3.Effects of simvastatin on expressions of uPA/PAI-1 in neutrophils in rats with septic shock
Xiaoling WU ; Li YU ; Ding LONG ; Xingwen DA ; Zhangyin MING
The Journal of Practical Medicine 2016;32(4):519-522
Objective To explore the effects of simvastatin on the protein expressions of urokinase-typeplasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). Methods Male Sprague–Dawley rats were divided into saline group , LPS group and LPS plus simvastatin group , and were then pretreated with simvastatin (1 mg/kg) for 30 minutes before addition of LPS (8 mg/kg). Changes in left ventricular pressure were recorded. Ninety minutes after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated. The neutrophils were then lysed to detect levels of uPA and PAI-1. Results Left ventricular systolic pressure (LVSP: mmHg), maximal differential of left ventricular pressure (+dp/dtmax:mmHg/s), and heart rate (beats/min) were markedly decreased at different time points after administration of LPS, and maximal differential of left ventricular pressure increased in the rats receiving LPS as compared with those receiving saline, although the differences between the control and LPS groups were not statistically significant. LPS caused a great decline in uPA content and an elevation in PAI-1 content in neutrophils, but simvastatin diminished the impact of LPS on neutrophils. Conclusion Simvastatin plays a role in protection of cardiac function in rats with LPS-induced septic shock , and controls expressions of uPA and PAI-1 in neutrophils.
4.Morphologic study of tonsillar B-cell lymphomas.
Miao-Xia HE ; Jian-Ming ZHENG ; Li-Li WU ; Da-Lie MA ; Ming-Hua ZHU
Chinese Journal of Pathology 2007;36(2):127-128
Adult
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Aged
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Antigens, CD20
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metabolism
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Diagnosis, Differential
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Female
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Humans
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Immunohistochemistry
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Leukocyte Common Antigens
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metabolism
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Lymphoma, B-Cell
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genetics
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metabolism
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pathology
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surgery
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Lymphoma, Extranodal NK-T-Cell
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pathology
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Lymphoma, Large B-Cell, Diffuse
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genetics
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metabolism
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pathology
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surgery
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Male
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Middle Aged
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Tonsillar Neoplasms
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genetics
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metabolism
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pathology
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surgery
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Tonsillectomy
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Tonsillitis
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pathology
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Young Adult
5.Effect of Kanli Granule on Myocardial Mechanics in Pressure Overload Induced Diastolic Heart Failure Rats.
Yong-ming LIU ; Da-zheng WU ; Yu-ya XU ; Ming-zi TENG ; Mei-xian JIANG
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(2):196-202
OBJECTIVETo observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.
METHODSTotally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.
RESULTS(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).
CONCLUSIONSThe ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.
Animals ; Colforsin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; physiopathology ; Heart Failure, Diastolic ; drug therapy ; Isoproterenol ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Wistar
6.Progress in small-molecule inhibitors of Bcl-2 family proteins.
Yong TANG ; Da-yong ZHANG ; Xiao-ming WU
Acta Pharmaceutica Sinica 2008;43(7):669-677
Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.
Antimycin A
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chemistry
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pharmacology
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Antineoplastic Agents
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chemistry
;
pharmacology
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Apoptosis
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drug effects
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Benzopyrans
;
chemistry
;
pharmacology
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Biphenyl Compounds
;
chemistry
;
pharmacology
;
Cell Line, Tumor
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Drug Design
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Drugs, Chinese Herbal
;
chemistry
;
pharmacology
;
Gossypol
;
chemistry
;
pharmacology
;
Humans
;
Nitriles
;
chemistry
;
pharmacology
;
Nitrophenols
;
chemistry
;
pharmacology
;
Piperazines
;
chemistry
;
pharmacology
;
Proto-Oncogene Proteins c-bcl-2
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antagonists & inhibitors
;
pharmacology
;
Structure-Activity Relationship
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Sulfonamides
;
chemistry
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pharmacology
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Thiazoles
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chemistry
;
pharmacology
;
bcl-X Protein
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antagonists & inhibitors
;
pharmacology
7.Classification and synthesis of ubiquitin-proteasome inhibitor.
Jing LI ; Da-Yong ZHANG ; Xiao-Ming WU
Acta Pharmaceutica Sinica 2009;44(12):1313-1319
The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular target for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, the proteasome complex inhibitor Bortezomib was approved for use in multiple myeloma patients by FDA in 2003. Drug discovery programs in academy and the pharmaceutical industry have developed a range of synthetic and natural inhibitors of the 20S proteasome core particle that have entered human clinical trials as significant anti-cancer leads. The main results from the use of proteasome inhibition in cancer chemotherapy, the structure of several proteasome inhibitors and their synthesis is going to be reviewed in this paper.
Acetylcysteine
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analogs & derivatives
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chemical synthesis
;
chemistry
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Antineoplastic Agents
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chemical synthesis
;
classification
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therapeutic use
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Boronic Acids
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chemical synthesis
;
chemistry
;
therapeutic use
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Bortezomib
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Cysteine Proteinase Inhibitors
;
chemical synthesis
;
classification
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Dipeptides
;
chemical synthesis
;
chemistry
;
Humans
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Multiple Myeloma
;
drug therapy
;
enzymology
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Peptides, Cyclic
;
chemical synthesis
;
chemistry
;
Proteasome Endopeptidase Complex
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metabolism
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Proteasome Inhibitors
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Pyrazines
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chemical synthesis
;
chemistry
;
therapeutic use
;
Ubiquitin
;
antagonists & inhibitors
;
metabolism
9.Transcription of chemokine receptors in villi and trophoblasts of human first trimes-ter gestation
Xia WU ; Da-Jin LI ; Min-Min YUAN ; Ming-Yan WANG ; Haidong CHENG ;
Chinese Journal of Immunology 1985;0(01):-
Objective: To investigate the mRNA expression of chemokine receptors in human villi and trophoblasts of first trimester gestation . Methods: The authors first obtained villous tissues from fifteen women who had undergone selective termination at 5 - 10 weeks of normal gestation. Total RNA was then extracted, using the TRIzol reagent, from villous tissues or Percoll-gradient purified trophoblasts. Consequently, the expressions of chemokine receptors in villous tissues and trophoblasts were investigated by way of semi-quantitative reverse transcriptase-polymerase chain reaction.Results: The chemokine receptors, CXCR4 and CXCR6, were highly expressed in each villous tissue, while the CCR6, CCR7, XCR1 and CX3CR1 were moderately expressed in villi. The chemokine receptors, CCR1- CCR5, CCR8 - CCR10, CXCR1 -CXCR3, were expressed only in some villous samples, while no CXCR5 mRNA was found in any villous tissue. The authors also found that the freshly isolated and Percoll-purified trophoblasts expressed CCR1, CCR3 - CCR5, CCR8 - CCR9, CXCR1 - CXCR4, CXCR6, XCR1 and CX3CR1 mRNA. Conclusion: A variety of chemokine receptors were expressed in villous tissues and trophoblasts of human first trimester gestation, hence, these receptors may play an important biological role at the materno-fetal interface in normal human pregnancy.
10.Investigation of root canal curvature of human maxillary first premolar in buccolingual directions.
Da-ming WU ; You-nong WU ; Rui-zhen LIANG
West China Journal of Stomatology 2007;25(2):149-152
OBJECTIVETo investigate root canal curvatures of human maxillary first premolars in buccolingual directions.
METHODSOne hundred extracted permanent maxillary first premolars were used. After access preparation, a K-file was inserted into the canals and gently advanced until it reached the apical foramen. Then standardized periapical radiovisiography (RVG) images were taken from mesiodistal direction. The angle of curvature was determined according to the method described by Schneider. The radiu of curvature and length of the curved part of the root canal were calculated.
RESULTS1) The total 50.00% (88/176) of root canal curves were in buccolingual directions, and 53 curves were showed in apical 1/3 of root region. 11.93% (21/176) of S-shaped canals were detected, and the first curves were mostly showed in middle 1/3 of root region, the secondary curves were totally showed in apical 1/3 of root region. 2) There was no difference of curvatures between buccal and lingual root canals, but the secondary curves of S-shaped canals were more complicated than other root canals. 3) There was no correlation between the angle of curvature and the radius of curvature (r=0.002, P>0.05), but significantly correlation between the angle of curvature and length of the curved part of the root canal (r=0.489, P<0.01).
CONCLUSIONThe occurrence of curved root canals in buccolingual directions may be high in human maxillary first premolars, and the curvatures of S-shaped canals were more complicated than others.
Bicuspid ; Dental Pulp Cavity ; Humans ; Root Canal Therapy ; Tooth Root