Xiang X.,Peking University |
Xiang X.,Key Laboratory of Molecular Cardiovascular Science |
Xiang X.,Central Hospital of Zibo |
Lan H.,Peking University |
And 14 more authors.
Diabetes | Year: 2015
Interconversion of white and brown adipocytes occurs between anabolic and catabolic states. The molecular mechanism regulating this phenotypic switch remains largely unknown. This study explores the role of tuberous sclerosis complex 1 (TSC1)-mechanistic target of rapamycin (mTOR) signaling in the conversion of brown to white adipose tissue (WAT). A colony of Fabp4-Tsc1-/- mice, in which the Tsc1 gene was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre, was established. Western blotting and immunostaining demonstrated the absence of TSC1 and activation of ribosomal protein S6 kinase 1, the downstream target of mTOR complex 1 (mTORC1) signaling, in the brown adipose tissues (BATs) of Fabp4-Tsc1-/- mice. Accumulation of lipid droplets in BAT was significantly increased. Levels of brown adipocyte markers were markedly downregulated, while white adipocyte markers were upregulated. Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1-/- mice. Deletion of the Tsc1 gene in cultured brown preadipocytes significantly increased the conversion to white adipocytes. FoxC2 mRNA, the transcriptional factor for brown adipocyte determination, was significantly decreased, while mRNAs for retinoblastoma protein, p107 and RIP140, the transcriptional factors for white adipocyte determination, increased in the BAT of Fabp4-Tsc1-/- mice. Our study demonstrates that TSC1-mTORC1 signaling contributes to the brown-to-white adipocyte phenotypic switch. © 2015 by the American Diabetes Association.
Wei Y.,Shandong University |
Ji X.-B.,Liaocheng Peoples Hospital |
Wang Y.-W.,Shandong University |
Wang J.-X.,Peoples Hospital of Rizhao |
And 9 more authors.
Blood | Year: 2016
This study compared the efficacy and safety of high-dose dexamethasone (HD-DXM) and conventional prednisone (PDN) on the largest cohort to date as first-line strategies for newly diagnosed adult primary immune thrombocytopenia (ITP). Patients enrolled were randomized to receive DXM 40 mg/d for 4 days (n 5 95, nonresponders received an additional 4-day course ofDXM) or prednisone 1.0mg/kg daily for 4 weeks and then tapered (n 5 97). One or 2 courses of HD-DXM resulted in a higher incidence of overall initial response (82.1% vs 67.4%, P 5 .044) and complete response (50.5% vs 26.8%, P 5 .001) compared withprednisone. Time to responsewas shorter in theHD-DXMarm(P .001), and a baseline bleeding score 8 was associated with a decreased likelihood of initial response. Sustained response was achieved by 40.0% of patients in the HD-DXM arm and 41.2% in the PDN arm (P 5 .884). Initial complete response was a positive indicator of sustained response, whereas presence of antiplatelet autoantibodies was a negative indicator. HD-DXM was generally tolerated better. We concluded that HD-DXM could be a preferred corticosteroid strategy for first-linemanagement of adult primary ITP. This study is registered at www.clinicaltrials.gov as #NCT01356511. © 2016 by The American Society of Hematology.
PubMed | Central Hospital of Zibo, Qingdao University and Peoples Hospital of Weifang
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2017
Intake of a high dosage of baicalin has previously been shown to attenuate hyperlipidemia induced by a high-fat diet. Baicalin functions as an activator of peroxisome proliferator-activated receptor- (PPAR-), which is the key regulator of reverse cholesterol transport (RCT). The present study aimed to test the hypothesis that baicalin could promote cholesterol efflux in macrophages through activating PPAR-. Phorbol 12-myristate 13-acetate-stimulated THP-1 cells were treated with oxidized low-density lipoprotein and (
Liu L.,First Peoples Hospital of Jining |
Liang Z.,First Peoples Hospital of Jining |
Li Y.,Central Hospital of Zibo
Solid State Sciences | Year: 2012
A highly sensitive and selective small molecule detection platform has been developed using aptamers immobilized on electrode surface. In our system, two aptamers were used - one of which is for ATP recognition and the other is for signal produce. We designed two probes L1 (containing ATP aptamer and a part of hemin aptamer) and L2 (containing the complementary strand of ATP aptamer and the rest of hemin aptamer) and immobilized L1 on electrode surface. L2 was used to hybridize to L1 and form L1-L2 duplex which brought the two parts of hemin aptamer into close proximity. Then hemin can be captured by this duplex and detected by electrochemical methods. When we introduced ATP into the system, the ATP binding destroyed the duplex and L2 diffused into the solution. As a result, hemin cannot be captured to bring electrochemical signal. © 2012 Elsevier Masson SAS. All rights reserved.
Zhang Q.-H.,Shandong University |
Zhang Q.-H.,Central Hospital of Zibo |
Dou H.-T.,Central Hospital of Zibo |
Xu P.,Peoples Hospital of ZhangQiu |
And 2 more authors.
Drug Research | Year: 2015
Introduction: The presence of subset of cancer stem cells (CSCs) called Side population (SP) cells has been identified in several solid tumors, responsible for treatment failure especially chemotherapy, and cancer relapse. The present study was aimed to isolate and characterize cancer stem like cells side population cells from high grade ovarian cancer. Methods: The collected cancer samples were analyzed for presence of SP cells by FACS using Hoechst 33342 exclusion technique. Further the FACS sorted SP and non-SP cells were subjected to analysis of stem cell surface protein expression by western blot and immunocytochemistry, drug resistance and sphere formation assay. Results: By FACS, we have identified 3.7% of cancer stem cell like side population cells in ovarian cancer whose prevalence was reduced to 0.5% upon treatment with verapamil an inhibitor of ABC transporter. Further, these sorted SP cells showed over expression of ABCG2 (ABC transporter), stem cell proteins such as CD144, CD44, EpCAM and antiapoptotic factor Bcl-2. Also the SP cells showed high resistance to chemotherapy drugs, have high survival rate and they are highly potential to form tumor spheres. Conclusion: Our data suggest that ovarian cancer contain small sub-population of side population cells which shares some characteristics of stem cells. The co-expression of ABC transporters and stem cells surface markers in SP cells may associate with resistance to chemotherapeutic agents, apoptosis and also supports a role for these cells in tumor recurrence, metastasis and invasion. © Georg Thieme Verlag KG Stuttgart. New York.
Zhang X.-C.,Weifang Peoples Hospital |
Chen J.-Q.,Weifang Peoples Hospital |
Li B.,Central Hospital of Zibo |
Li B.,Shandong University
Journal of Cardiovascular Pharmacology | Year: 2014
Objectives: The CC chemokine ligand-20 (CCL-20)/macrophage inflammatory protein-3a has been seen as one of the most important chemokines and played a key role in atherogenesis, but the mechanism that underlies the regulation of CCL-20 has not been established clearly yet. The aim of this study was to investigate the influence of salvianolic acid A (SAA) on the expression of CCL- 20 in macrophages and ApoE-deficient (ApoE2/2) mice. Methods: The expression of CCL-20 was detected both at protein and messenger RNA levels in RAW264.7 cells. We validated the result in ApoE2/2 mice that were intraperitoneally injected with SAA. Phosphorylation of p38 mitogen-activated protein kinase was detected with Western blot, and inhibitor of p38 was used to investigate the mechanism of regulation of CCL-20. Hematoxylin and eosin and Oil-Red-O staining were used to evaluate the atherosclerotic lesions and lipid accumulation in ApoE2/2 mice. Immunohistochemical analysis was used to detect the expressions of CCL-20 and CCR6 in the atherosclerotic lesions. Immunofluorescent analysis was used to certify the origination of CCL-20. Results: Recombinant tumor necrosis factor-α (TNF-α) upregulated CCL-20 production in dose- And time-dependent manners in RAW264.7 cells. The activity of TNF-α-induced CCL-20 production seemed to be significantly suppressed by SAA. Using p38 mitogen-activated protein kinase inhibitor, we found that p38 mediated the effects of TNF-α- And SAA-induced CCL-20 expression changes. In addition, immunohistochemical analysis of aortic root of ApoE2/2 mice also demonstrated that the expressions of CCL-20 and CCR6 were both downregulated significantly with SAA treatment. Furthermore, treatment of SAA inhibited the progression of the atherosclerotic plaques and lipid accumulation. Conclusions: These results demonstrate that TNF-a increased but SAA suppressed CCL-20 production significantly via a novel mechanism. © 2014 Lippincott Williams & Wilkins.
Sun M.,Shandong University |
Sun M.,Central Hospital of Zibo |
Su X.,Shandong University |
Ding B.,Shandong University |
And 5 more authors.
Nanomedicine | Year: 2012
Curcumin (CUR), a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of CUR in inflammatory disorders, cardiovascular disease, cancer, Alzheimers disease and neurological disorders have been shown. However, the clinical application of CUR is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based delivery approaches have been used to enhance the oral bioavailability, biological activity or tissue-targeting ability of CUR. This article reviews potential novel drug delivery systems for CUR including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanosuspensions, nanoemulsions, complexes and dendrimer/dimer, which provide promising results for CUR to improve its biological activities. © 2012 Future Medicine Ltd.
Zhang Q.-H.,Central Hospital of Zibo |
Dou H.-T.,Central Hospital of Zibo |
Tang Y.-J.,Central Hospital of Zibo |
Su S.,Central Hospital of Zibo |
Liu P.-S.,Shandong University
Archives of Gynecology and Obstetrics | Year: 2015
Purpose: Ovarian cancer is among the top diseases in the list of malignant gynaecologic tumors. In the present study, we aim to investigate the effect of lentivirus-mediated knockdown of Krüppel-like factor 9 (KLF9) on cell viability and tumor growth in ovarian cancer. Methods: Firstly, the expression of KLF9 was determined by real-time PCR and western blot in human ovarian cancer tissues. Then, endogenous KLF9 expression was silenced by lentivirus in SKOV3 and OVCAR3 ovarian cancer cells, and followed by MTT and BrdU incorporation assays, cell cycle analysis and tumor xenografts in nude mice. Results: Our results found that the expression of KLF9 is up-regulated in human ovarian cancer. As expected, KLF9 knockdown significantly inhibited cell proliferation and resulted in cell cycle arrest in the G0/G1 phase. Besides, KLF9 deficiency significantly inhibited tumor growth in nude mice. Conclusion: Therefore, our data reveal that lentivirus-mediated KLF9 silencing might be promising in the treatment of human ovarian cancer. © 2014, Springer-Verlag Berlin Heidelberg.
Gao Y.,Shandong University |
Wang C.,Shandong University |
Sun M.,Central Hospital of Zibo |
Wang X.,Shandong Academy of Sciences |
And 3 more authors.
Journal of Biomedical Nanotechnology | Year: 2012
The current study was aimed at preparing the curcumin nanosuspension (CUR-NS) to improve the solubility and oral absorption of CUR. Prepared from a tandem of ultra-turrax homogenization and high pressure homogenization, the CUR-NS showed spherical shape under transmission electron microscopy with an average diameter of 210.2 nm. The absorption of CUR-NS in the gastrointestinal (GI) tract was studied in rats using an in situ single pass perfusion method. It was found that the absorption percentage in stomach was 9.20% within 2 h. The absorption process in intestine was first-process with passive diffusion mechanism, and the main absorptive segments were proven to be in the duodenum and jejunum. A pharmacokinetic study was conducted in mice after oral administration of CUR at 250 mg/kg in the form of either CUR-NS or CUR suspension. The plasma concentration-time curves were both fitted to a one-compartment model and the relative bioavailability of CUR-NS to CUR suspension was 680.03%. The effects of CUR-NS on the structural properties of the intestinal mucosal membrane of rats were investigated by fluorescence polarization and circular dichroism in vitro. After treatment with CUR-NS, not only the fluidity of intestinal mucosal membrane increased but also the conformation of the membrane protein loosed, which increased the gastrointestinal absorption of CUR-NS. These studies provided the evidence that NS was valuable as an oral delivery carrier to enhance the absorption of CUR. Copyright © 2012 American Scientific Publishers All rights reserved.
Liu W.-F.,Huazhong University of Science and Technology |
Zuo H.-J.,Huazhong University of Science and Technology |
Chai B.-L.,Huazhong University of Science and Technology |
Peng D.,Huazhong University of Science and Technology |
And 5 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2011
Tetraspanin CD151 mainly associates with laminin-binding integrins and forms CD151-integrin complex. We previously reported that CD151 could be a potential target for angiogenesis, but the mechanisms involved are still unclear. This study investigated the role of CD151-integrin complex in angiogenesis and the signaling mechanisms involved. Here we showed that CD151 and CD151-AAA mutant were both well expressed at the protein level. CD151 gene transfer promoted angiogenesis and improved skin temperature of the lateral ischemic hindlimb, whereas CD151-AAA mutant abrogated the increase in capillary density and skin temperature. Further, CD151-AAA mutant failed to activate the FAK, ERK, PI3K/Akt/eNOS, and Rac1/Cdc42 signaling pathways. Moreover, CD151-AAA mutant was unavailable to promote bovine aortic endothelial cells (BAECs) proliferation and migration, in contrast to the effects of CD151. The results suggested that formation of CD151-integrin complex was likely to be a prerequisite for CD151-induced angiogenesis and signaling pathways. © 2011 Elsevier Ltd. All rights reserved.