PNAS-4 is a novel pro-apoptosis gene identified latetly. In recent years, there has been a large number of research reports on the basic studies about PNAS-4 in cancer gene therapy and gene therapy of PNAS-4 alone or combined with chemotherapy or radiotherapy manifested a good application prospect, but its molecular mechanisms to promote apoptosis is not clear yet. In this paper, recent research about PNAS-4 in cancer gene therapy is briefly reviewed, and recent hypotheses on its molecular mechanisms to promote apoptosis are especially elucidated. Based on its newly identified characteristics of structural domain, we made a point that PNAS-4 might regulate functions of some target protein related to apoptosis by deSumoylation as a new deSumoylating isopeptidase, and consequently promote apoptosis.
Apoptosis ; Apoptosis Regulatory Proteins ; genetics ; Genetic Therapy ; Humans ; Neoplasms ; therapy ; Sumoylation

Objective To compare the effect of natural antioxidants TA9001 and EGb761 on c-jun, NOS expression and survival of spinal motoneurons following brachial roots avulsion. Methods One hundred and eighty adult Sprague-Dawley female rats were randomly divided into TA9001, ECb761 and control groups. The right C 5～T 1 nerve roots were avulsed and then the introperitoneal injection of 1ml of 0.5% TA9001, 0.5% EGb761 or normal saline was given immediately and once daily to the rats, respectively. The rats were killed after survival for 4 h, 12 h 1 d,3 d,5 d,and 1 week, 2 weeks, 4 weeks and 6 weeks. The cryostat sections of C 7 segment were prepared and carried with c-jun immunocytochemistry, NADPH-d histochemistry and neutral red counter stain. Results The c-jun and nNOS gene expression was only appeared in injured motoneurons. c-jun was first appeared at 4 h, reached its maximum at 1 d, and grandually decreased till 2 weeks. NOS was first checked at 5 d, mostly at 2 weeks and decreased until 6 weeks. Avulsed motoneuron death started at 2 weeks, reached its peak at 4～6 weeks. Both TA9001 and EGb761 can cause c-jun up-regulation, nNOS down-regulation and more motoneuron survival as compared to control. Furthermore, EGb761 had more power to enhance c-jun expression than TA9901 at each time point. Conclusion It seems that nNOS is more important in motoneuron death mechanism than c-jun. Treatment of either TA9901 or EGb761 can protect the injured motoneurons following root avulsion.

Objective To evaluate the effect of vasodilators in different therapies on pulmonary hypertension of neonates. Methods Vasodilators were given by i.v infusion in the usual way and the air compressor pump was used as nebulizer to inhale Neb-NTG (20 ?g/kg) 2 times daily for 3 days. The changes of heart rate, breath, blood pressure and pulmonary artery mean pressure (PAMP) were monitored before and after the treatment. Results PAMP of the patients with abnormal heart structure was (31.7?6.4) mm Hg(1 mm Hg=0.133 kPa) while PAMP of the patients with oxygen deficiency was (26.9?4.2) mm Hg. There was a significant difference in PAMP between the two groups ( t=2.14,P 0.05 ). Conclusion Pulmonary artery pressure can be decreased by inhaling Neb-NTG and its therapeutic efficacy maybe equales that of vasodilators IV infusion. The nebulized inhalation of Neb-NTC may be an easy and effective therapy for the treatment of pulmonary hypertension in neonates.

Objective To detect the distribution of site-174G/C,site-572C/G and site-597G/A of interleukin-6 gene promoter regions in patients with endometriosis,and to analyze polymorphism of the promoter.Methods Interleukin-6 gene promoter region polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in patients with endometriosis(n=98)and normal controls(n=99).Among the 98 patients with endometriosis,22 were defined as stageⅡ,35 as stage Ⅲ and 41 as stage Ⅳ.Comparisons between the two groups on the genotype of IL-6 gene promoter and the distributed allele frequency were done,and also among the patients of stage Ⅱ,Ⅲ and Ⅳ once significant differences were detected in genotype frequency or allele frequency in disease group and control group.Results At the site-174,the frequencies of GG,GC and CC genotypes were 100%,0% and 0%,respectively,in patients with endometriosis,while 98.99%,1.01% and 0%,respectively,in normal controls.No significant difference was found in the distribution frequency of IL-6 genotype between patients with endometriosis and normal controls.At the site-572,the frequencies of CC,CG and GG genotypes were 55.10%,42.86% and 2.04%,respectively,in patients with endometriosis,while they were 70.71 %,28.28% and 1.01%,respectively,in normal controls.A significant difference existed between the two groups.At the site-597 of IL-6 gene,no GA and AA genotypes were found in the two groups.At the site-572,the frequencies of CC,CG and GG genotypes were 59.09%,40.90% and 0%,respectively,in patients with endometriosis of stage Ⅱ,54.29%,42.86% and 2.85% in patients of stage Ⅲ,and 53.66%,43.90% and 2.44% in patients of stage Ⅳ.No significant difference was found among the three groups.Conclusion Mutations at the sites-174 and-597 of IL-6 gene promoter region were rare.Their distribution frequencies have nothing to do with morbidity of endometriosis.While at the site-572,its distribution frequency of genotype shows correlation with morbidity of endometriosis but does not show correlation with the extent of endometriosis.

Objective To investigate some specific fluorescent substances in gastric juice from patients with gastric carcinoma and to establish biomarkers for the detection of gastric cancer. Methods We collected gastric juice from 10 patients with gastric carcinoma and 10 patients without gastric carcinoma respectively. After being condensed, the specimens of gastric juice were analyzed by means of high performance liquid chromatography (HPLC). We collected the specific fluorescent substance in the retention time of 11.5-12.5 min in fluorescence spectra of HPLC and then detected them through mass spectrometry. Comparing such spectra with those of L-tryptophan, we attempted to find the principle component of the fluorescent substances. Results There was a specific substance in gastric juice in the retention time of 11.5-12.5 min in fluorescent spectra of HPLC, which was more abundant in gastric malignancy than in gastric benigh diseases. With the mass charge ratio(m/z)of 205, the substance had the same mass spectrum as shown in the third level of L-tryptophan, which was confirmed by mass spectrometry. This substance was identified to be L-tryptophan. Conclusions L-tryptophan is one of the specific fluorescent substances in gastric juice from patients with gastric carcinoma.

BACKGROUND: Astrocyte distributes the most widely in the central nerve system,but the role of astrocyte in the pathogenisis of neurodegenerative diseases is still unclear.OBJECTIVE :To investigate the effects of lipopolysaccharide (LPS) on the level of the free intracelluar calcium, the production of reactive oxygen species (ROS) and nitric oxide (NO), and the cell viability of astrocytes.DESIGN: Randomized grouping controlled experiment.SETTING: The Brain Circulation Research Laboratory, Second Affiliated Hospital of Suzhou University.MATERIALS: The experiment was carried out in the Brain Circulation Research Laboratory, Second Affiliated Hospital of Suzhou University from May 2005 to August 2005. The astrocytes were derived from the cerebral cortex of 8 Newborn SD rats aged 1-3 days provided by the Animal Experimental Center of Suzhou University. LPS was purchased from Sigma, MTT assay kit and NO assay kit were obtained from Beyotime Biotechnology.METHODS: The astrocytes were isolated and cultured using the method described by Kevin St. P. McNaught. The cells were purified by proliferation repeatedly. Astrocytes were divided into control group, LPS5, 10, 20,40 mg/L group according to different dosage of LPS added. The cell viability at 30 min and 60 min respectively was measured using MTT method.The NO accumulation in cultured cell supernatant at 30 min was assayed with Griess reagent after the treatment of LPS. Calcium and ROS accumulation in cultured astrocyte of rats stimulated by different dosage of LPS was measured at 30 min and 60 min respectively by confocal laser scan microscope (CLSM).MAIN OUTCOME MEASURES: Cell viability of astrocyte, the change of level of NO, calcium and reactive oxygen species of astrocyte.RESULTS: ① The cell viability 60 min after administration of LPS 5 mg/L,LPS 10 mg/L and LPS 20 mg/L was higher than that of control group(P ＜ 0.05). The cell viability of LPS 10 mg/L group was higher than that of LPS 5, 20 mg/L group.② NO production 30 min after LPS treatment of LPS 40 mg/L group was higher than control and the other 3 experimental groups (P ＜ 0.05 ). ③ The calcium of the LPS 5, 10 and 20 mg/L group was 200-400 times higher than that of the base state. The calcium of the LPS 40 mg/L group was 1 000 times than its baseline state; Absolute fluorescence intensity of ROS was superior than the detect range of CLSM, we could speculate that the relative fluorescence intensity of the group LPS 40 mg/L was at least 300-400 times higher than that of its base state.CONCLUSION: LPS could increase the level of the free intracelluar calcium and induce the production of ROS and NO in astrocytes.

Objective To evaluate the impact of influenza virus hemagglutitin (HA) 306-318 peptide on T cell activation and to investigate the inhibitory effect of the altered HA306-318 peptide on T cell proliferation. Methods HA306-318 peptide and its mutant containing amino acid substitutions were synthesized. They were used in T cell activation assay using HLA-DR1 transfected cells. Responses were determined by MTT proliferation assays. The HA mutant without stimulating effect on T cells was then examined by inhibiting HLA-DR1-restricted T cell activation. Results It was demonstrated in this study that the altered HA306-318 peptide bound to HLA-DR1 molecule on L57.23 cells transfected with HLA-DR1 cDNA, but not on the control cells. The altered HA306-318 peptide had no stimulating effect on T cells compared with the wild type HA306-318 which induced T cell proliferation. It was shown that the altered HA peptide inhibited T cell activation mediated by wild type HA306-318 as well as by CⅡ263-272 which was the specific T cell antigen. Conclusions This study suggests that HA306-318 peptide is antigenic and can induce responses in HLA-DR1 specific T cells. Altered HA306-318 peptide is hyporesponsive in T cell activation with inhibitory effect on antigen-driven T cell responses, and it is potentially a therapeutic agent in rheumatoid arthritis.

Objective To summarize clinical imaging characters of the gastric lymphoma in gastroscopy and double contrast radiography of upper gastrointestinal tract.Methods We reviewed 24 cases of gastric lymphoma from January 1996 to June 2006 and analyzed their endoscopic and X-ray features,as well as their pathological results.Results The most frequently involved parts were gastric body(75%,18 cases) and antrum(67%,16 cases).The most common changes were: ①ulcer(71%,17 cases),especially multiple shallow ulcers which had different forms;②nodular protuberance(67%,16 cases),sometimes submucous giant protuberance;③giant duplicature(54%,13 cases);and ④involvement spreading along the gastrointestinal tract(21%,5 cases).Conclusions The characters of gastric lymphoma are ulcer,nodular protuberance,giant duplicature,and so on.The combination use of gastroscopy,radiography,endoscopic mucosal resection,endoscopic ultrasound,and laparoscopy is important for definite diagnosis.

AIM: To explore the expression changes of bone morphogenetic protein-7 (BMP-7) and its receptors (BMPR-Ⅱ, ALK-2, ALK-3, ALK-6) in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction (UUO). METHODS: Rats were divided into normal control, sham operation and UUO groups, and sacrificed at postoperative day 1, 3, 7 and 14. The mRNA levels of BMP-7, BMPR-Ⅱ, ALK-2, ALK-3 and ALK-6 were examined by RT-PCR. The protein expression site and level of BMP-7 was detected by immunohistochemistry staining. RESULTS: Compared to sham operation group, the mRNA levels of BMP-7, BMPR-Ⅱ, ALK-2 and ALK-3 were significantly decreased, but the change of ALK-6 mRNA was not marked in UUO rats. The reduction of mRNA expression levels of BMP-7, BMPR-Ⅱ, ALK-2 and ALK-3 in the kidney tissue aggravated along with the delayed post-operated days. The results of immunohistochemistry staining indicated that BMP-7 mainly expressed in renal tubular and interstitial, rarely in glomeruli. In UUO rats, the protein expression of BMP-7 decreased in varying degrees according to the post-operated days. CONCLUSION: The loss of BMP-7 and its receptors (BMPR-Ⅱ, ALK-2, ALK-3) were observed in the early phase of fibrotic process and this may play a very important role in mediating the renal tubulointerstital fibrosis.

?Objective: To study the effect of glial cell line derived neurotrophic factor (GDNF) on facial nerve regeneration after injury.Methods:Defect of 5 mm was made in each facial nerve on both sides in 32 rabbits.Silicon tubes were used to bridge the defects.Pure GDNF (15 ?g in 30 ?l silane) was injected into silicon tube on one side and saline (30 ?l) on the other side as the control.Nerve regeneration was studied by morphological observation with HE and Bielschowsky stainning,counting of nerve neurons and axon and measuring of motor nerve conduction velocity.The rest 3 rabbits was as blank contol. Results:7 d and 17 d after operation ,the neuron number in GDNF treated and control groups were 39.2?2.3 and 28.4?1.9,and 33.6?2.1 and 27.1?1.4,respectively ( P