Publications by authors named "Xinye Han"

8 Publications

  • Page 1 of 1

HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.

Aging (Albany NY) 2021 Apr 21;13(8):11542-11563. Epub 2021 Apr 21.

Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, People's Republic of China.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) are nano-sized membrane-bound vesicles that have been reported to facilitate skin regeneration and repair. However, the roles played by hucMSC-ex in ultraviolet (UV) radiation-induced skin photodamage and the underlying mechanisms remain unknown. To investigate the functions of hucMSC-ex in a rat model of acute skin photodamage, immunofluorescence and immunohistochemical staining, quantitative real-time-polymerase chain reaction (qRT-PCR), western blot, and gene silencing assays were performed. We found that the subcutaneous injection of hucMSC-ex elicited antioxidant and anti-inflammatory effects against UV radiation-induced DNA damage and apoptosis. Further studies showed that the sirtuin 1 (SIRT1) expression level in skin keratinocytes (HaCaT) decreased in a time- and dose-dependent manner under UV radiation induced-oxidative stress conditions, which could be reversed by treatment with hucMSC-ex. The activation of SIRT1 significantly attenuated UV- and HO-induced cytotoxic damage by inhibiting oxidative stress and promoting the activation of autophagy. Our study found that 14-3-3ζ protein, which was delivered by hucMSC-ex, exerted a cytoprotective function via the modulation of a SIRT1-dependent antioxidant pathway. Collectively, our findings indicated that hucMSC-ex might represent a new potential agent for preventing or treating UV radiation-induced skin photodamage and aging.
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http://dx.doi.org/10.18632/aging.202851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109102PMC
April 2021

Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway.

Cell Cycle 2021 Mar-Mar;20(5-6):616-629. Epub 2021 Mar 8.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Diabetic cutaneous wounds are one of the complications of diabetes mellitus (DM) and are difficult to cure at present. Autologous dermal fibroblasts (DFs) have shown great promise in skin regeneration and repair. However, whether exosomes derived from autologous dermal fibroblasts (DF-Ex) can be used to accelerate diabetic cutaneous wound healing is unclear. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose. We found that DF-Ex could reverse the damage produced by high glucose in HUVECs in vitro. A high-fat diet and streptozotocin were used to establish a rat model of type 2 diabetes mellitus (T2DM), and a diabetic cutaneous wound model was established in the T2DM rats. We discovered that subcutaneous injections of DF-Ex could significantly promote re-epithelialization, collagen deposition, skin cell proliferation, angiogenesis and inhibit inflammation to accelerate diabetic cutaneous wound healing. We further explored the underlying mechanism and found that DF-Ex exerted positive effects by activating the Akt/β-catenin pathway. This research revealed that DF-Ex may provide a new treatment strategy for diabetic cutaneous wound healing.
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http://dx.doi.org/10.1080/15384101.2021.1894813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018430PMC
March 2021

Roles of the BRD4 short isoform in phase separation and active gene transcription.

Nat Struct Mol Biol 2020 04 16;27(4):333-341. Epub 2020 Mar 16.

Bethune Institute of Epigenetic Medicine, The First Hospital, Jilin University, Changchun, Jilin, China.

BRD4, a major tandem-bromodomain-containing transcription regulator, has two isoforms. The long isoform (BRD4L) has an extended C terminus that binds transcription cofactors, while the short isoform (BRD4S) lacks this C-terminal extension. Unlike BRD4L, the role of BRD4S in gene transcription remains unclear. Here, we report that, in human cancer cells, BRD4S forms nuclear puncta that possess liquid-like properties and that colocalize with BRD4L, MED1 and sites of histone H3 lysine 27 acetylation. BRD4 puncta are correlated with BRD4S but not BRD4L expression levels. BRD4S knockdown reduces BRD4S condensation, and ectopic expression promotes puncta formation and target gene transcription. BRD4S nuclear condensation is mediated by its intrinsically disordered regions and binding of its bromodomains to DNA and acetylated chromatin, respectively, and BRD4S phosphorylation diminishes BRD4 condensation. Our study illuminates a previously unappreciated role of BRD4S in organizing chromatin and transcription factors through phase separation to sustain gene transcription in chromatin for cancer cell proliferation.
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http://dx.doi.org/10.1038/s41594-020-0394-8DOI Listing
April 2020

The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Stem Cells Int 2019 12;2019:2316834. Epub 2019 Jun 12.

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Mesenchymal stem cells derived from human umbilical cord (hucMSCs) are considered a promising tool for regenerative medicine. circRNAs as newly discovered noncoding RNAs are involved in multiple biological processes. However, little has been known about the function of circRNAs in the proliferation and differentiation of hucMSCs. In this study, we selected several circRNAs expressed in MSCs from circBase and found that CDR1as expression level was markedly significant. We observed that, compared with that of uninduced hucMSCs, the CDR1as expression level of induced hucMSCs decreased with cell induction differentiation. By using siRNA to knock down CDR1as of hucMSCs, we discovered that proliferation was inhibited but the apoptosis increased. In addition, we found that the expression of stemness transcription factors (STFs) was downregulated after CDR1as knockdown and the adipogenesis and osteogenesis potential of hucMSCs was impaired. Our findings suggest that CDR1as takes a part in maintaining proliferation and differentiation of hucMSCs, providing clues for MSC modification and further for stem cell therapy and tissue regeneration.
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http://dx.doi.org/10.1155/2019/2316834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594288PMC
June 2019

miR-373 suppresses gastric cancer metastasis by downregulating vimentin.

Mol Med Rep 2018 Mar 18;17(3):4027-4034. Epub 2017 Dec 18.

Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.

MicroRNA-373 (miR-373) has been reported to be an oncogene in a number of solid human tumors. However, the role of miR‑373 in gastric cancer has not been completely elucidated and the mechanisms remain unclear. In the present study, we compared miR‑373 expression between clinical gastric cancer tissues and paired non‑tumorous tissues by reverse transcription‑quantitative polymerase chain reaction. The impact of miR‑373 on proliferation, migration and invasion in gastric cancer cells was additionally investigated. Hsa‑miR‑373 mimics were applied to mimic the function of endogenous miR‑373. A colony formation assay and flow cytometry were performed to analyze the proliferation of gastric cancer cells. Wound healing and Transwell invasion assays were employed to detect the migratory and invasive abilities of gastric cancer cells. Western blotting was used to test the expression of epithelial‑mesenchymal transition‑associated proteins. The results demonstrated that the level of miR‑373 in gastric cancer was upregulated compared with paired non‑tumorous tissues. It was confirmed that miR‑373 inhibited the migration and invasion of the gastric cancer cell lines SGC‑7901 and HGC‑27 by downregulating vimentin expression. The results of the present study demonstrated an oncogenic role of miR‑373 in the metastasis of human gastric cancer, and may provide a novel therapeutic strategy for gastric cancer.
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http://dx.doi.org/10.3892/mmr.2017.8291DOI Listing
March 2018

BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice.

Proc Natl Acad Sci U S A 2017 03 6;114(11):2952-2957. Epub 2017 Mar 6.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4 T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.
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http://dx.doi.org/10.1073/pnas.1615601114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358349PMC
March 2017

[Increased apoptosis and down-regulation of RhoA in HepG2 cells infected by Listeria monocytogenes].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016 May;32(5):615-8, 624

School of Medicine, Jiangsu University, Zhenjiang 212013, China.

Objective: To explore the apoptosis of HepG2 cells infected by Listeria monocytogenes EGD strain (Lm-EGD) as well as Rho family small GTPases RhoA expression.

Methods: HepG2 cells were infected with Lm-EGD (MOI=10 and MOI=100) and collected 1 hour and 20 hours after infection. After harvesting, the apoptosis of HepG2 cells was determined by flow cytometry combined with annexin V-FITC/PI assay. RhoA and caspase 3 mRNAs were analyzed by reverse-transcription PCR. The caspase 3 activity was detected by colorimetric assay. And Western blotting was used to detect RhoA expression in HepG2 cells.

Results: Lm invasion promoted HepG2 cell apoptosis and down-regulated RhoA mRNA and protein expression. Additionally, caspase 3 expression was up-regulated following Lm infection.

Conclusion: Lm infection could promote host cell apoptosis and down-regulate RhoA expression.
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May 2016

Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells.

J Ginseng Res 2015 Jan 8;39(1):22-8. Epub 2014 Aug 8.

Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, Jilin, China.

Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models.

Methods: MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release.

Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells.

Conclusion: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.
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http://dx.doi.org/10.1016/j.jgr.2014.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268562PMC
January 2015