OBJECTIVETo study the effects of Jisuikang (Chinese characters) on Nogo-NgR gene expression, and to explore the protective effects and mechanism of Jisuikang (Chinese characters) on spinal cord injury in rats.

METHODSOne hundred eighty female rats were randomly assigned to 6 groups(30 rats per group). Sham group: T10 lamina was resected only and spinal cord was untreated. Model group: spine cord injury (SCI) was created with a modified impinger of Allen's by impacting on the T10 spinal cord. Prednisolone group: Prednisolone (0.06 g/kg) was given by intragastric administration at a time interval of 24 hours after operation. The Jisuikang (Chinese characters) high, moderate and low dose groups: Jisuikang (Chinese characters) was supplied with different dose (50 g/kg, 25 g/kg, 12.5 g/kg) by intragastric administration in rats after operation,for the first time at 30 min after surgery. Animals were killed 3, 7, 14 days after surgery. The expression levels of Nogo-A and NgR were observed by Western Blot and Real-time PCR.

RESULTSThe expression of Nogo-A and NgR was at the basic level at all time points in sham group. Compared with model group, the protein expression levels of Nogo-A and NgR in sham, prednisolone, Jisuikang (Chinese characters) moderate dose groups were statistically significant at all time points (P < 0.05). No difference was found in Jisuikang (Chinese characters) high and low dose groups (P > 0.05). Three days after surgery, the mRNA levels of Nogo-A and NgR in treatment group were significantly lower than that in model group (P < 0.01); 7 days after surgery,Nogo-A and NgR mRNA expression were dramatically upregulated and peaked; 14 days after operation, the expression was decreased, but still significantly higher than that in other treatment groups (P < 0.01). Prednisolone and Jisuikang (Chinese characters) moderate dose groups showed the most significant effects among all groups,but there was no statistically significant difference between two groups (P > 0.05).

CONCLUSIONThe decoction Jisuikang (Chinese characters) can promote the nerve cell regeneration by regulating Nogo-A and NgR gene expression, activating Nogo- NgR signaling pathways after acute spinal cord injury.

Animals ; Female ; GPI-Linked Proteins ; analysis ; genetics ; physiology ; Medicine, Chinese Traditional ; Myelin Proteins ; analysis ; genetics ; physiology ; Nerve Regeneration ; drug effects ; Nogo Proteins ; Nogo Receptor 1 ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; analysis ; genetics ; physiology ; Signal Transduction ; drug effects ; Spinal Cord Injuries ; drug therapy ; metabolism

OBJECTIVETo determine the role of extracellular signal-regulated kinase (ERK1/2) and p38 cascades in P2Y receptor-evoked effects on prostatic cancer cells.

METHODSHighly metastatic prostatic cancer cells 1E8 were transfected with dominant-negative MAPK kinase 1 (KA-MEK1). The activation of ERK1/2 was determined by Western blot technique. The role of ERK1/2 and p38 cascades in P2Y receptor-evoked effects on in vitro growth, colony formation and in vitro invasion was detected by cell count, soft agar colony formation assay and in vitro invasion assay. The effect of ATP on apoptosis was detected by flow cytometry.

RESULTSERK1/2 activity in 1E8-KA-MEK1 transfectants was significantly suppressed by dominant-negative MEK1 transfection. After culture of 6 days, 1E8-KA-MEK1 transfectants exhibited a growth inhibition of 71% as compared with 1E8-pcDNA3 control. Moreover, after continuous treatment with 100 micro mol/L ATP for 6 days, the growth of 1E8-KA-MEK1 transfectants was further inhibited by an additional 17.2%. Pretreatment with 10 micro mol/L p38 inhibitor SB203580 antagonized the effect of ATP-induced additional growth inhibition, suggesting that ERK1/2 and p38 pathways play an important role in ATP-induced growth inhibition. In soft agar assay, 1E8-KA-MEK1 transfectants formed smaller colonies and exhibited a 75% decrease in colony formation (as compared with control). Further treatment with ATP or SB203580 plus ATP did not show significant effect on colony formation of 1E8-KA-MEK1 cells, implying a potential role of ERK1/2, instead of p38, in P2Y receptor-mediated inhibitory effect on colony formation. In in vitro invasion assay, 1E8-KA-MEK1 cells showed a 41% decrease in passing through matrigel-coated membranes, as compared with control. Treatment with ATP could restore their invasive ability, and this effect by ATP could be blocked by pretreatment with SB203580, indicating the involvement of both ERK1/2 and p38 pathways in invasive ability of prostatic cancer cells.

CONCLUSIONSThe effects of ATP on in vitro growth, invasion and colony formation of prostatic cancer cells depend on the status of P2Y receptor activation by different treatment protocols. Continuous activation of P2Y receptor results in growth inhibition and transient activation of P2Y receptor stimulates in vitro invasion of prostatic cancer cells. Both ERK1/2 and p38 pathways are responsible for these effects; but only the ERK1/2 pathway is involved in regulation of colony formation of prostatic cancer cells.

Adenosine Triphosphate ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Imidazoles ; pharmacology ; MAP Kinase Kinase 1 ; metabolism ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Neoplasm Invasiveness ; Prostatic Neoplasms ; enzymology ; pathology ; Pyridines ; pharmacology ; Receptors, Purinergic P2 ; metabolism ; physiology ; Transfection ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors

BACKGROUNDIncretin-based therapies provide additional options for treating type 2 diabetes. We aimed to evaluate the efficacy and tolerability of exenatide monotherapy in obese patients with type 2 diabetes.

METHODSA 26-week, metformin controlled, parallel-group study was conducted among antidiabetic drug-naive obese patients aged > 18 years, and with type 2 diabetes. Participating patients were randomly assigned to receive exenatide or metformin treatments.

RESULTSFifty-nine patients (age (50.5 ± 8.6) years, body mass index (BMI) (30.2 ± 1.6) kg/m(2), and hemoglobin A1C (HbA(1C) (8.2 ± 1.2)%) were enrolled in the study. Glucose control and weight reduction improved in both groups receiving treatment. HbA(1C) and oral glucose tolerance test (OGTT) 2 hour glycemia reduction with exenatide was superior to that obtained with metformin ((-2.10 ± 1.79)% vs. (-1.66 ± 1.38)%, (-5.11 ± 2.68) mmol/L vs. (-2.80 ± 2.70) mmol/L, P < 0.05). Fast plasma glucose (FPG) reduction was not significantly different between the two groups ((-1.8 ± 2.0) mmol/L vs. (-1.6 ± 1.7) mmol/L, P > 0.05). Patients treated with exenatide achieved HbA(1C) of < 7% (97% of patients) and < 6.5% (79%) at end-point, vs. 93% and 73% with metformin (P > 0.05). Greater weight reduction was also achieved with exenatide ((-5.80 ± 3.66) kg) than with metformin ((-3.81 ± 1.38) kg, P < 0.01). Homeostasis model assessment of beta-cell function (HOMA-B) was not significantly increased, but the insulinogenic index and HOMA for insulin sensitivity (HOMA-S) were greatly improved in the exenatide group (P < 0.05). Nausea was the most common adverse effect in exenatide treatment (30% vs. 8%; P < 0.05), but most cases were of mild to moderate intensity. One case in the exenatide group was withdrawn early because of severe nausea. Hypoglycemia events were often observed during the first 4 weeks, with 12% of patients in the exenatide and 3.2% in metformin groups, respectively (P < 0.05). No incidents of severe hypoglycemia were reported.

CONCLUSIONSExenatide demonstrated more beneficial effects on HbA(1C), weight reduction and insulin resistance during 26 weeks of treatment, but there were more hypoglycemic events and mild-to-moderate nausea compared with metformin. These results suggested that exenatide monotherapy may provide a viable treatment option in newly developed type 2 diabetes.

Adult ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemia ; chemically induced ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Insulin Resistance ; Male ; Metformin ; adverse effects ; therapeutic use ; Middle Aged ; Nausea ; chemically induced ; Obesity ; blood ; drug therapy ; Peptides ; adverse effects ; therapeutic use ; Venoms ; adverse effects ; therapeutic use ; Weight Loss ; drug effects

Testis specific serine/threonine protein kinase 4 (TSSK4) belongs to the TSSK family, and its members play an important role in spermatogenesis and/or spermiogenesis. Mouse TSSK4 has been reported to be expressed exclusively in the testis and can maintain its kinase activity through autophosphorylation at Thr-197. However, its biological function remains poorly understood. Here we found that GFP-TSSK4-overexpressed HeLa cells showed apoptotic bodies, indicating TSSK4 can lead to apoptosis in vitro. Furthermore, TSSK4 induced apoptosis in different cell lines including HeLa, Cos-7 and H1299 tested by flow cytometry but not its kinase-dead mutant TSSK4-K54M. TSSK4 knockout mice showed increased testes weight and decreased apoptotic spermatogonia and spermatocytes at 21st day after birth tested by TUNEL technology. So TSSK4 was able to induce cell apoptosis in vitro depending on its kinase activity, which leads to abnormal testes weight and apoptosis, shedding light on its function in the process of spermatogenesis and/or spermiogenesis.
Animals ; Apoptosis ; physiology ; Base Sequence ; Cell Line ; DNA Primers ; Flow Cytometry ; Humans ; In Situ Nick-End Labeling ; Male ; Mice ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases ; physiology

Objective To evaluate the significance of platelet function monitoring in anti -platelet treatment of acute myocardial infarction . Methods The platelet maximum aggregation rates ( MAR ) induced by arachidonic acid , adenosine diphosphate and collagen were detected in 60 cases of acute myocardial infarction .The platelet aggregation function was compared before and after anti -platelet therapy for 24 h and 1 week.The plasma concentration of clopidogrel acid was detected and the correlation between concentration of clopidogrel acid and platelet aggrega-tion was analyzed.Results The MAR induced by arachidonic acid , adenosine diphosphate and collagen were significantly decreased after an-tiplatelet treatment for 24 h( P<0.01 );but after 1 week, no further re-duce in platelet aggregation rate was found , which showed some tole-rance.After 24 h, patients with MAR decreased by more than 30% ac-counted for 36.5%, 40.4% and 21.2%, respectively induced by arachidonic acid , adenosine diphosphate and collagen; patients with MAR decreased by 10% -29% accounted for 30.8%, 25%, and 34.6%,respectively,andthosewithMARdecreasedlessthan10%accountedfor34.6%,36.5%and44.2%,re-spectively.During half year follow -up, 34% of patients showed reoccurrence of cardiovascular events , and 55% of them were found aggregation rate less than 30%.Conclusion The aggregation rates under induction of arachidonic acid, adenosine diphosphate and collagen are all less than 30%when adopting the same anti -palate regime, but the incidence of cardiovascular events increased significantly and the platelet aggregation function and blood concentration of clopidogrel acid has no correlation .

Objective To assess if the modulating effect of platelet-derived growth factor(PDGF)BB on p21~(WAF1) was mediated by upregulating transforming growth factor(TGF)-β_1 expression in vascular smooth muscle cells(VSMC).Methods TGF-β_1 mRNA and protein expressions were measured by reverse transeription-PCR and ELISA,the protein expressions of p21~(WAF1) and the downstream TGF-βsignalling including TGF-β type I receptor(ALK-5 in VSMC),Smurf2,pSmad2/3,Smad4,Smad7 were detected by Western blot.Results PDGF-BB significantly upregulated the expressions of TGF-β_1 at mRNA(0.79-fold)and protein(1.98-fold)levels in VSMC,significantly inhibited the expression of p21WAF1(-67±12)%,and enhanced the expressions of ALK-5,pSmad2/3,Smad4,Smurf2 protein by 1.21-fold.0.95-fold,0.69.fold and 2.55-fold respectively,inhibited Smad7 expression(-65±9)%,these alterations were partially restored by anti-TGF-β_1 neutralizing antibody.Conclusions These findings suggested that PDGF-BB inhibited p21~(WAF1) expression in VSMC partially through upregulating TGF-β_1 expression via PDGFBB and TGF-β signalling pathways.

Objective To provide the detailed anatomic data of clinoid space for skull base surgery. Methods The anatomical structures and the adjacent structures of anterior clinoid process and clinoid space of 10 adult cadaver head specimens were observed under operating microscope. Thin slices of 0.05 mm were gotten on axial, coronal and sagittal planes from 3 of these 10 adult cadaver head specimens by freezing drilling technique. Sequential tracking was performed to observe the anatomical structure of clinoid space. Results Clinoid space is an useful space after drilling the anterior clinoid process. On the base, there is strut, clinoid portion of ICA and the anterior roof of the cavernous sinus.Cranial nerves of Ⅲ, Ⅳ, Ⅴ and Ⅵ were found beside the anterior clinoid process. This sclices of 0.05 mm by freezing drilling technique could fully demonstrate the anatomical structures clinoid space.Conclusion Micro-sectional anatomical methods can demonstrate the anatomical characteristics of the clinoid space, which provides detailed anatomical data for skull base operation.

Anti-Bacterial Agents ; Child ; China ; epidemiology ; Drug Resistance, Bacterial ; genetics ; Erythromycin ; Humans ; Molecular Epidemiology ; Streptococcus pyogenes ; genetics ; isolation & purification ; pathogenicity ; Virulence Factors ; genetics

OBJECTIVETo investigate the efficacy and feasibility of duodenojejunal bypass(DJB)on non-severe obese patients with type 2 diabetes mellitus(T2DM).

METHODSThe body mass index (BMI), fasting plasma glucose(FPG), 2h-postprandial plasma glucose(2hPG), fasting insulin(F-ins), fasting c-peptide(F-CP), glycated hemoglobin and hypoglycemic agents dose changes were tested in 7 patients with non-severe obese T2DM undergoing DJB, preoperatively and within 24 weeks after surgery during the follow-up. Data were collected and the clinical outcomes of T2DM were analyzed.

RESULTSIn 7 cases of non-obese T2DM who underwent DJB, one patient was weaned off hypoglycemic agents with normal FPG, 2hPG and HbA1c postoperatively. Five required significantly lower dosage. No significant improvement in 1 case. Complete remission rate of hyperglycemia was 1/7, effective rate was 6/7, and effective rate of HbA1c was 5/7. No significant changes in BMI were observed between the preoperative and postoperative phases.

CONCLUSIONPlasma glucose level can be markedly reduced by duodenojejunal bypass in non-obese T2DM, independent of weight loss, and the mechanism remains unclear.

Adult ; Aged ; Bariatric Surgery ; methods ; Diabetes Mellitus, Type 2 ; surgery ; Duodenum ; surgery ; Female ; Follow-Up Studies ; Humans ; Jejunum ; surgery ; Male ; Middle Aged ; Obesity ; Treatment Outcome

OBJECTIVETo observe the morphological and molecular biological peculiarities of the experimental autoimmune prostatitis (EAP) rat model made by SC purified prostate protein twice with immune adjuvant.

METHODSMale rats were intradermally immunized with a saline extract of male rat prostate glands (RPG) in Freund's complete adjuvant (FCA) and Pertussis-Diphtheria-Tetanus vaccine 0.5 ml i.p. at the 0 and 30th day, and the concentrations of the extract were respectively 5 mg/ml, 10 mg/ml and 15 mg/ml. At the 45th day, the rats were sacrificed and the morphological and molecular biological changes of the prostate specimens were observed to determine the effective concentration of RPG for a successful model.

RESULTSThe expression of inflammation genes such as TNF-alpha, IL-1beta, IL-2 and iNOS obviously increased in the high-dosage model group; LM, EM and in situ hybridization revealed appearant chronic inflammation response, but this was not the case in the other two dosage groups.

CONCLUSION15 mg/ml RPG mixed with FCA (1:1) 1.0 ml SC with Pertussis-Diphtheria-Tetanus vaccine 0.5 ml i.p. was an effective dosage for the successful model in our experiment.

Animals ; Autoimmune Diseases ; immunology ; metabolism ; pathology ; Diphtheria-Tetanus-Pertussis Vaccine ; administration & dosage ; Disease Models, Animal ; Freund's Adjuvant ; administration & dosage ; Injections, Intraperitoneal ; Male ; Prostate ; metabolism ; pathology ; Prostatitis ; immunology ; metabolism ; pathology ; Proteins ; administration & dosage ; Rats ; Rats, Wistar