Publications by authors named "Yunshu Su"

10 Publications

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Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells.

Int Immunopharmacol 2022 Jan 10;104:108521. Epub 2022 Jan 10.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

CD4+T cell-mediated acute rejection remains a major factor that affects the early survival of transplanted organs post-transplantation. Here, we reveal that nuclear receptor subfamily 4 Group A member 1 (Nr4A1) was upregulated during cardiac allograft rejection and that the increased Nr4A1 was primarily localized in intragraft-infiltrating CD4+T cells. Nr4A1 acts as a transcription factor with an important role in CD4+T cell apoptosis, differentiation and T cell dysfunction, which indicates that Nr4A1 may play a critical role in transplant rejection. Cytosporone B (Csn-B) is a naturally occurring agonist of Nr4A1, and the role of Csn-B in the physiological process of cardiac rejection is poorly defined. This study constructed an acute rejection model of abdominal heterotopic cardiac transplantation in mice and investigated whether Csn-B could attenuate acute transplant rejection by modulating the CD4+T lymphocyte response. The results showed that Csn-B prolonged murine cardiac allograft survival and reduced inflammation in allografts. Subsequently, it was confirmed that Csn-B functions by inducing non-Treg apoptosis and promoting Treg cell differentiation. Finally, we also confirmed that Csn-B attenuates acute rejection by directly targeting Nr4A1 in CD4+T cells. Our data suggest that Csn-B is a promising novel therapeutic approach for acute cardiac allograft rejection.
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http://dx.doi.org/10.1016/j.intimp.2022.108521DOI Listing
January 2022

The impacts of ubiquilin 1 (UBQLN1) knockdown on cells viability, proliferation, and apoptosis are mediated by p53 in A549 lung cancer cells.

J Thorac Dis 2020 Oct;12(10):5887-5895

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Little is known about the relationship between ubiquilin 1 (UBQLN1) and p53, both of them have been implicated in the development and progression of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the role of loss of UBQLN1 in cell viability and proliferation, and cell apoptosis in human lung adenocarcinoma A549 cells.

Methods: Cell viability, proliferation, and apoptosis were determined by MTT, BrdU, and TUNEL assays, respectively. Adenoviruses carrying cDNA or siRNA were used to overexpress or silence target protein. Dihydroethidium (DHE) staining was performed to measure the real-time formation of intracellular reactive oxygen species (ROS). The chymotrypsin-like activity of 20S proteasome core was determined by using synthetic fluorogenic peptide substrate.

Results: UBQLN1 silencing led to a reduction of p53 protein levels and overexpression of p53 reversed the effects of UBQLN1 knockdown (KD) on cell viability, proliferation, and apoptosis. Furthermore, deficiency of UBQLN1 activated autophagy activity but did not affect proteasome activity. Inhibition of autophagy restored p53 protein levels in UBQLN1-KD A549 cells. In addition, UBQLN1 KD markedly inhibited phosphorylation of mammalian target of rapamycin (mTOR) and its downstream ribosomal S6 kinase (S6K).

Conclusions: Our experiments suggested that the regulation of UBQLN1 on cell viability, proliferation, and apoptosis was mediated by mTOR/autophagy/p53 signaling pathway.
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http://dx.doi.org/10.21037/jtd-20-1362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656338PMC
October 2020

mA RNA Methylation Regulators Contribute to Malignant Progression and Have Clinical Prognostic Impact in Gastric Cancer.

Front Oncol 2019 18;9:1038. Epub 2019 Oct 18.

Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China.

N6-methyladenosine (mA) is the most common form of mRNA modification, and is dynamically regulated by the mA RNA methylation regulators. However, little is known about mA in gastric cancer. The aim of this work is to investigate the effects of mA RNA methylation regulators in gastric cancer. Here, we found that most of the 13 main mA RNA methylation regulators are higher expressed in 375 patients with gastric cancer. We identified two subgroups of gastric cancer (cluster1 and 2) by applying consensus clustering to mA RNA methylation regulators. Compared with the cluster1 subgroup, the cluster2 subgroup correlates with a poorer prognosis, and most of the 13 main mA RNA methylation regulators are higher expressed in cluster2. Moreover, the cancer-specific pathways are also significantly enriched in the cluster2 subgroup. This finding indicates that mA RNA methylation regulators are closely associated with gastric cancer. Based on this finding, we derived a risk signature, using 3 mA RNA methylation regulators (FTO, RBM15, ALKBH5), that is not only an independent prognostic marker but can also predict the clinicopathological features of gastric cancer. Moreover, FTO is higher expressed in high risk scores subtype in gastric cancer. Thus, this first finding provide us clues to understand epigenetic modification of RNA in gastric cancer.
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http://dx.doi.org/10.3389/fonc.2019.01038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813557PMC
October 2019

Transapical septal myectomy in the beating heart via a minimally invasive approach: a feasibility study in swine.

Interact Cardiovasc Thorac Surg 2020 02;30(2):303-311

Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: The aim of this study was to establish an original transapical septal myectomy procedure that can be performed in the beating heart via a minimally invasive approach for the treatment of hypertrophic obstructive cardiomyopathy.

Methods: We designed an original intracardiac septum resection device to conduct off-pump septal myectomy in swine. A subxiphoid minithoracotomy was performed to access the apex of the heart. This resection device was inserted into the left ventricular outflow tract of the heart via the apex. The basal anteroseptal myocardium beneath the right aortic cusp was identified using a combination of transoesophageal and transthoracic echocardiography and then resected and collected by the device.

Results: Six consecutive operations were successfully and accurately performed using the custom-made device under echocardiographic guidance. All pigs survived and appeared to be normal until planned euthanasia 1 week after operation. A 300-700 mg portion of the septal myocardium was resected from the normal swine heart. Echocardiography and electrocardiogram revealed no abnormalities after resection. One exception was the fifth pig, in which mild annular regurgitation of the aortic valve occurred after repetitive resection. Postmortem necropsy demonstrated that all resections were correctly located at the basal anteroseptal septum beneath the right aortic cusp.

Conclusions: Our study provides the first proof-of-concept evidence for a novel beating heart transapical septal myectomy procedure, which showed promising translational potential for the treatment of hypertrophic obstructive cardiomyopathy. This procedure would probably reduce operative risks and improve outcomes and reduce the demanding expertise required to perform conventional surgical myectomy.
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http://dx.doi.org/10.1093/icvts/ivz249DOI Listing
February 2020

Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-κB and MAPK signaling in in vitro and in vivo models.

Int Immunopharmacol 2019 Aug 23;73:321-332. Epub 2019 May 23.

Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address:

The aim of the present study is to explore the anti-inflammatory mechanism of lirioresinol B dimethyl ether via inhibition of multiple signaling pathways in both in vitro and in vivo pharmacological models. To determine the anti-inflammatory activity of the lirioresinol B dimethyl ether, RAW 264.7 macrophages challenged with lipopolysaccharide (LPS) were treated with various concentrations of lirioresinol B dimethyl ether (5, 15, 25, and 50 μM). The results indicated that pretreatment with lirioresinol B dimethyl ether significantly suppressed nuclear factor kappa B (NF-κB) activation, nitric oxide (NO) production, the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Lirioresinol B dimethyl ether inhibited LPS-induced activation of production of pro-inflammatory cytokines as well as prostaglandin E (PGE) release. The results obtained by electrophoretic mobility shift assay (EMSA) demonstrated a concentration dependent reduction of the LPS-stimulated activation of NF-κB and activator protein-1 (AP-1) by lirioresinol B dimethyl ether in in vitro and in vivo models. Moreover, lirioresinol B dimethyl ether also reduced the expression of toll-like receptor (TLR)-4 protein and myeloid differentiation primary response gene 88 (MyD88) as well as promoted the degradation of IκBα. Lirioresinol B dimethyl ether also significantly down-regulated the phosphorylation of Jun N-terminal kinase (JNK), p-38 and extracellular signal-regulated kinase (ERK). Furthermore, the results of acute and chronic inflammation demonstrated that lirioresinol B dimethyl ether (10 and 50 mg per kg) reduced paw edema and mechanical hyperalgesia in carrageenan- and Complete Freund's Adjuvant (CFA)-induced in vivo mouse models, respectively. Hence, the current results indicate that lirioresinol B dimethyl ether either act by inhibiting pro-inflammatory mediators through down-regulation of mitogen activated protein kinases (MAPKs) signaling pathways and reduction of NF-κB activation.
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http://dx.doi.org/10.1016/j.intimp.2019.05.020DOI Listing
August 2019

Melatonin protects circulatory death heart from ischemia/reperfusion injury via the JAK2/STAT3 signalling pathway.

Life Sci 2019 Jul 24;228:35-46. Epub 2019 Apr 24.

Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Aims: The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion.

Main Methods: Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3.

Key Findings: Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490.

Significance: Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.
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http://dx.doi.org/10.1016/j.lfs.2019.04.057DOI Listing
July 2019

Trop2 Guarantees Cardioprotective Effects of Cortical Bone-Derived Stem Cells on Myocardial Ischemia/Reperfusion Injury.

Cell Transplant 2018 08 16;27(8):1256-1268. Epub 2018 Jul 16.

1 Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Stem cell transplantation represents a promising therapeutic approach for myocardial ischemia/reperfusion (I/R) injury, where cortical bone-derived stem cells (CBSCs) stand out and hold superior cardioprotective effects on myocardial infarction than other types of stem cells. However, the molecular mechanism underlying CBSCs function on myocardial I/R injury is poorly understood. In a previous study, we reported that Trop2 (trophoblast cell-surface antigen 2) is expressed exclusively on the CBSCs membrane, and is involved in regulation of proliferation and differentiation of CBSCs. In this study, we found that the Trop2 is essential for the ameliorative effects of CBSCs on myocardial I/R-induced heart damage via promoting angiogenesis and inhibiting cardiomyocytes apoptosis in a paracrine manner. Trop2 is required for the colonization of CBSCs in recipient hearts. When Trop2 was knocked out, CBSCs largely lost their functions in lowering myocardial infarction size, improving heart function, enhancing capillary density, and suppressing myocardial cell death. Mechanistically, activating the AKT/GSK3β/β-Catenin signaling axis contributes to the essential role of Trop2 in CBSCs-rendered cardioprotective effects on myocardial I/R injury. In conclusion, maintaining the expression and/or activation of Trop2 in CBSCs might be a promising strategy for treating myocardial infarction, I/R injury, and other related heart diseases.
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http://dx.doi.org/10.1177/0963689718786882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434467PMC
August 2018

The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.

Drug Des Devel Ther 2015 1;9:5439-45. Epub 2015 Oct 1.

Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.
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http://dx.doi.org/10.2147/DDDT.S89861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598219PMC
July 2016

MicroRNA-152 targets ADAM17 to suppress NSCLC progression.

FEBS Lett 2014 May 26;588(10):1983-8. Epub 2014 Apr 26.

Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been suggested to play an essential role in tumorigenesis. In this study, we show that miR-152 is significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines. Restoration of miR-152 significantly reduces proliferation, colony formation, migration and invasion of NSCLC cells. In addition, ADAM metallopeptidase domain 17 (ADAM17) is identified as a target of miR-152 in NSCLC cells, and miR-152-induced suppression of cell proliferation, colony formation, migration and invasion is partially mediated by silencing of ADAM17 expression. Furthermore, ADAM17 inversely correlates with miR-152 in NSCLC tissues. Collectively, our findings indicate that miR-152 acts as tumor suppressor in NSCLC partially via targeting ADAM17.
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http://dx.doi.org/10.1016/j.febslet.2014.04.022DOI Listing
May 2014

Targeting PKCε by miR-143 regulates cell apoptosis in lung cancer.

FEBS Lett 2013 Nov 23;587(22):3661-7. Epub 2013 Sep 23.

Department of Throracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Non-small cell lung cancer (NSCLC) is one of the most common causes for lung cancer and cancer-related death. The imbalance between cell proliferation and apoptosis was suggested to play an important role in cancer pathogenesis and PKCε is one of the widely recognized targets. Here, we demonstrate that miR-143 is aberrantly downregulated in NSCLC tissue and negatively correlates with expression of PKCε. We show that miR-143 specifically targets the 3'-UTR of PKCε and regulates its expression. Treatment with miR-143 inhibitor mimics cell proliferation and apoptosis imbalance in NSCLC, while inhibition of PKCε can reverse it. Our findings suggest that targeting PKCε overexpression in NSCLC should be beneficial for lung cancer therapy.
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http://dx.doi.org/10.1016/j.febslet.2013.09.018DOI Listing
November 2013
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