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Biomedical subjects

Fan Jin

Publications and source records attributed to Fan Jin.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms of the CYP1B1 gene may be associated with the onset of natural menopause in Chinese women.

The Cytochrome P450 1B1 (CYP1B1) is one of the major CYP450 enzymes catalyzing 4-hydroxylation, an important elimination step for estrogens. Relatively little is known, however, about the impact of this gene on the onset and cessation of menstruation, which are significant milestones in a woman's life and predictors of many hormone related diseases. In this report, we described the association of four SNPs in the CYP1B1 gene, Arg48Gly, Ala119Ser, Leu432Val, and Asp449Asp, with the ages of menarche and menopause, years of menstruation and total number of menstrual cycles. Included in the study were 1958 community controls from two recently completed population-based case-control studies of breast cancer and endometrial cancer. No association was observed between the CYP1B1 polymorphisms and the age of menarche among either pre- or post-menopausal women. Among the women who experienced natural menopause, the three non-synonymous SNPs were significantly associated with menopausal age, years of menstruation, and total number of menstrual cycles. The Gly and Ser alleles of Arg48Gly and Ala119Ser were associated with later menopause, more years of menstruation and more menstrual cycles, while women with allele Val at Leu432Val had a 0.9 year earlier menopause, 1.0 year shorter reproductive span, and 12.6 fewer menstrual cycles than those women without this allele. In conclusion, the results from this study suggested that CYP1B1 genetic polymorphisms may be associated with the natural onset of menopause.

Adult↗
PubMed2006

Altered expression of interleukin-18 in the ectopic and eutopic endometrium of women with endometriosis.

OBJECTIVE: This study has investigated the expression of interleukin (IL)-18 in the eutopic and ectopic endometrium of women with endometriosis and the role of IL-18 on the pathogenesis of endometriosis. METHODS: Endometriotic tissue specimens and endometrium specimens were obtained from patients with endometriosis. IL-18 protein was determined by immunohistochemical analysis. Expression levels of IL-18 mRNA were analyzed by reverse transcriptase (RT)-PCR. RESULTS: IL-18 was detected in the glandular epithelial and stromal cells of eutopic and ectopic endometrium. RT-PCR analysis showed that endometrial IL-18 mRNA expression levels were significantly higher at the secretory phase than the proliferative phase in normal women, but not in patients with endometriosis. IL-18 mRNA expression levels were lower in the ectopic endometrium than in the eutopic endometrium of women with endometriosis. IL-18 mRNA levels in both ectopic and eutopic endometrium of patients with endometriosis were lower than in endometrium of women without endometriosis. CONCLUSION: Ectopic and eutopic endometrial IL-18 was down-regulated in women with endometriosis, suggesting that IL-18 might play a pathogenic role in the formation of endometriosis.

Adult↗
PubMed2006

Vascular endothelial growth factor and matrix metalloproteinase-2 expedite formation of endometriosis in the early stage ICR mouse model.

OBJECTIVE: To establish a mouse model for endometriosis and to evaluate roles of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the formation of disease. DESIGN: Experimental laboratory study. SETTING: A women's hospital in China. PATIENT(S) AND ANIMAL(S): Ten women with endometriosis and 10 control women, as well as ICR mice. INTERVENTION(S): Endometrial fragments were transplanted in the peritoneal cavities of mice at minilaparotomy. Transplants were observed and then removed for the assessment of morphology and immunohistochemical staining of VEGF and MMP-2. MAIN OUTCOME MEASURE(S): Observation of transplants, expression of VEGF and MMP-2. RESULT(S): On days 1 and 2, glandular and stromal cells were viable at the margins of transplants. On day 3, the transplants were surrounded by mesothelial cells, and the endometrial glands and stromal cells were clearly viable at the interface. The scores of VEGF and MMP-2 of viable glandular cells of transplants were increased compared with the ones before transplantation. The scores of VEGF and MMP-2 of transplants from women with endometriosis were higher than those of control women. CONCLUSION(S): Endometrial transplants from the patients with endometriosis express more VEGF and MMP-2 than endometrium in control women, suggesting that VEGF and MMP-2 may expedite the formation of endometriosis in its early stage.

Animals↗
PubMed2006

Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice.

BACKGROUND: The impact of different ovarian stimulation (OS) protocols on endometrial receptivity remains controversial. In this study, the effects of different OS on the expression of endometrial integrin beta3 subunit and leukaemia-inhibitory factor (LIF) during the implantation window and the implantation rate in mice were investigated. METHODS: Three OS protocols were used, involving either pregnant mare's serum gonadotrophin (PMSG) alone, PMSG plus GnRH agonist or PMSG plus GnRH antagonist. Uterus samples were collected at 48 h after OS or ovulation and were detected with immunohistochemistry, Western blot and RT-PCR analyses. Normal embryos at gestation day 4 were transferred into the uteri of mice in the control and OS groups. RESULTS: All OS groups showed a significant decrease in the expression of both the endometrial integrin beta3 subunit and LIF during the implantation window and the implantation rate. Among the three OS groups, GnRH agonist-treated mice showed a higher endometrial integrin beta3 subunit and LIF expression and a higher implantation rate. No significant difference was found in the measured indices between the GnRH antagonist and PMSG groups. CONCLUSIONS: OS may inhibit the expression of endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the endometrial physiological secretion and improve uterine receptivity.

Animals↗
PubMed2006

Observation of the first-order transition in ultrafiltration of flexible linear polymer chains.

Using a special double-layer membrane to avoid interaction among flow fields generated by different pores, we have, for the first time, observed the predicted discontinuous first-order transition in ultrafiltration of flexible linear polymer chains. Namely, the chain could pass through a pore much smaller than its unperturbed radius only when the flow rate is higher than a certain value. When only one chain and one pore are considered in theory, such a threshold is surprisingly independent of both the chain length and the pore size. Our results reveal that for a membrane with many pores and at a microscopic flow rate () lower than the threshold, the inevitable blocking of some pores by longer nonstretched coiled chains increases in those unblocked pores because the macroscopic flow rate () is a constant. Long chains have two populations, coiled and stretched, in a real ultrafiltration experiment when is lower than the threshold.

Computer Simulation↗
PubMed2006

Proteomic analysis on the alteration of protein expression in the placental villous tissue of early pregnancy loss.

Early pregnancy loss is the most common complication of human reproduction. Given the complexities of early development, it is likely that many mechanisms are involved. Knowledge of differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying early pregnancy loss. To identify proteins with different expression profiles related to early pregnancy loss, we applied a proteomic approach and performed two-dimensional gel electrophoresis (2-DE) on six placental villous tissues from patients with early pregnancy loss and six from normal pregnant women, followed by comparison of the silver-stained 2-DE profiles. It was found that 13 proteins were downregulated and 5 proteins were upregulated significantly (P < 0.05) in early pregnancy loss as determined by spot volume. Among them, 10 downregulated and 2 upregulated spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anomalies of these proteins, including three principal antioxidant enzymes (copper/zinc-superoxide dismutase, peroxiredoxin 3, and thioredoxin-like 1 protein), S100 calcium binding protein, galectin-1, chorionic somatomammotropin hormone 1, transthyretin, fas inhibitory molecule, eukaryotic translation elongation factor, RNA-binding protein, ubiquitin-conjugating enzyme E2N, and proteasome beta-subunit, indicate widespread failure in cell regulations and processes such as antioxidative defense, differentiation, cell proliferation, metabolism, apoptosis, transcription, and proteolysis in early pregnancy loss. This study has identified several proteins that are associated with placentation and early development, shedding a new insight into the proteins that may be potentially involved in the pathophysiological mechanisms underlying early pregnancy loss.

Abortion, Spontaneous↗
PubMed2006

A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS.

To investigate the association of single-nucleotide polymorphisms (SNPs) in exon 17 of the insulin receptor (INSR) gene with insulin resistance and INSR beta-subunit expression in polycystic ovary syndrome (PCOS) patients, a case-control study was carried out in an academic endocrinology clinic of China. One hundred and nine Chinese patients with PCOS and 107 healthy Chinese women as control were recruited. Their leukocytes and red blood cells were separated from blood samples, for SNP analysis with single-stranded conformation polymorphism and for the INSR beta-subunit expression detection by western blot analysis, respectively. A novel T/C SNP at codon Cys1008 (position 3128 of NM_000208) of INSR was found in two allele genotypes, i.e. the homozygous CC and the heterozygous TC. A higher frequency of the mutant homozygous CC was observed in the PCOS women with PCOS than that in the controls (21.1 versus 5.6%, P < 0.01). In contrast with the women with wild-type genotype, a significantly lower insulin sensitivity index in the women with each of the two mutant genotypes was revealed (CC: 0.335 +/- 0.026/TC: 0.346 +/- 0.027 versus TT: 0.367 +/- 0.029, P < 0.05). No relationship was found between the novel SNP and the INSR beta-subunit expression. We concluded that the novel T/C SNP at codon Cys1008 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS and that the association is not by the change of synthesis or secretion of INSR beta-subunit, but most possibly by the effects of this novel SNP on the function of INSR beta-subunit.

Adult↗
PubMed2006

Aquaporin-2 expression in human endometrium correlates with serum ovarian steroid hormones.

The aim of the present study was to examine the expression of aquaporin-2 (AQP2), a member of the water channel family aquaporins (AQPs), in human uterine endometrium and its modulation of ovarian steroid hormone at the proliferative and secretory phases. Western blot, immunohistochemistry, and RT-PCR were employed in the present study. Western blot revealed a 29-kDa band that represented AQP2 in human endometrium. The expression of AQP2 in endometrium was confirmed by RT-PCR and immunohistochemical results. The immunohistochemical analysis demonstrated that AQP2 was prominent in luminal and glandular epithelial cells of endometrium. The levels of endometrial AQP2 expression changed during the menstrual cycle and were higher in the secretory endometrium than in the proliferative endometrium. A significantly high level of AQP2 was detected at the mid-secretory phase. There was a positive correlation between the levels of the endometrial AQP2 expression and the concentrations of the serum 17beta-estradiol (E2) or/and progesterone (P4). These data for the first time corroborate that AQP2 is expressed in human endometrium and that the expression of AQP2 in human endometrium might be regulated by E2 or/and P4. The changed expression of AQP2 at different phases of the menstrual cycle may be essential to reproductive physiology in human. The high level of endometrial AQP2 expression was observed at the mid-secretory phase, the time of embryo implantation, suggesting that AQP2 might play physiological roles in the uterine receptivity.

Adult↗
PubMed2006

Inhalation of nebulized nitroglycerin, a nitric oxide donor, for the treatment of pulmonary hypertension induced by high pulmonary blood flow.

This study explores the effect and mechanisms of inhalation of nebulized nitroglycerin (Neb-NTG) on pulmonary hypertension induced by high pulmonary blood flow. An aortocaval shunt was produced in rats. Twelve weeks after the operation, rats started to inhale Neb-NTG. After 15 weeks, pulmonary and systemic hemodynamics as well as pathological changes were measured in all animals. Inhalation of Neb-NTG was able not only to markedly attenuate pulmonary artery pressure without impacting systolic pressure but also to ameliorate muscularization of small pulmonary arteries. The relaxation response of pulmonary artery ring to acetylcholine in shunt rats and Neb-NTG-treated rats was decreased. However, Neb-NTG did not impact the relaxation response of pulmonary artery ring to both nitroprusside and nitroglycerin (NTG). Neb-NTG successfully inhibited the increased expression of pulmonary artery smooth muscle cell (PASMC) proliferative cell nuclear antigen, collagen I, and collagen III, as well as pulmonary artery urotensin-II in shunt rats with high pulmonary blood flow. Neb-NTG selectively ameliorated pulmonary hypertension as well as pulmonary vascular structural remodeling induced by high pulmonary blood flow.

Administration, Inhalation↗
PubMed2006

Population-based case-control study of VEGF gene polymorphisms and breast cancer risk among Chinese women.

Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathologic processes, including neovascularization, a crucial step in the development of solid malignancies. Using data and specimens collected in the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai, China from 1996 to 1998, we evaluated the association of VEGF gene polymorphisms with breast cancer risk. Included in this study were 1,093 cases and 1,184 age-matched controls who had completed an in-person interview and donated a blood sample to the study. Polymorphisms in the promoter region (T -460C), 5' untranslated region (C +405G), and 3'untranslated region (C936T) were genotyped using the Taqman allelic discrimination assay. No statistically significant case-control difference was found for the C +405G and T -460C polymorphisms. However, the C936T polymorphism was associated with a reduced risk of breast cancer. Compared with CC genotype carriers, women who had the TT genotype showed a decreased risk [odds ratio (OR), 0.65; 95% confidence interval (95% CI) 0.41-1.02], and the inverse association was restricted to premenopausal women (OR, 0.45; 95% CI, 0.25-0.79). Six common haplotypes were identified. Compared with the most common haplotype (-460T/405C/936C), the -460T/405G/936T haplotype was associated with a reduced risk of breast cancer (OR, 0.67; 95% CI, 0.43-1.04), particularly in premenopausal women (OR, 0.47; 95% CI, 0.27-0.81). Our study suggests that the VEGF C936T polymorphism might be a susceptibility factor for breast cancer among Chinese women.

3' Untranslated Regions↗
PubMed2006

Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells.

The use of histone deacetylase (HDAC) inhibitors has shown promise for a variety of malignancies. In this investigation, we define the activity of this class of inhibitors in combination with traditional cytotoxic chemotherapy in endometrial cancer cells. Significant reductions in growth were observed in Ark2 and KLE endometrial cancer cells following treatment with paclitaxel, doxorubicin, carboplatin, or the HDAC inhibitor trichostatin A (TSA). However, only combined treatment with TSA/paclitaxel caused synergistic inhibition of cell growth. This combination also resulted in significant changes in cell morphology. Using cell cycle analysis, nuclear staining, and Western blot analysis for poly(ADP-ribose) polymerase and caspase-9 degradation products, TSA/paclitaxel showed the most dramatic activation of the apoptotic cascade. These effects were also observed when the HDAC inhibitors HDAC inhibitor-1 or oxamflatin were substituted for TSA. The anticancer properties of paclitaxel are known to result in part from inhibition of microtubule depolymerization, which results in apoptosis. We show that TSA administration also stabilizes microtubules via alpha-tubulin acetylation. Furthermore, using Western blot and immunohistochemical analysis, treatment with TSA/paclitaxel led to a significant increase in acetylated tubulin and microtubule stabilization. These effects were confirmed in a mouse xenograft model. Moreover, TSA/paclitaxel resulted in a 50% reduction in tumor weight compared with either agent alone. This study provides in vivo evidence of nonhistone protein acetylation as one possible mechanism by which HDAC inhibitors reduce cancer growth. The TSA/paclitaxel combination seems to hold promise for the treatment of serous endometrial carcinoma and other malignancies with limited sensitivity to paclitaxel.

Animals↗
PubMed2005

Two estrogen replacement therapies differentially regulate expression of estrogen receptors alpha and beta in the hippocampus and cortex of ovariectomized rat.

As estrogens have been implicated in altered cognitive function associated with menopause, the purpose of the present study was to determine the regulatory effects of different estrogen preparations on the expression of estrogen receptor subtypes in the hippocampus and cortex of ovariectomized rats. The expression of estrogen receptor mRNA and protein was determined with RT-PCR and immunohistochemistry, respectively. Two estrogen reagents, Premarin and Progynova, were used in the present study. Premarin, a conjugated equine estrogen, down-regulated ER alpha expression in the hippocampus and cortex of ovariectomized rats and had no effect on levels of ER beta expression in the same two regions. However, Progynova (valerate estradiol) was shown to up-regulate ER beta expression in the hippocampus and cortex and had no effect on the levels of ER alpha expression. Our present data suggest that different estrogen reagents used in estrogen replacement therapy could have different regulatory effects on the expression of estrogen receptor subtypes, which might, at least in part, explain why clinically, different estrogen preparations have distinct estrogenic effects on target organs.

Animals↗
PubMed2005

The Shanghai Women's Health Study: rationale, study design, and baseline characteristics.

Although cancer is a major cause of morbidity and mortality in most nations, the spectrum of cancer occurrence varies substantially worldwide. Most previous epidemiologic studies investigating cancer etiology were conducted in North American and western European countries that are relatively homogenous in terms of cancer spectrums and many lifestyle exposures. These limitations may have hindered these studies from evaluating some important etiologic hypotheses. From 1996 to 2000, the Shanghai Women's Health Study recruited 74,942 adult Chinese women from selected urban communities, with a 92% response rate. All participants completed a detailed baseline survey and anthropometrics. Approximately 88% of cohort members donated a urine sample (n = 65,755) and a blood (n = 56,832) or exfoliated buccal cell (n = 8,934) sample. Noteworthy characteristics of this cohort include low consumption of alcohol (1.9%) and use of tobacco (2.4%); high intake of fish (mean, 50.8 g/day), soy foods (mean, 142.3 g/day), and certain vegetables; low prevalence of obesity (5.1%); and nearly 100% employment outside the home. Currently, this cohort of women is being followed via biennial in-person recontact and periodic linkage to cancer and vital statistics registries. The resources from the cohort will be valuable in future studies of environmental exposures and biomarkers for the risk of cancer and other chronic diseases.

Adult↗
PubMed2005

[Expression of aquaporin 2, a water channel, in human endometrium during the menstrual cycle].

OBJECTIVE: To examine the expression of aquaporin 2 (AQP2) in human endometrium. METHODS: Specimens of human endometrium were collected from 87 women at different menstrual cycles, aged 30 +/- 3, 23 cases in the proliferative phase, 30 cases in the early secretory phase and 34 cases in the mid-secretory phase respectively. Immunohistochemistry and Western blotting were utilized to detect the localization and expression of AQP2 in the endometrium. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect its messenger RNA. The PCR product was cloned and sequenced. RESULTS: Positive immunoreactivity of AQP2 was found in the epithelia cells and glandular epithelial cells of all specimens of human endometrium at different phases of the menstrual cycle, and all stromal cells were not stained. The reactive substance was primarily distributed in the membrane and cytoplasm, but not in the nuclei of all positive cells. In Western blotting showed dominant bands with relative molecular weight between 35,000 Da and 50,000 Da, which was corresponded to the glycosylated form of AQP2 by the positive control from rat kidney. Semi-quantitative analysis showed that the relative expression of AQP2 in the mid-secretory phase was 1.63 +/- 0.15, significantly higher than those in the early secretory phase (1.33 +/- 0.14, P < 0.05) and that in the proliferative phase (1.03 +/- 0.10, P < 0.01). Message RNA was found out in all cases by RT-PCR and the PCR product was confirmed in nearly exact (99%) consistency with the GenBank by sequencing. AQP2 mRNA was expressed in all normal endometrium at different phases, and was weakly expressed in the endometrium at the proliferative phase. Sequencing showed that the AQP2 sequence was 99% homologous with that in the GenBank. CONCLUSION: AQP2 expression in the human endometrium suggests that AQP2 may be involved in the regulation of uterine fluid homeostasis influenced by ovarian steroid hormones in the menstrual cycle.

Adult↗
PubMed2005

Derivation and growing human embryonic stem cells on feeders derived from themselves.

Human embryonic stem cells (hESCs) are pluripotent. They have the potential to differentiate into every cell type of an organism. Since many human somatic cell types have the ability to support the growth of hESCs, cells differentiated from hESCs may also be able to support the growth of themselves. We tested this hypothesis by growing hESCs on feeders derived from themselves and demonstrated that such feeders did constitute an environment suitable for the derivation and long-term growth of hESCs. hESCs maintained in this system expressed all the markers indicative of the undifferentiated state and gave rise to cell types representative of all three primary germ layers upon differentiation. By modifying the genome of hESCs, feeders with special features can be derived and mass produced. The system will facilitate large-scale production of hESCs in a standardized animal pathogen-free environment.

Animals↗
PubMed2005

Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women.

BACKGROUND: Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. METHODS: The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS: Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.

Breast Neoplasms↗
PubMed2005

Histone deacetylase inhibitors decrease DNA methyltransferase-3B messenger RNA stability and down-regulate de novo DNA methyltransferase activity in human endometrial cells.

It is well known that the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) acts synergistically with the DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (ADC) to reactivate DNA methylation-silenced genes. Moreover, in several studies, TSA was capable of inducing DNA demethylation even in the absence of ADC. Here we describe a mechanism by which HDAC inhibitors affect DNA methylation through their regulation on DNMT3B, a methyltransferase responsible for de novo DNA methylation. Using quantitative real-time PCR and Western blot analysis, we show that TSA down-regulates DNMT3B mRNA and protein expression in human endometrial cancer cells. This decrease in DNMT3B mRNA results in a significant reduction in de novo methylation activities. Further experiments indicated that TSA decreases DNMT3B mRNA stability and reduces its half-life from approximately 4 to 2.5 hours. We established that protein synthesis is required for posttranscriptional regulation, suggesting the involvement of an RNase and/or key mRNA stabilization factor(s) controlling the DNMT3B mRNA stability. Therefore, TSA may not only modify histone acetylation, but also potentially alter DNA methylation. Since the HDAC inhibitors are frequently used in epigenetic studies and are considered to be promising anticancer drugs, these new findings will have implications in both laboratory and clinical settings.

Azacitidine↗