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1.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 156-160, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430027

RESUMO

To investigate whether Liraglutide combined with Jinlida granules affects glycolipid metabolism and islet function in the treatment of type 2 diabetes mellitus (T2DM), a control group and an observation group were established with 90 T2DM patients. The control group was given Jinlida treatment and the observation group was given liraglutide combined treatment for 12 weeks. The clinical efficacy, glycolipid metabolism, bone metabolism, islet function, and endothelial function. The curative effect of the observation group was better than that of the control group. After treatment, FBG, 2hPG, HbAlc, TC, TG, and LDL-C in the observation group were lower and HDL-C was higher than those in the control group (P < 0.05). After treatment, the observation group showed higher bone mineral density, osteocalcin, FINS, and HOMA-ß and lower HOMA-IR than the control group (P < 0.05). After treatment, endothelin-1 level in the observation group was lower than that in the control group, and the NO level was higher (P < 0.05). No significant difference was found in the incidence of adverse reactions between the two groups (P > 0.05). Liraglutide combined with Jinlida in T2DM can improve glucose, lipid, and bone metabolism, promote the recovery of islet function, and enhance vascular endothelial function.


Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Liraglutida/uso terapêutico , Glicemia/metabolismo , Glicolipídeos/uso terapêutico
2.
Environ Int ; 171: 107674, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463658

RESUMO

PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) is a well-known cytotoxic pollutant that capable to induce severe intracellular oxidative stress while the underlying mechanisms remain unclear. Herein, 4 types of PM2.5 derived from solid fuel burning were selected as stimuli in A549 cells exposure model to evaluate their effects on oxidative stress and inflammatory responses. Although resulting in different responses in cell viability, all PM2.5 exhibited over 50 % higher oxidative stress than control group, expression as intracellular reactive oxygen species, malondialdehyde and superoxide dismutase levels. The Pearson's correlation results indicated that cations (e.g., Ca2+), heavy metals (e.g., Cr and Pb), nPAHs (nitro-polycyclic aromatic hydrocarbons, e.g., 6-nitrochrysene) and oPAHs (oxygenated PAHs, e.g., 9-fluorenone) were the main functioning toxics (r > 0.6). A key finding was the dual-directional regulation function of ECG (epicatechin gallate), that is, it could either increase the low A549 cell viabilities in coal combustion PM2.5 group or reduce them in charcoal PM2.5 group (P < 0.05). The dual-directional effects were likely because ECG can activate Nrf2 oxidation signaling pathway then inhibit the inflammatory signaling pathway NF-κB accordingly. Therefore, evidences indicated cytotoxicity of solid fuel derived PM2.5 were mainly caused by oxidative stress, which was proved to be reversed by green tea, providing a potential therapy method to PM2.5 and other hazards.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Células A549 , Chá , Material Particulado/toxicidade , Material Particulado/análise , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/análise
3.
Environ Res ; 214(Pt 2): 113894, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35868580

RESUMO

Phosphates are the dominant phosphorus (P) source on Earth. The phosphates govern available P in soil, or even the complete ecosystem. The common deficiency of available P in carbonate-enriched soils suggests the tight correlation between P and C biogeochemistry, although the two elements have diverse abundance in soil. The influences of carbonates on P cycle were reviewed in this study, via both abiotic and biotic pathways. The abiotic processes at geochemical scale include element release, transport, sorption, desorption, weathering, precipitation, etc. The sorption of P on carbonate and buffering ability of carbonates were particularly addressed. Biotic factors are ascribed to various microorganisms in soil. As the most active P pool in soil, microorganisms prefer to consume abundant P, and then accumulate it in their biomass. Carbonates, however, are usually utilized by microorganisms after conversion to organic C. Meanwhile, extracellular precipitation of Ca-P phases significantly regulates the transportation of P in/out the cells. Moreover, they boost and complexify both carbonates and P turnover in soil via bioweathering and biomineralization, i.e., the intense interactions between biosphere and lithosphere. Based on this review, we proposed that carbonates may negatively affect P supply in soil system. This comprehensive review regarding the regulation by carbonates on P biogeochemistry would shed a light on predicting long-term P availability influenced by C biogeochemistry.


Assuntos
Fósforo , Solo , Carbonatos , Ecossistema , Fosfatos , Solo/química
4.
Ann Hepatol ; 27(4): 100710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35430357

RESUMO

INTRODUCTION AND OBJECTIVES: Both external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC. METHODS: Pubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis. RESULTS: The results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55-0.76) and 0.40 (95%CI: 0.24-0.56). The incidence of adverse events was 0.34 (95%CI: 0.25-0.44). CONCLUSIONS: The findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Sorafenibe/efeitos adversos , Resultado do Tratamento
5.
Pharm Biol ; 59(1): 1402-1414, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34672897

RESUMO

CONTEXT: Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear. OBJECTIVE: The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated. MATERIALS AND METHODS: An AD rat model was established by ovariectomy combined with d-galactose and Aß1-40 injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERß, Aß1-40, and p-tau404 was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins. RESULTS: Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERß-positive cells (57.42, 39.83); Aß1-40 (18.85, 36.83)- and p-tau404 (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3ß and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated. DISCUSSION AND CONCLUSION: Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides , Animais , Animais não Endogâmicos , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Galactose , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Ovariectomia , Fragmentos de Peptídeos , Fosfatidilinositol 3-Quinase/metabolismo , Proteômica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley
6.
Small ; 17(42): e2102527, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34528387

RESUMO

The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Fotoquimioterapia , Linhagem Celular Tumoral , Fluorescência , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Fototerapia , Nanomedicina Teranóstica , Termodinâmica , Microambiente Tumoral
7.
ACS Omega ; 6(1): 917-924, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33458543

RESUMO

Shuanglian decoction (SLD) is traditionally used to treat hepatocellular carcinoma (HCC) in the clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for the treatment of HCC are not clear. The active compounds of SLD were collected and their targets were identified. HCC-related targets were obtained by analyzing the differentially expressed genes between HCC patients and healthy individuals. Protein-protein interaction (PPI) data were then obtained and PPI networks of SLD putative targets and HCC-related targets were visualized and merged to identify the candidate targets for SLD against HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 35 active compounds and 31 targets of SLD were identified. In total, 245 differentially expressed genes with P values <0.005 and |log2 (fold change)| > 1 were identified between HCC patients and control groups, and 68 target genes associated with HCC were finally identified. Twenty-one pathways including cellular senescence, p53 signaling pathway, and cell cycle were significantly enriched. CYP3A4 was the core gene and other several genes including CYP1A2, PPP3CA, PTGS2, CCCNB1, and CDK1 were the key genes in the gene-pathway network of SLD for the treatment of HCC. The results indicated that SLD's effects against HCC may relate to the regulation of an antioxidant function through specific biological processes and related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.

8.
J Ethnopharmacol ; 259: 112940, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32389853

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora sinensis (Lour.) Merr. belongs to the family Menispermaceae. It is called LeZhe and is widely used as a kind of folk medicine especially in the Tibetan Plateau of China. T. sinensis has the functions of clearing away heat and detoxification, dispelling wind and dredging collaterals, calming and soothing the nerves. T. sinensis is an effective medicine for the prevention and treatment of aging diseases such as Alzheimer's disease (AD) in the Tibetan Plateau of China, whereas its material basis and underlying mechanisms are not clear. The aim of this study was to investigate the material basis and potential mechanisms of T. sinensis in the treatment of AD by using network pharmacology and molecular docking. MATERIALS AND METHODS: In this study, targets were collected from DrugBank database, Therapeutic Target Database (TTD) and literatures reports for the treatment of AD. Compounds were searched by literatures and systematic separation from T. sinensis. The molecular docking experiment was carried out by using Autodock Vina software to screen the bioactive compounds in T. sinensis and target proteins for AD. Then, the "compound-target network" was constructed by Cytoscape software. The drug-like properties of the active compounds were analyzed by pKCSM performs, and the protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway enrichment analysis was carried out by Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protective effect of neurons of two active compounds were verified with the injury cell model of PC12 and primary hippocampus neurons induced by Aß25-35. Finally, the key proteins of related pathways were quantitatively analyzed with Western blot method. RESULTS: In total, 105 compounds and 38 targets have been screened. The main active compounds contained berberine, which belongs to alkaloids, Aurantiamide acetate, N-P-coumaroyltyramine, which belongs to amides, Trans-syringin and 3-demethyl-phillyrin, which belongs to phenylpropanoids. The targets covered inflammation-related proteins, including Protein kinase B (AKT), Phosphoinositide 3-kinase (PI3K), Tyrosine-protein kinase JAK1 (JAK1), mammalian target of rapamycin (mTOR), tumor necrosis factor alpha (TNF-α), Neuronal NOS (NOS1), and cholinergic function-related proteins, including α4-Nicotinic acetylcholine receptor (α4 nAChR), Muscarinic acetylcholine receptor M1 (Muscarnic M1). Inflammation and cholinergic dysfunction were the center of the network and occupy a dominant position. And the results of enrichment analysis shown the pathways mainly contained phosphoinositide-3-kinase/Akt (PI3K/Akt) signal pathway, neurotrophic factors (NTFs) signal pathway, Hypoxia-inducible factor 1 (HIF-1) signal pathway, mechanistic Target of Rapamycin (mTOR) signal pathway, Tumor necrosis factor (TNF) signal pathway, insulin resistance (IR). The results of in vitro assays showed that the tested compounds could significantly improve the survival rate and inhibit the apoptosis of PC12 cells and primary hippocampal neurons injured by Aß25-35. Western blot results showed that T. sinensis had a significant effect on the expression of protein PI3K and Akt. CONCLUSION: Our results revealed that T. sinensis could prevent and treat AD through a multi-compound-multi-target-multi-pathway regulatory network. Our work also expected to provide new ideas and theoretical bases for searching for the active compounds in T. sinensis and potential mechanism in the prevention and treatment of AD by the network pharmacology and molecular docking. The results of in vitro assay and in vivo assay supported the results of molecular docking.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Biologia de Sistemas , Tinospora , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Animais , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Fragmentos de Peptídeos/toxicidade , Extratos Vegetais/isolamento & purificação , Mapas de Interação de Proteínas , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Tinospora/química
9.
J Proteomics ; 200: 11-27, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-30890455

RESUMO

An extract prepared from species of Paris is the most widely consumed herbal product in China. The genus Paris includes a variety of genotypes with different medicinal component contents but only two are defined as official sources. Closely related species have different medicinal properties because of differential expression of proteins and metabolites. To better understand the molecular basis of these differences, we examined proteomic and metabolomic changes in rhizomes of P. polyphylla var. chinensis, P. polyphylla var. yunnanensis, and P. fargesii var. fargesii using a technique known as sequential window acquisition of all theoretical mass spectra as well as gas chromatography-time-of-flight mass spectrometry. In total, 419 proteins showed significant abundance changes, and 33 metabolites could be used to discriminate Paris species. A complex analysis of proteomic and metabolomic data revealed a higher efficiency of sucrose utilization and an elevated protein abundance in the sugar metabolic pathway of P. polyphylla var. chinensis. The pyruvate content and efficiency of acetyl-CoA-utilization in saponin biosynthesis were also higher in P. polyphylla var. chinensis than in the other two species. The results expand our understanding of the proteome and metabolome of Paris and offer new insights into the species-specific traits of these herbaceous plants. SIGNIFICANCE: The traditional Chinese medicine Paris is the most widely consumed herbal product for the treatment of joint pain, rheumatoid arthritis and antineoplastic. All Paris species have roughly the same morphological characteristics; however, different members have different medicinal compound contents. Efficient exploitation of genetic diversity is a key factor in the development of rare medicinal plants with improved agronomic traits and malleability to challenging environmental conditions. Nevertheless, only a partial understanding of physiological and molecular mechanisms of different plants of Paris can be achieved without proteomics. To better understand the molecular basis of these differences and facilitate the use of other Paris species, we examine proteomic metabolomic changes in rhizomes of Paris using the technique known as SWATH-MS and GC/TOF-MS. Our research has provided information that can be used in other studies to compare metabolic traits in different Paris species. Our findings can also serve as a theoretical basis for the selection and cultivation of other Paris species with a higher medicinal value.


Assuntos
Melanthiaceae/metabolismo , Metaboloma , Metabolômica , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Proteômica
10.
Artigo em Inglês | MEDLINE | ID: mdl-29259644

RESUMO

Oxytropis falcata has long been used to treat inflammation, sores, and bleeding in Tibet. However, the burn remedy and underlying molecular mechanisms are not well understood. This study is aimed at assessing the effect of Oxytropis falcate gel (OFG) on deep second-degree burn rats and exploring its mechanism. Wistar rats with second-degree burn were treated with OFG and silver sulfadiazine. Immunohistochemical detections for EGF and VEGF were performed, and ELISA detections for EGF, VEGF, p38, and IL-1ß in serum were determined. Rats treated with OFG (25, 50 g/kg) consisted of the major rhamnocitrin-3-O-ß-neohesperidoside significantly accelerated incrustation (P < 0.001) and decrustation (P < 0.001). According to HE staining, edema and infiltration of inflammatory cells decrease apparently with good hyperplasia and incrustation in administration groups (7 d). The expressions of EGF and CD34 in OFG (25, 50 g/kg) treatment increased obviously from immunohistochemical assessment (7 d). Serum EGF expression reached 321.27 ± 7.20 ng/mL by OFG treatment, while p38 (P < 0.05) and IL-1ß (P < 0.05) levels were significantly lower than the model and vehicle groups from day 1 to day 7. OFG possesses potential wound healing activities. The mechanism may be related to the increasing of biosynthesis and the releasing of EGF and CD34 and the decreasing p38 and IL-1ß levels.

11.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4211-4217, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29271163

RESUMO

The present study is to explore the material basis and mechanism of Erzhi Wan the prevented Alzheimer's disease by using network pharmacology. The key target of Alzheimer's disease was docked with the Erzhi Wan compounds, and the drugs-target combined with target-signal pathway network model was established by Cytoscape 3.2.1 software. Thirty compounds have a strong interaction with key target of Alzheimer's disease and three key pathways related with Wnt, MAPK and PI3K-Akt-mTOR. There are 5 ingredients such as quercetin,geraniol,beta-sitosterol,nerol,eriodictyol that could be verified from literature.This result initially revealed the material basis for Erzhi Wan for Alzheimer's disease and the mechanism in terms of three signaling pathways. The network pharmacology method found that the active ingredients of Erzhi Wan for Alzheimer's disease may be quercetin,geraniol,beta-sitosterol,nerol,and eriodictyol, and the mechanism may be related to three signal pathways including Wnt, MAPK, and PI3K-Akt-mTOR.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Monoterpenos Acíclicos , Flavanonas , Humanos , Quercetina , Sitosteroides , Terpenos
12.
Sci Rep ; 6: 27136, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27256519

RESUMO

Achieving control of metastatic disease is a long-sought goal in cancer therapy. Treatments that encourage a patient's own immune system are bringing new hopes in reaching such a goal. In clinic, local hyperthermia and cryoablation have been explored to induce anti-tumor immune responses against tumors. We have also developed a novel therapeutic modality of cryo-thermal treatment by alternating liquid nitrogen (LN2) cooling and radio frequency (RF) heating, and better therapeutic effect was achieved in treating metastatic cancer in animal model. In this study, we investigated the mechanism of systemic immune response elicited by cryo-thermal therapy. In the 4T1 murine mammary carcinoma model, we found that local cryo-thermal therapy resulted in a considerable reduction of distant lung metastases, and improved long-term survival. Moreover, results of tumor re-challenge experiments indicated generation of a strong tumor-specific immune memory after the local treatment of primary tumors. Our further study indicated that cryo-thermal therapy caused an elevated extracellular release of Hsp70. Subsequently, Hsp70 induced differentiation of MDSCs into mature DCs, contributing to the relief of MDSCs-mediated immunosuppression and ultimately the activation of strong anti-tumor immune response. Our findings reveal new insight into the mechanism of robust therapeutic effects of cryo-thermal therapy against metastatic cancers.


Assuntos
Crioterapia/métodos , Proteínas de Choque Térmico HSP70/metabolismo , Hipertermia Induzida/métodos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Neoplasias Mamárias Experimentais/terapia , Células Supressoras Mieloides/citologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Células Dendríticas/citologia , Feminino , Regulação Neoplásica da Expressão Gênica , Camundongos , Transplante de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Regulação para Cima
13.
Clin Cancer Res ; 20(19): 4994-5000, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25096067

RESUMO

On August 17, 2011, the U.S. Food and Drug Administration (FDA) approved vemurafenib tablets (Zelboraf, Hoffmann-LaRoche Inc.) for the treatment of patients with unresectable or metastatic melanoma with the BRAF(V600E) mutation as detected by an FDA-approved test. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems, Inc.) was approved concurrently. An international, multicenter, randomized, open-label trial in 675 previously untreated patients with BRAF(V600E) mutation-positive unresectable or metastatic melanoma allocated 337 patients to receive vemurafenib, 960 mg orally twice daily, and 338 patients to receive dacarbazine, 1,000 mg/m(2) intravenously every 3 weeks. Overall survival was significantly improved in patients receiving vemurafenib [HR, 0.44; 95% confidence interval (CI), 0.33-0.59; P < 0.0001]. Progression-free survival was also significantly improved in patients receiving vemurafenib (HR, 0.26; 95% CI, 0.20-0.33; P < 0.0001). Overall response rates were 48.4% and 5.5% in the vemurafenib and dacarbazine arms, respectively. The most common adverse reactions (≥30%) in patients treated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous cell carcinomas or keratoacanthomas were detected in approximately 24% of patients treated with vemurafenib. Other adverse reactions included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.


Assuntos
Aprovação de Drogas , Indóis , Sulfonamidas , United States Food and Drug Administration , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Estados Unidos , Vemurafenib
14.
Zhongguo Zhen Jiu ; 34(2): 169-72, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24796057

RESUMO

OBJECTIVE: To observe the clinical effect of electric stimulation of long-term retaining needle on analgesia after laparoscopic cholecystectomy (LC) and the impacts on the post-surgical flatus time. METHODS: Under static absorptive composite general anesthesia, 90 cases of LC were randomized into three groups, 30 cases in each one. In the control group, the analgesia was not applied after LC. In the analgesia-pumper group, the patient controlled intravenous analgesia (PCIA) was used. In the needle-retaining group, the electric acupuncture stimulator was used. The needles were inserted transversely at Riyue (GB 24), Qichong (ST 30) and Yanglingquan (GB 34) and fixed with sterile sticker. Separately, in 8 h and 24 h after surgery, the electric acupuncture stimulation with disperse-dense wave, 2 Hz/100 Hz frequency was applied continuously for 30 min. Visual analogue scale (VAS), adverse reactions such as vomiting and nausea and the postoperative flatus time in 2, 4, 8, 12, 24 and 36 h after surgery were observed and recorded in the three groups. RESULTS: In 2, 4, 8, 12 and 24 h after surgery, VAS scores in the needle-retaining group and the analgesia-pumper group were all lower than those in the control group (P < 0.05, P < 0.01). The analgesia effect at the above time points in the needle-retaining group was better than that in the analgesia-pumper group (all P < 0.05). There was not adverse reaction in the needle-retaining group. But there were 3 cases of somnolence, 6 cases of nausea and 3 cases of vomiting in the analgesia-pumper group, and 2 cases of nausea and 1 case of vomiting in the control group. The flatus time was quite earlier in the needle-retaining group as compared with the other two groups [(14.77 +/- 4.99) h vs (18.50 +/- 4.22) h, P < 0.01; (14.77 +/- 4.99) h vs (18.17 +/- 4.69) h, P < 0.05]. CONCLUSION: The electric stimulation of long-term retaining needle is safe and effective in analgesia after LC. It avoids the adverse reactions of analgesics and promotes postoperative flatus.


Assuntos
Analgesia por Acupuntura , Eletroacupuntura , Dor Pós-Operatória/terapia , Analgesia por Acupuntura/instrumentação , Adulto , Idoso , Colecistectomia Laparoscópica/efeitos adversos , Eletroacupuntura/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Dor Pós-Operatória/etiologia
15.
J Surg Res ; 184(2): 1035-44, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23721934

RESUMO

BACKGROUND/AIMS: Endotoxin (lipopolysaccharide, LPS)-induced acute liver injury was attenuated by endotoxin tolerance (ET), which is characterized by phosphatidylinositol 3-kinase pathway/Akt signaling. Glycogen synthase kinase 3 (GSK-3) acts downstream of phosphatidylinositol 3-kinase pathway/Akt and GSK-3 inhibitor protects against organic injury. This study evaluates the hypothesis that ET attenuated LPS-induced liver injury through inhibiting GSK-3 functional activity and downstream signaling. METHODS: Sprague-Dawley rats with or without low-dose LPS pretreatment were challenged with or without large dose of LPS and subsequently received studies. Serum tumor necrosis factor-alpha, interleukin-10, alanine aminotransferase, lactate dehydrogenase, and total bilirubin levels were analyzed, morphology of liver tissue was performed, glycogen content, myeloperoxidase content, phagocytosis activity of Kupffer cells, and the expression and inhibitory phosphorylation as well as kinase activity of GSK-3 were examined. Survival after LPS administration was also determined. RESULTS: LPS induced significant increases of serum TNF-α, alanine aminotransferase, lactate dehydrogenase, and total bilirubin (P < 0.05), which were companied by obvious alterations in liver: the injury of liver tissue, the decrease of glycogen, the infiltration of neutrophils, and the enhancement of phagocytosis of Kupffer cells (P < 0.05). LPS pretreatment significantly attenuated these alterations, promoted the inhibitory phosphorylation of GSK-3 and inhibited its kinase activity, and improved the survival rate (P < 0.05). CONCLUSIONS: ET attenuated LPS-induced acute liver injury through inhibiting GSK-3 functional activity and its downstream signaling.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Endotoxinas/efeitos adversos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Lipopolissacarídeos/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Bilirrubina/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quinase 3 da Glicogênio Sintase/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Interleucina-10/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
16.
Zhongguo Zhen Jiu ; 33(10): 871-6, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24377213

RESUMO

OBJECTIVE: To compare the difference of the efficacy on knee osteoarthritis (KOA) between the combined therapy of acupuncture and moxibustion and western medication, and explore the better therapeutic method for KOA. METHODS: One hundred and sixty patients were divided into a combined therapy group and a western medication group, 80 cases in each one according to the visit sequence, with the random number table adopted. In the combined therapy group, the main points were selected from the local painful sites, combined with the acupoints based on the syndrome differentiation and distal acupoints on the affected meridians. The lifting, thrusting or rotating technique was used and the reinforcing or reducing manipulation was applied according to the syndrome differentiation. "Duanci" or "Shuci" needling technique was used specially at the extra points and Ashi points. The needling sensation relied on the patients' tolerance. After acupuncture, the heat-sensitive moxibustion with pure moxa stick was applied over the local painful sites around knee joint and Shenshu (BL 23) to detect the heat-sensitized points. Acupuncture and moxibustion were given once every day. The treatment of 5 days made 1 session. There were 2 days at the interval between two sessions. In the western medication group, glucosamine sulfate capsules were prescribed for oral administration, 2 capsules each time, three times a day. Additionally, the joint cavity injection was combined. On the first day, sodium hyaluronate 25 mg and triamcinolone acetonide acetate 50 mg were injected. Afterwards, on the 8th, 15th, 22nd and 29th days, sodium hyaluronate injection 25 mg was used only. The treatment was for 5 weeks totally in the two groups. The efficacy was analyzed statistically in 5 weeks. The follow-up visit was conducted in 3 months and 6 months after 5 weeks treatment, respectively. The Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) were adopted to assess the recovery of joint function. RESULTS: The efficacy in 5 weeks of treatment was different significantly between the two groups (P < 0.05). The efficacy in the western medication group was better than that in the combined therapy group. The difference in the safety assessment was remarkable (P < 0.01). The result in the combined therapy group was superior remarkably to the western medication group. In 3-month follow-up visit after treatment, the knee joint function was not different obviously between the two groups (P > 0.05). In 6-month followup visit after treatment, the knee joint function was different obviously between the two groups (P < 0.01). The result in the combined therapy group was better remarkably than that in the western medication group. CONCLUSION: The combined therapy of acupuncture and moxibustion achieves the safe and effective therapeutic effect with less adverse reactions in the treatment of KOA. The immediate effect in the combined therapy group is not so obvious as compared with the western medication, but the long-term efficacy is remarkably superior to western medication.


Assuntos
Terapia por Acupuntura , Moxibustão , Osteoartrite do Joelho/terapia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento
17.
PLoS One ; 7(9): e46574, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029551

RESUMO

Polydatin is one of main compounds in Polygonum cuspidatum, a plant with both medicinal and nutritional value. The possible hepatoprotective effects of polydatin on acute liver injury mice induced by carbon tetrachloride (CCl(4)) and the mechanisms involved were investigated. Intraperitoneal injection of CCl(4) (50 µl/kg) resulted in a significant increase in the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hepatic malondialdehyde (MDA), also a marked enhancement in the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclearfactor-kappa B (NF-κB). On the other hand, decreased glutathione (GSH) content and activities of glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were observed following CCl(4) exposure. Nevertheless, all of these phenotypes were evidently reversed by preadministration of polydatin for 5 continuous days. The mRNA and protein expression levels of hepatic growth factor-beta1 (TGF-ß(1)) were enhanced further by polydatin. These results suggest that polydatin protects mice against CCl(4)-induced liver injury through antioxidant stress and antiinflammatory effects. Polydatin may be an effective hepatoprotective agent and a promising candidate for the treatment of oxidative stress- and inflammation-related diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fallopia japonica/química , Glucosídeos/farmacologia , Estilbenos/farmacologia , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Expressão Gênica , Glucosídeos/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/uso terapêutico , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
18.
Artigo em Inglês | MEDLINE | ID: mdl-23326292

RESUMO

Hypertrophic scarring is a common proliferative disorder of dermal fibroblasts characterized by collagen overproduction and excessive deposition of extracellular matrix (ECM). There is no consensus about the best therapeutics to produce complete and permanent improvement of scars with few side effects. To investigate the therapeutic effects of oleanolic acid (OA) on hypertrophic scars and explore the possible mechanism of action involved, a rabbit ear model with hypertrophic scars was established. OA (2.5%, 5%, and 10%) was given once daily to the scars for 28 consecutive days. As a result, OA significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-ß(1), MMP-1, TIMP-1, and collagens I and III were notably decreased, and the number of apoptosis cells and mRNA expression of MMP-2, caspase-3, and caspase-9 were markedly increased in the scar tissue. The scar elevation index (SEI) was also evidently reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that OA has the favorable curative effects on formed hypertrophic scars in the rabbit ear model, and the possible mechanism of action is that OA decreases HSFs proliferation and increases HSFs apoptosis by reduction of P311 gene expression and TGF-ß(1) production, inhibition of TIMP-1 secretion, enhancement of MMP-2 activity, and subsequently facilitation of degradation of collagen types I and III.

19.
Zhong Yao Cai ; 35(10): 1557-61, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23627117

RESUMO

OBJECTIVE: To explore the relation between the quality of the Herb-Paris and their cultivation of soil nutritional status. METHODS: The soil nutrient status (0 - 30 cm) of Paris polyphylla var. yunnanensis, artificially cultivated areas were determined in 2009 and their rhizome qualities harvested in 2010 were evaluated respectively. Determination of 0 - 30cm depth soil ingredients status with soil conventional five nutritional analysis method of 29 artificial cultivation area, 9 Prefectures of Yunnan Province. RESULTS: Soil nutrient has effect on quality of Herb-Paris medicinal ingredients. CONCLUSION: The multiple linear stepwise regression analysis reveals that among a certain range, the steroidal saponin VII content is positively correlated with the content of soil organic matter and pH. Steroidal saponin H content is positively correlated with the content of soil organic matter, available P and pH. Steroidal saponin I is positively correlated with the content of available K, but negatively correlated with the content of available Herb-Paris, and steroidal saponin II is positively correlated with the content of soil organic matter and available K.


Assuntos
Liliaceae/química , Nitrogênio , Rizoma/química , Saponinas/análise , Solo/análise , Agricultura/métodos , China , Cromatografia Líquida de Alta Pressão , Fertilizantes , Concentração de Íons de Hidrogênio , Liliaceae/crescimento & desenvolvimento , Fósforo , Potássio , Controle de Qualidade , Análise de Regressão , Rizoma/crescimento & desenvolvimento , Solo/química
20.
Zhongguo Zhong Yao Za Zhi ; 34(6): 770-3, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19624026

RESUMO

OBJECTIVE: To investigate the origin of medicinal plants in Guizhou province, revise the incorrectly recorded species, and correct the erroneous and incomplete Latin names. METHOD: Examination was implemented on species, Latin name and geographical distribution of medicinal plants recorded in 'Medicinal Material Resources of Guizhou'. RESULT: It was found that 98 species and 4 varieties were absent in Guizhou province or their Latin names were incorrect in 17 families. CONCLUSION: The origin of medicinal plants in Guizhou province was studied and the incorrect Latin names were revised. It provides a basis for standardization of medicinal plants in Guizhou province.


Assuntos
Plantas Medicinais/classificação , China , Plantas Medicinais/crescimento & desenvolvimento , Terminologia como Assunto
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