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1.
Rev Med Virol ; 31(4): e2195, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260780

RESUMO

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , COVID-19/patologia , Citocinas/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Leucócitos/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia
2.
Acta Pharmacol Sin ; 37(6): 845-56, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27133297

RESUMO

AIM: Dexamethasone (DEX) is a widely used synthetic glucocorticoid, which has shown anti-cancer efficacy and anti-estrogenic activity. In this study we explored the possibility that DEX might be used as an endocrine therapeutic agent to treat human non-small cell lung cancer (NSCLC). METHODS: The viability and proliferation of human NSCLC cell lines A549 and H1299 were assessed in vitro. Anti-tumor action was also evaluated in A549 xenograft nude mice treated with DEX (2 or 4 mg·kg(-1)·d(-1), ig) or the positive control tamoxifen (50 mg·kg(-1)·d(-1), ig) for 32 d. The expression of estrogen sulfotransferase (EST) in tumor cells and tissues was examined. The intratumoral estrogen levels and uterine estrogen responses were measured. RESULTS: DEX displayed mild cytotoxicity to the NSCLC cells (IC50 >500 µmol/L) compared to tamoxifen (IC50 <50 µmol/L), but it was able to inhibit the cell proliferation at low micromolar ranges. Furthermore, DEX (0.1-10 µmol/L) dose-dependently up-regulated EST expression in the cells, and inhibited the cell migration in vitro. Triclosan, a sulfation inhibitor, was able to diminish DEX-caused inhibition on the cell viability. In A549 xenograft nude mice, DEX or tamoxifen administration remarkably suppressed the tumor growth. Moreover, DEX administration dose-dependently increased EST expression in tumor tissues, and reduced intratumoral estrogen levels as well as the volumes and weights of uterine. CONCLUSION: DEX suppresses the growth of A549 xenograft tumors via inducing EST and decreasing estradiol levels in tumor tissues, suggesting that DEX may be used as anti-estrogenic agent for the treatment of NSCLC.


Assuntos
Antineoplásicos Hormonais/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dexametasona/farmacologia , Antagonistas de Estrogênios/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Sulfotransferases/metabolismo , Células A549 , Animais , Antineoplásicos Hormonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Estrogênios/metabolismo , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Sulfotransferases/análise
3.
Acta Pharmacol Sin ; 37(7): 930-40, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27180983

RESUMO

AIM: Combined therapy of EGFR TKI and VEGFR TKI may produce a greater therapeutic benefit and overcome EGFR TKI-induced resistance. However, a previous study shows that a combination of EGFR TKI erlotinib (ER) with VEGFR TKI sunitinib (SU) did not improve the overall survival in patients with non-small-cell lung cancer (NSCLC). In this study we examined the anticancer effect of ER, SU and their combination in the treatment of A549 human NSCLC xenograft mice, and conducted PK/PD modeling and simulations to optimize the dose regimen. METHODS: ER (20, 50 mg·kg(-1)·d(-1)) or SU (5, 10, 20 mg·kg(-1)·d(-1)) alone, or their combination were administered to BALB/c nude mice bearing A549 tumors for 22 days. The tumor size and body weight were recorded daily. The experimental data were used to develop PK/PD models describing the quantitative relationship between the plasma concentrations and tumor suppression in different dose regimens. The models were further evaluated and validated, and used to predict the efficacy of different combination regimens and to select the optimal regimen. RESULTS: The in vivo anticancer efficacy of the combination groups was much stronger than that of either drug administered alone. A PK/PD model was developed with a combination index (φ) of 4.4, revealing a strong synergistic effect between ER and SU. The model simulation predicted the tumor growth in different dosage regimens, and showed that the dose of SU played a decisive role in the combination treatment, and suggested that a lower dose of ER (≤5 mg·kg(-1)·d(-1)) and adjusting the dose of SU might yield a better dosage regimen for clinical research. CONCLUSION: The experimental data and modeling confirm synergistic anticancer effect of ER and SU in the treatment of A549 xenograft mice. The optimal dosage regimen determined by the PK/PD modeling and simulation can be used in future preclinical study and provide a reference for clinical application.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/farmacocinética , Indóis/farmacologia , Indóis/farmacocinética , Neoplasias Pulmonares/tratamento farmacológico , Modelos Biológicos , Pirróis/farmacologia , Pirróis/farmacocinética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Simulação por Computador , Cálculos da Dosagem de Medicamento , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Nus , Sunitinibe , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Biomed Environ Sci ; 28(9): 627-33, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26464249

RESUMO

OBJECTIVE: In this study, we aimed at exploring the association between work-related musculoskeletal disorders (WMSDs) and work organization based on a case-control study. METHODS: A total of 1938 workers who claimed to suffer from WMSDs were selected from Beijing, Henan, Hubei, and the Guangdong province. The control group consisted of 2009 workers employed in similar industries without severe disease or musculoskeletal discomforts. We used a modified version of the questionnaire developed by the NMQ and the DMQ to investigate individual and work-related factors. RESULTS: A total of 13 variables (P<0.1) were selected by the chi-square test and finally, 7 variables entered into the equation, with 6 variables reaching statistical significance (P<0.05). The odds ratios (OR) of 'work changing with season' and 'sufficient rest time' did not reach 1 (0.749 and 0.441, respectively). In addition, 'sufficient rest time' seemed to be the stronger protective factor according to its higher standardized coefficient. And 'repetitive work every minute', 'constantly repetitive work' (every day), 'shortage of site personnel', and 'often switching shifts with others' seemed to be the risk factors. CONCLUSION: Work organization may have comprehensive effects on the occurrence of WMSDs. This pattern of associations suggests that further investigation into the mechanism of how work organization affects the prevalence of WMSDs is required.


Assuntos
Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Admissão e Escalonamento de Pessoal/organização & administração , Local de Trabalho/organização & administração , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos Transversais , Transtornos Traumáticos Cumulativos/epidemiologia , Transtornos Traumáticos Cumulativos/etiologia , Demografia , Ergonomia/normas , Feminino , Humanos , Modelos Logísticos , Masculino , Doenças Musculoesqueléticas/etiologia , Doenças Profissionais/etiologia , Prevalência , Fatores de Risco , Estações do Ano , Inquéritos e Questionários , Tolerância ao Trabalho Programado/fisiologia , Adulto Jovem
5.
Org Biomol Chem ; 12(21): 3446-58, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24752610

RESUMO

A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.


Assuntos
Desenho de Fármacos , Farmacorresistência Viral/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Indóis/síntese química , Indóis/farmacologia , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/farmacologia , Aldeídos/química , Alcinos , Benzoxazinas/química , Benzoxazinas/farmacologia , Carcinógenos/toxicidade , Catálise , Linhagem Celular , Ciclopropanos , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , Humanos , Indóis/química , Ligantes , Modelos Moleculares , Mutagênicos/toxicidade , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Inibidores da Transcriptase Reversa/química
6.
Org Biomol Chem ; 11(34): 5621-33, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23863885

RESUMO

Diverse reactivity by coupling of substituted anilines with ethyl trifluoropyruvate was developed under microwave irradiation without catalysts to generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The plausible mechanism for obtaining different products was proposed. Furthermore, the anti-HIV activity of aromatic hydroxy trifluoromethyl esters was first reported. The best inhibitory activity against wild-type HIV-1 IIIB was exemplified by trifluoromethyloxindole 3q with an IC50 = 5.8 µM, which also displayed potential activity against Y181C mutant virus with an IC50 = 7.5 µM. More significantly, the activities of oxindoles 3q and 3r to inhibit K103N/Y181C double mutant HIV-1 reverse transcriptase (RT) are probably similar to that of the second-generation nonnucleoside inhibitor HBY 097 by docking calculation.


Assuntos
Compostos de Anilina/farmacologia , Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Micro-Ondas , Ácido Pirúvico/análogos & derivados , Inibidores da Transcriptase Reversa/farmacologia , Compostos de Anilina/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Catálise , Relação Dose-Resposta a Droga , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/metabolismo , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Mutação , Ácido Pirúvico/química , Ácido Pirúvico/farmacologia , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
7.
J Med Genet ; 49(2): 79-82, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22209761

RESUMO

BACKGROUND: Paroxysmal dyskinesias (PDs), a clinically and genetically heterogeneous group of episodic movement disorders, include kinesigenic PD (PKD), exercise-induced PD (PED) and non-kinesigenic PD (PNKD). These disorders are all transmitted as autosomal dominant traits with incomplete penetrance. Several PD-related genetic disorders, including PKD and familial infantile convulsions with paroxysmal choreoathetosis (ICCA), mapped to the same region on chromosome 16. Independent genetic studies have recently revealed that PKD can be caused by loss-of-function mutations in the proline-rich transmembrane protein 2 gene (PRRT2). We tested the hypothesis that other forms of PDs are also due to PRRT2 mutations. METHODS/RESULTS: The whole genomic region of PRRT2 was sequenced in six Han Chinese families and 15 sporadic cases of PD-related phenotypes. The previously reported mutation, c.649dupC (p.R217Pfs*7), was found in two families with PKD, one family with ICCA, one family with PNKD-like phenotype, and two sporadic cases with PED. In an additional ICCA family, a novel frameshift mutation, c.904dupG (p.D302Gfs*38), was identified. A missense mutation, c.913G→A (p.G305R), and a synonymous substitution, c.1011C→T (p.G337G), were also detected in two sporadic PKD cases. CONCLUSION: This study shows that PKD, ICCA and some other PD-related phenotypes are part of the same phenotypic spectrum, caused by mutations in PRRT2. This underscores the complexity of the phenotypic consequences of PRRT2 mutations.


Assuntos
Coreia/genética , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética , Coreia/diagnóstico , Diagnóstico Diferencial , Ordem dos Genes , Humanos , Fenótipo
8.
Biomed Environ Sci ; 25(4): 421-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23026522

RESUMO

OBJECTIVE: To explore the risk factors of low back pain among the Chinese occupational population in several major industries. METHODS: A total of 7200 subjects (3600 cases and 3600 controls) were randomly sampled from a cross-sectional study, and they were investigated for individual and occupational factors of low back pain. The potential risk factors were first selected by using chi-square tests. Secondly, collinearity diagnosis proceeded by using the Kendall's rank correlation. Finally, binary logistic regression model was used for multi-factor analysis. RESULTS: Collinearity diagnosis showed that there was a severe collinearity problem among the potential risk factors of low back pain. Logistic regression model included 20 variables with statistical significance. Bending neck forward or holding neck in a forward posture for long periods (OR=1.408) was the most important risk factor inducing low back pain in this study, followed by bending heavily with the trunk (OR=1.402), carrying out identical work almost for the whole day (OR=1.340). Additionally, sufficient normal break was a protective factor of low back pain. CONCLUSION: Low back pain among the Chinese occupational population was associated with body height, occupation, work organization, physical work, working posture, and others. All these risk factors could be regarded as the indicators of low back pain, and some relevant preventive measures should be taken to reduce low back pain risk.


Assuntos
Dor Lombar/epidemiologia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Ocupações , Postura , Fatores de Risco , Adulto Jovem
9.
Zhonghua Yi Xue Za Zhi ; 92(4): 250-3, 2012 Jan 31.
Artigo em Zh | MEDLINE | ID: mdl-22490797

RESUMO

OBJECTIVE: To explore the prevalence and mutation pattern of H221Y at reverse transcriptase (RT) among the subtype B' of human immunodeficiency virus1 (HIV-1) in antiviral therapy-failure patients. METHODS: A total of 1363 sequences, comprising of 1205 therapy-failure individuals and 158 therapy-naive individuals, were submitted to the Stanford HIV drug resistance database (SHDB) to analyze the frequency and mutation pattern of H221Y. RESULTS: The prevalence of mutation H221Y in the therapy-failure population was significantly higher than that of the therapy-naive (6.59% vs 0.60%) (χ(2) = 6.59, P = 0.027). The emergence of H221Y usually accompanied the position mutations of T215, M184, K103 and Y181 of RT, and the pattern of TAMs/H221Y/Y181C/I was common. Frequency of H221Y in the regimen of AZT/ddI/NVP was more popular than the other 4 regimens (14.6% vs 3.5%, 4.9%, 2.3%, 2.6%, all P < 0.01). CONCLUSION: With a unique mutation pattern, H221Y has a low prevalence in the individuals of first-line therapy-failure patients.


Assuntos
Farmacorresistência Viral/genética , HIV-1/genética , Mutação , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Feminino , Genes Virais/genética , Genótipo , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Artigo em Zh | MEDLINE | ID: mdl-22804984

RESUMO

OBJECTIVE: To evaluate the reliability and validity of musculoskeletal questionnaire. METHODS: A self-administered modified musculoskeletal questionnaire was used to investigate 12 098 workers from eight occupations, i.e. coal mining, petroleum, metallurgical, mechanical manufacturing, chemical, garment and railroad transportation industries and education. The Cronbach's α coefficient, analysis of covariance and multiple logistic regression were used to assess the reliability and validity of musculoskeletal questionnaire. RESULTS: The consistent test between total items of Musculoskeletal Questionnaire and each factor showed that the range of Cronbach's α was 0.52 ∼ 0.92, except from vibration factor, other Cronbach's α was more than 0.7. All 55 items of Musculoskeletal Questionnaire were subjected to factor analysis, and ten latent factors were identified, which explained 55.17% of the total variance. The potentially hazardous working conditions could be categorized into seven dimensions (force, dynamic load, static load, repetitive load, climate factors, vibration exposure and environmental ergonomic factor), which consisted with the theory model. The results of covariance analysis indicated that there were significant difference among 7 dimension indices in different jobs (P < 0.01). CONCLUSION: The modified Musculoskeletal Questionnaire is a valid and reliable tool for measuring musculoskeletal workload.


Assuntos
Doenças Musculoesqueléticas , Inquéritos e Questionários , Análise Fatorial , Humanos , Saúde Ocupacional
11.
Zhonghua Yi Xue Za Zhi ; 91(21): 1443-7, 2011 Jun 07.
Artigo em Zh | MEDLINE | ID: mdl-21914277

RESUMO

OBJECTIVE: To analyze the occurring rules of human immunodeficiency virus (HIV) drug resistance under an unique therapy model among HIV-1 infected individuals on antiretroviral therapy (ART) in rural areas of Henan, China. METHODS: A cohort of 75 individuals on an ART regimen of zidovudine (ZDV), dideoxyinosine (ddI) and nevirapine (NVP) was established in March 2003. A total of 12 surveillance were conducted and 788 person-times were studied until 2010. The parameters of CD4 cell count and viral load (VL) were tested in each survey. And genotypic resistance testing was performed in patients with a failure of viral suppression. Survival analysis was used to estimate the occurrence time of resistance. RESULTS: The cumulative mortality rate was 16% (12/75) in the cohort. And the cumulative resistance rate was 88% (66/75) from 2004 to 2010. The rate of resistance reached 54.7% and the probability from susceptibility to drugs developing resistance decreased drastically from 100% to 45.3% within the first 1 year of initiation. The occurrence time of resistance for half of individuals in the cohort was at 12.0 months (95%CI 8.6 - 17.0) after initiation, 25.1 months (95%CI 19.0 - 33.3) in those whose VL was less than 4.0 lgU/ml and 4.8 months (95%CI 4.1 - 5.6) at VL > 4.0 lgU/ml during the first investigation. The individuals with an early occurrence of resistance within 12 months carried high risks for a failure of viral suppression and a decrease of CD4 counts. CONCLUSION: The occurrence of resistance rises with the course of therapy. And the greatest probability for resistance is within the first 1 year of initial therapy. A high level of VL has a significant impact on the development of resistance. Preventing the occurrence of resistance during the initial therapy remains a key goal.


Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , HIV-1/efeitos dos fármacos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural
12.
Artigo em Zh | MEDLINE | ID: mdl-21619811

RESUMO

OBJECTIVE: To study neck and shoulder work-related muscle fatigue of female sewing machine operators. METHODS: 18 health female sewing machine operators without musculoskeletal disorders work in Beijing garment industry factory as volunteers in participate of this study. The maximal voluntary contraction (MVC) and 20% MVC of bilateral upper trapezium and cervical erectors spinae was tested before sewing operations, then the whole 20 time windows (1 time window = 10 min) sewing machine operations was monitored and the surface electromyography (sEMG) signals simultaneously was recorded after monitoring the 20%MVC was tested. Use amplitude analysis method to reduction recorded EMG signals. RESULTS: During work, the median load for the left cervical erector spinae (LCES), right cervical erector spinae (RCES), left upper trapezium (LUT) and right upper trapezium (RUT) respectively was 6.78 ± 1.05, 6.94 ± 1.12, 5.68 ± 2.56 and 6.47 ± 3.22, work load of right is higher than the left; static load analysis indicated the value of RMS(20%MVC) before work was higher than that value after work, the increase of right CES and UT RMS(20%MVC) was more; the largest 20%MVE of bilateral CES occurred at 20th time window, and that of bilateral UT happened at 16th. CONCLUSIONS: The work load of female sewing machine operators is sustained "static" load, and work load of right neck-shoulder is higher than left, right neck-shoulder muscle is more fatigable and much serious once fatigued.


Assuntos
Fadiga Muscular/fisiologia , Ombro/fisiologia , Indústria Têxtil , Adulto , Eletromiografia , Feminino , Humanos , Postura , Trabalho , Adulto Jovem
13.
Artigo em Zh | MEDLINE | ID: mdl-22357530

RESUMO

OBJECTIVE: To develop a draft questionnaire (China Musculoskeletal Questionnaire, CMQ) for evaluating of musculoskeletal workload and associated potential hazardous working conditions as well as musculoskeletal symptoms of workers in Sitting Posture. METHODS: Multi-methods, which include the reviewing references, the summarizing results of preliminary studies, the reviewing ergonomic tools, the consulting experts and occupational health workers and the interviewing or discussing with individual workers in sitting posture, were used in developing item pool. The experts and epidemiologists of occupational health scored the importance of every single item in the item pool, and then the survey and sampling were carried out in 325 workers of sitting posture who completed the questionnaire. On the basis of these data, the methods including experts scoring, item analysis, Cronbach's α analysis and factor analysis were synthetically used to select the reliable items which consisted of the formal questionnaire. RESULTS: The standard of the CMQ, which consists of 34 items on musculoskeletal workload and associated potentially hazardous working conditions, can be divided into nine indices (dynamic loads, static loads, repetitive loads, forces-exertion, prolong time, climatic factors, vibration, position and ergonomic environmental factors). CONCLUSION: The CMQ possesses good content validity, and the items of CMQ are divergent, reliable and typical. However, the reliability and validity of CMQ should be validated.


Assuntos
Sistema Musculoesquelético , Saúde Ocupacional , Postura , Inquéritos e Questionários , China , Ergonomia , Humanos , Carga de Trabalho
14.
Analyst ; 135(11): 2826-31, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20830327

RESUMO

In this contribution, we report a molecular recognition between adenosine and its aptamer, which leads to the formation of a four-stranded tetraplex structures (G-quartet) of the aptamer. It is found that the formed G-quartet could induce the side-by-side self-assembly of gold nanorods (AuNRs) owing to the electrostatic interaction between the positive charge of cetyltrimethylammonium bromide (CTAB) on the AuNR surface and the negative charge of the formed G-quartet. Furthermore, the side-by-side self-assembly of AuNRs is characterized by the enhancement of plasmon resonance light scattering (PRLS) signals and the blue-shift of the longitudinal plasmon resonance absorption (LPRA) band owing to the plasmon resonance coupling. Then, based on the enhanced PRLS signals, a simple, highly selective and sensitive detection method for adenosine was developed in the range of 4.0-80.0 nM with the limit of determination of 2.0 nM, which is up to now the best sensitive optical detection method to our knowledge. This method has been successfully applied to the detection of adenosine phosphates in the brains of SD rats, which was in good agreement with a high-performance liquid chromatographic (HPLC) method.


Assuntos
Adenosina/análise , Aptâmeros de Nucleotídeos/química , Encéfalo , Ouro/química , Modelos Animais , Nanotubos/química , Animais , Cromatografia Líquida de Alta Pressão , Quadruplex G , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Ressonância de Plasmônio de Superfície
15.
Yao Xue Xue Bao ; 45(2): 241-6, 2010 Feb.
Artigo em Zh | MEDLINE | ID: mdl-21351434

RESUMO

JB25 and JB26 are new HIV-1 nonnucleoside reverse transcriptase inhibitors, and show potent anti-HIV activities. Sequential passage experiments with wild-type virus were performed to select and identify mutations induced by these two compounds in vitro. For the initial passage, compounds were present at approximately 2-fold IC50 in MT-2 cells. When cytopathic effect (CPE) was observed in more than 75% of the cells, the culture supernatants were collected. For the subsequent passages, fresh MT-2 cells were infected with 1 mL supernatants from the previous passage (regardless of the virus titer) and cultured in the presence of the compounds at concentrations that were increased 2-fold compared with that in the previous passage. This procedure was repeated with increasing concentrations for 12 passages. JB25 had amino acid substitution L100I (TTA-->ATA) at passage 6, and then changed into 100 M (ATA-->ATG) at passage 12, which was rare mutation form and had not been reported. At the same time, Y188C (TAT-->TGT) mutation appeared at passage 10. For JB26, there was a L100I (TTA-->ATA) mutation at passage 10. In a word, JB25 and JB26 showed a low genetic barrier to the development of resistance, and the resistance to JB26 developed slower than JB25. The mutations selected by JB25 and JB26 were mainly associated with codons 188 and 100 of HIV-1 reverse transcriptase.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Transcriptase Reversa do HIV/genética , HIV-1/enzimologia , Mutação , Inibidores da Transcriptase Reversa/farmacologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Linhagem Celular , Códon , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos
16.
Retrovirology ; 5: 72, 2008 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-18680593

RESUMO

BACKGROUND: Although APOBEC3G protein is a potent and innate anti-HIV-1 cellular factor, HIV-1 Vif counteracts the effect of APOBEC3G by promoting its degradation through proteasome-mediated proteolysis. Thus, any means that could prevent APOBEC3G degradation could potentially enhance its anti-viral effect. The UBA2 domain has been identified as an intrinsic stabilization signal that protects protein from proteasomal degradation. In this pilot study, we tested whether APOBEC3G, when it is fused with UBA2, can resist Vif-mediated proteasomal degradation and further inhibit HIV-1 infection. RESULTS: APOBEC3G-UBA2 fusion protein is indeed more resistant to Vif-mediated degradation than APOBEC3G. The ability of UBA2 domain to stabilize APOBEC3G was diminished when polyubiquitin was over-expressed and the APOBEC3G-UBA2 fusion protein was found to bind less polyubiquitin than APOBEC3G, suggesting that UBA2 stabilizes APOBEC3G by preventing ubiquitin chain elongation and proteasome-mediated proteolysis. Consistently, treatment of cells with a proteasome inhibitor MG132 alleviated protein degradation of APOBEC3G and APOBEC3G-UBA2 fusion proteins. Analysis of the effect of APOBEC3G-UBA2 fusion protein on viral infectivity indicated that infection of virus packaged from HEK293 cells expressing APOBEC3G-UBA2 fusion protein is significantly lower than those packaged from HEK293 cells over-producing APOBEC3G or APOBEC3G-UBA2 mutant fusion proteins. CONCLUSION: Fusion of UBA2 to APOBEC3G can make it more difficult to be degraded by proteasome. Thus, UBA2 could potentially be used to antagonize Vif-mediated APOBEC3G degradation by preventing polyubiquitination. The stabilized APOBEC3G-UBA2 fusion protein gives stronger inhibitory effect on viral infectivity than APOBEC3G without UBA2.


Assuntos
Citidina Desaminase/metabolismo , Citidina Desaminase/farmacologia , Expressão Gênica , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Enzimas Ativadoras de Ubiquitina/metabolismo , Replicação Viral/efeitos dos fármacos , Desaminase APOBEC-3G , Linhagem Celular , Inibidores de Cisteína Proteinase/farmacologia , Citidina Desaminase/genética , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Humanos , Leupeptinas/farmacologia , Poliubiquitina/genética , Poliubiquitina/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Enzimas Ativadoras de Ubiquitina/genética , Ubiquitinação , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 28(12): 1127-8, 2008 Dec.
Artigo em Zh | MEDLINE | ID: mdl-19317174

RESUMO

The structures of "V + -ing + N" and "N + V + ed + N" were proposed, and their characteristics and advantages as well as practical application were introduced aiming at the existent problems in the present translation of TCM terms and solving them.


Assuntos
Medicina Tradicional Chinesa/normas , Terminologia como Assunto , Tradução
18.
J Antibiot (Tokyo) ; 60(4): 272-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17456979

RESUMO

An unknown impurity named amphotericin B (2) (AmB(2)) isolated from amphotericin B (AmB) bulk material was identified as (1S,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(3-amino-3,6-dideoxy-beta-D-mannopyranosyl)oxy]-1-methyloxy-3,5,6,9,11,17,37-heptahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid according to the IUPAC. The structure was elucidated by various 1D and 2D NMR techniques, mass spectrometry and by comparison with the NMR data of AmB. Its activity against Candida albicans was evaluated by comparison with AmB.


Assuntos
Anfotericina B/análise , Antifúngicos/análise , Contaminação de Medicamentos , Anfotericina B/farmacologia , Candida albicans/efeitos dos fármacos , Espectroscopia de Ressonância Magnética
20.
Chin Med J (Engl) ; 119(23): 1972-7, 2006 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-17199941

RESUMO

BACKGROUND: This study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance. METHODS: The genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested. Fifty percent inhibitory concentrations (IC50) between resistant and sensitive viruses were compared. The resistance extent was determined by the folds of the increased IC50. The concordance between the phenotypic resistance and genotypic resistance was also analyzed. RESULTS: IC50 of resistant isolates were 0.0006 - 0.1300 micromol/L for zidovudine (AZT), 0.0016 - 0.0390 micromol/L for lamivudine (3TC), 0.0104 - 0.4234 micromol/L for nevirapine (NVP), and 0.0163 - 0.1142 micromol/L for indinavir (IDV), respectively. Genotypic and phenotypic resistance assays indicated that the resistant strains were intermediately and highly resistant to nucleotide analog reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase inhibitors. The phenotypic assay was consistent with the genotypic assay. For measuring the potential resistance, the genotypic assay was more sensitive than the phenotypic. In evaluating the resistance to protease inhibitors, these two assays were discrepant. CONCLUSIONS: Both the phenotypic and genotypic assays indicate that the resistant viruses exist in HIV-infected patients in China who have received treatment. Phenotypic and genotypic assays have high concordance, and the genotypic assay could replace the phenotypic assay to predict the HIV-1 resistance.


Assuntos
Farmacorresistência Viral/genética , HIV-1/efeitos dos fármacos , Antirretrovirais/farmacologia , China , HIV-1/genética , Humanos , Mutação , Fenótipo
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