ABSTRACT
Autophagy is being increasingly recognized as an important regulator of intestinal ischemia-reperfusion(I/R)injury, but its exact role is still debated. Emerging evidence suggests that miR-146a-5p is involved in the initiation and development of I/R injury, but its role in intestinal I/R injury remains unclear. The present study generated an intestinal I/R mouse model and an oxygen glucose deprivation/reoxygenation (OGD/R) Caco-2 cell model and found that autophagy was increased and contributed to the intestinal injury and cell death induced by I/R and OGD/R. In addition, in both I/R and OGD/R models, the miR-146a-5p expression level was decreased and accompanied by an increase in TXNIP expression. By transfecting cells with an miR-146a-5p inhibitor or mimic, we observed that miR-146a-5p inhibits autophagy during OGD/R by targeting TXNIP; this was confirmed by the dual luciferase reporter gene assay. Additionally, through overexpression and knockdown cell lines, we established that TXNIP regulates autophagy during intestinal I/R via the PRKAA/mTOR pathway. The interaction between TXNIP and p-PRKAA was verified by immunofluorescence co-localization and immunoprecipitation assays. Moreover, we confirmed that TXNIP is indispensable for miR-146a-5p-mediated cell protection. Finally, we observed that miR-146a-5p overexpression inhibits autophagy and attenuates intestinal I/R injury via the PRKAA/mTOR pathway by targeting TXNIP in vivo. In conclusion, this study highlights the role of miR-146a-5p in regulating autophagy by targeting TXNIP, suggesting that miR-146a-5p may be a novel drug target for intestinal I/R therapy.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Carrier Proteins/biosynthesis , Intestines/metabolism , MicroRNAs/biosynthesis , Reperfusion Injury/metabolism , TOR Serine-Threonine Kinases/metabolism , Thioredoxins/biosynthesis , Animals , Autophagy/physiology , Caco-2 Cells , Humans , Intestines/blood supply , Intestines/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Reperfusion Injury/pathology , Reperfusion Injury/prevention & control , Signal Transduction/physiologyABSTRACT
Objective To solve the problem of castration resistant prostate cancer (castrationresistant prostate cancer,CRPC) the problem of drug resistance by studing the expression of the CUDC-101 inhibitor of castration resistant prostate cancer androgen receptor splice variant 7.Methods In this study,the expression of AR-V7 protein in prostate cancer cell lines PC-3,VCaP,22Rv1,LNCap was detected by imnmunoblotting between April 2015 and April 2016,and the highest expression level of cell lines was selected follow-up experiments.Through the cell proliferation and activity experiments,the epigenetic inhibitors:histone deacetylase inhibitor CUDC-101,histone methylation inhibitor DZNeP,DNA methylation inhibitor gemcitabine,histone acetyltransferase inhibitor MG149 to select an inhibitor that reduces the expression of AR-V7 protein in CRPC cells.22Rv1 cells were treated with 30 nmol and 300 nmol of CUDC101 and 1,10 and 20 μmol of Enzalutamide (MDV3100),respectively,and their inhibitory effects on the growth of 22Rv1 cells were examined.Results The results of immunoblotting showed that AR-V7 protein was only expressed in CRPC cell line 22Rv1 and negative in non-CRPC cell line.The expression of AR-V7 in 22Rv1 cells treated with CUDC-101 was significantly lower than that of negative control.While other inhibitors had no effect on the expression of AR-V7.In the cell proliferation and activity assay,the inhibitory rates of 30 nmol CUDC-101 and 1,10 and 20 μmol MDV3100 were 10％,35％ and 45％,respectively,higher than that of MDV3100 alone.28％ and 42％,the difference was statistically significant (P ＜ 0.05).The inhibitory rates of 300 nmol CUDC-101 and MDV3100 were 30％,60％ and 65％,respectively,which were significantly higher than those of MDV3100 alone (P ＜ 0.05).Conclusions CUDC-101 can inhibit the castration resistant prostate cancer androgen receptor splice variant 7 expression,and solved the resistance problem of CRPC.
ABSTRACT
As a common Tibetan medicine, Potentilla anserine L. is a kind of important Chinese materia medica, which is mainly distributed in Gansu, Qinghai and Tibet Provinces. As the active constituent from Potentilla anserine L., potentilla anserine polysaccharide has received initial research by researchers in abroad and at home. It is suggested that potentilla anserine polysaccharide exhibits various functions including antioxidation, anti-aging, immunoregulation, inhibiting bacteria and anti-diabetic. This article reviewed the research on extraction, purification and bioactivities of potentilla anserine polysaccharide, which is expected to provide ideas for the further study and research and development.
ABSTRACT
Objective:To study the 3D accuracy of 4 impression materials.Methods:A metal mould with a custom tray was prepared for the measurement.Impression samples of 2 alginate and 2 rubber impression materials were prepared in the metal mould(n =3)re-spectively.The length of three tagged lines,along X,Y,Z axis directions of the samples was measured with a 3D optical scanner.Re-sults:120 min after sampling the variable rates of the length along X,Y,Z axis of Zhermark alginate samples were 3.615%,3.037%and 2.836%,those of CAVEX alginate samples were 2.836%,3.358% and 4.276% respectively;8 h after sampling the variable rates of Impregum Penta polyether rubber samples were 0.039%,0.071% and 0.057%,those of ExpressXT Penta H addition-curing silicone rubber samples were 0.033%,0.088% and 0.084% respectively.Conclusion:The variable rates of the 4 impression materi-als are in accordance with ISO1563∶1990.The variable rate of alginate impression material is greater than that of rubber.
