RESUMEN
A new type of heterogeneous palladium catalyst, PdMgAl-LDH, was facilely prepared by the immobilization of Pd2+ species in the layers of a Mg-Al layered double hydroxide (LDH) with co-precipitation, and then fully characterized by using powder XRD, thermogravimetric differential thermal analysis, TEM, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy techniques. These catalysts can efficiently catalyze copper-free Sonogashira, Suzuki and Heck coupling reactions of various aryl iodides, bromides, and chlorides in aqueous media under phosphine-ligand- and organic-base-free conditions. These catalysts feature easy recovery through simple filtration and could be reused at least six times without a marked loss in activity. Notably, they can be facilely reactivated by a combination of nitrolysis with co-precipitation. The basic LDH skeletons could effectively stabilize the Pd0 species created in situ and donate electron density to the Pd0 center to facilitate the oxidative addition of aryl halides, thus the PdMgAl-LDH catalysts are stable during catalysis.
RESUMEN
An efficient and green synthesis of 4-ferrocenylquinoline derivatives through a TsOH-catalyzed three-component reaction of aromatic aldehydes, amines and ferrocenylacetylene in water has been successfully developed. This strategy is a powerful method for the construction of diverse ferrocenyl-quinoline conjugates from simple available starting materials as it minimized the use of metal catalyst and organic solvent in the reaction process. The conjugates feature unique structures and excellent electronic properties. Moreover, a plausible mechanism for this TsOH-catalyzed three-component reaction was proposed and assessed.
RESUMEN
Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 µg/ml or vitamin D3 300 µg/ml or vitamin D3 320 µg/ml seperately combined with metformin 15000 µg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Colecalciferol/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Serina-Treonina Quinasas TOR/fisiología , Vitaminas/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Transducción de Señal/efectos de los fármacos , Sales de Tetrazolio , TiazolesRESUMEN
OBJECTIVE: To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism. METHODS: MTT assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K, p-S6. RESULTS: MTT results showed that 320 µg/ml vitamin D3 combined with 620 µg/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased. CONCLUSION: Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.
Asunto(s)
Colecalciferol/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Serina-Treonina Quinasas TOR/fisiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Vitaminas/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Transducción de Señal/efectos de los fármacos , Sales de Tetrazolio , TiazolesRESUMEN
OBJECTIVES: rh-IFNα2a-NGR is a promising anti-tumor candidate. The aim of present study was to compare pharmacokinetics of rh-IFNα2a-NGR with rh-IFNα2a. METHODS: Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh-IFNα2a-NGR and rh-IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh-IFNα2a-NGR and rh-IFNα2a in serum, tissue, bile and urine. KEY FINDINGS: After a single intravenous administration, the pharmacokinetic characters of rh-IFNα2a-NGR and rh-IFNα2a were described using a two-compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh-IFNα2a-NGR in tumor was 5.34 times and 1.52 times as high as that of rh-IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh-IFNα2a-NGR was predominantly located in tumor vascular tissues. CONCLUSIONS: rh-IFNα2a-NGR could be an agent for tumor vascular-targeting therapy and these findings provided references for further clinical study.
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Inhibidores de la Angiogénesis/farmacocinética , Sistemas de Liberación de Medicamentos , Drogas en Investigación/farmacocinética , Interferón-alfa/farmacocinética , Oligopéptidos/metabolismo , Plasmacitoma/metabolismo , Proteínas Recombinantes de Fusión/farmacocinética , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/sangre , Inhibidores de la Angiogénesis/orina , Animales , Bilis/metabolismo , Drogas en Investigación/administración & dosificación , Drogas en Investigación/metabolismo , Humanos , Inyecciones Intravenosas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/genética , Interferón-alfa/metabolismo , Ratones , Ratones Endogámicos , Modelos Biológicos , Trasplante de Neoplasias , Oligopéptidos/administración & dosificación , Oligopéptidos/química , Oligopéptidos/genética , Plasmacitoma/irrigación sanguínea , Plasmacitoma/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/sangre , Proteínas Recombinantes de Fusión/orina , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/sangre , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/orina , Distribución TisularRESUMEN
BACKGROUND: Currently, the most commonly used treatment methods for repairing alveolar furcation defects are periodontal guided tissue regeneration (GTR) and bone grafting. The objective of this study was to investigate the effects of simvastatin/methylcellulose gel on bone regeneration in alveolar defects in miniature pigs. METHODS: Alveolar defects were produced in 32 teeth (the third and fourth premolars) of 4 miniature pigs. The 32 experimental teeth were divided into 5 groups comprising control (C) and treatment (T) teeth: (1) empty defects without gel (group C0, n = 4); (2) defects injected with methylcellulose gel (group C1, n = 4); (3) defects injected with 0.5 mg/50 µl simvastatin/methylcellulose gel (group T1, n = 8); (4) defects injected with 1.5 mg/50 µl simvastatin/methylcellulose gel (group T2, n = 8); and (5) defects injected with 2.2 mg/50 µl simvastatin/methylcellulose gel (group T3, n = 8). Every week after surgery, the furcation sites were injected once with gel. At the eighth week after surgery, the 4 pigs were sacrificed and underwent macroscopic observation, descriptive histologic examination, and regenerate bone quantitative histologic examination. RESULTS: At 8 weeks after surgery, the defect sites in the treatment groups were completely filled in with new bone and fibrous tissue. There was little new bone in the C0 and C1 groups, and only a small number of osteoblasts and proliferative vessels could be seen on microscopic examination. CONCLUSIONS: Miniature pigs are an ideal experimental animal for establishing a model of alveolar defects using a surgical method. Local application of simvastatin/methylcellulose gel can stimulate the regeneration of alveolar bone in furcation defect sites, because it promotes the proliferation of osteoblasts. The best dose of simvastatin gel to stimulate bone regeneration is 0.5 mg.