1.Research progress of Nrf2/ARE pathway regulating mechanism
Tianjin Medical Journal 2015;43(5):573-575
Nuclear factor E2 related factor Nrf2 is a nuclear transcription factors involved in a variety of protein expression. As a center of oxidative stress regulation, it combines with antioxidant components (antioxidant responsive element, ARE) and activates downstream multiple anti-oxidation, anti-inflammatory and detoxifying enzyme protein expression. This signaling pathway is involved in the development of inflammation, tumor and other pathological process. This review describes the basic structure, biological effects and signaling pathways of Nrf2, summarizes the latest progress about mechanisms of factors, which are involved in the positive and negative regulations of signal pathway, providing a new target for anti-inflammatory, antioxidant, and antitumor biochemical treatment. Based on these, the paper also looks forward to applicating bioinformatics technology and providing better prospects for the development of target intervention.
2.Advances on the relationship between thrombin-activatable fibrinolysis inhibitor (TAFI) and recurrent pregnancy loss
Tianjin Medical Journal 2015;(3):327-329
Recurrent pregnancy loss (RPL) is a common complication of pregnancy, which affects 2%fertile women. A recent research has found that high level of thrombin-activatable fibrinolysis inhibitor (TAFI) can reduce the occurrence risk of early RPL. TAFI is one kind of carboxypeptidase, which can be activated as TAFIa. TAFIa can make the fibrinolysin lose its working site, which can interact with the fibrin to play a role in the regulation of fibrinolysis and the inhibition of throm?bus formation. The damage of fibrinolytic system is one of the risk factors for the occurrence of RPL in pregnant women, which has become one of the hotspots in the medical profession. In this paper, recent literature on TAFI and its relationship with recurrent pregnancy loss has been reviewed, hoping for new ways and clues in clinical treatment and prevention of RPL.
3.Comparison of efficacy and toxicity profile between intraperitoneal and intravenous topotecan in human ovarian cancer xenografts
Xiaofang YI ; Shiming FAN ; Ming YAO ; Youji FENG
Journal of Peking University(Health Sciences) 2006;38(1):88-91
Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.
4.Prognostic factors and survival of stage ⅠB-ⅡA cervical cancer
Xishi LIU ; Xiaofang YI ; Min ZHAO ; Sunwei GUO
Journal of Peking University(Health Sciences) 2006;38(1):80-87
Objective:This study investigated the prognostic significance of age at diagnosis, stage, tumor subtype, pelvic lymph node metastasis (PLNM), lymph-vascular space involvement (LVSI), presence or absence of deep cervical stromal invasion (DCSI) in stage ⅠB-ⅡA cervical cancer patients. It also investigated the inter-relationship among these factors. Methods: 152 patients treated with radical hysterectomy plus pelvic lymphadenectomy were followed up for a median of 49 months and were evaluated retrospectively. Results: The 5-year overall survival rate was 84.8%. The distribution of age at diagnosis is of bimodal shape, peaking at 42 and 68 years, respectively. Tumor subtype, PLNM, DCSI, and LVSI were found to be significant prognostic factors individually. After multivariate analysis, only tumor subtype and PLNM were found to be independent, significant prognostic factors for survival. The prognostic importance of LVSI appeared to be eclipsed by the presence of PLNM. DCSI was statistically related with FIGO stage, LVSI and PLNM. Conclusion: Tumor subtype and PLNM are the two most important independent prognostic factors for stages ⅠB-ⅡA cervical cancer. Some prognostic factors are inter-related and may reflect different facets of tumor progression.
5.Synthesis and photochemical virus inactivation of novel phenothiazines.
Hui WEN ; Xiaofang WANG ; Yi HUANG ; Jingxing WANG ; Guangzhong YANG
Acta Pharmaceutica Sinica 2010;45(1):72-6
Virus inactivation with photochemistry is being suitable for blood or blood products, methylene blue (MB)/light treatment has been used for viral inactivation of cellular blood components. Twelve new phenothiazines derivatives were designed and synthesized, and were used to test viral inactivation and red cell damage preliminary. Results showed that compound YWW-7 has a satisfactory activity, it could be developed as a new viral inactivation agent for blood products.
6.Optimum process for Kangfuxin Drop Pill by orthogonal design
Xiaofang LI ; Yi HUANG ; Lan BAI ; Ke LI
Chinese Traditional Patent Medicine 1992;0(12):-
AIM: To selecte the best process for Kangfuxin Drop Pills. METHODS: With appearance,weight coefficient of variation and dissolution time for index sign,orthogonal design was applied. RESULTS: The results indicated that the excellent factors and levels were as follows: the scale between PEG6000 and drug extraction was four to one,the temperature of drug fluid was at 85 ?C,drip rate was 40 drops/min. CONCLUSION: The method adopted is steady and feasible.
7.Construction of 3-D standard external nasal morphological database for nasal prostheses
Xiaofang LIU ; Yimin ZHAO ; Guofeng WU ; Yi WANG ; Le QU
Journal of Practical Stomatology 2000;0(06):-
Objective:To Construct 3-D standard external nasal morphological database for nasal prostheses.Methods:12 plaster models of 6 types of external nose were prepared and scanned by a lasser scanner.The data documents were primarily saved as .asc format. The digital noses were partitioned to six areas by the nasal anatomical features: Nasal bridge area,nasal tip and collumella area,left and right dorsal areas,left and right ala nostril areas, the surface model of each area was constructed and connected to a group. With adding the background color, the surface model of external nose was visualized from any observing angles; then the nasal length and width were measured and the original data were replaced by HAN standard data.12 digital nose models with the same size were obtained and the documents were saved by each type with both .asc format and .igs format.Results:Point-cloud data and surface model data of 6 types of standard external digital noses were obtained.Conclusion:The nasal morphological database may be used as the foundation for CAD/CAM technique preparation of nasal prostheses
8.Effect of changes in body composition and islet β-cell function on bone mineral density in obese women with normal glucose metabolism at child-bearing age
Sunjie YAN ; Meirong LI ; Ximei SHEN ; Liyong YANG ; Songjing ZHANG ; Ruhai YI ; Xiaofang YAN
Chinese Journal of General Practitioners 2009;8(12):875-879
Objective To investigate effects of changes in body composition and pancreas islet β-cell function on bone mineral density(BMD)in obese women with normal glucose metabolism at child-bearing age.Methods Ninety-five obese women with normal blood glucose at child-bearing age were recruited for the study,20 in non-obese group with body mass index(BMI)less than 23,20 in overweightgroup with BMI equal to or more than 23 and less than 25.28 in obesity Ⅰ group with BMI equal to or more than 25 and less than 30.and 27 in obesity Ⅱ group with BMI equal to or more than 30.Their BMD,body fat and lean mass were measured with by dual energy X-ray absorptiometer(DEXA),and intravenous -glucose tolerance test(IVGTT)was performed.Area under the Curve of insulin(AUCins)and acute jnsulin response(AIR)phase were calculated to assess their early insulin secretion.Homeostasis model assessment β-cell function index(HOMA2-%B)and homeostasis model insulin resistance index(HOMA2-IR)were used to assess their β-cell function and insulin resistance.Results Fat and lean mass in the upper and lower extremities.trunk and whole body and BMD in those women increased with increasing of their BMI(P<0.05),particularly in fat mass.as well as their otller parameters including plasma insulin level at zerominute of IVGTT(IVGTTins0),AUCins.HOMA2-%B and HOMA2.IR(all P<0.01).BMD in the upper and lower extremities,trunk and whole body showed a positive correlation with BMI,FPG,lean mass and/or fat mass.respectively(P<0.05).BMD of the trunk and whole body also had a positive correlation with TVGTTins0,AIR,AUCins and HOMA2-IR.respectively(P<0.05).Results of multivariate linear regression analysis showed that HOMA2-%B and HOMA2-IR correlated with BMD in a linear pattern.As the vailable body composition was added to the regression model.HOMA2 parameters would be removed from the model.Results of partial correlation analysis showed that islet β-cell function did not correlate with BMD after controlling body composition factors.Conclusions Insulin resistance or islet β-cell function compensation accompanied in obese women with main increase in fat mass have little benefit for their BMD,which may reflect indirectly their change in body compositions.Body composition,especially lean nlass,is the most important determinants of BMD in obese women.
9.Effects of carbachol on intestinal inflammation and mucosal blood flow in rats with gut ischemia-reperfusion
Xiaofang ZOU ; Shaowei WU ; Guoyong ZHOU ; Sen HU ; Yi LV ; Junyou LI ; Zhiyong SHEN
Journal of Chinese Physician 2008;10(12):1598-1601
Objective To investigate the effects of carbachol on intestinal inflammation and mucosal blood flow after gut ischemia-repedusion(I/R) in rat. Method A jejunal sac was formed in Wistar rats. The superior mesenteric artery (SMA) was occluded for 45 mi-nutes followed by 240 minutes of reperfusion. Animals were random divided into three groups: sham operation, L/R + saline injection (I/R + NS) and I/R + carbachol injection (0.1mg/kg, I/R + Ca). Immediately after occluded of SAM blood flow, either 0.1mg/kg of carba-chol or same account of 0.9% saline was injected into the jejunal sac. The pathological injury was observed with HE staining. The activity of DAO and content of TNF-α in intestinal mucosa tissue were determined. Mucosal blood flow was measured by laser Doppler. All measure-ments were done at 0 min, 30 min, 60 min, 120 min, and 240 min after reperfusion. Result In I/R group the activity of DAO in intestinal mucosa and mucosal blood flow deceased, meanwhile the content of TNF-α gut tissue was dramatically increased than those in sham operation (P<0.01). Severe pathological changes were observed in intestinal mucosa. After injection of carbachol, the activity of DAO and mucosal blood flow increased (P<0.01), but the content of TNF-α in intestinal mucosa were dramatically decreased (P<0.01), compared with those in I/R group. Conclusion Administration of carbachol protects intestinal ischemia-reperfusion injury by attenuating intestinal mucosa inflammation and increasing gut mueosal blood flow.
10.Expression and location of hypoxia inducible factor-1α and -2α in the remnant kidney of 5/6 nephrectomy rats
Xiaofang YU ; Xiaoqiang DING ; Jiaming ZHU ; Yi FANG ; Jianzhou ZOU ; Xunhui XU ; Suhua JIANG
Chinese Journal of Nephrology 2010;26(9):689-695
Objective To investigate the location and expression of hypoxia inducible factor (HIF) subunits in the remnant kidney of 5/6 nephrectomy rats. Methods Remnant kidneys were produced in adult male SD rats by 5/6 nephrectomy. The renal function and histopathological changes were evaluated at week 1, 2, 4, 6, 8 and 12 after operation. Tissues of remnant kidneys were collected to detect the location and expression of HIF-1α and HIF-2α by immunohistochemistry staining and Western blotting. The mRNA levels of HIF targeted genes vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) were determined by RTPCR. Results (1) 5/6 nephrectomy rats underwent one week of acute renal failure at first[Scr (122.8±22.1) μmol/L] and then developed compensative chronic renal failure [(66.0±3.7)-(66.4±8.4) μmol/L], but the level of Scr increased quickly after week 6 [(66.4±8.4)-(127.8±22.7) μmol/L],concomitantly with progressive tubulointerstitial fibrosis in remnant kidney cortex. (2) In cortex, HIF-1α was expressed only in the atrophic and dilated tubular cells while HIF-2α was located in endothelial, interstitial fibroblasts, and vascular smooth muscle cells. The semiquantitative results of imunohistochemistry and Western blotting revealed that HIF-1α and HIF-2α were both gradually up-regulated during the early stage of remnant kidney, peaked at week 4 and 6, and then gradually down-regulated. (3) The mRNA levels of HIF targeted genes VEGF and HO-1 transiently peeked at week 4 and 6, and then decreased gradually. Conclusions The increased stabilization of HIF-αprotein and transcription of HIF targeted genes at the early stage of this model is a compensation reaction towards hypoxia. The mechanism of decreased expression of HIF-α at the end stage of chronic kidney disease deserves further investigation.