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

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

Alanine Transaminase ; metabolism ; Animals ; Liver ; drug effects ; Male ; Mice ; Plant Extracts ; pharmacology

BACKGROUND: At present, there is few reports about using middl ecerebral artery obstraction (MCAO) model to determine the repair course of cerebral infarction during functional training.OBJECTIVE: To determine the effect of electro-stimulating therapy on promoting the rehabilitation of cerebral infarction and its mechanism.DESIGN: Randomized controlled study.SETTING: Animal Center and Electron Microscope Laboratory of Zhongshan University.MATERIALS: The experiment was carried out in the Animal Center of Zhongshan Medical College and Neurological Laboratory of the First Affiliated Hospital of Zhongshang University from January 2002 to December2004. A total of 200 healthy males SD rats, aged 3 months and weighing 90-110 g, were selected. According to the following criteria: SBP＞180mmHg (1 mmHg=0.133 kPa), BWT score of MCAO models which were reproduced by RHRSP was 1, totally 180 RHRSP were admitted to the research and divided into electro-stimulating therapy group (n=90) and control group (n=90).METHODS: Electro-stimulating was given to four accupuncture points of the paralyzed limbs of rats. The electro-stimulating treatment was given about 30 minutes once a day. And a therapy course was 6 days, and between two therapy courses there was one-day break. At the end of 1st, 3rd,6th and 9th therapy courses, the brain of motor function and tissue in marginal zone of cerebral infarction were assayed as follow: [1] The beam walking test (BWT, 1 as severe disorder and 7 as normal). [2] Electron microscope. [3] Astrpcyte glial fibriliary acidic protein, neurofilament protein and microtubule-associated protein-2 were assayed with immunohistochemistry. Five fields of each slice in the two groups were randomly selected to add up the positive cell number. Totally 30 positive cells of glial fibriliary acidic protein was selected to assay average absorbency (A) of positive cellular plasm. [4] Apoptosis of neurons were observed with in situ end-labeling (ISEL). [5] Brain-micro vasodilatatio was observed according to the criteria of one complete microvessel account under the field.MAIN OUTCOME MEASURES: [1] Scores of motor function; [2] Ultramicrostructure of cranial neurons and astrocyte; [3] Cranial glial fibriliary acidic protein, neurofilament protein and microtubule-associated protein-2;[4] Apoptosis of neurons; [5] Diastole of cerebral microvessel.RESULTS: Totally 180 rats were eligible while 20 rats were excluded because of their BWT score＞1 after MCAO operation. [1] Results of beam walking test (BWT): Functional recovery of paralysis limbs in electric stimulation group was better than that in control group from the third to the ninth course. In the ninth course, 6 points of rats in electric stimulation group was more than that in control group (42, 46, χ2=15.4, P ＜ 0.01). [2]Positive absorbency of cerebral glial fibriliary acidic protein: That in electric stimulation group was higher than that in control group in the 3rd, 6th,and 9th [(52.97±0.59)% vs (46.40±0.56)%; (49.44±0.80)% vs (46.40±0.56)%;(43.25±0.48)% vs (34.20±0.50)%, P ＜ 0.05]. [3] Assay of neurofilament protein: That in electric stimulation group was higher than that in control group in the 6th and 9th course [(22.9±2.7)% vs (11.9±2.3)%; (26.5±1.7)%vs (11.7±1.5)%, P ＜ 0.05]. [4] Assay of microtubule-associated protein-2:That in electric stimulation group was higher than that in control group in the 6th and 9th course [(21.7±1.3)% vs (11.3±1.1)%; (24.4±2.1)% vs(11.9±2.3)%, P ＜ 0.05]. [5] Apoptosis of neurons: There was not significantly different between the two groups. [6] Results of open number of cerebral microvessel: That in electric stimulation group was higher than that in control group in the 1st, 3rd, 6th and 9th course (33 vs 19; 48 vs 31;45 vs 25; 46 vs 23, Z=-2.309, P ＜ 0.05).CONCLUSION: Electro-stimulating treatment can promote motor function of paralyzed limbs, which was due to that electro-stimulating treatment may promote extinction of the swollen feet of astrocytes, reinforce neurons activity and arouse the dilatation of cerebral capillary which promote the microvascular dilatation in order to improve cerebral blood circulation.

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

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

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