Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

A HPLC method of analysis of Monascus citrinin was established. More than 30 strains of Monascus spp. were cultured in steamed rice at solid state or in MSG liquid medium composed of monosodium glutamate as sole nitrogen source and glucose as sole carbon to investigate their ability of producing citrinin. The results indicated that most of the Monascus strains are able to produce citrinin. MSG medium can be used as a specific culture medium to qualitatively identify if the strain is the potential citrinin producer. But to confirm whether the Monascus strains are potential citrinin producers, these strains should be cultured in several cultivation methods, as the culture states and culture conditions influence the citrinin production greatly.

AIMTo investigate the neural network and cellular mechanisms of hippocampal epileptogenesis contralateral or ipsilateral to the side of acute tetanization (60 Hz, 2 s, 0.4 - 0.6 mA) of the posterior dorsal hippocampus (ATPDH).

METHODS10 trains of the ATPDH were administered into the CA1 basal dendritic region of the right hemisphere at an interval of 10 minutes.

RESULTS(1) The firing rate of CA1 single neuron in the right or the left hippocampus was inhibited respectively after the ATPDH, and the effects weakened gradually while the trains of the ATPDH increased. The inhibited firing rate and the transformed firing pattern from tonic one to clonic one were more obvious at the side contralateral to the stimulation (62.94% +/- 3.68%, 36.61% +/- 3.14%, P < 0.01). (2) Synchronous primary afterdischarges of depth EEG and single unit discharges were more commonly observed at the side ipsilateral to the ATPDH (P < 0.01). (3) Primary or secondary hippocampal network afterdischarges at high frequency were only found in CA1 region ipsilateral to the ATPDH. (4) Secondary afterdischarges of CA3 basal dendritic neural network were completely synchronized with those of subicular single neuron, which reoccurred and persisted several hours.

CONCLUSIONIt is possible that post-inhibition bursting of single neuron and recurrent network seizures in the hippocampus contralateral to the artificial focus be the important manifestation of the formation of "epileptic networks" across from one hemisphere to another.

Animals ; Electric Stimulation ; Hippocampus ; physiology ; Male ; Neural Pathways ; physiology ; Rats ; Rats, Sprague-Dawley ; Seizures ; etiology

OBJECTIVETo investigate the enhancing effect of crystal sugar-vinegar solution on the tolerance of alcohol consumption in mice and rabbits.

METHODCrystal sugar-vinegar solution was given to mice or rabbits 30 min before feeding a dose of alcohol. The toxic behavior and percentage of animal death in 24 hours were observed. Meanwhile, blood alcohol levels in the rabbits were measured.

RESULTCrystal sugar-vinegar solution could prolong the latent period of righting reflex disappearing of the drunk mice(P < 0.01) and decrease death percentage of drunk mice in 24 hours(P < 0.01). Crystal sugar-vinegar could also decrease blood alcohol levels in the drunk rabbits, especially 30 min(P < 0.01) and 180 min(P < 0.05) after administration of alcohol.

CONCLUSIONCrystal sugar-vinegar solution has an evident sober-up effect on drunk model animal.

Acetic Acid ; therapeutic use ; Alcoholic Intoxication ; blood ; drug therapy ; Alcoholism ; blood ; drug therapy ; Alcohols ; blood ; Animals ; Carbohydrates ; chemistry ; therapeutic use ; Crystallization ; Drug Combinations ; Female ; Male ; Mice ; Rabbits

This paper introduces the application of a calling and queuing system for blood sample collection in a large hospital in China. Besides the basic function, it has following functions. (a) A real name system: get the number according to the laboratory application form to prevent the phenomena of buying a number and an empty number. (b) Two times waiting: the patient should wait at the main hall, then at the blood sampling window so as to improve the work efficiency. (c) The flowchart for an outpatient blood testing is as following: getting the number --> waiting --> blood sampling --> getting the test information report. This system is capable of not only optimizing the work flow, but also improving the clinical environment. It shortens the patient's waiting time and raises the laboratory quality as well.
Ambulatory Care ; methods ; Ambulatory Care Information Systems ; Blood Specimen Collection ; Laboratories, Hospital ; organization & administration

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.
Animals ; Chromatography, Liquid ; Dexamethasone ; blood ; Dipeptidyl-Peptidase IV Inhibitors ; blood ; pharmacokinetics ; Linagliptin ; blood ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry

OBJECTIVETo investigate the influences of verapamil preconditioning on cardiac function in vitro and intracellular free Ca2+ and L-type calcium current (I(Ca-L)) in rat cardiomyocytes post ischemia-reperfusion (I/R) injury.

METHODSThe isolated rat hearts in control group (37 degrees C Tyrode solution perfusion for 30 min, n = 6), I/R group (no flow for 30 min followed 30 min reperfusion with 37 degrees C Tyrode solution, n = 7) and verapamil preconditioning group [37 degrees C Tyrode solution perfusion for 10 min, adding verapamil (20 micromol/L) to Tyrode solution and perfusion for another 30 min, followed then by 30 min no flow and 30 min reperfusion, n = 7] using Langendorff perfusion system. The fluorescence intensity of intracellular Ca2+ was detected with Fluo-3/AM loading by the laser scanning confocal microscope. The I(Ca-L) was recorded via whole-cell patch clamp technique in enzymatically dissociated single rat ventricular myocytes.

RESULTSAs expected, arrhythmias and cardiac dysfunction were shown post I/R injury. The fluorescence intensities of intracellular free Ca2+ in cardiomyocytes were significantly increased compared with control group (P < 0.01). By voltage clamp protocol, peak current densities of I(Ca-L) was significantly reduced and I-V curve significantly elevated. Post I/R injury compared with control group (P < 0.01) which could be reversed by Verapamil preconditioning. Verapamil preconditioning also significantly improved diastolic and systolic functions, and reduced the incidence of arrhythmias.

CONCLUSIONSMyocardial I/R injury might significantly impair heart functions and induce arrhythmias via cellular Ca2+ overload. Verapamil preconditioning could prevent heart I/R injury and reduce arrhythmias by decreasing influx of I(Ca-L), thereby stabilizing cardiomyocytes in myocardial stunning and avoiding occurrence of Ca2+-induced Ca2+ release during I/R injury.

Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; drug effects ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Verapamil ; pharmacology

OBJECTIVETo study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer.

METHODSThe expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared.

RESULTSThe positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups.

CONCLUSIONBreast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.

Adult ; Age Factors ; Aged ; Breast Neoplasms ; chemistry ; pathology ; Female ; Fibroblast Growth Factor 2 ; analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Postmenopause ; Receptor, Fibroblast Growth Factor, Type 1 ; analysis ; Receptors, Estrogen ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

This study was aimed to investigate the influence of timing using G-CSF after chemotherapy on graft yield of mobilized peripheral blood stem cells for autoPBSCT. 39 patients with lymphoma or multiple myeloma (MM) received the same chemotherapy mobilization regimen, including CTX 400 mg/m² d1; VLB 2 mg/m(2) d1; Ara-C 60 mg/m ²× d1-5; VP-16 60 mg/m² × d1-5; and prednisone 40 mg/m² × d1-5. The historical control group (12 cases) received G-CSF subcutaneously (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (27 cases) received G-CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G-CSF was given in a single daily subcutaneous dose of 5 µg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1.0 × 10⁹/L respectively, leukapheresis was carried out using the COBE Spectra blood cell separator. The results indicated that despite there was comparable treatment with alkylating agents between 2 groups, a significantly increased yield of CD34 positive cells was observed in the experimental group (26.4 × 10⁶/kg), as compared to the historical control group (3.1 × 10⁶/kg) (p = 0.0031). It is concluded that the appropriate timing for the use G-CSF mobilization after chemotherapy is important to increase the CD34(+) cell yield in auto-graft.
Adult ; Antigens, CD34 ; Antineoplastic Combined Chemotherapy Protocols ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Lymphoma ; therapy ; Male ; Middle Aged ; Multiple Myeloma ; therapy ; Transplantation, Autologous ; Young Adult

OBJECTIVETo screen for genetic mutations in 35 patients with Leber's hereditary optic neuropathy (LHON).

METHODSPolymerase chain reaction and DNA sequencing were used to screen for the presence of mitochondrial DNA mutations.

RESULTSThe total detection rate of top 3 common LHON mutations were 20.0%, which included 6 cases of ND4 11778 G to A, 1 case of ND1 3460 G to A. No ND6 14484 T to C mutation was detected. A ND4 G11719A synonymous mutation was found in all patients. In addition, 21 other mutations were discovered among 23 patients, among which 13 had a single mutation, 8 had a second mutations, and 2 had a third mutation. Among the 21 mutations, ND4 11778 G to A had a frequency of 28.6%(6/21). ND1 3552 T to A, ND6 14470 T to C, ND4 11794 T to C, ND1 3497 C to T and 3644 T to C respectively had a frequency of 19.0% (4/21), 19.0%(4/21), 14.3%(3/21), 9.5%(2/21) and 9.5%(2/21). Among the 3 patients who harbored a ND4 11794 T to C mutation, 2 were heteroplasmic and one was homoplasmic in nature.

CONCLUSIONThe ND4 11778 G to A mutation is common in the Top "3" primary mutations of patients with LHON. Candidate LHON mutation ND1 3552 T to A or ND1 3644 T to C resulted in LHON pathogenesis as single or synergistic effect. The visual impairment at onset of the disease with candidate mutation were better than the eyes with the ND4 11778 G to A mutation.

Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Optic Atrophy, Hereditary, Leber ; genetics