Shanghai Geriatric Institute of Chinese Medicine

Shanghai, China

Shanghai Geriatric Institute of Chinese Medicine

Shanghai, China
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Gao Y.,Shanghai JiaoTong University | Liu T.,Shanghai JiaoTong University | Liu T.,Shanghai Geriatric Institute of Chinese Medicine | Cheng W.,Shanghai JiaoTong University | Wang H.,Shanghai JiaoTong University
Oncology Reports | Year: 2012

Although the highly proliferative, migratory and multidrug resistant phenotype of human type II endometrial carcinoma (EC) is well characterized, improved clinical treatments have not yet been developed. In this study, CD44 and CD133 were used as markers to screen, isolate and enrich carcinoma-initiating cells (CICs) from the human type II EC cell lines KLE and ANCA3. Using flow cytometry, we identified a subpopulation of KLE and ANCA3 cells which express high levels of both CD44 and CD133 on the cell membrane. CD44+/CD133+ EC-CICs exhibited high levels of stemness marker genes, and possessed a higher migratory and invasive ability than CD44-/CD133- endometrial carcinoma cells EC-CCs). CD44+/CD133+ EC-CICs were also more resistant growth inhibition induced by the chemotherapeutic drugs cisplatin and paclitaxel. Additionally, CD44+/CD133+ EC-CICs readily established tumors in vivo in a relatively short time. In conclusion, CD44 +/CD133+ cells possessing the characteristics of CICs can be reliably sorted from KLE and ANCA3 human type II EC cell lines, and represent a valuable model for studying cancer cell physiology and multidrug resistance. Further characterization of CD44+/CD133+ KLE and ANCA3 cells may have a profound impact on the selection of individual treatment strategies, clinical outcomes and design of the next generation of chemotherapeutic agents for type II EC.


Liu T.,Donghua University | Liu T.,Shanghai Geriatric Institute of Chinese Medicine | Guo L.,Chinese Academy of Sciences | Liu Z.,Tongji University | And 2 more authors.
International Journal of Molecular Medicine | Year: 2011

Parkinson's disease (PD) is a common age-associated neurodegenerative disorder. To date, stem cell transplantation therapy has been developed to replace lost or damaged neural cells in PD patients, in whom dopaminergic neuron cells are lost. Here, we show that CD44 + human amniotic fluid cells (HuAFCs) can be induced to become functional dopaminergic neuronal-like cells in vitro. Furthermore, when CD44 + or CD44 - HuAFCs were transplanted into 6-hydroxydopamine (6-OHDA)-treated PD rats, the results indicated that CD44 +HuAFCs expressed multiple dopaminergic neuron cell markers and were ameliorative to behavioral recovery in PD rats after induction both in vitro and in vivo. CD44 - HuAFCs did not fully differentiate into dopaminergic neuronal-like cells. When compared with CD44 - HuAFCs, CD44 + HuAFCs showed increased activity in regeneration of dopaminergic neuron cell-like cells, increased migration distances, and improvement of animal behavior in the PD rat model. Therefore, CD44 +HuAFCs could be a source of dopaminergic neuronal-like cells with a potential use in cell-replacement therapy for PD.


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.


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.


Liu T.,Donghua University | Liu T.,Shanghai Geriatric Institute of Chinese Medicine | Cheng W.,Shanghai JiaoTong University | Huang Y.,University of Toulon | And 3 more authors.
Experimental Cell Research | Year: 2012

Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. © 2011 Elsevier Inc.


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.


PubMed | Fudan University, Shanghai Geriatric Institute of Chinese Medicine and Engineering School of Information Technology and Communication
Type: | Journal: Brain research | Year: 2016

The prevailing -amyloid (A)-cascade hypothesis is the most classical Alzheimers disease (AD) pathogenesis. In this hypothesis, excessive A plaque deposition in human brain is considered to be the cause of AD. Carbon 11-labeled Pittsburgh compound B Positron emission tomography (11C-PiB PET) is the latest technology to detect A plaques in vivo. Thus, it is possible to investigate the difference of A brain networks between AD patients and Health Controls (HC) by analyzing 11C-PiB PET images. In this study, a graph-theoretical method was employed to investigate the topological properties of A networks in 18 Chinese AD patients and 16 HC subjects from Huashan Hospital, Shanghai. The results showed that both groups demonstrated small-world property, and this property was more obvious in AD group. Additionally, the clustering coefficients and path lengths were significantly lower in AD group. The global efficiency was larger in AD than in HC. A direct comparison between with and without regression found that sex, age and weight had no significant effect on the A network. Moreover, three altered regions in AD group were identified, including left cuneus (CUN.L), right caudate nucleus (CAU.R) and left superior frontal gyrus (SFGdor.L). A voxel-wise correlation analysis showed that in AD patients, the regions of strengthened connection with CUN.L were mainly located in frontal cortex and parietal cortex, the regions of strengthen connection with CAU.R were mainly located in temporal cortex. Finally, a machine learning based analysis demonstrated that the three regions could be better biomarkers than the whole brain for AD classification.


PubMed | Shanghai Geriatric Institute of Chinese Medicine
Type: Journal Article | Journal: Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine | Year: 2012

To observe the effects of Shoushen Granule, a compound traditional Chinese herbal medicine, on telomere length and telomerase activity in peripheral leukocytes and vascular cells, artery wall lesions and blood lipid in a Sprague-Dawley (SD) rat model of atherosclerosis.Forty SD rats were randomly divided into normal control group, model group, Shoushen Granule group and Western medicine group with 10 in each group. The rat model of atherosclerosis was established by high-fat diet and vitamin D3 loading. The model group was given gastric perfusion of double distilled water; The Shoushen Granule group and the Western medicine group were respectively given gastric perfusion of Shoushen Granule and pravastatin. After 12 weeks, pathological changes of abdominal aorta were determined by hematoxylin and eosin staining. Biochemical colorimetric method was used to detect the contents of total cholesterol (TC), triacylglycerol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C) in serum of the rats. Telomere length and telomerase activity in peripheral leukocytes and vascular cells of the rats were tested by quantitative real-time polymerase chain reaction method.When compared with the model group, atherosclerosis lesions of the arterial wall were significantly improved in the Shoushen Granule group. In addition, both TC and LDL-C levels in the Shoushen Granule group were decreased significantly compared with the model group (P<0.01). Besides, not only telomerase activity but also telomere length in peripheral leukocytes (P<0.01) and vascular cells (P<0.05) were increased significantly as compared to those in the model group. However, there was no significant difference between the Shoushen Granule group and the normal control group (P>0.05).Shoushen Granule improves the atherosclerosis lesions in rats, and the mechanism may be related to regulating telomere length and telomerase activity.


PubMed | Fudan University, Tongji University, Shanghai University, University of Melbourne and Shanghai Geriatric Institute of Chinese Medicine
Type: | Journal: Experimental gerontology | Year: 2016

Studies have shown that misfolded proteins and endoplasmic reticulum (ER) stress play pivotal roles in the progression of Alzheimers 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 A1-42 oligomer by increasing Hsp70, Grp78, IRE1 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.


PubMed | U.S. National Institute on Aging, Peking University and Shanghai Geriatric Institute of Chinese Medicine
Type: Journal Article | Journal: Oncotarget | Year: 2016

The tRNA methyltransferase NSUN2 delays replicative senescence by regulating the translation of CDK1 and CDKN1B mRNAs. However, whether NSUN2 influences premature cellular senescence remains untested. Here we show that NSUN2 methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC. Our results further show that the elevation of SHC expression by NSUN2-mediated mRNA methylation increased the levels of ROS, activated p38MAPK, thereby accelerating oxidative stress- and high-glucose-induced senescence of human vascular endothelial cells (HUVEC). Our findings highlight the critical impact of NSUN2-mediated mRNA methylation in promoting premature senescence.

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