RESUMO
Objective: To make preliminary exploration into the Golgi apparatus targeting of chondroitin sulfate-modified micelles (CSmicelles) co-loaded with pirarubicin (THP) and vinorelbine (VRL) in tumor cells, as well as their in vitro anti-tumor metastasis effect. Methods: The cellular uptake efficiency and internalization mechanism of CSmicelles in 4T1 mouse breast cancer cell line were investigated by flow cytometry. Preliminary study of the Golgi apparatus targeting CSmicelles in tumor cells was conducted by co-localization experiment. Then, the effect of CSmicelles co-loaded with THP and VRL (THP+VTL-CSmicelles) on the structure of Golgi apparatus was investigated by GM130 immunofluorescence experiment. Finally, the i n vitro anti-tumor metastasis ability of THP+VTL-CSmicelles was evaluated by wound healing assay and Transwell migration/invasion assay. Results: It was found that CSmicelles could significantly increase cellular uptake of drugs. CSmicelles were internalized into cells through clathrin-mediated and caveolin-mediated endocytosis, which was energy-dependent active transport and exhibited substantial ability of targeting Golgi apparatus in tumor cells. THP+VTL-CSmicelles could break down the structure of Golgi apparatus and significantly inhibit the migration and invasion of tumor cells. Conclusion: THP+VTL-CSmicelles demonstrate high affinity towards Golgi apparatus in tumor cells, exert targeted effects and inhibit tumor cell metastasis, which provides a novel idea and method for the treatment of cancer metastasis.
Assuntos
Micelas , Neoplasias , Animais , Sulfatos de Condroitina/química , Sulfatos de Condroitina/metabolismo , Sulfatos de Condroitina/farmacologia , Complexo de Golgi/metabolismo , Complexo de Golgi/patologia , Camundongos , Neoplasias/tratamento farmacológicoRESUMO
Previous studies have indicated that monocyte chemoattractant protein-1 (MCP1), also referred to as CC motif chemokine ligand 2, has a significant role in the pathogenesis of sepsis, however, how microRNAs (miRs) contribute to this process remains to be fully elucidated. In the present study, using a mouse model of disseminated candidiasis, the renoprotective effect of itraconazole (ITR) and adenovirusdelivered miR124 was investigated. The mice were treated with ITR (50 mg/kg) or transfected with miR124 mimics via tailvein injection 7 days prior to Candida albicans infection. The survival outcome was monitored following candidiasisinduced sepsis with ITR or miR124 mimics treatment. The levels of proinflammatory cytokines, including tumor necrosis factorα (TNFα), interleukin1ß (IL1ß) and IL6, were determined using enzymelinked immunosorbent assays. The mRNA and protein levels were assayed using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results showed that ITR and miR124 mimics improved the survival outcome in candidiasisinduced septic mice. The findings also indicated a significant downregulation in the serum levels of TNFα, IL1ß and IL6 in the septic mice treated with ITR or miR124 mimics. Of note, ITR treatment significantly increased the expression of miR124 and decreased the levels of MCP1 in the kidneys of the septic mice. It was also shown that the overexpression of miR124 reduced the expression of MCP1 and attenuated candidiasisinduced acute kidney injury (AKI) in septic mice. Transfection with miR124 mimics was equivalent to ITR in reducing the excessive inflammatory response and renal lesions in septic mice. These results provided evidence supporting the use of miR124 mimics as a therapeutic approach for attenuating candidiasis-induced AKI.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Candidíase/tratamento farmacológico , Candidíase/metabolismo , Quimiocina CCL2/metabolismo , Itraconazol/uso terapêutico , MicroRNAs/metabolismo , Injúria Renal Aguda/genética , Animais , Candidíase/genética , Quimiocina CCL2/genética , Modelos Animais de Doenças , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , MicroRNAs/genética , Sepse/tratamento farmacológico , Sepse/genética , Sepse/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To evaluate the quality of Angelica sinensis based on Grey incidence degree method. METHODS: Grey model was set up by determining four main compositions contained in the samples. RESULTS: The result of quality evaluation on 21 samples by this model was as same as that of genuine medicinal materials. CONCLUSION: Grey incidence degree method and the model can be used to evaluate the quality of Angelica sinensis.
Assuntos
Angelica sinensis/química , Modelos Estatísticos , Óleos Voláteis/análise , Polissacarídeos/análise , 4-Butirolactona/análogos & derivados , 4-Butirolactona/análise , Algoritmos , Angelica sinensis/crescimento & desenvolvimento , Ácidos Cumáricos/análise , Raízes de Plantas/química , Plantas Medicinais/química , Plantas Medicinais/crescimento & desenvolvimento , Controle de QualidadeRESUMO
AIM: To construct a sustained drug release system for basic fibroblast growth factor (bFGF). With this special system, bFGF can be used to repair an injured peripheral nerve, injured spinal cord, or as a carrier for other drugs that need to be released over a long time. METHODS: Microsphere composite was prepared by encapsulating bFGF into gelatin particles with poly(lactic-co-glycolic acid) (PLGA) as its outer-coating. The encapsulation was conducted by a phase separation method. RESULTS: The average diameter of the gelatin particle-PLGA microsphere composite was 5-18 mum, and bFGF-loading efficiency was up to 80.5%. The bFGF releasing experiment indicated that this new composite system could release bFGF continuously and protect bFGF from denaturation. CONCLUSION: A modified approach was successfully employed to develop a biodegradable system for sustained release of the drug of bFGF in vitro.
