Objective To evaluate the effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer (TNBC) xenografts in nude mice.Methods Human TNBC MDA-MB-231 cells were inoculated subcutaneously into BALB/c nude mice.The mice (n=32) were then randomly divided into 4 groups,the control group and the celecoxib group (receiving 25,50,100 mg·kg-1·d-1 respectively).At the end of the study,tumor tissues were collected and tumor volume was measured.Cell apoptosis was determined by flow cytometry (FCM) analysis.NF-κB p65 and pS0 protein levels were measured by immunohistochemistry.Caspase-3 and survivin protein levels were detected by western blotting.Results celecoxib at dose of 25,50 and 100 mg·kg-1·d-1 inhibited the tumor growth significantly,compared with the control group.FCM results showed that apoptotic rates were (13.58±3.16) ％ and (21.91±4.75) ％ in moderate and high dose of celecoxib-treated group,compared with (3.15±1.73) ％ in control group (t =6.736,P ＜ 0.05;t =12.151,P ＜ 0.05).p65 expressions were 79.3 ％,46.7 ％ and 23.9 ％ in low,moderate and high dose of celecoxib-treated group,compared with 89.7 ％ in control group (x2 =3.312,P ＜ 0.05; x2 =10.785,P ＜ 0.05;x2 =15.900,P ＜ 0.05).Besides,western blotting analysis demonstrated that celecoxib significantly downregulated survivin expression,while upregulated the active form of caspase-3 expression.Conclusion Celecoxib could suppress TNBC tumor growth and induce cell apoptosis,which might be partially associated with inactivation of p65 and downregulation of survivin.

It was hypothesized that the VPAC1 agonist may exert anti-obesity functions because VPAC1 is involved in the anorexigenic effects and the anti-inflammatory function of pituitary adenylate cyclase-activating polypeptide (PACAP)/vasoactive intestinal polypeptide (VIP). Furthermore, our in vitro test showed that the expression of VPAC1 increased significantly after the 3T3-L1 adipocytes were differentiated, and that incubation of adipocytes with VPAC1 agonist (10-1 000 nmol/L per 1x10(6) cells) resulted in stimulation of lipolysis. To test the effect of VPAC1 agonist [Lys15, Arg16, Leu27]-VIP (1-7) GRF (8-27) on diet-induced obesity (DIO), we further designed the following two in vivo experiments: (1) Mice were fed on high-fat diet (HFD) and intraperitoneally (i.p.) treated with VPAC1 agonist simultaneously for 28 d; (2) Mice were given HFD for 35 d, and subsequently fed on the same HFD and i.p. treated with VPAC1 agonist for the next 28 d. The physiological indices, including body weight, weight of white adipose tissue, plasma glucose and blood lipid, were collected. The results showed that treatment with VPAC1 agonist inhibited ingestion significantly and prevented the elevations in body weight and the weights of the white adipose tissues (epididymal and dorsal) induced by HFD. The increases in plasma glucose, cholesterol, triglycerides and LDL induced by HFD were also down-regulated in mice treated with VPAC1 agonist. VPAC1 agonist treatment also improved the glucose tolerance. Therefore, VPAC1 agonist treatment inhibits the development of the obesity induced by HFD and helps to improve the morbidities associated with DIO.
3T3-L1 Cells ; Adipocytes ; drug effects ; Animals ; Body Weight ; Diet, High-Fat ; Mice ; Obesity ; drug therapy ; Receptors, Vasoactive Intestinal Polypeptide, Type I ; agonists ; Vasoactive Intestinal Peptide ; pharmacology

OBJECTIVESTo analyse the control rate of irbesartan/hydrochlorothiazide (HCTZ) combination tablets (COAPROVEL) in the treatment of patients with mild to moderate primary hypertension.

METHODSIn this multi-center, open, single therapy trial, the enrolled patients aged 18-75 were treated with irbesartan/HCTZ combination tablets for 8 weeks. The initial dose comprised one tablet of irbesartan (150 mg)/HCTZ (12.5 mg) once a day during the first 2 weeks. If diastolic blood pressure was greater than 85 mm Hg at the end of the second or fourth weeks, irbesartan (300 mg)/HCTZ (12.5 mg) once a day or irbesartan (300 mg)/HCTZ (25 mg) once a day were added respectively.

RESULTSIn 968 patients with mild to moderate hypertension enrolled, 920 patients were followed up for 8 weeks. (1) After 1 week of treatment, irbesartan/HCTZ combination tablets lowered systolic blood pressure by 11.87 mm Hg and diastolic blood pressure by 8.54 mm Hg (P < 0.01). After 8 weeks of treatment, the corresponding decreases were 21.97 mm Hg and 16.08 mm Hg, respectively (P < 0.01). (2) After 2, 4 and 8 weeks of treatment, 526, 703 and 769 patients reached blood pressure target (diastolic blood pressure less than 85 mm Hg). The control rates were 57.17%, 76.41% and 83.59%, respectively. (3) Among the 920 patients who completed the trial, 637 patients took irbesartan (150 mg)/HCTZ (12.5mg) once a day (69.24%), 211 patients took irbesartan (300 mg)/HCTZ (12.5 mg) once a day (22.93%), and 72 patients took irbesartan (300 mg)/HCTZ (25 mg) once a day (7.82%). (4) In the intention-to-treat analysis, no adverse reaction was observed in 903 patients (93.29% of the patients enrolled).

CONCLUSIONSWhen irbesartan/HCTZ combination regimen are used in the treatment of patients with mild to moderate primary hypertension, the proportion of patients reaching blood pressure target is high and adverse reactions are rare.

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Biphenyl Compounds ; adverse effects ; therapeutic use ; China ; Drug Combinations ; Humans ; Hydrochlorothiazide ; adverse effects ; therapeutic use ; Hypertension ; drug therapy ; Middle Aged ; Tablets ; Tetrazoles ; adverse effects ; therapeutic use ; Young Adult

0.05).The expression rate of p53 protein in patients with cervical lymph nodes metastasis(≥4cm)was 81.8%(9/11),in cervical lymph nodes metastasis (

Adult ; Aged ; Bundle-Branch Block ; etiology ; Cardiomyopathy, Hypertrophic ; surgery ; Catheter Ablation ; adverse effects ; methods ; Female ; Heart Septum ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology

OBJECTIVETo study the the protective effects and mechanism of Shenfu injection on the global cerebral ischemia/reperfusion (I/R) injury of rats.

METHODSDivided 40 SD male rats into 4 groups randomly (n = 10): sham operation group, model control group, nimodipine group( 30 mg/kg) and Shenfu injection group (10 mg/kg). Made global cerebral ischemia/reperfusion injury model (CI/R) by adopting Pulsinelli's Four Arterial Acclusion method,and then practised administration three times, respectively one day before the surgery, one hour before the surgery and 30 minutes before reperfusion. Finally, measured the contents of brain tissue glutamate (Glu), aspartic acid (Asp) and Glycine (Gly) by means of High Performance Liquid Chromatography, the content of Ca2+ by means of Atomic absorption spectrophotometry, the brain water content by means of wet and dry weight, the activity of brain tissue superoxide dismutase (SOD) and content of malondialdehyde (MDA) by means of chemical colorimetry.

RESULTSCompared with the sham operation group, the contents of Glu, Ca2+, MDA and water in the brains of CI/R model group rats increased remarkably (P < 0.05 or P < 0.01), while the activity of SOD decreased apparently (P < 0.05); Shenfu injection could significantly decrease the contents of Glu, Ca2+ and water (P < 0.05, P < 0.01) in brain tissue and remarkably increased the activity if SOD and the ration of SOD/MDA (P < 0.05).

CONCLUSIONThe mechanism of Shenfu injection preventing cerebral ischemia/reperfusion injury is relevant to excitatory amino acid toxicity reduction, Ca2+ overload blockage and antioxidant capacity improvement.

Animals ; Antioxidants ; metabolism ; Brain Ischemia ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism

OBJECTIVETo evaluate the relationship between leukotriene expression in blood polymorphonuclear leukocytes (PMNL) and the efficacy of inhaled corticosteroids (ICS) in children with asthma.

METHODSThirty-two children with asthma (5-12 years) and ten healthy children (control group) were enrolled. The asthmatic children were subdivided into ICS well-controlled and ICS poorly-controlled groups based on their clinical symptoms and lung function. The level of leukotriene C4 synthase (LTC4S) mRNA in PMNL was detected by fluorescence quantitative polymerase chain reaction. The level of LTC4S mRNA was expressed by the value of qCt, and the value of qCt was diversely correlated with the level of LTC4S mRNA expression. The concentration of urinary leukotriene E4 (LTE4) was measured using ELISA.

RESULTSThe expression of LTC4S mRNA in PMNL was significantly higher in children with asthma (qCt: 1.12+/-0.27) than that in the control group (qCt: 1.42+/-0.12; P< 0.05). The expression of LTC4S mRNA in PMNL in the ICS poorly-controlled group (qCt: 1.03+/-0.17) was significantly higher than that in the ICS well-controlled group (qCt: 1.24+/-0.33; P< 0.05) and the control group(1.42+/-0.12; P< 0.01). There was no significant difference in the level of urinary LTE4 among the the ICS poorly-controlled, the ICS well-controlled and the control groups.

CONCLUSIONSLTC4S mRNA expression in PMNL in asthmatic children increases, and the LTC4S mRNA expression in the ICS poorly-controlled group is higher than that in the ICS well-controlled group. This suggests that an increased leukotriene expression might be associated with poorly-controlled asthma.

Administration, Inhalation ; Adrenal Cortex Hormones ; administration & dosage ; Asthma ; drug therapy ; Child ; Child, Preschool ; Female ; Glutathione Transferase ; genetics ; Humans ; Leukotriene E4 ; urine ; Male ; RNA, Messenger ; blood

To investigate the modulatory action of endogenous and exogenous nitric oxide (NO) on survival of alveolar macrophages (AMs) in different cellular states, AMs from normal rats (normal AMs) and from bleomycin (BLM)-treated rats (BLM AMs) were incubated by sodium nitroprusside (SNP, NO donor) and L-arginin (L-Arg, NO precursor), respectively. The survival of AMs was evaluated by apoptosis and cell cycles. The molecular mechanisms were investigated by the contents of Bcl-2, Bax proteins in AMs. The results are as follows: (1) The degree of BLM AMs apoptosis was higher than that of normal AMs; the number of BLM AMs in G(0)/G(1) phases was less than that of normal AMs; there was no significant difference in S+G(2)M phases between the number of BLM AMs and that of normal AMs. (2) Down-regulation of Bcl-2 and up-regulation of Bax occurred in BLM AMs, compared to those in normal AMs. (3) Apoptosis of AMs, either normal AMs or BLM AMs, was induced by both SNP and L-Arg, when compared to their respective control; only the number of BLM AMs in S+G(2)M phases was increased by L-Arg. (4) SNP and L-Arg induced a down-regulation of Bcl-2 and an up-regulation of Bax proteins in normal AMs, but did not induce the same change pattern in BLM AMs. (5) The Bax in BLM AMs was down-regulated by L-Arg. It is concluded that NO can induce the apoptosis of BLM AMs and normal AMs; that Bcl-2 and Bax are implicated in NO-induced apoptosis of normal AMs, whereas they are not involved in that of BLM AMs, suggesting the differential molecular mechanisms underlying the NO-induced apoptosis of normal AMs and BLM AMs; and that endogenous NO promotes proliferation of BLM AMs, which might be associated with down-regulation of Bax.
Animals ; Apoptosis ; drug effects ; Bleomycin ; Cell Survival ; drug effects ; Cells, Cultured ; Macrophages, Alveolar ; cytology ; pathology ; Male ; Nitric Oxide ; pharmacology ; physiology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pulmonary Fibrosis ; chemically induced ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

Objective To develop a method of quantitative analysis of multi-components by single marker (QAMS) for simultaneously determining five compounds in Curcumae Aromaticae Radix.Methods An HPLC method was developed as QAMS to determine curcuma diol,ocathydro-1,4-dihydroxy-1,4-dimethyl-7-(propan-2-ylidene)azulen-5(1H)-one,original curcumol and curcumin in Curcumae Aromaticae Radix,using curdione as intermal reference substance,and the relative correction factor (RCF) of the four components was determined by HPLC with good reproducibility.Their contents in 10 batches of samples,collected from different areas,were determined by both external standard method and QAMS.Result No significant differences were found in the quantitative results of four compounds in 10 batches of Curcumae Aromaticae Radix determined by external standard method and QAMS.Conclusion It is feasible and suitable to evaluate the quality of Curcumae Aromaticae Radix by QAMS.

Objective To study the effect of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats.Methods From 1 d to 4 d,Clozapine 5 mg·kg -1 ·d -1 was gavaged,and the dose increased to 25 mg·kg -1 ·d -1 from the 5th day.Metformin 100 mg·kg -1 ·d -1 or 400 mg·kg -1 ·d -1 or simvastatin 1 mg· kg -1 ·d -1 was gavaged from the 15th day.The total period of dosing was 8 weeks.Body mass,fasting blood sugar (FBS) and postprandial 2 hours blood glucose (2hPBG)were measured at baseline,3 d,1 week,2 weeks,4 weeks,6 weeks and 8 weeks.At the end of the 8th week,serum cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL -C), high density lipoprotein (HDL -C),fructosamine (FA)and insulin (IRS)were measured and liver HE staining was done.Results There were no significant differences of the measured indexes between control group and metformin group at the all test points.By the end of the 6th and 8th week,compared with control group,the body mass,FBS,2hPBG,IRS, FA,TC,TG and LDL -C were significantly increased in clozapine group (P <0.05 ),while HDL -C decreased in clozapine group (P <0.05).Compared with clozapine group,body mass,FBS,2hPBG,IRS,FA,TC,TG and LDL -C were significantly decreased by metformin or simvastatin administration (P <0.05),while HDL -C increased(P <0.05).Rat liver cells in clozapine group were not neat around the small blood vessels;there were more white fat cells and hepatocellular lipid calm far away from the blood vessels.However,in other groups,there were moderate white fat cells, and there were not much hepatocellular lipid calm far away from the blood vessels.Conclusion Metformin could effectively prevent and treat weight gain,glucolipid metabolic disorder and liver lipid deposition caused by clozapine.