1.Synthesis and characterization of N-octyl-N-arginine chitosan--a chitosan derivant with a mimetic structure of cell-penetrating peptides.
Chunyan LIU ; Ruirui PAN ; Tianyue JIANG ; Jianping ZHOU ; Huixia Lü
Acta Pharmaceutica Sinica 2012;47(6):797-802
A novel chitosan derivant, N-octyl-N-arginine chitosan (OACS) with a mimetic structure of cell-penetrating peptides was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino-group on chitosan's side chain. Structure of the obtained polymer was characterized by FT-IR and 1H NMR. The substitution degree of octyl and arginine groups was calculated through element analysis and spectrophotometric method, separately. The critical micelle concentration of OACS was 0.12 - 0.27 mgmL(-1) tested by fluorescence spectrometry. The solubility test showed OACS could easily dissolve in pH 1 - 12 solutions and self-assemble to form a micelle solution with light blue opalescence. The OACS micelles have a mean size of 158.4 - 224.6 nm, polydisperse index of 0.038 - 0.309 and a zeta potential of +19.16 - +30.80 mV determined by malvern zetasizer. AFM images confirmed free OACS micelle has a regular sphere form with a uniform particle size. MTT test confirmed that OACS was safe in 50 - 1 000 micromol-L(-1). The result of HepG2 cell experiment showed that the cell internalization of OACS micelles enhanced with increased substitution degree of arginine by 40 folds compared to chitosan. Thus, OACS micelles were a promising nano vehicle with permeation enhancement and drug carrier capability.
2.The effects and its mechanism of N-arginine chitosan as transdermal enhancer.
Fengyi CHENG ; Zhenhai ZHANG ; Jianping ZHOU ; Huixia Lü
Acta Pharmaceutica Sinica 2013;48(8):1325-32
The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
3.In situ rat intestine absorption of paclitaxel-loaded solid lipid nanoparticles modified with cell-penetrating peptides.
Caocao LI ; Zhenhai ZHANG ; Yinlong ZHANG ; Huixia Lü ; Jianping ZHOU
Acta Pharmaceutica Sinica 2013;48(1):131-7
To investigate the rat intestinal absorption of stearic acid-octaarginine (SA-R8) modified solid lipid nanoparticles containing paclitaxel (SA-R8-PTX-SLN), compared with the commercially available preparation of PTX (Taxol) and PTX-loaded solid lipid nanoparticles (PTX-SLN), the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique. The absorptions of the preparations were investigated at different intestinal segments, different drug concentrations and in the presence of P-glycoprotein inhibitor (verapamil). The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum. The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN > PTX-SLN > Taxol (P < 0.05). SA-R8-PTX-SLN showed a liner absorption manner at the duodenum in the examined drug concentration range. The cumulative absorptions of Taxol and PTX-SLN were significantly promoted after the addition of P-glycoprotein inhibitor (verapamil) into the preparation (P < 0.05), but absorption of SA-R8-PTX-SLN existed no significantly difference compared with the preparation without verapamil (P > 0.05). SA-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.
4.Effect of human germinal sheathed cells injected into the brain on neurological and motor function impairment in rats after traumatic brain injury
Yuhe HAN ; Ranbo Lü ; Wanhong ZHANG ; Jianping ZHANG
Chinese Journal of Tissue Engineering Research 2005;9(5):229-231
BACKGROUND: One of the main causes of the failure of central nerve regeneration is that the microenvironment (lack of nerve growth factor, inhibitory factor produced by excretion and formation of glial scar) in the injured central nerves is not favorable for the regeneration of axons. Therefore, it is important to improve the microenvironment of injured area for the regeneration of axons. Recently, olfactory ensheathing cells (OECs) have been attracting much attention as a key method to treat central nervous injury.OBJECTIVE: To investigate the effect of OECs on traumatic brain injury (TBI) in rats and whether they can reduce neurological impairment after TBI.DESIGN: A randomized controlled experimental trial based on experimental animals.SETTING: Department of neurosurgery in a hospital affiliated to a university.MATERIALS: The experiment was conducted in the Central Laboratory of Department of Neurosurgery, Kaifeng Railway Hospital from April 2003 to August 2003. Altogether 100 healthy adult SD rats of either gender,weighting 250- 350 g, were randomly divided into four groups: normal group, TBI group, normal saline group and OEC group with 25 rats in each. Each group was further divided into five subgroups with 5 rats in each.INTERVENTIONS: The models of TBI in rats were established, and OECs were transplanted into brain tissues immediately after injury. The scores of nerve injury were assessed in the rats at day 1, day 4, week 1, week 2 and week 4. The distribution of OECs in brain tissues was observed after the rats were sacrificed.MAIN OUTCOME MEASURES: Neurological function recovery of rats and distribution of OECs in brain tissues.RESULTS: At week 2 and week 4 after operation, neurological severity scores (NSS) in OEC group significantly differed from those of TBI group and normal saline group. HE staining or immunohistochemistry of GFAP and p75 revealed that OECs could survive in the transplanted site and migrate toward the surrounding tissues. The total number of p75 positive cells in five coronal tissue slices of 6 μm thick was added up at different intervals. The results showed that the number of OECs was decreased with the passing time.CONCLUSION: OECs can survive in the transplanted site and migrate to the surrounding tissues when they are transplanted into the iujured brain tissues immediately after TBI. Giving OECs can reduce neurological and motor dysfunction induced by TBI.
5.Idea of public relationship and the quality education of medical students
Wen LI ; Chuan ZHAO ; Yue Lü ; Jianping SI
International Journal of Traditional Chinese Medicine 2010;32(2):133-
Public relationship has an outstanding effect on virtue education. Public relationship can regulate behavior, culture noble ethics, coordinate interpersonal relations and improve the ability of society adaptation for medical students. Public relationship can also build up good image of medical students, and improve their comprehensive qualities.
6.Shortening Transfer Time of Critical Inpatients from Ward to Intensive Care Unit:Based on Six Sigma
Jianping SONG ; Yan FENG ; Minfang Lü ; Juehua XU ; Yuping ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2017;23(7):843-847
Objective To shorten the transfer time of critical inpatients from wards to intensive care unit (ICU). Methods From Novem-ber to December, 2015, 30 critical inpatients transferred from wards to ICU were investigated, and analyzed with Six Sigma DMAIC five-step method. There were 7 main processes and 22 sub-processes refined in transfer procedure, as well as the key quality points and the factors influencing the safety of transferring. Some improvement advice were recommended, including multifunctional transfer cart, Check-list before Transfer to Intensive Care Unit for Critical Patients, setting up transport group, training for young nurses and application of SBAR communication. Other 30 critical inpatients transferred from wards to ICU, from May to June, 2016, after the series of control pro-grams, were investigated. Results After improvement, the total transfer time from wards to ICU decreased (t=15.052, P<0.001), without the increase of human power and unsafety issues. The rescue success rate increased from 91.67%to 98.01%. Conclusion The process transfer-ring patient from wards to ICU has been reengineered based on Six Sigma DMAIC management, that reduces the time and improve the res-cue success rate.
7.An overview of glycoconjugates for cancer targeting therapy and diagnosis.
Weiqin WANG ; Zhenhai ZHANG ; Jianping ZHOU ; Hui PANG ; Huixia Lü
Acta Pharmaceutica Sinica 2013;48(12):1763-70
Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.
8.Analysis of risk factors of death in patients with redo-CABG
Benqing ZHANG ; Hansong SUN ; Shengshou HU ; Jianping XU ; Wei WANG ; Yunhu SONG ; Feng Lü ; Hengchao WU
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(1):32-34
ObjectiveTo assess the prognostic efficiency of three different risk socres in patients underwent redo-coronary artery bypass grafting (redo-CABG).MethodsFrom January 1997 to July 2011,57 patients underwent redo-CABG in Fu Wai Hospital.All patients were prospectively scored for operative mortality using EuroScore,STS Score and Sinoscore.The overall expected mortality were compared with the observed mortality.Discrimination was evaluated by receiver operating characteristic (ROC) cures and area under a ROC curve (AUC).ResultsFour patients died in the whole group,the observed mortality was 7%.The overall predicted mortality of EuroScore,STS Score and SinoScore were 5.6%,2.2% and 1.5%,all lower than the observed mortality.The AUC of the three kinds of score were respectively 0.495,0.557 and 0.535,which indicated that the discrimination of the three kinds of score are poor.ConclusionThe predictive value of EuroScore,STS Score and SinoScore for early postoperative mortality in patients undergoing redo-CABG is poor.Surgical technology is an important predictor for early postoperative mortality.
9.Study on the resource of cytokine gene modified seed cells in bone tissue engineering: the stable expression of fibroblasts after bone morphogenetic protein-3 transfection
Jian LIU ; Guolin MENG ; Yunyu HU ; Zhi YUAN ; Rong Lü ; Jun WANG ; Xinzhi XU ; Jianping BAI
Chinese Journal of Tissue Engineering Research 2005;9(2):226-227
BACKGROUND: Bone morphogenetic protein(BMP) is one of the most important cytokines that induce and promote seed cells to be transformed into osteocytes. Insoluble natural BMP can hardly affect the life of cultured seed cells. The expensive soluble recombinant BMP is also hard to work on the seed cells at the appropriate time and dose. Therefore, gene therapy technique provides us with a brand new idea of using gene-modified seed cells.OBJECTIVE: To transfect exogenous BMP-3 gene into the fibroblasts and screen the positive fibroblast clones that can express BMP-3 stably.DESIGN: Simple sample study.SETTING: Orthopaedic Research Institute, Xijing Hospital, Fourth Military Medical University of Chinese PLA.MATERIALS: The fibroblasts(NIH3T3) were kindly presented by Professor Situ Zhen-qiang of the Stomatological College of Fourth Military Medical University of Chinese PLA.METHODS: This experiment was conducted in the Key Laboratory of Chinese PLA, which belongs to the Orthopaedic Research Institute of Fourth Military Medical University. BMP-3 gene was transfected into the fibroblasts through lipofectamin. The transfected cells were screened by G418. The separated cloned cells were identified through immunohistochemistry. The positively stained cells were the clones of BMP-3 expressing fibroblasts.MAIT OUTCOME MEASURES: The screening concentration of NIH3T3 cells, screening of positive transfected cells, and expression of BMP-3 in screened cells.RESULTS: BMP-3 gene was successfully transfected into the fibroblasts. BMP-3 expressing fibroblast clones were creened and identified through immunohistochemistry. Fibroblast strains with stable BMP-3 expression were obtained.CONCLUSION: The transfection of BMP-3 gene eukaryonic expression vector into the fibroblasts and obtaining of fibroblast strains with BMP-3 expression have laid foundation for the usage of gene-modified seed cells in future research of bone tissue engineering.
10.Antisense CTGF inhibits the expression of CTGF in hypertrophic scar of rabbit ears
Shaohua WANG ; Jian LI ; Yanhua WANG ; Jianping Lü ; Jisen LI ; Yong WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2011;17(4):290-293
Objective To investigate a medicine which can inhibit the expression of connective tissue growth factor (CTGF) in hypertrophic scar of rabbit ears. Methods 24 bigears white rabbits were used to establish a model of hypertrophic scar of rabbit ears, which was randomly divided into four groups. The hypertrophic scar was injected intralesionally with antisense CTGF (group A), betamethason (group B), triamcinolone acetonide (group C) and physiological saline (group D). Some scar tissue samples were sectioned in every group when the scar was treated after 7, 14, 30, and 60 days, respectively. The expression of CTGF mRNA in the scar was assessed by in situ hybridization and hematoxylin and eosin stain (HE stain) in every samples. Results The expression of CTGF mRNA and the counting of fibroblasts decreased in group A, which showed statistical difference as compared with groups B, C and D. Conclusions The results suggesz that antisense CTGF is able to inhibit the proliferation process of hypertrophic scar in rabbit ears and to remarkably decrease the degree of fiborsis in the scar.