1.Anti-angiogenic mechanism of cordycepin on rhesus macaque choroid - retinal endothelial cell line cultured in high glucose condition
Xiao-Li, ZHU ; Xiao-Feng, SUN ; Ming-Ying, LAI
International Eye Science 2016;16(7):1237-1241
AIM: To investigate the angiogenesis effect and protective mechanism of cordycepin on rhesus macaque choroid- retinal endothelial ( RF/ 6A) cell line cultured in high glucose condition.
METHODS: Cultured RF/ 6A cells were divided into normal control group, high glucose group and high glucose (HG) + different concentration cordycepin groups (HG+ 10μ g/ mL group, HG+ 50μ g/ mL group, HG+ 100μ g/mL group). The cell proliferation was assessed using cholecystokinin octapeptide dye after treated for 48h. The cell migration was investigated by a Transwell assay. The tube formation was measured on Matrigel. Furthermore, the impact of cordycepin on high glucose - induced activation of VEGF and VEGF receptor 2 (VEGFR-2) was tested by Western blot analysis.
RESULTS: Compared with normal control group, cell viability markedly increased in high glucose group ( P <0. 05). Cordycepin inhibited RF/ 6A cell proliferation in a dose- dependent fashion: 10. 2 ± 0. 9%, 23. 4 ± 1. 5% and 31. 1±1. 2% inhibition as the concentrations of cordycepin were 10, 50 and 100μ g/ mL, respectively. The difference had statistically significant (P<0. 05) compared with high glucose group. The number of cell migration were 55. 6±2. 70, 87. 4 ± 2. 40, 65. 4 ± 2. 7, 57. 8 ± 2. 38, 62. 4 ± 2. 77 in normal control group, high glucose group and HG+10μ g/mL group, HG + 50μ g/ mL group, HG + 100μ g/ mL group respectively. Migration of RF/ 6A conspicuously increased in high glucose group ( P < 0. 05) compared with normal control group; while showing a gradually reducing trend with the increase of cordycepin dose and a statistically significant difference compared with high glucose group (P<0. 05). The number of tube formation were 18. 7±2. 08, 25. 7 ± 1. 52, 19. 9 ± 1. 57, 16. 3 ± 2. 51, 5. 67 ± 1. 72 in the abovementioned group. Similarly showing a gradually reducing trend with the increase of cordycepin dose and a statistically significant difference with high glucose group (P< 0. 05). In addition, the number of tube formation of RF/ 6A in high glucose group significant increased compared with normal control group ( P < 0. 05 ). The expression of VEGF and VEGFR-2 dramaticlly increased in high glucose group vs normal control group, oppositely gradually decreased with the increase of cordycepin concentrations, and had a statistically significant difference vs high glucose group (P<0. 05).
CONCLUSION: Cordycepin can suppress the proliferation, migration and tubu formation of RF/ 6A in high glucose condition, might via inhibiting expression of VEGF and VEGFR-2.
2.Clinical significance of standard large trauma craniectomy to treat the patients with severe bump brain injury
Yunhui LI ; Zhongpin LIN ; Jianlong HUANG ; Haibiao LAI ; Gelin XIAO ; Weiye LAI ; Liang ZHONG
Journal of Chinese Physician 2001;0(04):-
Objective To evaluate the efficacy of standard large trauma craniectomy to treat the patients with severe bump brain injury. Methods Thirty-two bump brain injured patients with cerebral hernia were treated with inside and outside decompression of standard large trauma craniectomy compared with 24 cases of routine temporoparietal craniectomy between Oct 2001 and Aug 2004.Results In standard large trauma craniectomy group,21 cases got good recovery(65.6%) and 5 were dead(15.6%).In routine temporoparietal craniectomy group,9 cases got good recovery(37.5%) and 10 were dead(41.7%).There was significant difference between the two groups in good recovery and mortality(P
3.Research progress of hypoxia-inducible factor 1 inhibitors against tumors.
Fei NIU ; Yan LI ; Fang-Fang LAI ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(6):832-836
Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death
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Humans
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Hypoxia-Inducible Factor 1
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antagonists & inhibitors
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metabolism
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Hypoxia-Inducible Factor 1, alpha Subunit
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antagonists & inhibitors
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metabolism
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Neoplasms
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drug therapy
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Oxygen
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metabolism
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Signal Transduction
4.The in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and in vitro-in vivo correlation by the method of area under the absorbance-wavelength curve.
Hong-qiang LAI ; Yue HU ; Xiao-dong LI
Acta Pharmaceutica Sinica 2015;50(6):788-792
To discuss the availability of evaluation on the dissolution studies of the multicomponents in traditional Chinese medicine, the in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and its correlation with the in vivo were studied by the method of area under the absorbance-wavelength curve (AUAWC). Taken the tablet of rhizomes of Ligusticum chuanxiong components which is composed of sodium ferulate and ligustrazine hydrochloride as subject model, the dissolution tests were carried out with basket method. The plasma concentrations of tablets in different rats were determined by AUAWC at different interval times. The in vivo absorption percentage was calculated by Wagner-Nelson equation to evaluate the in vitro and in vivo correlation. According to the results, the cumulative dissolution in vitro of total composition of tablets of rhizomes of Ligusticum chuanxiong components at 60 min was 90.65% in water by AUAWC. The in vivo pharmacokinetics is fitted with an one-compartment model. The linear equation based on the cumulative dissolution rate (fr) and absorption percentage (fa) at 5, 10, 20, 30 and 60 min was fa = 0.819 7 fr+0.183 and the correlation coefficient was 0.959 5, which showed a good correlation between the in vitro dissolution and the in vivo absorption percentage. The method of AUAWC can be used accurately, feasibly and conveniently to evaluate the in vitro and in vivo correlation of total composition of tablets of rhizomes of Ligusticum chuanxiong components, which will provide better guidance to study the in vitro and in vivo correlation of sustained release preparation etc under complex system of traditional Chinese medicine in the future.
Animals
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Coumaric Acids
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chemistry
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Delayed-Action Preparations
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Drugs, Chinese Herbal
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chemistry
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pharmacokinetics
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Ligusticum
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chemistry
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Rats
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Rhizome
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chemistry
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Solubility
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Tablets
5.Internal fixation with lag screws plus an anti-sliding plate for the treatment of Hoffa fracture of the lateral femoral condyle.
Li-lai ZHAO ; Pei-jian TONG ; Lu-wei XIAO
China Journal of Orthopaedics and Traumatology 2016;29(3):266-269
OBJECTIVETo explore the clinical effects of internal fixation with lag screws plus an anti-sliding plate for the treatment of Hoffa fractures of the lateral femoral condyle.
METHODSFrom May 2006 to May 2014, 17 patients with Hoffa fractures of the lateral femoral condyle were treated with lag screws plus an anti-sliding plate. There were 13 males and 4 females, ranging in age from 27 to 59 years, with a mean of 32.5 years. All the fractures were fresh and closed fractures. According to the Letenneur's classification, 8 cases were type I, 4 cases were type II, 5 cases were type III. All the patients had no injuries of the cruciate ligament and the another part of the knee. Operative incision and fracture healing time were observed, knee joint function was evaluated by Letenneur system and HSS standard.
RESULTSThe patients were followed up from 10 to 24 months with a mean of 14.6 months. All incisions achieved primary healing, and no internal fixation breakage, malunion, femoral candyle necrosis, deep vein thrombosis of lower extremity were found. Fracture healing time was from 4 to 9 months with an average of 4.7 months. According to Letenneur's functional assessment, 10 patients got an excellent results, 4 good, 3 fair. Total HSS score was 91.1 +/- 4.7 on average,15 cases obtained excellent results, 2 good.
CONCLUSIONInternal fixation with lag screws and an anti-sliding plate can result in excellent effects for Hoffa fractures of the lateral femoral condyle. The key to a successful surgery is an anatomic reduction and rigid fixation of the fracture.
Adult ; Bone Plates ; Bone Screws ; Female ; Femoral Fractures ; physiopathology ; surgery ; Femur ; injuries ; surgery ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Closed ; physiopathology ; surgery ; Humans ; Ligaments, Articular ; surgery ; Male ; Middle Aged
6.The study of genome DNA methylation in rheumatoid arthritis
Xiao-Yan XU ; Mei-Mei WANG ; Chuan-Shi XIAO ; Xiao-Feng LI ; Lai-Yuan WANG ;
Chinese Journal of Rheumatology 2003;0(08):-
Objective To study the genome DNA methylation in rheumatoid arthirits(RA)and the re- lated factors of DNA methylation.Methods Twenty-first cases with RA and 20 controls were recruited to par- ticipate the study.Plasma Hcy,SAM,SAH,the MTHFR gene C677T polymorphism and the expression of LFA-1 in CD4~+T cells was measured in all patients and controls.Results①The SAM levels were lower sig- nificantly in RA groups than in controls.The SAH levels were higher significantly in RA groups than in con- trols.②There was significant inverse correlation between plasma Hcy level and SAM level(r=-0.932,P<0.01). There was significant positive correlation between plasma Hcy level and SAH level(r=0.924,P<0.01).③The expression of LFA-1 in CD4~+T cells was higher significantly in RA groups than in controls.There was a signif- icant positive correlation between LFA-1 expression level and Hcy level(r=0.557,P<0.01),a significant in- verse correlation between LFA-1 expression level and SAM level(r=-0.651,P<0.01).④The MTHFR gene mu- tation lead to dramatically increase of Hcy,SAH level and the expression of LFA-1 level in CD4~+T cells and genome DNA hypomethylation.Conclusion①Hypomethylation of genome DNA is found in most RA pa- tients.②The factors associated with genome DNA hypomethylation include MTHFR gene mutation and hyper- homocysteinemia.③The expression of LFA-1 in CD4~+ T cells is higer in RA groups than in controls,which re- lates to the DNA methylation level and the MTHFR gene C677T polymorphism.
7.Protective effect of vitamin D3 on ocular structure in diabetic rat
Ming-ying, LAI ; Mei, LIU ; Fang-wei, YING ; Zhi, LI ; Xiao-li, ZHU ; Hua, WEI ; Ping-hong, LAI
Chinese Journal of Experimental Ophthalmology 2012;30(2):117-120
BackgroundResearch demonstrated that vitamin D3 mediated by its receptor has the potent nonclassical effects,including immunomodulatory,antiinflammatory,and neuroprotective properties,and it can enhance the secretion and sensitivity of insulin and therefore down-regulate hyperglycemia and attenuate the corneal edema.ObjectiveThe present study was to investigate the protective effect of vitamin D3on ocular structure in experimental diabetic rat.Methods Twenty-two healthy SPF C57BL/6 rats were randomly divided into vitamine D3 group (8 rabbits),diabetic control group ( 11 rabbits) and normal control group ( 3 rabbits).2% streptozotocin ( STZ,175 mg/kg)was intraperitoneally injected to create the diabetic models in the rats of the vitamine D3 group and diabetic control group.Blood glucose was examined for 3 times in the third day after STZ injection,and the rats with the blood glucose concentration >16.7 mmol/L was identified as the successful diabetic models.After modeling,the rat tail blood was collected for the monitoring of blood glucose.Two weeks after modeling,vitamine D3 was intraperitoneally injected in each week for 5 times.The fundus was examined using direct ophtalmoscope,and the eyeballs were obtained under the excessive anesthesia for the measurement of thickness of the central cornea,retina and choroids by histopathological examination once a week for 7 weeks after administration of vitamin D3.The administration of the animals complied with the Statement of ARVO.ResultsThe corneal edema appeared with the corneal thickness of (339.14± 11.13) μm in the first week and gradually attenuated with time elapse after modeling in the diabetic group ( F =382.446,P =0.000).The corneal thickness values were significantly decreased from the second week through the seventh week in the vitamin D3 group compared with diabetic control group(P<0.05).The atrophy of the corneal epithelium was found from the fifth week to the seventh week in diabetic control group,but that in vitamin D3 group was slight (P<0.05).The gradually thinning of the choroids was seen from the first week to the seventh week in the diabetic control group ( F =437.411,P =0.000 ),however,the thickness values in the vitamin D3 group were significantly increased in comparison with the diabetic control group in various time points (P<0.05).The retina thickness was gradually reduced during the seven-week duration in the diabetic control group (F =91.859,P =0.000),but no significant change was identified in retina thickness in the vitamin D3 group(P>0.05).ConclusionsVitamin D3 has prevent and therapeutic effects on experimental diabetic oculopathy.
8.A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth.
Fang-Fang LAI ; Xiao-Yu LIU ; Fei NIU ; Li-Wei LANG ; Ping XIE ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(5):622-626
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals
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Antineoplastic Agents
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pharmacology
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Breast Neoplasms
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metabolism
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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Heterografts
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Humans
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Hypoxia-Inducible Factor 1
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metabolism
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Lignans
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pharmacology
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Mice, Nude
9.Total flavonoid from Glycyrrhizae Radix et Rhizoma and its ingredient isoliquiritigenin regulation M2 phenotype polarization of macrophages.
Yuan-lai WANG ; Xi TAN ; Xiao-lu YANG ; Xiao-yun LI ; Ka BIAN ; Dan-dan ZHANG
China Journal of Chinese Materia Medica 2015;40(22):4475-4481
To study the mechanisms of total flavonoid from Glycyrrhizae Radix et Rhizoma (TFGR) and its ingredient isoliquiritigenin (ISL) on their regulation of M2 phenotype polarization of macrophages. IL-4 (60 μg x L(-1)) induced RAW264.7 cells for 6 h to establish the M2 macrophage model. TFGR and ISL restrained breast cancer cells migration with the aid of M2 macrophages in vitro. TFGR and ISL inhibited gene and protein expression of Arg-1, up-regulated gene of HO-1 and protein expression of iNOS, enhanced the expression of microRNA 155 and its target gene SHIP1, meanwhile down-regulated.the phosphorylation of STAT3 and STAT6. So TFGR and ISL were the bioactive fraction and ingredient in Glycyrrhizae Radix et Rhizoma to reverse M2 phenotype macrophages polarization. TFGR and ISL inhibited the promotion of M2 macrophages to breast cancer cells migration in vitro, STAT signal pathways and miR155 were partly involved.
Animals
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Cell Line, Tumor
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Cell Movement
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drug effects
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Cell Polarity
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drug effects
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Chalcones
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pharmacology
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Flavonoids
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pharmacology
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Glycyrrhiza
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chemistry
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Interleukin-4
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genetics
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metabolism
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Macrophages
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cytology
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drug effects
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metabolism
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Mice
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RAW 264.7 Cells
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Rhizome
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chemistry
10.Urinary iodine level and influencing factors of university students in Tianjin in 2011
Li, LI ; Hong-wei, LI ; Yan, SONG ; Ming-xiao, LANG ; Yuan, ZHANG ; Lai-xiang, LIN
Chinese Journal of Endemiology 2012;31(3):308-310
ObjectiveTo evaluate the iodine nutritional status of university students in Tianjin and analyze influencing factors affecting urinary iodine levels.MethodsStudents of Tianjin Medical University,Tianjin Nankai University,Tianjin University of Finance and Economics and Tianjin University of Traditional Chinese Medicine were selected as survey subjects,and 50 - 100 morning urinary samples were collected from each university,respectively.Urinary iodine was measured by arsenic-cerium catalytic spectrophotometry.The students were surveyed with questionnaires,which included family information,age, sex, specialty, iodine nutrition knowledge,source of drinking water,smoking or not and dietary habits.ResultsA total of 269 urine samples were collected,and the median urinary iodine was 213.68 μg/L.Urinary iodine levels(263.86 μg/L) of medical students was significantly higher than that( 168.01 μg/L,x2 =12.144,P < 0.01 ) of non-medical students.There was an increasing trend of the level of urinary iodine of students with iodine nutrition knowledge scores > 5 points (223.70 μg/L) over that of ≤5 points( 185.56 μg/L),but the difference was not significantly different statistically (x2 =2.297,P > 0.05).Different gender and water sources had no significant effect on urinary iodine level(x2 =0.002,0.687,respectively,all P > 0.05).Smokers urinary iodine levels( 154.55 μg/L) decreased compared with non-smokers(215.38 μg/L),but the difference was not statistically significant (x2 =0.515,P> 0.05).Vegetarian urinary iodine levels were lower than that of non-vegetarians,but the difference was not statistically significant(x2 =0.594,P > 0.05).ConclusionsIodine nutritional status of students in university of Tianjin are generally at an appropriate level,but professional knowledge,habits and other factors may affect the intake of iodine,so students should develop good dietary habits to ensure a normal iodine nutrition status.