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. Source
Zhang J.-Z.,Third Hospital of Armed Beijing Corps |
Xie S.-Z.,Armed Police General Hospital |
Chen H.-Y.,Third Hospital of Armed Beijing Corps
World Chinese Journal of Digestology | Year: 2015
AIM: To assess the value of carbohydrate antigen (CA) 242 in the diagnosis of pancreatic cancer (PC) to provide the best evidence to clinical decision-making. METHODS: Medline, EMBASE, Science Direct, Springer link, CBM, CNKI, Wan fang and VIP database were searched by computer before December 31, 2014 to collect the articles assessing the diagnostic value of CA242 in pancreatic cancer. Quality assessment was performed using the QUADAS scale. Meta-Disc 1.4 software was used to analyze the heterogeneity of the included articles, plot the SROC curve, and calculate the pooled sensitivity and specificity. RESULTS: A total of 13 English articles were included. The summary sensitivity of CA242 in diagnosing pancreatic cancer was 71% (95%CI: 69%-74%), the summary specificity was 87% (95%CI: 85%-88%), the diagnostic odds ratio (DOR) was 16.51 (95%CI: 10.38-26.37), the positive likelihood ratio was 5.26 (95%CI: 3.87-7.14), the negative likelihood ratio was 0.34 (95%CI: 0.28-0.42), and the area under the SROC curve was 0.8487. CONCLUSION: Serum CA242 has higher value in diagnosing pancreatic cancer than CA19-9, and it can be used as an diagnostic marker for pancreatic cancer. © 2015 Baishideng Publishing Group Inc. All rights reserved. Source
Shi W.-Z.,Chinese PLA General Hospital |
Miao Y.-L.,PLA No. 306 Hospital |
Guo W.-Z.,Chinese Peoples Liberation Army |
Wu W.,PLA No. 306 Hospital |
And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2014
Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors. ©2014 Elsevier Inc. All rights reserved. Source
Liu X.-J.,Chinese PLA General Hospital |
Tan Y.,Chinese PLA General Hospital |
Geng Y.-Q.,Armed Police General Hospital |
Wang Z.,94 Hospital of Chinese PLA |
And 3 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. Source
Lu H.-W.,Chinese Peoples Liberation Army |
Lu H.-W.,Xian Jiaotong University |
Chen Y.-B.,Beijing Military Region General Hospital |
Li Y.-M.,Xian Jiaotong University |
And 2 more authors.
Chinese Medical Journal | Year: 2010
Background In clinical liver transplantation, whether the delay of hepatic arterial ischaemia increases biliary fibrosis or not is controversial. We designed a liver transplantation model to test this controversy and explore its mechanism. Methods Twelve dogs were divided into two groups randomly: hepatic arterial ischaemia (HAI) and control groups. In HAI group, hepatic artery was perfused 60 minutes after portal perfusion, but in control group, hepatic arterial perfusion was simultaneous with portal perfusion. The pathological changes of intrahepatic bile ducts were observed. Transforming growth factor beta 1 (TGF-β1), expressed in epithelial cells of intrahepatic bile duct, was detected by immunohistochemical streptoadividin-biotin complex method. Expressions of Smad3, P-Smad3 and the transcriptional levels of alpha smooth muscle actin (α-SMA) mRNA in intrahepatic bile ducts were detected by Western blotting and RT-PCR respectively. Results Compared with the control group, more collagen deposition and leucocytic infiltration could be seen in biliary vessel walls. Significantly more buffy particles, which are the proteins of TGF-β1, could be seen in biliary epithelial cells. P-Smad3 and α-SMA mRNA (as ratio to corresponding β-actin) in intrahepatic bile ducts were 1.82±0.18 and 1.86±0.73 respectively in HAI group, significantly higher than those in control group (0.59±0.09 and 0.46±0.18, respectively). Conclusions Hepatic arterial ischaemia could increase the deposition of collagen fibres, trigger the transdifferentiation of myofibroblasts in intrahepatic bile duct and might result in biliary fibrosis by activating the TGF-β1 signalling pathway. Source