1.Physical damage -the origin of nanotoxicity
Xingguo MEI ; Zhenbo YANG ; Mingyuan LI ; Xiangyang XIE ; Guangyu GAO
Chinese Journal of Pharmacology and Toxicology 2014;(2):154-160
Despite tre mendous research efforts have been devoted to the analysis of nanoparticles (NPs)biohazard,the potential mechanism for nanotoxicity has not yet been syste mati-cal y elucidated.This review intends to point out the confusions about nanotoxicity in the field and tries to look into the mecha-nism from a new perspective.Currently,there are three puzzles:① no relationship between dose and toxicity could be observed in nanotoxicity;②there is a theory for the″size effects″,however, it cannot explain some cases contrary to the doctrine;③ NPs made of different materials with various sizes could have the same toxic effects through sti mulating oxidative stress.In fact, human body is co mposed of various biological molecules,and the biological function of a living syste m is reflected by the inter-actions and conversions of those molecules.NPs,on the other hand,are the invader of human body which has no ability to transport or convert or digest the foreigner.Thus,NPs could cause celldamage due to the physical blockage of micro-circula-tion,celldestruction due to membrane rando m insertion,and celldysfunction due to physical contacting with big biological mole-cules.The physical damages caused by various NPs could be divided into three categories:adhesion lesion,card inlay and puncture.Above al ,by analyzing wide spectrum of NPs varying in co mposition,shape and size,the author draws a conclusion that physical damage is the origin of nanotoxicity.
2.Differentially expressed microRNAs in the early and late transformed cells and their parental BEP2D cells
Gang GAO ; Yingjie YANG ; Jianxiang LIU ; Mei TIAN ; Xu SU
Chinese Journal of Radiological Medicine and Protection 2013;(3):261-264
Objective To identify the differentially expressed microRNAs in the early transformed cells,the late transformed cells and their parental BEP2D cells.Methods The differentially expressed microRNAs in the above cells were identified by microRNAs microarray assay.Results There were 38differentially expressed microRNAs in R15H20 cells versus BEP2D cells,with 18 upregulated and 20downregulated microRNAs.R15H20 and RHT35 cells shared 25 differentially expressed microRNAs compared with BEP2D cells,with 15 down-regulated and 10 up-regulated microRNAs.There were 87differentially expressed microRNAs in RHT35 cells versus BEP2D cells,with 47 upregulated and 40 downregulated microRNAs.There were 38 differentially expressed microRNAs in RHT35 cells versus R15H20 cells with 20 upregulated and 18 downregulated microRNAs.Conclusions microRNAs are differentially expressed in the different stages of carcinogenesis of BEP2D cells induced by α particles,which suggests that microRNAs may play an important role in α particle-induced malignant transformation of BEP2D cells.
3.Aberration test of injectable tissue engineered bone carriers with algin-gelatin blend system
Zhenkui GAO ; Jing ZHANG ; Yang XIA ; Fang MEI
Chinese Journal of Tissue Engineering Research 2009;13(38):7477-7480
BACKGROUND: Utilizing tissue engineering technique, various gel systems are served as scaffolds to repair bone defect. The scaffolds should have features of nontoxic and no teratological effects to the body. OBJECTIVE: To observe the effect of sodium alginate-gelatin/osteoblast gel on chromosomal pattern aberration in rabbits. DESIGN, TIME AND SETTING: The in vivo material animal experiments were conducted at the Beijing Shijitan Hospital and Department of Histology and Embryology, Peking University Health Science Center from October 2007 to March 2008. MATERIALS: A total of 12 New Zealand rabbits, aged 2 months, with clean grade, were randomly divided into 2 groups. The experimental group contains 4 female and 4 male rabbits, and the remaining 4 females were served as the control group. Sodium alginate dried powder were purchased from Sigma, USA, and the gelatin dried powder were supplied by Liidao Company, Hebei, China. METHODS: Following numbering, bone marrow was collected from 12 rabbits. Bone marrow stromal stem cells (BMSCs) were isolated by the density gradient centrifugation, and then in vitro cultured with osteoblast inductor. Osteoblasts following passage were an order of magnitude of 10~7. Bright pink gelatiniform liquid with mass ratio of sodium alginate and gelatin at ratio of 2:3 was prepared. Rabbit osteoblasts with final concentration of 5×10~9/L were mixed with CaCb solution to form fruit jelly-shaped sodium alginate-gelatin/osteoblast gel. Critical-sized calvarial defects were created in diameter of 1.5 cm in 12 rabbits. After 1 week, cell/scaffold complex (0.5 mL) was implanted to repair the bone defect in the experimental group. There was no treatment in the control group. MAIN OUTCOME MEASURES: The change of chromosomal pattern was observed at 3 months following reparation. RESULTS: No Chromosome somatotype aberration was found in 100 metaphases in the experimental group. From 400 metaphases of the control group, 4 abnormal cells were found, with 1% chromatid-type aberration ratio. Meantime, 12 abnormal cells in 800 metaphases of the control group were found, with 1.5% chromatid-type aberration ratio. The numerical value was within the normal range. Chromosome karyotype analysis: the chromosome number of each experimental rabbit was 2n=44, karyotype of the control rabbit was 44, XX, which was normal female; or 44, XY, normal male, no abnormal was found. The female rabbit in the experiment group was 44, XX, no abnormal was seen. CONCLUSION: From the cytogenetoxicity point of view, sodium alginate-gelatin/osteoblast gel is safe in repairing bone defects.
4.Analysis on Social Support Status and Associated Factors among Breast Cancer Patients in Yunnan
Dan LIAN ; Juan YANG ; Xuejun MEI ; Wanhong GAO ; Lichun TIAN
Journal of Kunming Medical University 2016;37(6):38-42
Objectives To understand the social support levels among breast cancer patients in Yunnan, as well as to explore the factors associated with social support. Methods According to the unified inclusion and exclusion criteria,121 breast cancer in-patients with chemotherapy were interviewed with structured questionnaire. Social demographic characteristics, Xiao's Social Support Rating Scale,General Self-Efficacy Scale,clinical and experimental data were collected. SPSS version19.0 was used to analyze the frequency and the correlation between social support and influential variables were analyzed by using the chi-square test and non-parametric test. Results The levels of social support in total, objective social support, subjective social support and utilization degree for breast cancer patients were (49.43 ±5.69), (13.35 ±2.51), (27.59 ±3.78), (8.50 ±1.98) respectively. Marriage status and self-efficacy were associated with social support level significantly. The influencing factors such as age, education level, marital status, occupation, income, place of residence, religion, medical expenses payment type, self-efficacy were included in the univariate analysis. However, only marital status and self efficacy were positively correlated with social support (p<0.05) . Conclusions The breast cancer patients in Yunnan have a higher social support level overall. Having-marriage status and higher self-efficacy have a positive influence on breast cancer in patients' social support level.
5.A randomized controlled trial study on the appropriate time of replacing drainage bags after trans-cervical resection of adhesion
Xiaowei GAO ; Xiaoping LI ; Mei LUO ; Li GAO ; Jingjing LI ; Wenhui YANG ; Tao MI
Chinese Journal of Nursing 2017;52(8):901-904
Objective To investigate the appropriate time of replacing drainage bags after trans-cervical resection of adhesion(TCRA) surgery.Methods Totally 156 patients underwent TCRA were randomly divided into three groups:Group A,the drainage bags were replaced daily;Group B,the drainage bags were replaced every 3 days;Group C,the drainage bags were never replaced.The drainage bags were removed on the 6th day after TCRA for all groups.Bacterial culture results from the balloon surface of drainage bag,outer cervical orifice,and the connector of drainage bag for 3 groups were observed.The positive rates of bacterial cultures were analyzed statistically.Results The bacterial culture results from the drainage bag connector of 3 groups indicated that the positive rate of Group C was significantly lower than that of other two groups(P<0.05).The bacterial culture from the drainage bag balloon surface also indicated the same result,but the result did not showed statistically significant difference(P>0.05).There was no statistically significant difference in the culture result firom outer cervical orifice and the volume of drainage fluid within three groups(P>0.05).Conclusion It is indicated that the patient may enjoy a lower rate of bacterial infection without replacing any drainage bags connected to balloon drainage tubes placed after TCRA within 6 days.We suggest that the intrauterine drainage hags may be kept without replacement until direct removing the drainage tube on day 6 after TCRA.
6.Etiologic identification and drug susceptibility analysis of a Citrobacter freundii food poisoning event
YANG Yi ; CHEN Guo-li ; SUN Gao-feng ; YANG Yan-mei ; SHANG Yue-mei ; GUAN Lei ; MU Wen-ting
China Tropical Medicine 2023;23(1):94-
Abstract: Objective In order to provide reference for emergency treatment of a sudden food poisoning incident, pathogen detection and drug resistance analysis were carried out. Methods Diarrheal stool and surplus food samples were detected by GB 4789 and the isolates were identified by VITEK2 and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), at the same time, the bacterial drug sensitivity test was carried out by using the method of microbroth dilution, and the isolates from different sources were molecularly classified by pulsed field gel electrophoresis (PFGE), and the correlation between the strains was analyzed by BioNumerics software. Results Totaly 13 leftovers and 3 diarrhea patients were isolated and identified, The total number of colonies and coliforms in 7 leftovers samples all exceeded the standard, and Citrobacter freundii was detected in 5 leftovers and 2 stools. The results of drug sensitivity test showed that seven strains of Citrobacter freundii were sensitive to ciprofloxacin, tetracycline, chloramphenicol, gentamicin, amikacin, cefotaxime and meropenem, but completely resistant to ampicillin, and there was no multiple drug resistance. The results of pulsed field gel electrophoresis (PFGE) showed that 7 strains of Citrobacter freundii had the same PFGE bands and 100% homology, showing the same clone. Conclusions This food poisoning incident was caused by Citrobacter freundii. The pathogen of food poisoning can be quickly and accurately determined by MALDI-TOF MS, which is beneficial to the early diagnosis and treatment of infectious diseases. It is suggested to strengthen the corresponding management, improve food safety awareness and prevent similar incidents.
7.Targetting microbubbles of tumor lymphangiogenesis and ultrasound contrast imaging in vivo
Yang YANG ; Mei ZHU ; Zheng LIU ; Lu LI ; Wenhong GAO ; Fei WANG ; Fei LI
Chinese Journal of Ultrasonography 2016;25(6):536-540
Objective To optimizing preparate for target microbubbles of tumor lymphangiogenesis which load anti-VEGFR-3 and anti-Podoplanin and to evaluate the imaging of this microbubbles Methods The biotinylated anti-VEGFR-3 and anti-Podoplanin were conjugated to biotinylated microbubbles through biotin-avidin its technology of preparation and progress were optimized The proportion of reagents were adjusted The targeted microbubbles were evaluated by immunofluorescence method and its effect was tested in vivo Results High adhesion rate target microbubbles were successfully achieved which average particle size was 0 99 μm and the average antibody combined rate was 81 3% Confirmed by flow cytometry and fluorescence microscope it can clearly show the lymphangiogenesis and the metastasis of lymph nodes in vivo Time-intensity curve showed more microbubbles more intensity more stay and better image Conclusions These target microbubbles have a small particle size and high adhesion rate and a better contrast imaging It is a more value ultrasound target contrast agents of lymph vessel with tumor and sentinel node.
8.Current status and prospect of translational medicine in nanotechnology.
Guang-yu GAO ; Mei-ling CHEN ; Ming-yuan LI ; Zhen-bo YANG ; Zhi-ping LI ; Xing-guo MEI
Acta Pharmaceutica Sinica 2015;50(8):919-924
Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.
Biocompatible Materials
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toxicity
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Translational Medical Research
9.Abnormal expression of bcl-2 gene family in development of Barrett's esophagus
Xingwei WANG ; Dianchun FANG ; Hengjun GAO ; Mei XU ; Jiangtao XU ; Shiming YANG ; Yonggang SUN
Chinese Journal of Digestive Endoscopy 2009;26(4):194-197
Objective To detect the differential expression genes(DEGs)between Barrettg esophagus(BE)and normal esophagus with oligomicroarray,and to explore the target genes related to the development of BE.Methods The total RNAs of matched BE and normal esophagus mucosa from saIne patient were isolated with one step Trizol method.Matched RNAs were qualified with 10g/L agarose gel electrophoresis.After tRNA purification,cRNAs were synthesized and labeled with fluorescence.which were tIlen hybridized with Agilent oligomicroarray containing 30,968 probes.The fluorescence intensity features were detected by Agilent scanner and quantified by software Feature Extraction.Results On average,2 biopsies by disposable jumbo biopsy forceps provided approximately 5μg RNA required for microarray.The total RNA,reverse transcription product and fluorescence labeled cRNA were all of high quality.Among 2-fold DEGs,there were 142 up-regulated genes and 284 down-regulated genes including 15 bel-2 related genes such as bel-2,MCL1,BAX,BIK and BCLAF1 Conclusion Microarray-based studies are feasible in endoscopically obtained tissues.The development of BE is a complicated process involving multi-genes,in which abnormal expression of bel-2 family related genes might be involved,but the exact mechanism needs further research.
10.Optimization of isolation and culture conditions of highly homogenous human adipose-derived mesenchymal stem cells
Xufang YANG ; Xu HE ; Lihong ZHANG ; Mei SUN ; Hong XU ; Yunhe GAO ; Yulin LI
Chinese Journal of Tissue Engineering Research 2009;13(45):8861-8864
BACKGROUND:Up to date,there is not an acceptable method for isolating,culture and amplifying human adipose-derived mesenchymal stem cells (hADSCs).OBJECTIVE:To explore the most effective way to obtain highly homogenous and undifferentiated hADSCs.DESIGN,TIME AND SETTING:The in vitro cytology experiment was performed at the Key Laboratory of Pathobiology,Ministry of Education,Jilin University from June to December 2008.MATERIALS:Human abdominal adipose tissue resected in the surgery was supplied by the Affiliated Hospital of Jilin University,The informed consent was obtained from patients.METHODS:Human adipose tissue was removed connective tissue and blood vessel,followed by incubation in 0.1% type I collagenase for 60 minutes at 37℃,filtrated then centrifuged.Consequently,the subnatant precipitation was cultured with LG-DMEM containing 10% fetal bovine serum,incubated at 6-well plate with density of 1×10~9/L,and placed in incubator of 5% CO_2 at 37 ℃.The cultured cells were passaged when the cells reached 80%-90% confiuency,and the 3~(rd) passage of cells were induced to osteogenic and adipogenic differentiation.MAIN OUTCOME MEASURES:Morphological characteristics of hADSCs were observed by laser scanning confocal microscope.Immunophenotypes,cell cycle and growth curve of hADSCs were detected by flow cytometry and immunofiuorescent techniques.In addition,the multiple differentiation potential of hADSCs was detected.RESULTS:hADSCs presented fibroblast-like morphological feature with a flocked array.The 3~(rd) passage of hADSCs had unique immunophenotypes and they were positive for CD73,CD44,CD166,CD105 and CD29,but negative for CD31,CD34,CD45 and HLA-DR.Cell cycle result showed that they had the typical growth characteristics of stem calls,namely,83.81% cells stayed at G_0/G_1 stage,only 16.19% cells were stayed at S+G_2/M stage;The latent phase of the primary culture cells was 2 days prior to and after incubation,followed by 3-6 days of logarithmical proliferation,reached a peak at day 6,and entering the growth platform phase with lower growth speed.The alkaline phosphatase was positive expressed at week 2 of osteogenic induction.And the positive expression of oil-O red staining could be seen at day 3 of adipogenic induction.CONCLUSION:Cells contamination can be reduced by removing connective tissue and blood vessel of adipose tissue,and 0.1% type Ⅰ collagenase for 60 minutes can effective separated stroma cell to matrix fiber,furthermore,ensure a sufficient contact between collagenase and tissures,which provide an supportive for harvesting highly homogenous hADSCs.