Publications by authors named "Huiyi Liang"

7 Publications

  • Page 1 of 1

Vorinostat targets UBE2C to reverse epithelial-mesenchymal transition and control cervical cancer growth through the ubiquitination pathway.

Eur J Pharmacol 2021 Oct 29;908:174399. Epub 2021 Jul 29.

Foshan Maternal and Child Health Research Institute, South Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, 528000, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Vorinostat is a histone deacetylase inhibitor (HDACi) that was demonstrated in our previous study to inhibit the proliferation, migration, and invasion of cervical cancer cells by regulating the PI3K/Akt signaling pathway. However, the molecular mechanism of vorinostat in cervical cancer treatment remains to be further elucidated. A nude mouse xenograft model was established to analyze the antitumor effect of vorinostat in vivo. The combination of iTRAQ-based proteomics and parallel reaction monitoring (PRM) technology has proven to be an efficient and reliable method to identify potential targets for cancer chemotherapy. In this study, 254 differentially expressed proteins in vorinostat-treated cervical cancer cells, among which 180 were upregulated and 74 were downregulated, were identified by using an iTRAQ-based proteomic strategy. Subsequent bioinformatic and PRM analysis of these differentially expressed proteins indicated that UBE2C is a promising target of vorinostat in the inhibition of cervical cancer cell proliferation. We confirmed that the expression of endogenous UBE2C in cervical cancer cell lines was significantly higher than that in normal cervical epithelial cell lines. Additionally, we found that vorinostat downregulated the expression of UBE2C, SQSTM1/p62, N-cadherin, vimentin and upregulated E-cadherin in SiHa and HeLa cells. Our results also showed that vorinostat can downregulate the expression of SQSTM1/p62, N-cadherin, and vimentin during the treatment of cervical cancer cells by regulating UBE2C, while upregulating the expression of E-cadherin. In conclusion, vorinostat reverses epithelial-mesenchymal transition by targeting UBE2C and controls the proliferation of cervical cancer cells through the ubiquitination pathway. UBE2C can be used as a promising target for the development of vorinostat treatment strategies.
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http://dx.doi.org/10.1016/j.ejphar.2021.174399DOI Listing
October 2021

Topical cationic hairy particles targeting cell free DNA in dermis enhance treatment of psoriasis.

Biomaterials 2021 Sep 15;276:121027. Epub 2021 Jul 15.

School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, 510275, Guangzhou, China. Electronic address:

Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121027DOI Listing
September 2021

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys.

Sci Adv 2020 Jul 31;6(31):eabb5274. Epub 2020 Jul 31.

Center for Functional Biomaterials, School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China.

Cell-free DNA (cfDNA) released from damaged or dead cells combines with LL37 and is converted into an immune response activator to exacerbate psoriasis. Here, we show that cationic nanoparticles (cNPs) efficiently compete for DNA from the DNA-LL37 immunocomplex and inhibit DNA-LL37-induced cell activation. Using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cNPs on psoriasiform skin of a mouse model relieves psoriatic symptoms. It is noteworthy that the results were confirmed in a cynomolgus monkey model. Moreover, topically administrated cNPs showed low in vivo toxicity because of their retention in skin. Mechanistic analyses of cytokine expression in the psoriatic site, cfDNA levels in circulation and inflamed skin, skin permeation, and biodistribution of cNPs also matched the therapeutic outcomes. Therefore, we present a previously unidentified strategy of nanomedicine to treat skin inflammatory diseases, which demonstrates great potential for clinical application.
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http://dx.doi.org/10.1126/sciadv.abb5274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457336PMC
July 2020

Identification of Specific Joint-Inflammatogenic Cell-Free DNA Molecules From Synovial Fluids of Patients With Rheumatoid Arthritis.

Front Immunol 2020 28;11:662. Epub 2020 Apr 28.

Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Center for Functional Biomaterials, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China.

Elevated cell-free DNA (cfDNA) levels in the plasma and synovial fluid of rheumatoid arthritis (RA) patients are proposed to be pathologically relevant. However, direct evidence to support this perception is lacking, and molecular feature of the cfDNA molecules with assumed pathological function is not well characterized. Here, we confirm remarkably increased levels of total synovial fluid and plasma cfDNAs in a large cohort of patients with rheumatoid arthritis compared to the counterparts in osteoarthritis, and demonstrate the potent inflammatogenic effects of RA synovial fluid cfDNA on both human monocyte cell line and primary cells related to RA. Massively parallel sequencing identifies distinct molecular pattern of cfDNA in RA, as characterized by enriching CpG-motif containing sequences. Importantly, these identified CpG-motif-rich sequences are hypomethylated in RA patients and induce severe inflammatory responses both and . Our data demonstrate the pathological role of global and specific cfDNA molecules in RA, thereby identifying novel therapeutic target candidate and potential biomarker for RA.
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http://dx.doi.org/10.3389/fimmu.2020.00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198838PMC
March 2021

Comparisons of Landscape Preferences through Three Different Perceptual Approaches.

Int J Environ Res Public Health 2019 11 27;16(23). Epub 2019 Nov 27.

College of Landscape Architecture and Arts, Northwest A&F University, Xianyang 712100, Shaanxi, China.

In order to identify the effects and divergences of the different landscape perception approaches on landscape preference, this study investigated people's preferences for urban green spaces with different vegetation structures in the early spring through using three approaches, which were on-site survey, photo elicitation and VR technology. The results showed that: (a) There were significant differences among the three approaches for landscape preference, among which there was a significant difference between VR technology and the other two approaches, while no differences between on-site survey and photo elicitation were found. (b) The respondents showed significant differences in their preferences for the urban green spaces with the different vegetation structures through VR technology, and the semi-open green space received the highest preference score. (c) Whatever the approach employed, there were no significant differences in gender and professional background groups for landscape preference. (d) In the comparisons of the three different approaches, the respondents were more willing to choose physical recreational activities to be conducted in the early spring. Based on the above results, the three approaches of landscape perception were divergent and irreplaceable. It is, thus, suggested that the approach of landscape perception should be carefully selected for a specific landscape in a certain season, so as to provide a scientific basis for the evaluation of landscape perception and preference in the future.
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http://dx.doi.org/10.3390/ijerph16234754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926958PMC
November 2019

Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment.

Angew Chem Int Ed Engl 2019 03 18;58(13):4254-4258. Epub 2019 Feb 18.

School of Materials Science and Engineering, and Center of Functional Biomaterials, Key Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou, 510275, China.

Cell-free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll-like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic-acid-induced inflammation. The structure-property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment.
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http://dx.doi.org/10.1002/anie.201813362DOI Listing
March 2019

Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation.

Nat Commun 2018 10 16;9(1):4291. Epub 2018 Oct 16.

Center for Functional Biomaterials, School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, 510275, Guangzhou, China.

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
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http://dx.doi.org/10.1038/s41467-018-06603-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191420PMC
October 2018
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