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1.
Chin J Traumatol ; 22(1): 1-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30850324

RESUMO

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.


Assuntos
Abdome/cirurgia , Drenagem/métodos , Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto , Sociedades Médicas/organização & administração , Infecção da Ferida Cirúrgica/prevenção & controle , Traumatologia/organização & administração , Vácuo , China , Humanos
2.
Chin Med J (Engl) ; 131(5): 567-573, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29483391

RESUMO

Background: Intestinal fistula is one of the common complications of Crohn's disease (CD) that might require surgical treatment. The clinical characteristics and outcomes of CD with intestinal fistula are much different from CD alone. This study was to investigate whether the coagulation status of CD is changed by intestinal fistula. Methods: Data were retrospectively analyzed for 190 patients with a definitive diagnosis of CD who were registered at the Jinling Hospital between January 2014 and September 2015. Baseline clinical characteristics and laboratory indices of initial admission and 7 days after intestinal fistula resections were collected. Student's t-test and the Wilcoxon rank-sum test were used to compare differences between the two groups. Results: Compared with CD patients without intestinal fistula, prothrombin time (PT) in patients with intestinal fistula was significantly longer (12.13 ± 1.27 s vs. 13.18 ± 1.51 s, P < 0.001 in overall cohort; 11.56 ± 1.21 s vs. 12.61 ± 0.73 s, P = 0.001 in females; and 12.51 ± 1.17 s vs. 13.37 ± 1.66 s, P = 0.003 in males). Platelet (PLT) count was much lower in intestinal fistula group than in nonintestinal fistula group (262.53 ± 94.36 × 109/L vs. 310.36 ± 131.91 × 109/L, P = 0.009). Multivariate logistic regression showed that intestinal fistula was significantly associated with a prolonged PT (odds ratio [OR] = 1.900, P < 0.001), a reduced amount of PLT (OR = 0.996, P = 0.024), and an increased operation history (OR = 5.408, P < 0.001). Among 65 CD patients receiving intestinal fistula resections, PT was obviously shorter after operation than baseline (12.28 ± 1.16 s vs. 13.02 ± 1.64 s, P = 0.006). Conclusions: Intestinal fistula was significantly associated with impaired coagulation status in patients complicated with CD. Coagulation status could be improved after intestinal fistula resections.


Assuntos
Coagulação Sanguínea/fisiologia , Doença de Crohn/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Fístula Intestinal/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tempo de Protrombina , Estudos Retrospectivos , Adulto Jovem
3.
World J Gastroenterol ; 23(41): 7489-7494, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29151703

RESUMO

Enterocutaneous fistulas (ECFs) are great challenges during the open abdomen. The loss of digestive juice, water-electrolyte imbalance and malnutrition are intractable issues during management of ECF. Techniques such as "fistula patch" and vacuum-assisted closure therapy have been applied to prevent contamination of open abdominal wounds by intestinal fistula drainage. However, failures are encountered due to high-output fistula and anatomical complexity. Here, we report 3D-printed patient-personalized fistula stent for ECF treatment based on 3D reconstruction of the fistula image. Subsequent follow-up demonstrated that this stent was well-implanted and effective to reduce the volume of enteric fistula effluent.


Assuntos
Traumatismos Abdominais/cirurgia , Acidentes de Trânsito , Fístula Intestinal/cirurgia , Impressão Tridimensional , Stents , Traumatismos Abdominais/etiologia , Humanos , Fístula Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Modelagem Computacional Específica para o Paciente
4.
Molecules ; 22(10)2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-29057806

RESUMO

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1ß, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.


Assuntos
Emodina/administração & dosagem , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Pneumonia/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Influenza Humana/genética , Influenza Humana/virologia , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Fator 2 Relacionado a NF-E2/genética , Pneumonia/etiologia , Pneumonia/patologia , Pneumonia/virologia , RNA Interferente Pequeno/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/genética , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genética , Replicação Viral/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/genética
5.
Int J Oncol ; 48(1): 421-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26647875

RESUMO

Long non-coding RNA MEG3 is suggested to function as a tumor suppressor. However, the activation mechanism of MEG3 is still not well understood and data are not available on its role under adenosine-induced apoptosis. In this study, HepG2 cells were treated with adenosine or 5-Aza­cdR. Methylation status of MEG3 promoter was detected by methylation specific PCR (MSP) and MEG3 expression was determined by qRT-PCR. PcDNA3.1-MEG3 recombinant plasmid was constructed and transfected to hepatoma HepG2 and Huh7 cells. Cell growth, morphological changes, cell-cycle distribution and apoptosis were analyzed by MTT assay, fluorescence microscopy and flow cytometry. The mRNA and protein expression levels were detected by qRT-PCR and western blot analysis. MEG3 binding proteins were screened by the improved MS2 biotin tagged RNA affinity purification method. The co-expression network of MEG3 was generated by GO analysis and ILF3 was identified as MEG3 binding protein by RNA pulldown and western blot analysis. Both adenosine and 5-Aza-CdR increased MEG3 mRNA expression and the CpG island of MEG3 gene in HepG2 cells was typical hypermethylation. Ectopic expression of MEG3 inhibited hepatoma cell growth in a time-dependent manner, resulted in cell cycle arrest and induced apoptosis. Ectopic expression of MEG3 increased p53, caspase-3 mRNA and protein levels, decreased MDM2 and cyclin D1 mRNA and protein levels, as well as ILF3 protein expression in HepG2 cells. These findings are the first to identify that adenosine increases MEG3 expression by inhibition of DNA methylation and its antitumor effects is involved in MEG3 activation. ILF3 may participate in the anticancer regulation of MEG3 by interacting with MEG3.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/biossíntese , Adenosina/administração & dosagem , Azacitidina/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Ilhas de CpG/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/biossíntese , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética
6.
Molecules ; 20(4): 6794-807, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25884554

RESUMO

Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-ß/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-ß1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-ß/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.


Assuntos
Areca/química , Benzofuranos/farmacologia , Ácidos Cafeicos/farmacologia , Diterpenos de Abietano/farmacologia , Lactatos/farmacologia , Nozes/química , Fibrose Oral Submucosa/etiologia , Exsudatos de Plantas/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno/genética , Colágeno/metabolismo , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Fibrose Oral Submucosa/tratamento farmacológico , Fibrose Oral Submucosa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador beta/biossíntese
7.
World J Gastroenterol ; 20(35): 12559-65, 2014 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-25253958

RESUMO

AIM: To investigate whether the heat shock protein 70-2 (HSP70-2) polymorphism is associated with enterocutaneous fistulas in a Chinese population. METHODS: This study included 131 patients with enterocutaneous/enteroatmospheric fistulas. Patients with inflammatory bowel disease or other autoimmune diseases were excluded from this study. All patients with enterocutaneous/enteroatmospheric fistulas were followed up for three months to observe disease recurrence. In addition, a total of 140 healthy controls were also recruited from the Jinling Hospital, matched according to the sex and age of the patient population. Genomic DNA was extracted from peripheral blood from each participant. The HSP70-2 restriction fragment length polymorphism related to the polymorphic PstI site at position 1267 was characterized by polymerase chain reaction (PCR). First PCR amplification was carried out, and then PCR products were digested with PstI restriction enzyme. The DNA lacking the polymorphic PstI site within HSP70-2 generates a product of 1117 bp in size (allele A), whereas the HSP70-2 PstI polymorphism produces two fragments of 936 bp and 181 bp in size (allele B). RESULTS: The frequency of the HSP70-2 PstI polymorphism did not differ between patients and controls; however, the A allele was more predominant in patients with enterocutaneous fistulas than in controls (60.7% vs 51.4%, P = 0.038, OR = 1.425, 95%CI: 1.019-1.994). Sixty-one patients were cured by a definitive operation, drainage operation, or percutaneous drainage while 52 patients were cured by nonsurgical treatment. There was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who had surgery compared to those who did not (P = 0.437, OR = 1.237, 95%CI: 0.723-2.117). Moreover, 11 patients refused any treatment for economic reasons or tumor burden, and 7 patients with enterocutaneous fistulas (5.8%) died during the follow-up period. However, there was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who survived compared to those who died (P = 0.403, OR = 0.604, 95%CI: 0.184-1.986). CONCLUSION: The A allele of the HSP70-2 PstI polymorphism was associated with enterocutaneous fistulas in this Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteínas de Choque Térmico HSP70/genética , Fístula Intestinal/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Fístula Intestinal/diagnóstico , Fístula Intestinal/etnologia , Fístula Intestinal/terapia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
J Oral Pathol Med ; 43(6): 464-70, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24484214

RESUMO

BACKGROUND: Oral submucous fibrosis (OSF) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca nut. Panax notoginseng Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca nut-induced OSF, we have developed a chewable tablet, in which one of the major medicines is total Panax notoginseng saponins (PNS). In this study, we have investigated the antifibrotic effect and mechanism of PNS on areca nut-induced OSF in vitro. METHODS: Through human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, qRT-PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)-induced cell growth, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion, and the activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFß/Smads pathways were detected. RESULTS: Panax notoginseng saponins could inhibit the ANE-induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration-dependent manner. PNS (25 µg/ml) could significantly inhibit the ANE-induced expression of Col1A1 and Col3A1, augment the ANE-induced decrease of MMP-2/-9 activity, inhibit the ANE-induced increase of TIMP-1/-2 expression, and decrease the ANE-induced transcription and release of CTGF, TGFß1, IL-6, and TNFα. PNS (25 µg/ml) also significantly inhibited the ANE-induced activation of AKT and ERK/JNK/p38 MAPK pathways in oral mucosal fibroblasts and the ANE-induced activation of TGFß/smad pathway in HaCaT cells. CONCLUSION: Panax notoginseng saponins possess excellent anti-OSF activity, and its mechanism may be related to its ability to inhibit the ANE-induced activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFß/smad pathways.


Assuntos
Areca/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Nozes/efeitos adversos , Fibrose Oral Submucosa/patologia , Panax notoginseng , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Animais , Técnicas de Cultura de Células , Linhagem Celular , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo III/efeitos dos fármacos , Fator de Crescimento do Tecido Conjuntivo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Hidroxiprolina/análise , Interleucina-6/análise , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Bucal/citologia , Fibrose Oral Submucosa/etiologia , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Smad/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-2/efeitos dos fármacos , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos
9.
Antimicrob Agents Chemother ; 57(9): 4433-43, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23836164

RESUMO

It has been reported that autophagy is involved in the replication of many viruses. In this study, we screened 89 medicinal plants, using an assay based on the inhibition of the formation of the Atg12-Atg5/Atg16 heterotrimer, an important regulator of autophagy, and selected Silybum marianum L. for further study. An antiviral assay indicated that silybin (S0), the major active compound of S. marianum L., can inhibit influenza A virus (IAV) infection. We later synthesized 5 silybin derivatives (S1 through S5) and found that 23-(S)-2-amino-3-phenylpropanoyl-silybin (S3) had the best activity. When we compared the polarities of the substituent groups, we found that the hydrophobicity of the substituent groups was positively correlated with their activities. We further studied the mechanisms of action of these compounds and determined that S0 and S3 also inhibited both the formation of the Atg12-Atg5/Atg16 heterotrimer and the elevated autophagy induced by IAV infection. In addition, we found that S0 and S3 could inhibit several components induced by IAV infection, including oxidative stress, the activation of extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) and IκB kinase (IKK) pathways, and the expression of autophagic genes, especially Atg7 and Atg3. All of these components have been reported to be related to the formation of the Atg12-Atg5/Atg16 heterotrimer, which might validate our screening strategy. Finally, we demonstrated that S3 can significantly reduce influenza virus replication and the associated mortality in infected mice. In conclusion, we identified 23-(S)-2-amino-3-phenylpropanoyl-silybin as a promising inhibitor of IAV infection.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Cardo Mariano/química , Extratos Vegetais/química , Silimarina/análogos & derivados , Animais , Antivirais/síntese química , Antivirais/isolamento & purificação , Autofagia/efeitos dos fármacos , Proteína 12 Relacionada à Autofagia , Proteína 5 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cercopithecus aethiops , Cães , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Células Madin Darby de Rim Canino , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plasmídeos , Multimerização Proteica/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Silimarina/síntese química , Silimarina/isolamento & purificação , Silimarina/farmacologia , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/antagonistas & inibidores , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Células Vero
10.
PLoS One ; 8(4): e61026, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23613775

RESUMO

Autophagy is involved in many human diseases, such as cancer, cardiovascular disease and virus infection, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza A virus (IAV) and coxsackievirus B3/B4 (CVB3/B4), so a drug screening model targeting autophagy may be very useful for the therapy of these diseases. In our study, we established a drug screening model based on the inhibition of the dissociation of Beclin1-Bcl2 heterodimer, an important negative regulator of autophagy, using bimolecular fluorescence complementation (BiFC) technique for developing novel autophagy inhibitors and anti-IAV agents. From 86 examples of traditional Chinese medicines, we found Syzygium aromaticum L. had the best activity. We then determined the anti-autophagy and anti-IAV activity of eugenol, the major active compound of Syzygium aromaticum L., and explored its mechanism of action. Eugenol could inhibit autophagy and IAV replication, inhibited the activation of ERK, p38MAPK and IKK/NF-κB signal pathways and antagonized the effects of the activators of these pathways. Eugenol also ameliorated the oxidative stress and inhibited the expressions of autophagic genes. We speculated that the mechanism underlying might be that eugenol inhibited the oxidative stress and the activation of ERK1/2, p38MAPK and IKK/NF-κB pathways, subsequently inhibited the dissociation of Beclin1-Bcl2 heterodimer and autophagy, and finally impaired IAV replication. These results might conversely display the reasonableness of the design of our screening model. In conclusion, we have established a drug screening model for developing novel autophagy inhibitor, and find eugenol as a promising inhibitor for autophagy and IAV infection.


Assuntos
Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Eugenol/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Linhagem Celular , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Syzygium/química
11.
PLoS One ; 8(12): e83753, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24386270

RESUMO

Cardiomyocytes are quite resistant to gene transfer using standard techniques. We developed an expression vector carrying an attenuated but infectious and replicative coxsackievirus B3 (CVB3) genome, and unique ClaI-StuI cloning sites for an exogenous gene, whose product can be released from the nascent viral polyprotein by 2A(pro) cleavage. This vector was tested as an expression vehicle for green fluorescent protein (GFP). The vector transiently expressed GFP in cell cultures for at least ten passages and delivered functional GFP to the infected cardiomyocytes for at least 6 days. Moreover, the recombinant viruses showed virulence attenuation in vitro and in vivo. The findings suggest that the recombinant CVB3 vector could be a useful tool for viral tracking study and delivering exogenous proteins to cardiomyocytes.


Assuntos
Enterovirus Humano B/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Animais , Linhagem Celular , Enterovirus Humano B/patogenicidade , Infecções por Enterovirus/patologia , Infecções por Enterovirus/virologia , Expressão Gênica , Ordem dos Genes , Genoma Viral , Humanos , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Transdução Genética , Transgenes , Virulência
12.
PLoS One ; 7(8): e42706, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22900043

RESUMO

In this research, we have established a drug screening method based on the autophagy signal pathway using the bimolecular fluorescence complementation-fluorescence resonance energy transfer (BiFC-FRET) technique to develop novel anti-influenza A virus (IAV) drugs. We selected Evodia rutaecarpa Benth out of 83 examples of traditional Chinese medicine and explored the mechanisms of evodiamine, the major active component of Evodia rutaecarpa Benth, on anti-IAV activity. Our results showed that evodiamine could significantly inhibit IAV replication, as determined by a plaque inhibition assay, an IAV vRNA promoter luciferase reporter assay and the Sulforhodamine B method using cytopathic effect (CPE) reduction. Additionally, evodiamine could significantly inhibit the accumulation of LC3-II and p62, and the dot-like aggregation of EGFP-LC3. This compound also inhibited the formation of the Atg5-Atg12/Atg16 heterotrimer, the expressions of Atg5, Atg7 and Atg12, and the cytokine release of TNF-α, IL-1ß, IL-6 and IL-8 after IAV infection. Evodiamine inhibited IAV-induced autophagy was also dependent on its action on the AMPK/TSC2/mTOR signal pathway. In conclusion, we have established a new drug screening method, and selected evodiamine as a promising anti-IAV compound.


Assuntos
Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Vírus da Influenza A/efeitos dos fármacos , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adenilato Quinase/metabolismo , Animais , Autofagia/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular , Citocinas/biossíntese , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/metabolismo , Replicação Viral/efeitos dos fármacos
13.
Chin Med J (Engl) ; 125(14): 2405-10, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882911

RESUMO

BACKGROUND: There is little information of non-perianal fistulating Crohn's disease in the consensus published by the European Crohn's and Colitis Organization in 2006 and 2010. This study was designed to demonstrate the clinical characteristics of non-perianal fistulating Crohn's disease among homogenous Chinese population. METHODS: One-hundred-and-eighty-four patients were retrospectively collected. All of these patients were diagnosed of Crohn's disease between February 2001 and April 2011. RESULTS: The male-to-female ratio was 2.7:1. The most common symptoms at onset were abdominal pain (88.0%), diarrhea (34.7%), and fever (28.3%). The most common disease location and behavior at diagnosis were small bowel (56.0%) and penetrating (51.6%). Among 324 non-perianal fistulae, the most common types were ileocolonic anastomotic (30.9%), terminal ileocutaneous (19.7%), and enteroenteric anastomotic (11.4%). One-hundred-and-thirty- eight (75.0%) patients received antibiotics, and ß-lactam (85.5%) and metronidazole (67.4%) are most frequently used. One-hundred-and-seventy-eight (96.7%) patients suffered 514 surgical operations, and the cumulative surgical rates after 1, 3, and 5 years were 38.0%, 52.2%, and 58.7% respectively. Nine patients died during the follow-up period, and the cumulative survival rates after 1, 3, and 5 years were 97.8%, 96.7%, and 96.2% respectively. CONCLUSIONS: This study displayed the clinical characteristics of non-perianal fistulating Crohn's disease in our center. Large population-based studies are required for further investigation in China.


Assuntos
Doença de Crohn/patologia , Fístula Retal/patologia , Adolescente , Adulto , China , Doença de Crohn/tratamento farmacológico , Doença de Crohn/mortalidade , Doença de Crohn/cirurgia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Glicosídeos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Retal/tratamento farmacológico , Fístula Retal/mortalidade , Fístula Retal/cirurgia , Tripterygium/química , Adulto Jovem
14.
Am J Med Sci ; 344(2): 122-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22143125

RESUMO

Activated glial cells produce many toxic molecules, including cytokines and nitric oxide (NO). There is evidence that excess NO production plays a key role in neuronal cell death. Previous research has demonstrated that cortical glial cells from the left and right cortices of the brain secrete cytokines asymmetrically. However, no evidence to date exists about whether glial cell-produced NO is produced asymmetrically as well. The results of this study show that NO production and inducible NO synthase gene expression are both significantly higher in the right hemisphere-derived mixed glial cell compared with cultures derived from the left.


Assuntos
Córtex Cerebral/metabolismo , Neuroglia/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Animais , Animais Recém-Nascidos , Córtex Cerebral/citologia , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos BALB C
15.
Cell Biochem Funct ; 29(1): 50-4, 2011 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21264890

RESUMO

Lipopolysaccharide (LPS)-induced inflammatory factors production by the cerebral cortical glial cells in two sides of the murine brain are different. To determine if microglial cells, a subset of glial cells, are involved in asymmetric production, interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and nitric oxide (NO) responses to LPS by microglial cells in the right and left cerebral cortices were examined. Primary microglial cells were isolated from BALB/C neonatal mice, treated with LPS (10 µg ml(-1) ) for 24 h and examined for IL-6, IL-1ß and NO production. At untreated state, the levels of IL-6, IL-1ß and NO showed no statistical difference between left and right. However, after LPS treatment, the levels of IL-6, IL-1ß and NO for the right microglial cells was statistically significant higher than the left (P < 0·05). Our results denote that enhanced production of IL-6, IL-1ß and NO after LPS treatment in microglia is directly proportional to their basal-state levels, and right cortical microglia produce higher levels of IL-6, IL-1ß and NO than left cortical microglia.


Assuntos
Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Lipopolissacarídeos/toxicidade , Neuroglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Animais , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroglia/metabolismo
16.
Virol J ; 7: 170, 2010 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-20653952

RESUMO

Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85beta regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85beta interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection.


Assuntos
Regulação para Baixo , Vírus da Influenza A/fisiologia , Influenza Humana/enzimologia , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/metabolismo , Replicação Viral , Animais , Linhagem Celular , Cães , Humanos , Vírus da Influenza A/genética , Influenza Humana/genética , Influenza Humana/virologia , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Ligação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Domínios de Homologia de src
17.
ANZ J Surg ; 80(4): 258-64, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20575953

RESUMO

BACKGROUND: Since introduction of damage control (DC) approach to non-trauma setting is relatively late, the risk factors associated with this procedure remain undefined. This study was aimed at identifying factors responsible for the mortality. METHODS: Over a 5-year period (from February 2002 to February 2007), consecutive non-trauma patients who required DC laparotomy (DCL) with gauze packing for control of indomitable abdominal haemorrhage in our institute were included. Clinical, laboratorial and operative factors influencing in-hospital or 30-day mortality were analysed. RESULTS: A total of 26 patients underwent DCL with packing in an attempt to control severe abdominal haemorrhage. There were seven (26.9%) deaths in hospital or within 30 days of DCL. Increase in age, higher initial physiological score and operative severity score assessed by the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity scoring system, lower initial body temperature, lower initial platelet (PLT) counts, greater intra-operative blood loss, presence of perioperative multiple organ dysfunction syndrome were all associated with increased risk of mortality on univariate analysis (P < 0.05). On multivariate analysis, only decrease in PLT counts (P = 0.042, OR = 0.969, 95% CI = 0.940-0.999) and increase in age (P = 0.035, OR = 1.152, 95% CI = 1.010-1.313) were significant independent factors affecting mortality. CONCLUSIONS: Decrease in PLT counts and increase in age are the independent risk factors related to death in non-trauma series that require DCL with packing. DCL should be performed early as for patients with these risk factors.


Assuntos
Exsanguinação/mortalidade , Exsanguinação/cirurgia , Adolescente , Adulto , Distribuição por Idade , Idoso , Causas de Morte , China/epidemiologia , Estudos de Coortes , Comorbidade , Exsanguinação/sangue , Feminino , Mortalidade Hospitalar , Humanos , Laparotomia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto Jovem
18.
Zhonghua Wai Ke Za Zhi ; 47(6): 441-5, 2009 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-19595232

RESUMO

OBJECTIVE: To assess the efficacy and safety of damage control surgery with abdominal packing in non-trauma patients with severe abdominal hemorrhage. METHODS: A retrospective review of consecutive non-trauma patients who underwent abdominal packing to control severe abdominal hemorrhage between February 2002 and February 2007 were performed. The demographics, physiological parameters, surgical indications and procedures, mortality, morbidity and volumes of resuscitation were retrieved. The observed mortality was compared to those calculated from the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) and Portsmouth Predictor Equation (P-POSSUM) scores. RESULTS: A total of 26 non-trauma patients were included in this study, with a mean age of (42.6 +/- 15.8) years (range, 18 - 72 years). The most common etiologies associated with the severe hemorrhage was necrotizing pancreatitis (11 cases), intestinal fistula (5 cases) and tumor (4 cases). Of the patients, 24 cases (92.4%) achieved hemostasis by simple packing, 1 achieved hemostasis by using packing and angiographic embolization, and the other one failed and died. The mean intra-operative blood loss during the initial procedure was 1253.8 ml. The physiological parameters which improved significantly after rewarming and resuscitation in ICU phase included: body temperature, systolic blood pressure, heart rate, arterial pH, base excess, hemoglobin, hematocrit, prothrombin time, and international normalized ratio. The mean duration of packing was 4.3 days. The mean length of SICU stay and hospital stay was 40.5 and 67.4 days, respectively. Mortality rate predicted by POSSUM and P-POSSUM was 77.7% and 63.4%, respectively. Seven patients (26.9%) died after operation, brought an observed mortality rate significantly lower than predicted (P = 0.001 and 0.025, respectively). The most common complications included pneumonia (57.7%), bacteremia (50.0%), and re-bleeding (26.9%). CONCLUSIONS: Damage control laparotomy with packing is an effective procedure in the management of severe non-trauma abdominal hemorrhage, it can prevent the aggravation of "lethal triad" characterized by hypothermia, coagulopathy and acidosis. Appropriate application of the technique in strictly selected patients can result in a lower mortality rate.


Assuntos
Hemoperitônio/terapia , Técnicas Hemostáticas , Adolescente , Adulto , Idoso , Bandagens , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Sci China C Life Sci ; 52(6): 545-50, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19557332

RESUMO

Influenza A virus NS1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis. In the present study, transcription-activating potential of NS1 from different influenza A virus subtypes was examined in yeast two-hybrid system. The bait vectors containing different NS1 genes, along with an empty prey vector, were transformed into yeast AH109(for growth assay on QDO plate and alpha-galactosidase assay), and Y187(for beta-galactosidase assay). AH109 transformants with NS1 gene from H1N1, H5N1, and H9N2 viruses grew vigorously on the QDO plate and secreted high level of alpha-galactosidase. Also, Y187 bearing the above NS1 genes exhibited enhanced beta-galactosidase activity. Nevertheless, H3N2-NS1-transformed AH109 and Y187 yeasts did not grow on QDO plate and secrete beta-galactosidase, respectively. These findings denote the remarkable variation in NS1 proteins from different influenza A virus subtypes on the transcription-stimulating capability in yeast.


Assuntos
Vírus da Influenza A/metabolismo , Ativação Transcricional , Proteínas não Estruturais Virais/metabolismo , Animais , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Técnicas do Sistema de Duplo-Híbrido , Proteínas não Estruturais Virais/genética , Leveduras/genética , Leveduras/metabolismo , alfa-Galactosidase/metabolismo , beta-Galactosidase/metabolismo
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 12(2): 167-9, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19296254

RESUMO

OBJECTIVE: To observe the efficacy of polyglycoside of Tripterygium wilfordii(GTW) in preventing postoperative recurrence of Crohn disease(CD). METHODS: Thirty-nine post-operative CD patients in whom all of the diseased gut had been removed from January 2005 to December 2006 were enrolled in a randomized, placebo-controlled trial. The patients took GTW(21 cases) or SASP(18 cases) in two weeks after operation. Crohn disease activity index(CDAI), ESR and CRP were collected at week 0, 13, 26, 52 or at the onset of symptoms. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. RESULTS: One patient in GTW group and 2 patients in SASP group were lost and 2 patients in GTW were excluded from the trial for non-compliance. Clinical recurrence was ascertained in one patient (5.6%) received GTW and in four (25.0%) received SASP. Four of eighteen patients in GTW(22.2%) had endoscopic recurrence compared with nine of sixteen(56.2%) in SASP. There were significant differences between the two groups(P<0.05). CONCLUSION: Tripterygium wilfordii showed good efficacy in preventing recurrence of postoperative CD which can maintain remission and prevent recurrence.


Assuntos
Doença de Crohn/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Fitoterapia , Tripterygium , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prevenção Secundária , Resultado do Tratamento
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