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Wang Y.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard | Wang Y.,College of Logistics | Niu X.L.,College of Logistics | Guo X.Q.,College of Logistics | And 6 more authors.
Journal of Molecular Endocrinology | Year: 2015

About 40–60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology Printed in Great Britain.


Wang Y.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard | Wang Y.,College of Logistics | Yang C.,College of Logistics | Xie W.L.,College of Logistics | And 5 more authors.
Phytomedicine | Year: 2014

Puerarin, a daidzein-8-C-glucoside, is the major isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, and has received increasing attention because of its possible role in the prevention of osteoporosis. In our previous studies, puerarin reduced the bone resorption of osteoclasts and promoted long bone growth in fetal mouse in vitro. Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat. However, the mechanisms underlying its actions on human bone cells have remained largely unknown. Here we show that puerarin concurrently stimulates osteoprotegerin (OPG) and inhibits receptor activator of nuclear factor-κB ligand (RANKL) and Interleukin-6 (IL-6) production by human osteoblastic MG-63 cells containing two estrogen receptor (ER) isotypes. Treatment with the ER antagonist ICI 182,780 abrogates the above actions of puerarin on osteoblast-derived cells. Using small interfering double-stranded RNAs technology, we further demonstrate that the effects of puerarin on OPG and RANKL expression are mediated by both ERα and ERβ but those on IL-6 production primarily by ERα. Moreover, we demonstrate that puerarin may promote activation of the classic estrogen response element (ERE) pathway through increasing ERα, ERβ and steroid hormone receptor coactivator (SRC)-1 expression. Therefore, puerarin will be a promising agent that prevents or retards osteoporosis. © 2014 Elsevier GmbH.


Wang Y.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard | Wang Y.,College of Logistics | Qu Y.,College of Logistics | Zhang X.L.,College of Logistics | And 4 more authors.
Molecular and Cellular Endocrinology | Year: 2014

Although 40-60% of ovarian cancer (OVCA)s express estrogen receptor (ER)α, only a minor proportion of patients respond to anti-estrogen treatment with ER antagonist tamoxifen (TAM). The mechanism underlying TAM resistance in the course of OVCA progression is incompletely understood. However, interleukin-6 (IL-6) plays a critical role in the development and progression of OVCA. Here we explore an association between IL-6 and TAM resistance. We demonstrate that both exogenous (a relatively short period of treatment with recombinant IL-6) and endogenous IL-6 (by transfecting with plasmid encoding for sense IL-6) induce TAM resistance in non-IL-6-expressing A2780 cells, while deleting of endogenous IL-6 expression in IL-6-overexpressing CAOV-3 cells (by transfecting with plasmid encoding for antisense IL-6) promotes the sensitivity of these cells to TAM. Further investigation indicates that TAM resistance caused by IL-6 is associated with the alteration of ERα, ERβ and steroid hormone receptor coactivator (SRC)-1 expression levels, the protein interactions between SRC-1 and ERα, but not ERβ, as well as blockage of estrogen-induced ER receptor nuclear translocation. These results show that IL-6 secreted by OVCA cells may contribute to the refractoriness of these cells to TAM via ER isoforms and SRC-1. Overexpression of IL-6 not only plays an important role in OVCA progression but also contributes to TAM resistance. Our studies suggest that TAM-IL-6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2013 Elsevier Ireland Ltd.


Wang Y.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard | Wang Y.,College of Logistics | Wang W.L.,College of Logistics | Xie W.L.,College of Logistics | And 5 more authors.
Phytomedicine | Year: 2013

Puerarin, the main isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, has received increasing attention because of its possible role in the prevention of osteoporosis. Previously, we showed that puerarin could inhibit the bone absorption of osteoclasts and promote long bone growth in fetal mouse in vitro. Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat. However, the mechanisms underlying its actions on human bone cells have not been well defined. Here we show that puerarin increases proliferation and differentiation and opposes cisplatin-induced apoptosis in human osteoblastic MG-63 cells containing two estrogen receptor (ER) isoforms. Puerarin promotes proliferation by altering cell cycle distribution whereas puerarin-mediated survival may be associated with up-regulation of Bcl-xL expression. Treatment with the ER antagonist ICI 182,780 abolishes the above actions of puerarin on osteoblast-derived cells. Using small interfering double-stranded RNA technology, we further demonstrate that the effects of puerarin on proliferation, differentiation and survival are mediated by both ERα and ERβ. Moreover, we also demonstrate that puerarin functions at least partially through activation of MEK/ERK and PI3K/Akt signaling. This agent also shows much weaker effect on breast epithelial cell growth than that of estrogen. Therefore, puerarin will be a promising agent that prevents or retards osteoporosis. © 2013 Elsevier GmbH. All rights reserved.


PubMed | Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, College of Logistics, Tianjin Stomatological Hospital and The General Hospital of Chinese Peoples Armed Police Forces
Type: | Journal: International immunopharmacology | Year: 2016

Daidzein is a major dietary source of isoflavones found in Leguminosae, and belongs to the family of diphenolic compounds. The estrogenic effects of daidzein to prompt bone formation and prevent bone resorption have been observed in animal models and cultured cells. In our study, we studied the effects of daidzein, raloxifene and E


PubMed | Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard and College of Logistics
Type: | Journal: Scientific reports | Year: 2016

Hypoxia-inducible factor (HIF)-1 plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1 expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1 signalling.


Li H.,Tianjin University | Li H.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard | Fan R.,Tianjin University | Sun M.,Tianjin University | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Nspc1 is an identified transcription repressor. However, transiently up-regulated or down-regulated Nspc1 in P19 embryonal carcinoma cells affects expression levels of Oct4, Sox2 and Nanog in a positive correlation. Luciferase activity assays verified that Nspc1 regulates the Oct4 promoter in a dose dependent manner. ChIP assay shows that Nspc1 activates Oct4 by directly binding to the (-1021 to -784) region of Oct4 promoter. Dominant negative analysis indicated the activation is dependent on the retinoid acid response element (RARE). We demonstrated Nspc1 has a positive role in maintaining the pluripotency of P19 cells by directly regulating Oct4. © 2013 Elsevier Inc. All rights reserved.


Liu D.-L.,Tianjin University | Zhang X.,Shenyang Pharmaceutical University | Zhao Y.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental hazard | Wang N.-L.,Shenyang Pharmaceutical University | Yao X.-S.,Shenyang Pharmaceutical University
Natural Product Research | Year: 2016

Three new triterpenoid saponins, ardisicrenoside O (1), ardisicrenoside P (2) and ardisicrenoside Q (3) together with three known compounds, 3β,16α-dihydroxy-30-methoxy-28, 30-epoxy-olean-12-en, cyclamiretin A 3-O-β-d-glucopyranosyl-(1→2) -α-l-arabinopyranoside and cyclamiretin A 3-O-β-d-glucopyranosyl-(1→4) -α-l-arabinopyranoside were isolated from the roots of Ardisia crenata Sims. Their structures were determined by one- and two-dimensional NMR techniques, including HSQC, HMBC and TOCSY experiments, as well as acid hydrolysis and GC analysis. All isolates were evaluated for the cytotoxic activities on two human cancer cell lines and compounds 3, 5 and 6 showed significant cytotoxicity. © 2016 Taylor & Francis


Zhang Y.,Tianjin University | Yang S.,Tianjin University | Li L.-Z.,Tianjin University | Li L.-Z.,Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard
Chinese Journal of New Drugs | Year: 2013

Hepatic targeted drug delivery system (HTDDS) can selectively deliver drugs to the liver lesion sites, increase the drug concentration in liver lesion tissue, reduce the side effect of drugs on other normal tissues, reduce the drug dosage and dosing frequency, improve the drug bioavailability, and therefore improve the therapeutic effects. In this paper, we summarized the general progress in research of HTDDS, such as active targeting preparation, passive targeting preparation, physical chemistry targeting preparation and prodrugs in recent years.


PubMed | Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Xinxiang Medical University and China Institute of Medical Equipment
Type: Journal Article | Journal: Anatomical record (Hoboken, N.J. : 2007) | Year: 2016

The accumulated data indicate that there is significant genetic heterogeneity underlying the etiology of silicosis. Recent reports have revealed that microRNAs (miRNAs) play an important role in regulating pulmonary fibrosis. This study, therefore, aimed to identify some miRNAs as biomarkers for silicosis, and to explore the early diagnostic value of biomarkers for silicosis. Total RNAs were collected from the peripheral blood leukocytes of 23 silicosis patients and 23 healthy controls, the different miRNAs were screened using microarrays. The potential biomarker miRNAs were identified by quantitative real-time polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curves. Eighteen differential miRNAs in leukocytes were up-regulated and twenty differential miRNAs were down-regulated in the silicosis group, compared with the control group. The expression levels of miR-181a and miR-19a were 0.88540.1037 and 0.29290.0342 by the relative quantitation method 2(-CT) of qPCR, respectively. The sensitivity and specificity for miR-181a at a cut-off value of 1.8917 were 70% and 75%, respectively, whereas, those for miR-19a at a cut-off value of 3.6828 were 95% and 95%, respectively. Thus, miR-19a in peripheral blood leukocyte could be used as an effective biomarker for silicosis. Anat Rec, 299:1300-1307, 2016. 2016 Wiley Periodicals, Inc.

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