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Zhang L.,Fudan University | Liu T.,Donghua University | Liu T.,Shanghai Geriatric Institute of Chinese Medicine | Huang Y.,University of Toulon | Liu J.,Rutgers University
International Journal of Molecular Medicine | Year: 2011

Lung cancer is one of the main causes of cancer death worldwide. The cortactin gene, CTTN, may play a pivotal role in the proliferation and invasion of tumors. A microRNA (miR-182) was cloned and used to study the expression of CTTN and its regulatory effects on the proliferation and invasion of the lung cancer cell line, A549. Cortactin protein and CTTN mRNA expression decreased in A549 cells that were transfected with the miR-182 expression plasmid. A cell proliferation assay indicated that miR-182 expression affected cell cycle regulation and suppressed proliferation of lung cancer cells in vitro. In addition, xenograft experiments confirmed the suppression of tumor growth in vivo, which was due to the promotion of apoptosis. In conclusion, endogenous mature miR-182 expression may have an important role in the pathogenesis of lung cancer through its interference with the target gene CTTN by epigenetic modification. Source

Jiang J.,Engineering School of Information Technology and Communication | Duan H.,Engineering School of Information Technology and Communication | Huang Z.,Fudan University | Yu Z.,Shanghai Geriatric Institute of Chinese Medicine
Bio-medical materials and engineering | Year: 2015

One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD. Source

Liu L.,Fudan University | Liu L.,Shanghai University | Zhang C.,Tongji University | Kalionis B.,University of Melbourne | And 5 more authors.
Experimental Gerontology | Year: 2016

Studies have shown that misfolded proteins and endoplasmic reticulum (ER) stress play pivotal roles in the progression of Alzheimer's disease (AD). It has also been reported that ER stress is considered to be a common mediator of apoptosis in neurodegenerative disorders like AD. However, the precise mechanisms leading to neuronal cell death caused by ER stress in AD remain unclear. Hsp70, the major inducible form of the heat shock protein family, functions at the level of chaperone-mediated protein folding. Enhanced expression of Hsp70 suppresses the neurotoxicity caused by protein misfolding. EGb761, an accepted traditional Chinese medicine used to treat AD, was used here to examine the molecular mechanism underlying its protective effect on ER stress and Hsp70. Our study shows that pretreatment with EGb761 overcomes the neurotoxicity of the Aβ1-42 oligomer by increasing Hsp70, Grp78, IRE1α and pAkt expression in a dose-dependent manner and significantly decreases cell apoptosis-related protein expression. Our findings suggest that the neuroprotective effect of EGb761 is related to ER stress activation and increased Hsp70 expression, and subsequent activation of Akt. However, the effect of EGb761 on these processes is not direct. © 2016 Elsevier Inc.. Source

Wan W.-B.,Fudan University | Cao L.,Fudan University | Liu L.-M.,Fudan University | Kalionis B.,University of Melbourne | And 4 more authors.
PLoS ONE | Year: 2014

Alzheimer's disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Ab) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aβ1-42 oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ1-42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ1-42 oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Ab cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ1-42 oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD. Copyright: © 2014 Wan et al. Source

Liu T.,Donghua University | Liu T.,Shanghai Geriatric Institute of Chinese Medicine | Huang Y.,University of Toulon | Huang Q.,Chinese Academy of Sciences | And 3 more authors.
Acta Biologica Hungarica | Year: 2012

Spermatogonial stem cells (SSCs) are defined by unique properties like other stem cells. However, there are two major challenges: long-term cultivation of normal SSCs into stable cell lines and maintaining the SSCs as undifferentiated and capable of self-renewal. Here, we compared different culture methods for mouse SSCs isolated and cultured from testicular tissue. We found that human amniotic epithelial cells (hAECs) can behave as feeder cells, allowing mouse SSCs to maintain a high level of alkaline phosphatase (AP) activity when cultured long-term. Also, we observed that expression of Nanog, Oct-4 and other important stem cells markers were higher in mouse SSCs cultured on hAECs compared to those cultured on MEF or without any feeder cells. Furthermore, we demonstrated that the CpG islands of the Nanog and Oct-4 promoters were hypomethylated in cells cultured on hAECs. In addition, mouse SSCs cultured on hAECs exhibited higher levels of H3AC and H3K4Me3 in the Nanog and Oct-4 promoters than those cultured on MEF or without feeder cells. Taken together, these results suggest that the hAECinduced epigenetic modifications at the Nanog and Oct-4 locus could be a key mechanism for maintaining mouse SSCs in an undifferentiated state capable of self-renewal. © 2012 Akadémiai Kiadó, Budapest. Source

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