Objective To investigate the effect of angiotenisn ⅡI (Ang Ⅱ) on RIN-m β-cell,and to explore the mechanism of β-cell function impairment caused by Ang Ⅱ.Methods RIN-m cells were cultured with various concentrations of AngⅡ (0.1,1,10,100 nmol/L).After incubation for 24 hours,the basal(3.3 mmol/L) and glucose-stimulated(16.7 mmol/L) insulin secretion(GSIS)were detected by radioimmunoassay,mRNA and protein expressions of uncoupling protein 2(UCP2)were determined by RT-PCR and Western blot,respectively.The intracellular ATP content was measured by luciferase bioluminescence.The mitochondrial membrane potential and cellular Ca~(2+) concentration were detected by flow cytometry.Results (1) Various concentrations of Ang Ⅱ had no significant influence on the basal insulin secrection of RIN-m cell(F=0.644,P = 0.634).Except for 0.1 nmol/L AngⅡ,the other concentrations of Ang Ⅱ markedly reduced GSIS of RIN-m cells(F= 118.528,P = 0.000).(2) Compared with the control group,Ang Ⅱ significantly increased mRNA and protein expression of UCP2(F= 1 370,P = 0.000;F=675.175,P = 0.000).(3)Except for 0.1 nmol/L Ang Ⅱ,the other concentrations of Ang Ⅱ significantly decreased the mitochondrial membrane potential,cellular ATP content,and cellular Ca2+ concentration of RIN-m cell(F=4.035,P=0.008;F=3.353,P = 0.013;F=5.867,P = 0.001).Conclusion Ang Ⅱ impairs GSIS of p-cell,the mechanism of impairment may be interpreted that Ang Ⅱ can increase the expression of UCP2,furthermore,it can reduce mitochondrial membrane potential,decrease the content of cellular ATP and the concentration of cellular Ca~(2+),can finally impair the function of β-cell.

To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Methacrylates ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the protecting actions of Peristrophe roxburghiane on liver functions and structure in fatty liver rats caused by insulin resistance.

METHODHigh-fat-sugar diet was fed in rats to produce insulin resistance and fatty liver model, and then P. roxburghiane was administered for 8 weeks, and the rats were killed and the blood was sampled to measure the levels of FFA, TC, TG, HDL-C and LDL-C, and the activities of AST, ALT. The fasting serum glucose (FBG) and insulin were measured, and insulin-sensitivity index was calculated. The liver was weighed and collected to calculate liver index and measured the activities of GSH-PX, SOD, CAT and the amount of MDA.

RESULTHigh and low dosage of P. roxburghiane can decrease the levels of FFA, TG and increase the level of HDL-C, reduce the activities of ALT, AST and liver index, and reduce the damaged degree of the liver tissue significantly. High and low dosage of P. roxburghiane can significantly enhance the activities of SOD, CAT, and GSH-PX, reduce the amount of MDA.

CONCLUSIONP. roxburghiane possesses regulating action on the serum lipid, blood glucose and insulin, and improving liver functions of fatty liver rats induced by high-fat-sugar diet, and the acting mechanism may be concerned with enhanced antioxidative ability.

Acanthaceae ; chemistry ; Animals ; Antioxidants ; pharmacology ; Blood Glucose ; metabolism ; Catalase ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fatty Liver ; blood ; physiopathology ; prevention & control ; Female ; Glutathione Peroxidase ; metabolism ; Insulin Resistance ; Lipids ; blood ; Liver ; drug effects ; metabolism ; pathology ; Liver Function Tests ; Male ; Malondialdehyde ; metabolism ; Phytotherapy ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

Child ; Humans ; Plasma Exchange ; Thrombotic Microangiopathies ; therapy

Estrogen receptor alpha (ERalpha) has been a primary target of treatment as well as a prognostic indicator for breast cancer. The level of human X-box binding protein 1 (XBP-1) mRNA was related with that of ERalpha in breast tumors and was over-expressed in some breast tumors. These previous studies suggested that XBP-1 may interact with ERalpha. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U bound to ERalpha in vitro. The binding of XBP-1S to ERalpha was stronger than that of XBP-1U to ERalpha. Co-immunoprecipitation revealed that the binding was in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of ERalpha that contains a DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region leucine zipper domain (bzip) and the C-terminal activation domain. These findings suggest that XBP-1S and XBP-1U may participate in ERalpha signaling pathway through the mediation of ERalpha.
Breast Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; metabolism ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Protein Interaction Domains and Motifs ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Regulatory Factor X Transcription Factors ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; X-Box Binding Protein 1

Objective To evaluate the results of hybrid procedure in treating infants and children with severe pulmonary stenosis (PS) and the clinic value of echocardiography in the whole procedure.Methods Hybrid therapy was performed in 43 patients [(7.1±6.8)months,ranging 5 days to 33 months] with severe PS.The echocardiography data in the whole procedure and follow up were reviewed.Results Aided by echocardiography,the hybrid therapy was successful in 43 cases without major complication.Immediately following valvuloplasty,the gradient across pulmonary valve decreased from (92.5±21.4)mm Hg to (23.6±13.0)mm Hg (P<0.05).The growth and development of 27 patients in follow-up study was well.No restenosis was found and tricuspid regurgitation decreased differently.Conclusions Hybrid procedure is effective and safe for the treatment of infants and children with severe PS.And echocardiography play an important role in the whole procedure.

Aged ; Giant Cells ; pathology ; Humans ; Male ; Stomach Neoplasms ; pathology

Objective To observe the curative effect of magnesium isoglycyrrhizinate in prevention of liver injury induced by oxaliplatin .Methods The control group used oxaliplatin ,leucovorin ,5‐fluorouracil chemotherapy ,the treatment group were treated with oxaliplatin ,leucovorin ,5‐fluorouracil chemotherapy and simultaneous magnesium isoglycyrrhizinate were used at the same time .With 28 d for 1 course of treatment ,the treatment period consisted of 2‐4 courses ,observation of pa‐tients and the proportion of liver injury were made .Results In the control group ,liver injury incidence rate was 44 .4% ,the rate of injury was 19 .4% in treatment group ,there was significant difference between the two groups (P<0 .01) .Conclusion Magnesium isoglycyrrhizinate could be effective in prevention of oxaliplatin induced liver injury .

OBJECTIVETo detect the expression of epidermal fatty acid-binding protein (E-FABP) and fatty acid synthase (FAS) in human breast cancer and identify the potential markers and therapeutic targets for breast cancer.

METHODSFAS and E-FABP expressions were detected in 76 patients with infiltrating ductal breast carcinoma using RT-PCR, immunohistochemistry and Western blotting. The possible associations of the expression of the two proteins with the major clinicopathological factors were analyzed.

RESULTSE-FABP and FAS expression levels were significantly decreased (P<0.05) in grade III as compared with grades I and II infiltrating ductal breast carcinoma. There was a positive correlation between E-FABP and FAS expressions, but their expressions were not correlated to the clinicopathological factors of the patients except for the tumor grades. High E-FABP expression level in grades I and II tumors were associated with an early increased responsiveness to FAS.

CONCLUSIONThe variation of the E-FABP and FAS expressions in the lesions is associated with increase of the risk for breast cancer, and the results of this study provide evidence for developing new molecular markers of high-risk lesions and identifying new the targets for breast cancer therapy.

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Blotting, Western ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Fatty Acid Synthases ; biosynthesis ; genetics ; Fatty Acid-Binding Proteins ; biosynthesis ; genetics ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction

This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.
Aged ; Alzheimer Disease ; cerebrospinal fluid ; Amyloid beta-Peptides ; cerebrospinal fluid ; Arginine ; analogs & derivatives ; cerebrospinal fluid ; Female ; Humans ; Male ; Malondialdehyde ; cerebrospinal fluid ; Middle Aged ; Nitric Oxide ; cerebrospinal fluid ; Nitric Oxide Synthase Type II ; cerebrospinal fluid ; Oxidative Stress ; Peptide Fragments ; cerebrospinal fluid ; Peroxynitrous Acid ; cerebrospinal fluid ; Reactive Oxygen Species ; cerebrospinal fluid ; Tyrosine ; analogs & derivatives ; cerebrospinal fluid