王心如
个性化签名
- 姓名:王心如
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师
- 职称:-
-
学科领域:
细胞生物学
- 研究兴趣:
王心如,男,汉族,1950年8月生,江苏通州市人。博士、教授、博士生导师。南京医科大学毒理学研究所所长、副校长。1993-1995年在美国加州大学毒理学与环境卫生研究院和Davis分校医学院,主要从事肺癌原癌基因Kappa opioid受体和农药生殖内分泌毒理学博士后课题(NIH)研究;在Toxicology(1994)、Cancer letters(1995)和Biochem Biophys Res Commun(1995)杂志上发表论著三篇。95年回国后,曾先后主持江苏省、卫生部、国家“九五”和“十五”科技攻关项目分题,中-美及中-日-韩国际合作项目、国家自然科学基金面上项目、国家基础研究重大项目、国家重点基础研究发展规划(“973”项目)和国家高技术研究发展计划(“863”计划)分题,以及江苏省和国家高等医学教育改革课题,发表论著100余篇,被SCI收录12篇。主编卫生部第五轮规划教材《毒理学基础》和《毒理学实验方法与技术》。先后获江苏省科技进步一、二等奖各一项、中华医学科技奖二、三等奖各一项、江苏省和卫生部科技进步三等奖各一项。现任中国毒理学会副理事长兼生殖毒理专业委员会副主任、全国高等医学教材建设研究会常务理事、江苏省预防医学会副会长、江苏省应用毒理学重点实验室主任、江苏省避孕药具不良反应监测和防治研究中心专家委员会主任、江苏省普通高校优秀学科带头人、江苏省先进科技工作者和有突出贡献的中青年专家、国家新药审评专家、中华预防医学杂志、中华劳动卫生职业病杂志、中国药理学与毒理学杂志、J Environ. Prevent. Med.、中华卫生杀虫药械、中国工业医学杂志、卫生研究、环境与职业医学、现代农药、工业卫生与职业病、国外医学卫生学分册编委。
-
主页访问
1319
-
关注数
0
-
成果阅读
579
-
成果数
12
王心如, Senping Cheng a, Jianfeng Chen a, Yang Qiu a, Xia Hong a, Yankai Xia a, Ting Feng b, Jiayin Liu b, Lin Song a, Zhengdong Zhang a, Xinru Wang a, ∗
Toxicology 220(2006)37-45,-0001,():
-1年11月30日
Carbaryl is known to impede female reproductive function,however,the mechanisms through which the adverse effects are mediated are not clearly elucidated.In order to get insight into the mechanisms,this study was conducted to raise fresh concerns about the potential effects of carbaryl on steroidogenesis by primary human granulosa-lutein cells(hGLCs)and explore the possible nature of this action.hGLCs were co-incubated with various concentrations of carbaryl at 0,1,5,25,125μmol/L for 24 h to examine effects of this carbamate pesticide on progesterone accumulation. We observed that the carbaryl inhibited basal and FSH-induced progesterone production in a dose-dependent manner.We also investigated the effects of carbaryl on 22(R)-hydroxycholesterol(22R-HC)-stimulated progesterone yield,basal and FSH-stimulated StAR gene expression and cyclic adenosine monophosphate(cAMP)production,as well as forskolin(non-specific activator of adenylyl cyclase)-induced progesterone and cAMP production of hGLCs.We found that the decreased progesterone biosynthesis was accompanied with a reduced cAMP abundance on both basal and FSH-induced condition.Furthermore, our results demonstrated that the 22R-HC could remove the carbaryl-induced restraint of progesterone biosynthesis,suggesting that carbaryl caused a disruption of cholesterol transport across mitochondrial membranes,which was further confirmed by the observation that carbaryl inhibited the gene expression of steroidogenic acute regulatory protein (StAR).In addition,the inhibitory effects of carbaryl on progesterone and cAMP production were completely reversed by addition of forskolin to the cell culture,which indicated a repaired site on the upstream components of adenylate cyclase or adenylate cyclase per se by carbaryl in the cAMP-mediated signal pathway.All the effects mentioned above were not due to a detrimental action of carbaryl on cell viability by MTS assay.In conclusion,carbaryl may inhibit steroidogenesis,at least in part,by obstructing the delivery of cholesterol over mitochondrial membranes and attenuating cAMP generation.
Carbaryl, Human granulosa-lutein cells (, hGLCs), , Steroidogenesis, Cyclic adenosine monophosphate (, cAMP), , Steroidogenic acute regulatory protein (, StAR),
-
50浏览
-
0点赞
-
0收藏
-
0分享
-
82下载
-
0评论
-
引用
王心如, Lunbiao Cui a, b, Yuan Shi b, Guidong Dai b, Hongxin Pan b, Jianfeng Chen a, Ling Song b, Shouling Wang b, Hebron C. Chang b, Hongbing Sheng b, Xinru Wang a, *
Toxicology and Applied Pharmacology 210(2006)24-31,-0001,():
-1年11月30日
The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined.Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU)(20mg/kg b.w.ip) twice a week for 4 weeks,then given basal diet containing 5% TPA,5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1%TPA for the next22weeks, and then euthanized. 5%TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate.Though 5% TPA plus 4% Sodium bicarbonate(NaHCO3)and 1% TPA treatment did not induce urinary bladder calculi formation,they resulted in a moderate increase in urinary precipitate.Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia,papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control.MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia(not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (Ca TPA) may also have weak promoting activity on urinary bladder carcinogenesis.
Terephthalic acid, Urinary bladder calculi, Urinary precipitate, Promotion, Carcinogenesis
-
50浏览
-
0点赞
-
0收藏
-
0分享
-
112下载
-
0评论
-
引用
王心如, Zhengdong Zhang, Qiuling Shi, Erich M. Sturgis, , Margaret R. Spitz, Waun Ki Hong, and Qingyi Wei
Clinical Cancer Research Vol. 10 (2004) 7903-7910,-0001,():
-1年11月30日
Purpose:Folate deficiency and reduced DNA repair capacity are established risk factors for squamous cell carcinoma of the head and neck(SCCHN). We hypothesized that polymorphisms of the thymidylate synthase(TYMS)gene,which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk. Experimental Design:In a hospital-based case-control study of 704 SCCHN cases and 1,085 controls, frequency matched by age,sex, nd ethnicity,we genotyped the TSER(thymidylate synthase in the 5'-untranslated enhanced region)and TS3ˊUTR(thymidylate synthase in the 3'-untrans-lated region) polymorphisms. Results: The TS3ˊUTR 0bp/0bp genotype was associated with a significantly decreased risk of SCCHN[adjusted odd ratio(OR)=0.67,95%confidence interval (CI)=0.47-0.94] compared with the 6bp/6bp genotype, but the TSER polymorphism had no main effect on risk of SCCHN. When we evaluated the two polymorphisms together by the number of protective alleles(the TSER 3R and TS3'UTR 0bp alleles), we found that the combined genotypes with four protective alleles(the TSER 3R3R and TS3'UTR 0bp/0bp) was associated with significantly decreased SCCHN risk (OR=0.60, 95%CI=0.37-0.98). In addition,the TS3ˊUTR 0bp genotypes were associated in an allele dose-dependent manner with a decreased risk of overall stage IV oral cancer (OR=0.84, 95%CI=0.52-1.34 for the 6bp/0bp genotype and OR=0.26, 95%CI=0.08-0.87 for the 0bp/0bp genotype; Ptrend=0.035). Conclusion: The TSER and TS3'UTR polymorphisms are associated with SCCHN risk. The TSER 3R and TS3ˊUTR 0bp alleles seemed to jointly protect against SCCHN. In particular, the 0bp allele seemed to protect against oral cancer progression.
-
61浏览
-
0点赞
-
0收藏
-
0分享
-
79下载
-
0评论
-
引用
【期刊论文】Effects of fenvalerate on progesterone production in cultured rat granulosa cells
王心如, Jianfeng Chen a, b, Haiyan Chen a, b, Ru Liub, Jun Heb, Lin Song a, Qian Bian a, Lichun Xua, Jianwei Zhou a, Hang Xiao b, Guidong Dai b, Hebron C. Chang b, Xinru Wang a, ∗
Reproductive Toxicology 20(2005)195-202,-0001,():
-1年11月30日
In this study,primary serum-free cultured rat granulosa cells (rGCs) were used as a cellular model to investigate the effects of fenvalerate on progesterone production. Various concentrations (0,1,5,25,125and625μM) of fenvalerate were added to the cell cultures for 24h.rGCs were stimulated by compounds such as follicle-stimulating hormone (FSH), 8-bromo-cAMP or 22(R)-hydroxycholesterol (22R-HC) Progesterone production and intracellular cAMP content were measured in control and treated groups.Expression of P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein(StAR)were monitored by real-time PCR and Western blotting.Results showed that fenvalerate inhibited basal progesterone production in rGCs in the absence of stimulators.This inhibition was stronger in the presence of FSH and was not fully reversed by 8-bromo-cAMP or 22R-HC.The increase of cAMP content,stimulated by FSH, was inhibited by fenvalerate implicating that the intracellular cAMP-dependent signal pathway was involved.Fenvalerate reduced mRNA and protein expression of P450scc.These results suggested that multi-site inhibition of progesterone production by fenvalerate including a cAMP-dependent protein kinase pathway and reduction on P450scc gene expression and/or its enzymatic activity in rGCs.
Fenvalerate, Steroidogenesis, Steroidogenic enzymes, Cultured rat granulosa cells
-
41浏览
-
0点赞
-
0收藏
-
0分享
-
66下载
-
0评论
-
引用
【期刊论文】The roles of metallothionein on cadmium-induced testes damages in Sprague–Dawley rats
王心如, Li-Chun Xu, Hong Sun, Shu-yi Wang, Ling Song, Hebron-C Chang, Xin-Ru Wang∗
Environmental Toxicology and Pharmacology 20(2005)83-87,-0001,():
-1年11月30日
The present study was to investigate whether metallothionein(MT)was involved in sensitivity of testis to cadmium (Cd) and protection of rats from Cd-induced testis damages.The rats were treated by intraperitoneal injection with 0.2,0.4,and 0.8mgCd/kg BW for 7days.The atomic absorption spectrophotometry and cadmium hemoglobin affinity assay were applied to evaluate the contents of Cd and MT in testis and liver.The testis glutathione(GSH),malondialdehyde(MDA)and daily sperm production were measured.There were substantial increases of both Cd and MT in the liver after Cd exposure.The testis Cd and MT contents were lower than those in the corresponding liver in Cd-exposed rats.Low doses of Cd (0.2and0.4 mg/kgBW) induced MT in testis,while a significant decline of MT was found in rats treated with 0.8mgCd/kgBW. By a concomitant decrease of MT,there was an obvious increase of MDA and marked decreases of GSH,daily sperm production in rats treated with 0.8mgCd/kgBW.These findings suggested MT was more difficult to be induced in the testis than in the liver by Cd,which might account for the high susceptibility of testis to Cd.MT, increased by a low dose of Cd,played an important role in protecting testis against Cd toxicity by sequestering and antioxidating.
Cadmium, Metallothionein, Glutathione, Malondialdehyde, Daily sperm production
-
104浏览
-
0点赞
-
0收藏
-
0分享
-
193下载
-
0评论
-
引用
【期刊论文】Genotoxic effects on spermatozoa of carbaryl-exposed workers
王心如, Yankai Xia, * Senping Cheng, * Qian Bian, * Lichun Xu, * Michael D. Collins, † Hebron C. Chang, * Lin Song, * Jiayin Liu, ‡ Shoulin Wang, * and Xinru Wang*,
ToxSci Advance Access published (2004)1-32,-0001,():
-1年11月30日
Carbaryl, one of the most important insecticides,is widely produced and used. To explore carbaryl-induced genotoxic effects of spermatozoa, particularly DNA damage and chromosome aberrations(CA),we firstly examined conventional semen parameters, the progression and motion parameters of the spermatozoa among 16 carbaryl-exposed workers and 30 internal and external control individuals.Sperm DNA damage represented as positive percentage of DNA fragmentation was detected by a modified terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay.Then numerical CA of chromosome X,Y and 18 were investigated by multicolor fluorescence in situ hybridization (FISH). The results showed significant differences in the percentage of sperm abnormality between carbaryl-exposed group and the external control group (P=0.008). Mean (
carbaryl, sperm, genotoxic effect, DNA fragmentation, TUNEL, chromosome aberration, aneuploidy, FISH.,
-
33浏览
-
0点赞
-
0收藏
-
0分享
-
33下载
-
0评论
-
引用
【期刊论文】Bladder epithelial cell proliferation of rats induced by terephthalic acid-calculi
王心如, Guidong Dai *, Lunbiao Cui, Ling Song, Jianfeng Cheng, Yihong Zhong, Renzhen Zhao, Xinru Wang *
Food and Chemical Toxicology 43(2005)217-224,-0001,():
-1年11月30日
Objective: Urinary bladder hyperplasia associated with terephthalic acid (TPA) treatment was examined with concomitant use of sodium bicarbonate (NaHCO3) or hydrochlorothiazide to allow assessment of the relationship among bladder stones,epithelial hyperplasia,and corresponding cell cycle checkpoint gene expression in Sprague–Dawley (SD)rat. Methods:A total of 112 weanling male SD rats that divided between six groups were given basal diet (control), diets containing 5% TPA or in combination with either 4% sodium NaHCO3 or 0.02% hydrochlorothiazide.After 90-day feeding,bladder samples were collected for histopathological diagnoses,and immunohistochemical method was used to characterize the expression of p16Ink4a,cyclin D1, CDK4, EGFr and cyclin E in relation to that of proliferating cell nuclear antigen (PCNA). Results:In TPA treatment groups, bladder stone incidence was 40% (21/52) with 14 cases of proliferative bladder.In control and other groups,neither stone nor epithelial cell proliferation was diagnosed.PCNA-positive focal hyperplasic lesions involved all epithelial layers.Overexpressions of cyclin D1, CDK4, EGFr are found in the corresponding lesion. p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone.In addition,no positive expression was detected on cyclin E. Conclusion: The present study provides a strong evidence of a link between induction of bladder hyperplasia, deregulation of the p16Ink4a-cyclin D1/CDK4 pathway,and abnormal EGFr mediated signal transduction pathway.
Bladder hyperplasia, Terephthalic acid, Calculi, Immunohistochemistry, Cell-cycle proteins, PCNA
-
47浏览
-
0点赞
-
0收藏
-
0分享
-
72下载
-
0评论
-
引用
王心如, Q Bian, L C Xu, S L Wang, Y K Xia, L F Tan, J F Chen, L Song, H C Chang, X R Wang
Fenvalerate exposure and sperm DNA damage (2004)999-1005,-0001,():
-1年11月30日
Aims: To determine sperm nuclear DNA integrity and to investigate the relation between fenvalerate(FE)exposure and spermatozoa DNA damage. Methods: Sperm DNA fragmentation was detected by a modified alkaline single cell gel electrophoresis (Comet) assay and a terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The olive tail moment (OTM) and percentage tail DNA were measured by the Comet assay, and cell positive percentage was measured by the TUNEL assay for DNA damage evaluation. Results: he DNA integrity of spermatozoa of external and internal control groups were both significantly greater than that of the FE exposed group. The median value of tail DNA percentage in the exposure group was 11.30, which was significantly higher than 5.60 in the internal control group and 5.10 in the external control group. The median value of OTM was 3.80 in the exposure group, significantly higher than 1.50 in the internal control group and 2.00 in the external control group.Mean cell positive was 31.2% in the exposure group, significantly higher than 17.4% in the internal control and 19.6% in the external control groups.Cell positive (%) was significantly correlated with tail DNA percentage and with OTM of whole subjects (n=63). Conclusions:Results showed that occupational FE exposure is associated with an increase in sperm DNA damage.A combination of the Comet and TUNEL assays would offer more comprehensive information for a better understanding of sperm DNA damage,and the biological significance of sperm DNA damage in sperm function and male infertility.
-
26浏览
-
0点赞
-
0收藏
-
0分享
-
40下载
-
0评论
-
引用
王心如, Jun He, Jianfeng Chen, Ru Liu, Shoulin Wang, Lin Song, Hebron C. Chang, Xinru Wang∗
Toxicology 203(2004)61-68,-0001,():
-1年11月30日
Fenvalerate,a synthetic pyrethroid,is widely used in agriculture and other domestic applications in China.Recently,Fenvalerate has been suspected to be one of the endocrine-disrupting chemicals(EDC).In this study, we investigated the effects of fenvalerate on follicle-stimulating hormone(FSH)-stimulated progesterone (P4) production by human ovarian luteinizing-granulosa cells (hGLCs). After 24 h incubation,fenvalerate inhibited FSH-stimulated P4 production.At the same time, FSH-stimulated cAMP also decreased.Due to calcium and Ca2+-calmodulin (CaM) system involving gonadotropin-stimulated steroidogenesis by granulosa cells,we then evaluated the effects of fenvalerate on trifluoperazine (TFP)-and verapamil-driven FSH-stimulated P4 production.The results showed that calcium or calmodulin might play a role in fenvalerate-induced alterations in FSH-stimulated P4 biosysthesis.Then,the effects of fenvalerate on calcium homeostasis in hGLCs were studied. The result showed that 5μM fenvalerate induced a slow increase in[Ca2+] in hGLCs by using a fluorescent Ca2+ indicator fluo-3/AM. The changes in total concentration of CaM in hGLCs induced by fenvalerate were evaluated by a method of immunofluorescence. There is a significant increase in all treated groups.In summary, fenvalerate could inhibit FSH-stimulated P4 production. Also, fenvalerate interferes with calcium homeostasis in hGLCs. The effects of fenvalerate on FSH-stimulated ovarian steroidogenesis may be mediated partly through calcium signal.
Endocrine disruptor, Pyrethroids, Granulosa cell, Progesterone, Calcium homeostasis
-
36浏览
-
0点赞
-
0收藏
-
0分享
-
74下载
-
0评论
-
引用
【期刊论文】Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate
王心如, Yankai Xia a, Qian Bian a, Lichun Xua, Senping Chenga, Lin Songa, Jiayin Liu b, Wei Wub, Shoulin Wang a, Xinru Wang a, ∗
Toxicology 203(2004)49-60,-0001,():
-1年11月30日
Fenvalerate,a synthetic pyrethroid insecticide,is widely produced and used worldwide.To explore fenvalerate-induced genotoxic effects, particularly numerical chromosome aberration (CA),we firstly examined conventional semen parameters, the progression and motion parameters of the spermatozoa among 12 fenvalerate-exposed workers and 30 donors of the internal and external control groups.Then numerical CA of chromosome X,Y and 18 were investigated by multicolor fluorescence in situ hybridization (FISH).The results showed the significant differences in the percentage of sperm abnormality between fenvalerate-exposed group and the external control group (P=0.024).In aneuploid parameters,the frequency (mean
Fenvalerate, Sperm, Genotoxicity, Chromosome aberration, Aneuploidy, FISH
-
36浏览
-
0点赞
-
0收藏
-
0分享
-
123下载
-
0评论
-
引用