It is now clear that both endogenous and exogenous sources of nitric oxide(NO) exert important modulatory effects on cardiac mitochondrial function.There is also growing evidence that NO can be produced within the mitochondria themselves.NO can influence respiratory activity,both through direct effects on the respiratory chain or indirectly via modulation of mitochondrial calcium accumulation.At pathological concentrations,NO causes irreversible alterations in respiratory function and also interacts with reactive oxygen species(ROS) to form reactive nitrogen species(RNS),which may further impair mitochondrial respiration and even lead to open the mitochondrial permeability transition pore and induce cell death.Diabetes,aging,myocardial ischemia,and heart failure are all associated with altered ROS generation,which can alter the delicate regulatory balance of effects of NO in the mitochondria.

Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Blood-Brain Barrier ; Brain Neoplasms ; metabolism ; Glioma ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metabolomics ; methods ; Microdialysis ; methods ; Neurotransmitter Agents ; pharmacokinetics ; Pharmaceutical Preparations ; metabolism ; Positron-Emission Tomography

Child, Preschool ; China ; epidemiology ; Humans ; Infant ; Infant, Newborn ; Language Development ; Sampling Studies

Objective To extract and purify a polysaccharide SEP from eggs of sea urchin Strongylocentrotus nudus. and to determine its purity, molecular weight and immunological activity in vitro. Methods The orthogonal design was employed to obtain the best possible combination of the critical parameters for polysaccharide extraction. By ultrafiltration, DE-AE Sepharose Fast Flow anion-exchange chromatography and Sephacryl S-400 gel filtration chromatography, the deproteinated crude polysaccharide was purified. The homogeneity of SEP was proved by HPLC, polyacrylamide gel electrophoresis and paper chromatography. Its molecular weight was determined by HPGPC in reference to standVd T-series Dextran. Lymphocyte proliferation assay was made to investigate the immuno-modulating activity of SEP. Results and Conclusion The results indicated SEP was a homogeneous polysaccharide. Its molecular weight was about 1950KD. SEP increased remarkably spleen lymphocyte proliferation. The homogeneous polysaccharide SEP showed significantly immunological activity in vitro.

Objective: To explore the effect of Fuzheng granules on immune function activities in animal models.Methods: The effects of Fuzheng granules were investigated in normal mice and immunosuppressive mice by macrophage englobement rate and index of phagocytosis,leucocyte quantity,lymphocyte conversion ratio induced by adhesin,serum hemolysin,content of serum con-complement.Results: Fuzheng granules could significantly elevate the macrophage englobement rate,index of phagocytosis,leucocyte quantity,lymphocyte conversion ratio induced by adhesin,serum hemolysin,content of serum con-complement in above mice.Conclusion: Fuzheng granules had the effect of improving immune function activities.

DNA ; DNA Fingerprinting ; Homicide ; Humans

In order to study the excretion of genistein (GEN) capsule, an estrogen drugs, in human, 30 healthy volunteers were selected and orally administered 50, 100, and 300 mg genistein in an parallel study. Genistein were determined in urine by LC-MS/MS and glucuronidated genistein (GENG) were indirectly determined with enzymatic hydrolysis in urine by LC-MS/MS, and the pharmacokinetic parameters were analyzed by DAS software (ver 2.0). The result showed that the concentrations of genistein in human urine were less than 1% of the GENG, and the cumulative excretion of GEN in 48 h were 0.037, 0.134, and 0.142 mg, separately, and the urinary excretion percentage were only 0.07%, 0.13%, and 0.05%, separately. But the cumulative excretion of GENG in 48 h was 5.3, 13.8, and 15.4 mg, separately, and the urinary excretion percentage were 10.6%, 13.8%, and 5.1%, separately, and the max urinary excretive rate was 0.4, 1.0, and 1.4 mg x h(-1), separately (tmax were 6 h). Studies showed that part of drug excreted through kidney in a form of GENG in human, and the cumulative urinary excretion and the maximum excretion rate of GENG showed a proportional increase conditioned with the dose in the range of 50-100 mg, but showed non-linear increase feature in 300 mg.

To study the sesquiterpenoid constituents in the whole plant of Sarcandra glabra, silical column chromatography, Sephadex LH-20, reverse phase ODS column chromatography and preparative HPLC were used to isolate 70% EtOH extract of Sarcandra glabra. The structures were elucidated based on spectroscopic data (HR-ESI-MS, 1H NMR, 13C NMR, HSQC, HMBC and NOESY). Four sesquiterpenoids were obtained and identified as 4alpha-hydroxy-5alphaH-lindan-8 (9)-en-8, 12-olide (1), chloranthalactone E (2), 8beta, 9alpha-dihydroxylindan-(5), 7 (1)-ieb-8alpha, 12-olide (3) and chloranoside A (4), respectively. Compound 1 is a new sesquiterpene lacone.

Objective:To express recombinant protein mIL-21-hIgGFc in 293E cells,and investigate its effect on CD8+T cell.Methods:Total RNA was extracted from the mouse spleen cells ,and then IL-21 gene was amplified by RT-PCR and inserted into expression vector PTT3-hIgGFc.PTT3-mIL-21-hIgGFc were transfected into 293E cells by calcium phosphate method.The supernatants were collected at 48 hours and 72 hours and concentrated by MOLLIPORE Labscale TM TFF system ( 5 kD membrane ).The mIL-21-hIgGFc fusion protein was purified with HiTrap TM Protein G column.The protein was quantified by SDS-PAGE and ELISA.The biological activity of the protein was determined by detecting the change of the phenotypes of CD 8+ T cells treated with the protein.Results: The constructed recombinant plasmid PTT 3-mIL-21-Fc was confirmed by sequencing.PTT3-mIL-21-Fc was transfected into 293E cells,mIL-21-Fc protein in culture supernatant was collected after 48 hours and 72 hours.The protein in cell su-pernatant reached a concentration of 787 ng/ml which was determined by ELISA.The protein was purified by Protein G chromatography column.P1A-specific T cells were treated with mIL-21-hIgGFc, and found that the CD44low CD62Lhi CD8+ population increased compared to the control.Conclusion:We built PTT3-mIL-21-hFc recombinant plasmid, expressed mIL21-hFc fusion protein in 293E cells,and purified by Protein G column.By treating mIL-21-hFc ,the antigen-primed CD8+T cells prefer to differentiate into CD44low CD62Lhi CD8+T cells which had been reported as a memory stem phenotype .This protein may be used to improve the effectness of adoptive T cell cancer therapy.

Objective To summarize the relationship between metabolic syndrome (MS),its components and T1 stage with high grade urothelial carcinoma (HGUC) of the Bladder.Methods The clinical data of 200 patients with T1 high grade bladder cancer who were admitted to our hospital from January 2010 to June 2014 were retrospectively analyzed,including 155 males and 45 females.Ages were 24 to 86 years old,average 66 years old.Based on the history or blood glucose levels,patients were divided into diabetic group (n =41) (20.5％) and non diabetes group 159 cases (79.5％);According to the body mass index (BMI) were divided into obese group (≥25 kg / m2) of 98 cases (49.0％) and non obese group (＜ 25 kg / m2) of 102 cases (51.0％).According to the blood pressure level,71 cases (35.5％) were divided into hypertension group and 129 cases of non hypertension group (64.5％).MS and its components and the relationship between the recurrence and progress of bladder cancer were analyzed.The Kaplan Meier method was used to assess MS and its components division of tumor progression free survival (progress-free survival,PFS) and recurrence free survival (recurrence-free survival,RFS) influence.Cox regression model of multi factor analysis were used to evaluate the PFS and RFs of MS and its components with bladder cancer.Results Of the 200 cases,16 cases (8.0％) were MS.Tumor recurrence occurred in 121 cases (60.5％),and 84 patients (42.0％) were in progress.Diabetes and non diabetes groups the average RFs were 21.7 and 29.3 months respectively,and the difference was statistically significant (x2 =10.115,P =0.001);The median PFS were 32.8 and 39.8 months respectively,the difference has statistical significance (x2 =14.760,P ＜0.001).Obese group and non obese group average RFs were 34.7 and 42.0 months respectively,and the difference were statistically significant (x2 =16.077,P ＜ 0.001);The median PFS were 22.8 and 32.6 months respectively,the difference was statistically significant (x2 =16.174,P＜0.001).The average RFS of MS group and non MS group were 21.5 and 28.4 months respectively,the difference was statistically significant (x2 =5.429,P =0.02);the average PFS was 35.1 and 38.7 months respectively,and the difference was statistically significant (x2 =3.854,P ＜ 0.05).Cox multivariate survival analysis showed that diabetes and obesity can increase the risk of recurrence and progression of T1 advanced stage bladder cancer (HR =1.792,P =0.013,HR =2.498,P ＜ 0.001;HR =0.559,P ＜ 0.001;HR =0.492,P ＜ 0.001).Conclusions Diabetes mellitus and obesity are high risk factors for the recurrence and progression of T1 advanced stage bladder cancer,but MS is not related to the prognosis of T1 patients with advanced bladder cancer.