Article
Medicine, General & Internal
Shunyi Wang, Yihe Kuai, Simin Lin, Li Li, Quliang Gu, Xiaohan Zhang, Xiaoming Li, Yajun He, Sishuo Chen, Xiaoru Xia, Zhang Ruan, Caixia Lin, Yi Ding, Qianqian Zhang, Cuiling Qi, Jiangchao Li, Xiaodong He, Janak L. Pathak, Weijie Zhou, Side Liu, Lijing Wang, Lingyun Zheng
Summary: Act1 downregulation in macrophages promotes adenoma-adenocarcinoma transition via CXCL9/10-CXCR3-axis in CRC cells and PD-1/PD-L1-axis in CD8(+) T cells. Macrophage depletion or anti-CD8a effectively inhibits metastatic nodules formation. Anti-PD-L1 treatment represses adenoma-adenocarcinoma transition.
Article
Genetics & Heredity
Haidong Xu, Guangwei Ma, Fang Mu, Bolin Ning, Hui Li, Ning Wang
Summary: Follistatin (FST) is a secretory glycoprotein belonging to TGF-beta superfamily that plays a role in hair follicle development. This study found a conserved STAT3 binding site in the promoter region of sheep FST gene, which directly negatively regulates FST and suppresses cell proliferation. Overexpression of sheep FST promotes cell proliferation, while overexpression of sheep STAT3 has the opposite effect.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Hyun-Ji Cho, Jeong-A Hwang, Eun Jae Yang, Eok-Cheon Kim, Jae-Ryong Kim, Sung Young Kim, Young Zoon Kim, Sang Chul Park, Young-Sam Lee
Summary: In this study, it was found that Nintedanib can be used as a new senolytic agent, selectively inducing the death of senescent cells. It achieves drug-induced death by inhibiting the STAT3 pathway and reduces the number of senescent cells and collagen deposition.
CELL DEATH & DISEASE
(2022)
Article
Biology
Qilong Li, Ning Jiang, Yiwei Zhang, Yize Liu, Ziwei Su, Quan Yuan, Xiaoyu Sang, Ran Chen, Ying Feng, Qijun Chen
Summary: Dihydroartemisinin (DHA) possesses immunomodulatory properties by promoting T-reg proliferation and suppressing B cell expansion. This is achieved through the upregulation of c-Fos expression, which enhances its interaction with target genes in both T-reg and circulating plasma cells, leading to different cell fates. DHA's immunoregulatory mechanism has been elucidated and its potential for the treatment of autoimmune diseases is further justified.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Ya Li, Zhenwei Song, Qiuju Han, Huajun Zhao, Zhaoyi Pan, Zhengyang Lei, Jian Zhang
Summary: STAT3 inhibition induces immunogenic cell death (ICD) of hepatocellular carcinoma (HCC) cells and enhances immune recognition and clearance of the tumor. Furthermore, it reshapes the tumor immune microenvironment and enhances anti-tumor immune responses.
MOLECULAR ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Yi-Ping Liu, Jin-Yu Heng, Xin-Yu Zhao, En-You Li
Summary: circNOLC1 plays a crucial role in the properties and progression of breast cancer CSCs by targeting the miR-365a-3p /STAT3 axis, while propofol inhibits circNOLC1 by repressing STAT3 in a feedback mechanism.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Xuejiao Li, Huan Du, Shenghua Zhan, Wenting Liu, Zhangyu Wang, Jing Lan, Longxiang PuYang, Yuqiu Wan, Qiuxia Qu, Sining Wang, Yang Yang, Qin Wang, Fang Xie
Summary: This study found significantly elevated levels of sPD-L1 and IL-10 in breast cancer patients, positively correlated with B-cell subsets. Blocking PD-L1 can promote tumor cell apoptosis, making it a potential therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Bo Deng, Xiao-Li Jiang, Zhang-Bin Tan, Min Cai, Sui-Hui Deng, Wen-Jun Ding, You-Cai Xu, Yu-Ting Wu, Shuang-Wei Zhang, Rui-Xue Chen, Jun Kan, En-Xin Zhang, Bin Liu, Jing-Zhi Zhang
Summary: This study demonstrated that Dauricine (Dau) inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways. Molecular docking, dynamics simulations, and surface plasmon resonance imaging further supported the strong binding affinity of Dau to Src, and its effectiveness in suppressing melanoma growth in vivo.
PHYTOTHERAPY RESEARCH
(2021)
Article
Cell Biology
Mary Mohrin, Justin Liu, Jose Zavala-Solorio, Sakshi Bhargava, John Maxwell Trumble, Alyssa Brito, Dorothy Hu, Daniel Brooks, Georgios Koukos, Lama Alabdulaaly, Jonathan S. Paw, Kayley Hake, Ganesh Kolumam, Mary L. Bouxsein, Roland Baron, Yuliya Kutskova, Adam Freund
Summary: PAPP-A deficiency modulates bone marrow homeostasis by regulating the number and activity of mesenchymal stromal cells (MSCs), which are not only the major source of extracellular matrix (ECM) but also play essential roles in the development of adult bone, regulation of marrow adiposity, and formation of the hematopoietic niche. This mechanism may contribute to the extended longevity and healthspan associated with PAPP-A deletion.
Article
Oncology
Fengen Liu, Binhui Xie, Rong Ye, Yuankang Xie, Baiyin Zhong, Jinrong Zhu, Yao Tang, Zelong Lin, Huiru Tang, Ziqing Wu, Heping Li
Summary: In this study, it was found that overexpression of TRIM47 is associated with tumor progression and poor prognosis in triple-negative breast cancer. The researchers demonstrated that TRIM47 directly interacts with BRCA1 and induces proteasome turnover of BRCA1, leading to a decrease in BRCA1 protein levels in TNBC. Additionally, TRIM47 overexpression confers sensitivity to the PARP inhibitor olaparib, while TRIM47 inhibition confers resistance to olaparib in TNBC. Overexpression of BRCA1 also increases resistance to olaparib in TRIM47-overexpression-induced PARP inhibition sensitivity. These findings suggest that targeting the TRIM47/BRCA1 axis may be a promising prognostic factor and therapeutic target for TNBC.
Article
Biochemistry & Molecular Biology
Woong Sub Byun, Eun Seo Bae, Jinsheng Cui, Hyen Joo Park, Dong-Chan Oh, Sang Kook Lee
Summary: Pulvomycin effectively inhibits cell proliferation, induces cell cycle arrest and apoptosis by suppressing STAT3 activation, significantly inhibits invasion and migration of TNBC cells, and in combination with docetaxel effectively inhibits tumor growth in xenograft mouse model through STAT3 regulation.
Article
Neurosciences
Rui Liu, Ying Li, Ziyue Wang, Peng Chen, Yi Xie, Wensheng Qu, Minghuan Wang, Zhiyuan Yu, Xiang Luo
Summary: After spinal cord injury (SCI), immune cells and proinflammatory cytokines infiltrate the spinal cord and disrupt the microenvironment, hindering axon regeneration and functional recovery. Previous studies have shown that regulatory T cells (Tregs) can enter the central nervous system and suppress microglia during conditions like multiple sclerosis and stroke. However, the interaction between Tregs and microglia and their role in modulating the injured microenvironment after SCI remains unknown.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Oncology
Ying Bai, Xuye Wang, Mengsi Cai, Chunbo Ma, Youqun Xiang, Wanle Hu, Bin Zhou, Chengguang Zhao, Xuanxuan Dai, Xiaokun Li, Haiyang Zhao
Summary: Cinobufagin, a natural product extracted from toad venom, exhibits high antitumor activity by inhibiting proliferation, migration, invasion, and promoting apoptosis of colorectal cancer cells in vitro and in vivo. The underlying mechanism involves suppression of the STAT3 pathway, leading to inhibition of epithelial-mesenchymal transition.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Plant Sciences
Mei-Yu Shen, Yu-Xi Di, Xiang Wang, Feng-Xiang Tian, Ming-Fei Zhang, Fei-Ya Qian, Bao-Ping Jiang, Xue-Ping Zhou, Ling-Ling Zhou
Summary: This study investigated the mechanisms of Panax notoginseng saponins (PNS) on Th17 cell differentiation in rheumatoid arthritis (RA) and the role of pyruvate kinase M2 (PKM2). PNS suppressed Th17 cell differentiation by inhibiting nuclear PKM2-mediated STAT3 phosphorylation. The results suggest that PNS may be beneficial for the treatment of RA.
PHARMACEUTICAL BIOLOGY
(2023)
Article
Oncology
Young-Il Hahn, Soma Saeidi, Su-Jung Kim, Se-Young Park, Na-Young Song, Jie Zheng, Do-Hee Kim, Han-Byoel Lee, Wonshik Han, Dong-Young Noh, Hye-Kyung Na, Young-Joon Surh
Summary: STAT3 and NF-kappa B are critical transcription factors in inflammation-associated tumorigenesis, working together at multiple levels. Breast carcinomas have a significant dependency on both classical and non-classical NF-kappa B pathways. STAT3 stabilizes and activates IKK alpha, leading to NF-kappa B activation and promoting breast cancer growth and progression.
Article
Cell Biology
Huazhi Zhang, Zhihui Cui, Du Cheng, Yanyun Du, Xiaoli Guo, Ru Gao, Jianwen Chen, Wanwei Sun, Ruirui He, Xiaojian Ma, Qianwen Peng, Bradley N. Martin, Wei Yan, Yueguang Rong, Chenhui Wang
Summary: The gene RNF186 has been identified in genome-wide association studies as a susceptibility gene for ulcerative colitis, and it plays a crucial role in autophagy activation in colonic epithelial cells and intestinal homeostasis by regulating the ubiquitination of EPHB2. The absence of RNF186 and EPHB2 leads to a more severe phenotype in a colitis model, while treatment with ephrin-B1-Fc recombinant protein shows promise as a potential therapy for inflammatory bowel diseases.
Article
Immunology
Ruirui He, Songfang Wu, Ru Gao, Jianwen Chen, Qianwen Peng, Huijun Hu, Liwen Zhu, Yanyun Du, Wanwei Sun, Xiaojian Ma, Huazhi Zhang, Zhihui Cui, Heping Wang, Bradley N. Martin, Yueying Wang, Cun-Jin Zhang, Chenhui Wang
Summary: The study showed that TRAF3IP2-AS1 regulates IL-17A signaling by recruiting SRSF10, indicating a therapeutic potential for IL-17-related autoimmune diseases.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Xiaojian Ma, Xi Tan, Bingbing Yu, Wanwei Sun, Heping Wang, Huijun Hu, Yanyun Du, Ruirui He, Ru Gao, Qianwen Peng, Zhihui Cui, Ting Pan, Xiong Feng, Junhan Wang, Chengqi Xu, Bin Zhu, Wei Liu, Chenhui Wang
Summary: Fungal infections cause millions of deaths each year and the mortality rate of disseminated candidiasis exceeds that of breast cancer and malaria. This study reveals the critical role of DOCK2 in promoting antifungal immune response and inflammation. DOCK2-deficient macrophages show reduced ability to kill intracellular fungi and activate downstream signaling pathways. Furthermore, nanoparticle-mediated delivery of IVT Rac1 mRNA enhances Rac1 activity and helps eliminate fungal infections in vivo.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yanyun Du, Qianwen Peng, Du Cheng, Ting Pan, Wanwei Sun, Heping Wang, Xiaojian Ma, Ruirui He, Huazhi Zhang, Zhihui Cui, Xiong Feng, Zhiqiang Liu, Tianxin Zhao, Wenjun Hu, Lei Shen, Wenyang Jiang, Na Gao, Bradley N. Martin, Cun-Jin Zhang, Zhanguo Zhang, Chenhui Wang
Summary: This study reveals that BTNL2 is a potent suppressor of anti-tumor immune response. Blockade of BTNL2 attenuates tumor progression and prolongs survival in tumor-bearing mice. BTNL2 interacts with γ δ T cell populations to promote IL-17A production, leading to a dysfunctional tumor immune microenvironment. High BTNL2 expression is associated with tumor types and negatively correlates with patient survival.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Xing Chen, Junjie Zhao, Tomasz Herjan, Lingzi Hong, Yun Liao, Caini Liu, Kommireddy Vasu, Han Wang, Austin Thompson, Paul L. Fox, Brian R. Gastman, Xiao Li, Xiaoxia Li
Summary: This study uncovers a novel mechanism in which IL-17 signaling activates a collagen deposition program mediated by HIF1 alpha, leading to immune exclusion. The deletion of IL-17 signaling promotes the infiltration of immune cells into the tumor mass and sensitizes resistant tumors to anti-PD-L1 treatment. This finding provides new insights for cancer therapy.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Quanri Zhang, Weiwei Liu, Han Wang, Hao Zhou, Katarzyna Bulek, Xing Chen, Cun-Jin Zhang, Junjie Zhao, Renliang Zhang, Caini Liu, Zizhen Kang, Robert A. Bermel, George Dubyak, Derek W. Abbott, Tsan Sam Xiao, Laura E. Nagy, Xiaoxia Li
Summary: The C-type lectin receptor Mincle plays a crucial role in promoting central nervous system inflammation by sensing danger signals on TH17 cells.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Weiwei Liu, Hao Zhou, Han Wang, Quanri Zhang, Renliang Zhang, Belinda Willard, Caini Liu, Zizhen Kang, Xiao Li, Xiaoxia Li
Summary: The Toll-like receptors/Interleukin-1 receptor signaling pathway has been found to play an important role in adipose tissue dysfunction and obesity-associated metabolic syndromes caused by high-fat diet. In this study, the authors discovered an unconventional IL-1R-IRAKM-Slc25a1 signaling axis in adipocytes that promotes diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduced weight gain, increased energy expenditure, improved insulin resistance, and decreased lipid accumulation and adipocyte cell sizes. The authors also found that IL-1 beta stimulation induced the translocation of IRAKM Myddosome to mitochondria, promoting de novo lipogenesis in adipocytes. Moreover, the IRAKM-Slc25a1 axis mediated IL-1 beta induced Pgc1a acetylation to regulate thermogenic gene expression in adipocytes. The inactivation of IRAKM kinase also attenuated high-fat diet-induced obesity. These findings highlight the tight connection between inflammation and adipocyte metabolism and suggest a potential therapeutic target for obesity.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Lishu Chen, Chao Zhou, Qi Chen, Jingzhe Shang, Zhaodan Liu, Yan Guo, Chunfeng Li, HongJiang Wang, Qing Ye, XiaoFeng Li, Shulong Zu, Fangye Li, Qing Xia, Tao Zhou, Ailing Li, Chenhui Wang, Yun Chen, Aiping Wu, Chengfeng Qin, Jianghong Man
Summary: Zika virus treatment can enhance immune cell infiltration and activation in glioblastoma and inhibit tumor growth. Additionally, Zika virus can activate the interferon signaling pathway in glioblastoma cells. This therapy can improve the sensitivity of glioblastoma to immune checkpoint blockade.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biochemistry & Molecular Biology
Yun Liao, Xing Chen, William Miller-Little, Han Wang, Belinda Willard, Katarzyna Bulek, Junjie Zhao, Xiaoxia Li
Summary: This study reveals that IQGAP1 acts as an adaptor to promote the biogenesis of exosomes containing GSDMD and IL-1 beta after inflammasome activation. This process is dependent on the activation of CDC42 induced by LPS.
Article
Biochemistry & Molecular Biology
Qianwen Peng, Ting Pan, Ruirui He, Ming Yi, Lingyun Feng, Zhihui Cui, Ru Gao, Heping Wang, Xiong Feng, Hui Li, Yuan Wang, Cun-jin Zhang, Du Cheng, Yanyun Du, Chenhui Wang
Summary: This study reveals that BTNL2 is necessary for colorectal IL-22 production and its knockout leads to decreased colonic tumorigenesis and more severe colitis phenotypes. BTNL2 acts on ILC3s, CD4(+) T cells, and gamma delta T cells to promote IL-22 production. Importantly, a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and mBTNL2-Fc recombinant protein shows therapeutic effect in a colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system, but also provides a potential therapeutic target for human colorectal cancer and inflammatory bowel diseases.
Article
Microbiology
Ruirui He, Jianwen Chen, Ziyan Zhao, Changping Shi, Yanyun Du, Ming Yi, Lingyun Feng, Qianwen Peng, Zhihui Cui, Ru Gao, Heping Wang, Yi Huang, Zhi Liu, Chenhui Wang
Summary: Recent research has found that common variants of the T-cell activation Rho GTPase-activating protein (TAGAP) are associated with susceptibility to inflammatory bowel diseases (IBDs) in humans, but the underlying mechanisms are still unclear. This study showed that TAGAP deficiency or downregulation of TAGAP expression caused by TAGAP gene polymorphism leads to decreased production of antimicrobial peptides (AMPs), such as reg3g, which in turn disrupts the gut microbiota, including Akkermansia muciniphila and Bacteroides acidifaciens strains. These strains can polarize T helper cell differentiation in the gut and exacerbate the phenotype of dextran sodium sulfate-induced disease in mice. Importantly, the study demonstrated that recombinant reg3g protein or anti-p40 monoclonal antibody had therapeutic effects in the treatment of dextran sodium sulfate-induced colitis, suggesting their potential as medicines for human IBD treatment, especially for patients carrying the common variant of TAGAP rs212388.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Quanri Zhang, Weiwei Liu, Katarzyna Bulek, Han Wang, Megan R. McMullen, Xiaoqin Wu, Nicole Welch, Renliang Zhang, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E. Nagy, Xiaoxia Li
Summary: This study investigated the association between the endogenous Mincle ligand beta-glucosylceramide (beta-GluCer) and the severity of alcohol-associated liver disease (ALD). The results showed that beta-GluCer concentrations were increased in the serum of patients with severe AH and correlated with disease severity. The study also revealed that beta-GluCer activates Mincle-dependent gasdermin D-mediated formation and release of IL-1 beta-containing extracellular vesicles (sEVs), which contribute to hepatocyte cell death and the pathogenesis of ALD.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Immunology
Runjing Cao, Zihao Li, Chuyu Wu, Senlin Ji, Yahui Li, Xiang Cao, Xiaohong Dong, Meiling Jiang, Tao Pang, Chenhui Wang, Jingwei Li, Yun Xu, Cun-Jin Zhang
Summary: Pyroptosis is a key inflammatory form of cell death that plays an important role in the progression of many inflammatory diseases. In this study, we conducted a screening of compounds based on in silico docking and found that C202-2729 could significantly attenuate the severity of experimental autoimmune encephalomyelitis (EAE) and showed comparable effects to the clinical drug teriflunomide. Furthermore, we found that C202-2729 did not affect GSDMD cleavage, upstream inflammasome activation, pore formation, and mature IL-1b release in mouse macrophages. These findings suggest that C202-2729 may have potential for translational application in GSDMD-associated inflammatory diseases.
JOURNAL OF IMMUNOLOGY
(2022)