RESUMO
To investigate clinical nurses' perception of adverse event risk and to analyze its influencing factors. A proportional stratified random sampling method was applied to recruit nurses from a hospital in Shiyan City, Hubei Province, China. The Nursing Adverse Event Risk Perception Scale, Organizational Support Questionnaire, Nurse Manager Leadership Behavior Questionnaire, Nursing Safety Behavior Questionnaire, and Burnout scale was used to investigate 1084 nurses. Univariate analysis, Pearson correlation analysis, and multiple linear regression analysis were used to analyze the influencing factors. The scores of the Nurses' Risk Perception of Adverse Nursing Event Scale, Organizational Support Questionnaire, Nurse Manager Leadership Behavior Questionnaire, Nursing Safety Behavior Questionnaire, and Burnout Scale were 14.98 ± 5.39, 52.57 ± 10.00, 88.98 ± 21.08, 56.42 ± 5.03, 30.90 ± 21.49, respectively. According to the correlation analysis, nurses' perception of adverse nursing events was positively correlated with the sense of organizational support (r = .457, P < .01), head nurses' leadership behavior (r = .348, P < .01), and nurse safety behavior (r = .457, P < .01), and negatively correlated with the level of burnout (r = -.384, P < .01). According to the Regression analysis, nurses' departments (ß = .226, P < .001), daily working hours (ß = 1.122, P < .001), adverse events experience (ß = -1.505, P < .001), organizational support (ß = .105, P < .001), head nurses' leadership behavior (ß = .072, P < .001), and burnout (ß = -.052, P < .001) held an influence on nurses' risk perception of adverse nursing event. These factors explained 42.5% of the total variation. Nurses' risk perception of adverse nursing events needs to be improved. Nursing managers need to strengthen organizational support for nurses, change the leadership behavior of nurse managers, reduce nurses' burnout, improve nurses' risk perception of adverse nursing events, prevent adverse events, and ensure patient safety.
Assuntos
Esgotamento Profissional , Liderança , Recursos Humanos de Enfermagem Hospitalar , Humanos , Estudos Transversais , Feminino , Adulto , China , Recursos Humanos de Enfermagem Hospitalar/psicologia , Masculino , Esgotamento Profissional/psicologia , Inquéritos e Questionários , Atitude do Pessoal de Saúde , Percepção , Erros Médicos/psicologia , Segurança do Paciente , Cultura Organizacional , Pessoa de Meia-IdadeRESUMO
Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.
Assuntos
Antineoplásicos , Oxaliplatina , Polissacarídeos , Pró-Fármacos , Espécies Reativas de Oxigênio , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Oxaliplatina/farmacologia , Oxaliplatina/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
Metabolic glycoengineering provides a powerful tool to label proteins with chemical tags for cell imaging and protein enrichment. The structures of per-O-acetylation on unnatural sugars facilitate membrane permeability and increase cellular uptake and are widely used for metabolic glycan labeling. However, unexpected S-glyco modification was discovered via a non-enzymatic reaction with protein cysteines, which was initially conducted with the hydrolysis of anomeric acetate by esterase. Herein, we synthesized a series of GalNAz derivatives that were protected with various lengths of short-chain fatty acid, including acetate, propionate, butyrate, valerate and pivalate, to detect differences in labeling efficiencies and occurrence of S-glyco modification. Our results demonstrate that all the GalNAz derivatives could effectively label proteins in HeLa cells, except the pivalate group. Of note, But4GalNAz exhibited excellent labeling abilities compared with Ac4GalNAz from the results for western blot, flow cytometry and confocal laser scanning microscopy. Moreover, the results for the S-glyco-modification assay by western blot and chemoproteomic analysis indicated that But4GalNAz generated negligible unexpected labeling signals compared to Ac4GalNAz. Our study uncovers the distinct labeling efficiency of different protected groups on unnatural sugars, which provides an alternative strategy to explore novel glycan probes.
Assuntos
Ácidos Graxos , Humanos , Células HeLa , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Coloração e Rotulagem , Proteínas/química , Proteínas/metabolismo , Estrutura MolecularRESUMO
Intercropping has been recommended as a beneficial cropping practice for improving soil characteristic and tea quality. However, there is limited research on the effects of intercropping fruit trees on soil chemical properties, soil aggregate structure, and tea quality components. In this study, intercropping fruit trees, specifically loquats and citrus, had a significant impact on the total available nutrients, AMN, and AP in soil. During spring and autumn seasons, the soil large-macroaggregates (>2 mm) proportion increased by 5.93% and 19.03%, as well as 29.23% and 19.14%, respectively, when intercropping loquats and citrus. Similarly, intercropping waxberry resulted in a highest small-macroaggregates (0.25 mm-2 mm) proportion at 54.89% and 77.32%. Soil aggregate stability parameters of the R0.25, MWD, and GMD were generally considered better soil aggregate stability indicators, and significantly improved in intercropping systems. Intercropping waxberry with higher values for those aggregate stability parameters and lower D values, showed a better soil aggregate distribution, while intercropping loquats and citrus at higher levels of AMN and AP in different soil aggregate sizes. As the soil aggregate sizes increased, the AMN and AP contents gradually decreased. Furthermore, the enhanced levels of amino acids were observed under loquat, waxberry, and citrus intercropping in spring, which increased by 27.98%, 27.35%, and 26.21%, respectively. The contents of tea polyphenol and caffeine were lower under loquat and citrus intercropping in spring. These findings indicated that intercropping fruit trees, specifically loquat and citrus, have immense potential in promoting the green and sustainable development of tea plantations.
Assuntos
Solo , Solo/química , Citrus/crescimento & desenvolvimento , Camellia sinensis/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Chá , Frutas/crescimento & desenvolvimento , Agricultura/métodos , Produção Agrícola/métodosRESUMO
It has been reported that lncRNA GAS5 can inhibit LPS-induced inflammation, indicating its involvement in sepsis. We observed the downregulation of GAS5 in plasma of sepsis patients. In addition, expression levels of GAS5 were positively correlated with the expression levels of miR-214. In cardiomyocytes, overexpression of GAS5 upregulated the expression of miR-214, while its knockdown resulted in decreased expression levels of miR-124. Methylation-specific PCR (MSP) revealed that GAS5 negatively regulated the methylation of miR-124. Cell apoptosis showed that overexpression of GAS5 and miR-214 suppressed the apoptosis of cardiomyocytes induced by LPS. In addition, overexpression of miR-214 also reduced the enhancing effects of silencing of GAS5 on cell apoptosis. Therefore, GAS5 may upregulate miR-214 through methylation pathway to inhibit the apoptosis of cardiomyocytes in sepsis.
Assuntos
MicroRNAs , RNA Longo não Codificante , Sepse , Apoptose/genética , Humanos , Lipopolissacarídeos , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Sepse/genéticaRESUMO
Many articles have reported that Rab1A was overexpressed in a variety of human cancers and involved in tumor progression and metastasis. However, the biological function and molecular mechanism of Rab1A in nasopharyngeal carcinoma (NPC) remained unknown until now. Here we found that Rab1A overexpression is a common event and was positively associated with distant metastasis and poor prognosis of NPC patients. Functionally, Rab1A depletion inhibited the migration and EMT phenotype of NPC cells, whereas Rab1A overexpression led to the opposite effect. Furthermore, we reveal an important role for Rab1A protein in the induction of radioresistance via regulating homologous recombination (HR) signaling pathway. Mechanistically, Rab1A activated Wnt/ß-catenin signaling by inhibiting the activity of GSK-3ß via phosphorylation at Ser9. Then Wnt/ß-catenin signaling induced NPC cells radioresistance and metastasis through nuclear translocation of ß-catenin and transcription upregulation of HR pathway-related and EMT-related genes expression. In general, this study shows that Rab1A may serve as a potential biomarker for predicting prognosis in NPC patients. Targeting Rab1A and Wnt/ß-catenin signaling may hold promise to overcome NPC radioresistance.
Assuntos
Movimento Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Tolerância a Radiação , Via de Sinalização Wnt , beta Catenina/metabolismo , Proteínas rab1 de Ligação ao GTP/metabolismo , Adulto , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/enzimologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/enzimologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Fosforilação , Proteínas rab1 de Ligação ao GTP/genéticaRESUMO
Deregulated microRNAs play an important role in the development and progression of various types of cancer. In our previous study, we observed that microRNA3423p (miR3423p) was one of the most markedly downregulated microRNAs in two nasopharyngeal carcinoma (NPC) cell lines compared to nonneoplastic cells by using whole genome small RNA sequencing. In the present study, we confirmed that the expression of miR3423p was significantly reduced in NPC tissues compared with normal nasopharyngeal epithelial tissues. Overexpression of miR3423p inhibited proliferation, epithelialmesenchymal transition (EMT), migration and invasiveness of NPC cells. In addition, we observed that Cdc42, a Rho GTPase family member involved in cell proliferation and metastasis, is a direct target of miR3423p. Additionally, ML141, a smallmolecule inhibitor of Cdc42, efficiently suppressed the invasion of NPC cells compared with the control cells. Finally, we analyzed NPC tissues derived from 10 NPC patients and subjected them to quantitative RTPCR and immunohistochemistry assays for concomitant determination of the expression levels of miR3423p and Cdc42. Our results revealed that miR3423p levels were significantly inversely correlated with the protein levels of its target Cdc42. The results of the present study indicated that miR3423p inhibited NPC tumor growth and invasion by directly targeting the Cdc42 pathway.
Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/genética , Proteína cdc42 de Ligação ao GTP/genética , Biópsia , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Epitélio/patologia , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Nasofaringite/patologia , Nasofaringe/citologia , Nasofaringe/patologia , Invasividade Neoplásica/genética , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Proteína cdc42 de Ligação ao GTP/antagonistas & inibidores , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. However, its expression profile and biological function in nasopharyngeal carcinoma (NPC) remains unclear. In this study, higher expression of EpCAM was found in NPC samples compared with non-cancer nasopharyngeal mucosa by qRT-PCR. Additionally, immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival. Multivariate survival analysis identified high EpCAM expression as an independent prognostic factor. Ectopic EpCAM expression in NPC cells promoted epithelial-mesenchymal transition (EMT), induced a cancer stem cell (CSC)-like phenotype, and enhanced metastasis in vitro and in vivo without an effect on cell proliferation. Notably, EpCAM overexpression reduced PTEN expression and increased the level of AKT, mTOR, p70S6K and 4EBP1 phosphorylation. Correspondingly, an AKT inhibitor and rapamycin blocked the effect of EpCAM on NPC cell invasion and stem-like phenotypes, and siRNA targeting PTEN rescued the oncogenic activities in EpCAM knockdown NPC cells. Our data demonstrate that EpCAM regulates EMT, stemness and metastasis of NPC cells via the PTEN/AKT/mTOR pathway.
Assuntos
Molécula de Adesão da Célula Epitelial/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Animais , Caderinas/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Molécula de Adesão da Célula Epitelial/antagonistas & inibidores , Molécula de Adesão da Célula Epitelial/genética , Transição Epitelial-Mesenquimal , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/mortalidade , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , Fosfoproteínas/metabolismo , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidoresRESUMO
Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Proliferação de Células/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/efeitos dos fármacos , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Neoplasias Nasofaríngeas/genética , Metástase Neoplásica , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores da Colecistocinina/biossíntese , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/α-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Histona Desacetilases/metabolismo , Proteínas Repressoras/metabolismo , Caderinas/genética , Caderinas/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Progressão da Doença , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Fosforilação , Prognóstico , Proteínas Repressoras/genética , Taxa de Sobrevida , Vimentina/genética , Vimentina/metabolismoRESUMO
Tripartite motif-containing 29 (TRIM29) has been reported to be dysregulated in human cancers. Up-regulation of TRIM29 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. However, its expression biological function and clinical significance in nasopharyngeal carcinoma (NPC) remain unclear. In this study, TRIM29 expression was validated by qRT-PCR and immunohistochemistry in 69 NPC samples. Notably, TRIM29 protein expression was significantly and positively correlated with the tumor size, clinical stage and metastasis. TRIM29 was identified as the direct target of miR-335-5p and miR-15b-5p, both of which were down-regulated and negatively associated with TRIM29 expression in NPC cell lines and clinical samples. Ectopic TRIM29 expression promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in NPC cells, while its depletion inhibited cell invasion and EMT phenotype. Mechanistically, TRIM29 overexpression reduced PTEN expression and increase phosphorylated protein level of AKT, p70S6K and 4E-BP1. Correspondingly, AKT inhibitor and Rapamycin blocked the effect of TRIM29 on cell invasion. In conclusion, our results suggest that miR-335-5p and miR-15b-5p down-regulation results in TRIM29 over-expression, which induces proliferation, EMT and metastasis of NPC through the PTEN/AKT/mTOR signaling pathway.
Assuntos
Carcinoma/patologia , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Movimento Celular , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , PTEN Fosfo-Hidrolase/genética , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the therapeutic effect of double fill nine tastes soup in treating children recurrent respiratory infection (RRTI) and the change of immune function. METHOD: 77 RRTI patients were randomly selected into observation and control groups. The observation group was treated with Chinese medicine- double fill nine tastes soup,water frying points 2 times oral. The control was treated with transfer factor oral liquid,every 10 mL,2 times daily oral. Treatment periods were both two months. IgA, IgG, IgM and IL-12, TNF-alpha, INF-gamma were detected before and after treatment to assess the clinical effects and the changes of immune factors, meanwhile, a health group was established. RESULT: Before treatment, compared with the health group, the serum IgA, IgG, IgM, IgE, IL-12, TNF-alpha, IFN-gamma in both groups were significantly different (P < 0.01). After treatment, the ratio of IgA, IgG, Ig M, IL-12, TNF-alpha, IFN-gamma in two groups were significantly different (P < 0.01). Compared with the recurrence rate and clinical effects, the observation group was better than control, and the differences were significant (P < 0.01). CONCLUSION: Double fill nine tastes soup has significant effects in treating recurrent respiratory infection (RRI) and enhance the immune function in children.