Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been ye...The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been yet demonstrated. In this study the nano size TiO2 is synthesized using citric acid and alpha dextrose and the enhancement effect of TiO2 nanoparticle on the antibacterial activity of different antibiotics was evaluated against Methicillin-resistant Staphylococcus aureus (MRSA). During the present study, different concentrations of nano-scale TiO2 were tested to find out the best concentration that can have the most effective antibacterial property against the MRSA culture. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of TiO2 nano particle. A clinical isolate of MRSA, isolated from Intensive Care Unit (ICU) was used as test strain. In the presence of sub-inhibitory concentration of TiO2 nanoparticle (20 μg/disc) the antibacterial activities of all antibiotics have been increased against test strain with minimum 2 mm to maximum 10mm. The highest increase in inhibitory zone for MRSA was observed against pencillin G and amikacin (each 10 mm). Conversely, in case of nalidixic acid, TiO2 nanoparticle showed a Synergic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the TiO2 nanoparticle potentate the antimicrobial action of beta lactums, cephalosporins, aminoglycosides, glycopeptides, macrolids and lincosamides, tetracycline a possible utilization of nano compound in combination effect against MRSA.展开更多
Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluate...Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y_6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter(ABCB1 or P-glycoprotein, P-gp). Our results showed that Y_6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y_6 significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y_6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mousetumor xenograft model, Y_6(110 mg/kg, intragastric administration), in combination with doxorubicin(2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y_6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.展开更多
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
文摘The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been yet demonstrated. In this study the nano size TiO2 is synthesized using citric acid and alpha dextrose and the enhancement effect of TiO2 nanoparticle on the antibacterial activity of different antibiotics was evaluated against Methicillin-resistant Staphylococcus aureus (MRSA). During the present study, different concentrations of nano-scale TiO2 were tested to find out the best concentration that can have the most effective antibacterial property against the MRSA culture. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of TiO2 nano particle. A clinical isolate of MRSA, isolated from Intensive Care Unit (ICU) was used as test strain. In the presence of sub-inhibitory concentration of TiO2 nanoparticle (20 μg/disc) the antibacterial activities of all antibiotics have been increased against test strain with minimum 2 mm to maximum 10mm. The highest increase in inhibitory zone for MRSA was observed against pencillin G and amikacin (each 10 mm). Conversely, in case of nalidixic acid, TiO2 nanoparticle showed a Synergic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the TiO2 nanoparticle potentate the antimicrobial action of beta lactums, cephalosporins, aminoglycosides, glycopeptides, macrolids and lincosamides, tetracycline a possible utilization of nano compound in combination effect against MRSA.
基金supported by the National Natural Science Foundation of China (No. 81160532)the Open Project of Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research (No. GXBMR201602, China)+1 种基金the Young and Middle-aged Teachers Foundation Ability Enhancement Project of Guangxi Colleges and Universities (No. 2018KY0102, China)US NIH (No. 1R15CA143701)
文摘Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y_6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter(ABCB1 or P-glycoprotein, P-gp). Our results showed that Y_6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y_6 significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y_6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mousetumor xenograft model, Y_6(110 mg/kg, intragastric administration), in combination with doxorubicin(2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y_6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.