Inhibitor of DNA binding 1 (ID1) has an aberrantly high expression in multiple cancer tissues, including colon cancer, lung cancer, breast cancer, and so on, which is closely related to cancer aggressiveness and poor clinical outcomes in cancer patients. It has been reported that ID1 maintains colorectal cancer cells (CRCs) stemness traits and contributes to the CRC drug resistance. While, the biological molecular mechanisms have not been fully elucidated. In this research, we found that ID1 upregulates octamer binding transcription factor (OCT4) protein level as well as OCT4 signaling pathway via Western blot, gene set enrichment analysis (GSEA), dual-luciferase reporter assay, and real-time PCR. Through the in vitro sphere formation assay, we found that overexpression of OCT4 reverses the inhibitory effect of knocking down ID1 on CRC sphere formation ability. With the help of JASPAR and GEPIA database, we predicted a novel transcriptional repressor—forkhead box D3 (FOXD3) of OCT4. Finally, by using co-immunoprecipitation (Co-IP), confocal and real-time PCR, we demonstrated that ID1 interacts with FOXD3 to inhibit its transcriptional repression activity and therefore to upregulate OCT4 transcription and OCT4 signaling pathway. In conclusion, this study provides a new theoretical basis for the regulation mechanism of colon cancer stem cells, and the newly found protein-protein interaction of ID1-FOXD3 provides a potential drug target for the therapy of CRC.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Aged ; Cholecystectomy ; Chondrosarcoma ; metabolism ; pathology ; surgery ; Female ; Gallbladder ; chemistry ; pathology ; surgery ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Keratin-3 ; metabolism ; S100 Proteins ; metabolism

Objective To evaluate the effect of off-pump coronary endarterectomy (CE) plus off-pump coronary artery bypass grafting (off-pump CABG) on patients with chronic total occlusion (CTO) combined with diffuse distal atherosclerosis. Methods From October 2006 to August 2009,65 CTO patients with 176 angiographically confirmed vascular stenosis or occlusive lesions, 70 of which were complete occlusion, underwent off-pump CABG. During the operation, diffuse intimal thickening distal to occlusive lesion was found, and blood flow of the bridges was unfavorable.Results Therefore endarterectomy was performed, followed by CABG. The blood flow in the bridges were 2-10 ml/min versus 14-37 ml/min before versus after endarterectomy. Pulsatility index (PI) was 5.1-15.6 versus less than 5 before versus after endarterectomy. Left ventricular ejection fraction was also improved significantly [before operation: (0.47±0.12)%, after operation: (0. 52±0.15)%, t=2.17, P＜0.05]. Peri-operative myocardial infarction occurred in 2 cases, but without significant cardiac homodynamic changes. And 23 patients underwent coronary angiography to evaluate graft patency 3-18 months after operation, all of them had favorable blood flow. Conclusions It is feasible to perform off-pump CABG plus coronary endarterectomy for patients of chronic coronary total occlusion combined with diffuse distal atherosclerosis. This treatment is safe and effective.

Adult ; Child ; Eosinophilia ; complications ; Female ; Hematologic Neoplasms ; complications ; Humans ; Male ; Middle Aged

In order to improve the efficiency of drug screening on serotonin transporter (SERT) inhibitors, a high-throughput screening (HTS) model is established in RBL-2H3 cells. The RBL-2H3 cells are very similar to the serotonin genetic neuro, in modulation of post-receptor mechanisms and transduction pathway of SERT reactivated. Depending on a fluorescence substrate ASP+ used in detection method of inhibitor rates, it's convenient, quick, accurate and effective, not making the environmental biohazard compared with radioactive experiments. Furthermore, biological screening model combined with computer aided virtual screening technique describing high-throughput virtual screening (HTVS). Bayesian classification method and molecular fingerprint similarity were applied to virtual screening technique, for screening compounds in compound library. Some compounds have been found, and then validated further by biological screening model. Combination of HTS and HTVS improves the efficiency of screening SERT inhibitors.
Animals ; Bayes Theorem ; Cell Line ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays ; Models, Biological ; Rats ; Serotonin Plasma Membrane Transport Proteins ; metabolism ; Serotonin Uptake Inhibitors ; pharmacology

To evaluate in vitro release and transdermal behaviors of Huoxue Zhitong gel, modified Franz diffusion cell methods was applied to investigate in vitro transdermal absorption of Huoxue Zhitong gel and the content of paeonolan in receptor fluid composed of PEG400%-95% ethanol-water (l:3:6)were determined by HPLC. The results were processed and different equations were fitted. The release law were in accordance with Weibull equation and the fitting equation was In[-1/(1 - Q)] = -0.790 51nt - 1.7012 (r = 0.9809). In 8 hours, cumulative release of paeonol was 85. 18% and the release rate was 2.827 µg . cm-2 h-1. Transdermal actions were consistent with zero-level model fit and the fitting equation was Q(t) = 1.7579t + 0. 7213 (r = 0.9991). In 8 hours, cumulative transdermal rate and transmission rate of paeonol was 54. 85%, 1. 820 µg . cm-2 h-1. So the Huoxue Zhitong gel had a good release and transdermal properties.
Acetophenones ; administration & dosage ; pharmacokinetics ; Administration, Cutaneous ; Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Gels ; Mice ; Skin Absorption

Adrenal Cortex Hormones ; therapeutic use ; Anemia, Hemolytic, Autoimmune ; diagnosis ; drug therapy ; Female ; Humans ; Infant ; Treatment Outcome

Adolescent ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Drug Interactions ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate ; adverse effects ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Sex Factors ; Tetrahydrofolates ; administration & dosage ; therapeutic use ; Treatment Outcome

Objective To evaluate the effect of three diamension-digital subtraction angiography (3D-DSA) or computed tomography angiography (CTA) on the patients with ruptured multiple intmcranial aneurysm (MIA). Methods A retrospective study on 21 patients with MIA was performed.After scanning with 3D-DSA or 3D-CTA, three-dimensional reconstruction of MIA was carried out by 3D workstation,then the diagnosis was decided and the treatment plan (endovascular treatment or microsurgery) was selected according to stereoscopic image of MIA. Results (1) 3D-DSA or CTA was performed in 21 patients with subarachnoid hemorrhage (SAH),it was revealed these patients carried with 48 aneurysms,including 35 small aneurysms (25 mm).Not only miero-aneurysms and small aneurysms could be precisely showed,also the size of aneurysmal neck,the relationship of the aneurysm and the parent vessel and contiguous branches by stereoscopic image.(2) According to the standard of classification,9 patients with MIA for gradeⅠ(42.9%),10 for gradeⅡ(47.6%),2 for gradeⅢ(9.5%),0 for gradeⅣ.Endovascular treatment was selected prior to microsargery for those high grade patients.In this group,17 patients with 40 aneurysms underwent endovascular embolotherapy with GDC coils.Twenty four anemysms were completely occlusioned,12 beyond 90%,4 were left without treatment because of their small size.In microsurgery group,3 aneurysrus were totally clipped,1 could not be found during operation.No any treatment was accepted in 2 patients with 4 aneurysms. Conclusions 3D-DSA or CTA,which is very useful for the diagnosis and treatment of MIA,could improve the accuracy of diagnosis of MIA and clearly show the stereoscopic image of MIA,also the relation of sac and parent artery.For those patients with high grade MIA,endovascular treatment was selected prior to microsurgery,pro re nata,used to combine with mierosurgery.

Objective To explore the relationship between blood lipids level with creatinine clearance rate(Ccr)in patients with heart failure(HF). Methods A total of 955 patients who were diagnosed with heart failure(cardiac function NYHAⅡ~Ⅳclassification)upon discharge from the Department of Cardiology of the Second Hospital of Tianjin Medical University, between January 2010 to June 2013 were enrolled as HF group. Healthy adults (n=200) with normal cardiac function which approximately matched basic condition with HF group were selected as control group. The HF group was fur?ther divided intoⅡ,Ⅲ,Ⅳclassification according to their cardiac function(NYHA classification). HF group was also divid?ed into normal renal function group, mild renal injury group and moderate-severe renal injury group based on their Ccr. Ef?fect of gender and lipid parameters were also compared. Binary logistic regression was used to analyze factors influencing renal function in patients with HF. Results Compared with people in the control group, the levels of triacylglycerol(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-c)and non high density lipoprotein cholesterol(non-HDL-c)in patients of HF group were increased while Ccr and high density lipoprotein cholesterol(HDL-c)were decreased. Ccr and lipids were obviously decreased in patients with HF of Ⅳclassification. TG and HDL-c were decreased in moderate-severe renal injury group. Females had a higher lipid levels than males in HF group(P<0.05 or P<0.01). Advanced age, coronary heart disease and hypertension were all risk factors for renal impairment in patients with HF by binary logistic re?gression. On the other hand, weight gain and HDL-c were the protection factors for renal function in HF patients. Conclu?sion Dyslipidemias may lead to renal insufficiency in patients with HF. It was important to control lipids and improve re?nal function in patients with HF.