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1.
Int J Biol Sci ; 15(10): 2182-2197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592234

RESUMO

Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in the vertebrae of patients with glucocorticoid (GC)-induced osteoporosis (GIOP). The study was performed to determine the role of let-7f-5p in GC-inhibited osteogenic differentiation of murine BMSCs in vitro and in GIOP in vivo. Here, we report that dexamethasone (Dex) inhibited osteogenic differentiation of BMSCs and let-7f-5p expression, while increasing the expression of transforming growth factor beta receptor 1 (TGFBR1), a direct target of let-7f-5p during osteoblast differentiation under Dex conditions. In addition, let-7f-5p promoted osteogenic differentiation of BMSCs, as indicated by the promotion of alkaline phosphatase (ALP) staining and activity, Von Kossa staining, and osteogenic marker expression (Runx2,Osx, Alp, and Ocn), but decreased TGFBR1 expression in the presence of Dex. However, overexpression of TGFBR1 reversed the upregulation of let-7f-5p during Dex-treated osteoblast differentiation. Knockdown of TGFBR1 reversed the effect of let-7f-5p downregulation during Dex-treated osteogenic differentiation of BMSCs. We also found that glucocorticoid receptor (GR) mediated transcriptional silencing of let-7f-5p and its knockdown enhanced Dex-inhibited osteogenic differentiation. Further, when injected in vivo, agomiR-let-7f-5p significantly reversed bone loss induced by Dex, as well as increased osteogenic marker expression (Runx2, Osx, Alp, and Ocn) and decreased TGFBR1 expression in bone extracts. These findings indicated that the regulatory axis of GR/let-7f-5p/TGFBR1 may be important for Dex-inhibited osteoblast differentiation and that let-7f-5p may be a useful therapeutic target for GIOP.

2.
J Appl Oral Sci ; 27: e20180693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596370

RESUMO

OBJECTIVES: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. METHODOLOGY: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. RESULTS: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). CONCLUSIONS: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.


Assuntos
Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Óxidos/farmacologia , Tecido Periapical/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Materiais Restauradores do Canal Radicular/farmacologia , Tratamento do Canal Radicular/métodos , Silicatos/farmacologia , Cicatrização/efeitos dos fármacos , Adolescente , Animais , Regeneração Óssea/efeitos dos fármacos , Contagem de Células , Células Cultivadas , Cães , Combinação de Medicamentos , Humanos , Masculino , Teste de Materiais , Osteogênese/efeitos dos fármacos , Tecido Periapical/citologia , Tecido Periapical/diagnóstico por imagem , Ligamento Periodontal/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de Tempo , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/efeitos dos fármacos , Raiz Dentária/cirurgia , Resultado do Tratamento , Microtomografia por Raio-X , Adulto Jovem
3.
J Zhejiang Univ Sci B ; 20(10): 838-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489803

RESUMO

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/ß-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ ß-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3ß (GSK-3ß), and ß-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3ß, and ß-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/ß-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Osteoporose/etiologia , Receptor IGF Tipo 1/fisiologia , beta Catenina/fisiologia , Idoso , Animais , Densidade Óssea , Diabetes Mellitus Experimental/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Transdução de Sinais , Estreptozocina
4.
Drug Dev Res ; 80(4): 438-445, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30680760

RESUMO

In this study, a series of new fluorine or chlorine-substituted cinnamic acid derivatives that contain tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results show that almost all the derivatives containing tertiary amine side chain (compounds 4a-9d) exhibit moderate or potent activity in AChE inhibition. By contrast, their parent compounds (compounds 3a-3f) in the absence of tertiary amine moitery exhibit poor inhibitory activity against AChE. For the compounds containing pyrroline or piperidine side chain, the bioactivity in AChE inhibition is much intense than those containing N,N-diethylamino side chain. The chlorine or fluorine substituted position produces a significant effect on the bioactivity and selectivity in AChE inhibition. Most of the compounds that contain para-substituted fluorine or chlorine exhibit potent activity against AChE and poor activity against BChE, while ortho-substituted analogs show the opposite effect. It is worth noticing that the compounds containing N,N-diethylamino side chain are exceptions to this pattern. Among the newly synthesized compounds, compounds 6d are the most potent in AChE inhibition (IC50 = 1.11 ± 0.08 µmol/L) with high selectivity for AChE over BChE (selectivity ratio: 46.58). An enzyme kinetic study of compounds 6d suggests it produces a mixed-type inhibitory effect in AChE.


Assuntos
Aminas/química , Cloro/química , Inibidores da Colinesterase/farmacologia , Cinamatos/farmacologia , Desenho de Drogas , Flúor/química , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Cinamatos/síntese química , Cinamatos/química , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
5.
J. appl. oral sci ; 27: e20180693, 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1040226

RESUMO

ABSTRACT Objectives: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. Methodology: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. Results: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). Conclusions: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.

6.
Cell Physiol Biochem ; 47(6): 2307-2318, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975930

RESUMO

BACKGROUND/AIMS: Plastrum testudinis extracts (PTE) show osteoprotective effects on glucocorticoid-induced osteoporosis in vivo and in vitro. However, the underlying molecular mechanism of PTE in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. METHODS: BMSC proliferation was investigated using the Cell Counting Kit-8 assay. BMSC differentiation and osteogenic mineralization were assayed using alkaline phosphatase and Alizarin red staining, respectively. The mRNA expression levels of Let-7f-5p, Tnfr2, Traf2, Pi3k, Akt, ß-catenin, Gsk3ß, Runx2, and Ocn were measured using real time quantitative polymerase chain reaction. Protein levels of TNFR2, TRAF2, p-PI3K, p-AKT, p-ß-CATENIN, and p-GSK3ß were analyzed by western blotting. The functional relationship of Let-7f-5p and Tnfr2 was determined by luciferase reporter assays. RESULTS: The optimum concentration for PTE was 30 µg/ml. PTE significantly promoted BMSC osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, ß-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3ß mRNA expression. PTE inhibited TNFR2, TRAF2, and p-ß-CATENIN protein expression, and promoted p-PI3K, p-AKT, and p-GSK3ß protein expression. In addition, Tnfr2 was a functional target of Let-7f-5p in 293T cells. CONCLUSIONS: Our results suggested that PTE may promote BMSC proliferation and osteogenic differentiation via a mechanism associated with the regulation of Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/biossíntese , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/biossíntese , Transdução de Sinais/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Animais , Células da Medula Óssea/citologia , Feminino , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Sprague-Dawley
7.
J Enzyme Inhib Med Chem ; 33(1): 110-114, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29166796

RESUMO

A series of benzamide and picolinamide derivatives containing dimethylamine side chain (4a-4c and 7a-7i) were synthesised and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity in vitro. Structure-activity relationship investigation revealed that the substituted position of dimethylamine side chain markedly influenced the inhibitory activity and selectivity against AChE and BChE. In addition, it seemed that the bioactivity of picolinamide amide derivatives was stronger than that of benzamide derivatives. Among them, compound 7a revealed the most potent AChE inhibitory activity (IC50: 2.49 ± 0.19 µM) and the highest selectivity against AChE over BChE (Ratio: 99.40). Enzyme kinetic study indicated that compound 7a show a mixed-type inhibition against AChE. The molecular docking study revealed that this compound can bind with both the catalytic site and the peripheral site of AChE.


Assuntos
Benzamidas/farmacologia , Inibidores da Colinesterase/farmacologia , Dimetilaminas/farmacologia , Ácidos Picolínicos/farmacologia , Acetilcolinesterase/metabolismo , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Animais , Benzamidas/síntese química , Benzamidas/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Dimetilaminas/química , Relação Dose-Resposta a Droga , Enguias , Humanos , Modelos Moleculares , Estrutura Molecular , Ácidos Picolínicos/síntese química , Ácidos Picolínicos/química , Relação Estrutura-Atividade
8.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3819-3825, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29235301

RESUMO

This paper systematically studies relevant literatures at home and abroad in recent years. China National Knowledge Internet (CNKI) was used to collect the literatures for acute pharyngitis treated with traditional Chinese medicine from January 1, 2006, to December 31, 2016, and the bibliometric method was employed for statistical analysis. A total of 493 papers were preliminarily selected. According to the inclusion criteria and exclusion criteria, 182 eligible articles were selected. According to the evaluation and analysis of the literatures, the Guidelines for Clinical Research of New Drugs is currently used as the common standards for the diagnosis and treatment of acute pharyngitis; Chinese patent medicines are the main traditional Chinese medicine for treating this disease; Decoctions for treatment of this disease include Lonicerae Japonicae Flos, Scutellariae Radix, Platycodonis Radix, Forsythiae Fructus, Glycyrrhizae Radix et Rhizoma, Scrophdlariae Radix, Isatidis Radix, and Ophiopogonis Radix; The bloodletting puncture is the common external therapy. Traditional Chinese medicine and Western medicine have their own characteristics in the treatment of this disease. Western medicine for the treatment of acute pharyngitis are mainly antiviral, antibiotic and glucocorticoid drugs, whose disadvantages are toxicity, side effects, drug resistance and double infections. Traditional Chinese medicine doctors have rich experiences in the treatment of the disease, which is characterized by treatment determination based on syndrome differentiation, safe and reliable medication, significant curative effect, low drug resistance, and wide varieties of traditional Chinese medicine forms, convenient portability and taking, low price, and low toxic and side effects. It is an arduous and significant task to explore traditional Chinese medicine, and study and develop new-type effective drugs.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Faringite/terapia , China , Humanos
9.
Oncotarget ; 8(43): 73559-73567, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088726

RESUMO

Osteoporotic vertebral fracture (OVF) is a worldwide health concern and lacks sufficient basic studies. Suitable animal models should be the foundation for basic study and treatment of OVF. There have been few studies on the development of animal models of osteoporotic vertebral bone defects. OVF models using various animal species should be developed to evaluate the therapeutic strategy in preclinical testing. We developed an OVF model in rats. Rat osteoporosis was induced by ovariectomy (OVX), and 3 months after OVX, a 3 mm diameter hemispheric vertebral bone defect was developed in lumbar vertebra 6 (L6). Sagittal plain X-rays of the rats, their bone quantity, bone microarchitecture, and histomorphology were analyzed: 3 months after OVX, rats showed significantly lower bone quantity, relative bone volume, and total volume bone mineral density. After the vertebral bone defect had developed for 16 weeks, no significant indication of self-healing could be observed from the sagittal plain X-rays, three-dimensional images, and histomorphology. These results indicate that the rat model of osteoporotic vertebral bone defect, induced by OVX and a 3 mm diameter hemispheric vertebral bone defect, can sufficiently mimic OVF patients in clinic and provide a sound basis for subsequent studies.

10.
J Enzyme Inhib Med Chem ; 32(1): 146-152, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27801600

RESUMO

A new series of tertiary amine derivatives of chlorochalcone (4a∼4l) were designed, synthesized and evaluated for the effect on acetylcholinesterase (AChE) and buthylcholinesterase (BuChE). The results indicated that all compounds revealed moderate or potent inhibitory activity against AChE, and some possessed high selectivity for AChE over BuChE. The structure-activity investigation showed that the substituted position of chlorine significantly influenced the activity and selectivity. The alteration of tertiary amine group also leads to obvious change in bioactivity. Among them, IC50 of compound 4l against AChE was 0.17 ± 0.06 µmol/L, and the selectivity was 667.2 fold for AChE over BuChE. Molecular docking and enzyme kinetic study on compound 4l suggested that it simultaneously binds to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Further study showed that the pyrazoline derivatives synthesized from chlorochalcones had weaker activity and lower selectivity in inhibiting AChE compared to that of chlorochalcone derivatives.


Assuntos
Acetilcolinesterase/metabolismo , Aminas/farmacologia , Butirilcolinesterase/metabolismo , Chalconas/farmacologia , Cloro/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cetonas/química , Aminas/síntese química , Aminas/química , Animais , Chalconas/química , Cloro/farmacologia , Inibidores da Colinesterase/síntese química , Relação Dose-Resposta a Droga , Cetonas/farmacologia , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
11.
Chin J Nat Med ; 15(11): 871-880, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29329615

RESUMO

Soy isoflavones exhibit various biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardiovascular protective effects. The present study was designed to investigate the effects of sixteen synthesized 3-amino-2-hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2 (Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements) pathway in human cancer cell lines. Most of the tested compounds exerted greater cytotoxic activity than genistein, as measured by MTT assay. Moreover, compound 8c showed the highest ARE-luciferase reporter activity among the test compounds. It strongly promoted Nrf2 nuclear translocation and up-regulated the expression of total Nrf2 and downstream targets NQO-1 and HO-1 at protein level. The present study may provide a basis for the application of isoflavone derivatives as Nrf2/ARE pathway inducers for cancer therapy and cancer prevention.


Assuntos
Genisteína/uso terapêutico , Neoplasias/tratamento farmacológico , Soja/química , Elementos de Resposta Antioxidante , Linhagem Celular Tumoral , Proliferação de Células , Genisteína/síntese química , Genisteína/farmacologia , Heme Oxigenase-1/metabolismo , Humanos , Isoflavonas , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Regulação para Cima
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(10): 1386-1389, 2016 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-27777203

RESUMO

OBJECTIVE: To study the serum level of carbohydrate antigen 125 (CA125) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its relation with pulmonary hypertension. METHODS: Forty-six patients with AECOPD complicated by pulmonary hypertension, 46 with AECOPD and 38 healthy control subjects were examined for their clinical data, pulmonary function, echocardiographic findings, and serum levels of lung tumor markers and brain natriuretic peptide (BNP). RESULTS: Compared with the healthy control group, COPD patients with or without pulmonary hypertension showed significantly decreased pulmonary function (P<0.05), especially in those with AECOPD and concurrent pulmonary hypertension (P<0.05). Serum CA125 level was obviously higher in AECOPD group than in the healthy control group, and further increased in AECOPD patients with pulmonary hypertension (P<0.05). The levels of lung tumor markers (CEA, NSE, CYFRA and PROGRP) were similar among the 3 groups (P>0.05). The serum level of BNP in patients with AECOPD and concurrent pulmonary hypertension was significantly higher than that in patients with AECOPD (P<0.05). Pearson linear correlation analysis showed that serum CA125 was positively correlated with pulmonary artery systolic pressure and BNP in AECOPD patients with pulmonary hypertension (P<0.01). CONCLUSION: Serum CA125 may serve as a serological index to identify AECOPD patients with pulmonary hypertension.


Assuntos
Antígeno Ca-125/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Aguda , Biomarcadores Tumorais , Estudos de Casos e Controles , Progressão da Doença , Humanos , Hipertensão Pulmonar/fisiopatologia , Pulmão , Peptídeo Natriurético Encefálico/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
13.
Chin J Nat Med ; 14(6): 462-72, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27473965

RESUMO

Soy isoflavones exert a wide variety of biological activities, such as antioxidant, anti-inflammatory and anti-cancer properties. Nuclear factor erythroid 2-related factor 2 (Nrf2), a bZip transcription factor, plays a key role in soy isoflavones induced protection against oxidative stress and cancer. To obtain more effective isofavones, a series of 7,4'-bis-(3-amino-2-hydroxypropoxy), 7 or 4'-(3-amino-2-hydroxypropoxy) isoflavone derivatives have been synthesized as potential antitumor agents and Nrf2/ARE (antioxidant response element) activators. The cytotoxicity of these compounds in human cancer cell lines MDA-MB-231, HT-29, HCT116, HepG2 and 7402 was tested by MTT assay. In this study, the cytotoxicity of compound 3b exhibited highest cytotoxic activity and at the safety dose range, it also strongly up-regulated antioxidant response element (ARE)-luciferase reporter activity. In addition, compound 3b induced Nrf2 nuclear translocation and upregulated its downstream target genes NQO-1 and HO-1 at protein level. Taken together, our results suggest that compound 3b could be a potential agent for cancer themotherapy or cancer chemoprevention.


Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Isoflavonas/síntese química , Isoflavonas/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Humanos , Isoflavonas/química , Estrutura Molecular , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
15.
BMC Infect Dis ; 15: 18, 2015 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-25595618

RESUMO

BACKGROUND: This report describes emergency response following an imported vaccine derived poliovirus (VDPV) case from Myanmar to Yunnan Province, China and the cross-border collaboration between China and Myanmar. Immediately after confirmation of the VDPV case, China disseminated related information to Myanmar with the assistance of the World Health Organization. METHODS: A series of epidemiological investigations were conducted, both in China and Myanmar, including retrospective searches of acute flaccid paralysis (AFP) cases, oral poliovirus vaccine (OPV) coverage assessment, and investigation of contacts and healthy children. RESULTS: All children <2 years of age had not been vaccinated in the village where the VDPV case had lived in the past 2 years. Moreover, most areas were not covered for routine immunization in this township due to vaccine shortages and lack of operational funds for the past 2 years. CONCLUSIONS: Cross-border collaboration may have prevented a potential outbreak of VDPV in Myanmar. It is necessary to reinforce cross-border collaboration with neighboring countries in order to maximize the leverage of limited resources.


Assuntos
Surtos de Doenças/prevenção & controle , Poliomielite/prevenção & controle , Vacina Antipólio Oral/provisão & distribução , Poliovirus/imunologia , Criança , Pré-Escolar , China/epidemiologia , Comportamento Cooperativo , Emigração e Imigração , Feminino , Humanos , Lactente , Masculino , Mianmar/epidemiologia , Estudos Retrospectivos , Vacinação , Organização Mundial da Saúde
16.
Chem Biol Drug Des ; 86(4): 517-22, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25588967

RESUMO

A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a˜3l) were designed, synthesized, characterized and evaluated for the inhibitory activity against acetylcholinesterase and butyrylcholinesterase. The results showed that the alteration of fluorine atom position and amino-alkyl groups markedly influenced the activity and the selectivity of chalcone derivates in inhibiting acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses the most potent inhibitory against acetylcholinesterase (IC50  = 0.21 ± 0.03 µmol/L), and the highest selectivity for acetylcholinesterase over butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and enzyme kinetic study on compound 3l supported its dual acetylcholinesterase inhibitory profile, simultaneously binding at the catalytic active and peripheral anionic site of the enzyme.


Assuntos
Acetilcolinesterase/química , Doença de Alzheimer/tratamento farmacológico , Chalconas/química , Inibidores da Colinesterase/química , Hidrocarbonetos Fluorados/química , Simulação de Acoplamento Molecular , Doença de Alzheimer/enzimologia , Animais , Chalconas/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Humanos , Hidrocarbonetos Fluorados/uso terapêutico
17.
Bioorg Med Chem ; 22(21): 6124-33, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25260958

RESUMO

A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The logP values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 µmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 µmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE.


Assuntos
Acetilcolinesterase/metabolismo , Chalcona/química , Chalcona/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Acetilcolinesterase/química , Animais , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Cristalografia por Raios X , Desenho de Drogas , Humanos , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Torpedo
18.
Bing Du Xue Bao ; 30(1): 66-72, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24772901

RESUMO

To investigate the epidemic and evolutionary trends of enterovirus (EV) in the external environment of Yunnan Province, China, molecular typing was performed on 4 EV strains that were isolated from environmental sewage in Yunnan. The VP1 region of isolates was amplified by RT-PCR using universal enterovirus primers, and the amplified VP1 region was sequenced for GenBank BLAST search and genotype analysis. The 4 EV strains were identified as ECHO7. Their nucleotide and amino acid homologies with the VP1 sequences of 68 ECHO7 strains retrieved from GenBank were measured by Mega software analysis. Our findings showed that ECHO7 strains from environmental sewage and population samples were in different evolutionary branches. These strains showed typical geographical and temporal differences; In addition, there were different transmission chains at the same time and in the same area. ECHO7 strains isolated from sewage water and patients with acute flaccid paralysis during the same period in Yunnan belonged to different clusters and evolved at different speeds. Special concerns are needed for this problem. Continuous molecular biological surveillance of human EV in the external environment of Yunnan will provide strong support for early warning of EV diseases.


Assuntos
Enterovirus/genética , Enterovirus/isolamento & purificação , Epidemiologia Molecular , Esgotos/virologia , China , Bases de Dados Genéticas , Evolução Molecular , Humanos , Análise de Sequência
19.
Bing Du Xue Bao ; 29(2): 169-75, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23757848

RESUMO

In order to explore the genotype distribution and molecular evolution of non-polio enterovirus (NPEVs)in Yunnan Province,the People's Republic of China, we sequenced and analyzed the partial VP1 coding region of 105 NPEVs isolated from acute flaccid paralysis (AFP) surveillance in Yunnan province during a 5- year study period from 2006 to 2010. The viral genomes of 105 NPEVs were translated to corresponding amino acid sequences and compared with those of the prototype strains, and the phylogenetic tree was constructed among these VP1 nucleotide sequences and other prototype strains from GenBank. Analysis showed that 18 isolates were classified into 7 serotypes of human enterovirus A species, while 77 isolates into 22 serotypes of B and 10 isolates into 4 serotypes of C species. However, we did not isolate any viruses which belonged to human enterovirus D species. Thus, under AFP surveillance, human enterovirus B species accounted for 73. 3% of the 105 isolates and was considered as the predominant one,followed by human enterovirus A(17. 1%) and human enterovirus C(9. 5%). Phylogenetic analysis showed that various serotypes of the virus and the corresponding prototype strains or other representative strains clustered into the same grooup, however, Yunnan strains and prototype strains were located in the different branches (except CA2,EV90 and EV76). The degree of variation was different even among the same genotype strains. This report showed that different genotype strains spread widely in Yunnan Province.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/classificação , Enterovirus/isolamento & purificação , China/epidemiologia , Enterovirus/genética , Infecções por Enterovirus/epidemiologia , Humanos , Dados de Sequência Molecular , Tipagem Molecular , Filogenia
20.
Bing Du Xue Bao ; 27(4): 342-6, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21874903

RESUMO

To explore the enteroviruses surveillance among healthy children under 15 years old in the border areas of Yunnan Province and Myanmar in 2009. The stool samples were collected from the healthy children under 15 years old who came from the border areas of Myanmar and Yunnan Province, virus isolation and sequencing were conducted for all the 271 samples. 6 strains of polioviruses (PVs) were detected from 271 stools with an isolation rate of 2.8%, which belonged to vaccine strains and 24 non-polioviruses (NPVs) were detected with an isolation rate of 8.9%. 24 NPVs belonged to human enterovirus group B (HEV-B) with 6 serotypes, HEV-A, HEV-C and HEV-D viruses were not isolated. Among them, 13 NPVs were E7 (54.17%) and 5 NPVs were E13 (20.83%). Our results showed that the enterovirus carrying rate in the border areas of Yunnan province was higher than the rate of routine acute flaccid paralysis (AFP) detection system. The HEV-B viruses were the only enteroviruses isolated. The phylogenetical analysis showed that Echovirus 7(E7) and 13 (E13) exhibited genetic polymorphism.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/genética , Enterovirus/isolamento & purificação , Fezes/virologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Enterovirus/classificação , Infecções por Enterovirus/epidemiologia , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Tipagem Molecular , População Rural
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