1.Inhibition of berberine on organ anion transporters and its bidirectional trans-membrane transport
Weidang WU ; Xingyan ZHANG ; Zihong WEI ; Xiaoyan CI ; Lixin JIANG ; Jiangjie LU ; Changxiao LIU ; Xiulin YI
Drug Evaluation Research 2017;40(6):778-782
Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)%,(69.13±1.28)%,(72.12±3.28)%,(79.77±6.49)%,(69.51 ±5.99)% and (38.4 ± 2.67)% respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.
2.Current research of L-amino acid transporter 1 in tumor diagnosis and treatment
Yan DONG ; Weidang WU ; Xiaoyan CI ; Jing GAO ; Yong ZENG ; Xiulin YI
Tianjin Medical Journal 2015;(12):1456-1459
L-amino acid transporter 1 ( LAT1) is a member of L-amino transporter family and an important heterodi?meric amino acid transporter that belongs to subfamily of SLC7. LAT1 mainly mediates trans-membrane transportation of those neutral amino acids that had cyclobenzene or long side chains with high molecular mass such as L-Leu, L-Met and L-Phe as well as some amino acid analogues such as melphalan, L-DOPA and thyroxine in a Na+and ATP-independent diffu?sion. As LAT1 was abnormally overexpressed in various transformed cell lines, it might be related with tumor stage and prog?nosis. It is not only a biomarker that specifically expressed in some tumor cells but also plays an important role in tumor diag?nosis and therapy. Here we demonstrate the structure of LAT1 and its mechanism in transport peculiarity. We also reviewed the development of LAT1 in tumor diagnosis and treatment.
3.Inhibition of berberine on organ cation transporters
Weidang WU ; Tao CUI ; Xingyan ZHANG ; Zihong WEI ; Xiaoyan CI ; Jiangjie LU ; Lixin JIANG ; Changxiao LIU ; Xiulin YI
Drug Evaluation Research 2017;40(5):633-637
Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.
4.Brushing abrasion of the enamel surface after erosion.
Lipei CHEN ; Xiangke CI ; Xiaoyan OU
West China Journal of Stomatology 2017;35(4):379-383
Objective A study was conducted to compare the effect of different enamel remineralization periods after erosion on the depth of brushing abrasion. Methods Ten volunteers were selected for a 4-day experiment. A total of 60 enamels were randomly assigned into six groups (A-F) and placed in intraoral palatal devices. On the first day, the palatal devices were placed in oral cavity (24 h) . On the following three days, brushing experiments were performed extraorally, two times per day. The specific experimental method of brushing follows these next steps. First, the group F specimens were covered with a film of wax, and then acid etched for 2 min. Subsequently, the film of wax was detached. The groups from A to D were brushed after remineralization at the following time intervals: group A, 0 min; group B, 20 min; group C, 40 min; group D, 60 min. Erosion and remineralization were performed on group E, but without brushing. Remineralization was performed on group F, but without acid etching and brushing. The depth of enamel abrasion was determined by a mechanical profilometer. The surface morphology of the enamel blocks was observed using a scanning electron microscope. Results 1) The depth of abrasion was different in varied enamel remineralization time after acid etching. The statistical significant differences between groups were as follows. 2) When the time of enamel remineralization after acid etching was short, the surface depression in the electron microscope was deep, and the surface morphology was rough. Conclusion Brushing immediately after acid etching would cause much serious abrasion to the enamel surface. Brushing after 60 min can effectively reduce the abrasion of acid etching enamel.
5.Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation
Tao CUI ; Weidang WU ; Xiaoyan CI ; Wei LI ; Chuanmin GUO ; Jing XU ; Xiulin YI ; Changxiao LIU
Journal of China Pharmaceutical University 2019;50(2):175-179
This study aimed to investigate the improvement of tolance and pharmacodynamics of nano-micelle irinotecan formulation compared with irinotecan hydrochloride injection(Campto). The toxic effects of the two formulations on colorectal cancer cells COLO205, HT-29, HCT-8 and SW480 were tested in vitro. COLO205 tumor-bearing mouse model was constructed. The two preparations were given via tail vein injection to investigate the maximum tolerance dose(MTD)of tumor-bearing mice to the two preparations, and then to explore the improvement of anti-tumor efficacy of nano-micelle irinotecan formulation near the MTD. The results showed that there was no significant difference in the inhibitory effect of the two formulations on the four colorectal cancer cells in vitro. The MTD of nano-micelle irinotecan formulation and Campto was 432. 0 and 276. 5 mg/m2 respectively. Both of the two formulations showed significant anti-tumor effect in vivo, and the relative tumor proliferation rate and tumor wet weight inhibition rate of nano-micelle irinotecan formulation at high dose(345. 6 mg/m2)were significantly better than those of Campto at two doses(177. 0 and 221. 2 mg/m2)(P< 0. 05).
6.The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort
Jiangbo DU ; Ye DING ; Lei HUANG ; Yangqian JIANG ; Qingxia MENG ; Ci SONG ; Hong LYU ; Xiaoyu LIU ; Bo XU ; Yuan LIN ; Hongxia MA ; Guangfu JIN ; Hong LI ; Xiufeng LING ; Xiaoyan KE ; Hongbing SHEN ; Zhibin HU
Chinese Journal of Epidemiology 2021;42(4):591-596
Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.