Zhang H.,Zhongda Hospital |
Wang C.,Zhongda Hospital |
Chen B.,Zhongda Hospital |
Wang X.,Nanjing Southeast University
International Journal of Nanomedicine | Year: 2012
Daunorubicin (DNR) has a broad spectrum of anticancer activity, but is limited in clinical application due to its serious side effects. The aim of this study was to explore a novel "smart" pH-responsive drug delivery system (DDS) based on titanium dioxide (TiO 2) nanoparticles for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic effciency of DNR. DNR was loaded onto TiO 2 nanoparticles by forming complexes with transition metal titanium to construct DNR-TiO 2 nanocomposites as a DDS. DNR was released from the DDS much more rapidly at pH 5.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. DNR-TiO 2 nanocomposites induced remarkable improvement in anticancer activity, as demonstrated by fow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nuclear 4′,6-diamidino-2-phenylindole staining. Furthermore, the possible signaling pathway was explored by western blot. For instance, in human leukemia K562 cells, it was demonstrated that DNR-TiO 2 nanocomposites increase intracellular concentration of DNR and enhance its anticancer effciency by inducing apoptosis in a caspase-dependent manner, indicating that DNR-TiO 2 nanocomposites could act as an effcient DDS importing DNR into target cancer cells. These fndings suggest that "smart" DNR delivery strategy is a promising approach to cancer therapy. © 2012 Zhang et al.
Cheng Y.,Peoples Hospital of Jiangsu Province |
Jiang S.,Jinling Hospital |
Hu R.,Zhongda Hospital |
Lv L.,Peoples Hospital of Jiangsu Province |
Lv L.,Jinling Hospital
Annals of Clinical and Laboratory Science | Year: 2013
Mounting evidence suggests that transplanting endothelial progenitor cells (EPCs) into the myocardium improves cardiac function after myocardial infarction (MI). However, the mechanism remains controversial. The aim of this study was to investigate the role played by the VEGF- PI3K/Akt-eNOS pathway in EPC-based cell therapy. Cultured EPCs, which were identified by morphology, function, and cell surface markers, were transplanted into the border zone after left anterior descending coronary artery ligation in mice. Expression levels of VEGF, p-Akt, and eNOS in the border zone were elevated three days after EPC transplantation. EPC therapy enhanced expression of VEGFR-2, increased microvessel density, and reduced interstitial fibrosis in the border zone after MI. The left ventricular fractional shortening was increased and the left ventricular diameter was smaller after EPC treatment. Wortmannin inhibited the expression of p-Akt and was associated with decreased cardiac function. Our study suggests that EPC transplantation improves cardiac function after MI, mediated at least partially by activation of the VEGF -PI3K/ Akt-eNOS pathway. © 2013 by the Association of Clinical Scientists, Inc.
Bai Y.-Y.,Zhongda Hospital |
Wang L.,Nanjing Southeast University |
Chang D.,Zhongda Hospital |
Zhao Z.,Zhongda Hospital |
And 3 more authors.
Stroke | Year: 2015
Background and Purpose-An immature vascular phenotype in diabetes mellitus may cause more severe vascular damage and poorer functional outcomes after stroke, and it would be feasible to repair damaged functional vessels using endothelial progenitor cell (EPC) transplantation. However, high glucose induces p38 mitogen-activated protein kinase activation, which can accelerate the senescence and apoptosis of EPCs. The aim of this study was to investigate the combined effects of EPC transplantation and p38 mitogen-activated protein kinase inhibitor administration on diabetic stroke outcomes. Methods-Bone marrow-derived EPCs were injected intra-arterially into db/db mice after ischemic stroke induction. RWJ 67657 (RWJ), a p38 mitogen-activated protein kinase inhibitor, was administered orally for 7 consecutive days, with the first dose given 30 minutes before stroke induction. Functional outcome was determined at days 0, 1, 7, 14, and 21. Angiogenesis, neurogenesis, infarct volume, and Western blotting assays were performed on day 7, and white matter remodeling was determined on day 14. Results-Neither EPC transplantation nor RWJ administration alone significantly improved diabetic stroke outcome although RWJ displayed a potent anti-inflammatory effect. By both improving the functioning of EPCs and reducing inflammation, EPC transplantation plus RWJ administration in vivo synergistically promoted angiogenesis and neurogenesis after diabetic stroke. In addition, the white matter remodeling, behavioral scores, and expressions of vascular endothelial growth factor and brain-derived neurotrophic factor were significantly increased in diabetic mice treated with both EPCs and RWJ. Conclusions-The combination of EPC transplantation and RWJ administration accelerated recovery from diabetic stroke, which might have been caused by increased levels of proangiogenic and neurotrophic factors. © 2015 American Heart Association, Inc.
Wang D.,Zhongda Hospital |
Wang Y.,Nanjing Southeast University |
Ji Z.-L.,Zhongda Hospital
ANZ Journal of Surgery | Year: 2012
Background: Laparoendoscopic single-site surgery is a revolution in minimally invasive surgery in recent years, and cholecystectomy is the most common intervention. However, laparoendoscopic single-site cholecystectomy (LESSC) is a controversial procedure. Its safety, cosmetic results, complications, post-operative pain and post-operative stay are not confirmed by multi-centre randomized controlled studies. Objectives: This review examined the impact of LESSC versus conventional laparoscopic cholecystectomy (CLC). The primary outcomes were conversional rate and intraoperative and post-operative complications, and other outcomes were cosmetic results, operative time, post-operative pain and post-operative stay. Data sources: Pubmed, EMbase, Web of Science, Ovid, clinical trials of the US National Institutes of Health and Cochrane Database of Systematic Reviews and Controlled Trials Register were searched to identify all possible randomized controlled trials (RCTs). Methods: Two reviewers completed article search, and eligible data were entered into a computerized spreadsheet for analysis. Results: Nine studies were obtained using the search strategy. Patients accepting LESSC had a higher conversion rate than those having CLC (7.17 (3.00, 17.11) (P < 0.01)). There was no significant difference for total complications between the two groups (1.17 (0.76, 1.80) (P= 0.46)), but incidence of incisional hernia and haemorrhage (seroma) in the LESSC group was obviously higher than that in the CLC group. Operative time was much longer in the LESSC group (mean difference: 10.69 (3.14, 18.24) (P= 0.006)). Cosmetic results favoured LESSC; however, post-operative abdominal pain and post-operative stay were not significantly different between the two groups in most of the nine studies. Conclusions: LESSC can be safely performed with better cosmetic results; however, it carries a higher conversion rate and a longer operative time, and offers no benefit in terms of post-operative abdominal pain and post-operative stay. Further RCTs, according to the CONSORT statement, are advocated to validate its objective benefits. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.
PubMed | Zhongda Hospital and Nanjing Southeast University
Type: Journal Article | Journal: Oncotarget | Year: 2016
To investigate the use of thermosensitive magnetoliposomes (TMs) loaded with magnetic iron oxide (Fe3O4) and the anti-cancer stem cell marker CD90 (CD90@TMs) to target and kill CD90+ liver cancer stem cells (LCSCs).The hepatocellular carcinoma cell line Huh7 was used to separate CD90+ LCSCs by magnetic-activated cell sorting. CD90@TMs was characterized and their ability to target CD90+ LCSCs was determined. Experiments were used to investigate whether CD90@TMs combined with magnetic hyperthermia could effectively eliminate CD90+ LCSCs.The present study demonstrated that CD90+ LCSCs with stem cells properties were successfully isolated. We also successfully prepared CD90@TMs that was almost spherical and uniform with an average diameter of 1304.6 nm and determined that magnetic iron oxide could be incorporated and retained a superparamagnetic response. CD90@TMs showed good targeting and increased inhibition of CD90+ LCSCs in vitro and in vivo compared to TMs.CD90@TMs can be used for controlled and targeted delivery of anticancer drugs, which may offer a promising alternative for HCC therapy.
PubMed | Linan Peoples Hospital, Zhongda Hospital and Zhejiang Chinese Medical University
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2016
Strong evidence suggests that cancer-associated inflammation promotes tumor growth and progression, and interleukin-6 (IL6) is an important modulator of inflammation. However, the roles of IL6 and mutations of its corresponding gene in prostate cancer have not been clearly documented. We retrieved data from the Oncomine database concerning IL6 expression in prostate cancer and its role in prostate-specific antigen (PSA) recurrence. We also performed a case-control study of the IL6 -572G/C polymorphism (rs1800796) in 236 sporadic prostate cancer patients and 256 healthy controls from a southern Han Chinese population. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between rs1800796 and prostate cancer susceptibility. A dual-luciferase reporter assay was used to test the transcriptional activity of the IL6 promoter G and C alleles. IL6 was overexpressed in prostate cancer tissues compared to normal tissues, especially in those with higher Gleason scores. Moreover, elevated IL6 expression was associated with high PSA recurrence rate in Oncomine data. Our case-control study demonstrated that compared with the -572C allele, the -572G allele conferred a borderline increased risk of prostate cancer (OR = 1.31, 95%CI = 0.99-1.74, P = 0.061). This was more pronounced in the subgroup of individuals having never smoked (OR = 1.85, 95%CI = 1.07-3.22). Moreover, the G allele showed increased activity relative to the C allele in the dual-luciferase reporter assay. Our results suggest that the -572G/C polymorphism may be associated with IL6 expression, which in turn plays a role in prostate cancer development.
Wang J.,Zhongda Hospital
International journal of nanomedicine | Year: 2011
The purpose of this study was to assess the induced apoptosis of self-assembled iron oxide magnetic nanoparticles (MNPs) co-loaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet) (DNR/Br Tet-MNPs), acting as a drug depot system for the sustained release of the loaded DNR and BrTet, in the drug resistant human leukemia K562/A02 cells and further to explore potential mechanisms. After being incubated for 48 hours, K562/A02 cells were treated with DNR/Br Tet-MNPs or DNR and Br Tet in solution (DNR/Br Tet-Sol). Morphologic characteristics of K562/A02 cells were observed under a fluorescence microscope; cell apoptosis and intracellular accumulation of DNR were analyzed by FACS Calibur flow cytometry. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting analyses were performed to study the apoptosis associated gene transcription and protein expression, respectively. Typical apoptotic characteristics, including chromatin condensation and fragmentation of nuclei, were observed and a high rate of apoptosis was detected in K562/A02 cells treated with DNR/Br Tet-MNPs and DNR/Br Tet-Sol. Detection of relative fluorescence intensity of intracellular DNR demonstrated that intracellular DNR was higher in K562/A02 cells treated with DNR/Br Tet-MNPs than that of DNR/Br Tet-Sol. Further study demonstrated that both DNR/Br Tet-MNPs and DNR/Br Tet-Sol reduced the gene transcriptions and protein expressions of bcl-2 and survivin and enhanced that of bax and caspase 3. It is concluded that self-assembled DNR/Br Tet-MNPs, as one of the potential antitumor agents for hematologic malignancies, may effectively induce apoptosis of K562/A02 cells through elevating the ratio of bax/bcl-2, activating caspase 3, and inactivating survivin.
Wang Y.,Nanjing Medical University |
Wang Y.,Zhongda Hospital |
Zhu Y.,Nanjing Medical University |
Gao L.,Nanjing Medical University |
And 5 more authors.
Molecules | Year: 2012
Several studies suggest that the inflammation plays a role in the pathogenesis of some glucose disorders in adults. Exposure of pancreatic β-cells to cytokines, such as interleukin-1β (IL-1β), is thought to contribute to β-cell apoptosis. One important event triggered by IL-1β is induction of nitric oxide synthase (iNOS), an enzyme that catalyzes intracellular generation of the cytotoxic free radical NO. Recent work have suggested that formononetin, as an O-methylated isoflavone found in a number of plants and herbs like Astragalus membranaceus, inhibited some pro-inflammatory cytokine production in macrophages. However, the roles of formononetin in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of formononetin on cell apoptosis induced by IL-1β in the rat insulinoma cell line, INS-1. Our results demonstrate that formononetin significantly prevents IL-1β-increased INS-1 cell death and blocks cytokine-induced apoptotic signaling (the reduction of Bax/Bcl-2 ratio and caspase-3 activity). Formononetin also inhibited the activation of nuclear factor-kappaB (NF-κB), which is a significant transcription factor for iNOS, so as to decease nitric oxide (NO) formation in a dose dependent manner in vitro. Our observations indicated that formononetin could protect against pancreatic β-cell apoptosis caused by IL-1β and therefore could be used in the future as a new drug improving diabetes mellitus. © 2012 by the authors.
Fisher E.B.,University of North Carolina at Chapel Hill |
Coufal M.M.,University of North Carolina at Chapel Hill |
Parada H.,University of North Carolina at Chapel Hill |
Robinette J.B.,University of North Carolina at Chapel Hill |
And 10 more authors.
Annual Review of Public Health | Year: 2014
As reviewed in the article by Perry and colleagues (2014) in this volume, ample evidence has documented the contributions of peer support (PS) to health, health care, and prevention. Building on that foundation, this article discusses characteristics, contexts, and dissemination of PS, including (a) fundamental aspects of the social support that is often central to it; (b) cultural influences and ways PS can be tailored to specific groups; (c) key features of PS and the importance of ongoing support and backup of peer supporters and other factors related to its success; (d) directions in which PS can be expanded beyond prevention and chronic disease management, such as in mental health or interventions to prevent rehospitalization; (e) other opportunities through the US Affordable Care Act, such as through patient-centered medical homes and chronic health homes; and (f) organizational and policy issues that will govern its dissemination. All these demonstrate the extent to which PS needs to reflect its contexts-intended audience, health problems, organizational and cultural settings-And, thus, the importance of dissemination policies that lead to flexible response to contexts rather than constraint by overly prescriptive guidelines. ©2014 by Annual Reviews. All rights reserved.
Wang Z.,U.S. National Institutes of Health |
Wang Y.,U.S. National Institutes of Health |
Wang Z.,Zhongda Hospital |
Gutkind J.S.,Zhongda Hospital |
And 7 more authors.
Stem Cells | Year: 2015
Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mesenchymal stem cells (MSCs) are promising for the treatment of various diseases and injuries. Many strategies have been applied to attract MSCs to injury site after systemic infusion. In this study, we evidenced that the CXC chemokine receptor 4 (CXCR4)-SDF1α (stromal cell-derived factor 1α) axis in engineered MSCs serves not only to attract MSC migration to TBI but also to activate Akt kinase signaling pathway in MSCs to promote paracrine secretion of cytokines and growth factors. This leads to enhanced vasculogenesis and neuroprotection at the boundary of TBI for improved blood supply, recovery of axon connectivity, and behavioral ability and results in positive feedback loop to enhance additional MSC tropism to injury. These findings indicate a new aspect of SDF1α in mediating CXCR4 engineered MSCs for brain trauma homing and recovery. This potential mechanism may be applicable to other injuries, where CXCR4-SDF1α interaction is highly associated. Stem Cells 2015;33:456-467 © 2014 AlphaMed Press.