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 investigate the clinical significance of thyroglobulin antibody (ATG) and thyroid peroxidase antibody (ATPO) in patients with vitiligo. Methods Venous blood samples were obtained from 87 patients with vitiligo and 90 age- and sex-matched normal human controls. Chemiluminescence was applied to measure the serum levels of ATG, ATPO, free triiodothyronine, free tetraiodothyronine and thyroid stimulating hormone (TSH). Results There was a significant increase in the positivity rates of ATG (23.0% vs 6.7%, P < 0.01) and ATPO (24.1% vs 7.8%, P < 0.01) as well as the serum level of TSH (3.4 ± 2.4 vs 2.4 ± 1.2 pmol/L, P < 0.05) in the patients with vitiligo compared with the normal human controls. It is worth mentioning that all patients positive for ATG or ATPO were diagnosed with vitiligo vulgaris. The positivity rates of ATG and ATPO in patients with vitiligo aged from 11 to 20 years and 21 to 40 years were significantly higher than those in age-matched normal controls (all P < 0.05). Also, female patients had a higher positivity rate of ATG and ATPO than female controls did (34.1% vs 8.5%, χ2 = 8.90, P < 0.01; 34.1% vs 10.6%,χ2 = 7.29, P < 0.05). The highest positivity rates of both ATG and ATPO were 53.3%, which were observed in vitiligo patients aged from 11 to 20 years, followed by patients from 21 to 40 years (ATG 34.5%, ATPO 34.5%). In patients with vitiligo positive for both ATG and ATPO, the occurrence of autoimmune thyroid disease was 70% (14/20), significantly higher than that in ATG- and ATPO- positive healthy controls (16.7%, χ2 = 5.4, P < 0.05). Conclusions ATG and ATPO were observed in young female patients with vitiligo vulgaris, and they may be associated with the development of autoimmune thyroid diseases.

Animals ; Anti-HIV Agents ; pharmacology ; HIV ; drug effects ; genetics ; physiology ; HIV Infections ; drug therapy ; immunology ; virology ; Humans ; Mucous Membrane ; immunology ; virology ; Virus Replication ; drug effects

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.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD56 Antigen ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Fever of Unknown Origin ; etiology ; Humans ; Lymphoma, Extranodal NK-T-Cell ; complications ; metabolism ; pathology ; therapy ; Male ; Prednisone ; therapeutic use ; Splenectomy ; Splenic Neoplasms ; complications ; metabolism ; pathology ; therapy ; Vincristine ; therapeutic use ; Young Adult

OBJECTIVETo evaluate whether or not administration of folic acid and resveratrol have preventive effects on cleft palate formation as well as the comparison of the two drugs' s effects.

METHODSPregnant mice were randomly divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28 microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13, followed hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group; resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same volume of water for 6 consecutive days from GD8 to GD13 and were given a single dose of corn oil on GD10. The pregnant mice weight and embryos, the number of live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by microscopy.

RESULTSTotal frequency of clefts was 92.86% in TCDD group, 84.00% (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD groups. The frequency of cleft was 0% in the control group. Compared with the control and the TCDD groups, there were significant differences in the number of live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P < 0.05). No significant differences in embryonic weight, live fetuses weight, the number of live, dead and resorption fetal mice were found in the other groups (P > 0.05).

CONCLUSIONTest dose of folic acid and resveratrol both had certain antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10 mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action. Effects of both the two drugs have no significant difference, but resveratrol (50 mg/kg, GD8-13) significantly affects the fetal mice's growth and development under TCDD exposure in utero.

Abnormalities, Drug-Induced ; prevention & control ; Animals ; Cleft Palate ; chemically induced ; prevention & control ; Female ; Fetus ; Folic Acid ; administration & dosage ; pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; antagonists & inhibitors ; Pregnancy ; Random Allocation ; Stilbenes ; administration & dosage ; pharmacology ; Teratogens

Objective To study the effects of CpG oligodeoxyribonuclentide (ODN)as adjuvant on the immune responses in PBMC and CD4+ T cell with chronic hepatitis B virus. Methods The selected 20 infections were averagely divided two groups. The frequency of IFN-γ secreting PBMC and CD4+ T cell in immune tolerant phase and in the immune clearance phase that had stimulated by CpG ODN, HBsAg and Mixture[CpG ODN+HBsAg] were analyzed by enzyme linked immune spot(ELISOT). Results The PBMC and CD4+ T cell were differently incubated by CpG ODN+ HBsAg and M[CpG ODN + HBsAg]. The number of IFN-γ spot differently are 3±8, 339±429, 375±496, 1±4, 5±16 and 5±12;the results of immume tolerance are 3±8,361±153, 375±276, 0±2, 2±2 and 4±4; but the results of immune clearance are 3±21, 289±345, 405±656, 2±14, 8±40 and 7±30. The IFN-γ spots statistical analysis of PBMC were differently incubated by HBsAg and M,the total is P = 0.720, The IFN-γ spots statistical analysis of CD4+ T cell were differently incubated by HBsAg and M, the total is P = 0. 890, The IFN-γ spots statistical analysis of PBMC and CD4+ T cell were differently incubated by M, the total is P=0.000. Conclusions The ability that CpG ODN can not significantly increase the IFN-γsecreting of PBMC and CD4+ T cell that were incubated by HBsAg to the infection in immune tolerant phase and in the immune clearance phase, but the PBMC outweighed The CD4+ T cell.

AIM: To evaluate the clinical effect of pars plana vitrectomy in patients with ocular injuries involving the posterior segment.

METHODS:A total of 90 patients(90 eyes)with ocular injuries involving the posterior segment underwent pars plana vitrectomy in our hospital from March 2014 to June 2015 were recruited to carry out a retrospective study. We recorded the age, gender, occurrence site of trauma, visual acuity, anatomical site, nature of injury, wound length, the presence of an afferent pupillary defect, and the timing of vitrectomy. The Ocular Trauma Score was measured. The minimum follow-up from presentation was 6mo.

RESULTS:The mean duration of follow up was 198d, ranged from 182 to 240d. There were 77 males and 13 females of all, with a mean age of 32.7±15.8 years old and 47 patients(52.2%)injured in the workplace, 14 patients(15.6%)at home. The mean visual acuity(LogMAR)of patients were significantly improved from 2.36±0.72 preoperatively to 1.50±1.14 postoperatively. There were 23 patients whose preoperative vision were better than 2.0 LogMAR, the postoperative visual acuity of these patients were significantly better than others(P<0.01). No significant difference of visual improvement was found between groups with early vitrectomy(<7d)or delayed vitrectomy(>7d)(P>0.05). There was no significant difference of postoperative visual acuity between patients with injury in Zone I and II(P>0.05), but visual acuity of patients with injury in Zone III were significant poorer(P<0.05). The postoperative visual acuity of patients with relative afferent pupillary defect were significant poorer(P<0.05). Preoperative visual acuity, the difference of preoperative and postoperative visual acuity, and postoperative visual acuity were significantly different between groups with different ocular trauma scores(P<0.01).

CONCLUSION:Trauma is more likely to occur in men under 40 years of age and in the workplace. The favorable final visual outcome is associated with the absence of afferent pupillary defect, ocular trauma score and presenting visual acuity as well as the zone of injury, and not associated with the timing of vitrectomy.

Objective To evaluate the associations between polymorphisms of LEPR Gln223Arg,LEPR Pro 1019Pro and the risk on obesity.Methods A computerized search on literature was carried out in Wanfang,CNKI,VIP databases and CBM,PubMed,EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro 1019Pro and risk of obesity in the Chinese population.Odds ratios (ORs) were used to assess the strength of the association,and 95％ confidence intervals (CIs) to present the precision of the estimates.Meta-analysis was performed using the STATA statistical software.Results Fifteen literature were collected for Meta-analysis by the uniform inclusion and exclusion criteria.There were 1096 obese patients and 949 controls for polymorphisms of LEPR Gln223Arg in 9 papers,together with 961 obese patients and 818 controls for polymorphisms of LEPR Prol019Pro in 8 papers.Overall,there were significant associations between decreased risk of obesity and LEPR Gln223Arg polymorphisms (-668 A→G) (G versus A,OR=0.66,95％CI:0.49-0.89; AG and GG versus AA,OR=0.50,95％CI:0.32-0.77; respectively).There were significant associations between increased risk of obesity and LEPR Prol019Pro polymorphisms (-3057 G→A) (A versus G,OR=1.61,95％CI:1.15-2.26; AG and AA versus GG,OR=1.50,95％CI:1.08-2.08; respectively).Conclusion Variant alleles at both LEPR-668 and LEPR-3057 were associated with obesity in the Chinese Han-dominated population.

Objective: To explore the mechanism of herbal cake-partitioned moxibustion in Crohn disease (CD) treatment by observing the effect of herbal cake-partitioned moxibustion on protein expressions of colonic M2 macrophage marker CD206, AMP-activated protein kinase (AMPK) and tuberous sclerosis complex (TSC) 2. Methods: Twenty-six specific pathogen free male rats were randomly divided into a normal group, a model group and a herbal cake-partitioned moxibustion group. The CD model was prepared by enema with the mixture of 5％ (W/V) 2,4,6- trinitrobenzene sulfonic acid (TNBS) and 50％ ethanol at 2:1 (volume ratio). After the model was successfully prepared, rats in the herbal cake-partitioned moxibustion group received herbal cake-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rat colon; immunohistochemical technique was used to detect the expression of colonic CD206 protein; Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) technologies were used to detect the protein and mRNA expressions of colonic AMPK and TSC2. Results: Compared with the normal group, rats in the model group showed damaged colonic mucosa, missing of the epithelial layer, thickened submucosa, vascular proliferation, massive infiltration of monocytes and lymphocytes, and cracked ulcers that reached the muscle layer. Rats in the herbal cake-partitioned moxibustion group showed reduced intestinal inflammation and healing intestinal epithelium ulcers. Compared with the normal group, rat colonic CD206 protein expression, and the protein and mRNA expressions of colonic AMPK and TSC2 were decreased in the model group (all P<0.01); compared with the model group, rat colonic CD206 protein expression was increased (P<0.01), as well as the protein and mRNA expressions of AMPK and TSC2 in the herbal cake-partitioned moxibustion (all P<0.05). Conclusion: Herbal cake-partitioned moxibustion can reduce intestinal inflammation in CD rats, increase colonic CD206 protein expression, and up-regulate the protein and mRNA expressions of colonic AMPK and TSC2.