OBJECTIVE: To explore alcohol pharmacokinetics as well as acetaldehyde level in peripheral blood in human subjects with different ALDH2 genotypes after drinking. METHODS: Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length polymorphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. RESULTS: According to the results of electrophoresis, 5 people carried ALDH2*1/*1 as wild group and 9 people carried ALDH2*1/*2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7 microg/mL and 0-5.1772 microg/mL, respectively. The AUC values of alcohol and acetaldehyde and the t1/2Z value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group (P<0.05). CONCLUSION After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2*1/*2 mutation group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.
Alcohol Drinking ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Ethanol/metabolism* ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic

With the advances in immunology and molecular biology, new recognition in the pathogenesis, progression, and metastasis of carcinoma have been achieved. Studies on gene therapy for pancreatic carcinoma have been attempted in different ways, such as inhibiting oncogene, activating tumor suppressor gene, inducing apoptosis, applying gene directed enzyme prodrug therapy, and immune activation. New specific target genes and further development of gene technology may bring the break-through in this field.
Animals ; Genes, Tumor Suppressor ; Genetic Therapy ; methods ; Humans ; Immunotherapy ; Pancreatic Neoplasms ; genetics ; immunology ; therapy

BACKGROUNDFunctional neuroimaging study has opened an avenue for exploring the pathophysiology of cluster headache (CH). The aim of our study was to assess the changes in brain activity in CH patients by the regional homogeneity method using resting-state functional magnetic resonance imaging technique.

METHODSThe functional magnetic resonance imaging scans were obtained for 12 male CH patients with spontaneous right-sided headache attacks during "in attack" and "out of attack" periods and 12 age- and sex-matched normal controls. The data were analyzed to detect the altered brain activity by the regional homogeneity method using statistical parametric mapping software.

RESULTSAltered regional homogeneity was detected in the anterior cingulate cortex, the posterior cingulate cortex, the prefrontal cortex, insular cortex, and other brain regions involved in pain processing and modulation among different groups.

CONCLUSIONIt is referred that these brain regions with altered regional homogeneity might be related to the pain processing and modulation of CH.

Adult ; Case-Control Studies ; Cluster Headache ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Young Adult

OBJECTIVETo explore the effects of different fertilization methods on the outcomes of elective blastocyst culture.

METHODSWe retrospectively analyzed the outcomes of elective blastocyst culture for 1 153 cycles of IVF and 205 cycles of ICSI performed between january 2009 and December 2012.

RESULTSA total number of 14 748 embryos in the IVF group and 2 655 embryos in the ICSI group underwent sequential blastocyst culture, with 7 871 blastocysts formed in the former and 1 210 in the latter. No cycles were canceled for no blastocyst formation in either of the two groups. The rates of quality embryos, blastocyst formation and embryo utilization were significantly higher in the IVF than in the ICSI group (64.77 vs 58.72%, 53.37 vs 45.57%, and 60.06 vs 52.17%, all P < 0.05), but the rates of implantation, clinical pregnancy and abortion showed no significant differences between the two groups (48.94 vs 51.43%, 49.03 vs 52.02%, and 11.69% vs 15.56, all P > 0.05).

CONCLUSIONWith the same inclusion criteria of selective blastocyst culture, IVF has a lower risk of cycle cancellation due to no blastocyst formation and therefore may effect higher rates of blastocyst formation and embryo utilization than ICSI. Our study suggested that appropriate inclusion criteria of selective blastocyst culture should be laid down according to different fertilization methods.

Adult ; Blastocyst ; Embryo Transfer ; Female ; Fertilization in Vitro ; methods ; Humans ; Pregnancy ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

OBJECTIVETo identify the effect of interleukin-8 in cell progression and invasion of human breast cancer.

METHODSHuman cytokine antibody arrays were applied to screen a panel of cytokine expression from 11 human breast cancer cell lines, and the mechanism of identified key factors involved in breast cancer progression was studied.

RESULTSProfiling of cytokine expression showed the expression of interleukin-8 was related to estrogen receptor status, metastasis and vimentin status in the 11 human breast cancer cell lines. Elevated expression of interleukin-8 in breast cancer cells had positive correlation with breast cancer invasion. Neutralization of antibody against interleukin-8 specifically blocked interleukin-8-mediated cell invasion. However, anti-interleukin-8 antibody did not influence the proliferation of breast cancer cells.

CONCLUSIONInterleukin-8 may be the key factor involved in human breast cancer progression and invasion, and play an important role in cell invasion of breast cancer.

Breast Neoplasms ; metabolism ; pathology ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Interleukin-8 ; biosynthesis ; physiology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Protein Array Analysis ; Receptors, Estrogen ; metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF.

METHODSMyocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed.

RESULTSCompared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).

CONCLUSIONSUpregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.

Acetylation ; E1A-Associated p300 Protein ; genetics ; Female ; Histone Acetyltransferases ; genetics ; Histone Deacetylases ; genetics ; Histones ; metabolism ; Humans ; Infant ; Male ; Myocardium ; metabolism ; Peptide Fragments ; genetics ; RNA, Messenger ; analysis ; Sialoglycoproteins ; genetics ; Tetralogy of Fallot ; metabolism

RHO-related GTPases of plants (ROPs) are a class of signal transduction G proteins (alsoknown as GTP binding proteins) widely existing in plants. ROP proteins act as " molecular switches" toregulate the signal transduction process during cellular activities such as plant cell polarity regulation, plant morphological development, hormone level regulation, stress responses and many other life activitiesby shifting between inactive GDP-binding and active GTP-binding forms in the cells. In this review, thedomain structure, classification, the mechanism of activity regulation and biological functions of ROPproteins were summarize. Furthermore, ROP proteins from Arabidopsis, maize, rice and barley werephylogenetically analyzed. The results show that ROP proteins were classified into two types based on thedomain structure of the proteins. However, these ROP proteins were divided into 4 clades based on thesimilarity of protein sequences. Furthermore, the mechanism of ROP proteins as a molecular switchregulating various signaling pathways in cells, and the specific functions and mechanisms of ROPs in thepolarized growth of pollen tubes, root hairs and plant pavement cells and other stress responses werecharacterized. In addition, the research progress of the function of ROPs in plant hormones such as ABA, IAA and BR mediated signal transduction were described as well. At last, the unanswered questions suchas why different ROP proteins play distinct roles in the same signaling pathway and how ROPs coordinatedifferent signal pathways to jointly regulate a plant’ s development or physiological process werediscussed, which may shed light on future research.

This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3β, β-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3β by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3β and down-regulating β-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.
Apoptosis ; drug effects ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology ; U937 Cells ; Wnt Signaling Pathway ; beta Catenin ; metabolism

BACKGROUNDThe role of B-cell remains an enigma in the pathogenesis of ankylosing spondylitis (AS). This study aimed to investigate the distributions of B-cells and subsets in peripheral blood of AS patients and observe their changes in etanercept-treated AS patents.

METHODSWe detected the proportions of CD19(+) B-cell, naive B-cell (CD19(+)CD27-), memory B-cell (CD19(+)CD27dim) and plasmablast (CD19(+)CD27high) in peripheral blood of 66 patients with AS (39 at active stage, 27 at stable stage; 35 patients with peripheral joint involvement, 31 patients with axial involvement alone), 30 patients with rheumatoid arthritis (RA) and 30 healthy volunteers using flow cytometry. And then we observed the changes of the above indexes of 39 active AS patients treated with etanercept in a randomized, double-blind, placebo-controlled trial.

RESULTS(1) Percentages of CD19(+) B-cells in active or peripheral joint involvement AS patients increased more obviously than those in stable or axial involvement alone AS patients (both P = 0.001), and percentage of CD19(+)CD27high B-cells in AS patients with peripheral joint involvement was significantly higher than that in cases with axial involvement alone or healthy volunteers (P = 0.005 and 0.006, respectively); (2) The percentage of CD19(+) B-cells in AS patients was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Patient's Global Assessment (PGA) scores, total back pain scores and nocturnal back pain scores (r = 0.270, 0.255, 0.251 and 0.266, P = 0.029, 0.039, 0.042 and 0.031, respectively); (3) At week 6 and week 12, there were no statistical differences of the percentages of B-cells and subsets between etanercept group and placebo group of AS patients (P > 0.05); the percentage of CD19(+) B-cells in etanercept group was higher than that in healthy volunteers at week 12 (t = 3.320, P = 0.003).

CONCLUSIONSMisbalance is present in B-cells and some subsets in peripheral blood of active AS patients with peripheral joint involved. B-cells might play an important role in the pathogenesis of AS patients. The high percentage of CD19(+) B-cells in active AS patients cannot be down-regulated after 12-week etanercept treatment.

Adolescent ; Adult ; Antigens, CD19 ; immunology ; B-Lymphocytes ; drug effects ; immunology ; Etanercept ; Female ; Flow Cytometry ; Humans ; Immunoglobulin G ; pharmacology ; therapeutic use ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Spondylitis, Ankylosing ; drug therapy ; immunology ; Tumor Necrosis Factor Receptor Superfamily, Member 7 ; immunology ; Young Adult

The aim of this study was to investigate the effect of sorafenib combined with daunorubicin on leukemic k562 cell line. The inhibitory effect of sorafenib alone and its combination with daunorubicin on K562 cell proliferation was detected by MTT method; the synergistic effect was measured by CDI (coefficient of drug interaction); the apoptosis of K562 cells was observed by flow cytometry with Hoechst 33258 staining. The results showed that the sorafenib alone or its combination with daunorubicin could significantly inhibit K562 cell proliferation and the combination of both drugs displayed synergistic effect on K562 cells, meanwhile the apoptotic cells increased. It is concluded that the combination of sorafenib and daunorubicin has a obviously synergistic inhibitory effect on leukemic cell line K562.
Apoptosis ; drug effects ; Benzenesulfonates ; pharmacology ; Daunorubicin ; pharmacology ; Drug Synergism ; Humans ; K562 Cells ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology