Publications by authors named "Yanshuang Zhang"

9 Publications

  • Page 1 of 1

Knockdown of CDK5 down-regulates PD-L1 via the ubiquitination-proteasome pathway and improves antitumor immunity in lung adenocarcinoma.

Transl Oncol 2021 Sep 12;14(9):101148. Epub 2021 Jun 12.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, PR China. Electronic address:

Although immunotherapy (anti-PD-1/PD-L1 antibodies) has been approved for clinical treatment of lung cancer, only a small proportion of patients respond to monotherapy. Hence, understanding the regulatory mechanism of PD-L1 is particularly important to identify optimal combinations. In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered. The PD-L1 protein degradation is mediated by E3 ligase TRIM21 via ubiquitination-proteasome pathway. Subsequently, we studied the function of CDK5/PD-L1 axis in LUAD. In vitro, the absence of CDK5 in mouse Lewis lung cancer cell (LLC) has no effect on cell proliferation. However, the attenuation of CDK5 or combined with anti-PD-L1 greatly suppresses tumor growth in LLC implanted mouse models in vivo. Disruption of CDK5 elicits a higher level of CD3, CD4 and CD8 T cells in spleens and lower PD-1 expression in CD4 and CD8 T cells. Our findings highlight a role for CDK5 in promoting antitumor immunity, which provide a potential therapeutic target for combined immunotherapy in LUAD.
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http://dx.doi.org/10.1016/j.tranon.2021.101148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215302PMC
September 2021

Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer.

Theranostics 2021 26;11(13):6526-6541. Epub 2021 Apr 26.

State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

The treatment for metastatic castration-resistant prostate cancer patients remains a great challenge in the clinic and continuously demands discoveries of new targets and therapies. Here, we assess the function and therapeutic value of SIRT6 in metastatic castration-resistant prostate cancer. The expression of SIRT6 was examined in prostate cancer tissue microarray by immunohistochemistry staining. The functions of SIRT6 and underlying mechanisms were elucidated by and experiments. We also developed an efficient method to silence SIRT6 by aptamer-modified exosomes carrying small interfering RNA and tested the therapeutic effect in the xenograft mice models. SIRT6 expression is positively correlated with prostate cancer progression. Loss of SIRT6 significantly suppressed proliferation and metastasis of prostate cancer cell lines both and . SIRT6-driven prostate cancer displays activation of multiple cancer-related signaling pathways, especially the Notch pathway. Silencing SIRT6 by siRNA delivered through engineered exosomes inhibited tumor growth and metastasis. SIRT6 is identified as a driver and therapeutic target for metastatic prostate cancer in our findings, and inhibition of SIRT6 by engineered exosomes can serve as a promising therapeutic tool for clinical application.
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http://dx.doi.org/10.7150/thno.53886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120217PMC
July 2021

Photocatalytic Performance of the MOF-Coating Layer on SPR-Excited Ag Nanowires.

ACS Omega 2021 Feb 19;6(4):2882-2889. Epub 2021 Jan 19.

School of Materials Science and Engineering, East China Jiaotong University, Shuanggang Road 808, Nanchang 330013, People's Republic of China.

The photoactive metal-organic frameworks (MOFs) were controllably coated on the surface plasmon resonance-excited Ag nanowires in a layer manner to adjust the photocatalytic activity. The influence of the thickness of the MOF coating layer on the photocatalytic activity was investigated. A thicker MOF coating layer not only facilitated the photogenerated electron-hole separation efficiency but also provided a larger Brunauer-Emmett-Teller surface area, thus enhancing the photocatalytic activity. This work provided a new way to adjust the photocatalytic activity of the photoactive MOF.
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http://dx.doi.org/10.1021/acsomega.0c05229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860077PMC
February 2021

Progressive Increasing of Pt Nanoparticles with Multiple-Layered Manner inside Metal-Organic Frameworks for Enhanced Catalytic Activity.

Inorg Chem 2020 Sep 3;59(18):13184-13189. Epub 2020 Sep 3.

School of Materials Science and Engineering, East China Jiaotong University, Shuanggang Road 808, Nanchang, 330013, People's Republic of China.

Single-layered, double-layered, and triple-layered Pt nanoparticles with a well-defined arrangement were encapsulated inside metal-organic frameworks (MOFs) to investigate the catalytic performance influenced by the progressive increasing of Pt nanoparticles inside MOFs; the results show that the catalytic activity of the Pt-MOF hybrid catalysts increases progressively with the progressive increasing of the Pt nanoparticles inside MOFs. Progressive increasing of Pt nanoparticles with a multiple-layered manner inside MOFs provides a new route for designing well-organized hybrid catalysts of noble metal nanoparticles and MOFs with enhanced catalytic activity.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01501DOI Listing
September 2020

Sirt3 Protects Against Ischemic Stroke Injury by Regulating HIF-1α/VEGF Signaling and Blood-Brain Barrier Integrity.

Cell Mol Neurobiol 2021 Aug 4;41(6):1203-1215. Epub 2020 Jun 4.

School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. In addition, Sirt3 KO mice showed more severe blood-brain barrier (BBB) disruption and inflammatory responses compared with WT group in the acute phase. Furthermore, specific overexpression of Sirt3 in astrocytes by injecting glial fibrillary acidic protein (GFAP)::Sirt3 virus in ischemic region showed protective effect against stroke-induced damage. Mechanistically, Sirt3 could regulate vascular endothelial growth factor (VEGF) expression by inhibiting hypoxia inducible factor-1α (HIF-1α) signaling after ischemia (OGD). Our results have shown that Sirt3 plays a protective role in ischemic stroke via regulating HIF-1α/VEGF signaling in astrocytes, and reversal of the Sirt3 expression at the acute phase could be a worthy direction for stroke therapy.
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http://dx.doi.org/10.1007/s10571-020-00889-0DOI Listing
August 2021

Inserting Pt Nanoparticles at the Designated Location inside Metal-Organic Frameworks for Promoted Catalytic Performance.

Inorg Chem 2020 May 22;59(9):6060-6066. Epub 2020 Apr 22.

School of Materials Science and Engineering, East China Jiaotong University, Shuanggang Road 808, Nanchang 330013, People's Republic of China.

Metal-organic frameworks (MOFs)-supported noble metal nanoparticles (NMNPs) catalysts attract increasing attention due to their high durability and efficiency in catalytic reactions. In this work, Pt nanoparticles are inserted at the designated location inside MIL-100(Fe) to investigate the location-effect of NMNPs inside MOFs on the catalytic reaction. The comparison test on the reduction of -nitrophenol suggests that the location of the Pt nanoparticles inside MIL-100(Fe) largely influences the catalytic performance and the Pt nanoparticles inside MIL-100(Fe) locate closer to the outer surface of the MIL-100(Fe), providing higher catalytic efficiency. Possible reasons are concluded as the location of the Pt nanoparticles inside MIL-100(Fe) dominates the reactants transport pathway and the loading amount of Pt nanoparticles.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00046DOI Listing
May 2020

Encapsulating Pt Nanoparticles through Transforming FeO into MIL-100(Fe) for Well-Defined [email protected]@MIL-100(Fe) Core-Shell Heterostructures with Promoting Catalytic Activity.

Inorg Chem 2019 Sep 6;58(18):12433-12440. Epub 2019 Sep 6.

School of Material Science and Engineering , East China Jiaotong University , Shuanggang Road 808 , Nanchang , 330013 , People's Republic of China.

Metal-organic framework (MOF)-based magnetic Pt catalyst [email protected]@MIL-100(Fe) core-shell heterostructures were prepared through transforming FeO into MIL-100(Fe) in benzene-1,3,5-tricarboxylic acid solution along with encapsulating the Pt nanoparticles successively adsorbed onto the surface of the FeO nanosphere and the continuously forming surfaces of the growing MIL-100(Fe) crystals. This method circumvented the obstacles, controlling the formation of metal nanoparticles (MNPs) inside MOFs or regulating growth of MOFs around the MNPs, for preparing an MNP-MOF composite catalyst. The obtained well-defined [email protected]@MIL-100(Fe) core-shell heterostructure was shown promoting catalytic activity on the reduction of 4-nitrophenol due to the synergistic effect between the Pt nanoparticles and the MIL-100(Fe) shell and recycling convenience due to the rapid separation of the FeO core under an external magnetic field.
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http://dx.doi.org/10.1021/acs.inorgchem.9b02114DOI Listing
September 2019

Sirt3 Mediates the Inhibitory Effect of Adjudin on Astrocyte Activation and Glial Scar Formation following Ischemic Stroke.

Front Pharmacol 2017 22;8:943. Epub 2017 Dec 22.

State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

In response to stroke-induced injury, astrocytes can be activated and form a scar. Inflammation is an essential component for glial scar formation. Previous study has shown that adjudin, a potential Sirt3 activator, could attenuate lipopolysaccharide (LPS)- and stroke-induced neuroinflammation. To investigate the potential inhibitory effect and mechanism of adjudin on astrocyte activation, we used a transient middle cerebral artery occlusion (tMCAO) model with or without adjudin treatment in wild type (WT) and Sirt3 knockout (KO) mice and performed a wound healing experiment in vitro. Both our and results showed that adjudin reduced astrocyte activation by upregulating Sirt3 expression. In addition, adjudin treatment after stroke promoted functional and neurovascular recovery accompanied with the decreased area of glial scar in WT mice, which was blunted by Sirt3 deficiency. Furthermore, adjudin could increase Foxo3a and inhibit Notch1 signaling pathway via Sirt3. Both the suppression of Foxo3a and overexpression of N1ICD could alleviate the inhibitory effect of adjudin indicating that Sirt3-Foxo3a and Sirt3-Notch1 signaling pathways were involved in the inhibitory effect of adjudin in wound healing experiment.
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http://dx.doi.org/10.3389/fphar.2017.00943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744009PMC
December 2017

Tubules of plant reoviruses exploit tropomodulin to regulate actin-based tubule motility in insect vector.

Sci Rep 2017 01 9;7:38563. Epub 2017 Jan 9.

Fujian Province Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, P.R. China.

Plant reoviruses are known to exploit virion-packaging tubules formed by virus-encoding non-structural proteins for viral spread in insect vectors. Tubules are propelled by actin-based tubule motility (ABTM) to overcome membrane or tissue barriers in insect vectors. To further understand which insect factors mediate ABTM, we utilized yeast two-hybrid and bimolecular fluorescence complementation assays to test interactions between tubule protein Pns10 of rice dwarf virus (RDV), a plant reovirus, and proteins of its insect vector, the leafhopper Nephotettix cincticeps. Tropomodulin (Tmod), vitellogenin, and lipophorin precursor of N. cincticep displayed positive and strong interaction with Pns10, and actin-associated protein Tmod interacted with Pns10 in pull-down assay and the co-immunoprecipitation system. Further, we determined Pns10 tubules associated with Tmod in cultured cells and midgut of N. cincticep. The expression dynamic of Tmod was consistent with that of Pns10 and the fluctuation of RDV accumulation. Knockdown of Tmod inhibited the Pns10 expression and viral accumulation, thus decreasing the viruliferous rates of leafhopper. These results suggested that Tmod was involved in viral spread by directly interacting with Pns10 tubules, finally promoting RDV infection. This study provided direct evidence of plant reoviruses utilizing an actin-associated protein to manipulate ABTM in insect vectors, thus facilitating viral spread.
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http://dx.doi.org/10.1038/srep38563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220352PMC
January 2017
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