1.LINGO-1-Fc Fusion Protein Prevents Apoptosis of Cerebellar Granule Neurons Induced by Low-potassium
Xianghui ZHAO ; Weilin JIN ; Sha MI ; Gong JU
Progress in Biochemistry and Biophysics 2006;0(04):-
Three myelin proteins, Nogo-A, MAG and OMgp, transduce their neurite-outgrowth inhibitory signal through a common receptor complex: NgR/ p75NTR (or TROY). Recently, LINGO-1 is identified as another essential component and regulator for the Nogo-66 receptor/p75 signaling complex. LINGO-1 is restricted to express in CNS, neuronal LINGO-1 is shown to be involved in the signal transduction from three myelin proteins, and Lingo-1 in oligodendrocyte negatively regulates the differentiation and myelination of oligodendrocyte. To investigate the potential activity of LINGO-1 in neuronal apoptosis, LINGO-1-Fc fusion protein including the extracellular LRR and IgC2 domain, was used as functional antagonist to study its protective effect on low-potassium induced apoptosis of cerebellar granule neurons (CGNs). In judgement of the apoptotic nuclei stained by Hoechst, LINGO-1-Fc pretreatment for 2 h significantly prevents apoptosis of CGNs. Although GST-LINGO-1 protein, including the LRR domain, binds to the CGN cultures in the same way with LINGO-1-Fc, it doesn't prevent the apoptosis of CGNs. These results indicate that LINGO-1-Fc fusion protein prevents low-potassium induced apoptosis of cerebellar granule neurons in certain conditions and this activity is probably IgC2 domain dependent.
2.Effects of shear stress on cytoskeleton alignment, adhesion, migration and apoptosis of endothelial cells on micropatterned substrates
Hongping HE ; Xixi ZHAO ; Bin LI ; Xianghui GONG
Chinese Journal of Tissue Engineering Research 2017;21(26):4240-4245
BACKGROUND: Micro-nano-sized modification of the material surface provides an effective way to enhance the endothelialization of cardiovascular implants. Shear stress plays an important role in the endothelialization of cardiovascular implants.OBJECTIVE: To review the effects of flow shear stress on endothelial cell cytoskeleton alignment, migration, adhesion and apoptosis on the micropatterned substrates.METHODS: The author performed a retrieval of PubMed and CNKI databases from 2002 to 2017 to search literatures about the effects of shear stress on endothelial cells on the micropatterned substrates. The keywords were micrometer topology, micropattern, flow shear stress, endothelial cells in English and Chinese, respectively.RESULTS AND CONCLUSION: The shear stress parallel to the long axis of the micropattern which is applied to the endothelial cells on micropatterned substrates promotes endothelial cell microfilaments alignment along the long axis direction of micropattern, strengthens endothelial cell migration along the flow direction, increases the level of FAK phosphorylation, enhances endothelial cell adhesion, and improves endothelial cell activity. However, there are some controversies on the effects of parallel shear stress on the microtubule arrangement of endothelial cells on micropatterned substrates. Some studies have reported that parallel shear stress promotes endothelial cell microtubules alignment along the long axis of micropatterns. But others have found that parallel shear stress has no effect on endothelial cell microtubule arrangement. There are different conclusions about the effects of shear stress perpendicular to the long axis of the micropattern on endothelial cells on the micropatterned substrates. Some literatures have found vertical shear stress destroys the structure of endothelial cell microfilaments and microtubules,weakens the degree of microfilaments and microtubules arranged along the long axis of micropatterns, and attenuates endothelial cell adhesion and cell activity. But some have found vertical shear stress does not destroy the structure and alignment of endothelial cell microfilaments and microtubules, and still can promote endothelial cell migration along the flow direction. The magnitude of shear force affects endothelial cell migration, and the number of endothelial cells on the micropatterned substrates migrating along the flow direction increases with the increasing intensity of shear stress.
3.The Standard and Advice for Animal Experiment Protocol Post-Approval Monitoring
Yufeng ZHU ; Yuanzhan WANG ; Li GONG ; Peiliang YANG ; Xianghui WU ; Junling ZENG ; Mourong LIU
Chinese Medical Ethics 2016;29(2):298-300
In this article, the authors expounded the necessary and problems of animal experiment post-ap-proval monitoring ( PAM) , which included who should do PAM, how to do PAM, and what the PAM can do. The authors also exposed the following suggestion: formulating the detailed rules, regulations and SOP, strengthening the training of PAM team member and animal experiment personnel, and monitoring the whole process of animal protocol review using the software.
4.Clinical value of fluorescence in situ hybridization positive of exfoliated urothelial cells in urothelial carcinoma
Jiayuan LIU ; Xiang PENG ; Xianghui NING ; Teng LI ; Shuanghe PENG ; Jiangyi WANG ; Shengjie LIU ; Yi DING ; Lin CAI ; Kan GONG
Journal of Peking University(Health Sciences) 2017;49(4):585-589
Objective: To analyze the clinical pathologic characteristics of cases with fluorescence in situ hybridization (FISH) positive of exfoliated urothelial cells, so as to evaluate the clinical utility of FISH in the diagnosis of urothelial carcinoma (UC).Methods: A total of 271 cases of FISH positive in Department of Urology of Peking University First Hospital from Apr.2012 to Sep.2015 were recruited in this study.Retrospective analysis was made on their clinical data.For FISH analysis, labeled probes specific for chromosomes 3, 7, 17, and the p16 (9p21) gene were used to assess chromosomal abnormalities indicative of malignancy.The positive predict values (PPV) of all the techniques were analyzed.Results: Of the 271 patients, 207 cases were UC, 7 cases were non-UC, and 57 cases were benign diseases.The PPV of FISH in detecting UC was 76.4%, while the 95% confidence interval (CI) 71.3% to 81.5%.In the cohort of FISH positive, this value was similar to that of urinary cytology (PPV 86.8%, 95% CI: 78.5%-95.0%).The PPV of FISH was lower than that of cystoscopy and ureteroscopy (PPV 96.1%, 95% CI: 91.7%-100.0%).There were significant differences between this study and the PPV of FISH reported abroad (PPV 53.9%, χ2=33.048, P<0.001).Of all the UC with FISH positive, bladder cancer showed an earlier pathological stage versus renal pelvic carcinoma and ureteral carcinoma, with significance (χ2=5.894, P=0.015, and χ2=13.601, P<0.001, respectively).However, no difference was found in the size, pathological stage and pathological grade of tumors between the urinary cytology positive group and the urinary cytology negative group.The rate of high-grade UC in ureteral carcinoma of FISH positive was 92.3%, much higher than that of ureteral carcinoma reported domestically.Conclusion: The PPV of FISH in detecting UC is higher relatively, with a better clinic value for Chinese patients.The ureteral carcinoma with FISH positive obtains a higher pathological grade, which is of great guiding significance for UC.