2.Cytotoxicity of epigallocatechin-3-gallate to LNCaP cells in the presence of Cu2+
Hai-Ning YU ; Sheng-Rong SHEN ; Yao-Kang XIONG
Journal of Zhejiang University. Science. B 2005;6B(2):125-131
Epigallocatechin-3-gallate (EGCG) has shown remarkably anti-cancer activity, with its bioactivity being related to reactive conditions, such as pH and metal ions. The present study investigated the degradation of EGCG and its effect on prostate cancer cell in the presence of Cu2+. EGCG was incubated with prostate cancer cells, LNCaP, pretreated with or without Cu2+.EGCG in F-12 medium was quantified using HPLC and the viability of cells was assessed by gel electrophoresis, flow cytometry,and electron microscope. The results of HPLC showed that EGCG degraded completely within 12 h in F-12 medium with or without Cu2+. Gel electrophoresis and flow cytometry did not detect apoptosis of LNCaP cells when they were incubated with EGCG. Electron microscopy examination revealed that EGCG-Cu2+ complex led to damage of cytoplasm membrane in LNCaP cells. It was speculated that not EGCG, but its oxide and complex with Cu2+, are the bioactive components responsible for its cytotoxicity to LNCaP prostate cancer cells.
3.Cytotoxicity of epigallocatechin-3-gallate to LNCaP cells in the presence of Cu2+.
Hai-ning YU ; Sheng-rong SHEN ; Yao-kang XIONG
Journal of Zhejiang University. Science. B 2005;6(2):125-131
Epigallocatechin-3-gallate (EGCG) has shown remarkably anti-cancer activity, with its bioactivity being related to reactive conditions, such as pH and metal ions. The present study investigated the degradation of EGCG and its effect on prostate cancer cell in the presence of Cu2+. EGCG was incubated with prostate cancer cells, LNCaP, pretreated with or without Cu2+. EGCG in F-12 medium was quantified using HPLC and the viability of cells was assessed by gel electrophoresis, flow cytometry, and electron microscope. The results of HPLC showed that EGCG degraded completely within 12 h in F-12 medium with or without Cu2+. Gel electrophoresis and flow cytometry did not detect apoptosis of LNCaP cells when they were incubated with EGCG. Electron microscopy examination revealed that EGCG-Cu2+ complex led to damage of cytoplasm membrane in LNCaP cells. It was speculated that not EGCG, but its oxide and complex with Cu2+, are the bioactive components responsible for its cytotoxicity to LNCaP prostate cancer cells.
Anticarcinogenic Agents
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administration & dosage
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Apoptosis
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drug effects
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Catechin
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administration & dosage
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analogs & derivatives
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Cell Line, Tumor
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Cell Proliferation
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drug effects
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Cell Survival
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drug effects
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Copper
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administration & dosage
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metabolism
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Dose-Response Relationship, Drug
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Drug Combinations
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Humans
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Male
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Prostatic Neoplasms
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drug therapy
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pathology
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physiopathology
4.Non-nucleoside reverse transcriptase inhibitors (Part 18): synthesis and anti-HIV activity of 4-allylamino or 4-azido substituted diaryltriazines.
Yuan-Zhen XIONG ; Hai-Rong HU ; Fen-Er CHEN ; Jan BALZARINI ; Christophe PANNECOUQUE ; Erik de CLERCQ
Acta Pharmaceutica Sinica 2009;44(2):145-149
Eight new diaryltriazine derivatives containing 4-allylamino and 4-azido substitutes guided by molecular docking have been designed and synthesized based on our previous work. The evaluation of HIV inhibitory activity demonstrated that all compounds were potent against HIV-1 replication. The most active compound 7c exhibited activity against HIV-1 (IC50 = 0.034 micromol x L(-1), SI = 6,475) and the double mutant strain (IC50 = 9.39 micromol x L(-1)) in the micromolar range, which was more potent than nevirapine.
Anti-HIV Agents
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chemical synthesis
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chemistry
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pharmacology
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Catalytic Domain
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HIV-1
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drug effects
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Inhibitory Concentration 50
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Molecular Structure
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Reverse Transcriptase Inhibitors
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chemical synthesis
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chemistry
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pharmacology
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Triazines
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chemical synthesis
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chemistry
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pharmacology
5.A case-control study on risk factors for nosocomial infection by extended-spectrum beta-lactamases-producing bacteria.
Rong JIN ; Xiang-yang LI ; Hai-shen KONG ; Guo-xiong LI ; Wei WANG
Chinese Journal of Preventive Medicine 2003;37(1):41-44
OBJECTIVETo explore the risk factors for nosocomial infection caused by extended-spectrum beta-lactamases (ESBLs)-producing bacteria in hospitals of Zhejiang province.
METHODSOne hundred and eighty-five cases with nosocomial infection (108 men and 77 women, with an average age of 55 +/- 17 years) caused by positive-ESBLs bacteria, including 59 cases of respiratory infection, 71 with urinary infection, ten with blood infection, 30 with wound infection and 59 with other infection, and 77 controls with nosocomial infection (54 men and 23 women, with an average age of 54 +/- 20 years) caused by negative-ESBLs bacteria, including 38 cases of respiratory infection, 20 with urinary infection, six with blood infection, eight with wound infection and five with other infection, from six hospitals in Zhejiang Province were studied during May 1999 to May 2000. Data were analyzed with unconditional logistic regression and principal component analysis (PCA).
RESULTSMultivariate unconditional logistic regression analysis showed that the independent risk factors for nosocomial infection were use of the third generation cephalosporins for more than three days (odds ratio, OR 4.52, 95% confidence interval of OR 2.30 - 8.89), combined use of antibiotics (OR 2.86, 95% CI 1.51 - 5.43), use of quinolones for more than three days (OR 2.44, 95% CI 1.18 - 5.04), use of adrenal cortical hormone (OR 2.16, 95% CI 1.08 - 4.31) and oxygen inhalation (OR 2.56, 95% CI 1.14 - 5.72). Five principal components were extracted from the 14 risk factors for nosocomial infection with ESBLs-producing bacteria by principal component analysis, with a contribution of cumulative variance of 60.2%, and arranged in an order as follows, use of ventilator, tracheal intubation or tracheotomy, oxygen inhalation, retaining needle in vein, indwelling urethral catheter, use of the third generation cephalosporins over three days, hospitalization over ten days, use of quinolones over three days, combined use of antibiotics, use of aminoglycosides antibiotic over a week, use of adrenal cortical hormone, catheterized examination and prophylactic use of antibiotics.
CONCLUSIONSNosocomial infection with ESBLs-producing bacteria could attribute to multiple factors, mainly to invasive manipulation and use of antibiotics.
Case-Control Studies ; Cephalosporins ; pharmacology ; China ; epidemiology ; Cross Infection ; epidemiology ; microbiology ; Drug Resistance, Bacterial ; physiology ; Drug Therapy, Combination ; pharmacology ; Drug Utilization ; Female ; Humans ; Length of Stay ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Multivariate Analysis ; Risk Factors ; beta-Lactamases ; metabolism
6.Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet.
Xi ZHANG ; Su-Li ZHANG ; Hai-Yan XIONG ; Yun-Hui DU ; Lin QUAN ; Jie YANG ; Xiu-Rui MA ; Hui-Rong LIU
Acta Physiologica Sinica 2011;63(2):149-154
Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values: 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These results suggest that the offspring of AT1-Ab-positive pregnant rats are more susceptible to vascular functional abnormality while being fed high-salt diet.
Animals
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Antibodies
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blood
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Cardiovascular Diseases
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etiology
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physiopathology
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Disease Susceptibility
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Female
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Fetal Growth Retardation
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physiopathology
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Immunization
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Pregnancy
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Prenatal Exposure Delayed Effects
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Rats
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Rats, Wistar
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Receptor, Angiotensin, Type 1
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immunology
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Sodium Chloride, Dietary
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administration & dosage
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adverse effects
7.hPARP1 genetic polymorphism in southern Chinese Han and Miao populations.
Huan-wen TANG ; Hai-rong LIANG ; Zhi-xiong ZHUANG ; Da-lin HU
Chinese Journal of Medical Genetics 2006;23(5):578-580
OBJECTIVETo study hPARP1 genetic polymorphism in southern Chinese Han and Miao populations.
METHODSBlood samples from 187 and 210 southern healthy Han and Miao populations were collected. The mutations of exons 12,13,16 and 17 of hPARP1 gene were investigated by PCR-single-strand conformation polymorphism(SSCP).
RESULTSFragments of 253 bp,313 bp,175 bp,362 bp within exons 12,13,16 and 17 respectively of hPARP1 gene were amplified by multiple PCR. An SSCP variant in exons 12,13,16 and 17 of PARP1 gene in 187 healthy Han and 210 healthy Miao individuals was identified. Seven single-base substitutions compared with the sequence of PARP1 gene were identified: a T to C transition in exon 12 (Phe548Ser), a G to T transition in exon 13 (Ala683Ser), a G to T transition in exon 16 (Asp798Tyr), and a A to G transition in exon 17 (His808Arg).
CONCLUSIONThere were polymorphism sites in exons 12,13,16,17 of hPARP1 gene in southern Chinese Han and Miao populations; these results may be useful for the establishment of PARP1 genotyping, and these newly described PARP1 alleles would be advantageous indicators for population studies.
Adult ; Alleles ; China ; Exons ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; Polymorphism, Single-Stranded Conformational
8.Low concentration of hydroquinone-induced adaptive response in hPARP-1 protein normal and deficient cells.
Huan-wen TANG ; Hai-rong LIANG ; Zhi-xiong ZHUANG ; Yun HE
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(4):274-277
OBJECTIVETo investigate whether or not adaptive response of hPARP-1 protein normal and deficient cells is induced by low dose of hydroquinone (HQ), and to analyze the relationship between the adaptive response and micronuclei formation, and cell cycle alteration in human embryo lung fibroblasts (HLF), so as to elucidate the mechanism of adaptive response.
METHODSHLF, HLFC and HLFP cells pretreated with low concentration were retreated by high concentration of HQ. Cellular viability, the rate of micronuclei and abnormal nuclei, cell cycle and DNA strand break were determined.
RESULTSThe tolerance to 80.0 micromol/L concentration of HQ was enhanced when HLF, HLFC and HLFP cells were pretreated with HQ from 0.001 - 0.050 micromol/L. There were varying degrees of micronuclei and abnormal nuclei in three cells pretreated with low concentration of HQ and then retreated with high concentration of HQ; the cell numbers of G1, G2, S phase in cell cycle were obviously different. When compared with only high attack dose, the micronuclei rate and abnormal nuclei rate of HLF, HLFC and HLFP decreased by pretreatment with HQ at high concentration (P < 0.05), meanwhile increased by pretreatment with HQ at low concentration (P < 0.05). HLF, HLFC and HLFP showed blockage in G2 phase when pretreated with HQ at 0 approximately 0.05 micromol/L, but HLFP showed blockage in G1 phase, and in S phase at 1.0 and 2.0 micromol/L.
CONCLUSIONThe level of adaptive response of hPARP-1 protein deficient cells was lower than normal cell, suggesting that hPARP-1 protein may play an important role in the adaptive response of cells, which may be related with the regulation of cell cycle.
Cell Cycle ; Cell Nucleus ; Cell Survival ; Cells, Cultured ; Dose-Response Relationship, Drug ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Hydroquinones ; toxicity ; Lung ; cytology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism
9.Epidemiologicai analysis of plague in Qinghai province from 2001 to 2010
Bai-qing, WEI ; Zu-yun, WANG ; Rong-jie, WEI ; Rui-xia, DAI ; Hai-hong, ZHAO ; Xiao-yan, YANG ; Hao-ming, XIONG ; You-quan, XIN ; Jun, LI
Chinese Journal of Endemiology 2011;30(5):521-523
Objective To explore the plague epidemical trend of nearly a 10 years data in Qinghai province to provide basis for making the prevention and control measures. Method The regional distribution and time distribution of animal and human plague, monitoring and plague foci of survey data in Qinghai from 2001 to 2010 were analyzed with Excel software 2003. Results In Qinghai province, a total of 167 strains of Yersinia pestis were isolated from infected animals and insects in 10 years. Yersinia pestis was mainly distributed in Wulan,Delinha, Geermu, and Tianjun, along the Qinghai-Xizang railway. Human plague was occurred every year from 2001 to 2010 except 2002, 2007, 2008, and 2010. In the 10 years, there were 37 plague cases and 16 of these cases died, the mortality was 43.24%. The plague cases were mainly distributed in Nangqian, Qumalai, Chenduo,Zhiduo, Xinghai, Tongde, Tianjun, Wulan and Qilian. And these cases were found mostly in the period from May to October, especially in the period from August to October. Major clinical type of the plague cases was lung-type (62.16%,23/37). Conclusions The plague epidemic situation in Qinghai province is still severe, animal plague occurred year after year, and human plague outbreaks occasionally. Monitoring and early warning in the key areas should be strengthened, and the comprehensive measures of plague prevention and control should be carried out to reduce the incidence and prevalence of plague.
10.Effects of triterpenoids from Psammosilene tunicoides on tunicamycin-induced endoplasmic reticulum stress in RA-FLS
Xing-Yue ZHOU ; Ling QUE ; Xiong DING ; Ying-Xue ZHAO ; Feng-Rong JIANG ; Hai-Feng CHEN
Chinese Traditional Patent Medicine 2024;46(5):1499-1507
AIM To investigate the mechanism of triterpenoids quillaic acid and gypsogenin-3-O-glucuronide from Psammosilene tunicoides on tunicamycin-induced rheumatoid arthritis fibroblasts-like synoviocytes(RA-FLS)via the endoplasmic reticulum pathway.METHODS The research objects of tunicamycin-induced RA-FLS intervened with quillaic acid and gypsogenin-3-O-glucuronide had their cell proliferation activity detected;their level of tumor nerosis factor-α(TNF-α)detected by ELISA;their apoptosis detected by flow cytometry;their cell migration ability detected by Transwell experiment;their expressions of transcription activator 6(ATF-6),glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),cysteine protease protein-12(caspase-12)and anti-apoptosis Bcl-2 protein detected by Western blot;and their mRNA expressions of ATF-6,GRP78 and CHOP detected by RT-qPCR.RESULTS Compared with the model group,each group intervened with quillaic acid or gypsogenin-3-O-glucuronide displayed decreased levels of TNF-α(P<0.01);weakened cell proliferation and migration ability(P<0.01);increased apoptosis rate(P<0.01);decreased protein expressions of ATF-6 and Bcl-2(P<0.05,P<0.01);and increased protein expressions of CHOP and caspase-12(P<0.05,P<0.01).In addition,decreased GRP78 protein expression in the low and medium dose groups(P<0.05,P<0.01);decreased mRNA expression of ATF-6,GRP78(P<0.01)and increased CHOP mRNA expression(P<0.01)in the medium dose groups of quillaic acid and gypsogenin-3-O-glucuronide were observed as well.CONCLUSION Quillaic acid and gypsogenin-3-O-glucuronide may play a protective role in rheumatoid arthritis by inhibiting the proliferation and migration of RA-FLS,inducing apoptosis and reducing the secretion of related inflammatory factors via endoplasmic reticulum signal pathway.