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1.
J Mater Chem B ; 8(34): 7766-7776, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32744285

RESUMO

Traditional techniques for the synthesis of nickel sulfide (NiS) nanoparticles (NPs) always present drawbacks of morphological irregularity, non-porous structure and poor long-term stability, which are extremely unfavorable for establishing effective therapeutic agents. Here, a category of hollow mesoporous NiS (hm-NiS) NPs with uniform spherical structure and good aqueous dispersity were innovatively developed based on a modified solvothermal reaction technique. Upon the successful synthesis of hm-NiS NPs, dopamine was seeded and in situ polymerized into polydopamine (PDA) on the NP surface, followed by functionalization with thiol-polyethylene glycol (SH-PEG) and encapsulation of the chemotherapeutic drug, doxorubicin (DOX), to form hm-NiS@PDA/PEG/DOX (NiPPD) NPs. The resultant NiPPD NPs exhibited a decent photothermal response and stability, attributed to the optical absorption of the hm-NiS nanocore and PDA layer in the near-infrared (NIR) region. Furthermore, stimulus-responsive drug release was achieved under both acidic pH conditions and NIR laser irradiation, owing to the protonation of -NH2 groups in the DOX molecules and local thermal shock, respectively. Lastly, a strong combinatorial photothermal-chemotherapeutic effect was demonstrated for tumor suppression with minimal systemic toxicity in vivo. Collectively, this state-of-the-art paradigm may provide useful insights to deepen the application of hm-NiS NPs for disease management and precision medicine.


Assuntos
Nanomedicina/métodos , Nanopartículas/química , Níquel/química , Fototerapia/métodos , Linhagem Celular , Técnicas de Química Sintética , Terapia Combinada , Doxorrubicina/química , Humanos , Indóis/química , Níquel/uso terapêutico , Polietilenoglicóis/química , Polímeros/química , Porosidade
2.
Shock ; 44(5): 496-502, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26196843

RESUMO

Lung fibrosis is an aggressive disease with uncontrolled fibrotic response and no effective therapeutic treatment. Epithelial-to-mesenchymal transition (EMT) has been proved to be an important pathological feature in lung fibrosis. In this study, we investigated whether MaR1, a kind of proresolving lipid mediators, could inhibit TGF-ß1-induced EMT in vitro and lung fibrosis in vivo. In vitro study, mouse type II alveolar epithelial cells were treated with different does of MaR1 for 30 min and were exposed to TGF-ß1 for 48 h. In vivo study, C57BL/6 mice were administered bleomycin intratracheally. After 14 days, MaR1 was injected intraperitoneally daily for 7 days. In day 28, mice were sacrificed. The results demonstrate that treatment of mouse type II alveolar epithelial cells with MaR1 (10 nM) significantly prevents TGF-ß1-induced fibronectin and α-SMA expression and restores E-Cadherin level. The down-regulation of profibrotic molecules of MaR1 is associated with suppression of Smad2/3 and Akt phosphorylation. In vivo, MaR1 treatment significantly prolongs survival rate and attenuates destruction of lung architecture, as well as collagen deposition after bleomycin inhalation. TGF-ß1 concentration in bronchoalveolar lavage and fibrotic markers (fibronectin and α-SMA) in lung tissues are inhibited by MaR1 administration. These data indicate that MaR1 inhibits TGF-ß1-induced EMT and attenuates bleomycin-induced pulmonary fibrosis. MaR1 may be a promising strategy for alleviation of lung fibrosis.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose Pulmonar/prevenção & controle , Animais , Bleomicina , Células Cultivadas , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/uso terapêutico , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/farmacologia
3.
Can J Physiol Pharmacol ; 90(7): 941-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22686837

RESUMO

To assess the effect of the drug combination of Schisandra sphenanthera extract (SchE) and Rapamycin (RAPA), 18 healthy subjects were given oral treatments of RAPA alone and with SchE. Pharmacokinetic investigations and indexes of hepatic and renal functions, as well as other indices of oral RAPA administration (2 mg), were performed both before and after the SchE treatment period. Whole-blood RAPA concentrations were determined by enzyme-linked immunosorbent assay. The research found that the mean whole-blood RAPA AUC(0-∞), C(max), and t(max) increased almost 2-, 2.1-, and 1.3-fold, respectively, and CL/F (-38.0%) decreased almost 1.6-fold in these subjects when RAPA was administered with SchE compared with oral RAPA administered alone. The results of this study proved that SchE can increase the oral bioavailability of RAPA and will add important information to the interaction area between drugs and herbal products.


Assuntos
Interações Ervas-Drogas , Extratos Vegetais/farmacologia , Schisandra/química , Sirolimo/farmacologia , Administração Oral , Adulto , Área Sob a Curva , Disponibilidade Biológica , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/sangue , Extratos Vegetais/farmacocinética , Sirolimo/sangue , Sirolimo/farmacocinética
4.
Molecules ; 16(10): 8684-94, 2011 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-22005833

RESUMO

In the present study the capacity of Radix Paeoniae Rubra aqueous extract (RPRAE) as an antioxidant to protect against carbon tetrachloride (CCl(4))-induced oxidative stress and hepatotoxicity in Wistar rats was investigated. Six groups of rats were used. Radix Paeoniae Rubra aqueous extract (100 or 200 or 300 mg/kg of bw) or bifendate (100 mg/kg of bw) were given daily by gavage to the animals on 28 consecutive days to elucidate the protective effects against CCl(4)-induced hepatotoxicity. The 20% CCl(4)/olive oil was gavage of gastric tube twice a week (on the third and seventh days of each week). The animals of normal control group were given only vehicle. The animals of CCl(4)-treated group were administered with CCl(4) twice a week (on the third and seventh days of each week) and with vehicle on rest of the days. The test materials were found effective as hepatoprotective agents, as evidenced by plasma and liver biochemical parameters. Therefore, the results of this study show that Radix Paeoniae Rubra aqueous extract can protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effects might be correlated with its antioxidant and free radical scavenger effects.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Paeonia/metabolismo , Animais , Antioxidantes/química , Compostos de Bifenilo/farmacologia , Tetracloreto de Carbono , Intoxicação por Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Fitoterapia , Raízes de Plantas/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar
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