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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 821-826, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880112

RESUMO

OBJECTIVE: To study the impact of atypical protein kinase Cι (PKCι) isoform PKC on the pancreatic cancer cells towards the tumoricidal effect of cytokine-induced killer (CIK) cells and explore its mechanisms. METHODS: CIK cells were prepared by inducing mononuclear cells isolated from the peripheral blood of healthy people with interleukin-2 (IL-2), interferon (IFN) and CD3 mAb and subsequently co-cultured with pancreatic epithelial cell HPDE6-C7, pancreatic cancer cells MiaPaCa and PANC-1 with or without PKC inhibitor named sodium thiomalate (ATM). All cells were divided into control group, ATM group, co-culture group with CIK and co-culture group with CIK+ATM. Cell count was used to detect the growth of each group from 1 to 8 d. Flow cytometry was used to detect the death rate of the cell lines after 48 h cell culture in each group. The small hairpin RNA (shRNA) was used for PKCι knockdown and the recombinant plasmid transfection was for PKCι overexpression in pancreatic cancer cells. Western blot and real-time fluorescent quantitative PCR (qRT-PCR) were utilized to determine the expression of PKCι protein and the impact on gene expression of transforming growth factor-ß (TGF-ß), a downstream effector modulated by PKC. Different mass concentrations of TGF-ß (1, 10, 20 ng/mL) were added into the co-culture of MiaPaCa and PANC-1 with CIK. The cell death rate was detected by flow cytometry 48 h later, so as to explore the possible mechanisms of the impact of PKCι on the tumoricidal effects of CIK cells. RESULTS: ATM and CIK were shown to suppress the growth and induce apoptosis or death of pancreatic cancer cells, meanwhile, ATM can enhance the tumoricidal effect of CIK on pancreatic cancer cells. Moreover, we found that PKCι knockdown in pancreatic cancer cells can down-regulate the gene expression of TGF-ß. In return, PKCι overexpression in pancreatic cancer cells can increase the gene expression of TGF-ß. The death rate of cancer cells with 10, 20 ng/mL TGF-ß was lower compared with the control group (P < 0.05). CONCLUSIONS: PKCι knockdown in pancreatic cancer cells can not only inhibit the growth of pancreatic cancer cells, but also enhance the tumoricidal effects of CIK on cancer cells. The possible mechanism of PKCι is to affect the immune escape of tumor cells by regulating the expression of TGF-ß.


Assuntos
Células Matadoras Induzidas por Citocinas , Neoplasias Pancreáticas , Apoptose , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Interleucina-2
2.
J Clin Nurs ; 28(23-24): 4488-4495, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31410906

RESUMO

AIMS AND OBJECTIVES: To explore whether the risk of peripheral venous catheters failure remained constant throughout catheter use in adult patients. BACKGROUND: Peripheral venous catheters, widely used in adult patients, may have a critical threshold dwell time associated with increased risk of catheter failure. DESIGN: Prospective, observational study. We have complied with the STROBE checklist of items. METHODS: This study was conducted from July-October 2018 in Hunan, China. Data on patient factors, catheter factors and catheter failure events were collected. Poisson regression was used to assess the effect of catheter dwell time on catheter failure while adjusting for other variables. RESULTS: A total of 1,477 patients were included in the analysis. There were 854 cases (57.8%) of catheter failure. The median dwell time to catheter failure was 52 hr (interquartile range: 36-73 hr). The incidence rate of catheter failure significantly increased by 1.1%/h in the first 38 hr after catheter insertion. From 39-149 hr, the incidence rate significantly decreased, and at >149 hr, there was no significant change in the incidence rate. Meanwhile, factors such as vascular quality and infused drugs showed having an impact on catheter failure events. CONCLUSIONS: The risk of catheter failure may not remain constant throughout the dwell time. The results suggest that nurses should assess the insertion site frequently in the first 38 hr. RELEVANCE TO CLINICAL PRACTICE: The significant increase in the risk of catheter failure per hour may warrant close and frequent inspection of insertion site during the first 38 hr.


Assuntos
Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Falha de Equipamento/estatística & dados numéricos , Adulto , Cateterismo Periférico/enfermagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Tempo
3.
J Virol ; 90(9): 4696-4705, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26912617

RESUMO

UNLABELLED: The NS1 protein encoded by influenza A virus antagonizes the interferon response through various mechanisms, including blocking cellular mRNA maturation by binding the cellular CPSF30 3' end processing factor and/or suppressing the activation of interferon regulatory factor 3 (IRF3). In the present study, we identified two truncated NS1 proteins that are translated from internal AUGs at positions 235 and 241 of the NS1 open reading frame. We analyzed the cellular localization and function of the N-truncated NS1 proteins encoded by two influenza A virus strains, Udorn/72/H3N2 (Ud) and Puerto Rico/8/34/H1N1 (PR8). The NS1 protein of PR8, but not Ud, inhibits the activation of IRF3, whereas the NS1 protein of Ud, but not PR8, binds CPSF30. The truncated PR8 NS1 proteins are localized in the cytoplasm, whereas the full-length PR8 NS1 protein is localized in the nucleus. The infection of cells with a PR8 virus expressing an NS1 protein containing mutations of the two in-frame AUGs results in both the absence of truncated NS1 proteins and the reduced inhibition of activation of IRF3 and beta interferon (IFN-ß) transcription. The expression of the truncated PR8 NS1 protein by itself enhances the inhibition of the activation of IRF3 and IFN-ß transcription in Ud virus-infected cells. These results demonstrate that truncated PR8 NS1 proteins contribute to the inhibition of activation of this innate immune response. In contrast, the N-truncated NS1 proteins of the Ud strain, like the full-length NS1 protein, are localized in the nucleus, and mutation of the two in-frame AUGs has no effect on the activation of IRF3 and IFN-ß transcription. IMPORTANCE: Influenza A virus causes pandemics and annual epidemics in the human population. The viral NS1 protein plays a critical role in suppressing type I interferon expression. In the present study, we identified two novel truncated NS1 proteins that are translated from the second and third in-frame AUG codons in the NS1 open reading frame. The N-terminally truncated NS1 encoded by the H1N1 PR8 strain of influenza virus that suppresses IRF3 activation is localized primarily in the cytoplasm. We demonstrate that this truncated NS1 protein by itself enhances this suppression, demonstrating that some strains of influenza A virus express truncated forms of the NS1 protein that function in the inhibition of cytoplasmic antiviral events.


Assuntos
Vírus da Influenza A/fisiologia , Fator Regulador 3 de Interferon/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Códon de Iniciação , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Humanos , Influenza Humana/metabolismo , Influenza Humana/virologia , Interferon beta/genética , Camundongos , Mutação , Fases de Leitura Aberta , Biossíntese de Proteínas , Transporte Proteico , Transcrição Genética , Proteínas não Estruturais Virais/química
5.
Biores Open Access ; 3(6): 297-310, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25469315

RESUMO

Hydrogels allow control of gel composition and mechanics, and permit incorporation of cells and a wide variety of molecules from nanoparticles to micromolecules. Peptide-linked hydrogels should tune the basic polymer into a more bioactive template to influence cellular activities. In this study, we first introduced the generation of 2D poly-(sulfobetaine methacrylate [SBMA]) hydrogel surfaces. By incorporating with functional peptide RGD and vascular endothelial growth factor-mimicking peptide KLTWQELYQLKYKG (QK) peptides, endothelial cells attached to the surface well and proliferated in a short-term culturing. However, the mechanical property, which plays a crucial role directing the cellular functions and supporting the structures, decreased when peptides graft onto hydrogels. Manipulating the mechanical property was thus necessary, and the most related factor was the monomer concentration. From our results, the higher amount of SBMA caused greater stiffness in hydrogels. Following the 2D surface studies, we fabricated 3D porous hydrogels for cell scaffolds by several methods. The salt/particle leaching method showed a more reliable way than gas-foaming method to fabricate homogeneous and open-interconnected pores within the hydrogel. Using the salt/particle leaching method, we can control the pore size before leaching. Morphology of endothelial cells within scaffolds was also investigated by scanning electron microscopy, and histological analysis was conducted in vitro and in vivo to test the biocompatibility of SB hydrogel and its potential as a therapeutic reagent for ischemic tissue repair in mice.

6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 32(10): 1037-42, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22333091

RESUMO

OBJECTIVE: To evaluate the associations between polymorphisms of LEPR Gln223Arg, LEPR Pro1019Pro and the risk on obesity. METHODS: A computerized search on literature was carried out in Wanfang, CNKI, VIP databases and CBM, PubMed, EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro1019Pro and risk of obesity in the Chinese population. Odds ratios (ORs) were used to assess the strength of the association, and 95% confidence intervals (CIs) to present the precision of the estimates. Meta-analysis was performed using the STATA statistical software. RESULTS: Fifteen literature were collected for Meta-analysis by the uniform inclusion and exclusion criteria. There were 1096 obese patients and 949 controls for polymorphisms of LEPR Gln223Arg in 9 papers, together with 961 obese patients and 818 controls for polymorphisms of LEPR Pro1019Pro in 8 papers. Overall, there were significant associations between decreased risk of obesity and LEPR Gln223Arg polymorphisms (-668 A→G) (G versus A, OR = 0.66, 95%CI: 0.49 - 0.89; AG and GG versus AA, OR = 0.50, 95%CI: 0.32 - 0.77; respectively). There were significant associations between increased risk of obesity and LEPR Pro1019Pro polymorphisms (-3057 G→A) (A versus G, OR = 1.61, 95%CI: 1.15 - 2.26; AG and AA versus GG, OR = 1.50, 95%CI: 1.08 - 2.08; respectively). CONCLUSION: Variant alleles at both LEPR-668 and LEPR-3057 were associated with obesity in the Chinese Han-dominated population.


Assuntos
Obesidade/genética , Receptores para Leptina/genética , Grupo com Ancestrais do Continente Asiático/genética , Frequência do Gene , Genótipo , Humanos , Razão de Chances , Polimorfismo Genético
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 45(10): 944-8, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22321599

RESUMO

OBJECTIVE: To comprehensively evaluate the effect of interventions on obesity in Chinese pupils. METHODS: A literature research was carried out in China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, PubMed and the Excerpts Medica Database (EMBASE) databases to collect articles published between 1979 and 2010 concerning the effect of interventions for preventing obesity in Chinese pupils. Rate difference (RD) of the rate of obesity as the evaluation indicator was selected to Meta-analyze the effect of interventions on obesity. There are total 215 articles, in which 211 articles were written in Chinese and other articles were written in English. RESULTS: 17 literatures were used for Meta-analysis by the uniform inclusion and exclusion criteria. The results showed that the RD of obesity rate for the students in the intervention group was 3% (95%CI: 1% - 5%) after the intervention. However, the RD of obesity rate for the students in the control group was -2% (95%CI: -4% - -1%) after the intervention. Results of stratified analysis for the RD of obesity rate showed that the obesity rate for the students in the intervention group were decreased significantly after the intervention of combined programs with health education, physical exercise and nutrition interventions with moderate intervention time (1 to 2 years), the RD (95%CI) of obesity rate were 5% (2% - 8%), 3% (1% - 4%), respectively. For the studies whose baseline obesity rates was insignificant difference between the intervention group and the control group, the obesity rate for the students in the intervention group was 4% (95%CI: -7% - -1%) lower than the obesity rate for the students in the control group after the intervention. CONCLUSION: Health-education-based comprehensive intervention is effective on obesity prevention in Chinese pupils; combined intervention programs with moderate intervention time (1 to 2 years) were effective in improving efficiency of obesity prevention in pupils.


Assuntos
Educação em Saúde , Obesidade/prevenção & controle , Criança , China , Humanos , Estudantes
8.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 28(2): 124-7, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20480650

RESUMO

OBJECTIVE: After sinboneHT bone replacement (SBR) was implanted in animals, to evaluate the biocompatibility of SBR and compounded in autogenetic bone in the proportion of one to one in order to prepare for the clinical applications in the future. METHODS: Bone defects of 10 mm x l0 mm x 2 mm was made at the mandibular of rabbits, then SBR with different granule diameter and autogenetic bone was compounded in the proportion of being applied in the left defects, while autogenetic bone was implanted in the right defects and nothing was used in the right reformed defects. Animals were sacrificed at 2, 4 and 8 weeks respectively. The biologic capacity was evaluated with anatomy, X-rays studies and histology. RESULTS: SBR has better biocompatibility, which can effectively accelerate the reconstruction of bone defects and help the new bone by being compounded with autogenetic bone. It provides the appropriate scaffold or template which would allow cellular infiltration, attachment and multiplication. CONCLUSION: SBR is a kind of bone substitute material with good biocompatibility. SBR compounded with self-bone has a better regeneration function.


Assuntos
Regeneração Óssea , Mandíbula , Animais , Substitutos Ósseos , Coelhos , Procedimentos Cirúrgicos Reconstrutivos
9.
Basic Clin Pharmacol Toxicol ; 103(5): 433-44, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18801030

RESUMO

The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of cyclosporine; thus, the aim was to conduct a meta-analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. A literature search was conducted to locate the relevant papers by using the PubMed electronic source from 1997 and onwards. The pharmacokinetic parameters, including AUC(0-4), AUC(0-12), AUC(0-inf), C(max), CL/F and trough concentration (C(0)), were extracted and a meta-analysis was performed by using Stata version 9.1. A total of 14 papers concerning 1036 individuals were included in the meta-analysis. The overall results showed no major influence of SNP C3435T on the pharmacokinetic parameters, including AUC(0-4), AUC(0-inf), CL/F, C(max) and C(0), although AUC(0-12) was lower in subjects with CC genotype. A subanalysis by ethnic population showed that C(0) was lower in Caucasian individuals harbouring CC genotype. In conclusion, our meta-analysis of available studies has thus far failed to demonstrate a definitive correlation between the SNP C3435T in MDR1 gene and alterations in P-glycoprotein function that can result in altered pharmacokinetics of cyclosporine, although it was indicated in this meta-analysis that the carrier of CC genotype of the SNP C3435T of MDR1 had lower cyclosporine exposure presented as AUC(0-12) than those with at least one T allele. There seems to be ethnic differences in the relationship between the SNP C3435T of MDR1 and cyclosporine pharmacokinetics.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP , Alelos , Área Sob a Curva , Grupo com Ancestrais do Continente Europeu/genética , Éxons , Genes MDR , Genótipo , Humanos
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