Maternal and Child Health care Hospital of Hainan Province

Haikou, China

Maternal and Child Health care Hospital of Hainan Province

Haikou, China

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PubMed | Maternal and Child Health Care Hospital of Hainan Province, Hubei University, Hainan General Hospital, Sichuan University and Zhumadian Central Hospital
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016

The natural product tetramethylpyrazine (TMP) and resveratrol have a variety of biologic activities, including anti-cancer effects. However the pharmacological function of CSTMP (a newly designed and synthesized TMP and resveratrol derivative) in cancer have not been elucidated.In RPMI8226 cells, the cytotoxic effects and apoptosis were detected by MTT and Double staining for Annexin V-FITC and propidium iodide (PI). The protein and mRNA expression levels were detected by Real Time PCR and Western blot, respectively. The localization of cleaved caspase-12 was evaluated by immunofluorescent staining. The activation of caspase were measured by colorimetric assays and Western blot.CSTMP showed significantly cytotoxic effects and induced apoptosis in RPMI8226 cells. Caspase activation, Cytochrome c release and Bax, Bcl-2 and Bcl-XL levels analyses demonstrated that the anti-cancer effect of CSTMP in RPMI8226 cells was mediated by promoting caspase- and mitochondria-dependent apoptosis. In addition, CSTMP induced the increased expression of endoplasmic reticulum (ER) stress related proteins (CHOP, GRP78, GRP94 and cleaved caspase-12) and the activation of multiple branches of ER stress transducers (PERK-eIF2, IRE1 and ATF6). Moreover, knockdown of CHOP by siRNA markedly inhibited CSTMP-induced cytotoxic effects, caspases activity and mitochondrial dysfunction in RPMI8226 cells.Our results indicated that CSTMP could induce apoptosis and mitochondrial dysfunction in RPMI8226 cells via CHOP-dependent ER stress.


Ding Y.,Hainan General Hospital | Ding Y.,Maternal and Child Health Care Hospital of Hainan Province | Liao W.,Hainan General Hospital | Yi Z.,Central South University | And 2 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Atherosclerosis is the key course of coronary heart disease. In this study, we investigated the effect of vitamin D receptor on serum 1,25-(OH)2D levels, lipid profiles, nitric oxide expression, apoptosis-related gene Bcl-2, fas protein levels, in ApoE-deficient mice. The proliferation activity of VDR-RNAi transfected endothelial cells was decreased, the ability of apoptosis was increased, nitric oxide concentration was decreased and eNOS protein level was significantly reduced. VDR-RNAi induced lipid metabolism abnormality, reduced eNOS and ApoE levels, promoted lipid peroxidation, damaged the endothelial function and accelerated the process of atheroscleros. Together, our data presented a novel role for VDR in the pathogenesis process of atheroscleros by up regulating eNOS protein expression which could lay a solid foundation of VDR-specific activator treatment for coronary artery disease. © 2015, E-Century Publishing Corporation. All rights reserved.


Ding Y.,Hainan General Hospital | Ding Y.,Maternal and Child Health Care Hospital of Hainan Province | He X.,Central South University | Liao W.,Hainan General Hospital | And 3 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

One of the major disease manifestations of systemic lupus erythematosus (SLE) is lupus nephritis (LN), and the underlying mechanisms are not yet understood. Epstein-Barr virus (EBV) reactivation was associated with the induction of SLE, with EBV-encoded latent membrane protein1 (LMP1) plays a vital role in this process. Although it was reported that LN was associated with LMP1, most of these results are from patients with ages differed greatly (range, 10-56 years). Given the increased prevalence of EBV infection in young patients, we focused on the association of LN and LMP1 expression in the renal tissues of young patients (range, 6-16 years) in this study. We found that the positive rate of LMP1 in the renal tissues was significantly higher in patients with LN compared with control (P<0.001), which is consistent with the previous reports. The positive rates of LMP1 were similar between the patients of initial onset and relapse, and there was no detectable difference between the patients with and without concurrent infection (P>0.05). However, we reported for the first time about the positive correlation of LMP1 with classification of LN. The proportion of young patients positive for anti-Sm antibody was significantly higher in the LMP1 positive group compared with the LMP1 negative control (P>0.05). These results indicate that EBV infection in the renal of young patients may lead to the increased severity of LN, and the expression of anti-Sm is likely contributed to this process. © 2015, E-Century Publishing Corporation. All rights reserved.


Ding Y.,Hainan General Hospital | Ding Y.,Maternal and Child Health Care Hospital of Hainan Province | Liao W.,Hainan General Hospital | Yi Z.,Central South University | And 2 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder which causes more severe clinical manifestations in juveniles than in adults. Many studies have shown the contribution of Epstein-Barr Virus (EBV) infection to the development of SLE. In this study, we investigated the role of EBV genes in the pathogenesis of SLE in juvenile patients. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 20 patients with SLE and 12 healthy donors. Supernatant of EBV secreting cells was obtained from JSLE patients who were diagnosed as EBV-IgG/IgM positive by ELISA. PBMCs and the cell supernatant were co-cultured, followed by extracting RNAs from the PBMCs before and after the culturing, and RT-PCR was performed to determine the expression of EBV genes. Among all the EBV latent and lytic genes, LMP1 is the only gene showed a significant higher expression rate and expression level for the juvenile SLE patients. Co-culturing the PBMCs with EBV secreting cell supernatant reactivated the infected EBV by initiating the expression of EBNA1 and BLLF1 gene. These data indicated the aberrant expression of EBV genes in JSLE patients may be involved in the pathogenesis of JSLE, and that the EBNA1 and BLLF1 genes may be the initiation of EBV entering the lytic phase. © 2016, E-Century Publishing Corporation. All rights reserved.


Ding Y.,Hainan General Hospital | Ding Y.,Maternal and Child Health care Hospital of Hainan Province | Liao W.,Hainan General Hospital | He X.,Central South University | And 2 more authors.
Inflammation | Year: 2016

(E)-2-(2-chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP), a novel stilbene derivative, have been shown to have cytoprotective effects against H2O2-induced oxidative stress in human endothelial cells. However, little is known about its anti-inflammatory effects in lupus nephritis (LN). In the present study, we investigated the anti-inflammatory effects of CSTMP on lipopolysaccharide (LPS)-induced human renal proximal tubular epithelial cells (hRPTECs) and elucidated its molecular mechanisms. CSTMP significantly attenuated the cytotoxicity and suppressed the release of proinflammatory mediators, including iNOS, COX-2, TNF-α, IL-6, IL-8, CCL-2, ICAM-1, IL-1β, and MCP-1 in LPS-induced hRPTECs. In addition, CSTMP decreased the expression of TLR4 and its adapter molecules (MyD88, phosphorylation of TAK1, TRAF6, and IRAK1) and abolished its interactions with these adapter molecules in LPS-induced hRPTECs, resulting in an inhibition of the TLR4/MyD88/TAK1/ TRAF6/IRAK1 complex. Moreover, CSTMP also attenuated phosphorylation of IκB and IKK-α/β, and P50-NF-κB and P65-NF-κB translocation to nucleus in LPS-induced hRPTECs. These findings provided new insights to understand the mode of action of CSTMP in treatment of inflammatory diseases, such as LN. © 2016, Springer Science+Business Media New York.


Ding Y.,Maternal and Child Health Care Hospital of Hainan Province | Ding Y.,Hainan General Hospital | Yang H.,General Hospital of Guangzhou Military Command | Xiang W.,Maternal and Child Health Care Hospital of Hainan Province | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Previous studies have revealed the anti-inflammatory effect of CD200Fc, an agonist of CD200R1 in autoimmune disease. However, little is known about its anti-inflammatory effects in kidney diseases. The aim of this study is to assess the function of CD200Fc in regulating lipopolysaccharide (LPS)-induced inflammatory response in human renal proximal tubular epithelial cells (hRPTECs) and the possible mechanisms. LPS reduced the CD200R1 expression in hRPTECs, and this effect was attenuated by CD200Fc in a dose-dependent manner. In addition, CD200Fc inhibited LPS-induced expressions of TLR4 and its adapter molecule (MyD88 and phosphorylation of TAK1), and abolished its interactions with MyD88 or TAK1 in hRPTECs cells. CD200Fc also attenuated LPS-induced phosphorylation of IκB, NF-κB-P65 translocation to nucleus, and increased phosphorylation of ERK1/2, p38 and JNK in hRPTECs. Moreover, CD200Fc suppressed the LPS-induced release of pro-inflammatory mediators in hRPTECs, including IL-1β, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, TNF-α, INF-α and INF-γ. Our results suggested that CD200Fc could inhibit the TLR4-mediated inflammatory response in LPS-induced hRPTECs, thus might be beneficial for the treatment of renal disease, such as lupus nephritis. © 2015 Elsevier Inc. All rights reserved.


PubMed | Maternal and Child Health care Hospital of Hainan Province, Hainan General Hospital and Central South University
Type: Journal Article | Journal: Inflammation | Year: 2016

(E)-2-(2-chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP), a novel stilbene derivative, have been shown to have cytoprotective effects against H2O2-induced oxidative stress in human endothelial cells. However, little is known about its anti-inflammatory effects in lupus nephritis (LN). In the present study, we investigated the anti-inflammatory effects of CSTMP on lipopolysaccharide (LPS)-induced human renal proximal tubular epithelial cells (hRPTECs) and elucidated its molecular mechanisms. CSTMP significantly attenuated the cytotoxicity and suppressed the release of proinflammatory mediators, including iNOS, COX-2, TNF-, IL-6, IL-8, CCL-2, ICAM-1, IL-1, and MCP-1 in LPS-induced hRPTECs. In addition, CSTMP decreased the expression of TLR4 and its adapter molecules (MyD88, phosphorylation of TAK1, TRAF6, and IRAK1) and abolished its interactions with these adapter molecules in LPS-induced hRPTECs, resulting in an inhibition of the TLR4/MyD88/TAK1/ TRAF6/IRAK1 complex. Moreover, CSTMP also attenuated phosphorylation of IB and IKK-/, and P50-NF-B and P65-NF-B translocation to nucleus in LPS-induced hRPTECs. These findings provided new insights to understand the mode of action of CSTMP in treatment of inflammatory diseases, such as LN.


PubMed | Maternal and Child Health Care Hospital of Hainan Province, General Hospital of Guangzhou Military Command, Hainan General Hospital and Central South University
Type: Journal Article | Journal: Biochemical and biophysical research communications | Year: 2015

Previous studies have revealed the anti-inflammatory effect of CD200Fc, an agonist of CD200R1 in autoimmune disease. However, little is known about its anti-inflammatory effects in kidney diseases. The aim of this study is to assess the function of CD200Fc in regulating lipopolysaccharide (LPS)-induced inflammatory response in human renal proximal tubular epithelial cells (hRPTECs) and the possible mechanisms. LPS reduced the CD200R1 expression in hRPTECs, and this effect was attenuated by CD200Fc in a dose-dependent manner. In addition, CD200Fc inhibited LPS-induced expressions of TLR4 and its adapter molecule (MyD88 and phosphorylation of TAK1), and abolished its interactions with MyD88 or TAK1 in hRPTECs cells. CD200Fc also attenuated LPS-induced phosphorylation of IB, NF-B-P65 translocation to nucleus, and increased phosphorylation of ERK1/2, p38 and JNK in hRPTECs. Moreover, CD200Fc suppressed the LPS-induced release of pro-inflammatory mediators in hRPTECs, including IL-1, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, TNF-, INF- and INF-. Our results suggested that CD200Fc could inhibit the TLR4-mediated inflammatory response in LPS-induced hRPTECs, thus might be beneficial for the treatment of renal disease, such as lupus nephritis.


PubMed | Maternal and Child Health Care Hospital of Hainan Province, Hainan General Hospital and Central South University
Type: | Journal: Journal of cellular and molecular medicine | Year: 2017

This study aims to explore effects of 1,25(OH)


PubMed | Maternal and Child Health Care Hospital of Hainan Province, Northwestern University, Hainan General Hospital, Vanderbilt University and Shandong University
Type: | Journal: BMC cancer | Year: 2015

Systematic analysis of cancer gene-expression patterns using high-throughput transcriptional profiling technologies has led to the discovery and publication of hundreds of gene-expression signatures. However, few public signature values have been cross-validated over multiple studies for the prediction of cancer prognosis and chemosensitivity in the neoadjuvant setting.To analyze the prognostic and predictive values of publicly available signatures, we have implemented a systematic method for high-throughput and efficient validation of a large number of datasets and gene-expression signatures. Using this method, we performed a meta-analysis including 351 publicly available signatures, 37,000 random signatures, and 31 breast cancer datasets. Survival analyses and pathologic responses were used to assess prediction of prognosis, chemoresponsiveness, and chemo-drug sensitivity.Among 31 breast cancer datasets and 351 public signatures, we identified 22 validation datasets, two robust prognostic signatures (BRmet50 and PMID18271932Sig33) in breast cancer and one signature (PMID20813035Sig137) specific for prognosis prediction in patients with ER-negative tumors. The 22 validation datasets demonstrated enhanced ability to distinguish cancer gene profiles from random gene profiles. Both prognostic signatures are composed of genes associated with TP53 mutations and were able to stratify the good and poor prognostic groups successfully in 82%and 68% of the 22 validation datasets, respectively. We then assessed the abilities of the two signatures to predict treatment responses of breast cancer patients treated with commonly used chemotherapeutic regimens. Both BRmet50 and PMID18271932Sig33 retrospectively identified those patients with an insensitive response to neoadjuvant chemotherapy (mean positive predictive values 85%-88%). Among those patients predicted to be treatment sensitive, distant relapse-free survival (DRFS) was improved (negative predictive values 87%-88%). BRmet50 was further shown to prospectively predict taxane-anthracycline sensitivity in patients with HER2-negative (HER2-) breast cancer.We have developed and applied a high-throughput screening method for public cancer signature validation. Using this method, we identified appropriate datasets for cross-validation and two robust signatures that differentiate TP53 mutation status and have prognostic and predictive value for breast cancer patients.

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