Publications by authors named "Da Wo"

21 Publications

  • Page 1 of 1

Network pharmacology-based analysis in determining the mechanisms of Huoxin pill in protecting against myocardial infarction.

Pharm Biol 2021 Dec;59(1):1191-1202

Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Context: Huoxin pill (HXP) is a commonly used TCM prescription for treatment of cardiovascular diseases. However, its mechanism in protecting against myocardial infarction (MI) remains unknown.

Objective: We performed a network pharmacology analysis to explore the bioactive ingredients, therapeutic effects, and mechanisms of HXP in protecting against MI.

Materials And Methods: HPLC was used to identify major bioactive compounds, and overlap with MI target genes were visualised. 10-Week old C57BL/6 mice were randomly assigned as: Sham-operated control, MI + Phosphate buffered saline (PBS), and MI + HXP (3 mg/mL and 9 mg/mL) treatment groups, received oral gavage administration once every two-days starting from 1-week prior to MI, and subsequently MI models were established for one-week before sacrifice.

Results: AKT1, VEGFA, TNF and RELA were identified as core target proteins among eighty-five candidate bioactive compounds identified in HXP with overlapping MI-related genes. HXP protection against MI was mainly via regulation of inflammatory pathways, notably TNF signalling pathway. Mouse models of MI and cardiac myoblasts demonstrated that HXP improved MI-induced injury via improving regulation of inflammatory response.

Discussion And Conclusion: Stellasterol, deoxycholic acid, kaempferol, and quercetin are important active compounds contained in HXP with anti-inflammatory properties in the therapeutic treatment of MI. Due to the straightforward nature and effectiveness of taking oral HXP medications, our findings provide a theoretical basis for the clinical application of HXP in treating patients with angina or myocardial ischaemia. Future research into the combination of surgical procedures or medications that restore blood flow together with HXP as supportive medication would be worthwhile.
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http://dx.doi.org/10.1080/13880209.2021.1964542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425702PMC
December 2021

Babao Dan is a robust anti-tumor agent via inhibiting wnt/β-catenin activation and cancer cell stemness.

J Ethnopharmacol 2021 Nov 28;280:114449. Epub 2021 Jul 28.

Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. Electronic address:

Ethnopharmacological Relevance: Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown.

Aim Of The Study: Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/β-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD).

Materials And Methods: We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of β-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/β-catenin signaling.

Results: BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/β-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness.

Conclusion: Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/β-catenin signaling, and implicate its use in the clinical treatment of cancers.
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http://dx.doi.org/10.1016/j.jep.2021.114449DOI Listing
November 2021

IGFBP-4 enhances VEGF-induced angiogenesis in a mouse model of myocardial infarction.

J Cell Mol Med 2020 08 28;24(16):9466-9471. Epub 2020 Jun 28.

Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed to investigate whether dual treatment with insulin-like growth factor binding protein-4 (IGFBP-4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP-4 enhanced VEGF-induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin-1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen-I and collagen-III following MI. Importantly, while the protective action of IGFBP-4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post-ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease.
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http://dx.doi.org/10.1111/jcmm.15516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417680PMC
August 2020

Deletion of low-density lipoprotein-related receptor 5 inhibits liver Cancer cell proliferation via destabilizing Nucleoporin 37.

Cell Commun Signal 2019 12 27;17(1):174. Epub 2019 Dec 27.

Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, 350122, Fujian, China.

Background: LRP5/6 are co-receptors in Wnt/β-catenin pathway. Recently, we discovered multiple β-catenin independent functions of LRP5/6 in tumor cells and in the diseased heart. Nucleoporin 37 (NUP37) is an important component of the nuclear pore complex (NPC), whose elevated expression is associated with worsened prognosis in liver cancer. Previous studies have shown that NUP37 interacted with YAP and activated YAP/TEAD signaling in liver cancer. Our preliminary findings showed a nuclear location of LRP5. We thus tested the hypothesis that LRP5 may act as a genuine regulator of YAP/TEAD signaling via modulating NUP37 in a β-catenin-independent way.

Methods: We performed siRNA knockdown of LRP5, LRP6, or β-catenin in liver cancer HepG2 cells to determine the effect on tumor cell proliferation. Protein expressions and interaction between LRP5 and NUP37 were determined using immunoprecipitation and western blot analyses.

Results: HepG2 cell proliferation was markedly inhibited by knockdown of LRP5 but not LRP6 or β-catenin, suggesting that LRP5 has a specific, β-catenin-independent role in inhibiting HepG2 cell proliferation. Knockdown of NUP37 by siRNA inhibited the proliferation of HepG2 cells, whereas overexpression of NUP37 reversed the decrease in cell proliferation induced by LRP5 knockdown. Immunoprecipitation assays confirmed that LRP5 bound to NUP37. Furthermore, LRP5 overexpression restored NUP37 knockdown-induced downregulation of YAP/TEAD pathway.

Conclusions: LRP5 deletion attenuates cell proliferation via destabilization of NUP37, in a β-catenin-independent manner. LRP5 therefore acts as a genuine regulator of YAP/TEAD signaling via maintaining the integrity of the NPC, and implicates a therapeutic strategy in targeting LRP5 for inhibiting liver cancer cell proliferation.
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http://dx.doi.org/10.1186/s12964-019-0495-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935199PMC
December 2019

LRP6 Ectodomain Prevents SDF-1/CXCR4-Induced Breast Cancer Metastasis to Lung.

Clin Cancer Res 2019 08 22;25(15):4832-4845. Epub 2019 Apr 22.

Clinical and Translational Research Center, Research Institute of Heart Failure Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Tongji University School of Medicine, Shanghai, China.

Purpose: Lung metastasis is an important cause of breast cancer-related deaths, in which SDF-1/CXCR4 signaling pathway plays a critical role. Single transmembrane protein LRP6 is viewed as an oncogene via activating the Wnt/β-catenin signaling pathway. Our work aims to investigate the relationship between SDF-1/CXCR4 and LRP6 in breast cancer lung metastasis.

Experimental Design: We examined the expressions and functions of SDF-1/CXCR4 and LRP6 as well as their relationship in breast cancer and .

Results: LRP6 ectodomain (LRP6N) directly bound to CXCR4 and competitively prevented SDF-1 binding to CXCR4. LRP6N prevented SDF-1/CXCR4-induced metastasis to lung and prolonged survival in mice bearing breast tumors, whereas LRP6 knockdown activated SDF-1/CXCR4 signal transduction and promoted lung metastasis and tumor death. Furthermore, patients with breast cancer with high CXCR4 expression had poor prognosis, which was exacerbated by low LRP6 expression but improved by high LRP6 expression. Interestingly, a secreted LRP6N was found in the serum of mice and humans, which was downregulated by the onset of cancer metastasis in both mice bearing breast cancer as well as in patients with breast cancer.

Conclusions: LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis. LRP6N also provides an interesting link between Wnt signaling and SDF-1/CXCR4 signaling, the two key pathways involved in cancer development.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3557DOI Listing
August 2019

Alkaloids from Nelumbinis Plumula (AFNP) ameliorate aortic remodeling via RhoA/ROCK pathway.

Biomed Pharmacother 2019 Apr 20;112:108651. Epub 2019 Feb 20.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, PR China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, PR China. Electronic address:

The protective role of alkaloids from Nelumbinis Plumula (AFNP) on the aorta during hypertension is not yet fully understood. We hypothesize that AFNP exerts protective effects against Ang II-induced hypertension by mediating RhoA/ROCK pathway and phenotypic switching during hypertension. In the present study, we evaluated the effect of AFNP on angiotensin II (Ang II)-induced actin cytoskeleton reorganization and aorta remodeling, as well as the involvement of RhoA/Rho-associated coiled kinase (ROCK) pathway in protecting against hypertension. We used rat aortic tissues to investigate the vasodilatation effect of AFNP on Ang II-induced constriction. AFNP was shown to significantly relax the endothelium-intact arteries induced by Ang II. We further investigated the vasodilation effect of AFNP in endothelium denuded arteries, which showed that the action of AFNP was endothelial independent. Male SHR rats were treated with saline or AFNP and morphological changes were examined following 8 weeks. AFNP treatment normalized the effects of hypertension in SHRs. HE staining showed that AFNP treatment improved the tunica media and wall thickness and ratio of MT/LD and MA/LA. Western blotting showed that AFNP treatment markedly decreased the Ang II-induced expression of collagen I and increased α-SMA in aorta. Furthermore, MTT assay showed that AFNP inhibited the proliferation of Ang II treated VSMCs in a concentration-dependent manner. AFNP treatment also ameliorated F-actin cytoskeleton remodeling in Ang II treated VSMCs, as visualized under fluorescence microscopy. Western blot analysis showed that RhoA transposition and ROCK activation and phosphorylation of MYPT1 was increased following Ang II treatment but were inhibited by AFNP treatment, showing that the cardio-protective effect of AFNP is likely mediated by the RhoA/ROCK signaling pathway. The anti-hypertension and aortic protection effects of AFNP are due to non-endothelial dependent inhibition of the VSMC cytoskeleton remodeling and regulation of RhoA/ROCK pathway.
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http://dx.doi.org/10.1016/j.biopha.2019.108651DOI Listing
April 2019

Effects of midwife-led maternity services on postpartum wellbeing and clinical outcomes in primiparous women under China's one-child policy.

BMC Pregnancy Childbirth 2018 Aug 13;18(1):329. Epub 2018 Aug 13.

Division of Psychology, Nottingham Trent University, Chaucer Building 4013, Burton Street, Nottingham, NG1 4BU, UK.

Background: The Midwife-led maternity services have been implemented in China in response to the high rates of primiparous women and Caesarean Sections (CS) which may be related to China's one-child policy. However, few studies in China have been reported on the effectiveness of Midwife-led Care at Delivery (MCD) and the Continuity of Midwife-led Care (CMC) on postpartum wellbeing and other clinical outcomes. Therefore, evidence-based clinical validation is needed to develop an optimal maternity service for childbearing women in China.

Methods: A concurrent cohort study design was conducted with 1730 pregnant women recruited from 9 hospitals in Shanghai. Among the 1730 participants at baseline, 1568 participants completed the follow-up questionnaire, with a follow-up rate of 90.6%.

Results: Compared with the routine Obstetrician-led Maternity Care (OMC), Midwife-led Care at Delivery (MCD) was associated with CS rate (OR were 0.16; 95%CI: 0.11 to 0.25) and a higher total score of postpartum wellbeing (βwere 2.70; 95%CI: 0.70 to 4.70) when adjusting for the baseline differences and other confounders during delivery or postpartum period. Moreover, continuity of Midwife-led Care (CMC) was associated with CS rate (OR were 0.30; 95%CI: 0.23 to 0.41), as well as increased rate of breastfeeding within the first 24 h (OR were 2.49; 95% CI: 1.47 to 4.23), higher postpartum satisfaction (β = 4.52; 95% CI: 1.60 to 12.68), lower anxiety (βwere 0.66; 95% CI: 0.16 to 1.17), increased self-control (βwere 0.39; 95% CI: 0.02 to 0.76) and a higher total score of postpartum wellbeing (βwere 3.14; 95% CI: 1.54 to 4.75).

Conclusion: CMC is the optimal service for low-risk primiparous women under China's one-child policy, and is worthwhile for a general implementation across China.
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http://dx.doi.org/10.1186/s12884-018-1969-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090670PMC
August 2018

Baicalin alleviates H2O2‑induced injury of H9c2 cardiomyocytes through suppression of the Wnt/β‑catenin signaling pathway.

Mol Med Rep 2017 Dec 10;16(6):9251-9255. Epub 2017 Oct 10.

Fujian Key Laboratory of Integrative Geriatric Medicine, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

Baicalin is one of the active ingredients extracted from the dry root of Scutellaria baicalensis Georgi, which has been reported to be effective in preventing myocardial ischemia reperfusion injury. However, the mechanisms underlying its cardioprotective activities remain to be elucidated. In the present study, H2O2‑treated cardiomyocyte H9c2 cell line served as an in vitro model of oxidation‑damaged cardiomyocytes to evaluate the effects of baicalin on the cardiac injury, and to investigate the underlying molecular mechanism. The results of the TOPFlash/Renilla reporter gene assay indicated that baicalin significantly suppressed the activation of proto‑oncogene Wnt‑1 (Wnt)/β‑catenin in 293 cells, in a dose dependent manner. In addition, baicalin significantly inhibited H2O2‑induced loss of H9c2 cell viability in MTT assay. Furthermore, western blotting analysis demonstrated that baicalin markedly attenuated H2O2‑induced cell apoptosis, as demonstrated by the down‑regulation of cleaved caspase‑3 and the increase in the apoptosis regulator Bcl‑2 (Bcl‑2)/apoptosis regulator BAX (Bax) ratio following baicalin treatment in H2O2‑treated H9c2 cells. Furthermore, baicalin markedly decreased the expression of β‑catenin and downstream Axin‑2 and myc proto‑oncogene protein in H2O2‑treated H9c2 cells. Knockdown of β‑catenin expression inhibited H2O2‑induced cell apoptosis. Finally, LiCl (a β‑catenin stabilizer) induced apoptosis of H9c2 cells by upregulating the expression of β‑catenin, which was significantly neutralized by the treatment with baicalin. Taken together, it is hypothesized that baicalin exerts cardioprotective effects via suppression of the Wnt/β‑catenin signaling pathway.
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http://dx.doi.org/10.3892/mmr.2017.7748DOI Listing
December 2017

Opposing Roles of Wnt Inhibitors IGFBP-4 and Dkk1 in Cardiac Ischemia by Differential Targeting of LRP5/6 and β-catenin.

Circulation 2016 Dec 1;134(24):1991-2007. Epub 2016 Nov 1.

From Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, China (D.W., Jinhui Peng, D.-n.R., J.C., Y. Zhu, Y.Y., H.Y., E.M., Y.C., Zhongmin Liu, S.L., L.A., W.Z.); Department of Orthopedics, Changzheng Hospital, Shanghai, China (Jinhui Peng, Q.Q.); Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China (L.Q., Jun Peng); Shanghai Key Laboratory of Signaling and Disease Research, The School of Life Sciences and Technology, Tongji University, China (Zhenping Liu, C.J.); State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai, China (Y.Y., T.Z.); and Institutes of Biomedical Sciences, Fudan University, Shanghai, China (J.W., Y. Zou).

Background: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation. However, their roles in the adult heart remain unexplored.

Methods: To understand the role of LRP5/6 and β-catenin in the adult heart, we constructed conditional cardiomyocyte-specific LRP5/6 and β-catenin knockout mice and induced surgical myocardial infarction. We also directly injected recombinant proteins of insulin-like growth factor binding protein 4 and Dkk1 into the heart immediately following myocardial infarction to further examine the mechanisms through which these proteins regulate LRP5/6 and β-catenin.

Results: Deletion of LRP5/6 promoted cardiac ischemic insults. Conversely, deficiency of β-catenin, a downstream target of LRP5/6, was beneficial in ischemic injury. It is interesting to note that although both insulin-like growth factor binding protein 4 and Dkk1 are secreted Wnt/β-catenin pathway inhibitors, insulin-like growth factor binding protein 4 protected the ischemic heart by inhibiting β-catenin, whereas Dkk1 enhanced the injury response mainly through inducing LRP5/6 endocytosis and degradation.

Conclusions: Our findings reveal previously unidentified dual roles of LRP5/6 involved in the cardiomyocyte response to ischemic injury. These findings suggest new therapeutic strategies in ischemic heart disease by fine-tuning LRP5/6 and β-catenin signaling within the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024441DOI Listing
December 2016

Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells.

Mol Med Rep 2016 May 30;13(5):4372-8. Epub 2016 Mar 30.

Division of Preventive Medicine, Tongji University School of Medicine, Shanghai 200092, P.R. China.

Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of several key metabolic genes required for cellular growth and respiration. A previous study by our group indicated that NRF‑1 is involved in mitochondrial dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE human bronchial epithelial cell line. In the present study, it was observed that its genotoxic metabolite, anti‑benzopyrene‑7,8‑diol‑9,10‑epoxide (BPDE), triggered cell cycle arrest in S‑phase in 16HBE cells by activating ataxia-telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1 signaling pathways. NRF‑1 expression was suppressed by BPDE after treatment for 6 h. Flow cytometric analysis revealed that NRF‑1 overexpression attenuated cell cycle arrest in S‑phase induced by BPDE. In line with this result, DNA‑damage checkpoints were activated following NRF‑1 overexpression, as demonstrated by increased phosphorylation of ATM, Chk2 and γH2AX, but not ATR and Chk1, according to western blot analysis. It was therefore indicated that NRF‑1 overexpression attenuated BPDE‑induced S‑phase arrest via the ATM/Chk2 signaling pathway.
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http://dx.doi.org/10.3892/mmr.2016.5065DOI Listing
May 2016

Effects of home and education environments on children's motor performance in China.

Dev Med Child Neurol 2016 08 19;58(8):868-76. Epub 2016 Feb 19.

Public Health School of Fudan University, Shanghai, China.

Aim: The aim of this study was to examine the effects of home and educational environments on children's motor performance in China.

Method: We conducted a cross-sectional study of 4001 preschool children selected from 160 classes. The children's motor performance was assessed using the Movement Assessment Battery for Children, 2nd edition (MABC-2). Home and educational environments were evaluated using validated checklists. The effects of home and educational environments on motor performance were analysed using mixed and multilevel logistic regression models.

Results: The results showed that one score increase in the outside space of the family home was positively associated with the increase in total test score (0.104) subtest score of aiming and catching (0.037), and balance (0.034) of the MABC-2, after adjusting for potential confounders (each p<0.05). Possession of motor toys at home and parental rearing behaviours were also related to total test score, manual dexterity, and balance (β=0.022-0.104, each p<0.05). Space and furnishings, activity, and interaction in the classroom had a significant positive association with total test score (β=0.069-0.201), and with subtest scores of manual dexterity, aiming and catching, and balance respectively (β=0.115-0.206). Space and furnishings of classrooms and possession of toys in the household were protective factors for 'at risk' or significant poor performance (odds ratio 0.942-0.973, each p<0.05).

Interpretation: A permissive and accepting family and educational environment made a positive contribution to children's motor performance. Access to sufficient space and furnishings within the classroom, as well as toys in the family, were protective factors for poor motor performance. Future assistance is needed to support an advantageous environment in early childhood programmes in China.
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http://dx.doi.org/10.1111/dmcn.13073DOI Listing
August 2016

Wnt3a suppresses Wnt/β-catenin signaling and cancer cell proliferation following serum deprivation.

Exp Cell Res 2016 Feb 28;341(1):32-41. Epub 2015 Nov 28.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address:

Canonical Wnt/β-catenin signaling is often aberrantly activated in tumor cells and required for tumor growth. The internalization of Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) induced by Wnt ligands is commonly thought to be critical for Wnt/β-catenin signaling activation. However, in contrast to theses previous studies, we here show that persistent excessive stimulation with a canonical Wnt ligand Wnt3a could induce a long-term decreased expression level of membrane LRP6, which prevented nuclear β-catenin accumulation and tumor cell;proliferation. Importantly, Wnt3a was robustly upregulated following serum deprivation. The upregulated Wnt3a under serum deprivation was responsible for LRP6 internalization, decreased accumulation of nuclear β-catenin, and further inhibition of tumor cell proliferation. It has well been known that insufficient blood supply during tumor development occurs frequently, causing a worsening environment for tumor growth. Therefore, these results reveal a novel inhibitory role of Wnt3a on canonical Wnt/β-catenin signaling and cancer cell proliferation when there is an insufficient blood supply during tumor development, which might be a potential mechanism for tumor evasion within a worsening environment.
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http://dx.doi.org/10.1016/j.yexcr.2015.11.025DOI Listing
February 2016

The reliability and validity of the Developmental Coordination Disorder Questionnaire'07 for children aged 4-6 years in mainland China.

Res Dev Disabil 2015 Dec 27;47:405-15. Epub 2015 Oct 27.

Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, China. Electronic address:

An effective population-based screening tool is needed to identify possible cases of Developmental Coordination Disorder (DCD) among preschool children in mainland China. We examined the psychometric properties of the DCD questionnaire'07 (DCDQ'07) in Chinese children aged 4-6. A total of 3316 children from 10 nursery schools were involved in the study. Internal consistency and test-retest reliability of the DCDQ'07 were estimated using Cronbach's alpha, item-total correlation and intraclass correlation co-efficient (ICC). The construct validity was evaluated using the exploratory and confirmatory factor analysis. Receiver operating characteristic (ROC) analysis was used to measure the accuracy of the DCDQ'07. The results showed that both internal consistency (Cronbach's alpha value of all items were above 0.85) and test-retest reliability (ICCs of 13 items and subscales were above 0.9) were excellent. Confirmatory factor analysis showed that each goodness-of-fit indices of the 3-factor model was above 0.9, indicating a satisfactory fit of the data to the model. Area under the ROC curve was comparatively small (0.641). With the exception of construct validity in younger children (4 years old) and discriminative validity, the Chinese version of the DCDQ'07 achieves satisfactory reliability and construct validity in mainland China. Nevertheless, the questionnaire should be not used in younger children, and further studies are needed to explore the use of Little DCD-Q in Chinese preschool children.
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http://dx.doi.org/10.1016/j.ridd.2015.10.006DOI Listing
December 2015

Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

J Clin Neurosci 2015 Jul 19;22(7):1123-7. Epub 2015 May 19.

Department of Central Laboratory, Shanghai East Hospital, Tongji University, 150 Jimo Road, Pudong New District, Shanghai 200120, People's Republic of China. Electronic address:

The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1.
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http://dx.doi.org/10.1016/j.jocn.2014.12.027DOI Listing
July 2015

LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis.

Nat Commun 2015 Apr 22;6:6906. Epub 2015 Apr 22.

1] Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Shanghai, China [2] Tongji University School of Medicine, Shanghai, China.

How Wnt signalling including canonical and non-canonical pathways are initiated at the cell surface is not completely understood. Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. Importantly, through direct binding to Frz, LRP5/6 are able to prevent Frz-regulated non-canonical pathway activation and further non-canonical pathway-mediated tumour metastasis. Knockdown of endogenous LRP5/6 promotes otherwise-nonaggressive tumour cells to migrate in vitro, whereas a soluble recombinant protein of LRP6 ectodomain suppresses migration and metastasis of otherwise-aggressive tumour cells in vitro and in vivo. Furthermore, the expression level of membrane LRP5/6 correlates inversely with metastasis in mouse and human breast cancer. Our study suggests a previously unrecognized mode of receptor interaction, revealing the mechanism of LRP5/6 in inhibition of non-canonical pathway, and a possible clinical use of the LRP6 ectodomain to impede metastasis.
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http://dx.doi.org/10.1038/ncomms7906DOI Listing
April 2015

Can we early diagnose metabolic syndrome using brachial-ankle pulse wave velocity in community population?

Chin Med J (Engl) 2014 ;127(17):3116-20

Tongji University Medical School, Shanghai 200092, China. Email:

Background: The prevalence of metabolic syndrome (MetS) increased recently and there was still not a screening index to predict MetS. The aim of this study was to estimate whether brachial-ankle pulse wave velocity (baPWV), a novel marker for systemic arterial stiffness, could predict MetS in Chinese community population.

Methods: A total of 2 191 participants were recruited and underwent medical examination including 1 455 men and 756 women from June 2011 to January 2012. MetS was diagnosed according to the criteria of the International Diabetes Federation (IDF). Multiple Logistic regressions were conducted to explore the risk factors of MetS. Receiver operating characteristic (ROC) curve was performed to estimate the ideal diagnostic cutoff point of baPWV to predict MetS.

Results: The mean age was (45.35±8.27) years old. In multiple Logistic regression analysis, the gender, baPWV and smoking status were risk factors to MetS after adjusting age, gender, baPWV, walk time and sleeping time. The prevalence of MetS was 17.48% in 30-year age population in Shanghai. There were significant differences (χ(2) = 96.46, P < 0.05) between male and female participants on MetS prevalence. According to the ROC analyses, the ideal cutoff point of baPWV was 1 358.50 cm/s (AUC = 60.20%) to predict MetS among male group and 1 350.00 cm/s (AUC = 70.90%) among female group.

Conclusion: BaPWV may be considered as a screening marker to predict MetS in community Chinese population and the diagnostic value of 1 350.00 cm/s was more significant for the female group.
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April 2015

H2O 2 induces myocardial hypertrophy in H9c2 cells: a potential role of Ube3a.

Cardiovasc Toxicol 2015 Jan;15(1):23-8

Department of Prevention, Tongji University School of Medicine, Shanghai, China.

Myocardial hypertrophy that often leads to eventual heart failure is a leading cause of mortality worldwide. While both apoptosis and cell proliferation have been reported to play an important part in heart failure, its exact triggering mechanism is still unclear. Reports have shown that low concentrations of H2O2 (10-30 µM) can induce myocardial hypertrophy without affecting survival. The ubiquitin ligase Ube3a has been reported to have a close affiliation with Angelman syndrome; but many ubiquitin ligases have been reported in a variety of cardiovascular conditions including myocardial hypertrophy. However, the relationship between Ube3a and myocardial hypertrophy has never been reported in literature. The rat cardiac myoblast cell line H9c2 and primary neonatal cardiomyocytes showed similar hypertrophic responses in vitro. In this report, we utilized H2O2 treatment on H9c2 cells to induce myocardial hypertrophy and determined the relationship between Ube3a and myocardial hypertrophy. Our results showed that 10-20 μM H2O2 can induce myocardial hypertrophy without affecting cell viability and inducing cell apoptosis, while the corresponding transcription and translation levels of Ube3a are significantly increased during the process. Therefore, these findings underline that Ube3a may play an important role in myocardial hypertrophy.
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http://dx.doi.org/10.1007/s12012-014-9264-0DOI Listing
January 2015

Chlorogenic acid prevents isoproterenol-induced hypertrophy in neonatal rat myocytes.

Toxicol Lett 2014 May 28;226(3):257-63. Epub 2014 Feb 28.

Tongji University School of Medicine, Shanghai, China. Electronic address:

Cardiac hypertrophy is an independent risk factor for cardiovascular disease and its subsequent progression to heart failure represents a major cause of morbidity and mortality in the world. CGA is an important component of Chinese herbal medicine, acting as an antioxidant, scavenging free radicals and preventing inflammation. This study found that with the pre-treatment of chlorogenic acid in Iso-induced neonatal rat myocytes, the levels of the hypertrophic markers, ANP, BNP and β-MHC decreased. The nuclear translocation of NF-κB was blocked, whereas NF-κBIA, an inhibitor of NF-κB, was upregulated accordingly. And the level of the intracellular ROS was also reduced. These data reveal that chlorogenic acid may inhibit Iso-induced cardiac hypertrophy by attenuating NF-κB signaling pathway and suppressing ROS.
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http://dx.doi.org/10.1016/j.toxlet.2014.02.016DOI Listing
May 2014

LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation.

Cell Signal 2014 May 8;26(5):1068-74. Epub 2014 Jan 8.

Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Shanghai, China; Tongji University School of Medicine, Shanghai, China. Electronic address:

Canonical Wnt/β-catenin signaling pathway plays important roles in multiple aspects of cellular responses in development and diseases. It is currently thought that Wnt receptor Frizzled (Frz) exists separately to Wnt coreceptors LRP5 and LRP6 (LRP5/6), and that Wnt-Frz-LRP5/6 triple complex formation bridged by Wnt ligand is needed for canonical pathway activation. We recently showed that Frz and LRP5/6 interact with each other in the absence of Wnt ligand binding and this interaction maintains the Frz-LRP5/6 complex in an inactive state. Here, we further show that Wnt ligand stimulation induces conformational change of the Frz-LRP6 complex and leads to hexamer formation containing the core LDLR domain-mediated LRP6 homodimer that is stabilized by two pairs of Wnt3a and Frz8, that is, Wnt3a-Frz8-LRP6-LRP6-Frz8-Wnt3a. This LDLR-mediated LRP6 dimerization is essential for robust canonical Wnt pathway activation. Our study thus suggests a previously unrecognized mode of receptor interaction in Wnt signal initiation.
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http://dx.doi.org/10.1016/j.cellsig.2013.12.020DOI Listing
May 2014

A novel spectrophotometric method for indirect determination of nitric oxide (NO) in serum.

Clin Chim Acta 2013 Sep 18;424:187-90. Epub 2013 Jun 18.

Department of Central Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.

Background: It is essential in clinical medicine to develop a simple and accurate analytical method for detecting nitric oxide (NO) in blood or other body fluid. In order to overcome the shortcomings of previous methods, this experiment developed a novel indirect analytical method of NO in serum.

Methods: After nitrate was reduced by copper-coated cadmium granules, the nitrite produced was determined by diazotization of fuchsin acid and coupling to resorcinol. The maximum absorption appeared at 436 nm, with which the concentration of NO can be determined indirectly.

Results: NO concentration and absorbance were linearly correlated over the concentration ranging from 0 to 198 μmol/l, r=0.999. The CVs were 7.16% for within-run and 9.07% for between-run assays, respectively. The average recovery rate ranged from 90.6% to 105.2%. The mean concentration of NO3(-)/NO2(-) was 59.2±17.0 μmol/l in serum of 30 normal volunteers. The serum concentration of NO3(-)/NO2(-) decreased significantly in patients with congestive heart failure (CHF) compared to the normal volunteers, P<0.05.

Conclusions: This method offers a reliable, simple, reagent safe and inexpensive analytical platform for the determination of NO in serum. Using this approach, we determined that the synthesis of endogenous NO decreased in patients with CHF.
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http://dx.doi.org/10.1016/j.cca.2013.06.008DOI Listing
September 2013
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