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1.
INTRODUCTION In 1998 gastrointestinal pathologists reached aconsensus on the definition of chronic atrophic gas- tritis (CAG), which was described as programmed loss of gastric gland and/or replacement by intestinal glands in gastric mucosa. CAG was recognized to be closely related with development of gastric cancer and listed as precancerous lesions in this meeting (Genta, 1998). According to Correa (1992)’s cascade of gas-tric carcinogenesis, gastric cancer was believed to develop fr…  相似文献   

2.

Objective

The present study is designed to investigate the cellular expressions and immunolocalizations of three different nitric oxide synthase (NOS) isoforms and the related nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the ovaries of neonatal and immature rats.

Methods

The ovaries were obtained from ICR (Institute for Cancer Research) female Sprague-Dawley rats at postnatal days 1, 5, 7, 10, and 19. Then we carried out the histologic examination, immunohistochemistry, measurement of NOS activity, and modifications within the NO/cGMP pathway.

Results

During postnatal days 1, 5, 7, 10, and 19, all three isoforms of NOS were mainly localized to the oocytes and expressed as a gradual increase in granulosa cells and theca cells within the growing follicle. The ovarian total NOS activities and NO levels were increased at postnatal days 7 and 10 compared with other days.

Conclusions

Our findings suggest that the locally produced NO and the NO/NOS signaling systems are involved in the follicular development to puberty.  相似文献   

3.
The study was conducted to investigate the effects of follicle-stimulating hormone (FSH) on embryonic chicken ovarian germ cell proliferation and its possible involvements of protein kinases A (PKA) and C (PKC) pathways. Ovarian cells were treated with FSH alone or in the presence of forskolin (FRSK), PKA inhibitor (H89), PKC activator (PMA) or inhibitor (H7). The germ cell number was counted from micropictures. The immunocytochemistry of proliferating cell nuclear antigen (PCNA) was applied to identify the proliferating cells. The germ cell labeling index (LI) was determined for cell proliferation. The FSH treatment increased the germ cell number, and this stimulating effect was enhanced by FRSK or PMA, but inhibited by H89 or H7 in a dose-dependent manner. Moreover, the PCNA-LI showed parallel changes with germ cell numbers. This study suggests that FSH may stimulate proliferation of cultured chicken ovarian germ cells by activation of both the PKA and PKC signaling pathways.  相似文献   

4.
Bone morphogenetic proteins (BMPs) play a critical role in the growth and steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types. The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs. A strategy of RNA interference (RNAi)-mediated ‘gene silencing’ of Smad4, a core molecule mediating the intracellular BMP/Smad signal transduction pathways, was used to interrupt endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited growth, and induced apoptosis of porcine GCs, while decreasing estradiol production. In addition, interrupted BMP/Smad signaling significantly (P<0.05) changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.  相似文献   

5.
在不考虑月经周期的情况下连续灌喂氯地酚5天,每天50mg,第8天肌注hCG2000IU,对猕猴具有一定的卵泡超数发育作用,最多可使双侧卵巢共24个卵泡发育,最大卵泡直径5—6mm,但不同个体反应变化较大。FSH hCG超排方案(考虑或不考虑月经周期,连续肌注FSH6天,共80—90IU,第8天肌注hCG2500IU)比氯地酚效果较好,最多可使双侧卵巢共28个卵泡发育,卵泡最大直径10mm,另外在1只猕猴观察到5个卵泡破裂将卵排出。电刺激采得之猕猴精子经洗涤后与用以上两种超排方案以卵泡吸得之卵子一同输入兔输卵管进行受精,获得2个原核期受精卵和1个桑椹胚。  相似文献   

6.
There is a lack of appropriate classification criteria for the determination of atretic follicles in guinea pigs.In the present study,new criteria were established based on the latest morphologic criteria for cell death proposed by the Nomenclature Committee on Cell Death(NCCD) in 2009.Ovaries of guinea pigs were sampled on different stages of estrous cycle,and the morphologic observations of atretic follicles were investigated in serial sections.The results showed that the process of follicular atresia cou...  相似文献   

7.
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8.
Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.  相似文献   

9.
Objective  This study is to determine the effect of the natural product parthenolide, a sesquiterpene lactone isolated from extracts of the herb Tanacetum parthenium, on the proliferation of vascular smooth muscle cells (VSMCs). Methods  Rat aortic VSMCs were isolated and cultured in vitro, and treated with different concentrations of parthenolide (10, 20 and 30 μmol/L). [3H]thymidine incorporation was used as an index of cell proliferation. Cell cycle progression and distribution were determined by flow cytometric analysis. Furthermore, the expression of several regulatory proteins relevant to VSMC proliferation including IκBα, cyclooxygenase-2 (Cox-2), p21, and p27 was examined to investigate the potential molecular mechanism. Results  Treatment with parthenolide significantly decreased the [3H]thymidine incorporation into DNA by 30%∼56% relative to control values in a dose-dependent manner (P<0.05). Addition of parthenolide also increased cell population at G0/G1 phase by 19.2%∼65.7% (P<0.05) and decreased cell population at S phase by 50.7%∼84.8% (P<0.05), which is consistent with its stimulatory effects on p21 and p27. In addition, parthenolide also increased IκBα expression and reduced Cox-2 expression in a time-dependent manner. Conclusion  Our results show that parthenolide significantly inhibits the VSMC proliferation by inducing G0/G1 cell cycle arrest. IκBα and Cox-2 are likely involved in such inhibitory effect of parthenolide on VSMC proliferation. These findings warrant further investigation on potential therapeutic implications of parthenolide on VSMC proliferation in vivo. Project (No. 491020-W50315) supported by the Foundation of the Health Bureau of Zhejiang, China  相似文献   

10.
Busulfan/cyclophosphamide (Bu/Cy) conditioning regimen has been widely used to treat cancer patients, while their effects on major internal organs in females are not fully understood. We treated female mice with Bu/Cy, and examined the histopathology of major internal organs on Day 30 after the treatment. The results show that Bu/Cy treatment affected the ovaries most extensively, while it had less effect on the spleen, lungs, and kidneys, and no effect on the heart, liver, stomach, and pancreas. To better understand the effect of Bu/Cy on the ovaries, we counted follicles, and determined the levels of ovarian steroids. The Bu/Cy-treated mice showed a reduction of primordial and primary follicles (P<0.01) on Day 30 and a marked loss of follicles at all developmental stages (P<0.01) on Day 60. Plasma levels of estradiol and progesterone in Bu/Cy-treated mice decreased by 43.9% and 61.4%, respectively. Thus, there was a gradual process of follicle loss and low estradiol in Bu/Cy-treated mice; this is a profile similar to what is found in women with premature ovarian failure (POF). The Bu/Cy-treated mice may serve as a useful animal model to study the dynamics of follicle loss in women undergoing POF.  相似文献   

11.
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12.
[目的]新的大肠癌相关性抗原EID3的基因克隆及其诊断价值研究.[方法]利用大肠癌病人体内血清中所含的对肿瘤抗原产生的特异性抗体筛选睾丸组织cDNA噬菌体表达文库和大肠癌组织cDNA噬菌体表达文库(SEREX),并用RT-PCR技术研究EID3 mRNA在正常组织和大肠癌传代细胞表达.[结果]睾丸组织cDNA噬菌体表达文库筛选得到了可以诱导大肠癌病人抗体免疫应答的新抗原EID3基因(Gen-bank NM_001008394.1).它们定位于染色体19q13.2,EID3含1个外显子.通过RT-PCR分析发现,EID3基因在43例大肠癌传代细胞株中,39例阳性,阳性率为90.7%.在正常组织中,除睾丸组织外不表达或有极低水平转录.[结论]EID3 mRNA表达检测用于诊断大肠癌,可能具有高特异性和高敏感性的特点.EID3蛋白被首次发现在大肠癌病人中能够诱导机体的抗体免疫应答,为一个新的大肠癌相关性抗原分子.其功能可能与抑制细胞的恶性增殖相关,并可进一步研究其用于治疗和诊断大肠癌的可行性.  相似文献   

13.
目的探讨银杏叶总黄酮时体外培养的人肝癌细胞HepG2的增殖抑制作用及其对Bcl-2基因mRNA水平的影响。方法采用MTT法检测银杏叶总黄酮对HepG2细胞增殖的影响,提取Bcl-2基因的mRNA,以RT—PCR方法研究银杏叶总黄酮对Bcl-2基因表达的影响。结果银杏叶总黄酮使人HepG2细胞增殖率明显下降,且呈剂量依赖效应;Bcl-2基因mRNA水平随银杏叶总黄酮浓度升高而降低。结论银杏叶总黄酮对人He-pG2细胞增殖有抑制作用,并能下调癌基因Bcl-2的表达,从而起到抗肿瘤的治疗作用。  相似文献   

14.
Objective: We dynamically measured serum inhibin B and estradiol in the early stage of hormonal stimulation to predict the ovarian response in in vitro fertilization (IVF) treatment. Methods: A total of 57 patients (<40 years of age) who un-derwent the first cycle of long protocol IVF or introcytoplasmic sperm injection (ICSI) treatment were included. Serum inhibin B, estradioi, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured four times: (i) on Day 3 of the menstrual cycle (basal); (2) on the day before the first administration of gonadotrophin (Gn) (Day 0); (3) on Day 1 of Gn therapy; and (4) on Day 5 of Gn therapy. Comparisons of these measurements with ovarian responses and pregnancy outcomes were made and analyzed statistically. Results: (1) On Day 1 and Day 5 of recombinant FSH (rFSH) stimulation, ovarian response, i.e., numbers of follicles, oocytes, fertilized oocytes, and embryos, had a positive correlation (rS=0.46～0.61, P=0.000) with raised inhibin B and estradiol concentrations, but a negative correlation (rS=-0.67～-0.38, P=0.000 or P<0.01) with total rFSH dose and total days ofrFSH stimulation. (2) No significant variation (P>0.05) between the pregnant and non-pregnant groups on the basis of mean age or on all hormone concentrations at four times of the IVF cycle was observed. However, all the seven patients aged >35 years did not reach pregnancy. Conclusions: (1) Serum inhibin B and estradiol concentrations obtained shortly after Gn therapy may offer an accurate and early prediction of ovarian response; (2) Low levels of serum inhibin B and estradiol obtained shortly after Gn stimulation indicate the need for a longer period of Gn treatment and a higher daily dosage; (3) No obvious pregnancy difference among patients of age <35 years was found; however, IVF pregnancy outcome is significantly lower in women of age >35 years.  相似文献   

15.
Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. How ever, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry. The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.  相似文献   

16.
INTRODUCTION Homoharringtonine (HHT) is a cephalotoxin alkaloid with anti-leukemic activity and had been used successfully in the treatment of acute and chronic myeloid leukemias (O払rien et al., 1995; 1999; Feldman et al., 1992). The principal mecha-nism of action by HHT is the inhibition of protein synthesis in a dose- and time-dependent manner by binding to ribosome and inhibiting polypeptide chain elongation (Tujebajeva et al., 1989; Zhou et al., 1995). HHT had been shown to indu…  相似文献   

17.
To study the influence of negative or positive experience of the ingestion of ethanol in femaleDrosophila with thefast form of the Adh gene on the acceptance of a medium containing this substance as site for egg laying, flies raised on a medium without alcohol were kept (1) on a regular medium, (2) on a medium supplemented with ethanol, (3) on a medium supplemented with 4-methylpyrazole (4-MP, an inhibitor of the enzyme ADH), and (4) on a medium containing both ethanol and this inhibitor. Whereas theDrosophila exhibited no spontaneous egg-laying preference for ethanol, a preference was induced by the ingestion of this substance, which also led to an increase in the number of eggs laid. By contrast, ingestion of ethanol, associated with the inhibitor, reduced the number of eggs laid and led to an avoidance of ethanol-containing media. Flies treated with ethanol and 4-MP exhibited signs of sickness (reduction in locomotor activity and loss of balance). The egg-laying preference for the ethanol results from learning linked to the metabolic utilization of this alcohol. The adaptative significance of this learning is discussed.  相似文献   

18.
Royal jelly (RJ) is a well-known bioactive substance. It contains large amounts of major royal jelly proteins (MRJPs), which express growth-factor-like activity in several animal and human cell lines. However, the question on whether MRJPs possess growth-factor-like activity on all types of cell cultures remains. In order to determine whether MRJPs can be used as an alternative to fetal bovine serum (FBS) in different types of human cell culture, the proliferation of the complex serum with different ratios of MRJPs/FBS (M/F) was evaluated on five cell lines: 293T, HFL-I, 231, HCT116, and Changliver using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The proliferation activity of the combination of the complex M/F serum with cytokines on the test cell lines was also measured. The results demonstrated that the complex serum with M/F 6/4 possessed the highest proliferation activity similar to or in excess of FBS. However, no activity of complex medium with M/F 6/4 was observed in 231 cells, indicating a selectivity of MRJPs on cell types. Compared with the complex medium with M/F 6/4, the complex medium with M/F 6/4 together with two cytokines, epidermal growth factor (EGF) and insulin-transferrin-selenium (ITS), promoted proliferations of Changliver, 293T, HCT116, and HFL-I by 18.73%?56.19% (P<0.01). Our findings demonstrate that MRJPs could partially replace FBS in culturing many human cell lines.  相似文献   

19.
Objective: To investigate the infection of human embryo fibroblast cell line HF cells by CMV as well as the effects of CMV on β-actin mRNA and microfilaments. Methods: HF cells shape was observed after the infection of CMV. RT-PCR assay was used to detect the mRNA expression of CMV immediate early (IE) gene, β-actin and GAPDH genes of HF cells infected by CMV. CMV particles and cell microfilaments were detected with electron microscope. Results: Shape of HF cell changed after the infection by CMV. HF cells infected by CMV could express IE mRNA and the expression of β-actin mRNA decreased in a time-and titer-dependent manner compared with the uninfected HF cells whose expression of GAPDH mRNA did not change much. CMV particles were found with electron microscope in the cells. Microfilaments were ruptured and shortened after the infection of CMV. Conclusion: CMV can not only infect human embryo fibroblast cells line HF cells and replicate in the cells, but can also affect the expression of β-actin mRNA and the microfilaments. Project (No. 001103058) supported by the Key Program of Science and Technology Bureau of Zhejiang Province, China  相似文献   

20.
Background and objective: Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors. A variety of genetic factors have been reported, whereas few investigations have focused on epigenetic regulation during liver regeneration. In the present study, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, was used to investigate the effect of HDAC on liver regeneration. Methods: VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration. The mice were sacrificed, and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment. DNA synthesis was detected via a BrdU assay, and cell proliferation was tested using Ki-67. The expressions of cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), and CDK4 were detected by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot. Results: Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased, and the peak of BrdU was delayed in the VPA-administered mice. Consistently, cyclin D1 expression was also delayed. We identified B-myc as a target gene of HDACs by complementary DNA (cDNA) microarray. The expression of B-myc increased in the VPA-administered mice after hepatectomy (PH). The ChIP assay confirmed the presence of HDACs at the B-myc promoter. Conclusions: HDAC activities are essential for liver regeneration. Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest, thereby causing an anti-proliferative effect on liver regeneration.  相似文献   

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