Publications by authors named "Yifang Sun"

14 Publications

  • Page 1 of 1

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma.

Front Cell Dev Biol 2021 28;9:673838. Epub 2021 May 28.

Department of Ophthalmology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.

Background: CD8+ T cells work as a key effector of adaptive immunity and are closely associated with immune response for killing tumor cells. It is crucial to understand the role of tumor-infiltrating CD8+ T cells in uveal melanoma (UM) to predict the prognosis and response to immunotherapy.

Materials And Methods: Single-cell transcriptomes of UM with immune-related genes were combined to screen the CD8+ T-cell-associated immune-related genes (CDIRGs) for subsequent analysis. Next, a prognostic gene signature referred to tumor-infiltrating CD8+ T cells was constructed and validated in several UM bulk RNA sequencing datasets. The risk score of UM patients was calculated and classified into high- or low-risk subgroup. The prognostic value of risk score was estimated by using multivariate Cox analysis and Kaplan-Meier survival analysis. Moreover, the potential ability of gene signature for predicting immunotherapy response was further explored.

Results: In total, 202 CDIRGs were screened out from the single-cell RNA sequencing of GSE139829. Next, a gene signature containing three CDIRGs (, , and ) was identified, which was considered as an independent prognostic indicator to robustly predict overall survival (OS) and metastasis-free survival (MFS) of UM. In addition, the UM patients were classified into high- and low-risk subgroups with different clinical characteristics, distinct CD8+ T-cell immune infiltration, and immunotherapy response. Gene set enrichment analysis (GSEA) showed that immune pathways such as allograft rejection, inflammatory response, interferon alpha and gamma response, and antigen processing and presentation were all positively activated in low-risk phenotype.

Conclusion: Our work gives an inspiration to explain the limited response for the current immune checkpoint inhibitors to UM. Besides, we constructed a novel gene signature to predict prognosis and immunotherapy responses, which may be regarded as a promising therapeutic target.
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http://dx.doi.org/10.3389/fcell.2021.673838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194278PMC
May 2021

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.

Protein Cell 2021 Apr 17. Epub 2021 Apr 17.

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC values ranging from 1.39 to 5.63 μmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.
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http://dx.doi.org/10.1007/s13238-021-00836-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052528PMC
April 2021

Glycine max NNL1 restricts symbiotic compatibility with widely distributed bradyrhizobia via root hair infection.

Nat Plants 2021 01 15;7(1):73-86. Epub 2021 Jan 15.

Center of Integrative Biology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.

Symbiosis between soybean (Glycine max) and rhizobia is essential for efficient nitrogen fixation. Rhizobial effectors secreted through the type-III secretion system are key for mediating the interactions between plants and rhizobia, but the molecular mechanism remains largely unknown. Here, our genome-wide association study for nodule number identified G. max Nodule Number Locus 1 (GmNNL1), which encodes a new R protein. GmNNL1 directly interacts with the nodulation outer protein P (NopP) effector from Bradyrhizobium USDA110 to trigger immunity and inhibit nodulation through root hair infection. The insertion of a 179 bp short interspersed nuclear element (SINE)-like transposon into GmNNL1 leads to the loss of function of GmNNL1, enabling bradyrhizobia to successfully nodulate soybeans through the root hair infection route and enhancing nitrogen fixation. Our findings provide important insights into the coevolution of soybean-bradyrhizobia compatibility and offer a way to design new legume-rhizobia interactions for efficient symbiotic nitrogen fixation.
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http://dx.doi.org/10.1038/s41477-020-00832-7DOI Listing
January 2021

Clopidogrel Resistance in a Murine Model of Diet-Induced Obesity Is Mediated by the Interleukin-1 Receptor and Overcome With DT-678.

Arterioscler Thromb Vasc Biol 2020 06 9;40(6):1533-1542. Epub 2020 Apr 9.

From the Department of Internal Medicine, Cardiovascular Research Center, University of Michigan Medical Center, Ann Arbor (Y.S., J.V., C.G., Y.F., Y.E.C., D.T.E.).

Objective: Clopidogrel is a commonly used P2Y inhibitor to treat and prevent arterial thrombotic events. Clopidogrel is a prodrug that requires bioactivation by CYP (cytochrome P450) enzymes to exert antiplatelet activity. Diabetes mellitus is associated with an increased risk of ischemic events, and impaired ability to generate the active metabolite (AM) from clopidogrel. The objective of this study is to identify the mechanism of clopidogrel resistance in a murine model of diet-induced obesity (DIO). Approach and Results: C57BL/6J mice and IL-1R mice were given high-fat diet for 10 weeks to generate a murine model of diet-induced obesity. Platelet aggregation and carotid arterial thrombosis were assessed in response to clopidogrel treatment. Wild-type DIO mice exhibited resistance to antiplatelet and antithrombotic effects of clopidogrel that was associated with reduced hepatic expression of CYP genes and reduced generation of the AM. IL (Interleukin)-1 receptor-deficient DIO (IL1R DIO) mice showed no resistance to clopidogrel. Lack of resistance was accompanied by increased exposure of the clopidogrel AM. This resistance was also absent when wild-type DIO mice were treated with the conjugate of the clopidogrel AM, DT-678.

Conclusions: These findings indicate that antiplatelet effects of clopidogrel may be impaired in the setting of diabetes mellitus due to reduced prodrug bioactivation related to IL-1 receptor signaling. Therapeutic targeting of P2Y in patients with diabetes mellitus using the conjugate of clopidogrel AM may lead to improved outcomes.
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http://dx.doi.org/10.1161/ATVBAHA.120.314146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296442PMC
June 2020

Expression and Functional Analysis of CXCL12 and Its Receptors in Human Term Trophoblast Cells.

Reprod Sci 2020 01 1;27(1):46-54. Epub 2020 Jan 1.

Department of Obstetrics and Gynecology, Medicine Center for Human Reproduction, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei Province, China.

Chemokine CXCL12 and its receptors CXCR4/CXCR7 play a pivotal role in many physiological and pathological situations, while the expression and function in human term trophoblast cells remain largely unknown. In the study, the expression and function of CXCL12 and its receptors CXCR4/CXCR7 in human term trophoblast cells were investigated. Immunocytochemistry and flow cytometry showed that the expression of CXCL12/CXCR4/CXCR7 could be detected in term trophoblast cells while expression level differed. The secretion of CXCL12 in human term trophoblast cells was confirmed by enzyme-linked immunosorbent assay (ELISA). In order to reveal the function of CXCL12, exogenetic recombinant human CXCL12 protein (rhCXCL12) was added to the cultured term trophoblast cells; results showed that cell proliferation ability was increased while cell apoptosis rate was decreased. Moreover, the effects of rhCXCL12 on term trophoblast cells could be diminished or attenuated by antibodies against CXCL12, CXCR4, or CXCR7, respectively. Therefore, these results revealed the important role of CXCL12 on human term trophoblast cells. Our study will provide new insights into understanding the role of CXCL12 on human term trophoblast cells.
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http://dx.doi.org/10.1007/s43032-019-00134-0DOI Listing
January 2020

Can systemic inflammatory response syndrome score at admission predict clinical outcome in patients with severe burns?

Burns 2019 06 21;45(4):860-868. Epub 2018 Dec 21.

Department of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, People's Republic of China. Electronic address:

Introduction: The use of SIRS score as a predictor of outcomes in patients with severe burns has not been fully evaluated. Here, we aimed to test that whether admission SIRS score, combining with other predictors, could be used in predicting outcomes in patients with severe burns. Additionally, we compared the prognostic accuracy of admission SIRS score with other score systems and newly developed models.

Methods: We performed a retrospective study of adult patients with ≥40% total body surface area burns admitted to a burn center from 2005 to 2017. The primary outcome was in-hospital mortality, and the secondary outcomes were hospital and intensive care unit length of stay. SIRS score, rBaux score, ABSI and newly developed models were compared using area under the receiver operating characteristic curve analysis.

Results: Out of the total 144 patients, 128 (88.9%) met SIRS criteria on admission; with a predominant SIRS scores of 3. Patients with admission SIRS were more likely to have larger burns and have higher rBaux and ABSI scores when compared with non-SIRS patients. With the each increment of admission SIRS score, total and full-thickness burn areas, proportion of inhalation injury, tracheostomy and mortality increased significantly. However, SIRS score at admission was not increasingly predictive of deleterious outcomes when analyzed by multivariable regression analysis. Although the combination of SIRS score, age, and burn-specific variables showed better or equal prognostication of outcomes than that of other score systems, the contribution of the variable SIRS score was negligible.

Conclusions: The model with the variables age, percentage full-thickness burns, and inhalation injury provided excellent prediction of poor outcomes in patients with severe burns, while SIRS score has limited use for prognostic determinations.
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http://dx.doi.org/10.1016/j.burns.2018.11.011DOI Listing
June 2019

Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells.

J Ophthalmol 2016 14;2016:6538051. Epub 2016 Apr 14.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou 510000, China.

Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.
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http://dx.doi.org/10.1155/2016/6538051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848450PMC
May 2016

Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses.

PLoS One 2016 10;11(3):e0150114. Epub 2016 Mar 10.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510064, China.

Purpose: To explore the possibility that inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) and Dendritic cell-associated C-type lectin-1(Dectin-1) could modulate the innate immune response and alleviate the severity of corneal fungal keratitis.

Method: TREM-1 and Dectin-1 expression was detected in fungus-infected human corneal specimens by real-time PCR. C57BL/6 (B6) mice were injected with Aspergillus fumigatus and divided into 4 groups that received subconjunctival injections of PBS and IgG as a control (group I), mTREM-1/IgG fusion protein (group II), the soluble β-glucan antagonist laminarin (group III), or mTREM-1/Fc and laminarin (group IV). Corneal virulence was evaluated based on clinical scores. TREM-1 and Dectin-1 mRNA levels were assayed using real-time PCR. The distribution patterns of TREM-1, Dectin-1 and cellular infiltrates in fungus-infected corneas were examined by immunohistochemistry. Moreover, changes in T Helper Type1 (Th1)-/ T Helper Type1 (Th2)- type cytokines and proinflammatory cytokines were measured.

Results: The expression of TREM-1 and Dectin-1 increased significantly and correlated positively with the progression of fungal keratitis. Most infiltrated cells were neutrophils and secondarily macrophages in infected cornea. The clinical scores decreased after interfering with TREM-1 and Dectin-1 expression in infected mouse corneas. Levels of Th1-type cytokines including interleukin-12 (IL-12), IL-18 and interferon-γ (IFN-γ) were decreased in the cornea, while the levels of Th2-type cytokines, including IL-4, IL-5 and IL-10, showed obvious increases.

Conclusion: TREM-1 and Dectin-1 function concurrently in the corneal innate immune response by regulating inflammatory cytokine expression in fungal keratitis. Inhibition of TREM-1 and Dectin-1 can alleviate the severity of corneal damage by downregulating the excessive inflammatory response.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150114PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786258PMC
August 2016

Tacrolimus (FK506) suppresses TREM-1 expression at an early but not at a late stage in a murine model of fungal keratitis.

PLoS One 2014 2;9(12):e114386. Epub 2014 Dec 2.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China.

Purpose: To investigate the efficacy and mechanism of tacrolimus(FK506), which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) expression in a murine keratitis model induced by Aspergillus fumigatus.

Method: TREM-1 was detected in 11 fungus-infected human corneas by quantitative real-time PCR (qRT-PCR). RAW264.7 macrophages were divided into four groups, which received treatment with zymosan (100 µg/ml), zymosan (100 µg/ml) + mTREM-1/Fc protein (1 µg/ml), or zymosan (100 µg/ml) + FK506 (20 µM) or negative-control treatment. After this treatment, the expression of TREM-1, interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) was assayed using qRT-PCR and ELISA. The mouse model of fungal keratitis was created by intrastromal injection with Aspergillus fumigatus, and the mice were divided into 2 groups: group A received vehicle eye drops 4 times each day, and group B received 4 doses of FK506 eye drops each day. Corneal damage was evaluated by clinical scoring and histologic examination,and myeloperoxidase (MPO) protein levels were also detected by ELISA. The expression of TREM-1, IL-1β and TNFα was then determined at different time points using qRT-PCR and ELISA.

Results: TREM-1 expression dramatically increased in the human corneas with fungal keratitis. In contrast, FK506 reduced the expression of TREM-1, IL-1β and TNFα in RAW264.7 macrophages stimulated with zymosan. In the mouse model, at day 1 post-infection, the corneal score of the FK506-treated group was lower than that of the control, and polymorphonuclear neutrophil (PMN) infiltration was diminished. TREM-1, IL-1β and TNFα expression was significantly reduced at the same time point. However, the statistically significant differences in cytokine expression, clinical scores and infiltration disappeared at 5 days post-infection.

Conclusions: FK506 may inhibit the inflammation induced by fungi and alleviate the severity of corneal damage at an early stage of fungal keratitis by downregulating TREM-1 expression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114386PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252117PMC
January 2016

Comparison of deep anterior lamellar keratoplasty and penetrating keratoplasty with respect to postoperative corneal sensitivity and tear film function.

Graefes Arch Clin Exp Ophthalmol 2014 Nov 31;252(11):1779-87. Epub 2014 Jul 31.

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China.

Purpose: To investigate tear film function, central and peripheral corneal sensitivity and corneal subbasal nerve morphology in the cornea after deep anterior lamellar keratoplasty (DALK) compared with penetrating keratoplasty (PK).

Methods: This prospective study compared the changes in 16 eyes of 16 patients who underwent DALK (DALK group) with those in 28 eyes of 28 patients who underwent PK (PK group). Thirty healthy volunteers were also included as controls. Tear functions were evaluated using tear break-up time (TBUT), tear meniscus height (TMH) and corneal fluorescein staining. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Corneal subbasal nerve morphology was evaluated using in vivo confocal microscopy (IVCM). The patients were examined 1, 3, 6, 9 and 12 months after keratoplasty.

Results: Postoperatively, TMH recovered significantly faster in the DALK group than in the PK group (p < 0.05), and the postoperative TBUT was much higher in the DALK group compared with the PK group (p < 0.05). Central and peripheral corneal sensitivity remained lower in both the PK and DALK groups at 12 months after surgery compared with the control group (p < 0.05). The peripheral corneal sensitivity of the host cornea was significantly higher than the central corneal sensitivity (p < 0.05). No significant difference was found in corneal sensitivity between the PK and DALK groups. There was no significant correlation between corneal sensitivity and tear film function after PK or DALK.

Conclusions: Tear film function was restored more rapidly after DALK compared with PK, but there was no significant difference in corneal sensitivity between PK and DALK.
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http://dx.doi.org/10.1007/s00417-014-2748-6DOI Listing
November 2014

[Study on antibacterial active components from Viola yedoensis].

Zhongguo Zhong Yao Za Zhi 2011 Oct;36(19):2666-71

Northwest A&F University, College of Life Science, Yangling 712100, China.

Objective: Study on the antibacterial activity of Viola yedoensis and the antibacterial active compounds.

Method: The chemical compositions were isolated by means of solvent extraction, column chromatography on silica gel, sephadex LH-20 and crystallization. The antibacterial activities were tested by Neo-Sensitab disk-diffusion method, nephelometric analysis and plating method.

Result: One new compound (4) along with three known compounds were isolated from this plant for the first time and were identified as aesculetin (1), 6,7-dimethoxycoumarin (2), scopoletin (3) and 5-methoxy-7-hydroxymethylcoumarin (4), respectively. All the compounds showed antibacterial and antibactericidal activities at varying degree on Streptococcus Aureas, S. agalactiae, S. uberis, S. dysgalactiae, E. coli and Salmonella, of which 1 was most active with 0.031- 0.313 g x L(-1) of minimal inhibitory concentrations (MIC) and 0.313 - 0.625 g x L(-1) of minimal bactericidal concentrations (MBC).

Conclusion: Viola yedoensis has a broad spectrum of antibacterial activity on animal pathogenic bacteria, and coumarins may be the main antibacterial activity ingredients.
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October 2011

2-(2-Iodo-phen-yl)-1,2,3,4-tetra-hydro-isoquinoline-1-carbonitrile.

Acta Crystallogr Sect E Struct Rep Online 2011 Jun 20;67(Pt 6):o1484. Epub 2011 May 20.

In the title compound, C(16)H(13)IN(2), the two benzene rings make a dihedral angle of 67.26 (5)°. The six-membered heterocycle of the tetra-hydro-isoquinoline unit adopts a half-chair conformation. In the crystal, adjacent mol-ecules are linked by pairs of weak inter-molecular C-H⋯N hydrogen bonds, forming inversion dimers. An intra-molecular C-H⋯I close contact is also observed.
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http://dx.doi.org/10.1107/S1600536811015212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120457PMC
June 2011

Accuracy of 16-row multislice computerized tomography angiography for assessment of intracranial aneurysms.

Surg Neurol 2009 Jan 18;71(1):32-42. Epub 2008 Oct 18.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.

Background: Sixteen-row multislice CT has great potential for use in vascular studies. The aim of the study was to assess the diagnostic accuracy of 16-row multislice CTA in detecting intracranial aneurysms compared with 2D-DSA and surgical findings.

Methods: One hundred fifty-two consecutive patients were included in the study and successively underwent 16-slice CTA, 2D-DSA, and surgery in some patients. This was performed with a 16-row multislice CT machine, detector slice of 0.75 mm, reconstruction interval of 0.40 mm, and timing determined by bolus trigger. The 16-slice CTA and 2D-DSA results were evaluated independently by 3 different neuroradiologists who performed aneurysm detection using MIP, SSD, and VRT.

Results: With the combination of 16-slice CTA, 2D-DSA, and intraoperative findings, 92 aneurysms were detected in 86 of the 152 patients. Two aneurysms were missed when 16-slice CTA was used. Three aneurysms were not clearly depicted at 2D-DSA, but proven at surgery. There was no statistically significant difference in sensitivity between 16-slice CTA and 2D-DSA (P = 1.0). The sensitivity of 16-slice CTA for detecting aneurysms <4 mm, between 4 and 10 mm, and >10 mm was 96% (95% CI: 79.6%-99.9%), 98.1% (95% CI: 89.7%-100%), and 100% (95% CI: 78.2%-100%), respectively, on a per-aneurysm basis. The sensitivity, specificity, and accuracy of 16-slice CTA for detecting aneurysms were 97.8% (95% CI: 92.4%-99.7%), 100% (95% CI: 94.6%-100%), and 98.7% (95% CI: 95.5%-99.8%), respectively, on a per-aneurysm basis.

Conclusion: Sixteen-slice CTA shows promising diagnostic accuracy that appears to be comparable with 2D-DSA for the detection of suspected intracranial aneurysms, and 16-slice CTA is sensitive enough to replace 2D-DSA in detecting aneurysms.
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http://dx.doi.org/10.1016/j.surneu.2007.08.005DOI Listing
January 2009