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1.
J BUON ; 24(4): 1526-1531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646803

RESUMO

PURPOSE: To investigate the expression of miR-335 in triple-negative breast cancer (TNBC) and its effect on chemosensitivity. METHODS: The expression of miR-335 in cancer tissues and adjacent tissues of 42 patients with TNBC who underwent mastectomy in our hospital was detected by qRT-PCR. Liposome was used to transfect miR-335 mimics (miR-335-mimic) and empty vectors (miR-NC) into cells of TNBC cell line MDA-MB-231, and untransfected cells were used as blank control cells (NC). Three groups of cells were cultured in culture Levbeit's medium supplemented with 2 µmol/L paclitaxel, 5 µmol/L cisplatin and 4 µmol/L doxorubicin. Proliferation rate and apoptosis rate of tumor cells were measured by MTT assay and TUNEL assay 48 h after transfection. RESULTS: The relative expression level of miR-335 in cancer tissues was significantly lower than that in adjacent tissues of TNBC patients (p<0.05). After paclitaxel, cisplatin and doxorubicin treatment, the proliferation and apoptosis rates of the three groups were statistically different (p<0.05). There was no significant difference in cell proliferation rate and apoptosis rate between NC group and miR-NC group (p>0.05), but the proliferation rate of cells was higher and apoptosis rate was lower in the NC group and miR-NC group than that in miR-335-mimic group (p<0.05). CONCLUSION: The expression level of miR-335 in cancer tissues of TNBC patients is lower than that in adjacent tissues. Overexpression of miR-335 can increase the sensitivity of tumor cells to paclitaxel, cisplatin and doxorubicin, and improve the effect of chemotherapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mastectomia , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/cirurgia
2.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

PURPOSE: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. MATERIALS AND METHODS: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. RESULTS: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. CONCLUSION: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
3.
Carbohydr Polym ; 161: 261-269, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28189238

RESUMO

To improve the small intestinal absorption efficacy of Astragalus polysaccharides (APS) through oral administration, amphiphilic chitosan derivatives conjugated with deoxycholic acid residues in the absence and presence of vitamin B12 residues (DA-Chit and VB12-DA-Chit, respectively) were synthesized and characterized by FTIR and NMR spectroscopy. APS and the amphiphilic chitosan derivatives formed the nano-complexes with positive zeta potentials in the size of 100-150nm observed using scanning electron microscopy. To investigate the fluorescent properties of APS, a Congo red residue-conjugated APS derivative (CR-APS) was synthesized. Fluorescence spectroscopy and resonance light scattering spectroscopy confirmed the formation of the CR-APS/DA-Chit nano-complex as a result of electrostatic interaction. The APS/DA-Chit and APS/VB12-DA-Chit nano-complexes were not toxic against the human colon adenocarcinoma (Caco-2) cells. The APS/VB12-DA-Chit nano-complex exhibited high permeation through intestinal enterocytes using the Caco-2 cell model, which could be beneficial to small intestinal absorption of humans.


Assuntos
Astrágalo/química , Quitosana/química , Nanocompostos/química , Polissacarídeos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Humanos , Polissacarídeos/síntese química , Polissacarídeos/toxicidade
4.
Int J Biol Macromol ; 94(Pt A): 669-678, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27756641

RESUMO

To understand the mechanism responsible for the α-amylase inhibitory activity of tea polysaccharides, the interaction between α-amylase and an acidic branched tea polysaccharide (TPSA) was investigated using fluorescence spectroscopy and resonance light scattering analysis. TPSA, exhibiting inhibitory activity towards α-amylase (the maximum inhibition percentage of 65%), was isolated from green tea (Camellia sinensis) and characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, and gas chromatography. Synchronous fluorescence spectroscopy revealed that the binding interaction between the tryptophan residues of α-amylase and TPSA was predominant. Based on the fluorescence quenching effect of tryptophan residues induced by TPSA, the binding constants between α-amylase and TPSA were determined to be 18.6×106, 8.0×106 and 4.6×106 L·mol-1 at 20, 30 and 37°C, respectively. The calculated Gibbs free-energy changes were negative, indicating that the bonding interaction was a spontaneous process. The enthalpy and the entropy changes were -62.13 KJ·mol-1 and -0.0728 KJ·mol-1·K-1, suggesting that hydrogen bonding interactions might play a major role in the binding process. The formation of an α-amylase/TPSA complex was evidenced by fluorescence quenching and resonance light scattering analysis, and this complex could be the main contributor to the α-amylase inhibitory activity of TPSA.


Assuntos
Camellia sinensis/química , Inibidores Enzimáticos/química , Polissacarídeos/química , Chá/química , alfa-Amilases/antagonistas & inibidores , Animais , Inibidores Enzimáticos/isolamento & purificação , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Cinética , Pâncreas/química , Pâncreas/enzimologia , Polissacarídeos/isolamento & purificação , Ligação Proteica , Suínos , Termodinâmica , Triptofano/química , alfa-Amilases/química
5.
Carbohydr Polym ; 137: 375-381, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26686141

RESUMO

Quaternized chitosan/organic montmorillonite (QCS/OMMT) nanocomposites were synthesized under microwave irradiation. XRD and TEM analyses confirmed that QCS intercalated into the interlayer of OMMT and clay layers distributed uniformly in QCS matrix. QCS/OMMT nanocomposites were used as retention and drainage-aid agents in pulp suspension, during which the interface behavior of positively charged QCS/OMMT nanocomposites on negatively charged cellulosic substrate and CaCO3 substrate was investigated. With the addition of QCS/OMMT nanocomposites, the particle size of cellulosic substrate increased, while the beating degree and the total residual carbohydrate concentration decreased. The results indicated that QCS/OMMT nanocomposite made a difference in paper making process through the charge patch interaction. Moreover, QCS/OMMT nanocomposites had a strong interaction with CaCO3, which was significant in fiber fines retention and paper production. When the mass ratio of QCS to OMMT was 8:1, the QCS/OMMT nanocomposite demonstrated the strongest retention and drainage-aid effect.


Assuntos
Bentonita/química , Celulose/química , Quitosana/química , Nanocompostos/química
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