2.Preparation and in vitro release of 5-fluorouracil-loaded poly (lactic-co-glycolic-acid)/ nano-hydroxyapatite microspheres
Xiang LI ; Kun WEI ; Yun LUO ; Xin GAO ; Na ZHAO ; Wusheng GUO
Chinese Journal of Tissue Engineering Research 2009;13(47):9282-9286
BACKGROUND: Poly (lactic-co-glycolic-acid) (PLGA)/nano-hydroxyapatite (nHA) composite microspheres may continuously release drug in phosphate buffer solution in vitro.OBJECTIVE: To prepare 5-fluorouracil (5-Fu)-loaded PLGA/nHA microspheres, and research the effect of nHA on drug loading,encapsulation efficiency and in vitro release.DESIGN, TIME AND SETTING: An in vitro materials observation was performed at Laboratory of College of Materials Science and Engineering, South China University of Technology between February and July 2009.MATERIALS: PLGA was provided by Jinan Daigang Biomaterial Co., Ltd.; nHA by Key Lab for Special Functional Materials,Ministry of Education; 5-Fu by Shanghai Kaiyang Biomaterial Co., Ltd.METHODS: 5-Fu, a water-soluble anti-cancer drug, was used as model drug, and was firstly adsorbed by nHA and coated with biodegradable and blocompatible materials of PLGA so as to prepare PLGA/nHA-5-Fu composite microspheres by a single-emulsion solvent evaporation method (S/O/W). nHA and drug-loaded nHA were analyzed by transmission electron microscope (TEM), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). Drug loading and encapsulation efficiency as well as in vitro release of microspheres were studied with SEM, laser particle size analyzer, and UV-spectrophotometer.MAIN OUTCOME MEASURES: Interaction between nHA and 5-Fu; drug loading, encapsulation efficiency, and in vitro release of Microspheres RESULTS: FTIR showed that nHA had a strong adsorption with 5-Fu. Drug loading and encapsulation efficiency of PLGA/nHA-5-Fu composite microspheres were 3.83% and 86.78%, respectively, which were significantly greater than PLGA-5-Fu microspheres. After initial burst, composite microspheres released more slowly than PLGA microspheres alone. At day 27, the cumulative release rate of composite microspheres and PLGA microspheres alone were 84.87% and 99.87%,respectively.CONCLUSION: Because nHA has a strong adsorption with 5-Fu, PLGA/nHA-5-Fu composite microspheres compared to PLGA-5-Fu microspheres alone enhances drug loading and encapsulation efficiency, and has a better drug delivery effect.
3.Design, synthesis and antiproliferative activity in cancer cells of novel 18β-glycyrrhetinic acid derivatives.
Min HUANG ; Kun LI ; Shu-yu JIN ; Ting-xiu CUI ; Dan LIU ; Lin-xiang ZHAO
Acta Pharmaceutica Sinica 2015;50(10):1263-1271
To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents
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chemistry
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pharmacology
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Cell Line, Tumor
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drug effects
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Cell Proliferation
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drug effects
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Drug Design
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Glycyrrhetinic Acid
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analogs & derivatives
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chemistry
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HL-60 Cells
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drug effects
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Humans
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Male
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Prostatic Neoplasms
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pathology
4.Association study of disrupted in schizophrenia 1 gene polymorphisms with autism in Chinese Han children
Xiaoyan MA ; Yiqun HE ; Xiang LI ; Guanglei XUN ; Kun XIA ; Zhengmao HU ; Jingping ZHAO
Chinese Journal of Applied Clinical Pediatrics 2014;29(11):857-861
Objective To investigate the relationship between the single nucleotide polymorphisms(SNPs) of disrupted in schizophrenia 1 (DISC1) gene and autism in Chinese Han children.Methods Genome-wide SNP genotyping was performed by using Illumina HumanHap CNV370-Duo Chip in 278 autistic trios,157 autistic individuals and 435 healthy controls.Genotype data of SNPs within DISC1 gene were selected.The association between these SNPs loci and autism was analyzed through case-control association analysis and family-based transmission disequilibrium test.Results Fifty-two SNPs were involved for further analysis.1.Case-control association analysis showed that 6 SNPs (rs4658939,rs2793093,rs10495309,rs2492367,rs1 1122362,rs1073179) and 7 haplotypes (AGAAAG constructed with rs823163-rs823161-rs4658933-rs1417585-rs10864693-rs6541281,GGG and AAA constructed with rs4658939-rs2793093-rs10495309,GG and AG constructed with rs2492367-rs12046794,GAA constructed with rs9432040-rs2356606-rs1 1122362 and GG constructed with rs9431714-rs1073179) had significant differences between autistic patients and controls(x2 =4.704,4.915,5.568,8.087,4.043,5.183,5.369,5.295,4.440,5.304,7.615,4.018,4.811,P =0.030,0.027,0.018,0.005,0.044,0.023,0.021,0.021,0.035,0.021,0.006,0.045,0.028).2.In the transmission disequilibrium test analysis,2 SNPs (rs4658945,rs11122362) and 2 haplotypes (AG constructed with rs10495310-rs4658945,GAA constructed with rs9432040-rs2356606-rs11122362) showed significant transmission disequilibrium(x2=4.445,5.400,3.973,5.126,P =0.035,0.020,0.046,0.024).Conclusions The polymorphism of rs11122362 and GAA haplotype constructed with rs9432040-rs2356606-rs11122362 are associated with autism,and DISC1 gene is a susceptibility gene for autism in Chinese Han children.
5.An increased expression of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease
Hong, WANG ; Pei-Zeng, YANG ; Xiao-Yan, PENG ; Meng, ZHAO ; Hong-Yan, ZHOU ; Xiang-Kun, HUANG
International Eye Science 2007;7(4):883-886
· AIM: To investigate the expression and the possible implication of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease.· METHODS: Sampling was done from erythema nodosum of 5 patients with Beh(c)et's disease and normal skin of 2 healthy individuals. Immunohistochemical staining was performed to examine the expression of CD4, CD8, CD19, CD68, HLA-DR,CD40 and CD40L molecules in the obtained tissues.· RESULTS: Approximately 90% of epidermic cells in erythema nodosum expressed CD40 molecule. In the dermis and subcutaneous tissue, a significantly increased number of CD4+Tcells, CD8+Tcells, CD19+cells, CD68+cells, HLA-DR+cells,CD40L+cells, and CD40+cells were observed in the erythema nodosum as compared with that in normal skin. Double staining showed that CD40L molecules were expressed on 45% of CD4+T cells. CD40 molecules were expressed on 100% CD68+ cells and 59.2% of HLA-DR+cells respectively.· CONCLUSION: A number of CD40/CD40L costimulatory molecules are upreguiated in the erythema nodosum of patients with Behcet's disease.
6.High-Level Expression of Penicillinase Gene in Bacillus Subtilis
Hong-Kun ZHAO ; Xing-Wang LIU ; Qiang QIU ; Xiu-Xing LI ; Lian-Xiang DU ;
China Biotechnology 2006;0(12):-
To obtain a number of extracellular penicillinase,the gene(penp)encoding penicillinse of Bacillus cereus ATCC10987 was cloned into expression vector in Bacillus subtilis,transformed into Bacillus subtilis DB104 deficient in two proteases.When recombinant bacteria was cultured in LB medium for 24 hours,the result of SDS-PAGE showed that the molecular weight of the protein was 28kDa and the penicillinase activity reached 339U/ml.By screening seven different fermentation media,the result showed that 4# medium is favorable to producing penicillinase by the recombinant cells than the others,with the yield of the enzyme being 1580U/ml.When the recombinant cells was cultured in 7 liter fermentor for 24h,the penicillinase activity reached 1255.8U/ml.
7.Study on Heterologous Expression of Penicillinase Gene and the Penicillinase Degrading Residual Penicillin in Milk
Hong-Kun ZHAO ; Lian-Xiang DU ; Yu LI ; Xiao-Juan WANG ; Fu-Ping LU ;
Microbiology 1992;0(06):-
To obtain a number of penicillinases and degrade penicillin in milk by using the penicillinases,the gene encoding penicillinase was amplified by PCR from Bacillus cereus ATCC10987,cloned into pET28a(+) ,transformed into E. coli BL21;analysis of SDS-PAGE and penicillinase activity of the recombinant protein were done under induction of IPTG and the result showed that the maximum penicillinase activity reached 480 U/mL;the purity of penicillinase purified by Ni2+ Purification System was more than 90%;the immobilized penicillinases were obtained by sodium periodate method and the residual quantity of penicillin in milk(containing 0.5 U penicillin G/mL) was less than 4 ppb after degraded by the immobilized penicillinase.
8.Prognostic value of CD4+CD25+ Tregs as a valuable biomarker for patients with sepsis in ICU
Kun CHEN ; Qiu-Xiang ZHOU ; Hong-Wei SHAN ; Wen-Fang LI ; Zhao-Fen LIN
World Journal of Emergency Medicine 2015;6(1):40-43
BACKGROUND: Sepsis is a common complication of infections, burns, traumas, surgeries, poisonings, and post-cardiopulmonary resuscitation. The present study aimed to investigate prognostic value of CD4+CD25+ regulatory T cells (Treg) in peripheral blood of patients with sepsis. METHODS: Periphery blood from 28 patients diagnosed with sepsis was collected on day 1 and 7 after hospitalization in the ICU of Shanghai Changzheng Hospital between December 2013 to April 2014. The blood was used for analyses of Treg ratio using flow cytometry and for analyses of blood routine test, C-reactive protein (CRP), bilirubin, procalcitonin (PCT), and coagulation. APACHE II and sequential organ failure assessment (SOFA) scores were also investigated. The results were compared between two outcome groups of survival or death to evaluate prognostic value for sepsis. RESULTS: The patients had an average age of 60.36±15.03 years, APACHE II score 16.68±7.00, and SOFA score 7.18±3.78. Among the 28 patients, 12 had severe trauma (42.9%), 10 had septic shock (35.7%), and 9 (32.2%) died. The median ratio of Tregs was 2.10% (0.80%, 3.10%) in the survival group vs. 1.80% (1.15%, 3.65%) in the death group (Z=–0.148, P=0.883) on day 1; however it was significantly changed to 0.90% (0.30%, 2.80%) vs. 5.70% (2.60%, 8.30%) (Z=–2.905, P=0.004). CONCLUSION: With better prospects for clinical application, dynamic monitoring of Tregs ratio in peripheral blood has potential value in predicting prognosis of sepsis.
9.Correlation between cerebral perfusion and cognitive impairment in patients with acute ischemic stroke of anterior circulation
Xiaoxiao CUI ; Jianxin YUAN ; Zhuo WANG ; Yansheng ZHAO ; Kun DUAN ; Lihong XIANG
Clinical Medicine of China 2021;37(1):12-22
Objective:To analyze the changes of cerebral perfusion level and its relationship with cognitive impairment in patients with first anterior circulation acute ischemic post-stroke cognitive impairment.Methods:From March 2018 to March 2020, 70 patients with acute ischemic stroke in the first anterior circulation who were treated in the Department of Neurology of Kailuan General Hospital affiliated to North China University of Technology and met the inclusion and exclusion criteria were retrospectively analyzed.The mini-mental state examination was used to divide 36 cases of post-stroke cognitive impairment group and 34 cases of post-stroke cognitive impairment group.All the selected patients were examined by computed tomography(CT) and diffusion-weighted MR imaging(MRI-DWI) to determine the diagnosis and distribution of lesions; detection of cerebral artery stenosis by MRA; apply 3D pseudo-continuous arterial spin labeling(3D-pCASL) perfusion imaging, set the post label delay 1.5 s and 2.5 s to detect cerebral perfusion level.Results:(1)There was no statistical significance between the two groups in the comparison of basic clinical data.(all P>0.05). (2) The proportion of patients with middle cerebral artery, anterior cerebral artery and internal carotid artery ≥1 or ≥2 moderate and severe stenosis / occlusion on the focal side in the post-stroke cognitive impairment group (91.67%(33/36), 33.33%(12/36)) was higher than that in the post-stroke non-cognitive impairment group (23.53%(8/34), 8.82%(3/34)); the proportion of patients with moderate and severe stenosis / occlusion of MCA and ICA on the focal side in the post-stroke cognitive impairment group (69.44%(25/36), 44.44%(16/36)) was higher than that in the post-stroke cognitive impairment group (14.71%(5/34), 11.76%(4/34)), and the difference was statistically significant(χ 2 values were 33.455, 6.239, 21.394, 9.150, all P<0.05). (3) The proportion of patients with ≥ 2 cerebral infarction lesions in the post-stroke cognitive impairment group (61.1%(22/36))was higher than that in the post-stroke cognitive impairment group (38.03%(27/71))than that in the non-stroke group (20.6%(7/34), 19.05%(8/42)), and the difference was statistically significant(χ 2=11.833, 4.447, all P<0.05). PLD 2.5 s, the CBF value of frontal lobe infarction in post-stroke cognitive impairment group((31.516±8.333) mL/(100 g·min)) was lower than that in post-stroke non-cognitive impairment group((45.442±8.281) mL/(100 g·min)), the difference was statistically significant( t=3.835, P<0.05). Correlation analysis showed that the CBF value of PLD 2.5 s frontal infarction lesion was positively correlated with MMSE score( r=0.738, P<0.05). (4) The proportion of patients with ≥ 1 or ≥ 2 hypoperfusion areas (frontal lobe, temporal lobe, parietal lobe) on the focal side of PLD 1.5 s and 2.5 s after stroke (88.89%(32/36), 88.89%(32/36), 77.78%(28/36), 66.67%(24/36)) were higher than those without cognitive impairment after stroke (67.65%(23/34), 8.82%(3/34), 29.41%(10/34), 0), the difference was statistically significant(χ 2 values were 4.686, 44.837, 16.483, 34.493, all P<0.05). At PLD 1.5 s, CBF values of frontal lobe and parietal lobe in cerebral hypoperfusion area ((20.260±5.266) mL/(100 g·min), (17.664±3.947) mL/(100 g·min)) in patients with cognitive impairment after stroke were lower than those in patients without cognitive impairment ((33.442±10.563) mL/(100 g·min), (28.071±6.913) mL/(100 g·min)), the difference was statistically significant( t values were 3.392, 6.225, all P<0.05), at PLD 2.5 s, the CBF value after compensatory perfusion of frontal lobe, parietal lobe and temporal lobe in the post-stroke cognitive impairment group ((37.732±8.355) mL/(100 g·min), (32.942±6.459) mL/(100 g·min), (39.282±7.443) mL/(100 g·min)) was lower than that in the non cognitive impairment Group ((57.189±9.965) mL/(100 g·min), (52.415±7.017) mL/(100 g·min), (49.258±8.912) mL/(100 g·min)), the difference was statistically significant( t values were 5.443, 10.227, 2.950, all P<0.05). Correlation analysis found that the CBF value of the frontal lobe and parietal lobe of the PLD 1.5 s lesion area and the CBF value of the PLD 2.5 s hypoperfusion brain area after the perfusion of the frontal lobe, parietal lobe, and temporal lobe were positively correlated with the MMSE score( r values were 0.693, 0.675, 0.823, 0.799, 0.545, all P<0.05). Conclusion:Patients with first anterior circulation acute ischemic post-stroke cognitive impairment often have extensive hypoperfusion in the peripheral cerebral region, the occurrence of cognitive impairment after the first anterior circulation acute ischemic post-stroke cognitive impairment is related to the decrease of the perfusion level of the infarct lesion and the brain area around the lesion.
10.Application of diffusion tensor imaging and 1H-magnetic resonance spectroscopy in diagnosis of traumatic brain injury.
Zhao ZHAO ; Jian-yun YU ; Kun-hua WU ; Hua-lin YU ; Ao-xiang LIU ; Yu-hua LI
Journal of Forensic Medicine 2012;28(3):207-210
Mild traumatic brain injury (mTBI) is a common type of brain disorders among young adults. The dysfunction of the brain is often exacerbated due to diffuse axonal injury (DAI) which based on the injury of white matter fibers and axons. Since mild and moderate brain injury or DAI are diffuse and subtle, conventional CT and MRI are difficult to make a positive diagnosis. Recent clinical study indicated that functional magnetic resonance imaging has a high detection rate in the diagnosis of acute mild and moderate brain injury, especially the diffusion tensor imaging (DTI) and 1H-magnetic resonance spectroscopy (1H-MRS). This paper has reviewed the principles and characteristics of DTI and 1H-MRS, and recent research in the clinical and animal experiments on brain injury.
Animals
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Axons/pathology*
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Brain/pathology*
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Brain Concussion/pathology*
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Brain Injuries/pathology*
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Diagnosis, Differential
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Diffuse Axonal Injury/pathology*
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Diffusion Tensor Imaging
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Humans
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Magnetic Resonance Spectroscopy/methods*
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Nerve Fibers, Myelinated/pathology*
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Severity of Illness Index