1.Relationship between serum levels of vascular endothelial growth factor and matrix metalloproteinase-9 and Suzuki' s grading in adult moyamoya disease
Wenhua LIU ; Wusheng ZHU ; Xianjun HUANG ; Wen SUN ; Guanzhong NI ; Minmin MA ; Gelin XU ; Xinfeng LIU
Chinese Journal of Neurology 2012;45(6):404-408
Objective To investigate the relationship between serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and Suzuki' s grading system in adult moyamoya disease (MMD).Methods Fifty-two adult patients with MMD,who were diagnosed in Jinling hospital between April 2009 and January 2010,were retrieved from the Nanjing Stroke Registry Program (NSRP).Sixteen sex- and age-matched healthy individuals with MMD patients consisted of the control group.Using enzyme-linked immunosorbent assay,serum concentrations of VEGF and MMP-9 were compared between adult MMD patients and healthy individuals.By Suzuki' s six-grading system,patients were divided into different subgroups,and the correlation of serum levels of VEGF and MMP-9 corresponding to different subgroup and Suzuki's grading was respectively analyzed.In addition,the correlation of serum levels of VEGF and MMP-9 was also evaluated.Results Serum VEGF concentrations in ischemic and hemorrhagic MMD patients was respectively ( 289.4 + 69.2 ) pg/ml and ( 324.3 ± 95.6 ) pg/ml and were significantly higher compared to those in healthy controls ( ( 63.5 ± 7.6 ) pg/ml; F =69.43,P < 0.01 ).Similar findings were observed for MMP-9 ( ( 499.4 ± 76.2 ) ng/ml and ( 531.2 + 100.2 ) ng/ml versus (257.1 ±30.7) ng/ml; F =66.023,P <0.01 ).With the increase of Suzuki' s grading,serum levels of VEGF and MMP-9 respectively showed a high trend ( r =0.879,P < 0.01:r =0.838,P < 0.01 ).In addition,a positive correlation between serum levels of VEGF and MMP-9 was found in the MMD group( r =0.590,P <0.01 ).Conclusion The results show that serum levels of VEGF and MMP-9 in adult MMD are higher than those in healthy controls,which may play a role in neovascularization in MMD,and moreover,serum levels of VEGF and MMP-9 show a high trend with the progression of MMD,which suggest that serum levels of VEGF and MMP-9 can reflect the severity of MMD.
2.Patterns of collateral distribution in adult moyamoya disease
Wenhua LIU ; Guanzhong NI ; Xianjun HUANG ; Wen SUN ; Wusheng ZHU ; Gelin XU ; Xinfeng LIU
Chinese Journal of Neurology 2012;45(3):149-153
Objective To study the patterns of collateral circulation in adults moyamoya disease (MMD). Methods One hundred and nineteen consecutive adult patients with MMD (ischemic or hemorrhagic type) were identified by digital cerebral angiography in Nanjing Stroke Registry Program of Jinling Hospital between August 2004 and January 2010.The extracranial and (or) intracranial collateral circulations ipsilateral to stroke hemisphere were regarded as the research objects,and furthermore,these collateral circulations were divided into three different grades:Grade 1 collateral (anterior cerebral artery (ACA) → meningeal arteries (MLA) → middle cerebral artery (MCA) ),Grade 2 collateral ( dilating and extensing anterior choroidal artery beyond choroid fissure,patent posterior communicating artery → posterior cerebral artery→MLA→ ACA and(or) MCA,posterior cerebral artery→MLA→ACA and (or) MCA and posterior choroidal artery → posterior pericallosal arteries → ACA ) and Grade 3 collateral (collateral originating from the external carotid artery supplying to cerebral blood flow). The relationship between collateral distribution patterns in adult MMD and Suzuki' s classification was analyzed.Results In 117 assessed vessel units of the collateral circulation ipsilateral to stroke hemisphere,there were a total of 200 collateral circulations.The percentage of numbers in Grade 1,Grade 2 and Grade 3 collateral was 11.5%(23/200),52.0% (104/200) and 36.5% (73/200),respectively.The distribution percentage of Grade 1 was gradually decreased from Suzuki's Ⅰ to Ⅵ,mainly distributed in the early stage of MMD ( Suzuki's Ⅰ -Ⅱ ) and accounted for 91.3% (21/23; Z =- 7.270,P < 0.01 ).The distribution percentage of Grade 3 was gradually increased from Suzuki' s Ⅰ to Ⅵ,especially in the late stage of MMD ( Suzuki' s Ⅴ-Ⅵ) and accounted respectively for 37.0% (27/73) and 63.0% (46/73; Z =-7.270,P <0.01 ).Compared with the total distribution of Grade 1 and 3 collateral circulation,the distribution percentage of Grade 2 was 6.7% (7/104),7.7% (8/104),15.4% ( 16/104),40.4% (42/104),14.4% (15/104)and 15.4% (16/104) from Suzuki' s Ⅰ to Ⅶ.Although there was not significant difference,Grade 2 mainly distributed in the medium stage of MMD ( Suzuki' s Ⅲ-Ⅳ ).Conclusions The patterns of collateral distribution is various,changing with the progression of MMD. Grade 2 collateral circulation accounts for a higher proportion,especially in the medium stage of the disease,which suggests that these collaterals play an important compensatory role of blood flow.
3.Chemical constituents from Artemisia annua.
Yi-wu ZHAO ; Fu-yong NI ; Ya-ling SONG ; Sheng-yang WANG ; Wen-zhe HUANG ; Zhen-zhong WANG ; Wei XIAO
China Journal of Chinese Materia Medica 2014;39(24):4816-4821
OBJECTIVETo investigate the chemical constituents of dried whole plants of Artemisia annua.
METHODThe chemical constituents were isolated by repeated silica gel chromatography, medium pressure column chromatography, and semi-preparative HPLC, and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literature.
RESULT15 compounds were isolated and identified to be 5-O-[(E)-Caffeoyl] quinic acid(l), 1,3-di-O-caffeoylquinic acid(2), 4 5-di-O-caffeoylquinic acid(3), 3, 5-di-O-caffeoylquinic acid (4), 3, 4-di-O-caffeoylquinic acid (5), methyl-3,4-di-O-caffeoylquinic acid(6), methyl-3,5-di-O-caffeoylquinic acid(7), 3,6'-O-diferuloylsucrose(8), 5'-β-D-glucopyranosyloxyjasmonic acid(9), Scopoletin(10), scoparone (11), 4-O-β-D-glucopyranosyl-2-hydroxyl-6-methoxyacetophenone (12), chrysosplenol D (13), casticin (14), chrysosplenetin(15).
CONCLUSIONCompounds 2, 6, 8 and 9 are obtained from the Artemisia genus for the first time. Compounds 7 and 15 are obtained from this plant for the first time.
Artemisia annua ; chemistry ; Chromatography, Gel ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Medicine, Chinese Traditional ; Plants, Medicinal ; Quinic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Silica Gel
4.A preliminary study of cerebral microbleeds in adult patients with moyamoya disease
Wen SUN ; Wenhua LIU ; Cuiping YUAN ; Song YANG ; Xianjun HUANG ; Guanzhong NI ; Shuangyin ZHU ; Jin FAN ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2010;18(9):641-645
Objective To investigate the incidence,distribution patterns,and influencing factors of cerebral microbleed (CMB) in Chinese adult patients with moyamoya disease.Methods Thirty consecutive patients with moyamoya disease confirmed by digital subtraction angiography from the Nanking Stroke Registry Program were included.All patients performed conventional MRI sequences (3.0 T) and susceptibility-weighted imaging.The clinical data,such as medical history,systolic blood pressure,diastolic blood pressure,mean arterial pressure,and white matter lesions were collected.Their fasting blood glucose levels and fibrinogen levels were detected.The numbers of CMB lesion,distribution information,and their relationship with various clinical parameters in patients with moyamoya disease were analyzed.Results Among the 30 subjects included,14 CMBs were detected in 10 patients from 11 hemispheres.The distribution of the lesions was mainly in deep brains (71.4%),especially in the periventricular white matter (50.0%).There was no statistical difference in age,gender,hemorrhage symptoms,blood pressure,white mater lesions,and plasma fibrinogen levels between the CMB positive group and CMB negative group.However,the fasting blood glucose levels in the former was significantly higher than those in the latter (8.0 ± 4.1 mmol/Lvs.4.8 ± 0.4 mmol/L;P =0.035).Multivariate regression analysis showed that the increased fasting blood glucose level was an independent risk factor for the occurrence of CMBs in adult patients with moyamoya disease (OR = 10.992,95% CI 1.325-91.218;P=0.026).Conclusions The CMB lesions are susceptible to Chinese adult patients with moyamoya disease in deep brains,especially in the periventricular white matter.The fasting blood glucose level may influence the incidence of CMBs in patients with moyamoya disease.
5.Studies on Screening,Identification and Fermentation Characters of a Yeast Strain Fermentation Ethanol from Xylose-Glucose
Deng-Feng YANG ; Li-Xia PAN ; Ni GUAN ; Hui-Zhi MI ; Wen-Pu ZUO ; Ri-Bo HUANG ;
China Biotechnology 2006;0(10):-
A model for screening the yeast which can ferment xylose to produce the ethanol was constructed.An ethanol yeast was obtained using the lignocellulose as substrate production the ethanol.By malt extract medium pre-culturing,soil samples use the plate with xylose as sole carbon source as the primary screening,then finally screen by the potassium dichromate color-displaying method.A strain named Y2-3 was screened from the soil.Phenotypic analysis including morphology and physiology and biochemical characteristics and 26D1/D2 sequence analysis were carried out.Based on taxonomy results,the Y2-3 was identified as Pichia caribbica.The strain Y2-3 ferments using xylose as sole carbon source: biomass 23.5 g/L,xylose utilization rate 94.7 %,ethanol final yield 4.57 g/L;using mixture sugar:biomass 28.6 g/L,xylose utilization rate 94.2 %,glucose utilization rate 95.6%,ethanol final yield 20.6 g/L.Pichia caribbica is a yeast which can utilize xylose and mixture sugar as substrate.It established the foundation for further research fermentation of ethanol by yeast using lignocellulose.
6.Pharmacokinetics and Tolerability of Oral Dosage Forms of Huperzine A in Healthy Chinese Male Volunteers: a Randomized,Single Dose, Three-period, Six-sequence Crossover Study
WU SAN-LAN ; GAN JUN ; RAO JING ; HE SI-JIE ; ZHU WEN-WEN ; ZHAO YING ; LV YONG-NING ; HUANG JIAN-GENG ; LIU YA-NI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2017;37(5):795-802
Huperzine A is a potent,reversible,and blood-brain barrier permeable acetylcholinesterase irhibitor.The aim of this study was to compare the pharmacokinetics,tolerability,and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting,healthy Chinese male population.This was a randomized,single-dose,3-period,6-sequence crossover study.The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry.Tolerability was assessed based on subject interview,vital sign monitoring,physical examination,and routine blood and urine tests.The mean (SD) pharmacokinetic parameters of the reference drug were Cmax,1.550 (0.528) ng/mL;t1/2,12.092 (1.898) h;AUC0-72h,17.550 (3.794) ng.h/mL.Those of the test formulation A and test formulation B were Cmax,1.412 (0.467),1.521 (0.608) ng/mL;t1/2,12.073 (2.068),12.271 (1.678) h;AUC0-72h,15.286 (3.434) ng.h/mL,15.673 (3.586) ng.h/mL.The 90% confidence intervals for the AUC0-72h and Cmax were between 0.80 and 1.25.No adverse events were reported by the subjects or found with results of clinical laboratory test.The test and reference products met the regulatory criteria for bioequivalence in these fasting,healthy Chinese male volunteers.All three formulations appeared to be well tolerated.
7.Effects of low-level lead exposure on the neurobehavioral development of infants and early intervention.
Hui ZHENG ; Wen-Xuan LIN ; Hua-Yun HU ; Jian-Hong HUANG ; Meng-Ni HUANG ; Yan-Shi HE
Chinese Journal of Preventive Medicine 2008;42(3):165-168
OBJECTIVETo explore the effects of low-level lead exposure on infant's neurobehavioral development and evaluate the effects of early intervention.
METHODSThe study population consisted of 276 infants whose blood lead, cadmium, iron, zinc, copper, magnesium and calcium concentrations were measured by atomic absorption spectroscopy and developmental status were assessed using the Gesell developmental Diagnosis scales (GDDS) at 6 months of age. All study subjects was divided into three groups: 58 infants in control group, 162 infants in low lead group and 56 infants in high lead group. On the basis infants of both the low and high lead groups were provided with interventional measures for 3 months, and tests for the blood lead, cadmium, iron, zinc, copper, magnesium, calcium and GDDS were repeated for all infants both 12 and 18 months of ages.
RESULTSInfant' s developmental outcome revealed the developmental quotient was the lowest in the high lead group (86.74 +/- 9. 35), the lesser low in the low lead group (91.52 +/- 10.12) and the highest in control group (100.71 +/- 6.92). Changes in developmental quotient were detected in both the low and high lead groups with statistical significance (P < 0.05) after intervention measures adopted. However, the changes of developmental quotient were more remarkable in the low lead group and after the 18th month there was no statistical significance than control group (t = 1.721, P > 0.05) while the significant difference was found in between the high lead group and the control group (t = 23.495, P < 0.05).
CONCLUSIONLow-level lead exposure interfered infant's neurobehavioral development and early intervention might improve infant's developmental quotient.
Child Development ; drug effects ; Early Intervention (Education) ; Humans ; Infant ; Infant Behavior ; drug effects ; Lead ; adverse effects ; blood ; Lead Poisoning ; complications ; prevention & control
8.Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor.
Tao ZHU ; Wei ZHANG ; Dao-xin WANG ; Ni-wen HUANG ; Hong BO ; Wang DENG ; Jia DENG
Chinese Medical Journal 2012;125(8):1457-1464
BACKGROUNDAsthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma.
METHODSBALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid (BALF) and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-α in BALF. Periodic acid-Schiff (PAS) staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor (GABAAR) β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.
RESULTSRosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-α in BALF, along with the histological mucus index (HMI) and GABAAR β2 expression. Changes occurred in a dose-dependent manner.
CONCLUSIONSBased on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.
Animals ; Asthma ; drug therapy ; metabolism ; Chronic Disease ; Disease Models, Animal ; Female ; Fluorobenzenes ; pharmacology ; therapeutic use ; GABA-A Receptor Antagonists ; pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Lung ; chemistry ; Mice ; Mice, Inbred BALB C ; Mucus ; secretion ; Pyrimidines ; pharmacology ; therapeutic use ; Receptors, GABA-A ; analysis ; Rosuvastatin Calcium ; Sulfonamides ; pharmacology ; therapeutic use
10.Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives.
Liu-zhou GAO ; Yu-suo XIE ; Qiang YAN ; Shu-min WU ; Li-li NI ; Hui ZHAO ; Wen-long HUANG ; Guo-qiang HU
Acta Pharmaceutica Sinica 2015;50(8):1008-1012
To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.
Amides
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chemical synthesis
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pharmacology
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Antineoplastic Agents
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chemical synthesis
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pharmacology
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Cell Line, Tumor
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Fluoroquinolones
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chemical synthesis
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pharmacology
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HL-60 Cells
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Humans
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Ketones
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chemical synthesis
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pharmacology
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Rhodanine
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chemical synthesis
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pharmacology