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Objective: To investigate the reversal effect of astragaloside IV on multidrug resistance of MDA-MB-231/DOX in breast cancer cells. Methods: The cytotoxicity of astragaloside IV and sensitivity or drug resistance of breast cancer cells to doxorubicin (DOX) before and after treatment were determined by MTT assay. Liposome co-delivery system containing doxorubicin and astragaloside IV (LPs-DOX/AS) was constructed by ethanol injection-ammonium sulfate gradient method. The reversal effect of LPs-DOX/AS on multidrug resistance of breast cancer cells was determined by MTT method. The effect of LPs-DOX/AS on apoptosis was determined by flow cytometry. Results: Astragaloside IV had no significant cytotoxicity to breast cancer cells in the experimental concentration range. After combined with astragaloside IV, the IC50 values of DOX on MDA-MB-231 and MDA-MB-231/DOX cells decreased (P < 0.05), and the intervention effect on drug-resistant cells was more significant (P < 0.01). Compared with free DOX/AS-IV, the IC50 values of LPs-DOX/AS-IV on both breast cancer cells decreased (P < 0.05), and the effect on drug-resistant strains was more significant (P < 0.01). The apoptosis rate of drug-resistant strains treated with LPs-DOX/AS-IV was also significantly higher than that of free drug group (P < 0.05). Conclusion: Astragaloside IV has reversal effect on multidrug resistance of human breast cancer cell MDA-MB-231 to doxorubicin. The combination of astragaloside IV and doxorubicin and its liposome co-delivery system can effectively reverse or sensitize multidrug resistance in breast cancer.
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OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .
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Qual metodologia de ensino produz umaaprendizagem mais eficiente: a metodologia ondea aprendizagem é completamente dirigida ou a metodologia onde a aprendizagem é minimamentedirigida, tal como ocorre com o ensino construtivista? Iniciamos este artigo apresentando três argumentoscontrários à aprendizagem minimamente dirigida. Demonstra-se, em seguida, que apesar desses trêsargumentos contrários a todo tipo de ensino no qual a aprendizagem seja minimamente dirigida, este tipo de ensino passa a ser, à medida que oestudante vai aumentando o seu nível de expertise, uma metodologia mais eficiente do que o ensino completamente dirigido. Este efeito é conhecido como Efeito Reverso da Expertise. Como este efeitoexplica o comprovado sucesso do uso da transição da metodologia dos exemplos resolvidos paraa metodologia da resolução de problemas, propomos, também em razão deste efeito, que será igualmente benéfico, para a aprendizagem, autilização de uma transição entre duas metodologias mais amplas: a transição gradual da aprendizagem completamente orientada para a aprendizagem minimamente orientada. A utilização desta transição gradual de metodologias, aqui proposta,possibilitará ao construtivismo realizar plenamente o seu potencial metodológico
Which teaching methodology produces a more efficient learning: the teaching methodology in which learning is completely guided or the methodology in which learning is minimally guided, as occurs in constructivism? We begin this article by presenting three arguments against minimally guided learning. It is shown then that in spite of these three arguments against all kinds of teaching in which learning is minimally guided, this type of teaching becomes, as the student increases his level of expertise, a more efficient methodology than the completely guided teaching. This effect is known as the Expertise Reversal Effect. As this effect explains the proven successful use of the transition from the worked out examples methodology to the problem solving methodology, we propose, also due to this effect, that it will be equally beneficial for learning, to use a transition between two broader methodologies: the gradual transition from completely guided learning to minimally guided learning. The use of this gradual transition of methodologies proposed here will enable constructivism to fully realize its methodological potential.
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Learning , Memory, Short-TermABSTRACT
Clinical suggestion for the limitation of application time of NaOCl solution is needed to avoid large reductions in resin-dentin bond strength. The aim of this study was to measure the change of micro-tensile bond strength after the various application time of 5.25% NaOCl solution to pulp chamber dentin in endodontic access cavity, and to evaluate the effect of 10% sodium ascorbate application for 10 min on bond strength after the treatment of 5.25% NaOCl solution. In this experiment, there were no statistical differences(p>0.05) in bond strengths between upper chamber dentin and lower chamber dentin. NaOCl-treated group for 20 min did not show any significant decrease(p>0.05) in bond strength than non-treated control group. In contrast to that, bond strengths of NaOCl-treated groups for 40 & 80 min were significantly lower(p<0.05) than that of non-treated control group. 10% sodium ascorbate retreated group for 10 min after 5.25% NaOCl application for 40 min to chamber dentin showed the recovery of bond strength significantly. However, the bond strength of sodium ascorbate retreated group after 5.25% NaOCl application for 80 min was still significantly lower(p<0.05) compared to the non-treated control group, which means the reductions in resin-dentin bond strength were not fully reversed. On the contrary, sodium ascorbate retreated group after 5.25% NaOCl application for 5 min showed significantly higher(p<0.05) bond strength compared to the control group, which demonstrates its superior recovery effect. In SEM exminations of specimens retreated with 10% sodium ascorbate after NaOCl application for 40 & 80 min showed that resin tags were formed clearly and densely, but weakly in density and homogeneity of individual resin tag compared to the control specimen.
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Ascorbic Acid , Dental Pulp Cavity , Dentin , SodiumABSTRACT
Objective:To investigate the reversal effect of MDR1 and MRP antisense oligodooxynucleotide (ASODN) on adriamycin-resistant SGC7901/ADM cells. Methods:SGC7901/ADM cells were transfected by MDR1 or MRP ASODNs or the combination of two. Then the mRNA expressions of proteins MDR1 and MRP were checked by RT-PCR,and the expressions of P-gp and MRP by immunocytochemistry;the intracellular fluorescence intensity of Rhodamine 123 in these cells were determined by flow cytometry;and the sensitivity of these cells to adriamycin,carboplatin and other anticancer drugs were determined by MTT assay. Results:The expression of MDR1mRNA and MRP mRNA in SGC7901/ADM cells decreased at 12h after transfection of ASODNs,decreased to the lowest level at 24h and returned to the level before transfection after 48h. The expression of P-gp and MRP decreased significantly at 48h after transfection with ASODNs compared with the control cells. The retention of Rhodamine 123 in SGC7901/ADM cells was significantly higher than that before transfection, and the intracellular fluorescence intensity significantly increased in ASODNs cotransfection SGC7901/ADM cells, compared with those transfected by MDR1 or MRP ASODNs respectively;In addition,the sensitivity of SGC7901/ADM cells to adriamycin, carboplatin and other anticancer drugs obviously increased after cotransfection of MDR1 and MRP ASODNs compared with transfection of MDR1 or MRP ASODN respectively. Conclusion:The transfection of MDR1 or MRP ASODN can partly reverse the multidrug resistance of gastric glandular carcinoma cells SGC7901/ADM,while cotransfection of MDR1 and MRP ASODNs can significantly reverse drug-resistance of these tumor cells.