Stanford Advisors

All Publications

  • Autophagy is required for human umbilical cord mesenchymal stem cells to improve spatial working memory in APP/PS1 transgenic mouse model STEM CELL RESEARCH & THERAPY Li, W., Li, K., Gao, J., Yang, Z. 2018; 9: 9


    Recent studies have shown that autophagy plays a central role in mesenchymal stem cells (MSCs), and many studies have shown that human umbilical cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of mechanisms. However, no studies have looked at the effects of autophagy on neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we investigated whether inhibition of autophagy could weaken or block the function of huMSCs through in vitro and in vivo experiments.In vitro we examined huMSC migration and neuronal differentiation by inhibiting or activating autophagy; in vivo autophagy of huMSCs was inhibited by knocking down Beclin 1, and these huMSCs were transplanted into the APP/PS1 transgenic mouse. A series of related indicators were detected by T-maze task, electrophysiological experiments, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and Western blotting.We demonstrated that regulation of autophagy can affect huMSC migration and their neuronal differentiation. Moreover, inhibition of autophagy in huMSCs could not realize neuroprotective effects via anti-apoptosis or promoting neurogenesis and synapse formation compared with those of control huMSCs.These findings indicate that autophagy is required for huMSCs to maintain their function and improve cognition impairment in APP/PS1 transgenic mice.

    View details for DOI 10.1186/s13287-017-0756-2

    View details for Web of Science ID 000419962400001

    View details for PubMedID 29335016

    View details for PubMedCentralID PMC5769333

  • Autophagy is involved in mouse kidney development and podocyte differentiation regulated by Notch signalling JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Zhang, C., Li, W., Wen, J., Yang, Z. 2017; 21 (7): 1315-1328


    Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down-regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT-treated cells, and as a result, nephrin was recovered and DAPT-induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.

    View details for DOI 10.1111/jcmm.13061

    View details for Web of Science ID 000404367800007

    View details for PubMedID 28158917

    View details for PubMedCentralID PMC5487928

  • Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure MOLECULAR AND CELLULAR BIOCHEMISTRY Li, W., Wang, L., Chu, X., Cui, H., Bian, Y. 2017; 428 (1-2): 203-212


    At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

    View details for DOI 10.1007/s11010-016-2930-8

    View details for Web of Science ID 000399249400019

    View details for PubMedID 28116543

  • Etidronate rescues cognitive deficits through improving synaptic transmission and suppressing apoptosis in 2-vessel occlusion model rats JOURNAL OF NEUROCHEMISTRY Li, W., Yuan, H., Yu, Y., Cheong, Y., Ren, G., Yang, Z. 2017; 140 (3): 476-484


    Vascular dementia is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus, in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce vascular dementia model. Two weeks later, 2VO model rats were treated with ET (20 mg/kg/day i.p.) for 1 week. Results showed that ET improved the spatial learning and memory function in 2VO rats detected by Morris water maze experiment. A reduced long-term potentiation was also rescued by ET treatment in 2VO rats. Moreover, the long-term potentiation-related proteins, calcium/calmodulin-dependent protein kinase II (CaMKII), NMDAR 2B and PSD95 were up-regulated after treatment with ET. By testing the levels of malondialdehyde and superoxide dismutase in 2VO rats, we discovered that ET lowered oxidative stress. Furthermore, ET displayed a better anti-apoptosis ability through detecting the levels of Bcl-2 and Bax protein and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. In conclusion, ET shows neuroprotective effects on 2VO rats through rescuing spatial working memory deficits, and a possible mechanism may be related to the increased synaptic transmission and the inhibition of oxidative stress and apoptosis.

    View details for DOI 10.1111/jnc.13904

    View details for Web of Science ID 000394641200011

    View details for PubMedID 27874976

  • Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells NEUROCHEMICAL RESEARCH Li, W., Cheong, Y., Wang, H., Ren, G., Yang, Z. 2016; 41 (4): 844-854


    Etidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a 'germinal bisphosphonate' unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P-C-P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca(2+) channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca(2+), are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter-reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 μM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10-100 μM TrisPP showed remarkable cell protection (78-86 %). Moreover, pre-treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca(2+) overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents.

    View details for DOI 10.1007/s11064-015-1761-4

    View details for Web of Science ID 000373860300023

    View details for PubMedID 26559687

  • Toxicology of nanosized titanium dioxide: an update ARCHIVES OF TOXICOLOGY Zhang, X., Li, W., Yang, Z. 2015; 89 (12): 2207-2217


    Nanosized titanium dioxide (nano-TiO2) has tremendous potential for a host of applications, and TiO2 nanoparticles (NP) possess different physicochemical properties compared to their fine particle analogs, which might alter their bioactivity. Their adverse effects on living cells have raised serious concerns recently for their use in health care and consumer sectors such as sunscreens, cosmetics, pharmaceutical additives and implanted biomaterials. Many researches have demonstrated that the physicochemical properties including shape, size, surface characteristics and inner structure of nano-TiO2 particles have different degrees of toxicity to different organism groups under different conditions. Some former reports have demonstrated that nano-TiO2 materials could enter into human body through different routes such as inhalation, dermal penetration and ingestion. After being taken by human body, NP might induce oxidative stress, cytotoxicity, genotoxicity, inflammation and cell apoptosis ultimately in mammal organs and systems. Here, we summarized the update about toxicity of nano-TiO2 and aimed to supply a safety usage guideline of this nanomaterial.

    View details for DOI 10.1007/s00204-015-1594-6

    View details for Web of Science ID 000366155200002

    View details for PubMedID 26391178

  • Nucleus-staining with biomolecule-mimicking nitrogen-doped carbon dots prepared by a fast neutralization heat strategy CHEMICAL COMMUNICATIONS Kang, Y., Fang, Y., Li, Y., Li, W., Yin, X. 2015; 51 (95): 16956-16959


    Biomolecule-mimicking nitrogen-doped carbon dots (N-Cdots) were synthesized from dopamine by a neutralization heat strategy. Fluorescence imaging of various cells validated their nucleus-staining efficiency. The dopamine-mimicking N-Cdots "trick" nuclear membranes to achieve nuclear localization and imaging.

    View details for DOI 10.1039/c5cc06304c

    View details for Web of Science ID 000367468300016

    View details for PubMedID 26445735