Objective To determine whether the susceptibility to ischemia-reperfusion injury in aged heart is higher than that in adult heart and,if so,to clarify the mechanisms underlying this change.Methods Wister rats(5-or 20-month-old)were randomly divided into 4 groups(6 animals in each group).The rats were subjected to 30 minutes of myocardial ischemia via ligating the left anterior descending coronary artery,followed by 3 hours of reperfusion(Young-MI/R group and Old-MI/R group);A silk suture around the left anterior descending coronary artery was not ligated in young and old rats(Young-sham group and Old-sham group).Myocardial apoptosis was detected by terminal deoxynueleotidyl transferase biotin-d UTP nick end labeling(TUNEL)staining and caspase-3 activity was detected by using a caspase-3 colorimetrie assay.Nitrotyrosine content,a footprint of in vivo ONOO~-formation,and total NO content were determined by ELISA and chemiluminescence method respectively.Results A significantly exacerbated cardiac reperfusion injury was found in Old-MI/R group as evidenced by increased TUNEL positive myocytes[(19.0?2.1)% vs.(14.6?1.7)%],and increased myocardial caspase-3 activity[(436?35)?mool/mg vs.(340?32)?mol/mg] compared with Young-MI/R group(P＜0.05).Aged hearts had a markedly increased basal NOx level compared with young adult hearts.Marked higher myocardial nitrotyrosine content was found in OId-MI/R group[(7.25?0.18)nmol/g]than that in Young-MI/R group[(4.68?0.15)nmol/g] (P＜0.05).Conclusions In aged hearts,high levels of NO might form highly toxie derivant, ONOO~-,and its subsequent nitrified protein.This may attribute to the increased susceptibility of the aged heart to isehemic-reperfusion injury.

The biological properties of cultured mesenchymal stem cells (MSC) have been intensively investigated, while there is still a paucity of information about the definite in vivo sites that harbor these stem cells due to the lack of specific surface markers. Previous data have demonstrated that human and murine MSC can be isolated from the compact bones. To investigate if it is the case for other species, the femurs from Wistar rats, Beagles, C57 mice and New Zealand rabbits were collected, minced and digested with collagenase type I. The digested bone fragments were seeded into the medium for human bone marrow culture after removal of the suspended cells in the digestion. The results showed that the fibroblast-like cells were observed to migrate from the bone fragments after several days of culture, and they gradually formed an adherent confluent layer. The adherent cells could be passaged and expressed homogenously the mesenchymal cell marker vimentin. Differentiation assays showed that these cells had the capacity to differentiate into osteoblasts and adipocytes. In conclusion, the results here provide new information for the further investigations on the in vivo biological features of MSC in the context of the simplicity of the compact bone structure.
Animals ; Bone and Bones ; cytology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dogs ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Rabbits ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the antitumor activity of a novel class of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones in vitro, and to screen potential anticancer compounds for further study.

METHODSSeventeen compounds of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones were synthesized with solid-phase method for biological evaluation of EGFR tyrosine kinase. MTT method was used to evaluate the cytotoxic activity in vitro against three human cancer cell lines (human lung carcinoma cell line A549, human leukemia cell lines K562 and human gastric carcinoma cell line SGC7901).

RESULTSCompound 7-13 and 7-14 showed potent antitumor activities against A549 cells, with IC(50) values of 8.10 and 8.12 mol/L, respectively. Eight compounds showed proliferative inhibition effect on K562 cells, especially 7-2, 7-13 and 7-17, with IC(50) values of 2.22,0.57 and 7.20 mol/L,respectively.And compound 7-13 and 7-3 showed potent antitumor activity against SGC7901 cells, with IC(50) values of 4.20 and 9.71 mol/L, respectively.

CONCLUSIONThe synthesized compounds 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g] quinazoline-7(6H)-ketones show inhibition effects on human cancer cell lines in vitro. Compound 7-13 has anticancer activity in all three cancer cell lines, which might be used as a potential antitumor drug for further study.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Lung Neoplasms ; pathology ; Molecular Structure ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Quinazolines ; chemical synthesis ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Stomach Neoplasms ; pathology ; Structure-Activity Relationship

Cost-utility analysis(CUA) was widely used for health care decision-maker.It systematically introduced ShortForm 6D(SF-6D) and described the latest international research and application progress.Compared with EuroQol 5 Dimensions Questionnaire(EQ-5D),SF-6D had higher time validity and more reliable result on estimating patients in some fields.On the other hand,the unity value of SF-6D was estimated based the investigation result of Short Form-36(SF-36) through transferring literature and reports.Based on the method,estimating the health unity of patients' health could make the maximized use of the current data of SF-36,so as to save the costs of pharmacoeconomic.However,further research needs to verify that this transformation model is suitable for Chinese.

Objective To investigate the effects of functional magnetic resonance imaging (fMRI)with acute ischemic stroke (AIS) patients,and to evaluate the relationship between brain reorganization and motor recovery.Methods Nine AIS patients and 9 healthy volunteers were assessed by fMR1 during passive finger clenching at a pace of 1 Hz.The fMRI results were analyzed using SPM2 software.Lateral indices (LIs) and activated regions were calculated,and the relationship between LI and muscle strength was examined.Results In the control group,activation was observed in the contralateral sensorimotor cortex (SMC) and the bilateral supplementary area (SMA) during the passive movement.In the AIS group,similar results were recorded dur- ing unaffected hand movement,but the ipsilateral activation areas were greater than those on the eontralateral side during movement of the affected hand.LI results confirmed that movement of the affected hand mainly elici- ted activation in the ipsilateral hemisphere.Conclusion The different fMRI manifestations of patients and nor- mal subjects reflect brain compensation,and fMRI is valuable for studying the correlation between motor function and brain reorganization.

Background::In consideration of the difficulty in diagnosing high heterogeneous glioma, valuable prognostic markers are urgent to be investigated. This study aimed to verify that connective tissue growth factor (CTGF) is associated with the clinical prognosis of glioma, also to analyze the effect of CTGF on the biological function.Methods::In this study, glioma and non-tumor tissue samples were obtained in 2012 to 2014 from the Department of Neurosurgery of Nanfang Hospital of Southern Medical University, Guangzhou, China. Based on messenger RNA (mRNA) data from the Cancer Genome Atlas (TCGA) and CCGA dataset, combined with related clinical information, we detected the expression of CTGF mRNA in glioma and assessed its effect on the prognosis of glioma patients. High expression of CTGF mRNA and protein in glioma were verified by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blotting. The role of CTGF in the proliferation, migration, and invasion of gliomas were respectively identified by methylthiazoletetrazolium assay, Transwell and Boyden assay in vitro. The effect on glioma cell circle was assessed by flow cytometry. For higher expression of CTGF in glioblastoma (GBM), the biological function of CTGF in GBM was investigated by gene ontology (GO) analysis. Results::In depth analysis of TCGA data revealed that CTGF mRNA was highly expressed in glioma (GBM, n= 163; lowly proliferative glioma [LGG], n = 518; non-tumor brain tissue, n = 207; LGG, t = 2.410, GBM, t = 2.364, P < 0.05). CTGF mRNA and protein expression in glioma (86%) was significantly higher than that in non-tumor tissues (18%) verified by collected samples. Glioma patients with higher expression of CTGF showed an obviously poorer overall survival (35.4 and 27.0 months compared to 63.3 and 55.1 months in TCGA and Chinese Glioma Genome Atlas (CGGA) databases separately, CGGA: χ2 = 7.596, P = 0.0059; TCGA: χ2 = 10.46, P = 0.0012). Inhibiting CTGF expression could significantly suppress the proliferation, migration, and invasion of gliomas. CTGF higher expression had been observed in GBM, and GO analysis demonstrated that the function of CTGF in GBM was mainly associated with metabolism and energy pathways ( P < 0.001). Conclusions::CTGF is highly expressed in glioma, especially GBM, as an unfavorable and independent prognostic marker for glioma patients and facilitates the progress of glioma.

OBJECTIVE: To study the distribution and metabolism of methamphetamine in the hair of guinea pig. METHODS: Determination of methamphetamine and its metabolite amphetamine in hair was performed by GC/MS and GC/NPD. Concentration-time course of methamphetamine and amphetamine in hair of guinea were recorded. Relationship between hair color, administrated dose and drug concentration in hair were also discussed. RESULTS: The concentration of amphetamine is higher than the concentration of methamphetamine in the hair of guinea administrated a single dose or seven doses of methamphetamine. The concentration of methamphetamine and amphetamine were significantly related with administration dose and the incorporation rate into white and brown hair is much poorer than that of black hair. CONCLUSION Administration methods, dose and the color of hair affect the concentration of methamphetamine and amphetamine.
Amphetamine/metabolism* ; Animals ; Guinea Pigs ; Hair/metabolism* ; Hair Color ; Male ; Methamphetamine/metabolism*

OBJECTIVEA stable primary breast cancer model in liver-specific insulin-like growth factor 1 (IGF-1) deficient (LID) mice and control mice was established. To screen apoptosis related genes expression in different serum IGF-1 levels by gene chip and flow cytometry.

METHODSThe LID mice and control mice were used. Induction of breast cancer was achieved by using the 7,12-dimethylbenz(a) anthracene. Ginsenoside Rg3 was used to interfering therapy treatment. The incidence of breast cancer in every group was compared, and expression of apoptosis associated genes was detected by gene chip and flow cytometry.

RESULTSThe incidence of tumor in none ginsenoside Rg3 injected control mice was 66.7%. The incidence of tumor in ginsenoside Rg3 injected LID mice was 12.0% which was significantly lower than any other group (P < 0.05). The apoptosis percentage in none ginsenoside Rg3 injected control mice was (2.7 +/- 0.7)%. The apoptosis percentage in ginsenoside Rg3 injected LID mice was (14.0 +/- 1.7)%. The results of gene chip indicated that in contrast to LID mice, LTA, LTB, TNF-alpha, TRAIL, TRANCE, BLK, BOK, CASP8, TRAF5, and APAF1 genes were down-regulated, and LTBR, TRAF4 genes were up-regulated in the breast cancer tissues of control mice. Application of ginsenoside Rg3 therapy could change the expression of these genes.

CONCLUSIONSCirculating IGF-1 levels play a role in the onset and development of breast cancer. Degrade serum IGF-1 level is able to promote apoptosis by affecting the expression of a series of apoptosis related genes consequently inhibit the growth of breast cancer. There was a synergistic effect with the application of ginsenoside Rg3.

Animals ; Apoptosis ; Breast Neoplasms ; metabolism ; pathology ; Cell Proliferation ; Disease Models, Animal ; Female ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis

The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.
Animals ; Glycyrrhiza ; chemistry ; Kelp ; chemistry ; Kidney ; drug effects ; Liver ; drug effects ; Metabolomics ; Plant Preparations ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy.

METHODSThe clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).

RESULTS141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS.

CONCLUSIONER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

Adult ; Aged ; Aged, 80 and over ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms ; metabolism ; pathology ; surgery ; therapy ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; secondary ; surgery ; therapy ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; surgery ; therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Young Adult