1.The signal transduction and drug development of epithelial-mesenchymal transition
Siyun XU ; Jing LI ; Meiyu GENG
Chinese Pharmacological Bulletin 2003;0(09):-
Epithelial-mesenchymal-transition(EMT) plays a key role in the formation of embryo.At present,it is believed that EMT also contribute to the metastasis of primary tumors.A lot of signaling pathways participate in EMT,such as Wnt/?-catenin,Notch,Hedgehog,TGF? and growth factor receptors.The drugs that affect these pathways may play an important part in oncotherapy.
2.ULTRASTRUCTURAL CHARACTERISTICS OF SUBSTANCE P-LIKE IMMUNOREACTIVE TERMINALS IN THE MARGINAL DIVISION OF THE STRIATUM OF THE RAT
Xu ZHANG ; Siyun SHU ; Xinmin BAO
Acta Anatomica Sinica 1954;0(02):-
Using the immunohistochemical method combined with tract tracing techniques, a new subdivision, the marginal division, was found in the striatum of the rat. In this subdivision, substance P, enkephaline and dynorphin B terminals were densely localized. The present study investigated the synaptic organization of the substance P-like immunoreactive nerve terminals in the marginal division. Four major types of substance P immunoreactive synapses were identified. Axodendritic and axospinous synapses were the most common ones. Compound synapses with more than two synaptic components were also observed. One axo-axonic synapse was present. Both symmetric and asymmetric substance P-like immunoreactive synapses were seen in the marginal division. The existence of asymmetric synapses, small postsynaptic dendrites and axo-axonic synapses, distinguished the substance P-like immunoreactive nerve terminals in the marginal division from those in the other part of the striatum. The characteristics and complexity of the synaptic organization suggested that the substance P-like immunoreactive nerve terminals in the marginal division probably orginate from a different source and have a different function, as compared to those in the rest part of striatum.
3.Establishment of in vitro evaluation model for CYP2B6 induction and its application to screen inducers among TCMs.
Cong XU ; Siyun XU ; Haihong HU ; Lushan YU ; Su ZENG
Acta Pharmaceutica Sinica 2013;48(1):119-24
This paper is to report the development of a high-throughput in vitro system to screen hPXR/CAR mediated CYP2B6 drug inducers, and the application of it into the quick determination of induction activity toward CYP2B6 by various commonly used traditional Chinese medicines (TCMs) extract. Dual reporter gene assays were performed. The hPXR/CAR expression vectors and the reporter vector pGL3-CYP2B6-Luc involved in the distal and proximal promoters of CYP2B6 were co-transfected into HepG2 cells. Relative luciferase activities in cell lysate were analyzed after 48 h treatment of blank vehicle or drugs to determine the induction activity toward CYP2B6 by various commonly used TCMs extract. The positive hPXR/hCAR activators rifampicin and CITCO were applied to make sure that the reporter gene model was successfully established. Then 5 kinds of commonly used TCM extracts and 1 herbal compound were successfully investigated, some were found to activate hPXR or hCAR and therefore have the potential to induce CYP2B6 enzyme. This is the first domestic article to report the hCAR3-mediated CYP2B6 induction model and the establishment of a reporter gene system for hPXR/CAR-mediated CYP2B6 induction can be an effective and systemic in vitro method to investigate the drug inducers of CYP2B6 and to explain the mechanism involved.
4.Differentiation of benign from malignant lesions of heart and pericardium: the feasibility of Fluorine-18 fluorodeoxyglucose positron emission tomography CT
Dan SHAO ; Shuxia WANG ; Changhong LIANG ; Siyun WANG ; Weiping XU
Chinese Journal of Radiology 2010;44(10):1061-1065
Objective To assess the feasibility of integrated 18F-FDG PET-CT for the differentiation of malignancy from benign lesions of heart and pericardium. Methods A total of 23 cases (malignancy∶benign= 13∶10) with cardiac and pericardial lesions confirmed by pathology or clinic were analyzed in the present study. All lesions were evaluated semi-quantitatively using maximum standard uptake values (SUVmax) and SUVmax lesion/blood, and the density of the heart and pericardium lesions and the relationship with surrounding tissues were evaluated. The differences of SUVmax and SUVmax lesion/blood between benign and malignant lesions were analyzed using Mann-Whitney test. Subsequently, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for CT and PET-CT respectively. Results The maximum SUV showed significant difference between malignancy(6. 5 ) and benign ( 1.5 ) ( Z = - 3. 601, P < 0. 01 ), the SUVmax Lesion/Blood of malignancy and benign were 3.4 and 0. 9 respectively, also with significant difference(Z = -3. 600, P <0. 01 ). The optimal cut-off value of SUVmax is 3.5-4. 0 and SUVmax Lesion/Blood is 1.3-2. 0. The sensitivity, specificity, accuracy, PPV and NPV of CT and PET-CT were 76. 9% ( 10/13 ), 100. 0% ( 10/10) ,87.0% (20/23), 100. 0% ( 10/10 ), 76. 9% ( 10/13 ) and 100. 0% ( 13/13 ), 90. 0% (9/10), 95.7%(22/23),92.9% (13/14),100.0% (9/9) respectively. Conclusion 18F-FDG PET-CT can correctly differentiate benignity and malignancy of cardiac and pericardial lesions.
5.Changes of blood indicators in blood donors after COVID-19 vaccination
Siyun XU ; Songyan WU ; Yunfeng PU ; Suochun CAO
Chinese Journal of Blood Transfusion 2022;35(6):602-604
【Objective】 To explore the changes of blood routine, biochemical indexes and coagulation indexes of voluntary blood donors after COVID-19 vaccination, so as to provide a scientific basis for blood donation strategy and to ensure blood safety. 【Methods】 From March to August 2021, 55 blood donors who had received COVID-19 vaccination were sampled at the 2nd, 4th and 8th weeks after vaccination for blood routine, biochemical and coagulation indexes testing. The changes were analyzed. 【Results】 At the second week after vaccination, abnormal blood routine indicators occurred 16(5.82%) occasions, abnormal biochemical indicators 159(36.14%) occasions; at the 4th week after vaccination, abnormal blood routine indicators 14(5.10%) occasions and abnormal biochemical indexes 151(34.32%) occasions. There was no difference in blood routine and biochemical indexes before and after vaccination(P>0.05). Among the coagulation indexes, the incidence of abnormal increase of FⅧ activity at the 2nd, 4th and 8th weeks after vaccination were 34.5%(19/55), 40%(22/55) and 50.9%(28/55), respectively. The the incidence of abnormal increase of TT were 3.6%(2/55), 7.2%(4/55) and 21.8%(12/55), respectively. Both TT and FⅧ activity had a tendency of increasing(P<0.05), APTT had an decreasing trend(P<0.05), and FIB content took on dynamical changes(P<0.05). 【Conclusion】 The blood indicators of blood donors after receiving COVID-19 vaccination are almost within the normal reference values. They can donate regularly according to the required interval, which may help to improve the potential transient changes of coagulation function.
6.A nomogram based on CT enterography signs for prediction of intestinal penetrating lesions in patients with Crohn disease
Zhengping SONG ; Ping XU ; Xuehua LI ; Siyun HUANG ; Haiyi TAN ; Wen LYU ; Canhui SUN
Chinese Journal of Radiology 2023;57(9):990-997
Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.
7.Changes of specific antibody and neutralizing antibody after voluntary blood donors received COVID-19 vaccine
Songyan WU ; Yunfeng PU ; Suochun CAO ; Siyun XU
Chinese Journal of Blood Transfusion 2023;36(1):25-29
【Objective】 To analyze the changes in antibody titer of voluntary blood donors after receiving the COVID-19 vaccine, so as to provide reference for blood donation strategy, follow-up vaccine development and COVID-19 prevention and treatment for healthy people. 【Methods】 1) The serum from voluntary blood donors 2, 4, 8, 12, 16 and 20 weeks after inoculation with two-shot vaccines (inactivated vaccine or recombinant protein vaccine) was collected, and SARS-CoV-2 total antibody (IgG+ IgM+ IgA) detection (colloidal gold method) and neutralizing antibody detection (UPT immunoluminescence method) were conducted. 2) The obtained data were grouped according to collection time, age and gender, and differences between groups were analyzed by t test and ANOVA using SPSS 2.0 statistical software to clarify the trend of total antibodies and neutralizing antibodies. 【Results】 Neutralizing antibodies and total antibodies (IgG+ IgM+ IgA) from voluntary blood donors vaccinated inactivated vaccine or recombinant vaccine had the same trend of change, both reached their peak at the 2nd and 4th week, respectively, after inoculation, and then decreased gradually. The antibody produced by the recombinant protein vaccine had a higher titer than that from inactivated vaccine, and had slower decline and more lasting protection. The neutralizing antibody and total antibody (IgG+ IgM+ IgA) from different genders and ages were not statistically different. 【Conclusion】 Neutralizing antibodies reached its peak in the second week after vaccination, and total antibody titer reached its peak in the fourth week; both were independent of age and gender. After receiving the vaccine, voluntary blood donors should follow the latest instructions on blood donation intervals issued by the government.
8.Three new shRNA expression vectors targeting the CYP3A4 coding sequence to inhibit its expression.
Siyun XU ; Yongsheng XIAO ; Li LI ; Lushan YU ; Huidi JIANG ; Aiming YU ; Su ZENG
Acta Pharmaceutica Sinica B 2014;4(5):350-357
RNA interference (RNAi) is useful for selective gene silencing. Cytochrome P450 3A4 (CYP3A4), which metabolizes approximately 50% of drugs in clinical use, plays an important role in drug metabolism. In this study, we aimed to develop a short hairpin RNA (shRNA) to modulate CYP3A4 expression. Three new shRNAs (S1, S2 and S3) were designed to target the coding sequence (CDS) of CYP3A4, cloned into a shRNA expression vector, and tested in different cells. The mixture of three shRNAs produced optimal reduction (55%) in CYP3A4 CDS-luciferase activity in both CHL and HEK293 cells. Endogenous CYP3A4 expression in HepG2 cells was decreased about 50% at both mRNA and protein level after transfection of the mixture of three shRNAs. In contrast, CYP3A5 gene expression was not altered by the shRNAs, supporting the selectivity of CYP3A4 shRNAs. In addition, HepG2 cells transfected with CYP3A4 shRNAs were less sensitive to Ginkgolic acids, whose toxic metabolites are produced by CYP3A4. These results demonstrate that vector-based shRNAs could modulate CYP3A4 expression in cells through their actions on CYP3A4 CDS, and CYP3A4 shRNAs may be utilized to define the role of CYP3A4 in drug metabolism and toxicity.