Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

Objective To systematically evaluate the association between protein C and Legg -Calve -Perthes disease.Methods A literature research was performed through PubMed,Embase,Cochrane library,Web of Science,Chinese Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI)and Wan-fang Database from inception to February 201 6 on the association between protein C and Legg -Calve -Perthes disease.According to the Newcastle -Ottawa Scale(NOS)criteria,the quality of studies was evaluated and data were extracted.Meta -analysis was performed with Stata 1 1 .0 software.Results A total of 1 4 articles were included.Twelve articles on protein C and Legg -Calve -Perthes disease in the study group and the control group were compared.The results of Meta -analysis showed that there was no significant difference in protein C levels between the study group and the control group[odds radio(OR)=1 .41 ,95% confidence interval(CI)(0.87,2.28),P =0.1 47];five articles on protein C and the white race of Legg -Calve -Perthes disease between the study group and the control group were com-pared,The results of Meta -analysis showed that there was no significant difference in protein C levels between the whiteskin patients′group and the control group[OR =0.61 2,95%CI(1 .83,7.29),P =0.61 2];three articles on pro-tein C and the yellow race of Legg -Calve -Perthes disease between the study group and the control group were com-pared,and the results of Meta -analysis showed that there was no significant difference in protein C levels between the yellow skin patients group and the control group[OR =0.59,95%CI(0.05,6.72),P =0.080].Conclusion There is no significant correlation between protein C and Legg -Calve -Perthes disease.

Objective:To provide scentific evidence for determining the harvest period of Cortex Abizziae by studying the dynamic variation of the content of lignan glycoside I in Cortex Abizziae.Methods:Chromatography was performed on a Boston Green ODS C18 (250 mm×4.6 mm,5 μm) column,the mobile phase was acetonitrile-0.04% phosphate (18∶82),the flow rate was 1.0 ml·min-1,the detection wavelength was 204 nm,and the column temperature was at 25℃.Results:There were differences in the contents of lignan glycoside I in Cortex Abizziae at different harvest periods.The content of lignan glycoside I reached the highest level in January,decreased quickly from January to March,and gradually increased from April to December.Conclusion:The content of lignan glycoside I in Cortex Abizziae at different harvest periods is different,and the optimum harvest time of Cortex Abizziae is determined from November to January of the following year.

AIM: To compare intraocular pressure (IOP) fluctuations measured at home and in the clinic over a 24-hour period.METHODS: A prospective investigational study.A total of 120 Chinese participants were selected from five communities in the Chengdu area.Patients underwent a clinical interview and IOP was measured both at home and in the clinic.IOP were measured at 8 a.m., 10 a.m., 12 a.m., 2 p.m., 4 p.m., 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m.using the same pneumatonometer.Measurements were taken in the sitting position.RESULTS: The average 24-hour IOP measured in the clinic was slightly lower than that at home.The mean difference in 24-hour IOP measurements between home and clinic was 0.27 mmHg.The IOP fluctuation in the clinic was higher than at home (the mean difference was 0.01 mmHg).There was no statistically significant difference in the average 24-hour IOP measured at home vs in the clinic.The average IOP measured at 2 p.m.at home (16.04±5.95 mmHg) was significantly higher compared with the measurement in the clinic (15.43±5.16 mmHg) (P<0.05).The overall agreement between 24-hour IOP measurements made in the clinic and at home in diagnosis of primary open angle glaucoma was 85.0% (K coefficient: 0.68).CONCLUSION: The 24-hour IOP measured in the clinic was similar to that measured at home, and the method of measuring IOP in the clinic is acceptable in diagnosing primary open angle glaucoma.

Animals ; Cromolyn Sodium ; administration & dosage ; Disease Models, Animal ; Intestines ; blood supply ; Mast Cells ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; mortality ; pathology ; p-Methoxy-N-methylphenethylamine ; administration & dosage

A 1 270 bp full-length cDNA fragment was obtained from the Schistosoma japonicum (Chinese strain) adult cDNA library after the '3' and 5' ends of the incomplete expression sequence tag (EST) of hypoxanthine-guanine phosphoribosyltransferase of Schistosoma japonicum (SjHGPRT) were amplified by the anchored PCR with 2 pairs of primer that were designed according to the published incomplete SjHGPRT EST and the sequence of multiclone sites of library λgt1 1 vector. Sequence analysis indicated that this fragment, with an identity of 82% to hypoxanthine-guanine phosphoribosyltransferase ofSchistosoma mansoni (SmHGPRT), contained a complete open reading frame(ORF). The deduced amino acid sequence showed 83% identity to that of SmHGPRT. This fragment was cloned into the prokaryotic expression vector pQE30, and subsequently sequenced and expressed in Escherichia coli. SDS-PAGE revealed that M of the recombinant protein was about 28 ku. Western-blot analysis showed that the recombinant protein was recognized by the polyclonal antisera from rabbits immunized with Schistosoma japonicum adult worm antigen. Mice vaccinated with recombinant protein revealed significant worm burden, liver eggs per gram (LEPG), fecal eggs per gram (FEPG) and intrauterine eggs of the female worms reduction percentage, compared with the controls. Taken together, the SjHGPRT full-length cDNA can be cloned and expressed in E. coli as a recombinant protein that elicited immunity against the challenge infection with Schistosoma japonicum, indicating its potential as a partia1 protection vaccine candidate.

A 1 270 bp full-length cDNA fragment was obtained from the Schistosoma japonicum (Chinese strain) adult cDNA library after the 3′ and 5′ ends of the incomplete expression sequence tag (EST) of hypoxanthine-guanine phosphoribosyltransferase of Schistosoma japonicum (SjHGPRT) were amplified by the anchored PCR with 2 pairs of primer that were designed according to the published incomplete SjHGPRT EST and the sequence of multiclone sites of library ?gt11 vector. Sequence analysis indicated that this fragment, with an identity of 82% to hypoxanthine-guanine phosphoribosyltransferase of Schistosoma mansoni (SmHGPRT), contained a complete open reading frame(ORF). The deduced amino acid sequence showed 83% identity to that of SmHGPRT. This fragment was cloned into the prokaryotic expression vector pQE30, and subsequently sequenced and expressed in Escherichia coli. SDS-PAGE revealed that M of the recombinant protein was about 28 ku. Western-blot analysis showed that the recombinant protein was recognized by the polyclonal antisera from rabbits immunized with Schistosoma japonicum adult worm antigen. Mice vaccinated with recombinant protein revealed significant worm burden, liver eggs per gram (LEPG), fecal eggs per gram (FEPG) and intrauterine eggs of the female worms reduction percentage, compared with the controls. Taken together, the SjHGPRT full-length cDNA can be cloned and expressed in E.coli as a recombinant protein that elicited immunity against the challenge infection with Schistosoma japonicum, indicating its potential as a partial protection vaccine candidate.

OBJECTIVETo explore the effect of arsenic trioxide (As2 O3) on the level of VEGF, VEGFR and the activity of MMP-2, 9 in K562 cells.

METHODSThe inhibition ratio of K562 cell was detected by MTT assay, the level of VEGF by Enzyme-linked immunosorbent assay (ELISA), the expression ratio of VEGFR by flow cytometry (FCM), and the activity of MMP-2, 9 by gelatin zymography assay.

RESULTS(1) The IC50 of K562 cells was (2.12 +/- 0.11) micromol/L. Proliferation of K562 cells was significantly inhibited at the concentration of 0.4 - 6.4 micromol/L As2 O3 (P < 0.05). (2) The expression of VEGF was slightly up-regulated by 0.05 micromol/L As2 O3 (P > 0.05) and prominently inhibited by 0.4 micromol/L and 3.2 micromol/L As2 O3 (P < 0.05). As2 O3 had no influence on VEGFR. (3) The activity of MMP-2 and 9 was partly inhibited by 0.05 micromol/L As2 O3 incubated 72 hours and by 0.4, 3.2 micromol/L, As2 O3. With the increase of As2 O3 concentration and the incubation time, the inhibited effect on MMP-2 and 9 was enhanced.

CONCLUSIONSAs2 O3 may down-regulate the expression of VEGF and inhibit the activity of MMP-2 and 9.

Arsenicals ; pharmacology ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Oxides ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

ObjectiveTo evaluate the application of multi-slice CT (MSCT) perfusion scan technique in predicting renal function recovery after unilateral hydronephrosis treatment.MethodsThirtyeight patients with unilateral obstructive hydronephrosis not shown on intravenous urography (IVU) and a normal contralateral kidney were recruited for this study.Patients were divided into detected (D) and undetected (UD) groups depending on whether the IVU detected urinary tract obstruction.All patients underwent plain abdominal X-ray,gray-scale ultrasonography,excretory urography and MSCT perfusion scan before and after the treatment.Patients were followed-up at six months or more after the treatment for a mean duration of 12.5 months (range from 6 to 22 ).ResultsOf the 38 cases,22 cases were in group D,16 cases were in group UD.On MSCT,renal cortex blood flow (BF) and blood volume ( BV ) value after treatment in group D were 561.1 ± 165.4 ml/( 100 g · min) and 35.9 ± 11.3 ml/100 g compared with before treatment rates of 361.6 ±109.7 ml/(100g· min) and24.1 ±10.2 ml/100g,t=-3.38,-2.34,P＜0.01,0.05.In the UD group,the differences of these parameters were after treatment 38.7 ± 15.4 ml/(100 g · min),10.306 ± 4.925 ml/100 g and before treatment 39.1 ± 22.5 ml/( 100 g · min) and 8.7 ± 4.4 ml/100 g,P ＞ 0.05.In the aspects of BF and BV,there were statistically significant differences between group D and group U D both before and after the treatment,t=9.09,4.15,P ＜ 0.01.ConclusionsM SCT perfusion can provide a valuable prediction technique of the renal function recovery in patients with unilateral obstructive hydronephrosis.Improvement of renal function can be expected after relief of obstructive hydronephrosis if the patients have a BF 361.6 ml/( 100 g · min) and BV 24.1 ml/100 g or greater measured by MSCT perfusion.

To investigate changes of 14-3-3beta from apoptosis induced by PrP106-126 polypeptide, HeLa cell was incubated with PrP106-126 for 4h or 8h. Nucleus changes and the expression of PARP were detected differently by Hoechst staining and Western blotting. Expressing of protein and mRNA from 14-3-3beta was determined by Western blotting and Real-time PCR. The results show that typical nucleus pyknosis and chip of apoptosis and degradation of PARP were induced by PrP106-126 peptide in HeLa cells. Degradation of 14-3-3beta appeared in apoptosis groups induced by PrP106-126 peptide. However, 14-3-3beta mRNA did not display any changes in apoptosis groups. This study indicated that degradation of antiapoptosis protein 143-3beta induced by PrP106-126 peptide may be one of pathogenesis mechanism of prion disease.
14-3-3 Proteins ; metabolism ; Apoptosis ; drug effects ; HeLa Cells ; Humans ; Peptide Fragments ; pharmacology ; Prions ; pharmacology ; Proteolysis ; drug effects