Adenoviridae ; genetics ; Cell Death ; Genetic Vectors ; HT29 Cells ; Humans ; Interleukins ; biosynthesis ; genetics ; RNA, Catalytic ; biosynthesis ; genetics ; RNA, Messenger ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism

To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Humans ; Isoenzymes ; genetics ; metabolism ; Liver Cirrhosis ; drug therapy ; enzymology ; genetics ; Male ; Mass Spectrometry ; Rats ; Rats, Wistar

AIMTo investigate the effect of hypothalamic thyrotropin-releasing hormone (TRH) on cardiac function and its mechanism.

METHODSThe Sprague-Dawley rats were mounted in a stereotaxic apparatus and a guide cannula placed in the left hypophysiotropic area, through which TRH were microinjected in presence or absence of L-NAME and atropine. The left ventricular systolic pressure (LVSP), heart rate (HR) and the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) were recorded.

RESULTS(1) TRH microinjected into the hypophysiotropic area induced a significant increase of LVSP, HR, dp/dt and-dp/dt(max) (P < 0.05, P < 0.01). (2) L-NAME significant increased LVSP and pretreatment with L-NAME inhibited the positive effects induced by TRH. (3) Atropine increased LVSP and dp/dt(max) (P < 0.05), but it significantly descended heart rate (P < 0.05). Pretreatment with atropine weakened the tachycardiac response induced by TRH.

CONCLUSION(1) Hypothalamic TRH can produce positive inotropic and chronotropic response to myocardium. (2) Hypothalamic endogenous NO can descend LVSP, but has no effects on HR, dp/dt(max), and-dp/dt(max). The effect of TRH is through nitric oxide-dependent pathway. (3) Hypothalamic endogenous cholinergic transmitter can produce negative chronotropic and positive inotropic response to myocardium. Hypothalamic TRH mediates cardiac function maybe partly through cholinergic M receptor.

Animals ; Blood Pressure ; Heart Rate ; Heart Ventricles ; drug effects ; Hypothalamus ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Thyrotropin-Releasing Hormone ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects

To optimize the immunization strategy against HIV-1, a DNA vaccine was combined with a recombinant vaccinia virus (rTV) vaccine and a protein vaccine. Immune responses against HIV-1 were detected in 30 female guinea pigs divided into six groups. Three groups of guinea pigs were primed with HIV-1 DNA vaccine three times, boosted with rTV at week 14, and then boosted with gp140 protein at intervals of 4, 8 or 12 weeks. Simultaneously, the other three groups of animals were primed with rTV vaccine once, and then boosted with gp140 after 4, 8 or 12 weeks. The HIV-1 specific binding antibody and neutralizing antibody, in addition to the relative affinity of these antibodies, were detected at different time points after the final administration of vaccine in each group. The DNA-rTV-gp140 immune regimen induced higher titers and affinity levels of HIV-1 gp120/gp140 antibodies and stronger V1V2-gp70 antibodies than the rTV-gp140 regimen. In the guinea pigs that underwent the DNA-rTV-gp140 regimen, the highest V1V2-gp70 antibody was induced in the 12-week-interval group. However, the avidity of antibodies was improved in the 4-week-interval group. Using the rTV-gp140 immunization strategy, guinea pigs boosted at 8 or 12 weeks after rTV priming elicited stronger humoral responses than those boosted at 4 weeks after priming. In conclusion, this study shows that the immunization strategy of HIV-1 DNA vaccine priming, followed by rTV and protein vaccine boosting, could strengthen the humoral response against HIV-1. Longer intervals were better to induce V1V2-gp70-specific antibodies, while shorter intervals were more beneficial to enhance the avidity of antibodies.
AIDS Vaccines ; administration & dosage ; genetics ; immunology ; Animals ; DNA, Viral ; administration & dosage ; genetics ; immunology ; Female ; Guinea Pigs ; HIV Infections ; immunology ; prevention & control ; virology ; HIV-1 ; genetics ; immunology ; Humans ; Immunization ; methods ; Vaccines, DNA ; administration & dosage ; genetics ; immunology ; Vaccinia virus ; genetics ; immunology ; env Gene Products, Human Immunodeficiency Virus ; administration & dosage ; genetics ; immunology

OBJECTIVETo explore the interrelationship among dorsal motor nucleus of the vagus (DMV), locus coeruleus (LC) and raphe magnus nucleus (NRM) in the mechanism of the descending regulation on gastric motility, which may constitute a parasympathetic local circuit, work as a neural center of gastric modulation in brainstem.

METHODSUsing nucleus location, electric stimulation and lesion, together with microinjection, and recording the inter-gastric pressure.

RESULTS(1) LC stimulation could inhibit the gastric motility significantly (P < 0.01), DMV lesion weaken this effect, while blocking the a receptor on DMV could reverse the effect. (2) NRM stimulation reduced the amplitude of gastric constriction (P < 0.01), DMV lesion could abolish the effect, but blocking the 5-HT2A receptor on DMV depressed the gastric motility heavily (P < 0.01) like NRM stimulation. While LC lesion could abolish the effect of NRM stimulation, and microinjection of ritanserin into LC could likewise abolish it.

CONCLUSION(1) LC inhibit the gastric motility via a receptor in DMV, and meanwhile may excite it through 5-HT2A receptor in DMV, these two ways work together to keeping the gastric motility amplitude normally. (2) NRM inhibit the gastric motility via 5-HT2A receptor in LC.

Animals ; Brain Stem ; physiology ; Female ; Gastrointestinal Motility ; physiology ; Locus Coeruleus ; physiology ; Male ; Motor Neurons ; physiology ; Raphe Nuclei ; physiology ; Rats ; Rats, Sprague-Dawley ; Vagus Nerve ; physiology

The next-generation sequencing (NGS), as the most practical and reliable method, has replaced the classical Sanger sequencing to help scientists to discover the genetics secrets of human tumor diseases. With the technique development, the whole genome sequencing will be no longer out of reach. Recently, some scientists used the NGS in the research of hematological malignancies and pushed the progress of the whole genome sequencing in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) actively in order to find out the pathogenesis of some hematological malignancies. The NGS and the application of the whole genome sequencing, the exome sequencing, the transcriptome sequencing in AML and MDS are reviewed in this article.
Base Sequence ; Genome, Human ; Hematologic Neoplasms ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Myelodysplastic Syndromes ; genetics ; Sequence Analysis ; methods

Objective To assess the effect of ultrasound contrast agent SonoVue on the dimensions and systolic function of left and right ventricle in pigs. Methods Sixteen pigs were randomly assigned to two groups. Intravenous injection of 1 ml of SonoVue were given in study group, and repeated 20 min later. The control group was given the same doses of saline. Before and after the administration of contrast agent, the end-diastolic dimension (LVEDD, RVEDD). end-systolic dimension ( LVESD, RVESD) and fractional shortening(LVFS,RVFS) of left and right ventricle were measured. The time to reach the extreme value of these parameters and the time to return to the baseline were recorded. Results There was no significant difference regarding the parameters at baseline between the two groups. After injection of SonoVue,RVEDD significantly increased from (25. 88 ± 1. 38) mm at baseline to its maximum of (33. 26 ± 0. 99)mm( P < 0. 05). Accordingly,RVFS significantly increased from (26. 90 ± 1. 92) % to (33. 92 ± 2. 53) % ( P <0. 05). Meanwhile,LVEDD remarkably decreased from (38.10 ± 1. 39)mm at baseline to its minimum of (26.25 ± 0. 65)mm( P <0. 05) and LVFS remarkably decreased from (36. 24 ± 1. 93) % to (29.13 ± 3.00) % ( P < 0. 05). There was no change in the control group after administration of the saline. When SonoVue was given repeatedly, the maximum RVEDD and RVFS was (29. 98 ± 1. 23) mm and (31. 09 + 1.90) % , respectively, which had less increase compared to the first time. Minimum LVEDD and LVFS was (31. 91 ± 1, 64)mm and (32. 17 ± 2. 31)%,respectively,with less decrease compared with which at first injection. It took (10. 15±0. 59) min for the right and left ventricle to reach the extreme value and (9.00± 0. 56) min to return to the baseline at the first injection. The time used for the right and left ventricle to reach its peak change and back to baseline after second injection of SonoVue were shorter [(8.73± 0.55) min and (6.89± 0.43) min, respectively,both P <0.05]. Conclusions Administration of SonoVue was associated with acute, transient dilation of right ventricle and compression of left ventricle. The influence of SonoVue on the right and left ventricle became less at it second injection.

Objective To study the influence of different microembolism on left ventricular systolic synchronism in pigs by detecting the real-time dypyridamole stress contrast echocardiography (RT-MCE).Methods Eighteen miniature pigs were randomly divided into three groups and underwent microembolization injection procedure through the middle of anterior descending coronary artery with different numbers of microsphere injection,as:group A(dosage 50 thousands,3 pigs),group B (dosage 120 thousands,8 pigs) and group C (dosage 150 thousands,7 pigs).The peak values and the time-to-peak circumferential strain(Circ.Strain),radial velocity (Radial Vel.) and radial strain (Radial Strain) were obtained both at mitral valve level and papillary muscle level at left ventricle short axis views using two-dimensional speckle tracking imaging(STI)analyzed by Philips Q-Lab 8.1 workshop,respectively.Results No significant difference in the presence of contraction synchrony was observed using RT-MCE.The time-to-peak Circ.Strain of microembolism related segments were prolonged at 1 week after microembolism detecting with dypyridamole stress RT-MCE (P＜0.05,both intro-group and inter-group).While time-to-peak radial strain were extended since 6 hours after the intervention to 1 week after the procedure.Conclusions Dypyridamole stress RT-MCE can be used to measure the myocardial perfusion accurately.The elongation of time-to-peak circ.strain and radial strain were developed with time in microembolism related segments.

OBJECTIVE To observe the effects of glycogen synthase 3β (GSK-3β) in the regula-tion of NLRP3 inflammasome activation after acute myocardial infarction (MI) in Sprague Dawley(SD) rats. METHODS Ligation of the left anterior descending (LAD) in SD rats was used to establish an acute myocardial infarction model. SD rats were randomly divided into 3 groups (n=10, each group):sham group,MI group,and MI+SB group:the GSK-3β inhibitor(SB216763)was given 1 h by intrave-nous injection(0.6 mg·kg-1·d-1)before surgery.The serum and heart tissue were collected to measure lactate dehydrogenase (LDH) and IL-1β content and mRNA and protein levels of NLRP3, ASC, Cas-pase-1,IL-1β and GSK-3β after 2 days and 7 days operation,respectively.RESULTS The serum levels of LDH and IL-1β in the MI group were significantly higher than those in the sham group(P<0.01),and the MI+SB group was obviously lower than the MI group(P<0.01).In addition,mRNA and protein levels of NNLRP3, ASC, Caspase-1, IL-1β and GSK-3β expressions in MI group were clearly increased (P<0.01) compared with those in sham group.These indicators were significantly decreased in SB+MI group (P<0.01). Interestingly, the indicators were all higher at 7 days than 2 days. CONCLUSION GSK-3β inhibition induces cardioprotection via attenuating the activation of NLRP3 inflammasome after the acute myocardial infarction in rats.

Objectives To investigate the relationship between single nucleotide polymorphism (SNP)H558R in SCN5A gene and chronic Keshan disease (KSD) complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD complicated with hypertension.MethodsThirty nine patients with chronic KSD complicated with hypertension and 63 geographical region matched hypertension control subjects were recruited in our study in Fuyu county,Qiqihaer city,Heilongjiang province between 2006 and 2010.H558R polymorphism in case and control groups was genotyped using the polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) and sequenced,and electrocardiography(ECG) characteristics were examined in the two groups.Case-control study analytical methods were applied to analyze the relationship between H558R and chronic KSD complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD patients complicated with hypertension.Results Subjects of genotype 558 TC in the case group had a decreased risk of chronic KSD complicated with hypertension with odds ratio of 0.288[95％ confidence interval (CI):0.104 - 0.794],and subjects of genotype TC in chronic KSD complicated hypertension patients had a decreased risk of QRS prolongation with odds ratio of 0.061 (95％CI:0.006 - 0.612).Conclusions Polymorphism H558R in SCN5A gene may be a predisposition factor of chronic KSD complicated with hypertension and occurrence of arrythmia in chronic KSD complicated with hypertension.