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Shao-Cong Sun

Xiangbo Meng, Xiwei Liu, Xingdong Guo, Shutan Jiang, Tingting Chen, Zhiqiang Hu, Haifeng Liu, Yibing Bai, Manman Xue, Ronggui Hu, Shao-Cong Sun, Xiaolong Liu, Penghui Zhou, Xiaowu Huang, Lai Wei, Wei Yang, Chenqi Xu
Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4 . The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells...
November 28, 2018: Nature
Jing Tian, Jinhui Shao, Cong Liu, Hsin-Yu Hou, Chih-Wei Chou, Mohammad Shboul, Guo-Qing Li, Mohammad El-Khateeb, Omar Q Samarah, Yao Kou, Yu-Hsuan Chen, Mei-Jen Chen, Zhaojie Lyu, Wei-Leng Chen, Yu-Fu Chen, Yong-Hua Sun, Yi-Wen Liu
Low-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. Why different LRP4 mutation alleles cause distinct and even contrasting disease phenotypes remain unclear. Herein, we utilized the zebrafish model to search for pathways affected by a deficiency of LRP4. The lrp4 knockdown in zebrafish embryos exhibits cyst formations at fin structures and the caudal vein plexus, malformed pectoral fins, defective bone formation and compromised kidney morphogenesis; which partially phenocopied the human LRP4 mutations and were reminiscent of phenotypes resulting form a perturbed Notch signaling pathway...
October 16, 2018: Cellular and Molecular Life Sciences: CMLS
Yu-Shui Ma, Fei Yu, Xiao-Ming Zhong, Gai-Xia Lu, Xian-Ling Cong, Shao-Bo Xue, Wen-Ting Xie, Li-Kun Hou, Li-Juan Pang, Wei Wu, Wei Zhang, Le-Le Cong, Tie Liu, Hui-Deng Long, Ran Sun, Hong-Yan Sun, Zhong-Wei Lv, Chun-Yan Wu, Da Fu
Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS)...
September 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Zuliang Jie, Jin-Young Yang, Meidi Gu, Hui Wang, Xiaoping Xie, Yanchuan Li, Ting Liu, Lele Zhu, Jianhong Shi, Lingyun Zhang, Xiaofei Zhou, Donghyun Joo, Hans D Brightbill, Yingzi Cong, Daniel Lin, Xuhong Cheng, Shao-Cong Sun
Dendritic cells (DCs) play an integral role in regulating mucosal immunity and homeostasis, but the signaling network mediating this function of DCs is poorly defined. We identified the noncanonical NF-κB-inducing kinase (NIK) as a crucial mediator of mucosal DC function. DC-specific NIK deletion impaired intestinal immunoglobulin A (IgA) secretion and microbiota homeostasis, rendering mice sensitive to an intestinal pathogen, Citrobacter rodentium. DC-specific NIK was required for expression of the IgA transporter polymeric immunoglobulin receptor (pIgR) in intestinal epithelial cells, which in turn relied on the cytokine IL-17 produced by TH 17 cells and innate lymphoid cells (ILCs)...
November 2018: Nature Immunology
Huanle Luo, Evandro R Winkelmann, Shuang Zhu, Wenjuan Ru, Elizabeth Mays, Jesus A Silvas, Lauren L Vollmer, Junling Gao, Bi-Hung Peng, Nathen E Bopp, Courtney Cromer, Chao Shan, Guorui Xie, Guangyu Li, Robert Tesh, Vsevolod L Popov, Pei-Yong Shi, Shao-Cong Sun, Ping Wu, Robyn S Klein, Shao-Jun Tang, Wenbo Zhang, Patricia V Aguilar, Tian Wang
The E3 ubiquitin ligase Pellino 1 (Peli1) is a microglia-specific mediator of autoimmune encephalomyelitis. Its role in neurotropic flavivirus infection is largely unknown. Here, we report that mice deficient in Peli1 (Peli1-/-) were more resistant to lethal West Nile virus (WNV) infection and exhibited reduced viral loads in tissues and attenuated brain inflammation. Peli1 mediates chemokine and proinflammatory cytokine production in microglia and promotes T cell and macrophage infiltration into the CNS. Unexpectedly, Peli1 was required for WNV entry and replication in mouse macrophages and mouse and human neurons and microglia...
November 1, 2018: Journal of Clinical Investigation
Jing Zhu, Yu-Ling Jia, Yong-Wei Luo, Dong-Yan Huang, Cong-Cong Shao, Lei Li, Li Zhou, Zu-Yue Sun
PURPOSE: Folic acid (FA) intake has increased to high levels in many countries for the prevention of neural tube defects. However, the impact of excess FA intake, particularly before and during pregnancy, requires further investigation. Our aim was to investigate the effect of maternal folic acid supplementation on prostatitis risk in the rat offspring. METHODS: Female SD rats were administrated with different doses of FA by oral gavage from 2 weeks prior to mating to GD14: 0 mg/kg (distilled water), 0...
November 2018: International Urology and Nephrology
Jian-Hong Shi, Shao-Cong Sun
Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of structurally related proteins that transduces signals from members of TNFR superfamily and various other immune receptors. Major downstream signaling events mediated by the TRAF molecules include activation of the transcription factor nuclear factor κB (NF-κB) and the mitogen-activated protein kinases (MAPKs). In addition, some TRAF family members, particularly TRAF2 and TRAF3, serve as negative regulators of specific signaling pathways, such as the noncanonical NF-κB and proinflammatory toll-like receptor pathways...
2018: Frontiers in Immunology
Ming-Shu Mo, Gui-Hua Li, Cong-Cong Sun, Shu-Xuan Huang, Lei Wei, Li-Min Zhang, Miao-Miao Zhou, Zhuo-Hua Wu, Wen-Yuan Guo, Xin-Ling Yang, Chao-Jun Chen, Shao-Gang Qu, Jian-Xing He, Ping-Yi Xu
Background: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. Methods: In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo ...
2018: Translational Neurodegeneration
Zi-Bing Hu, Bo Wei, Shao-Ke Wu, Jie-Cong Sun, Min Xiang, Zhong-Min Zhang
Changes in bone mineral density and bone metabolic indexes in a model of ankylosing spondylitis (AS) mice complicated with osteoporosis (OP) were investigated. BLAB/c mice were used as the subjects. AS was induced using proteoglycan, and OP was induced using tail suspension method. The mice were randomly divided into four groups: AS group, OP group, AS + OP group and negative control group. Changes in bone mineral density, bone strength, serum calcium (Ca), phosphorus, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRACP), in mice of each group were detected and compared...
August 2018: Experimental and Therapeutic Medicine
Xiaoyan Yu, Xiao-Lu Teng, Feixiang Wang, Yuhan Zheng, Guojun Qu, Yan Zhou, Zhilin Hu, Zhongqiu Wu, Yuzhou Chang, Lei Chen, Hua-Bing Li, Bing Su, Liming Lu, Zhiduo Liu, Shao-Cong Sun, Qiang Zou
Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg-specific deletion of Traf3ip3 impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)-mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells...
September 3, 2018: Journal of Experimental Medicine
Xiao-Dong Yang, Shao-Cong Sun
T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs)...
August 2018: Frontiers of Medicine
Hui-Jiao Sun, Yu-Hua Wang, Cong-Min Yuan, Ling-Hui Kong, Xue-Jun Xu, Yu-Jun Wang, Hai-Hao Wu, Cheng Lin, Yuan-Yuan Qian, Huo-Ming Huang, Li Xiao, Xiao Liu, Qian He, Sheng-Yang Fang, Deng-Qi Xue, Xi-Cheng Yang, Hao Chen, Yi-Lin Zheng, Lan Zheng, Lin-Qian Yu, Qiong Xie, Wei Fu, Wei Li, Jing-Gen Liu, Zhui-Bai Qiu, Li-Ming Shao
With the purpose of identifying novel selective κ opioid receptor (KOR) antagonists as potential antidepressants from nepenthone analogues, starting from N-nor-N-cyclopropylmethyl-nepenthone (SLL-020ACP), a highly selective and potent KOR agonist, a series of 7β-methyl-nepenthone analogues was conceived, synthesized and assayed on opioid receptors based on the concept of hybridization. According to the pharmacological results, the functional reversal observed in orvinol analogues by introduction of 7β-methyl substituent could not be reproduced in nepenthone analogues...
August 7, 2018: Bioorganic & Medicinal Chemistry
Lele Zhu, Xiaoping Xie, Lingyun Zhang, Hui Wang, Zuliang Jie, Xiaofei Zhou, Jianhong Shi, Shuli Zhao, Boxiang Zhang, Xuhong Cheng, Shao-Cong Sun
The cytokine IL-15 mediates development and survival of immune cells, including natural killer T (NKT) cells, but the underlying mechanism of IL-15 function is incompletely understood. Here we show that IL-15 induces autophagy in NKT cells with a mechanism that involves a crucial signaling component, TBK-binding protein 1 (Tbkbp1). Tbkbp1 facilitates activation of the autophagy-initiating kinase Ulk1 through antagonizing the inhibitory action of mTORC1. This antagonization involves the recruitment of an mTORC1-opposing phosphatase to Ulk1...
July 18, 2018: Nature Communications
Norah A Alturki, Scott McComb, Ardeshir Ariana, Dikchha Rijal, Robert G Korneluk, Shao-Cong Sun, Emad Alnemri, Subash Sad
Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins...
May 22, 2018: Cell Death & Disease
Ji-Chang Wang, Xin Sun, Qiang Ma, Gui-Feng Fu, Long-Long Cong, Hong Zhang, De-Fu Fan, Jun Feng, Shao-Ying Lu, Jian-Lin Liu, Guang-Yue Li, Pei-Jun Liu
Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells...
May 4, 2018: Journal of Cellular and Molecular Medicine
Peijing Zhang, Zhenna Xiao, Shouyu Wang, Mutian Zhang, Yongkun Wei, Qinglei Hang, Jongchan Kim, Fan Yao, Cristian Rodriguez-Aguayo, Baochau N Ton, Minjung Lee, Yumeng Wang, Zhicheng Zhou, Liyong Zeng, Xiaoyu Hu, Sarah E Lawhon, Ashley N Siverly, Xiaohua Su, Jia Li, Xiaoping Xie, Xuhong Cheng, Liang-Chiu Liu, Hui-Wen Chang, Shu-Fen Chiang, Gabriel Lopez-Berestein, Anil K Sood, Junjie Chen, M James You, Shao-Cong Sun, Han Liang, Yun Huang, Xianbin Yang, Deqiang Sun, Yutong Sun, Mien-Chie Hung, Li Ma
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC)...
April 17, 2018: Cell Reports
Shigeru Tanaka, Christian Pfleger, Jen-Feng Lai, Florence Roan, Shao-Cong Sun, Steven F Ziegler
Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease...
April 17, 2018: Cell Reports
Yu Jiang, Ying Liu, Huiping Lu, Shao-Cong Sun, Wei Jin, Xiaohu Wang, Chen Dong
Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt...
April 12, 2018: Nature Communications
Peng Zhou, Hang Fan, Tian Lan, Xing-Lou Yang, Wei-Feng Shi, Wei Zhang, Yan Zhu, Ya-Wei Zhang, Qing-Mei Xie, Shailendra Mani, Xiao-Shuang Zheng, Bei Li, Jin-Man Li, Hua Guo, Guang-Qian Pei, Xiao-Ping An, Jun-Wei Chen, Ling Zhou, Kai-Jie Mai, Zi-Xian Wu, Di Li, Danielle E Anderson, Li-Biao Zhang, Shi-Yue Li, Zhi-Qiang Mi, Tong-Tong He, Feng Cong, Peng-Ju Guo, Ren Huang, Yun Luo, Xiang-Ling Liu, Jing Chen, Yong Huang, Qiang Sun, Xiang-Li-Lan Zhang, Yuan-Yuan Wang, Shao-Zhen Xing, Yan-Shan Chen, Yuan Sun, Juan Li, Peter Daszak, Lin-Fa Wang, Zheng-Li Shi, Yi-Gang Tong, Jing-Yun Ma
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms...
April 2018: Nature
Yu Zhang, Michelle Zoltan, Erick Riquelme, Hanwen Xu, Ismet Sahin, Susana Castro-Pando, Maria Fernanda Montiel, Kyle Chang, Zhengyu Jiang, Jianhua Ling, Sonal Gupta, William Horne, Melissa Pruski, Huamin Wang, Shao-Cong Sun, Guillermina Lozano, Paul Chiao, Anirban Maitra, Steven D Leach, Jay K Kolls, Eduardo Vilar, Timothy C Wang, Jennifer M Bailey, Florencia McAllister
BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to pancreatic interepithelial neoplasia (PanIN) initiation and progression. We investigated the effects that IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KCiMist ;G) and Kras(G12D);Trp53(R172H);Pdx1-Cre (KPC) mice (which upon tamoxifen induction spontaneously develop PanINs) and control littermates...
July 2018: Gastroenterology
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