Pyruvate dehydrogenase kinases(PDKs 1-4) can regulate the activity of mitochondrial pyruvate dehydrogenase complex(PDC) to catalyse the oxidative decarboxylation of pyruvate,and then to link glycolysis to the tricarboxylic acid cycle and ATP production.In this review,we summarize up-to-date information of mechanisms regulating PDKs and the function of PDKs inhibitors in lowering blood glucose level,alleviate damage during heart ischemia and also triggering apoptosis in cancer cells.PDKs will be a possible pharmacological targets in diabetes,heart ischemia and cancer therapy.

Objective To study on the changes of the IL-6、IL-8、TNF-? in the type 2 diabetes with insulin resistance and the relation of plasma glucose or insulin resistance and cytokines. Methods (1) To assay the serum level of cytokines in 90 cases with type 2 diabetes mellitus (T2DM) and 30 normal controls. (2)To measure the level of fasting plasma glucose (FPG),hemoglohin A_1c (HBA_1c),fasting insulin(FINS),fasting C-peptide (FCP).(3) To analysis the relation of the level of FPG,HBA_1c,FINS,FCP and cytokines. Results (1) The serum levels of cytokines in T2DM group were significantly increase than in control groups,IL-6 and TNF-? in T2DM group with insulin resistance were significantly increase than in T2DM group without insulin resistance (2) There was significantly positively correlated between insulin resistance and the increasing of cytokine levels. Conclusion There is an excess activation of cytokines in T2DM,which is significantly correlated with insulin resistance. Cytokines play the important role in the occurrence and development of T2DM and insulin resistance.

Administration, Cutaneous ; Amoxicillin ; therapeutic use ; Child ; Child, Preschool ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Penicillins ; therapeutic use ; Phytotherapy ; Respiratory Tract Infections ; drug therapy ; prevention & control ; Secondary Prevention

Adolescent ; Antibody Formation ; drug effects ; Asthma ; drug therapy ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Powders ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology

Adenocarcinoma ; therapy ; Breast Neoplasms ; therapy ; Carcinoma, Endometrioid ; therapy ; Carcinoma, Squamous Cell ; therapy ; Cystadenocarcinoma, Serous ; therapy ; Endometrial Neoplasms ; therapy ; Female ; Genital Neoplasms, Female ; therapy ; Hormone Replacement Therapy ; Humans ; Ovarian Neoplasms ; therapy ; Treatment Outcome ; Uterine Cervical Neoplasms ; therapy

Objective To investigate the impact of gantry angles on the position accuracy of buildin multi-leaf collimator (MLC) during static (step & shoot) intensity modulated radiotherapy (IMRT).Methods The position accuracy of MillenniumTM 60 pairs multi-leaf collimator (MLC) in Varian 23EX medical linear accelerator during 10 fractions of treatments with static intensity modulated radiotherapy (IMRT) was retrospectively analyzed by resolving dynamic therapy log files and MLC planning files.The single leaf position deviation and gap deviation of each MLC pairs were compared between expected values and actual outcomes.The impact of gantry angle on MLC position accuracy was also investigated with paired t-test between vertical and horizontal beams.Results All the MLC position deviations ranged within ± 1.0 mm,while the gap deviations were at the range of ± 1.5 mm.The statistical standard deviation of MLC position deviations among fractions was less than 0.06 mm.After all the 60 pairs of MLC leaves were taken into account,the M LC position deviation in the field of 103° was smaller than in the field of 0° (t =58.74,P ＜ 0.01),but there was no significant difference between 257° and 0°,while only the moving leaves were put into consideration,the MLC position deviation in the field of 103° was still smaller than in the field of 0°,but the MLC position deviation in the field of 257° was slightly higher than in thefield of 0° (t =41.95、-4.47,P ＜ 0.01).Conclusions The MillenniumTM 60 pairs MLC in Varian 23EX medical linear accelerator meets the mechanical quality assurance requirement during static IMRT treatments.The MLC positioning showed stable repeatability among treatment fractions.Although the MLC position accuracy is slightly affected by gravity from different gantry angles,but still meets the mechanical QA requirements for medical linear accelerator.This dynamic analysis method is expected to be a novel strategy which may improve the existing QA protocols.

Objective To study ischemic tolerance induced by acanthopannx senticosus saponins(ASS) on ischemia in PC12 cells and involve expression of hypoxia inducible factor-1?(HIF-1?).Methods An ischemic model was developed in PC12 cell line with treatment of oxygen glucose deprivation(OGD).The protective effects of ASS pretreatment on ischemic tolerance of PC12 cells and whether protective effects of ASS could be inhibited by LY294002(PI3K inhibitor) were analyzed through MTT assay.The induction of phospho-glycogen synthesis kinase-3?(p-GSK-3?) and HIF-1? after pretreatment of ASS and possible blocking effects of LY294002 were detected by Western-blot.Results MTT results showed that after 9 h ischemia,the viability of PC12 cells decreased dramatically(P

Azacitidine ; analogs & derivatives ; therapeutic use ; Clinical Trials, Phase III as Topic ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Multicenter Studies as Topic

Humans ; Leukemia, Large Granular Lymphocytic

Objective To explore the effects of estrogen on stress-induced senescence of vascular smooth muscle cells (VSMCs) and the underlying mechanisms. Methods The VSMCs of passage 2-3 cultured from female SD rats were induced into senescence by exposing to 150μmol/L H2O2 in the presence or absence of different concentrations(10-10mol/L-10-8mol/L) of 17β-estradiol (E2). The expressions or activities of senescence associated marker DcR2, senescence-associated beta-galactosidase (SA-β-Gal), oncogene Ras and p21WAF1 were detected by flow cytometry, cytochemical staining, pull-down assay or Western blotting analysis. Results Flow cytometry analysis showed that in the physiological concentrations, E2 significantly inhibited the H2O2-promoted high-level expression of DcR2 of VSMCs in a dose-dependent manner, with a highest inhibitive rate at 14.48%±0.6%(E2=10-8 mol/L;P<0.05, n =3);this inhibitive effect could be blocked by a E2 receptors inhibitor ICI 182,780. Cytochemistry staining showed that the rate of SA-β-Gal positive VSMCs induced by H2O2 decreased in presence of 10-8mol/L E2 (20.5%±1.4% vs 9.6%±0.9%;P<0.05, n =9). Pull-down assay and Western blotting analysis revealed that administration of 10-8mol/L E2 obviously reduced the H2O2-induced activity of Ras (0.60±0.06 vs 0.26±0.04;P<0.05, n =3) and expression of p21WAF1 (0.46±0.04 vs 0.33±0.02;P<0.05, n =3). Conclusion E2 exerts, an inhibitive effects on stress-induced senescence of VSMCs by suppressing the activity of Ras and expression of p21WAF1. This finding suggests a novel mechanism for the hormone's anti-atheroschlerotic effects.