Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Animals, Newborn ; Cerebral Cortex ; cytology ; metabolism ; Drug Synergism ; Female ; Fentanyl ; administration & dosage ; pharmacology ; Male ; Midazolam ; administration & dosage ; pharmacology ; Neurons ; metabolism ; Patch-Clamp Techniques ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Voltage-Gated Sodium Channels ; drug effects

OBJECTIVETo explore the mechanism of male reproductive toxicity induced by acrylonitrile (ACN).

METHODSMale Sprague-Dawley rats were daily administrated ACN by intraperitoneal injection 5 times a week for 13 weeks at the dose of 0, 7.5, 15.0 and 30.0 mg/kg body weight, respectively. The rats were sacrificed and testes were removed at the end of 4, 8, 13 or 15 weeks, respectively. The activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of glutathione (GSH) and malonaldehyde (MDA) were detected in testes.

RESULTSFollowing ACN treatment of 4 weeks, the levels of GSH in ACN 15.0 mg/kg and 30.0 mg/kg group were (7.44 +/- 0.77) mg/g pro and (6.95 +/- 0.77) mg/g pro respectively, and the activity of GSH-Px was (70.89 +/- 4.01) U/mg pro in 30.0 mg/kg group, all of which were significantly higher than the control group (P < 0.05, P < 0.01). After 8 weeks, the levels of GSH decreased to (2.50 +/- 0.94) mg/g pro in ACN 30.0 mg/kg group (P < 0.01); the activities of SOD increased to (102.08 +/- 16.08) NU/mg pro and (113.30 +/- 17.20) NU/mg pro in ACN 15.0 mg/kg and 30.0 mg/kg group (P < 0.01). After 13 weeks, the levels of GSH declined in ACN 15.0 mg/kg and 30.0 mg/kg group, and the activities of GST decreased in ACN 30.0 mg/kg group, and of GSH-Px decreased in both doses group. However, the level of MDA [(0.68 +/- 0.16) nmol/mg pro] were significantly higher in 30.0 mg/kg group than that in control group [(0.38 +/- 0.12) nmol/mg pro] (P < 0.01). 2 weeks after stopping ACN treatment, the level of GSH restored to normal but the levels of MDA or the activity of GSH-Px in 30.0 mg/kg group were still higher or lower respectively than those of control (P < 0.05).

CONCLUSIONACN may impair the balance of antioxidant system, thus induce lipid peroxidation damage to rat testes.

Acrylonitrile ; toxicity ; Animals ; Dose-Response Relationship, Drug ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Glutathione Transferase ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Testis ; drug effects ; metabolism

Identification of genetic risk factors is the hotspot of adolescent idiopathic scoliosis (AIS). Through candidate gene approach and genome-wide association studies (GWAS), some genes were preliminary identified. To review AIS related genes,and construct the gene network map of AIS gene. We searched on NCBI PubMed and Web of Science database using search terms "adolescent idiopathic scoliosis" and "gene", to classify induction genes. We then constructed gene diagram using string-db. We found 35 AIS genes relating to connective tissue, nervous system active substances, melatonin synthesis and metabolism, puberty and growth, and genes whose function is unknown. Gene diagram shows that a network relationship between gene and other genes,in which IL6, ESR1, ESR2, VDR, TGFB1, IGF1 gene may as the key gene about AIS' genetic mechanism. Two sites of 3 GWAS results outside the network, it is suggesting new pathway that need to be explored. The study about AIS susceptibility gene is still preliminary, requiring in-depth research to identify the new networks.
Adolescent ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Insulin-Like Growth Factor I ; genetics ; Matrilin Proteins ; genetics ; Scoliosis ; genetics ; Transforming Growth Factor beta1 ; genetics

Neuritin is a new neurotrophic factor found recently. In order to identify the function of Neuritin clearly, the coding sequence of human neuritin was amplified by PCR from neuritin cDNA , this fragment digested by NocI and NotI was inserted into pET32a by T4 ligase and transformed into E. coli BL21 then the recombinant plasmid named pET32a-neuritin was constructed successfully . Neuritin was expressed distinctly after inducing by EPTG. The product was identified as neuritin by SDS-PAGE and Western blot analysis . The expression production was purified on Ni2+-NTA column.

The way of "extracting-salting-chromatography" was used to purify the phycoerythrin and phycocyanin from Porphyra yezoensis in process scale-up.First,by comprehensive comparison of efficiency,the Sephadex G-25 was selected from four resins (Sephadex G-25、G-100、S-300 and CL-6B) as the best choice used in crude extract desalting of phycobiliprotein.Then the preparation process of phycobiliprotein was scaled-up with raw material(Porphyra yezoensis) increased from 1g to 20g,and finally to 400g.The results indicated that the yields of purified phycoerythrin and phycocyanin (absorption spectra purity above 3.2) increased during according to process scale-up,with 0.323% phycoerythrin and 0.148% phycocyanin obtained from 400g frozen Porphyra yezoensis blades respectively.It is no doubt that the process involved in the experiment is a potential way for large scale preparation of phycobiliproteins of high purity.

Tumor angiogenesis provides adequate oxygen and nutrition for tumor development and supports tumor growth and metastasis. Stromal cell derived factor 1 (SDF-1) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) in pancreatic cancer microenvironment are involved in tumor growth such as promoting tumor cell proliferation, migration, and angiogenesis. In this study, anti-CXCR4 nanobody (CXCR4 Nb) and anti-programmed cell death ligand 1 (PD-L1) &CXCR4 bispecific nanobody (PX4 BsNb) were expressed in Escherichia coli system and purified by nickel column affinity chromatography. We investigated the anti-angiogenesis activity and mechanism of CXCR4 Nb by in vivo and in vitro experiments. Ethical approval was obtained for collection of human peripheral blood mononuclear cell (hPBMC) samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University. The results showed that CXCR4 Nb at 0.1 μmol·L^-1 could effectively inhibit the proliferation and migration of human umbilical vein endothelial cells (HUVEC) promoted by pancreatic stellate cells in vitro. CXCR4 Nb and PX4 BsNb at 0.3 mg·kg^-1 obviously decreased tumor angiogenesis and inhibited the tumor growth in NOD/SCID mice, the inhibitory rates were 28.8% and 36.1%, respectively. CXCR4 Nb significantly inhibited tumor growth and angiogenesis with great safety, which provides support for application of CXCR4 Nb and anti-angiogenesis therapy of pancreatic cancer.

Objective The aim of this trial is to compare the efficacy and safety between national-made and imported ablation catheters for the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT). Method A total of 1342 patients with AVNRV or AVRT were randomly treated with national-mode ablation catheter (Group 1, n = 672) or imported ablation catheter (Group 2, n=670). Results The immediate ablation success rate was similar in Group 1 and Group 2 (97.9% vs. 99.1%, P > 0.05). There were also no significant differences in the procedure time [(68±36) min vs. (67±34 ) min], the fluoroscopic time [(14±14) min vs. (10±11) min], the number of energy delivery [(4.5±4.5) beats vs. (4.6±3.9) beats], the ablation time [(260±218) s vs. (257±207) s] and the score of ablation catheter performance evaluation[(4.4±0.5) vs. (4.5±0.4)] between the two groups (all P > 0.05). Three patients developed pericardial effusion (1 in Croup 1 and 2 in Group 2, P>0.05). Incidence of recurrence of tachycardia during the 3 months follow up was similar between the 2 groups (14 in Group1 vs. 16 in Group 2, P > 0.05). Conclusion National-made and imported radiofrequency ablation catheters have similar efficacy and safety for treatment of AVNRT and AVRT.

The purpose of this study was to investigate the repair of the osteoarthritis(OA)-induced cartilage injury by transfecting the new TGF-β3 fusion protein (LAP-MMP-mTGF-β3) with targeted therapy function into the bone marrow-derived mesenchymal stem cells (MSCs) in rats. The recombinant of pIRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector pIRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat embryos by RT-PCR and inserted into the upstream and downstream of MMP from pIRES-EGFP-MMP respectively, so as to construct the recombinant plasmid of pIRES-EGFP-LAP-MMP-mTGF-β3. pIRES-EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cultured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction (ACLT). The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Green and graded by Mankin's scale. pIRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein (39 kD) was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.

OBJECTIVETo explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.

METHODSSixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.

RESULTSDutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).

CONCLUSIONDutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.

Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism