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Featured researches published by Jiedong Wang.


Human Reproduction | 2013

A critical period of progesterone withdrawal precedes endometrial breakdown and shedding in mouse menstrual-like model

Qianxing Wang; Xiangbo Xu; Bin He; Yunfeng Li; Xihua Chen; Jiedong Wang

STUDY QUESTION Is there a critical period of progesterone (P4) withdrawal in a mouse menstrual-like model, and at what time after P4 withdrawal endometrial breakdown become irreversible? STUDY ANSWER Our results showed that a 12-16 h critical period of P4 withdrawal exists in the mouse menstrual-like model. WHAT IS KNOWN ALREADY P4 withdrawal is the trigger for endometrial breakdown and shedding during menstruation. To date, the molecular mechanisms responsible for endometrial breakdown have not been fully elucidated. In an ovariectomized macaque model, P4 replacement could reduce or block menses during a period of 36-48 h after P4 withdrawal, but after this, P4 supplementation did not reduce or block menses. Thus, in the macaque, a critical period of P4 withdrawal lasting 36-48 h exists before menses. STUDY DESIGN, SIZE, DURATION We created a mouse menstrual-like model and restored P4 at four time points. The total number of mice was 120 and the duration of treatment was 26 days. PARTICIPANTS, SETTING, METHODS A mouse menstrual model was characterized by endometrial morphology and plasma P4 levels. P4 was then replaced at 8, 12, 16 and 20 h after the removal of P4 implants. Vaginal smears, endometrial morphology, plasma P4 levels and expression patterns of matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-10, MMP-11 and MMP-13) were investigated. MAIN RESULTS AND THE ROLE OF CHANGE Replacement of P4 at 8 and 12 h blocked menstrual-like bleeding and endometrial shedding; however, replacement at 16 and 20 h did not suppress bleeding or shedding. Furthermore, P4 replacement at 12 h inhibited the expression of all latent or active MMPs; however, replacement at 16 h inhibited only pMMP-13. LIMITATIONS, REASONS FOR CAUTION Although determination of the critical period in vivo using a mouse model was successfully demonstrated, the mechanisms of P4 regulation need to be further explored. WIDER IMPLICATIONS OF THE FINDINGS The experimental opportunities provided by the mouse model will facilitate understanding the role of P4 in the regulation of menstruation and help to identify new targets for the clinical intervention of menstrual disorders.


PLOS ONE | 2011

Comprehensive Analysis of Leukocytes, Vascularization and Matrix Metalloproteinases in Human Menstrual Xenograft Model

Yong Guo; Bin He; Xiangbo Xu; Jiedong Wang

In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.


Endocrinology | 2013

Cyclooxygenase-2 Regulated by the Nuclear Factor-κB Pathway Plays an Important Role in Endometrial Breakdown in a Female Mouse Menstrual-like Model

Xiangbo Xu; Xihua Chen; Yunfeng Li; Huizi Cao; Cuige Shi; Shuo Guan; Shucheng Zhang; Bin He; Jiedong Wang

The role of prostaglandins (PGs) in menstruation has long been proposed. Although evidence from studies on human and nonhuman primates supports the involvement of PGs in menstruation, whether PGs play an obligatory role in the process remains unclear. Although cyclooxygenase (COX) inhibitors have been used in the treatment of irregular uterine bleeding, the mechanism involved has not been elucidated. In this study, we used a recently established mouse menstrual-like model for investigating the role of COX in endometrial breakdown and its regulation. Administration of the nonspecific COX inhibitor indomethacin and the COX-2 selective inhibitor DuP-697 led to inhibition of the menstrual-like process. Furthermore, immunostaining analysis showed that the nuclear factor (NF)κB proteins P50, P65, and COX-2 colocalized in the outer decidual stroma at 12 to 16 hours after progesterone withdrawal. Chromatin immunoprecipitation analysis showed that NFκB binding to the Cox-2 promoter increased at 12 hours after progesterone withdrawal in vivo, and real-time PCR analysis showed that the NFκB inhibitors pyrrolidine dithiocarbamate and MG-132 inhibited Cox-2 mRNA expression in vivo and in vitro, respectively. Furthermore, COX-2 and NFκB inhibitors similarly reduced endometrial breakdown, suggesting that NFκB/COX-2-derived PGs play a critical role in this process. In addition, the CD45(+) leukocyte numbers were sharply reduced following indomethacin (COX-1 and COX-2 inhibitor), DuP-697 (COX-2 inhibitor), and pyrrolidine dithiocarbamate (NFκB inhibitor) treatment. Collectively, these data indicate that NFκB/COX-2-induced PGs regulate leukocyte influx, leading to endometrial breakdown.


Endocrinology | 2014

ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

Bin Wu; Xihua Chen; Bin He; Shuyan Liu; Yunfeng Li; Qianxing Wang; Haijun Gao; Shufang Wang; Jianbing Liu; Shucheng Zhang; Xiangbo Xu; Jiedong Wang

Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.


PLOS ONE | 2012

Expression of PRB, FKBP52 and HB-EGF Relating with Ultrasonic Evaluation of Endometrial Receptivity

Ning Wang; Linlin Geng; Shucheng Zhang; Bin He; Jiedong Wang

Background To explore the molecular basis of the different ultrasonic patterns of the human endometrium, and the molecular marker basis of local injury. Methodology/Principal Findings The mRNA and protein expression of FKBP52, progesterone receptor A (PRA), progesterone receptor B (PRB), and HB-EGF were detected in different patterns of the endometrium by real-time RTPCR and immunohistochemistry. There were differences in the mRNA and protein expression of FKBP52, PRB, and HB-EGF in the triple line (Pattern A) and homogeneous (Pattern C) endometrium in the window of implantation. No difference was detected in PRA expression. After local injury, the mRNA expression of HB-EGF significantly increased. In contrast, there was no difference in the mRNA expression of FKBP52, PRB, or PRA. The protein expression of FKBP52, PRB, and HB-EGF increased after local injury. There was no difference in the PRA expression after local injury. Conclusions PRB, FKBP52, and HB-EGF may be the molecular basis for the classification of the ultrasonic patterns. HB-EGF may be the molecular basis of local injury. Ultrasonic evaluation on the day of ovulation can be effective in predicting the outcome of implantation.


Herz | 2015

Mechanisms of new-onset atrial fibrillation complicating acute coronary syndrome

Jiedong Wang; Yanmin Yang; Jun Zhu

Atrial fibrillation (AF) is one of the most common arrhythmia complications of acute coronary syndrome (ACS). The incidence of new-onset AF is 2.3–37 %, and it is an important predictor of a patient’s morbidity, mortality, and prolonged hospitalization. Various risk factors for the development of new-onset AF after ACS have been identified, including: old age, higher Killip class, relevant history (e.g., hypertension), and enlarged left atrium. Insights into the pathophysiological mechanisms of new-onset AF have been provided by both experimental and clinical investigations and show that new-onset AF is multifactorial, involving atrial ischemia and atrial stretch, inflammation, autonomic nervous system activity, and hormone activation. An understanding of the mechanisms underlying new-onset AF complicating ACS can provide new insight of therapeutic importance.ZusammenfassungVorhofflimmern (VF) ist eine der häufigsten Arrhythmien, die als Komplikationen des akuten Koronarsyndroms („acute coronary syndrome“, ACS) auftreten. Die Inzidenz eines neu auftretenden VF liegt bei 2,3–37 %. Es stellt einen bedeutenden Prädiktor der Morbidität, Mortalität und verlängerten stationären Behandlung von Patienten dar. Verschiedene Risikofaktoren für die Entstehung eines neu auftretenden VF nach ACS sind bekannt. Dazu gehören hohes Alter, eine höhere Killip-Klasse, eine entsprechende Vorgeschichte (wie Hypertonie usw.) sowie ein vergrößerter linker Vorhof. Einblicke in die pathophysiologischen Abläufe des neu auftretenden VF sind sowohl durch experimentelle als auch durch klinische Studien gewonnen worden und zeigen, dass das neu auftretende VF „multifaktoriell“ bedingt ist – unter Beteiligung von Ischämie und Dehnung des Vorhofs, Entzündungsprozessen, Aktivität des autonomen Nervensystems und Hormonaktivierung. Das Verständnis der Vorgänge, die dem neu aufgetretenen VF als Komplikation eines ACS zugrunde liegen, kann auch zu neuen Erkenntnissen im Hinblick auf die therapeutische Bedeutung führen.


Journal of Asian Natural Products Research | 2014

Tanshinol protects hippocampus and attenuates vascular dementia development

Cuige Shi; Yishu Yang; Hui Li; Ying Zhang; Ning Wang; Shang-Ming Wang; Jiedong Wang; Shucheng Zhang

Tanshinol (3-(3′,4′-dihydroxyphenyl)-(2R)-lactic acid, TSL) is widely used in traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases. Here, we assessed whether TSL protected hippocampus and attenuated vascular dementia (VD) development in rats. The behavioral analysis showed that TSL could decrease the distance and latency time, and increase the swim speed in water maze in rats subjected to VD. TSL remarkably increased acetylcholine level and decreased acetylcholinesterase activity in rats subjected to VD. Likewise, TSL remarkably decreased malondialdehyde and increased superoxide dismutase levels in rats subjected to VD. Furthermore, treatment with TSL reduced the level of dead neurons in dentate gyrus. In addition, TSL upregulated growth-associated protein 43 (GAP43) and vascular endothelial growth factor (VEGF) expression and downregulated phosphorylated Akt (p-AKt) and phosphorylated glycogen synthase kinase (p-GSK3β) expression in hippocampus in rats subjected to VD. These results suggest that TSL may be a potential compound in VD model.


Asia Pacific Journal of Clinical Nutrition | 2014

Effect of daily milk supplementation on serum and umbilical cord blood folic acid concentrations in pregnant Han and Mongolian women and birth characteristics in China

Yunfeng Li; Na-Shun Hu; Xiao-Bin Tian; Li Li; Shang-Ming Wang; Xiangbo Xu; Ning Wang; Cuige Shi; Jin-Cai Zhu; Jing-Sheng Sun; Jin-Hua Bao; Si-Hai Lang; Chang-Jiang Li; De-Gang Fan; Ling Zhang; Bin Zhang; Yu Gao; Bin He; Jiedong Wang; Shucheng Zhang

Many studies have demonstrated the efficacy of folic acid (FA) supplementation in prevention of neural tube defects (NTDs), although the extent of NTDs varies among individuals of different races and ethnic origin. China is a multi-ethnic country with no standard practice for FA-fortified food. Milk is consumed by women, but little is known about the effects of milk on folate concentration in maternal blood and neonatal umbilical cord blood in Han and Mongolian women after stopping taking the supplement for a month and five month, respectively. The objective of this study was to determine whether only daily consumption of liquid milk can increase the blood folate concentration in pregnant women and whether there are differences in blood folate concentrations between Han and Mongolian women after cessation of FA supplementation. Of the 4052 women enrolled in the parallel group design study. Three thousand five hundred and twenty-six women had confirmed pregnancies and were randomized to receive liquid milk or not until delivery. Women who consumed the liquid milk had significantly increased serum folate concentrations at 16 and 32 weeks of gestation as well as cord blood at birth compared to control groups in both ethnic groups. Infants born to women drinking milk also had better the term birth weight and height, which may be related to the increased concentration of folate. In conclusion, daily consumption of milk can increase the serum folate concentration in pregnant Han and Mongolian women in China (differences in the efficacy of FA and milk supplementation) and may enhance birth outcomes.


Ultrastructural Pathology | 2012

Sperm Head Vacuoles—Light Microscopic and Ultrastructural Observations: A Case Report

Shucheng Zhang; Ning Wang; Bin He; Jie Cheng; Shui Xi; Shang-Ming Wang; Yu Gao; Jiedong Wang

Background: Sperm head vacuoles are easily detectable in human spermatozoa under the electron microscope. A sperm head vacuole is considered abnormal when it exceeds 20% of the head’s cross-sectional area. The authors report a rare case of primary spermatozoa deformity with 100% vacuolated head and evaluate the correlation between presence of head vacuoles/nucleus vacuoles and abnormal transformation of nucleoprotamine types, defects of nucleoprotamine, and gene disorders of chromatin/chromosome/spermatogenesis. Methods: A 43-year-old male patient with infertility came to the Reproduction Health Center, Hebei, China. Semen was examined in accordance with the WHO criteria, and the spermatozoa were counted. Two hundred spermatozoa were observed both under light microscope and the electronic microscope. Results: About 50% of the spermatozoa had head deformities. In the intact spermatozoa, the heads were 100% vacuolated. Under ultrastructural observation, abnormalities were observed and two major types of spermatozoa were detected. In the head of those incompletely mature spermatozoa, four kinds of the nucleus vacuoles were observed. Conclusion: Abnormal spermatozoa with head vacuoles account for the patient infertility.


PLOS ONE | 2012

Repeated Abortion Affects Subsequent Pregnancy Outcomes in BALB/c Mice

Fang Lv; Xiangbo Xu; Shucheng Zhang; Lili Wang; Ning Wang; Bin He; Jiedong Wang

Aim In this study, we aimed to establish a mouse model of repeated medical termination of pregnancy in order to determine subsequent outcomes. Methods A model of mifepristone (RU 486)-induced medical abortion was established in BALB/c mice to facilitate the investigation of the impact of medical abortion on subsequent pregnancies, including litter sizes and newborn birth weights. Pregnant mice were sacrificed to examine midterm pregnancy status, investigate the frequency of fetal resorption, and measure placental function gene expression by real-time PCR and immunohistochemistry. Offspring liver mRNA was harvested for real-time PCR to determine gene expression and assess the effects of abortion on offspring development. Results Mice subjected to 2 previous medical abortions experienced spontaneous abortions in subsequent pregnancies. Medical abortion caused reduced reproductive capacity and affected placental dysfunction, with reduced expression of tissue factor (TF) and genes encoding proteins involved in metabolic functions relevant to pregnancy, such as 11β-hydroxysteroid dehydrogenase 1/2 (11β-HSD1/2) and glucocorticoid receptor (GR). Reduced expression was also observed for platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF). In offspring from subsequent pregnancies, genes involved in lipid metabolism, which may enhance key lipid transcription factors, such as PPARA and PPARG, as well as GR/11β-HSD1, were downregulated in the liver. In addition, the sperm motility of the F1 males reduced. Conclusion Repeated medical abortion impaired the reproductive function of female mice, significantly affecting the outcomes of subsequent pregnancies. The impact of repeated abortions on the offspring of subsequent pregnancies was also noteworthy and deserves further exploration. Thus, this model provides a useful means to study the mechanisms underlying the above phenomena, which will ultimately benefit the health of women and their children.

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Bin He

Peking Union Medical College

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Xiangbo Xu

Peking Union Medical College

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Ning Wang

Peking Union Medical College

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Yunfeng Li

Hebei Medical University

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Xihua Chen

Peking Union Medical College

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Cuige Shi

Capital Medical University

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Lili Wang

Peking Union Medical College

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Bin Wu

Peking Union Medical College

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Hui Li

Capital Medical University

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Huizi Cao

Peking Union Medical College

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