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 study the time-and dose-effect of mitochondrial DNA (mtDNA) 4934 bp and 4977 bp deletions in the human peripheral blood irradiated by137 Cs γ-rays,and to evaluate its implication in biological dosimetry.Methods The peripheral blood from five healthy adults was collected and irradiated with γ-rays.The peripheral blood of one healthy adult was irradiated with 5 Gy and cultured for 2,24,48 and 72 h after irradiation.The peripheral blood from the other four healthy adults was cultured for 2 h after 0,0.5,1,2,5 and 10 Gy irradiation.The peripheral blood mtDNA 4934 bp and 4977 bp deletions were detected by real-time polymerase chain reaction and gel electrophoresis.The doseeffect curves were fitted using Curve Expert 1.4 Software.Results mtDNA 4934 bp and 4977 bp deletions were induced at 2 h post-irradiation and the mtDNA 4934 bp deletion had relative high levels at 2 h and 48h after radiation (t =10.782 and 8.966,P ＜ 0.05),and mtDNA 4977 bp deletion reached the highest level at 48 h after radiation (t =7.433,P ＜0.05).mtDNA 4934 bp (t =2.895-8.105,P ＜0.05) and 4977 bp deletion (t =3.006-7.715,P ＜0.05) irradiated at 0.5-10 Gy increased with a dosedependent manner.The incidence of mtDNA 4977 bp deletion was higher than that of 4934 bp deletion for those samples exposed with same dose of irradiation,especially at 10 Gy (t =2.919,P ＜ 0.05),which suggested that 4977 bp deletion might be more sensitive than 4934 bp deletion at high dose.But larger individual differences were found in 4977 bp deletion compared with 4934 bp deletion.The dose-effect equations for 4934 bp deletion and 4977 bp deletion were Y1 =1.178 + 0.1219D (R2 =0.9269) and Y2 =1.2578 +0.1933D (R2 =0.9016),respectively.Conclusions The induction of mtDNA deletion was correlated with radiation dose,and thus it may be a available method for biological dose estimation and prognostic evaluation.

On the basis of the summarization about some MPH education experience in Sun Yat-sen University,we make the assumption concerning construction of MPH training quality assurance system ,expound the content and operating mode of this training quality system,and then offer reference for improvement of MPH training quality.

Aim To establish and evaluate the simple and effective animal model of rheumatoid arthritis in SD rats induced by heat-killed mycobacterium tuberculosis H37Ra(Mtb).Methods SD rats were immunized s.c.at the base of the tail with Mtb(1 mg/rat) in mineral oil,and then body weight,blood routine,clinical signs of arthritis were observed regularly.And also hind paw volume in SD rats with AA was tested.Meanwhile,T-lymphocyte subset was determined by flow cytometry in peripheral blood,the level of TNF-?in serum and IL-1 and IL-6 and vascular endothe-lial growth factor(VEGF) in joint tissue were tested by ELISA.The ankle pathological change and radiographic evidence of the hind paws of SD rats were observed to evaluate the AA model effects and availability in SD rats.Results When compared with normal control rats,the total number of white blood cells,platelets and monocytes in peripheral blood and ratio of CD4/CD8 was markedly raised after immunization with Mtb.But body weight of model rats was significantly low from day 14 to 28 after injection of Mtb.The inflammatory arthritic lesions such as edema and erythema in the paws appeared after 9～10 d.The peak of inflammation was 14～16 d.The level of TNF-?in serum and IL-1,IL-6 and VEGF in joint tissue was significantly higher in SD rats with Mtb than that in normal control rats at d 28.The histopathological examination revealed cellular infiltration,synovial and cartilage hyperplasia in ankle joints of SD rats.Conclusions The model induced by Mtb in SD rats is more similar in clinical characterization of rheumatoid arthritis in human being.It is a more efficient and simpler manipulative procedure for screening of new anti-arthritis drugs and experimental studying of anti-rheumatoid arthritis.

Objective To explore the feasibility of using glycophorin A somatic mutation in peripheral erythrocytes,in order to evaluate the cancer risk of occupational medical exposure to ionizing radiation.Methods Totally 336 medical radiation workers were recruited as three groups (general radiation group,computer tomography group,intervention and radiation treatment group) and 112 healthy adults were selected as control by using stratified random cluster sampling method,where 176 medicalradiation workers and 58 health controls had a MN-heterozygous type.The erythrocytes were fixed and bound with fluorescent-labeled monoclonal antibody,and the glycophorin A somatic mutation frequency was assayed by a modified BR6-1W1 method using a FACScan flow cytometer.The individual susceptibility to radiation was investigated using micronuclei test and 3-Aminobenzamide index test.Results The GPA somatic mutation frequency of medical-radiation workers was significantly higher than that of healthy control ( t =2.29 - 11.48,P ＜ 0.05 ).In particular,the NO GPA aberration frequency of interventional radiology workers was much higher than that of the general medical diagnostic workers (t =2.01,P ＜ 0.05).In addition,the NO GPA variant frequency changed significantly with the years of radiation service,cumulative doses,and 3AB index.However,the NN GPA variant frequency was only associated with the years of radiation service,and no significant correlations were found between NN GPA variant frequency and cumulative dose of radiation exposure or 3AB index. Conclusions GPA mutation frequency,especially NO GPA mutation frequency could be used as a sensitive biomarker to predict the DNA damage and individual susceptibility for the population exposed to professional low-dose ionizing radiation.

The antitussive activity assay for the root extraction of Disporum cantoniense was carried out with coughing mice induced by ammonia liquor. The results showed that the ethanol and water extractions of D. cantoniense possess strong antitussive activity, and the high dose of the former was better than positive control, and then the constituents of the ethanol extraction were separated and purified by various modern chromatographic techniques. Their structures were identified by physico-chemical properties and spectroscopic data. As a result, eight compounds were isolated and identified as stigmast-4-en-3-one(1), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol(2), obtucarbamate A(3), obtucarbamate B(4), neotigogenin(5), azo-2, 2'-bis[Z-(2,3-dihydroxy-4-methyl-5-methoxy) phenyl ethylene] (6),dimethyl {[carbonylbis (azanediyl)] bis( 2-methyl-5, 1-phenylene) j dicarbamate (7) , and quercetin-3-O-pB-D-glucopyranoside(8). All compounds were isolated from this plant for the first time, and the result of bioactivity-directed isolation showed that compounds 3, 4, and 6 had obvious effect on antitussive activity, and compound 6 had the same level as positive control.
Animals ; Antitussive Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Liliaceae ; chemistry ; Male ; Mice

The practice and exploration of bilingual teaching for the course of microbiology has been made in order to improve the students foreign lingual level and to meet the higher requirement on tip-top person with the social development. As a result,bilingual teaching is welcome,and the teaching effect is so distinct that the aim was reached to either study the fundamental knowledge or enhance the English level.

Objective To investigate the relationship between refractory hypertension and renal hemodynamics in end stage renal diseases (ESRD) patients.Methods ESRD patients were classified into:patients with refractory hypertension (group A) and patients with normal blood pressure(group B).Renal hemodynamic indices were ex- amined by duplex ultrasonography.Fasting serum lipid (TC,TG,HDL-C,LDL-C,Lp(a),ox-LDL) and serum parathyroid hormane (PTH) were determined in all patients.Results Significant differences were found in renal hemodynamic indices such as peak systolic velocity (PSV),mean flow velocity (MV),pulsatility index (PI),renal- aortic ratio (RAR) and in clinical index such as Lp(a) and ox-LDL between the two group.Refractory hyperten- sion patients had lower renal hemodynamic indices and higher Lp(a) and ox-LDL levels than in patients with con- trolled BP.Logistic regression analysis revealed that refractory hypertension was related with PSV,EDV,Pl and RAR,but not relevant with sex,age,dialysis time,hematocrit,BUN,creatinine,TC,TG,HDL-C,LDL-C, PTH,MV and RI.Conclusion Atherosclerotic renal artery stenosis and severe disorder in renal hemodynamics is likely the cause for refractory hypertention in ESRD patients.The rise of serum Lp(a) and ox-LDL might acceler- ate renal artery atherosclerosis.

The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer.After designing specific gRNA sequences targeting HPV 16 E6,generating hCas9-EGFP and E6-gRNA-RFP plasmids,and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids,we determined the titer of the pseudotype virus using the TCID50 method.We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells.Experimental subjects were divided into control group,empty virus group,E6-gRNA transfected group,Cas9 transfected group and Cas9+E6-gRNA transfected group.The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis,and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time.RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups;the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups.Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6.The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells,and there were two cutting zones in the Cas9+E6-gRNA transfected group.However,the empty virus group,E6-gRNA transfected group and Cas9 transfected group had no corresponding zone.Compared with those in the control group,the empty virus group,E6-gRNA transfected group and Cas9 transfected group,the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9+E6-gRNA transfected group (P＜0.01).In addition,the proliferation and migration abilities of SiHa cells were significantly inhibited (P＜0.01).There were no significant differences among the other groups.In contrast to the control group,the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model (P＜0.01).The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells,which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors.Taken together,these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease,particularly in HPV-related tumors.

Objective To investigate the feasibility and clinical significance of fecal DNA tests for colon tumor diagnosis and screening,we inspected the mutations of APC,p53 and K-ras genes in the tissue and feces of patients with colorectal tumor.Methods We collected 46 patients with colorectal cancer(CRC),60 patients with colorectal adenomas( CRA) and 30 cases of normal person in Huizhou First People Hospital in Guangdong Province from Nov.2011 to Aug.2012.Then all the tumor tissues and feces of these people were detected the mu-tation rate about the APC,p53 and K-ras genes using polymerase chain reaction single strand conformation poly-morphism analysis method(PCR-SSCP).Results The mutation rates of APC,p53,K-ras genes of feces in CRC group,CRA group and normal group were 58.7%(27/46),65.2%(30/46)and 60.9%(28/46),20.0%(12/60),25.0%(15/60)and 23.3%(14/60),3.33%(1/30),0%(0/30)and 0%(0/30),respectively.How-ever the mutation rate in tissues were 63.0%(29/46),69.6%(32/46)and 63.0%(29/46),25.0%(15/60), 26.7%(16/60)and 26.7%(16/60),0%(0/30),0%(0/30) and 0%(0/30).Corresponding mutations could be found in feces and tumor tissues.Consistency checking for mutations rate in feces and tumor tissues of CRC group and CRA group showed that the Kappa value were 0.818(P<0.001),0.901(P<0.001),0.862(P<0.001)and 0.857(P<0.001),0.870(P<0.001),0.822(P<0.001).It means an excellent consistency.Con-clusion Fecal DNA testing is expected to become an effective noninvasive colon tumor early diagnosis and screening method.