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1.
Artigo em Inglês | MEDLINE | ID: mdl-35966745

RESUMO

Objective: To investigate the external application of traditional Chinese medicine in the prevention and treatment of nausea and vomiting caused by chemotherapy of non-small-cell lung cancer. Methods: This is a prospective trial. A total of 114 patients with non-small-cell lung cancer who were hospitalized in our hospital from October 2020 to March 2022 were selected and randomly divided into the research group and the control group at the ratio of 1 : 1. The control group received chemotherapy + tropisetron 4 mg intravenous drip 30 minutes before chemotherapy./day × 3 days. The research group received chemotherapy + intravenous infusion of tropisetron 4 mg 30 minutes before chemotherapy, once a day for 3 days + external application of traditional Chinese medicine for 5 days. The therapeutic effects of the two groups of patients were compared. Results: After treatment, the serum creatinine, urea nitrogen, and endogenous creatinine in the research group were better than those in the control group (t = 15.943, 12.005, and 13.325; P=0.001, 0.005, and 0.005). After treatment, ALT and TBIL in the research group were superior to those in the control group (t = 11.583, 10.012, and 9.426; P=0.001, 0.002, and 0.001). After treatment, the physiological status, social/family status, emotional status, and family status of the research group were significantly better than those in the control group (t = 16.274, 5.379, 5.142, and 8.153; P=0.005, 0.000, 0.002, and 0.001). After treatment, the ECOG score and KPS score (82.46 ± 4.61) of the research group were significantly different from those of the control group (t = 11.913 and 9.357; P=0.035 and 0.001). The effective rate (χ 2 = 11.724; P=0.000) of the research group was higher but the incidence of adverse reaction (χ 2 = 4.294; P=0.001) was lower than that of the control group. Conclusion: External application of traditional Chinese medicine can significantly reduce nausea and vomiting caused by chemotherapy of non-small-cell lung cancer and can improve the patient's body and quality of life, which is worthy of clinical research and promotion.

2.
Pharm Biol ; 60(1): 1190-1197, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35758248

RESUMO

CONTEXT: Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. OBJECTIVE: To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. RESULTS: The t1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·µg/mL) and t1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 µmol/L for CYP2C8, and 27.31, 7.57, and 4.59 µmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. DISCUSSION AND CONCLUSIONS: The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.


Assuntos
Diabetes Mellitus Tipo 2 , Ginkgo biloba , Animais , Citocromo P-450 CYP2C8/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Microssomos Hepáticos , Folhas de Planta , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Rosiglitazona/farmacologia , Comprimidos/metabolismo , Comprimidos/farmacologia
3.
Xenobiotica ; 52(4): 353-359, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35621148

RESUMO

This study aimed to assess the effects of total flavonoid extracts (TFDG) and the monomers of Daphne genkwa on the CYP2C8 activity in vitro and in vivo.The 50% inhibitory concentration (IC50) values were used to determine the inhibitory effect of TFDG and its four monomers for the CYP2C8 activity by recombinant human CYP2C8 (RHCYP2C8) yeast microsome system in vitro, and the volume per dose index (VDI) was predicted the potential inhibition in vivo. The effects of multiple-dose administration of TFDG on the pharmacokinetic parameters of rosiglitazone in rats were evaluated.The IC50 values of apigenin, luteolin, hydroxy-genkwanin, genkwanin, and TFDG were 7.27 µmol/L, 11.9 µmol/L, 28.1 µmol/L, 127 µmol/L, and 13.4 µg/mL, respectively. The VDI values of apigenin and TFDG were 2.15 L and 6.60 L. In vivo study, compared with the control group, the elimination phase half-life and mean residence time in the TFDG treatment group were significantly increased by 96.9% and 106.8% (p <.05), respectively.Apigenin showed a moderate inhibitory effect on the CYP2C8 activity in vitro, while the other three monomers were weak inhibitors. TFDG had a strong inhibitory effect on CYP2C8 in vitro and in vivo, and also inhibited the metabolism of rosiglitazone in rats.


Assuntos
Daphne , Animais , Apigenina/farmacologia , Citocromo P-450 CYP2C8 , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Ratos , Rosiglitazona/farmacologia
4.
Artif Cells Nanomed Biotechnol ; 48(1): 159-168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852298

RESUMO

Accumulating evidence links osteopontin (OPN), a pro-fibrogenic extracellular matrix protein, to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In this study, liver tissues isolated from non-alcoholic steatohepatitis (NASH) patients expressed higher OPN than those of controls. However, the exact mechanism(s) for this phenomenon is yet to be clarified. Autophagy is the natural, regulated degradation and recycling of a cell's dysfunctional components, in order to maintain homeostasis. Increasing evidence supports that autophagy can constitute an effective Defence mechanism against NAFLD conditions. Herein, we constructed NAFLD mice model by high-fat (HF) and methionine-choline-deficient (MCD) diet and found that OPN is upregulated in livers of NAFLD mice. Besides, secreted OPN inhibited autophagosome-lysosome fusion via binding with its receptors integrin αVß3 and αVß5 in HepG2 cells supplemented with free fatty acids (FFA) and the livers of NAFLD mice. Silencing of OPN attenuated autophagy impairment and reduced lipid accumulation, while supplementation of OPN exhibited the opposite effect. Furthermore, treatment with anti-OPN Ab significantly attenuated steatosis as well as autophagy impairment in the liver. Our findings indicated that OPN plays a vital role in the pathogenesis of the development of NAFLD via autophagy impairment, which might represent a potential new therapeutic target for the treatment of NAFLD.


Assuntos
Autofagia , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Osteopontina/metabolismo , Animais , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Integrina alfaVbeta3/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos
5.
Acta Pharmacol Sin ; 39(11): 1706-1715, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30266998

RESUMO

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.


Assuntos
Berberina/uso terapêutico , Proteína HMGB1/antagonistas & inibidores , Infarto da Artéria Cerebral Média/tratamento farmacológico , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Regulação para Baixo , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Infarto da Artéria Cerebral Média/etiologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Mol Nutr Food Res ; 62(13): e1800144, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29797417

RESUMO

SCOPE: Lycium barbarum polysaccharide (LBP) is a water fraction of wolfberry, which has been demonstrated to possess a hepatoprotective effect in several liver disease models. However, the anti-alcoholic liver disease (anti-ALD) mechanism of LBP has not been investigated thoroughly. Its protective effects on both male and femal mice are investigated in the current study. METHODS AND RESULTS: A chronic ethanol-fed ALD in vivo model is applied to study the effect of LBP in both male and female mice. It is observed that ethanol causes more severe liver injury in female than male mice, and the ameliorative effects of LBP are also more significant in female mice, which are impaired after complete bilateral oophorectomy. The hepatic SCD1 expression is found to be positively correlated with the severity of the liver damage and the main mediator of LBP inducer of protection. The AMPK-CPT pathway is also activated by LBP to rebalance the dysregulated lipid metabolism during ALD development. By using concurrent sodium palmitate and an ethanol-induced in vitro cell damage model in AML-12 cell line, it is characterized that LBP directly interacts with ERα instead of ERß to activate the SCD1-AMPK-CPT pathway. CONCLUSIONS: LBP is an effective and safe hepatoprotective agent against ALD primarily through the SCD1-AMPK-CPT pathway after ERα agonist.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hepatopatias Alcoólicas/prevenção & controle , Estearoil-CoA Dessaturase/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/fisiologia , Animais , Células Cultivadas , Suplementos Nutricionais , Receptor alfa de Estrogênio/fisiologia , Receptor beta de Estrogênio/fisiologia , Feminino , Masculino , Camundongos , Ovariectomia , Transdução de Sinais/fisiologia , Estearoil-CoA Dessaturase/fisiologia
7.
Minerva Med ; 108(6): 554-567, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28602070

RESUMO

Alcoholic hepatitis (AH) is an acute and severe form of alco1holic liver disease associated with high morbidity and mortality of 30-50% worldwide, severity ranging from asymptomatic derangement of liver biochemistries to fulminant liver failure or death. Rapidly progressing jaundice and coagulopathy in prolonged excessive alcohol abusers with or without fever, malnutrition, and tender liver are the clinical hallmarks. The prognostic models (Model for end-stage liver disease, Maddrey's discriminant function [MDF], age, serum bilirubin, INR, creatinine [ABIC], Glasgow Alcoholic Hepatitis Score [GAHS], Lille's Score) not only predict the short term mortality, but also guide the clinicians to choose appropriate specific therapy (corticosteroid or pentoxifylline) and as a stopping rule if there is no significant benefits of it. MDF Score is commonly followed in clinical practice, score of >32 would predict short term mortality of around 20-30% at 1 month and 30-40% within 6 months after presentation. The GAHS on day 1 can predict 28 day overall survival outcome accuracy of 81%, which is comparatively higher than MDF Score. Moreover, ABIC Score categorizes risk of deaths (based on 90 days) into low risks (0%), intermediate risk (30%), and high risk (75%). Corticosteroid and pentoxifylline have significant benefits in decreasing mortality (corticosteroid improves survival on 28 day and 84 day of 78% and 59%) in severe disease state (MDF >32 or Lille's Score >0.45 or GAHS >9). Corticosteroid is the initial treatment of choice with infections screening before initiating; however, pentoxifylline is better preferred in case of AH with severe infections and hepatorenal syndrome. Additionally, combination of corticosteroids and N-acetylcysteine decreases development of hepatorenal syndrome, infections, and short-term mortality. However, the Lille Score after corticosteroid therapy of >0.45 after day 7 indicates poor responders or >0.56 indicates null responders. Therefore, in these cases, either therapy has to be stopped or changed to pentoxifylline. In treatment failure cases, liver transplantation is the ultimate option. However, the facilitating of this service in most transplant centers is a challenge. Beside these specific therapies, alcohol abstinence and recommendation of nutritional supplements with high calorie, protein diet and vitamin E, C, thiamine regardless of other treatment plays a prime role in preventing disease progression and survival benefits even in pre and post-transplant cases.


Assuntos
Hepatite Alcoólica/diagnóstico , Acetilcisteína/uso terapêutico , Corticosteroides/uso terapêutico , Abstinência de Álcool , Bilirrubina/sangue , Biomarcadores , Biópsia , Terapia Combinada , Creatinina/sangue , Substituição de Medicamentos , Hepatite Alcoólica/complicações , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/terapia , Síndrome Hepatorrenal/etiologia , Humanos , Fígado/patologia , Testes de Função Hepática , Transplante de Fígado , Modelos Biológicos , Apoio Nutricional , Pentoxifilina/uso terapêutico , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
8.
Hepatol Int ; 11(3): 221-241, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28405790

RESUMO

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Colestase/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Hepatopatias/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , China/epidemiologia , Colestase/complicações , Colestase/patologia , Diagnóstico Diferencial , Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Guias como Assunto , Humanos , Incidência , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Masculino , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(9): 826-830, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-27655538

RESUMO

OBJECTIVE: To investigate the therapeutic effects of oral zinc supplement in infants and young children with rotavirus enteritis, and its preventive effects against diarrhea recurrence within 3 months after treatment. METHODS: A total of 103 infants and young children with rotavirus enteritis were randomly divided into zinc supplement group (n=51) and conventional treatment group (n=52). Both groups were equally treated with a comprehensive therapy, besides which the zinc supplement group received zinc gluconate granules for 10 days. The treatment outcomes were examined at 72 hours after treatment, and the time required for the disappearance of positive symptoms and the recovery of injured extra-intestinal organs were determined. In addition, these patients were followed up for 3 months to determine the incidence of diarrhea recurrence after treatment. RESULTS: The overall response rate in the zinc supplement group was significantly higher than that in the conventional treatment group (90% vs 75%; P<0.05). The durations of diarrhea, high fever, and vomiting in the zinc supplement group were significantly shorter than that in the conventional treatment group (P<0.05). In addition, the recurrence rate of diarrhea and the incidence of severe diarrhea within 3 months after treatment in the zinc supplement group were significantly lower than in the conventional treatment group (P<0.05). CONCLUSIONS: Oral zinc supplement as adjunctive therapy is effective in treating infants and young children with rotavirus enteritis, and reducing the incidence and severity of diarrhea recurrence in the subsequent 3 months.


Assuntos
Enterite/tratamento farmacológico , Infecções por Rotavirus/tratamento farmacológico , Zinco/administração & dosagem , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Masculino , Recidiva
10.
Front Plant Sci ; 7: 638, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242840

RESUMO

Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, ß-myrcene. Although both Mg(2+) and Mn(2+) were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn(2+) for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography-mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant-environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant.

11.
Sci Bull (Beijing) ; 61: 3-17, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26844006

RESUMO

Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.

12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(1): 51-5, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24520788

RESUMO

OBJECTIVE: To investigate the effect of Qingyi Decoction (QYD) on pancreatic gene expression profiles in rats with severe acute pancreatitis (SAP). METHODS: Totally 60 Sprague-Dawley (SD) rats were randomly divided into the sham-operation group (SO group), the SAP group, and the QYD group, 20 in each group. SAP model was replicated by the pancreatic duct retrograde injection with 4% sodium taurocholate. Rats in the QYD group was intragastrically intervened by QYD (0.75 mL/100 g) for 3 times. Pancreatic RNA expression was analyzed using Illuminate whole genome expression profiles. Changes of mRNA and protein in specific genes [heat shock proteins a8 (Hspa8) and heat shock proteins b1 (Hspb1)] were verified by real-time quantitative PCR and Western blot analysis. RESULTS: Compared with the SAP group, 575 differential genes were screened in the QYD group, including 92 up-regulated genes and 483 down-regulated genes. Gene Ontology (GO) categories indicated the genes are associated with negative regulation of transcription regulator activity, oxidoreductase activity and enzyme inhibitor activity. Effects of QYD on the SAP rats were major related to mitogen-activated protein kinase (MAPK), NOD like receptors (NLR) receptor-like signaling pathway, cell cycle, metabolic pathways, oxidoreductase activity. Protein and mRNA changes of Hspa8 and Hspb1 in microarray were verified [relative mRNA expression for Hspa8 and Hspb1 was increased by (13.24 +/- 1.22) times and (7.55 +/- 1.09) times respectively, P < 0.01]. CONCLUSION: QYD was effective in treating experimental SAP involved the MAPK and NLR signaling pathways, cell cycle, metabolic pathways, and oxide reductase activities.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Pancreatite/genética , Fitoterapia , Transcriptoma , Animais , Feminino , Perfilação da Expressão Gênica , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Pancreatite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
13.
PLoS One ; 8(11): e80464, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24260395

RESUMO

Salvia miltiorrhiza Bunge, a perennial plant of Lamiaceae, accumulates abietane-type diterpenoids of tanshinones in root, which have been used as traditional Chinese medicine to treat neuroasthenic insomnia and cardiovascular diseases. However, to date the biosynthetic pathway of tanshinones is only partially elucidated and the mechanism for their root-specific accumulation remains unknown. To identify enzymes and transcriptional regulators involved in the biosynthesis of tanshinones, we conducted transcriptome profiling of S. miltiorrhiza root and leaf tissues using the 454 GS-FLX pyrosequencing platform, which generated 550,546 and 525,292 reads, respectively. RNA sequencing reads were assembled and clustered into 64,139 unigenes (29,883 isotigs and 34,256 singletons). NCBI non-redundant protein databases (NR) and Swiss-Prot database searches anchored 32,096 unigenes (50%) with functional annotations based on sequence similarities. Further assignments with Gene Ontology (GO) terms and KEGG biochemical pathways identified 168 unigenes referring to the terpenoid backbone biosynthesis (including 144 MEP and MVA pathway genes and 24 terpene synthases). Comparative analysis of the transcriptomes identified 2,863 unigenes that were highly expressed in roots, including those encoding enzymes of early steps of tanshinone biosynthetic pathway, such as copalyl diphosphate synthase (SmCPS), kaurene synthase-like (SmKSL) and CYP76AH1. Other differentially expressed unigenes predicted to be related to tanshinone biosynthesis fall into cytochrome P450 monooxygenases, dehydrogenases and reductases, as well as regulatory factors. In addition, 21 P450 genes were selectively confirmed by real-time PCR. Thus we have generated a large unigene dataset which provides a valuable resource for further investigation of the radix development and biosynthesis of tanshinones.


Assuntos
Abietanos/biossíntese , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Transcriptoma , Alquil e Aril Transferases/metabolismo , Vias Biossintéticas , Biologia Computacional/métodos , Sistema Enzimático do Citocromo P-450/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Dados de Sequência Molecular , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/classificação , Terpenos/metabolismo , Fatores de Transcrição/metabolismo
14.
J Clin Pharmacol ; 53(1): 96-102, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23400749

RESUMO

To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii, carbapenem consumption was expressed as defined daily dose based on the World Health Organization (WHO) anatomical therapeutic chemical classification index. Clinical isolates from 2001-2009 were collected and analyzed using WHONET 5.4 software. Results show that the consumption of imipenem/cilastatin, meropenem, and total carbapenem is significantly correlated with imipenem resistance in A baumannii (r = 0.818, P = .007; r = 0.817, P = .007; r = 0.827, P = .006). Furthermore, total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii (r = 0.900, P = .037). In addition, consumption of imipenem/cilastatin, meropenem, and total carbapenem is associated with A baumannii resistance to piperacillin-tazobactam, ceftazidime, cefepime, amikacin, and levofloxacin. These drugs are mainly ß-lactams, aminoglycosides, and fluoroquinolones. The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs (eg, ß-lactams, aminoglycosides, and fluoroquinolones) in A baumannii. Therefore, increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem, meropenem, and other antimicrobial drugs. Cross-resistance possibly occurs among imipenem/cilastatin and meropenem, as well as with ß-lactams, aminoglycosides, and fluoroquinolones.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Anti-Infecciosos/uso terapêutico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Anti-Infecciosos/farmacologia , Carbapenêmicos/farmacologia , China , Uso de Medicamentos/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Testes de Sensibilidade Microbiana
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(12): 926-9, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21186415

RESUMO

OBJECTIVE: To investigate the role of integrin α4ß7 in the development of ulcerative colitis (UC) in rats. METHODS: Sixty Sprague-Dawley rats were randomly divided into the control group (acetone enema), the model group (2,4-dinitrochlorobenzene, DNCB enema), and the α4 intervention group. Colonic mucosa of different groups was observed and compared in terms of pathology and cytokine changes(IL-2 and IL-6) using ELISA. Semi-quantitative RT-PCR was used to detect the colon α4ß7 expression. Integrin α4ß7(+) lymphocytes in the portal vein of rats were determined by flow cytometry. RESULTS: The expression of α4 mRNA was 0.68±0.24 in the model group and 0.58±0.37 in the intervention group, and the expression of ß7 mRNA was 0.84±0.37 in the model group and 0.65±0.30 in the intervention group, which were all significantly higher as compared to those in the control group(0.15±0.13 for α4 and 0.24±0.62 for ß7, P<0.01). The proportions of integrin α4ß7 positive lymphocytes in the portal vein in the model group and intervention group were significantly higher than that in the control group [(76.7±8.2)% and (68.2±7.6)% vs. (14.7±6.7)%, P<0.01]. The expression of IL-2 and IL-6 and the result of macroscopic and microscopic scores in the intervention group were lower than those in the model group(P<0.05). CONCLUSIONS: High expression of α4ß7 may play an important role in experimental colon mucosa inflammation in rats with ulcerative colitis. The blockade of integrin α4ß7 may be a potential target to reduce colonic mucosa inflammation.


Assuntos
Colite Ulcerativa/patologia , Integrinas/fisiologia , Animais , Colite Ulcerativa/metabolismo , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Feminino , Integrinas/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/patologia , Ratos
16.
Biol Pharm Bull ; 33(8): 1438-42, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20686245

RESUMO

The effects of Sho-seiryu-to (TJ-19), an ethical Kampo formulation, on bleomycin (BLM)-induced pulmonary fibrosis in rats was examined. Pulmonary fibrosis was induced by intratracheal instillation of a single dose of BLM (5 mg/kg). The TJ-19 used consisted of at least 21 constituents, as determined by three-dimensional HPLC analysis, and was administered orally twice a day at a dose of 1.5 g/kg until the end of the study period. Changes in general appearance and body weight were monitored. Twenty-eight days after BLM instillation, the animals were sacrificed and the study parameters were measured. TJ-19 attenuated the loss in body weight, increase in lung/body weight ratio and concentration of hydroxyproline and malondialdehyde in the lung tissues induced by BLM administration. TJ-19 also prevented BLM-induced fibrotic changes in the lung histology. These protective effects of TJ-19 were observed when administration was started 1 week before and simultaneously with the instillation of BLM. These results suggest that TJ-19 has prophylactic potential against BLM-induced pulmonary fibrosis, and may therefore be a promising drug candidate and medicinal resource for preventing BLM-induced and idiopathic pulmonary fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose Pulmonar Idiopática/prevenção & controle , Pulmão/efeitos dos fármacos , Medicina Kampo , Animais , Bleomicina , Cromatografia Líquida de Alta Pressão , Colágeno/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley
17.
J Pharm Pharmacol ; 61(7): 925-32, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19589235

RESUMO

OBJECTIVES: The effect of a herbal medicine, Sho-seiryu-to (TJ-19), on oleic acid-induced lung injury, an animal model of acute respiratory distress syndrome or acute lung injury (ARDS/ALI), was examined. METHODS: Acute lung injury was induced by an intravenous injection of 15 microl/kg oleic acid to guinea-pigs. TJ-19 was administered by a single oral dose (3 g/kg) or by multiple oral doses (0.75 g/kg). KEY FINDINGS: The decrease in partial oxygen pressure of arterial blood (Pao(2)) and the increase in airway vascular permeability induced by the oleic acid injection were attenuated by a single dose of TJ-19. When TJ-19 was administered orally twice a day for two weeks and then oleic acid was injected, a potent prophylactic effect of the drug was observed. TJ-19 also prevented airway vascular hyperpermeability, lung cell injury, oxidative stress and thromboxane A(2) generation, associated with the oleic acid injection. CONCLUSIONS: TJ-19 significantly attenuated the oleic acid-induced lung injury probably through the antioxidative effect and inhibitory effect of thromboxane A(2) generation, although the precise inhibitory mechanisms were not fully elucidated due to the diversity in constituents of the herbal medicine. We suggest that TJ-19 is a promising drug candidate and a medicinal resource for preventing ARDS/ALI.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Permeabilidade Capilar/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Cobaias , Medicina Herbária , Masculino , Ácido Oleico , Estresse Oxidativo/efeitos dos fármacos , Plantas Medicinais , Tromboxano A2/antagonistas & inibidores , Tromboxano A2/biossíntese
18.
Biol Pharm Bull ; 32(3): 500-3, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19252304

RESUMO

To determine whether or not a "bolus injection" of soybean-based fat emulsion (SFE), which contains oleic acid (OA), a potent lung-toxic unsaturated C-18 fatty acid, can induce pulmonary dysfunction, we examined the effect of SFE injection on the partial oxygen pressure of arterial blood (Pao2) and pulmonary vascular permeability. In addition, we compared the effect of an injection of SFE with that of OA, soybean oil (a source of SFE), emulsified OA and C-18 fatty acids. Bolus injection of SFE (0.3-4.8 ml/kg) had little effect on Pao2) and pulmonary vascular permeability. Injection of an equivalent amount of OA, on the other hand, significantly decreased Pao2 and increased pulmonary vascular hyper-permeability. This decrease in Pao2 was attenuated by emulsification. Unemulsified soybean oil also induced a decrease in Pao2, although the effect was weaker than that of OA. Other unsaturated C-18 fatty acids (linoleic and linolenic acid) induced a decrease in Pao2 as potent as OA while stearic acid, a C-18 saturated fatty acid, had little effect. Although we did not observe pulmonary toxicity as a result of "bolus injection" of SFE, the chemical form, for example, emulsification and the degree of saturability of the carbon chain, seems to influence the pulmonary toxicities of lipids and fatty acids. Furthermore, the potent pulmonary toxicity of OA seems to depend not only on pulmonary vascular embolization but also pharmacological and/or inflammation-inducing properties.


Assuntos
Emulsões Gordurosas Intravenosas/toxicidade , Ácidos Graxos/toxicidade , Glycine max , Pulmão/efeitos dos fármacos , Troca Gasosa Pulmonar/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/fisiopatologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Emulsões , Cobaias , Ácido Linoleico/toxicidade , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Ácido Oleico/toxicidade , Oxigênio/sangue , Pressão Parcial , Óleo de Soja/toxicidade , Ácidos Esteáricos/toxicidade , Ácido alfa-Linolênico/toxicidade
19.
Zhonghua Yi Xue Za Zhi ; 88(44): 3112-5, 2008 Dec 02.
Artigo em Chinês | MEDLINE | ID: mdl-19159591

RESUMO

OBJECTIVE: To explore the impact of secondary lymphoid tissue chemokine (SLC) on lymphocyte migration and the significance thereof in the pathogenesis of ulcerative colitis (UC). METHODS: Sixty SD rats were randomly divided into 3 equal groups: model group undergoing dripping of 40% acetone solution of dinitro-chlorobenzene (DNCB) on the back for 2 weeks and then enema of 6% DNCB acetone solution so as to establish models of UC, and then intravenous injection of normal saline (NS) for 5 days; SLC antibody intervention group undergoing intravenous injection of SLC antibody 15 microg x ml(-1) x kg(-1) immediately after the establishing of model; and control group undergoing enema of NS nly and then intravenous injection of NS for 5 days. Six days after the establishing of model venous blood samples were collected from the portal veins of the 3 groups. Lymphocytes were isolated and cultured. RT-PCR was used to detect the mRNA expression of the SLC receptor CCR7. Boyden chamber system was used to examine the migration ability of the lymphocytes exposed to SLC of 20, 40, 60, 80, and 100 ng/ml respectively. ELISA was used to detect the expression of interleukin (IL)-10 and interferon (IFN)-gamma in the supernatants of the lymphocytes of different groups. RESULTS: RT-PCR showed that the CCR7 mRNA expression level of the model group was (0.792 +/- 0.108), significantly higher than that of the intervention group (0.386 +/- 0.115, P = 0.0429), and the CCR7 mRNA expression levels of these 2 groups were both significantly higher than that of the control group (0.106 +/- 0.029, both P < 0.01). SLC dose-dependently promoted the migration ability of the lymphocytes, but there existed a saturation phenomenon. Exposed to 80 ng/ml SLC the migration level of the lymphocytes of the model group peaked to (85.9 +/- 16.0), 3.7 times as high as that of the control group (20.5 +/- 1.8, P < 0.01), and the migration level of the lymphocytes of the intervention group was 38.2 +/- 6.3, significantly higher than that of the control group too (P < 0.05). SLC enhanced the expression of IFN-gamma of the lymphocytes of the model group, while reduced the IL-10 level, and both effects peaked at the concentration of 80 ng/ml (P = 0.042, P = 0.036). CONCLUSION: SLC promotes the lymphocyte migration and boosts the differentiation of lymphocytes, thus participating in the pathogenesis of UC.


Assuntos
Quimiocina CCL21/metabolismo , Colite Ulcerativa/metabolismo , Linfócitos/citologia , Animais , Movimento Celular , Células Cultivadas , Quimiocina CCL21/administração & dosagem , Colite Ulcerativa/imunologia , Feminino , Interferon gama/metabolismo , Interleucina-10/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores CCR7/metabolismo
20.
Integr Cancer Ther ; 6(1): 36-41, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17351025

RESUMO

There is an emerging consensus that between one fifth and one half of breast cancer patients experience chemotherapy-associated cognitive dysfunction. Research shows that patients with cancer are often interested in acupuncture for symptom relief. A clinical question thus arises: What should physicians advise their patients regarding the use of acupuncture to alleviate or ameliorate chemotherapy-associated cognitive dysfunction? The authors review and synthesize 2 bodies of relevant research literature: (1) the developing literature on the etiology and nature of chemotherapy-associated cognitive dysfunction and (2) the literature concerning acupuncture for neurological diseases and psychological issues. There is evidence that acupuncture may be effectively used to manage a range of psychoneurological issues, some of which are similar to those experienced by patients with chemotherapy-associated cognitive dysfunction. The evidence of efficacy is more promising for psychological than neurological conditions. Given evidence of possible efficacy combined with evidence of demonstrated safety, we suggest that physicians should support patient decisions to use acupuncture services for chemotherapy-associated cognitive dysfunction, especially given the lack of proven alternatives.


Assuntos
Acupuntura , Antineoplásicos/efeitos adversos , Transtornos Cognitivos/terapia , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Quimioterapia Adjuvante/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Humanos , Modelos Biológicos , Doenças do Sistema Nervoso/terapia
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