Armed Police General Hospital
Armed Police General Hospital
He H.,Harvard University |
He H.,Children's Hospital of Philadelphia |
Tao H.,Harvard University |
Tao H.,Armed Police General Hospital |
And 6 more authors.
Toxicological Sciences | Year: 2014
This study aims to test the hypothesis that thiazolidinedione rosiglitazone (RSG), a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, causes cardiotoxicity independently of PPARγ. Energy metabolism and mitochondrial function were measured in perfused hearts isolated from C57BL/6, cardiomyocyte-specific PPARγ-deficient mice, and their littermates. Cardiac function and mitochondrial oxidative stress were measured in both in vitro and in vivo settings. Treatment of isolated hearts with RSG at the supratherapeutic concentrations of 10 and 30μM caused myocardial energy deficiency as evidenced by the decreases in [PCr], [ATP], ATP/ADP ratio, energy charge with a concomitant cardiac dysfunction as indicated by the decreases in left ventricular systolic pressure, rates of tension development and relaxation, and by an increase in end-diastolic pressure. When incubated with tissue homogenate or isolated mitochondria at these same concentrations, RSG caused mitochondrial dysfunction as evidenced by the decreases in respiration rate, substrate oxidation rates, and activities of complexes I and IV. RSG also increased complexes I- and III-dependent O2 - production, decreased glutathione content, inhibited superoxide dismutase, and increased the levels of malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine in mitochondria, consistent with oxidative stress. N-acetyl-L-cysteine (NAC) 20mM prevented RSG-induced above toxicity at those in vitro settings. Cardiomyocyte-specific PPARγ deletion and PPARγ antagonist GW9662 did not prevent the observed cardiotoxicity. Intravenous injection of 10 mg/kg RSG also caused cardiac dysfunction and oxidative stress, 600 mg/kg NAC antagonized these adverse effects. In conclusion, this study demonstrates that RSG at supratherapeutic concentrations causes cardiotoxicity via a PPARγ-independent mechanism involving oxidative stress-induced mitochondrial dysfunction in mouse hearts. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Qiu Y.,Inner Mongolia Medical College |
Yun M.M.,University College London |
Xu M.B.,Armed Police General Hospital |
Wang Y.Z.,Peking University |
And 2 more authors.
International Journal of Clinical Oncology | Year: 2013
Background: Dendritic cell (DC)-based and cytokine-induced killer cell (CIK)-based therapy can induce specific antitumor T-cell responses. This clinical pilot study examined the safety, the feasibility, and the outcome of tumor-specific immunotherapy for patients with advanced pancreatic adenocarcinoma. Methods: Alpha-Gal epitopes were synthesised on pancreatic carcinoma cell membranes with α1,3-galactosyltransferase in vitro. Subsequently, the addition of natural human anti-Gal IgG to the processed membranes resulted in opsonization and effective phagocytosis by DCs, which were co-cultured with newly differentiated CIKs from bone marrow stem cells to generate tumor-specific immune responders ex vivo. Fourteen patients with inoperable stage III/IV pancreatic adenocarcinoma were enrolled in the study; the treatment procedure consisted of injections of DCs and CIKs. Results: Clinical observation showed that the procedure was safe and lacked serious side effects. Tests showed that 12 patients had strong positive delayed-type IV hypersensitivity to the autologous cancer cell lysate; robust systemic cytotoxicity elicited by interferon (IFN)γ expression by peripheral blood mononuclear cells; and significant increases in CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells in peripheral blood lymphocytes after 3 injections. During the follow up, the percentages of CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells returned to the normal range at 6 to 9 months after the third injection and IFNγ expression in the cells stayed at the higher level from the third injection to 24 months after the treatment. Conclusions: This new tumor-specific immunotherapy is safe, feasible, and has great potential for pancreatic carcinoma treatment. © 2012 Japan Society of Clinical Oncology.
Fan H.,Armed Police General Hospital |
Song J.,Armed Police General Hospital |
Hou S.,Armed Police General Hospital
Prehospital and Disaster Medicine | Year: 2011
Field first-aid data from the Wenchuan Earthquake in China was analyzed retrospectively in order to probe into ways to develop field first-aid operations and provide a reference for future emergency rescue. Related documents about the Wenchuan Earthquake were collected and reviewed. The state of injury and leading causes of death during the disaster were identified. The presnece of emergency medical resources on-site after the earthquake was relatively insufficient. Deaths mainly were due to cardiopulmonary arrest, severe craniocerebral injury, incurable hemorrhagic shock, and crush syndrome that caused multiple organ system dysfunction syndrome. Only by strengthening the on-site emergency medical resources, speeding-up triage, and equipping responders with professional, portable medical equipment, can field first-aid operations be delivered more efficiently. © World Association for Disaster and Emergency Medicine 2011.
Li Z.,Peking Union Medical College |
Wei H.,Peking Union Medical College |
Liu X.,Peking Union Medical College |
Hu S.,Peking Union Medical College |
And 2 more authors.
Journal of Cellular Biochemistry | Year: 2010
Poor viability of transplanted mesenchymal stem cells (MSCs) in the infracted heart has limited their therapeutic efficacy in cardiac repair after myocardial infarction. We previously demonstrated that hypoxia and serum deprivation (hypoxia/SD) induced mitochondria-dependent apoptosis in MSCs, while lysophosphatidic acid (LPA) could almost completely block this apoptotic process. However, the role of endoplasmic reticulum (ER) stress and its upstream signaling events in hypoxia/SD-induced MSC apoptosis remain largely unknown. Here we found that hypoxia/SD-induced MSC apoptosis was associated with ER stress, as shown by the induction of CHOP expression and procaspase-12 cleavage, while the effects were abrogated by LPA treatment, suggesting ER stress is also a target of LPA. Furthermore, hypoxia/SD induced p38 activation, inhibition of which resulted in decreases of apoptotic cells, procaspase-12 cleavage and mitochondrial cytochrome c release that function in parallel in MSC apoptosis. Unexpectedly, p38 inhibition enhanced hypoxia/SD-induced CHOP expression. Interestingly, p38 activation, a common process mediating various biological effects of LPA, was inhibited by LPA in this study, and the regulation of p38 pathway by LPA was dependent on LPA1/3/Gi/ERK1/2 pathway-mediated MKP-1 induction but independent of PI3K/Akt pathway. Collectively, our findings indicate that ER stress is a target of LPA to antagonize hypoxia/SD-induced MSC apoptosis, and the modulation of mitochondrial and ER stress-associated apoptotic pathways by LPA is at least partly dependent on LPA1/3/Gi/ERK/MKP-1 pathway-mediated p38 inhibition. This study may provide new anti-apoptotic targets for elevating the viability of MSCs for therapeutic potential of cardiac repair. © 2010 Wiley-Liss, Inc.
Yin Q.,Chinese Academy of Sciences |
Yin Q.,Wenzhou Medical College |
Jin P.,Wenzhou Medical College |
Liu X.,Armed Police General Hospital |
And 6 more authors.
Molecular Biology Reports | Year: 2011
Bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to be a promising cell sources for cardiac regeneration. Poor survival rate of transplanted BMSCs in infarcted myocardium attenuated its clinical application. It's reported that stromal-derived factor-1 (SDF-1) could protect progenitor cells including endothelial progenitor cells and embryonic stem cells from apoptosis. But little is known whether SDF-1α protein has the same protective effects on BMSCs under conditions of hypoxia and serum deprivation (hypoxia/SD). In present study, we verified that SDF-1α (0.50-2.0 μg/ml) inhibited hypoxia/SD induced apoptosis of BMSCs through mitochondrial pathway. After administration of SDF-1α, the loss of mitochondrial membrane potential and cytochrome c released from mitochondria to cytosol were significantly inhibited, and caspase 3 activity also declined. Furthermore, the effect of SDF-1α on mitochondrial pathway was neutralized by using PI3K inhibitor (Wortmannin) and ERK1/2 inhibitor (U0126). Our observations suggested that SDF-1α inhibits hypoxia/SD induced BMSCs apoptosis through PI3K/Akt and ERK1/2 signaling pathways. These data also imply that the anti-apoptotic effect mediated by SDF-1α may enhance cell survival after cell transplantation. © 2010 Springer Science+Business Media B.V.
Nie Y.,Peking Union Medical College |
Han B.-M.,Peking Union Medical College |
Han B.-M.,Armed Police General Hospital |
Liu X.-B.,Peking Union Medical College |
And 4 more authors.
International Journal of Biological Sciences | Year: 2011
The use of bone marrow mesenchymal stem cell- (MSC) transplantation therapy for car-diac diseases is limited due to poor survival of implanted cells. MicroRNAs (miRNAs) have been reported to be involved in regulating almost all cellular processes, including apoptosis. In this study, we found that the miRNA profile was altered during apoptosis induced by hypoxia and serum deprivation (hypoxia/SD). We further revealed that over-expression of miR-21, miR-23a and miR-210 could promote the survival of MSCs exposed to hypoxia/SD. In contrast, down-regulation of miR-21, miR-23a and miR-503 aggravated apoptosis of MSCs. It was indicated that these miRNAs may play important roles during MSC apoptosis induced by hypoxia/SD. © Ivyspring International Publisher.
Qin G.,Armed Police General Hospital |
Ji X.,Armed Police General Hospital
Chinese-German Journal of Clinical Oncology | Year: 2010
Melanotic medullary carcinoma is extremely rare. We described a 35-year-old man who was found swelling in the left neck accidently, and no clinic evidences. A left total and right subtotal thyroidectomy and neck lymph nodes dissection were done. Lymph nodes metastasis was not shown. Postoperative of four months, computerized tomography scan liver showed multiple focal lesion. Microscopic examination showed that abundant melanin pigmentation was observed in many of tumor cells. Tumor cells were diffusely immunopositive for vimentin, CK, CgA, syn, CEA, Calcitonin, HMB45, S-100 and negative for TG, TTF-1. Melanotic medullary carcinoma is very rare. It is necessary to report more cases for exact biological behavior and prognosis. © 2010 Springer-Verlag Berlin Heidelberg.
Liu X.-J.,Chinese PLA General Hospital |
Liu X.-J.,94 Hospital of Chinese PLA |
Tan Y.,Chinese PLA General Hospital |
Geng Y.-Q.,Armed Police General Hospital |
And 4 more authors.
American Journal of Nephrology | Year: 2014
Background: Toll-like receptor 4 (TLR4) plays a key role in mediating kidney damage during ischemia/reperfusion (I/R) injury, and its expression is enhanced following renal I/R injury. Our study focused on TLR4 silencing-mediated downstream antiapoptotic pathways during hypoxia/ reoxygenation (H/R) and investigated whether TLR4 overexpression exacerbates the renal damage induced by I/R injury. Methods: Proximal tubule epithelial cells (PTECs) were isolated and H/R injury mediated by ATP depletion, and replenishment was performed to mimic in vivo I/R injury. PTECs were transfected with either TLR4 siRNA or TLR4-overexpressing vectors to determine the contribution of TLR4 to H/R injury-induced apoptosis and inflammatory response. Results: H/R injury significantly enhanced PTEC apoptosis (p < 0.01) and the production of tumor necrosis factor (TNF)-α and interleukin (IL)-8; however, TLR4 silencing significantly reversed these effects (p < 0.05). Moreover, compared to PTECs or PTECs-siCon exposed to H/R injury, overexpression of TLR4 further upregulated TNF-α and IL-8 (p < 0.05), but did not enhance apoptosis. The expression of cytochrome C and caspases 3, 8, and 9 was decreased in the siTLR4 group compared to controls after H/R injury, whereas TLR4 silencing did not alter CHOP expression. TLR4 overexpression failed to promote the expression of cytochrome C and caspases 3, 8, and 9, and reduced the expression of CHOP and GPR78. Conclusions: Knockdown of TLR4 could protect PTECs from H/R injury via inhibiting mitochondrial and death receptor pathways. TLR4 overexpression did not increase PTEC apoptosis induced by H/R injury due in part to the downregulation of CHOP. © 2014 S. Karger AG, Basel.
Li H.,Armed Police General Hospital |
Wu Z.,Armed Police General Hospital
Chinese Journal of Ophthalmology | Year: 2015
Intraocular pressure(IOP) is considered the main risk factor for the development and progression of glaucoma. The major treatment is to reduce the intraocular pressure. However, the damage of optic nerve may continue to progress despite lowering patients' IOP to the target levels. High ocular perfusion pressure (OPP) fluctuations could have detrimental effects in eyes with glaucoma which confirmed that vascular factor is one of the pathogenesis of glaucoma. This review article discussed the research progress of relationship between ocular perfusion pressure and glaucoma including its definition, calculation, epidemiological studies, fluctuation and autoregulation. We also discussed whether it was secondary to changes in intraocular pressure, blood pressure or both. We expect ocular perfusion pressure fluctuations could provide evidence for evaluating glaucoma progress. Copyright © 2015 by the Chinese Medical Association.
PubMed | Armed Police General Hospital
Type: Journal Article | Journal: [Zhonghua yan ke za zhi] Chinese journal of ophthalmology | Year: 2015
Intraocular pressure (IOP) is considered the main risk factor for the development and progression of glaucoma. The major treatment is to reduce the intraocular pressure. However, the damage of optic nerve may continue to progress despite lowering patients IOP to the target levels. High ocular perfusion pressure (OPP) fluctuations could have detrimental effects in eyes with glaucoma which confirmed that vascular factor is one of the pathogenesis of glaucoma. This review article discussed the research progress of relationship between ocular perfusion pressure and glaucoma including its definition, calculation, epidemiological studies, fluctuation and autoregulation. We also discussed whether it was secondary to changes in intraocular pressure, blood pressure or both. We expect ocular perfusion pressure fluctuations could provide evidence for evaluating glaucoma progress.