Objective To investigate the protective effect of c-jun N-terminal kinase (JNK)inhibitor SP600125 against acute liver failure in mice.Methods Fifty-five male C57/BL6 mice were divided into control group (n =30) and SP600125 group (n =25).The animals were given an intraperitoneal injection of D-galactosamine (D-GalN,400 mg/kg body weight)/lipopolysaccharide (LPS,30 μg/kg body weight).The control group and SP600125 group were given 10％ dimethyl sulfoxide (15 mL/kg body weight) or SP600125 (75 mg/kg body weight) subcutaneously 12 h and 1 h before D-GalN/LPS administration,respectively.D GalN/LPS induced mouse JNK activation was detected by immunohistochemistry for phospho JNK (p-JNK).D-GalN/LPS induced mouse liver cell apoptosis was detected by immunohistochemistry for Caspase-3 and TdT-mediated-dUTP nick endlabeling (TUNEL).Serum alanine transaminase (ALT) level was tested to assess liver injury.Survival rate of mice within 24 h after D-GalN/LPS administration was observed.The comparison between groups was done by t test and survival rate was analyzed by Kaplan-Meier method.Results JNK activity in liver tissues,as indicated by observation of p-JNK positive cells by immunohistochemistry,was diminished 4 h after D-GalN/LPS administration in SP600125 group.Reduced Caspase-3 activity was observed 6 h after D-GalN/LPS administration in SP600125 group (as indicated in immunohistochemistry by Caspase-3 positive cells).Mice in SP600125 group showed significantly lower TUNEL-positive cell count than control group (43.0±24.5 vs 194.7±73.8; t=9.743,P=0.000).Serum ALT level 6 h after D-GalN/LPS administration was (24.0±54.7) U/L in SP600125 group,which was significantly lower than that in control group [(1234.4±478.4) U/L; t=4.734,P=0.0015].SP600125 also significantly improved the survival rate within 24 h after D-GalN/LPS administration (4/5 vs 1/10； x2=5.225,P=0.0223).Conclusions JNK inhibitor SP600125 exerts protective effects against D-GalN/LPS induced acute liver failure in mice by suppressing JNK activation and hepatocyte apoptosis.

Objective To study their chemical components of xianglingcao(Crotalaria ferruginea) and identify their chemical structures.Methods The compounds were isolated by chromatography and their structures were identified by spectral analysis and compared with the published data.Results Ten compounds were isolated and identified as vomifolilol(Ⅰ),genistein(Ⅱ),p-hydroxybenzoic acid(Ⅲ),5,7-dihydroxy-4-methoxy-flavone-7-O-?-D-glycopyranoside(Ⅳ),octadecoic acid(Ⅴ),octacosanol(Ⅵ),?-stitosterol(Ⅶ),?-daucosterol(Ⅷ),stigmasterol(Ⅸ),and ?5,22 stigmasterol-3-O-?-D-glycopyranoside(Ⅹ).Conclusion The ten compounds are obtained from xianglingcao for the first time.

Background: Creatine transporter (CRTR) deficiency is the most common creatine deficiency syndrome, of which the final diagnosis relies on mutation in the X-linked CRTR gene. To date, more than 90 mutations in the SLC6A8 gene have been reported. This paper discusses a novel mutation detected via the thorough sequencing of all the X-chromosome-specific exons investigated in a four and a half year old boy with an intellectual disability, speech and language delay and motor disturbance. Methods: A brain magnetic resonance imaging (MRI) and a proton magnetic resonance spectroscopy (MRS) were carried out, the creatine and creatinine concentrations in the urine were checked and all exons were sequenced. Results: A detailed clinical investigation revealed a reduction in the cerebral creatine levels in the brain by the MRS, elevated creatine and creatinine concentrations in the urine and signal abnormalities in the left frontal cortex of the brain by the MRI. A novel change was identified in the heterozygosity of the exon 10: c.1395-c.1401 deletion. Conclusion: The use of a combination of powerful new technologies, such as thorough exome-nextgeneration sequencing and a brain MRS, should be considered, in order to determine any neurometabolic diseases, especially when the signal abnormalities in the brain MRI cannot be explained by any other factors. This mutation results most likely in a dysfunction of the creatine transport and synthesis, hence causing central nervous system symptoms.
Carrier Proteins

[Summary] The aim of this study was to examine the association between obstructive sleep apnea-hypopnea syndrome ( OSAHS ) and microalbuminuria in type 2 diabetes mellitus patients. We found that severe OSAHS significantly increases the risk of early renal damage in type 2 diabetes mellitus patients with HbA1C<7% ( lowest oxygen saturation:OR=2. 41, 95% CI 1. 19-8. 08; apnea hyponea index: OR=2. 91, 95% CI 1. 50-9. 11), suggesting that OSAHS may increase the risk for early renal damage in type 2 diabetes mellitus, especially in those with successful control of glucose.

OBJECTIVETo investigate the impact of sodium nitroprusside (a nitric oxide donor) in the ductus arteriosus in preterm rabbits on hydrogen sulfide (H(2)S)-cystathionine-γ-lyase (CSE) system.

METHODSFor 16 Japanese white rabbits pregnant for 21 days were randomly divided into four groups, each of the following groups had 4 rabbits: control group, intraperitoneal injection of sodium nitroprusside 1 mg/kg, 2.5 mg/kg, and 5.0 mg/kg groups. The rabbits in control group had a peritoneal puncture with a simple hollow needle, and those in the other groups were given corresponding dose of intraperitoneal injection of sodium nitroprusside at gestational age 23 and 25 days, respectively. At gestational age 26 days the fetuses of the pregnant rabbits were removed surgically, and 28 fetal rabbits were obtained from the control group, 27 from the sodium nitroprusside small dose group, 29 from the medium dose group, and 26 from the large dose group. The fetal heart blood sample of 1 ml was taken from each fetus, and immediately after sampling the arterial ductal tissues were dissected. Fetal rabbit plasma proteins hydrogen sulfide content was determined by using de-protein method, and real time quantitative RT-PCR was used for determination of arterial tissue CSE gene and western-blotting was used for measuring protein expression of CSE.

RESULTSIn control group hydrogen sulfide content of fetal rabbits plasma (55.68 ± 6.57) µmol/L and arterial tissue CSE mRNA expression was 1.07 ± 4.12; the parameters in intraperitoneal injection of sodium nitroprusside group 1 mg/kg were (60.02 ± 6.09) µmol/L and 3.46 ± 0.18; in intraperitoneal injection of sodium nitroprusside group 2.5 mg/kg, were (64.71 ± 7.12) µmol/L and 10.95 ± 0.22; and in intraperitoneal injection of sodium nitroprusside group 1 mg/kg were (70.63 ± 8.07) µmol/L and 19.56 ± 0.17. Comparison between small dose group and control group, medium dose group and small dose group, high dose group and medium dose group showed that the above data were significantly different P < 0.05, with the injection of sodium nitroprusside CSE protein expression increased gradually with increasing doses.

CONCLUSIONSodium nitroprusside showed an enhancing effect on preterm CSE-H(2)S system in rabbit ductus arteriosus in a certain range of concentration in a dose-dependent manner.

Animals ; Cystathionine gamma-Lyase ; blood ; Ductus Arteriosus ; metabolism ; Female ; Hydrogen Sulfide ; blood ; Nitric Oxide ; blood ; Nitroprusside ; administration & dosage ; pharmacology ; Pregnancy ; Rabbits

In order to demonstrate PTB bind to HPRE,reverse transcription,PCR-mediated detection,were used.HepG2.2.15 cell line and HBs-HPRE transient expression cells were adopted to identify PTB function in HBV life cycle.The results showed that PTB could directly bind to HPRE RNA.Functional analysis indicated that PTB could inhibit the expression of HBs antigen and this inhibition was in a dose-dependent manner in HepG2.2.15 cells.Higher expression of HBs in cells transfected pcDNA3-HBs-HPRE comparing with pcDNA3-HBs,and this high expression could also be inhibited by PTB.The data demonstrated that PTB inhibits HBs expression by interacting with HPRE.

OBJECTIVETo explore the experience on venoarterial extracorporeal membrane oxygenation (ECMO) in adult patients with cardiac failure.

METHODSFrom February 2005 to June 2008, 45 patients (male 34, female 11) undergoing cardiogenic shock required temporary ECMO support. Average age was (49.0 +/- 14.1) years. Average body weight was (67.0 +/- 12.8) kg. Coronary heart disease occupied in 21 cases, valve disease occupied in 8 cases, and cardiomyopathy occupied in 7 cases. All the patients could be divided into 3 groups: post-cardiotomy (group 1, n = 31), post-transplantation (group 2, n = 5), decompensate of chronic heart failure (group 3, n = 9). Fourteen patients need cardiac resuscitation before ECMO support. ECMO implantation was performed through the femoral vessels or axillary artery or through the right atrium and ascending aorta.

RESULTSAverage support duration of ECMO was (126.7 +/- 104.3) h. Twenty-seven patients could be successfully weaned from support (60.0%), additionally, 5 were bridged to heart transplantation. The in-hospital mortality was 42.2% (19/45). Twenty-six patients (57.8%) could be successfully discharged. The discharge rate was 58.1% in group 1, 4/5 in group 2 and was 4/9 in group 3. Twelve patients were re-operated for hemostasis. Three patients need femoral arterial thrombectomy because of ischemia of lower extremity. Additional intra-aortic balloon pumps were used in 11 patients, with 6 patients successfully discharged. The mortality rate for patients with acute renal failure treated by continuous renal replacement therapy under ECMO support was obviously high (7/9). The dominant mode of death was multisystem organ failure (9/19).

CONCLUSIONEarly indication, control of complications, and paying attention to the treatment after ECMO support could improve our results with increasing experience.

Adolescent ; Adult ; Aged ; Extracorporeal Membrane Oxygenation ; Female ; Heart Failure ; therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the feasibility of reconstruction of rabbit urethra using urethral extracellular matrix.

METHODSExtracellular matrix was obtained from the urethra of 20 donor New Zealand rabbits. In experimental group, 20 rabbits underwent segmental urethral resection (about 1.0 to 1.5 cm in length) and the defects were replaced by a tube of extracellular matrix. The serum TNFalpha was detected by ELISA to assess the immunity response preoperatively and 12, 24, 48 h postoperatively. The regenerated urethral segments were taken for histologic and pathologic study 10 days, 3 weeks, 6 weeks and 24 weeks after operation. The urodynamics, urethroscopy and urethrography were also performed.

RESULTSThe serum TNFalpha in experiment group slightly rised, with no significant difference when compared with that in control group. 10 days after operation, epithelial cell migrated into the extracellular matrix from two ends, and small vessels were also found. 3 weeks later, several layers of urothelium covered the whole surface of the matrix tube. 6 weeks later, the irregularly arranged smooth muscle fibers were fist observed by Van Gieson staining. 24 weeks after operation, the smooth muscle cells increased, the appearance of the regenerated urethra segments were very similar to normal urethral wall components. The urethrography and urodynamic evaluation revealed no difference between the normal and the regenerated urethral tube.

CONCLUSIONSThe urethral extracellular matrix might be an ideal replacement material for urethral defect.

Absorbable Implants ; Animals ; Biocompatible Materials ; Extracellular Matrix ; transplantation ; Male ; Rabbits ; Reconstructive Surgical Procedures ; methods ; Regeneration ; Tumor Necrosis Factor-alpha ; metabolism ; Urethra ; surgery

OBJECTIVETo investigate the curative effect and histocompatibility of reconstruction of traumatic urethral defect of rabbit using urethral extracellular matrix (ECM).

METHODSUrethral ECM was obtained by excision of the urethra in 20 donor rabbits. In experimental group, 20 rabbits were resected a 1.0 cm-1.5 cm segment of the urethra and artificially made a model of traumatic urethral defect, then reconstructed by the urethral extracellular matrix of the same length. The rabbit immunity response was assessed by lymphocyte transformation test and serum TNF-alpha level. The reconstructed urethral segments were stained with hematoxylin-eosin and Van Gieson stain and observed by histological examination postoperatively. The urethrography, urethroscopy and urodynamic examinations were performed.

RESULTSThere was no significant difference in stimulative index of lymphocyte transformation between ECM group and control group. The serum TNF-alpha levels of ECM group slightly rose, but the increase was not significant as compared with control group. On postoperative day 10, epithelial cell had migrated from each side and small vessels were found in the extracellular matrix. In the 3rd week, several layers of urothelium covered the whole surface of the matrix tube. In the 6th week, the disorganized arrangements of smooth muscle fibers were firstly observed by Van Gieson staining. In the 24th week, the smooth muscle cells increased and the matrix tube appeared fairly similar to normal urethral wall components. The urethroscopy and urodynamic evaluation revealed that the surface of reconstructed urethra was smooth and emiction was unobstructed.

CONCLUSIONThe urethral extracellular matrix might be an ideal and safe biomaterial for the reconstruction of urethral traumatic defect.

Animals ; Extracellular Matrix ; immunology ; physiology ; Female ; Immunohistochemistry ; Lymphocyte Activation ; Rabbits ; Reconstructive Surgical Procedures ; methods ; Tumor Necrosis Factor-alpha ; blood ; Urethra ; immunology ; injuries ; surgery

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.
Anti-Bacterial Agents ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Ciprofloxacin ; analogs & derivatives ; Fluoroquinolones ; chemical synthesis ; pharmacology ; HL-60 Cells ; Humans ; Ketones ; pharmacology ; Structure-Activity Relationship