KD children hospitalized in the Department of Cardiology of Guangzhou Women's and Children's Medical Center from July 2019 to December 2020 were collected. All patients were treated with intravenous gamma globulin (2 g/kg) for 1 week. According to the results of the treatment with C-ball, 171 children with C-ball sensitive KD were selected to collect the four diagnostic data, and the representative syndromes of defensive level, qi level, yin level, and nutritive level were observed. Factor analysis was used to analyze the evolution of syndrome in 171 children with KD c-ball sensitivity.Results:The result of factor analysis showed that the KMO statistics of 171 children with c-ball sensitivity before treatment was 0.792, and Bartley test was significant ( P<0.01). 16 common factors were extracted, and 23 syndromes were screened, mainly including defensive level disorder, qi level disorder,nutritive level disorder,yin level disorder, heat stagnation and blood stasis syndrome. One week after treatment, the statistic of KMO test was 0.787, and Bartley test was significant ( P<0.01). 9 common factors were extracted, and 10 syndromes were screened, mainly including qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome. Conclusion:Before treatment, the TCM syndromes in KD C-cell sensitive children are mainly nutritive level disorder, defensive level disorder, qi level disorder yin level disorder, and heat stagnation and blood stasis syndrome; after treatment, the main TCM syndromes are mainly qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome.

2.
Chinese Journal of Epidemiology ; (12): 544-551, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985525

RESUMO

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Doenças em Gêmeos/genética , Hiperlipidemias/genética , Doenças Metabólicas , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
3.
Chinese Journal of Epidemiology ; (12): 536-543, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985524

RESUMO

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.


Assuntos
Adulto , Feminino , Humanos , Masculino , Consumo de Bebidas Alcoólicas , Doenças em Gêmeos/genética , Hipertensão/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
4.
Nat Chem Biol ; 18(11): 1214-1223, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35982226

RESUMO

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.


Assuntos
COVID-19 , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Glutamina/metabolismo , SARS-CoV-2 , Ubiquitinação , Antivirais , Proteínas com Motivo Tripartido/metabolismo
5.
Addict Biol ; 27(2): e13129, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35229938

RESUMO

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.


Assuntos
Fumar Cigarros , Fumar , Adulto , Consumo de Bebidas Alcoólicas/genética , China , Fumar Cigarros/epidemiologia , Fumar Cigarros/genética , Humanos , Masculino , Fatores de Risco , Fumar/genética , Chá , Gêmeos/genética
6.
Chinese Journal of Epidemiology ; (12): 649-654, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935438

RESUMO

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.


Assuntos
Adulto , Humanos , China/epidemiologia , Doença das Coronárias/genética , Doenças em Gêmeos/genética , Estilo de Vida , Gêmeos/genética , Gêmeos Dizigóticos , Gêmeos Monozigóticos
7.
Chinese Journal of Epidemiology ; (12): 641-648, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935437

RESUMO

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , China/epidemiologia , Doença das Coronárias/genética , Doenças em Gêmeos/genética , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
8.
Chinese Journal of Epidemiology ; (12): 634-640, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935436

RESUMO

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Diabetes Mellitus Tipo 2/genética , Doenças em Gêmeos/genética , Sistema de Registros , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
9.
BMJ Open ; 11(8): e046745, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376445

RESUMO

OBJECTIVE: Recently, China has experienced a considerable influence of the COVID-19 pandemic on the local people's health and economy. Hence, the current research aims to investigate the psychological and socioeconomic impact of COVID-19 on rural communities in the Sichuan Province of China. METHODS: A total of 499 participants (village representatives of Sichuan Province) were approached to partake in a cross-sectional online survey and share their experience regarding the ongoing pandemic. The descriptive statistics and ordinary least squares (OLS) regression were used to analyse the data. RESULTS: Our analysis revealed that the pandemic has significantly affected local people psychologically, leading to socioeconomic vulnerability. Notably, we find that local households are worried about their income losses regardless of their socioeconomic status (40%-43%), level of income (37%-43%) and industry involvement (38%-43%). However, as income increases, the level of stress decreases. The results further show that government transfer payment is a significant factor in reducing stress due to its reliable and uninterrupted income flow. Contrary to our proposition, the pandemic stress was less observed, which might be because of people's trust in government and effective antiepidemic countermeasures to contain the disease. CONCLUSION: This study finds that COVID-19 has a significant impact on local people's health, psychology and income. This study is one of the first to provide empirical evidence regarding the early health and socioeconomic effects of COVID-19 at the household level in rural communities, which are very important to devise policies to ease the outbreak and prevent further losses at the local community level.


Assuntos
COVID-19 , Pandemias , China/epidemiologia , Estudos Transversais , Humanos , População Rural , SARS-CoV-2 , Inquéritos e Questionários
10.
PLoS One ; 16(4): e0249270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914745

RESUMO

This paper investigates economic impacts of COVID-19 on households based on differences in the socio-economic status (SES). We determine the household-level effects of the COVID-19 shock using income sources, types of industries, communities' resilience, household susceptibility, and relevant policy measures. For this purpose, we used primary data of 555 households collected through snowball sampling technique using an online survey questionnaire from different villages mostly located in Sichuan Province, China. Using step-wise binary logistic regression analysis, we estimated and validated the model. Results suggest the use of SES as a better measure for understanding the impacts of COVID-19 on different households. We find that households with low SES tend to depend more on farmland income and transfer payments from the government. Contrarily, high SES households focus more on business and local employment as sources of income generation. Poor households were less resilient and more likely to fall back into poverty due to COVID-19, while the opposite stands true for non-poor households with high SES. Based on the estimations, policies encouraging employment and businesses complemented with loans on lower interest rates are recommended, which may increase the SES, thus minimizing vulnerability and enhancing the households' resilience towards poverty alleviation and economic shocks.


Assuntos
COVID-19 , Emprego , Pobreza , COVID-19/epidemiologia , China/epidemiologia , Status Econômico , Características da Família , Humanos , SARS-CoV-2/isolamento & purificação , Classe Social , Fatores Socioeconômicos
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-908838

RESUMO

Objective:To study the application of scenario interaction combined with phased goal teaching method in nursing teaching of cardiovascular medicine.Methods:A total of 55 nursing students who interned in our department before the implementation of scenario interaction combined phased goal teaching method (from September 2017 to February 2019) were randomly selected into control group, and 55 nursing students who had internship in our department after the implementation of the nursing teaching model (from March 2019 to September 2020) were randomly selected as study group. One week before the students leaving the department, the comprehensive ability (theoretical assessment and practical assessment), thinking ability (Critical thinking disposition inventory-Chinese version, CTDI-CV), work satisfaction (Minnesota satisfaction questionnaire, MSQ) and psychological states (Maslach burnout inventory, MBI) were compared between the two groups of intern nursing students. SPSS 19.0 was used for chi-square test and t test. Results:One week before the students leaving the department, the scores of theoretical assessment, practical assessment, CTDI-CV scale, MSQ scale and personal achievement of MBI scale of intern nursing students in study group were higher than those in control group ( P<0.05). The scores of emotional exhaustion and depersonalization tendency of MBI scale in study group were lower than those in control group ( P<0.05). Conclusion:Scenario interaction combined with phased goal teaching method is beneficial to improve the comprehensive ability and job satisfaction, and strengthen the thinking ability and psychological states of intern nursing students.

12.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-056853

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness and death. Currently, there are no specific antiviral drugs that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein and the highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-865537

RESUMO

Objective:To introduce some rare clinical features of the variant Guillain-barre syndrome (GBS) and to explore its possible pathogenesis for the early diagnosis.Methods:The clinical data, laboratory data and treatment outcomes of four patients, who admitted to Shenzhen People′s Hospital from October 2017 to June 2018 and diagnosed with variant GBS were analyzed and summarized.Results:All the four patients presented limb weakness as a first manifestation. However, they all had clinical features that were inconsistent with typical GBS, and the clinical features were shown differently in each patient. One patient showed asymmetrical limb paralysis. The first manifestation of one patient was severe and persistent back pain accompanied by paraplegia. One patient was accompanied by obvious headache and positive meningeal irritation. One patients had the plane of sensory obstacles, paraplegia, and positive pathological sign. Cerebrospinal fluid examination showed protein cell dissociation in four patients. Electromyogram was consistent with peripheral neurogenic damage. Magnetic resonance imaging (MRI) of the brain and the spinal cord showed no obvious abnormalities. The four patients with obvious improvement in symptoms were treated with gamma globulin and glucocorticoid.Conclusions:Variant GBS is rare and clinical symptoms are various. Patients with atypical clinical symptoms should still be diagnosed by relevant auxiliary examinations to avoid delayed illness.

14.
Cell Physiol Biochem ; 52(6): 1398-1411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075190

RESUMO

BACKGROUND/AIMS: Visfatin is known to act as a mediator in several metabolic disorders, such as obesity, diabetes, and cardiovascular diseases. This study aimed to investigate the effect of visfatin on the adhesion of THP-1 monocytes to human vascular endothelial cells and the underlying mechanism. METHODS: Monocytes adhesion to endothelial cells was determined by using fluorescence-labeled monocytes. ICAM-1 and VCAM-1 expression in endothelial cells were measured by western blotting. Production of reactive oxygen species (ROS) was measured by using a fluorescent dye. The amounts of nuclear factor-kappa B (NF-κB) and phosphorylation of inhibitory factor of NF-κB (IκB) were determined by using western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined by using immunofluorescence. RESULTS: Here we showed that visfatin significantly caused the upregulation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, as well as enhanced monocyte adhesion to endothelial cells. Moreover, we found that inhibition of PI3K, Akt, and p38 MAPK activation significantly prevented visfatin-enhanced expression of ICAM-1 and VCAM-1 and monocyte adhesion to endothelial cells. Visfatin enhanced ROS production and IKK/NF-кB activation and then led to upregulation of ICAM-1 and VCAM-1 and enhanced monocyte adhesion to endothelial cells. These effects were also p38/PI3K/Akt-dependent. CONCLUSION: These results demonstrated that visfatin promoted monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression via the activation of p38/PI3K/Akt signaling and downstream ROS production and IKK/NF-кB activation.


Assuntos
Adesão Celular/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Monócitos/citologia , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Chinese Medical Journal ; (24): 1572-1581, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-771229

RESUMO

BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

16.
Chinese Medical Journal ; (24): 1572-1581, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-802556

RESUMO

Background@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*Methods@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*Results@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*Conclusion@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-742863

RESUMO

Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by various physical and chemical factors,which causes immature lung injury and abnormal repair after injury.In recent years,BPD has become one of the most difficult problems in neonatal intensive care unit.Notch signaling pathway is a conservative pathway that plays a regulatory role in embryonic development.Notch signaling pathways have a wide range of biological effects.By mediating cell-to-cell interactions,Notch signals can finely regulate the growth,development and apoptosis of cells.This article reviews the relationship between Notch signaling pathway and BPD in lung development,hyperoxia-induced lung injury and lung regeneration.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-701113

RESUMO

AIM:To investigate the effect of Fufang Zhenzhu Tiaozhi capsule(FTZ)on serum lipids and in-flammatory factors in rabbits with abdorminal aortic restenosis after balloon angioplasty.METHODS: New Zealand white rabbits(n=30)were divided into 5 groups.Except blank control group,the rabbits in other groups were used to establish abdominal aortic endothelium exfoliative vascular stenosis model.After 4 weeks of high-fat diet feeding,the animals in rest-enosis model group and drug treatment groups underwent percutaneous balloon dilatation in the stenosis.The angiographic stenosis was analyzed by a two-dimensional quantitative coronary angiography workstation with a digital subtraction X -ray machine.Blood samples were taken during angiography and the profiles of serum lipids and cytokines were measured.The expression of nuclear factor-κB(NF-κB)in the blood vessels was determined by immunohistochemistry.RESULTS:An-giography confirmed that the rates of area stenosis and diameter stenosis were significantly decreased in treatment groups compared with restenosis model group(P<0.01).Compared with restenosis model group,the serum lipid profiles and cy-tokine concentrations in drug treatment groups were significantly decreased(P<0.05).Immunohistochemistry showed the expression of NF-κB in restenosis model group was significantly higher than that in blank control group and drug treatment groups(P<0.05).CONCLUSION: FTZ significantly reduces the blood lipids and inflammatory factors in abdominal aortic restenosis model,and the anti-inflammatory effect may be related to the regulation of NF-κB pathway to inhibit the production of various inflammatory factors.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-696473

RESUMO

Objective To investigate the effects of Rapamycin and mammalian target of rapamycin - small in-terfering RNA (mTOR siRNA)on the proliferation,apoptosis and collagen Ⅰ(COLⅠ),collagen Ⅲ(COLⅢ)and fi-bronectin(FN)in premature rats lung fibroblasts exposed to hyperoxia. Methods 900 mL/ L volume fraction of oxygen was used to establish hyperoxia - damaged cell models,and the premature rats lung fibroblasts were divided into air control group,hyperoxia group,hyperoxia + rapamycin group and mammalian target of rapamycin - small interfering RNA transfection group. Cell proliferation was assessed by using 3 -(4,5 - Dimethylthiazol - 2 - yl)- 2,5 - dipheny-ltetrazolium bromide assay. Apoptosis were detected by Annexin V - FITC and propidium lodide (PI)double staining. The expressions of COLⅠ,COLⅢ and fibronectin was assessed by using enzyme linked immunosorbent assay and Bcl - 2,P53 and pro - fibrotic factors of connective tissue growth factor(CTGF)and transforming growth factor β(TGF - β)by using Western blot. Results Compared with the air control group,the proliferation of lung fibroblasts decreased and the apoptosis increased in the hyperoxia group,while the contents of COLⅠ(28. 30 ± 0. 53 vs. 17. 43 ±0. 37),COLⅢ(27. 86 ± 1. 02 vs. 17. 43 ± 0. 37)and fibronectin(32. 87 ± 0. 42 vs. 21. 57 ± 0. 47),P53(0. 810 ± 0. 119 vs. 0. 160 ± 0. 018),TGF - β(0. 580 ± 0. 108 vs. 0. 210 ± 0. 008)and CTGF(0. 590 ± 0. 017 vs. 0. 220 ± 0. 007)were also increased but the expression of Bcl - 2(0. 150 ± 0. 004 vs. 0. 600 ± 0. 130)protein was decreased, and the differences were all statistically significant (all P < 0. 01). Compared with the hyperoxia group,the proliferation of lung fibroblasts was increased in the hyperoxia + rapamycin group,but the apoptosis was decreased,the contents of COLⅠ(23. 17 ± 0. 60 vs. 28. 30 ± 0. 53),COLⅢ(17. 09 ± 0. 58 vs. 27. 86 ± 1. 02)and fibronectin(28. 11 ± 0. 68 vs. 32. 87 ± 0. 42),P53(0. 430 ± 0. 008 vs. 0. 810 ± 0. 119),TGF - β(0. 380 ± 0. 008 vs. 0. 580 ± 0. 108)and CTGF (0. 040 ± 0. 006 vs. 0. 590 ± 0. 017)were decreased while the expression of Bcl - 2(0. 290 ± 0. 009 vs. 0. 150 ± 0. 004) protein was increased,and the differences were all statistically significant (all P < 0. 01). In the mTOR siRNA transfec-tion group,compared with the hyperoxia + rapamycin group,the proliferation of lung fibroblasts was increased,but the apoptosis was decreased;the contents of COLⅠ(15. 71 ± 0. 34 vs. 23. 17 ± 0. 60),COLⅢ (13. 85 ± 1. 36 vs. 17. 09 ± 0. 58)and fibronectin(20. 18 ± 0. 28 vs. 28. 11 ± 0. 68),P53(0. 300 ± 0. 006 vs. 0. 430 ± 0. 008),TGF - β(0. 150 ± 0. 002 vs. 0. 380 ± 0. 008)and CTGF(0. 140 ± 0. 004 vs. 0. 040 ± 0. 006)were decreased while the expression of Bcl - 2 (0. 460 ± 0. 012 vs. 10. 290 ± 0. 009)protein was increased,and the differences were all statistically significant (all P < 0. 01). Conclusion Rapamycin and mTOR siRNA can protect lung injury caused by hyperoxia and have a certain inhibitory effect on pulmonary fibrosis,and mTOR siRNA effect is more obvious,so the mechanism may be through the inhibition of mTOR signaling pathway.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-710209

RESUMO

AIM To investigate the effect and mechanism of methanolic extract of Eupatorium (MEOE) to model rats with chronic soft tissue injury.METHODS The model rats were established by mechanical injury and a subsequent two-week normal feeding for respective administration of high,medium and small dosage of MEOE once a day successively for 14 days.An array of indices,the level of superoxide dismutase (SOD),malondialdehyde (MDA),prostaglandin E2 (PGE2),nitric oxide (NO),interleukin-6 (IL-6) and histamine,the expression of tumor necrosis factor-alpha (TNF-α),nitric oxide (NO) and Collagen-Ⅰ/Ⅲ,and the activity of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured to analyze the effect of MEOE to model rats with chronic muscle injury.RESULTS MEOE resulted in apparent reduction of contents of MDA,PGE2 and NO,and the levels of TNF-α and IL-6 in muscular tissue (P < 0.05),significantly increased of the SOD in muscular tissue (P < 0.01),a remarkably inhibited expression of the tissue Collagen-Ⅰ/Ⅲ protein (P < 0.01),and significantly improved activity of tissue VEGF and bFGF (P < 0.01).CONCLUSION The certain therapeutic effects of MEOE to rats with chronic muscle injury may correlate with its influence to the levels of inflammatory factors inhibition,the oxidative stress relief,the overexpression of collagen-Ⅰ/Ⅲ inhibition,the VEGF and bFGF activity improvement,and the time spare from the repairing.

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