A5101658551- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Microtubule and mitosis dynamics
- Angiogenesis and VEGF in Cancer
- Reproductive Biology and Fertility
- Cytokine Signaling Pathways and Interactions
- Chronic Myeloid Leukemia Treatments
- Nitric Oxide and Endothelin Effects
- Cardiovascular Disease and Adiposity
- Sperm and Testicular Function
- Nuclear Receptors and Signaling
- Birth, Development, and Health
- 14-3-3 protein interactions
- Chronic Lymphocytic Leukemia Research
- Eicosanoids and Hypertension Pharmacology
- Bioactive Compounds and Antitumor Agents
- Adipose Tissue and Metabolism
- Sodium Intake and Health
- Cancer-related gene regulation
- Inflammatory mediators and NSAID effects
- Menopause: Health Impacts and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Uterine Myomas and Treatments
- Esophageal and GI Pathology
Tufts Medical Center
2013-2024
Zhongda Hospital Southeast University
2015-2023
Tufts University
2002-2021
Fudan University Shanghai Cancer Center
2020
Shanghai Medical College of Fudan University
2020
Cincinnati Children's Hospital Medical Center
2014-2019
Southeast University
2019
Boston University
2012
Northeastern University
2012
Southern Medical University
2008
Steroid hormone receptors (SHRs) are ligand-activated transcription factors that regulate gene expression. SHRs also mediate rapid, nongenomic cellular activation by steroids. In vascular endothelial cells, the SHR for estrogen, estrogen receptor (ER) α, is targeted unknown mechanisms to a functional signaling module in membrane caveolae enables rapidly activate mitogen-activated protein kinase and phosphatidylinositol 3–Akt pathways, NO synthase (eNOS). Here we identify 110-kDa...
Abstract Insulin‐like growth factor‐I (IGF‐I) has been shown to be a potent agent in promoting the and differentiation of oligodendrocyte precursors, stimulating myelination during development following injury. To definitively determine whether IGF‐I acts directly on cells lineage, we generated lines mice which type 1 IGF receptor gene ( igf1r ) was conditionally ablated either Olig1 or proteolipid protein expressing (termed IGF1R pre‐oligo‐ko oligo‐ko mice, respectively). Compared with wild...
Oligodendrocytes are myelin-forming glia that ensheath the axons of neurons in CNS. Recent studies have revealed <i>Wnt</i>/β-catenin signaling plays important roles oligodendrocyte development and myelin formation. However, there conflicting reports on specific function <i>Wnt</i> components specification differentiation. In present study, we demonstrate activation β-catenin neural progenitor cells before gliogenesis inhibits generation progenitors (OLPs) mice. Once OLPs formed, becomes...
Primary open-angle glaucoma is associated with elevated intraocular pressure, which in turn believed to result from impaired outflow of aqueous humour. Aqueous humour passes mainly through the trabecular meshwork (TM) and then pores formed endothelium Schlemm's canal (SC), experiences a basal-to-apical pressure gradient. This gradient dramatically deforms SC endothelial cell potentially contributes formation those pores. However, mechanical properties are poorly defined. Using optical...
Clinical trial and epidemiological data support that the cardiovascular effects of estrogen are complex, including a mixture both potentially beneficial harmful effects. In animal models, protects females from vascular injury inhibits atherosclerosis. These mediated by receptors (ERs), which, when bound to estrogen, can bind DNA directly regulate transcription. ERs also activate several cellular kinases inducing rapid nonnuclear signaling cascade. However, biological significance this...
The steroid hormone aldosterone (aldo) contributes to cardiovascular disease in animal models and humans. Aldo activates the mineralocorticoid receptor (MR), a hormone-activated transcription factor, indeed, pharmacological MR inhibition improves outcomes. Because incidence of is lower premenopausal women, we hypothesized that estrogen (E2) signaling through (ER) may protect vasculature by inhibiting detrimental effects aldo MR. We demonstrate E2-activated ER inhibits MR-mediated gene from...
The incidence of obesity is rising, particularly among women. Microvascular dysfunction more common with female sex, obesity, and hyperlipidemia predicts adverse cardiovascular outcomes, but the molecular mechanisms are unclear. Because associated mineralocorticoid receptor (MR) activation, we tested hypothesis that MR in endothelial cells contribute to sex differences resistance vessel response cardiometabolic risk factors.Male cell-specific knockout mice MR-intact littermates were...
Compelling clinical evidence indicates that obesity and its associated metabolic abnormalities supersede the protective effects of female sex-hormones predisposes premenopausal women to cardiovascular disease. The underlying mechanisms remain poorly defined; however, recent studies have implicated overactivation aldosterone-MR (mineralocorticoid receptor) axis as a cause sex-specific risk in obese females. Experimental MR on endothelial cells contributes obesity-associated, leptin-induced...
Objective: MR (mineralocorticoid receptor) activation is associated with cardiovascular ischemia in humans. This study explores the role of atherosclerotic mice both sexes and identifies a sex-specific for endothelial cell (EC)-MR vascular inflammation. Approach Results: In AAV-PCSK9 (adeno-associated virus-proprotein convertase subtilisin/kexin type 9) mouse atherosclerosis model, inhibition attenuated inflammation males but not females. Further studies comparing male female littermates...
Preeclampsia is a syndrome of high blood pressure (BP) with end organ damage in late pregnancy that associated circulating soluble VEGF receptor (sFlt1 [soluble Fms-like tyrosine kinase 1]). Women exposed to preeclampsia have substantially increased risk hypertension after pregnancy, but the mechanism remains unknown, leaving missed interventional opportunity. After preeclampsia, women enhanced sensitivity hypertensive stress. Since smooth muscle cell mineralocorticoid receptors (SMC-MR) are...
The interaction of beta III-depleted tubulin with taxol was investigated. A monoclonal antibody against the III isotype immobilized on a sepharose 4B column and used to remove from unfractionated tubulin. assembly in presence enhanced compared critical concentration 10 microM is 0.4 mg/ml, while 0.16 mg/ml. At different taxol, increased relative that reaches maximum at about 1:1 ratio taxol. has also been studied by electron microscopy. After 2 minutes 37 degrees C, results only ribbon-like...
The proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in diseases, such as atherosclerosis and restenosis, after percutaneous coronary intervention. Many studies have shown that estrogen inhibits VSMC response to injury the mouse carotid model. However, mechanisms mediate these effects remain unclear. Here, we investigated by which proliferation.We established novel transgenic line, referred disrupting peptide mice, rapid receptor (ER)-mediated signaling is abolished...
Vascular stiffness increases with aging, obesity and hypertension predicts cardiovascular risk. The levels of histone H3-lysine-27 methylation (H3K27me) the methyltransferase EZH2 both decrease in aging vessels, driving vascular stiffness. impact inhibitors on is unknown. We tested hypothesis that inhibitor GSK126, currently development for cancer treatment, explored underlying molecular mechanisms. Young (3 month) middle-aged (12 male mice were treated GSK126 1-2 months primary human aortic...
Microtubule assembly of different beta tubulin isotypes in the presence 4 M glycerol and 6 mM magnesium ion demonstrates significantly characteristics. alpha II IV assembled faster to a greater extent than did unfractionated phosphocellulose-purified (PC-tubulin). from III showed distinctive delay nucleation, proceeded at slower rate those other isotypes, had highest critical concentration. However, treatment with subtilisin remove C-terminal domain dimer abolished these differences...
Objective— Estradiol (E2) regulates gene transcription by activating estrogen receptor-α and receptor-β. Many of the genes regulated E2 via receptors are repressed, yet molecular mechanisms that mediate E2-induced repression currently unknown. We hypothesized E2, acting through receptors, expression microRNAs (miRs) leading to specific target genes. Methods Results— Here, we report significantly upregulates 26 miRs downregulates 6 in mouse aorta. E2-mediated upregulation one these miRs,...
Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs), which likely underlies its ability to accelerate re-endothelialization reduce adverse remodeling after injury. In previous studies, we have shown that protective effects E2 (the active endogenous form estrogen) in injury require estrogen receptor alpha (ERα). ERα transduces via a classical DNA binding, "genomic" signaling pathway more recently-described "rapid" is mediated by subset localized cell...
To investigate whether peer support would reduce diabetes distress and improve glycaemic control when added to usual education among adults with Type 2 in China.We conducted a cluster randomized trial involving 400 from eight communities Nanjing. All participants received for an average of h each month physicians, certified educators, dieticians, psychologists podiatric nurses. Peer was led by trained leaders included knowledge- skills-sharing at least once month, as well peer-to-peer...
Abstract Background The benefit and harm of three-field lymphadenectomy for oesophageal cancer are still unknown. aim this study was to compare overall survival morbidity mortality between three- two-field in patients with squamous cell carcinoma. Methods Between March 2013 November 2016, carcinoma the middle or distal oesophagus were assigned randomly open oesophagectomy (cervical–thoracic–abdominal) (thoracic–abdominal) lymphadenectomy. No chemo(radio) therapy given before surgery. This...
Abstract Aims Vascular stiffness increases with age and independently predicts cardiovascular disease risk. Epigenetic changes, including histone modifications, accumulate but the global pattern has not been elucidated nor are regulators known. Smooth muscle cell-mineralocorticoid receptor (SMC-MR) contributes to vascular in ageing mice. Thus, we investigated regulatory role of SMC-MR epigenetics stiffness. Methods results Mass spectrometry-based proteomic profiling all modifications...
Estrogen receptor α (ERα) mediates the effects of estrogen by altering gene expression following hormone binding. It has recently been shown that kinase-mediated phosphorylation ERα also transcriptionally activates in absence estrogen. We now report ERα-dependent is regulated protein phosphatase 2A (PP2A). co-immunoprecipitates with enzymatically active PP2A. binds directly to catalytic subunit PP2A, which dephosphorylates serine 118 receptor. Amino acids 176–182 A/B domain are required for...
Vascular MR (mineralocorticoid receptor) expression increases with age driving aging-associated vascular stiffness and hypertension. has two isoforms (1α 1β) distinct 5'-untranslated promoter sequences (P1 P2), but the gene regulatory mechanisms remain unknown. We investigated transcriptional regulation in aging human smooth muscle cells (SMC).
In addition to mediating the classical transcriptional effects of estrogen, estrogen receptors (ERs) are now known regulate gene expression in absence by ligand‐independent activation pathways, and mediate rapid, non‐genomic as well. ERs have been shown associate with cell membrane, recent studies demonstrate that this subpopulation membrane‐associated ER mediates rapid estrogen. To date, however, little is regarding pathways distribution between nuclear membrane fractions. current study, we...
Mitogen-activated protein (MAP) kinase, kinase C (PKC), cAMP, and okadaic acid (OA)-sensitive phosphatases (PPs) have been suggested to be involved in oocyte meiotic resumption. However, whether these kinases act by independent pathways or interact with each other regulating meiosis resumption is unknown. In the present study, we aimed determine regulation of MAP phosphorylation PKC, OA-sensitive PPs rat oocytes using an vitro maturation system Western blot analysis. We found that ERK1 ERK2...
Mitogen-activated protein kinase (MAPK) and phosphatase 2A (PP2A) regulate oocyte meiosis, yet little is known regarding their mechanisms of action. This study addressed the functional importance active MAPK PP2A in regulating meiosis. Experiments were conducted to identify activation, activity, intracellular enzyme trafficking, ultrastructural associations during Questions requisite and/or activity chromatin condensation, microtubule polymerization, spindle formation addressed. At level,...