Aldehyde Oxidoreductases ; deficiency ; Child, Preschool ; Female ; Humans ; Metabolism, Inborn Errors ; diagnosis ; enzymology ; metabolism ; Succinate-Semialdehyde Dehydrogenase ; gamma-Aminobutyric Acid ; metabolism

Adolescent ; Athletes ; Cortisone ; blood ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Hemoglobins ; analysis ; Humans ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Testosterone ; blood

BackgroundResearches demonstrated that the levels of soluble CD44 (sCD44)molecule in aqueous is significantly higher in primary open-angle glaucomous(POAG) eye than normal eye,but how the sCD44 would affect the expression of apoptosis protein in trabecular meshwork cells is below understanding.Objective The present study was to investigate the effect of sCD44 on the expression of regulatory proteins bcl-2 associated death factor bad in trabecular meshwork cells in the patients with POAG.MethodsHuman scleral tissue with trabecular meshwork were obtained from POAG patients during the surgery.The trabecular meshwork cells were primarily cultured by explant culture method and identified by immunochemistry.The third generation of cells were incubated with free-serum DMEM/F12 medium added differnt dosages of sCD44 (0,1,5,10,25,50 mg/L) for 48 hours.The expression of bad protein in cultured cells was detected using cell counting kit-8 (CCK-8) as the absorbance values at 490 nm(A,90 value),and the bad protein level in cultured cells was assayed by ELISA.ResultsThe cultured cells showed the positive response for laminin ( LM ),neuron specific enolase ( NSE ),fibronectin ( FN ) monoclonal antibodies.The CCK-8 assay showed that the A490 values of the trabecular meshwork cells in 0,1,5,10,25,50 μg/L of sCD44 groups were 0.2460±0.0019,0.1874±0.0015,0.1570±0.0016,0.1302±0.0019,0.1084±0.0018,0.0940±0.0020 respectively with a statistically significant difference among the 6 groups( F =14.922,P =0.000 ),and the A490 values in various dosages of sCD44 groups were significantly lower than the 0 μg/L sCD44 group (P=0.013,0.008,0.011,0.005,0.004).The ELISA assay showed that bad protein levels in 0,1,5,10,25,50 μg/L of sCD44 groups were ( 114.8461 ± 2.9560 ),( 137.8270 ± 2.4259 ),( 161.4194 ± 3.7381 ),( 170.9453 ± 3.2006 ),( 221.2252 ±4.3738 ),( 324.6167±4.4220) ng/L,showing a total difference among them ( F =16.610,P =0.000 ),and the bad protein levels in various dosages of sCD44 groups were significantly lower than the 0 μg/L sCD44 group( P =0.017,0.013,0.008,0.007,0.006).ConclusionssCD44 can contribute to the apoptosis of the trabecular meshwork cells in patients with POAG in certain dose range by regulating the apoptosis regulatory proteins bcl-2 associated death factor bad.

Cryptococcosis ; etiology ; pathology ; Glycogen Storage Disease Type I ; complications ; pathology ; Humans ; Infant ; Male ; Meningitis, Fungal ; etiology ; pathology

AIMDesign, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.

METHODS AND RESULTSCoupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.

CONCLUSIONFive target compounds were found to be potential farnesyltransferase inhibitors.

Alkyl and Aryl Transferases ; antagonists & inhibitors ; drug effects ; Benzodiazepines ; chemical synthesis ; chemistry ; pharmacology ; Farnesyltranstransferase ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Molecular Conformation ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo study the effects of nimesulide, a selective COX-2 inhibitor, on cell viability, telomerase and PKB activities in human gastric cancer cell line SGC7901 and to explore its molecular mechanism of selective growth inhibition.

METHODSMTT assay was used to determine cell viability after incubation for 0, 12, 24, and 48 h in different concentrations (0, 25, 50, 100, 200 micro mol/L) of nimesulide and/or okadaic acid (300 nmol/L). Telomerase and protein kinase B (PKB) activities were detected using TRAP PCR-ELISA and nonradioactive IP-kinase assay.

RESULTSNimsulide caused a time and dose-dependent reduction of cell numbers of SGC7901. The telomerase and PKB activities were significantly inhibited, and the inhibition of telomerase activity was partly associated with decrease in PKB activity.

CONCLUSIONSelective COX-2 inhibitor nimesulide inhibits telomerase activity of gastric cancer cells by partly blocking the activation of protein kinase B. The results suggest an additional signaling pathway underlying the anti-cancer effect of COX-2 inhibitor.

Adenocarcinoma ; enzymology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase Inhibitors ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; drug effects ; Humans ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-akt ; Stomach Neoplasms ; enzymology ; pathology ; Sulfonamides ; pharmacology ; Telomerase ; metabolism ; Time Factors

BACKGROUNDNeuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.

METHODSWe used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.

RESULTSSNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.

CONCLUSIONSSNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.

Amino Acid Transport System X-AG ; genetics ; metabolism ; Animals ; Disease Models, Animal ; GABA Plasma Membrane Transport Proteins ; Male ; Neuralgia ; genetics ; metabolism ; Neuroglia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Synaptic Transmission ; genetics ; physiology ; Synaptosomal-Associated Protein 25 ; genetics ; metabolism

AIMTo build a three dimensional structure model that correlates the biological activities and the structures of a series of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta-[1,2-]pyridin-11-yl) piperazines farnesyl protein transferase (FPTase) inhibitors.

METHODS AND RESULTSMutation in the ras oncogene takes place in many human cancers, involving 30%-50% of colon and 90% of pancreatic cancer. Ras proteins function as central switches for signals given by growth factors that direct cell growth and cell differentiation. The dependence of the transforming activity of Ras on the farnesylation has led to intense search for FPTase inhibitors that may have therapeutic pontetial as anticancer agents. This paper is to build a three dimensional structural model that correlates the biological activities and the structures of a series of FPTase inhibitors. The investigated sixty-nine inhibitors contain six types of structures, the optimal conformations of which were studied using system search. A three dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed using the method of comparative molecular field analysis (CoMFA). The resulting cross-validation R2 is 0.581, non-cross-validation R2 0.968, SE 0.148, F 198.7. The predicted activities of 10 inhibitors using this 3D-QSAR model are comparable to the experimental activities, indicating that the 3D-QSAR model has ability to predict activities of new inhibitors and offers an approach to design new FPTase inhibitors.

CONCLUSIONThe information of CoMFA model offers an approach to designing new FPTase inhibitors.

Alkyl and Aryl Transferases ; antagonists & inhibitors ; Enzyme Inhibitors ; chemistry ; pharmacology ; Humans ; Molecular Conformation ; Molecular Structure ; Pyridines ; chemistry ; pharmacology ; Quantitative Structure-Activity Relationship

OBJECTIVETo study the burning characteristics of moxa stick.

METHODSA self-designed moxa stick burning temperature measuring device, which was assembled with ALTEC intelligence digital setter and SJ-600 thermocouple, was used to conduct next four experiences: 1) embedding a thermocouple inside a moxa stick to measure peak burning temperature; 2) pulling a thermocouple embedded in the moxa stick at the proper rate to detect combustion stability; 3) elucidating temperature distribution of transverse section by measuring the temperature in the center, radius midpoint and lateral; 4) drawing temperature-time-space curves by pulling the thermocouples in the former three observation points.

RESULTSThe experiment indicated that the burning temperature peak of three-year moxa stick (Hubei Herbal Medicine St. Qichun Technology Co., Ltd.) was 848 degrees C which had good combustion stability. Furthermore, the temperature in the center, radius midpoint and lateral of transverse section were 843 degrees C, 731 degrees C and 410 degrees C, respectively, and its burning temperature-time-space curves was drawn, which showed the real-time burning temperature and the peak burning temperature and were regarded as ultimate indice to integrate the formers.

CONCLUSIONThe measuring system elaborately reflecting the burning features of moxa stick may provide reference for manufacture industry of moxa stick quality criteria for its convenience and accuracy.

Humans ; Moxibustion ; instrumentation ; Temperature ; Time Factors

Child, Preschool ; Humans ; Male ; Mucopolysaccharidosis II ; diagnosis ; genetics ; therapy ; Siblings