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Huangshi, China

Ma B.,Tianjin Medical University | Zhang H.,Tianjin Medical University | Zhang H.,Tianjin University | Wang J.,Tianjin Huan Hu Hospital | And 3 more authors.
Oncology Reports | Year: 2012

Colorectal cancer is a significant health problem, and the advanced stages of the disease have a low response rate to chemotherapy and easily acquire chemoresistance. HIV-1 viral protein R (Vpr) has been shown to possess inhibitory effects on various malignant cells in vivo and in vitro. In this study, an Ad-Vpr construct was used to infect the multidrug-resistant human colorectal cancer HCT-8/5-FU(MDR) cell line in vitro for cell viability, apoptosis, gene expression and gene activity using the MTT, flow cytometry, immunoblotting and gel shift assays, respectively. The data showed that Ad-Vpr significantly reduced HCT-8/5-FU(MDR) cell viability in a dose- and time-dependent manner. Ad-Vpr infection promoted HCT-8/5-FU(MDR) cells to undergo apoptosis and to arrest at the G2 phase of the cell cycle. The G2 cell cycle protein Cyclin B1 accumulated in the cells after Ad-Vpr infection. Furthermore, Ad-Vpr induced activation of caspase-3 and -9, but not caspase-8, in HCT-8/5-FU(MDR) cells. Ad-Vpr suppressed expression of the Bcl-xl protein, but upregulated Bax expression and cytochrome c release from the mitochondria in HCT-8/5-FU(MDR) cells. Ad-Vpr infection also resulted in a time-dependent decrease in nuclear translocation of NF-κB/p65 protein and p65 DNA-binding activity in HCT-8/5-FU(MDR) cells. The data from the current study provide mechanistic insights into understanding the molecular basis and utility of Ad-Vpr as a novel anticancer agent for multidrug resistance in human colorectal cancer. Source


Luo Z.,Tianjin First Center Hospital | Li J.,Tianjin Medical University | Nabar N.R.,University of South Florida | Lin X.,University of South Florida | And 5 more authors.
Journal of Neuroimmune Pharmacology | Year: 2012

Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 proinflammatory response. Previously, we published the first report of an Aβ sensitized dendritic cell vaccine as a therapeutic treatment for AD in BALB/c mice. Our vaccine elicited an anti-Aβ titer, with indications that a Th1 response was not present. This study is the first to investigate the efficacy and safety of our dendritic cell vaccine for the prevention of AD in transgenic mouse models (PDAPP) for AD. We also used Immunohistochemistry to characterize the involvement of LXR, ABCA1, and CD45 in order to gain insight into the potential mechanisms through which this vaccine may provide benefit. The results indicate that (1) the use of mutant Aβ1-42 sensitized dendritic cell vaccine results in durable antibody production, (2) the vaccine provides significant benefits with regards to cognitive function without the global (Th1) inflammation seen in prior Aβ vaccines, (3) histological studies showed an overall decrease in Aβ burden, with an increase in LXR, ABCA1, and CD45, and (4) the beneficial results of our DC vaccine may be due to the LXR/ABCA1 pathway. In the future, mutant Aβ sensitized dendritic cell vaccines could be an efficacious and safe method for the prevention or treatment of AD that circumvents problems associated with traditional anti-Aβ vaccines. © Springer Science+Business Media, LLC 2012. Source


Dong C.,Tianjin Huan Hu Hospital
Drug research | Year: 2015

Cadmium (Cd) is a potent neurotoxic heavy metal, known to induce oxidative stress and membrane disturbances in brain. Proanthocyanidins (PACs), the most abundant polyphenol class in the human diet, have protective effects on oxidative stress and other metabolic disorders. Based on the cellular protective effect of PACs, we aimed to investigate whether PACs could protect the neuronal cells from Cd-induced excitotoxicity. The experiment was carried out on mice model and also in primary culture of hippocampal neurons isolated from neonatal mice. The Cd-induced changes in acetylcholinesterase (AChE) activity, oxidative stress markers (lipid peroxidation/lipid hydroperoxidation), antioxidant status and Akt phosphorylation were measured in the mice brain with or without PACs treatment. Mice intoxicated with cadmium (5 mg/kg/day) for 4 weeks had significantly (p<0.05) reduced the AChE levels, elevated the levels of oxidative stress markers along with the significant (p<0.05) decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants in mice brain tissue. In contrast, administration of PACs (100 mg/kg/day) for 4 weeks in cadmium-intoxicated mice had significantly (p<0.05) protected the cadmium-mediated changes. In addition, PACs treatment in cultured mice hippocampal neurons had protected Cd-induced excitotoxicity by activating Akt phosphorylation, decreasing the caspase-3 level and improving the neuronal cell survival rate up to 24 h. Altogether, our data suggest that PACs plays a crucial role on neuroprotection in combating the cadmium induced oxidative neurotoxicity in mice brain by influencing the activation of AChE/Akt phosphorylation, antioxidant status, controlling the membrane damage (lipid peroxidation) and apoptotic protein caspase-3. © Georg Thieme Verlag KG Stuttgart · New York. Source


Wu Z.,McMaster University | Li S.,Capital Medical University | Lei J.,Tianjin Huan Hu Hospital | An D.,Capital Medical University | And 3 more authors.
American Journal of Neuroradiology | Year: 2010

BACKGROUND AND PURPOSE: SWI is an MR imaging technique that is very sensitive to hemorrhage. Our goal was to compare SWI and CT to determine if SWI can show traumatic SAH in different parts of the subarachnoid space. MATERIALS AND METHODS: Twenty acute TBI patients identified by CT with SAH underwent MR imaging scans. Two neuroradiologists analyzed the CT and SWI data to decide whether there were SAHs in 8 anatomical parts of the subarachnoid space. RESULTS: Fifty-five areas with SAH were identified by both CT and SWI. Ten areas were identified by CT only and 13 by SWI only. SAH was recognized on SWI by its very dark signal intensity surrounded by CSF signal intensity in the sulci or cisterns. Compared with the smooth-looking veins, SAH tended to have a rough boundary and inhomogeneous signal intensity. In many instances, blood in the sulcus left an area of signal intensity loss that had a "triangle" shape. SWI showed 5 more cases of intraventricular hemorrhage than did CT. CONCLUSIONS: SAH can be recognized by SWI through its signal intensity and unique morphology. SWI can provide complementary information to CT in terms of small amounts of SAH and hemorrhage inside the ventricles. Source


Zhang C.,Tianjin Huan Hu Hospital | Peng G.,University of Texas M. D. Anderson Cancer Center
Mutation Research - Reviews in Mutation Research | Year: 2015

Non-coding RNAs play a crucial role in maintaining genomic stability which is essential for cell survival and preventing tumorigenesis. Through an extensive crosstalk between non-coding RNAs and the canonical DNA damage response (DDR) signaling pathway, DDR-induced expression of non-coding RNAs can provide a regulatory mechanism to accurately control the expression of DNA damage responsive genes in a spatio-temporal manner. Mechanistically, DNA damage alters expression of a variety of non-coding RNAs at multiple levels including transcriptional regulation, post-transcriptional regulation, and RNA degradation. In parallel, non-coding RNAs can directly regulate cellular processes involved in DDR by altering expression of their targeting genes, with a particular emphasis on miRNAs and lncRNAs. MiRNAs are required for almost every aspect of cellular responses to DNA damage, including sensing DNA damage, transducing damage signals, repairing damaged DNA, activating cell cycle checkpoints, and inducing apoptosis. As for lncRNAs, they control transcription of DDR relevant gene by four different regulatory models, including signal, decoy, guide, and scaffold. In addition, we also highlight potential clinical applications of non-coding RNAs as biomarkers and therapeutic targets for anti-cancer treatments using DNA-damaging agents including radiation and chemotherapy. Although tremendous advances have been made to elucidate the role of non-coding RANs in genome maintenance, many key questions remain to be answered including mechanistically how non-coding RNA pathway and DNA damage response pathway is coordinated in response to genotoxic stress. © 2014 Elsevier B.V. Source

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