Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Choristoma ; complications ; Cleft Palate ; complications ; Humans ; Salivary Glands ; Tongue ; abnormalities

Objective To investigate the effect of 2-methoxyestradiol (2ME2) on phosphorylation of Tau protein (p-Tau) and mortor function of rats after spinal cord injury (SCI).Methods A total of 72 adult male Sprague-Dawley rats were randomly divided into 3 groups:sham-operated group (n=24),SCI group (n=24) and SCI+2ME2 treated group (n=24); models of SCI were created by modified Allen's method; one d after SCI,rats in the SCI+2ME2 treated group were given intraperitoneal injection of 2ME2 (24 mg/kg) for seven d,and rats in the SCI group were given the same volume of normal saline.Basso,Beatti,Bresnahan (BBB) scale was performed to evaluate the hindlimb function one,three,seven,14,21 and 28 d after SCI; the expression changes ofp-Tau (Ser 262) seven d after SCI were observed by immunofluorescence and Western blotting.Results BBB scale scores in the SCI group and SCI+2ME2 group were significantly increased following the prolonging of injury times (1-28 d of injury,P＜0.05); on the 7th,14th,21st and 28th d of injury,the scores in the SCI+2ME2 group were significantly higher than those in the SCI group (P＜0.05).The p-Tau positive cells in the spinal cord and the p-Tau (Ser 262) expression in the SCI group and SCI+2ME2 group were significantly increased as compared with those in the sham-operated group (P＜0.05),and those in the SCI+2ME2 group (19.05± 1.34 and 0.283±0.094) were obviously lower as compared with those in the SCI group (10.36±1.28 and 0.607±0.105,P＜0.05).Conclusion 2ME2 offers protection in rats with SCI by reducing the level of tau phosphorylation.

Objective To investigate the effect of propofol on the activation of c-Jun N-terminal kinase (JNK) in hippocampus following asphyxial cardiac arrest-resuscitation in rats.Methods Forty male Sprague-Dawley rats,aged 6 months,weighing 350-380 g,were randomly divided into 4 groups (n =l0 each):sham operation group (group S),asphyxial cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR),propofol group (group P) and normal saline group (group NS).All the rats were tracheostomized and mechanically ventilated after anesthetization.Cardiac arrest was induced by clamping the tracheal tube at the end of exhalation until ECG activity disappeared and MAP ＜ 10 mm Hg.Resuscitation was started 3 min later.MAP ＞ 60 mm Hg and HR ＞ 250 bpm were considered to be signs of successful resuscitation.Propofol 2 mg/kg was injected intravenously at 30 min before asphyxia,followed by propofol infusion at a rate of 4 mg· kg-1 · h-1 until the start of resuscitation in group P,while the equal volume of normal saline was given in group NS.At 12 h after successful resuscitation,the animals were sacrificed and brains were harvested for determination of wet/dry brain weight (W/D) ratio in brain tissues and expression of phosphor-JNK (p-JNK) in hippocampus (by immuno-histochemistry and Western blot),and for examination of the pathological changes of hippocampus.Results Compared with group S,W/D ratio was significantly increased and the expression of p-JNK in hippocampus was up-regulated in CA-CPR,P and NS groups (P ＜ 0.05 or 0.01).Compared with group CA-CPR,W/D ratio was significantly decreased and the expression of p-JNK in hippocampus was down-regnlated in group P (P ＜ 0.05 or 0.01),and no significant change was found in the indexes mentioned above in group NS (P ＞ 0.05).The pathological changes of hippocampus were significantly attenuated in group P compared with group CA-CPR.Conclusion Propofol can inhibit the activation of JNK in hippocampus following asphyxial cardiac arrest-resuscitation in rats and thus reducing brain injury.

Objective To evaluate the role of JNK signal pathway in brain injury after resuscitation in a rat model of asphyxia cardiac arrest.Methods Forty healthy male SD rats 'weighing 300-350 g were randomly divided into 4 groups ( n =10 each):sham operation group (group SH) ; cardiac arrest group (group CA) ; group SP600125-JNK inhibitor (group SP) and dimethyl sulfexide (DMSO) group.The rats were anesthetized with intraperitoneal pentobarbital 45 mg/kg,tracheostomized and mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Femoral artery and vein were cannulated for BP monitoring and fluid infusion.Cardiac arrest was induced by clamping tracheal tube until ECG activity disappeared and MAP ＜ 10 mm Hg.Resuscitation was started at 3 min after cardiac arrest.MAP ＞ 60 mm Hg and HR ＞ 250 bpm were considered to be signs of successful resuscitation.SP600125 20 mg/kg and DMSO 0.2 ml were injected iv as soon as chest compression was started in groups SP and DMSO respectively.The animals were sacrificed at 5 h after successful resuscitation and their brains were removed for determination of wet/dry (W/D) weight ratio and microscopic examination of hippocampus.Neuronal apoptosis was detected by TUNEL.Results Cardiac arrest significantly increased W/D ratio and the number of apoptotic cells in group CA.SP600125 iv significantly attenuated the cardiac arrest-induced increase in W/D ratio and the number of apoptotic cells but DMSO did not.Conclusion JNK signal pathway is involved in the brain injury after resuscitation in a rat model of asphyxia cardiac arrest.

ObjectiveTo investigate the effect of dexamethasone on mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in lung tissues in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).MethodsFifty-four male SD rats weighing 180-230 g were randomly divided into 3 groups:control group (group C,n =6) ;ALI group ( n =24) and dexamethasone group (group D,n =24).LPS 5 mg/kg was injected via tail vein in groups ALI and D,while the equal volume of normal saline was given in group C.Dexamethasone 6 mg/kg was injected intraperitoneally at 30 min before LPS administration in group D.Eight rats in each group were sacrificed at 1 h after normal saline administration (T1) in group C and at 1,3,and 6 h after LPS administration (T1-3 ) in groups ALI and D.The lung tissues were then removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) and MKP-1.The concentrations of albumin and TNF-α in bronchoalveolar lavage fluid (BALF) were detected and histopathological changes were observed at T3 ·Another 32 SD rats weighing 180-230 g were randomly divided into 2 groups ( n =16 each):group ALI1 and group D1.The rats were treated as the method mentioned above and the 48 h survival condition was observed.Results Compared with group C, the concentrations of protein and TNF-α in BALF were significantly increased,p-p38MAKP expression was up-regulated at T1.3,and MKP-1 expression was down-regulated at T2,3 in group ALI,and TNF-α concentration in BALF was significantly increased and the expression of p-p38MAKP and MKP-1 was up-regulated at T1-3 in group D ( P ＜ 0.05).Compared with group ALI,the concentrations of protein and TNF-α in BALF were significantly decreased,p-p38MAKP expression was down-regulated and MKP-1 expression was up-reg-ulated at T1-3 ( P ＜ 0.05 ),and the pathological damage was attenuated in group D.The 48 h survival rate was significantly higher in group D1 than in group ALI1 ( P ＜ 0.05).ConclusionThe mechanism by which dexamethasone attenuates the ALI induced by LPS may be related to up-regulation of MKP-1,inhibition of phosphorylation of p38MAPK and decrease in inflammatory response.

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) in lipopolysaccharide (LPS)-induced acute lung injury ( ALI) in rats.Methods Eighty male SD rats weighing 250-300 g were randomly divided into 4 groups ( n = 20 each) : control group (group C) ; ALI group; LPS + SP600125 (JNK inhibitor)group (group S) and LPS+ DMSO (the solvent) group (group DMSO) . ALI was induced by intravenous LPS 5mg/kg. In S and DMSO groups, SP600125 30 mg/kg and DMSO 0.2 ml were injected intravenously after LPS administration respectively. Ten animals were sacrificed by exsanguinafions at 4 h after LPS administration in each group. The broncho-alveolar lavage fluid (BALF) was colleted. The TNF-α and IL-1β concentrations in BALF were measured. The lungs were removed for microscopic examination and determination of W/D lung weight ratio. The other 10 animals in each group were observed for 48 h survival rate. Results Intravenous LPS significantly increased TNF-α and IL-1β concentrations in BALF and W/D lung weight ratio, decreased 48 h survival rate and induced histologic damage. Intravenous SP600125 30 mg/kg significantly attenuated the above-mentioned LPS-induced changes. Conclusion Activation of JNK is involved in the development of endotoxin-induced ALI in rats.

Objective To investigate the effects of sevoflurane anesthesia on the expression of c-Jun N-terminal kinase (JNK) and neuronal apoptosis in hippocampus in juvenile rats.Methods Forty healthy male SD rats, aged 30-35 days, weighing 100-110 g, were randomly divided into 2 groups (n = 20 each): control group (group C) and sevoflurane group (group S) . Group C inhaled a gas mixture of oxygen and air for 5 h and group S 3% sevoflurane for 5 h. The concentration of oxygen in both groups was maintained at 30% . Ten rats in each group were scarified at 1 h after regaining consciousness and the hippocampi removed for determination of phospho-JNK expression (by immuno-histochemistry and Western blot) and neuronal apoptosis (by TUNEL) . Another 10 rats were selected at 24 h after regaining consciousness to assess the cognitive function using Morris water maze. Results Compared with group C, phospho-JNK expression was significantly up-regulated, the number of apoptotic neurons increased, the latency prolonged and the duration of staying at the original platform quadrant shortened in group C ( P ＜ 0.05 or 0.01) . Conclusion Inhalation of 3.0% sevoflurane can induce neuronal apoptosis in hippocampus by activating JNK signaling pathway, thus leading to cognitive decline in juvenile rats.

Objective To evaluate the role of MLK3-MKK3/6-p38MAPK signal transduction pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Methods Seventy-eight healthy adult male SD rats weighing 200-250 g were randomly divided into 4 groups: control group (group C, n = 6), ALI group ( n =24), MLK3 inhibitor K252a group (group MK, n = 24) and p38MAPK specific inhibitor SB203580 group (group MS, n = 24). ALI was induced by iv injection of LPS 5 mg/kg via tail vein, while the equal volume of normal saline was given instead in group C. K252a 75 μg/kg and SB203580 10 mg/kg were injected intravenously via tail vein 30 min before LPS administration in group MK and MS respectively. The rats were killed at 1, 3, 6 and 12 h (T1-4) after LPS administration in group ALI, MK and MS (6 rats at each time point) and immediately after normal saline administration in group C. The lungs were removed for microscopic examination. The left lung was lavaged.The broncho-alveolar lavage fluid (BALF) was collected. The concentration of TNF-α in the BALF was determined by ELISA. W/D lung weight ratio was calculated. The expression of p-MLK3, p-MKK3/6 and p-p38MAPK were determined by Western blot. Results The concentration of TNF-α in the BALF, W/D lung weight ratio, and expression of p-MLK3, p-MKK3/6 and p-p38MAPK were significantly higher in the other three groups than in group C (P ＜ 0.01). The parameters mentioned above were significantly lower in group MK, and the concentration of TNF-α in the BALF, W/D lung weight ratio, and p-p38MAPK expression were significantly lower in group MS than in group ALI (P ＜ 0.05). The microscopic examination showed that LPS-induced ALI was less severe in group MK and MS than in group ALI. Conclusion MLK3-MKK3/6-p38MAPK signal transduction pathway plays an important role in LPS-induced ALI in rats.

Objective:To summarize the influencing factors and the preventative strategies of transurethral resection syndrome(TURS) in transurethral vaporization of the prostate(TVP). Methods:Among the consecutive 1360 patients who underwent TVP from Feb 1998 to 2004 Dec,using Circon vaporization device and vaporizaton-resection electrode,irrigating with 5% GS,TURS occured in 12 cases.The clinical materials were reviewed retrospectively. Results:At the end of operation,serum sodium declined and blood glucose rose apparently in the TURS cases.Of the 12 patients,mean operative time was 136 min(90-180min),prostate volume were Ⅲ?(50-75 g),perforation of the prostate capsule occurred in 8 cases,chill occued in 8 cases.TURS occurrence rate was relatively high in the high risk cases.The 12 patients were cured. Conclusion:The risk of TURS that still exists during TVP is relevant to: perforation of the prostate capsule,operative time,irrigating pressure,the high risk cases,prostate volume and(so on.)