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1.
Pharmacology ; 104(5-6): 235-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31357205

RESUMO

BACKGROUNDS: (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits better anti-inflammatory activity. This study was designed to evaluate the protective effect of MASM on acute and chronic liver injuries and explore the possible mechanisms. METHODS: Acute and chronic liver injury models were established by the CCl4 intraperitoneal injection and the protective effect of MASM was assessed by biochemical and histological examination. The infiltration of different monocyte subsets into the liver was characterized and analyzed by flow cytometry. The in vitro effect of MASM on liver nonparenchymal cells was evaluated by real-time PCR and transwell chemotaxis assays. RESULTS: Administration of MASM markedly attenuated acute liver injury and liver fibrosis induced by CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in injured livers and induced hepatic expression of monocyte chemoattractant protein-1 (MCP-1) were greatly inhibited. Cellular experiments demonstrated that MASM not only decreased the expression of MCP-1 but also inhibited its chemotactic activity. CONCLUSIONS: This study demonstrates that the protective effect of MASM on liver injury could be contributed to the suppression of Gr1hi monocyte infiltration to the liver and the inhibition of MCP-1 production and activity. These findings provide new insights into the protective role of MASM in liver injury.


Assuntos
Alcaloides/uso terapêutico , Antracenos/farmacologia , Anti-Inflamatórios/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Monócitos/efeitos dos fármacos , Quinolizinas/uso terapêutico , Tionas/farmacologia , Alcaloides/farmacologia , Animais , Antracenos/uso terapêutico , Anti-Inflamatórios/farmacologia , Antígenos Ly/imunologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quimiocina CCL2/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Quinolizinas/farmacologia , Tionas/uso terapêutico , Matrinas
2.
Carbohydr Polym ; 213: 411-418, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879686

RESUMO

Despite some efforts have been made in the research of supramolecular hyperbranched polymers (SHPs) self-assemblies, the study which has not been consideration to date is the influence of incoming stimuli-responsive polymer chain on their self-assembly property undergo outer stimuli. The introduction of stimuli-responsive segments which could maintain their hydrophilic property are expected to affect the self-assembly behaviour of SHPs and expand their further biomedical application. In this paper, AB2-type macromolecular monomer, LA-(CD-PDMA)2, which consisted one lithocholic acid (LA) and two ß-cyclodextrin terminated poly(2-(dimethylamino)ethyl methacrylate) segments (CD-PDMA) was synthesized. LA-(CD-PDMA)2 based SHP were obtained based on the host-guest inclusion interactions of CD/LA moietes and with PDMA as pH-responsive hydrophilic chains. As a control to study the influence of incoming PDMA chains, both LA-(CD-PDMA)2 based SHPs-1 and LA-CD2 based SHPs-2 self-assemblies were comparatively investiged through 2D 1H NMR ROESY, transmission electron microscopy (TEM) and dynamic light scattering (DLS). The results suggested that except for the higher drug loading efficiency LA-(CD-PDMA)2 based SHPs-1 pocessing, the release rates of SHPs-1 increased notably at pH 5.0 than that of pH 7.4 due to the repulsion and stretch of protonated PDMA chains while the release rates of SHPs-2 showed no obvious difference. Finally, basic cell experiments demonstrated that the SHPs based self-assemblies can be internalized into cancer cells, indicating their potential application in the drug delivery field.


Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Polímeros/farmacologia , beta-Ciclodextrinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ácido Litocólico/química , Ácido Litocólico/farmacologia , Células MCF-7 , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Conformação Molecular , Imagem Óptica , Polímeros/síntese química , Polímeros/química , beta-Ciclodextrinas/química
3.
World J Gastrointest Oncol ; 8(10): 735-744, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27795813

RESUMO

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

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