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Sheng Jiang San, traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidaseinhibition and immune regulation

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中国药理学与毒理学杂志 2019年第9期33卷 738-739页

作者： ZHANG Tian-bo XIAO Meng-jie Chun-Kwok WONG Ka-Pun CHRIS MOK ZHAO Xin TI Hui-hui Pang-Chui SHAW State key laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina The School of Life Sciences The Chinese University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in ***,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza *** study aims to investigate the anti-influenza effect of SJS and its possible *** In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney *** virus infected BALB/c mice were employed as in vivo model to evaluate the *** challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 *** survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were *** underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of *** SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent *** IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-*** also protected 50%of mice from influenza virus PR8 *** lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated *** 2 g·L^-1 inhibited 80%of neuraminidase enzymatic *** also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced *** SJS is a useful formulation for treating influenza virus infection.

关键词： Sheng Jiang San anti-influenza activity neuraminidase inhibition immuno-regulation

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USP19 suppresses inflammation and promotes M2-like macrophage polarization by manipulating NLRP3 function via autophagy

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Cellular & molecular Immunology 2021年第10期18卷 2431-2442页

作者： Tao Liu Liqiu Wang Puping Liang Xiaojuan Wang Yukun Liu Jing Cai Yuanchu She Dan Wang Zhi Wang Zhiyong Guo Samuel Bates Xiaojun Xia Junjiu Huang Jun Cui MOE key laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen University510275GuangzhouGuangdongPeople’s Republic of China Department of Experimental Medicine State Key Laboratory of Oncology in South ChinaSun Yat-sen University510275GuangzhouPeople’s Republic of China Guanghua School of Stomatology Guangdong Provincial Key Laboratory of StomatologyStomatological HospitalSun Yat-Sen University510060GuangzhouGuangdongPeople’s Republic of China Organ Transplant Center The First Affiliated HospitalSun Yat-Sen University510080GuangzhouGuangdongPeople’s Republic of China Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical SchoolBostonMA02115USA

Macrophage polarization to proinflammatory M1-like or anti-inflammatory M2-like cells is critical to mount a host defense or repair *** exact molecular mechanisms controlling this process are still ***,we report that ubiquitin-specific protease 19(USP19)acts as an anti-inflammatory switch that inhibits inflammatory responses and promotes M2-like macrophage ***19 inhibited NLRP3 inflammasome activation by increasing autophagy flux and decreasing the generation of mitochondrial reactive oxygen *** addition,USP19 inhibited the proteasomal degradation of inflammasome-independent NLRP3 by cleaving its polyubiquitin ***19-stabilized NLRP3 promoted M2-like macrophage polarization by direct association with interferon regulatory factor 4,thereby preventing its p62-mediated selective autophagic *** with these observations,compared to wild-type mice,Usp19−/−mice had decreased M2-like macrophage polarization and increased interleukin-1βsecretion,in response to alum and chitin ***,we have uncovered an unexpected mechanism by which USP19 switches the proinflammatory function of NLRP3 into an anti-inflammatory function,and suggest that USP19 is a potential therapeutic target for inflammatory interventions.

关键词： Inflammasome Autophagy Macrophage polarization Deubiquitinating enzyme NLRP3

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Association of chromosome 7 aneuploidy measured by fluorescence in situ hybridization assay with muscular invasion in bladder cancer

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Cancer Communications 2020年第4期40卷 167-180页

作者： Xiayao Diao Jinhua Cai Junjiong Zheng Jianqiu Kong Shaoxu Wu Hao Yu Hao Huang Weibin Xie Xiong Chen Chengran Huang Lifang Huang Haide Qin Jian Huang Tianxin Lin Department of Urology Sun Yat-sen Memorial HospitalSun Yat-senUniversityGuangzhouGuangdong510120P.R.China guangdong provincial key laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong510120P.R.China Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong510120P.R.China State key laboratory of Oncology in South China GuangzhouGuangdong510120P.R.China

Background:The preoperative prediction of muscular invasion status is important for adequately treating bladder cancer(BC)but nevertheless,there are some existing dilemmas in the current preoperative diagnostic accuracy of BC with muscular ***,we investigated the potential association between the fluorescence in situ hybridization(FISH)assay and muscular invasion among patients with BC.A cytogenetic-clinical nomogram for the individualized preoperative differentiation of muscle-invasive BC(MIBC)from non-muscle-invasive BC(NMIBC)is also ***:All eligible BC patients were preoperatively tested using a FISH assay,which included 4 sites(chromosome-specific centromeric probe[CSP]3,7,and 17,and gene locus-specific probe[GLP]-p16 locus).The correlation between the FISH assay and BC muscular invasion was evaluated using the Chi-square *** the training set,univariate and multivariate logistic regression analyses were used to develop a cytogenetic-clinical nomogram for preoperative muscular invasion ***,we assessed the performance of the nomogram in the training set with respect to its discriminatory accuracy and calibration for predicting muscular invasion,and clinica usefulness,which were then validated in the validation ***,model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the individual variables incorporated in the ***:Muscular invasion was more prevalent in BC patients with positive CSP3,CSP7 and CSP17 status(OR[95%CI],2.724[1.555 to 4.774],P<0.001;3.406[1.912 to 6.068],P<0.001 and 2.483[1.436 to 4.292],P=0.001,respectively).Radiologydetermined tumor size,radiology-determined clinical tumor stage and CSP7 status were identified as independent risk factors of BC muscular invasion by the multivariate regression analysis in the training ***,a cytogenetic-clinical nomogram incorporating these three independent risk factors was constructed and was observed

关键词： chromosome aneuploidy fluorescence in situ hybridization muscular invasion nomogram preoperative prediction urinary bladder neoplasms

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targeted Genome Editing in Genes and cis- Regulatory Regions Improves Qualitative and Quantitative Traits in Crops

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molecular Plant 2017年第11期10卷 1368-1370页

作者： Xitao Li Yongyao Xie Qinlong Zhu Yao-Guang Liu State key laboratory for Conservation and Utilization of Subtropical Agro- Bioresources South China Agricultural University Guangzhou 510642 China key laboratory of Plant Functional Genomics and Biotechnology of guangdong provincial Higher Education Institutions South China Agricultural University Guangzhou 510642 China College of Life Sciences South China Agricultural University Guangzhou 510642 China

The Clustered Regularly Interspaced Short Palindromic Repeats （CRISPR）-associated protein 9 （CRISPR/Cas9）-based genomeediting system is a revolutionary technology for targeted muta- genesis in molecular biology research and genetic improvement of traits in crops （Cong et al., 2013; Ma et al., 2015, 2016）. Agronomic traits of crops are controlled by major genes and quantitative trait loci （QTL）. Therefore, the CRISPR/Cas9 system can be used to effectively and rapidly produce mutant traits by different strategies （Figure 1A-1C）. The most common application of the targeted editing system in genetic improvement is to knock out completely the functions of target genes, usually by editing site（s） in the coding sequences （CDS） to produce null-allele mutants （Figure 1A）.

关键词： targeted Genome Editing Genes and cis- Regulatory Regions Improves Qualitative Quantitative Traits in Crops

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Fabrication of multifunctional polydopamine-coated gold nanobones for PA/CT imaging and enhanced synergistic chemo-photothermal therapy

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Journal of Materials Science & Technology 2021年第4期63卷 97-105页

作者： Jingwei Xu Xiaju Cheng Fuxian Chen Weijie Li Xiaohui Xiao Puxiang Lai Guopeng Xu Li Xu Yue Pan Department of Cardiothoralic Surgery Suzhou Municipal Hospital InstitutionSuzhou 215002China Jiangsu key laboratory of Infection and Immunity Institutes of Biology and Medical SciencesSoochow UniversitySuzhou 215123China guangdong provincial key laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research CenterSun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Center for Precision Medicine Sun Yat-Sen UniversityGuangzhou 510080China The Hong Kong Polytechnic University Department of Biomedical EngineeringHong Kong SARChina Department of Respiratory Medicine Suzhou Municipal Hospital InstitutionSuzhou 215002China

Multimodal imaging-guided chemo-photothermal therapy is an excellent cancer treatment,which can not only efficiently against tumor,but also can offer precise treatment window and real-time monitoring of the treatment *** our work,polydopamine(PDA)-coated gold nanobones(AuNBs@PDA nanocomplexes)were designed for this *** AuNBs@PDA nanocomplexes have strong absorbance in the near infrared(NIR)region and higher photothermal conversion efficiency(75.48%)than gold nanobones alone,which was facilitated for photoacoustic imaging and photothermal ***,the loading efficiency of doxorubicin(DOX)by AuNBs@PDA nanocomplexes could be up to about 70%and DOX release from AuNBs@PDA/DOX nanocomplexes sensitively response to the lower pH environment and NIR laser irradiation,which makes them become the excellent nano-carrier for the delivery of chemotherapy *** vitro and in vivo studies showed significant cytotoxicity and antitumor efficacy by the AuNBs@PDA/DOX nanoplatform with negligible side ***,the nanoplatform was also successfully employed for computed tomography(CT)imaging,attributing to the high atomic number and high X-ray attenuation coefficient of ***,we believed that the proposed PDA-coated gold nanobones would be a novel multifunctional theranostic nanoagent to realize the PA/CT imaging-guided chemo-photothermal therapy of cancer.

关键词： dopamine treatment bones

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Intricacies in the cross talk between metabolic enzymes,RNA,and protein translation

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Journal of molecular Cell Biology 2019年第10期11卷 813-815页

作者： Yuan Lv Muqddas Tariq Xiangpeng Guo Shahzina Kanwal Miguel AEsteban Joint School of Life Sciences Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical UniversityGuangzhou 511436China key laboratory of Regenerative Biology and guangdong provincial key laboratory of Stem Cells and Regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China laboratory of RNA Chromatinand Human DiseaseGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China guangzhou Regenerative Medicine and Health guangdong laboratory Guangzhou 510005China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cells and Regeneration Chinese Academy of SciencesBeijing 100101China

The development of tech niq ues allowing the systematic capture of the RNA-bound proteome has yielded many *** these,metabolic enzymes have been frequently detected as RNA-binding proteins(RBPs)by different profiling methodologies in various cell types(Hentze et al.,2018).Compared to previous-more simplistic-views,it is now known that cellular metabolism(not only limited to the tricarboxylic acid,TCA,cycle)is *** fact,metabolic enzymes translocate to the nucleus and are enriched at actively transcribed loci,where they sustain epigenetic/epitranscriptomic marks through localized metabolite production(Mews et al.,2017).It has been proposed that the in teraction with nascent RNAs facilitates the anchorage of metabolic enzymes at target loci(Bao et al.,2018),and it is plausible that mature RNAs work in the same way to assist metabolic reactions in the cytoplasm.

关键词： al. metabolism metabolic

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Hypoxia signaling in human health and diseases:implications and prospects for therapeutics

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Signal Transduction and targeted Therapy 2022年第8期7卷 2787-2816页

作者： Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu guangdong provincial key laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632China Foshan Institute of Medical Microbiology Foshan 528315China The First Affiliated Hospital of Jinan University Guangzhou 510632China The Affiliated Shunde Hospital of Jinan University Foshan 528303China

molecular oxygen(O2)is essential for most biological reactions in mammalian *** the intracellular oxygen content decreases,it is called *** process of hypoxia is linked to several biological processes,including pathogenic microbe infection,metabolic adaptation,cancer,acute and chronic diseases,and other stress *** mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during ***-inducible factors(HIFs)sense hypoxia to regulate the expressions of a series of downstream genes expression,which participate in multiple processes including cell metabolism,cell growth/death,cell proliferation,glycolysis,immune response,microbe infection,tumorigenesis,and ***,hypoxia signaling also interacts with other cellular pathways,such as phosphoinositide 3-kinase(PI3K)-mammalian target of rapamycin(mTOR)signaling,nuclear factor kappa-B(NF-κB)pathway,extracellular signal-regulated kinases(ERK)signaling,and endoplasmic reticulum(ER)*** paper systematically reviews the mechanisms of hypoxia signaling activation,the control of HIF signaling,and the function of HIF signaling in human health and *** addition,the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted,which would provide novel strategies for the design and development of therapeutic drugs.

关键词： diseases metabolism drugs

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Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion

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Cellular & molecular Immunology 2023年第8期20卷 867-880页

作者： Hua Yu Tiezhu Shi Linli Yao Dongwei Xu Yufeng Ding Qiang Xia Wei Liu Xiongjun Wang Precise Genome Engineering Centre School of Life SciencesGuangzhou UniversityGuangzhou510006China State key laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteRen Ji HospitalShanghai Jiaotong University School of MedicineShanghai200240China Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China guangdong provincial key laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong510630China

To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC *** analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection *** depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell ***,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T *** phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and ***,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in ***,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.

关键词： Nuclear PIGL cMyc PD-1 antibody CCL2/20 Tumor immune evasion

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Silencing MYH9 blocks HBx-induced GSK3βubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

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Signal Transduction and targeted Therapy 2020年第1期5卷 2361-2372页

作者： Xian Lin Ai-min Li Yong-Hao Li Rong-Cheng Luo Yu-Jiao Zou Yi-Yi Liu Chen Liu Ying-Ying Xie Shi Zuo Zhan Liu Zhen Liu Wei-Yi Fang Cancer Center Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouGuangdongPeople’s Republic of China510310 Department of Hepatobiliary Surgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouPeople’s Republic of China550004 Department of Gastroenterology and Clinical Nutrition The First Affiliated Hospital(People’s Hospital of Hunan Province)Hunan Normal UniversityChangshaHunanPeople’s Republic of China410002 guangzhou municipal and guangdong provincial key laboratory of Protein Modification and Degradation State Key Laboratory of Respiratory DiseaseSchool of Basic Medical SciencesGuangzhou Medical UniversityAffiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouGuangdongPeople’s Republic of China510095 Cancer Institute School of Basic Medical ScienceSouthern Medical UniversityGuangzhouGuangdongPeople’s Republic of China510515

MYH9 has dual functions in ***,its role in inducing tumor stemness in hepatocellular carcinoma(HCC)is not yet ***,we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma ***,targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in *** analysis suggested that MYH9 interacted with GSK3βand reduced its protein expression by ubiquitin-mediated degradation,which therefore dysregulated theβ-catenin destruction complex and induced the downstream tumor stemness phenotype,epithelial–mesenchymal transition,and c-Jun signaling in HCC.C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop.X protein is a hepatitis B virus(HBV)-encoded key oncogenic protein that promotes HCC ***,we observed that HBV X protein(HBX)interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun *** MYH9 blocked HBX-induced GSK3βubiquitination to activate theβ-catenin destruction complex and suppressed cancer stemness and *** on TCGA database analysis,MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma *** clinical samples,high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma *** findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration,invasion,growth,and sorafenib resistance in HCC *** study demonstrated that MYH9 is a crucial therapeutic target in HCC.

关键词： GSK3β hepatocellular MYH9

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Arabidopsis NF-YCs Mediate the Light-Controlled Hypocotyl Elongation via Modulating Histone Acetylation

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molecular Plant 2017年第2期10卷 260-273页

作者： Yang Tang Xuncheng Liu Xu Liu Yuge Li Keqiang Wu Xingliang Hou key laboratory of South China Agricultural Plant molecular Analysis and Genetic Improvement & guangdong provincial key laboratory of Applied Botany South China Botanical Garden Chinese Academy of Sciences Guangzhou 510650 China University of the Chinese Academy of Sciences Beijing 100049 China Institute of Plant Biology College of Ufe Science National Taiwan University Taipei 106 Taiwan These authors contributed equally to this article.

Light is a crucial environmental signal that promotes photomorphogenesis, the developmental process with a series of light-dependent alterations for plants to adapt various external challenges. Chromatin modification has been proposed to be involved in such light-mediated growth, but the underlying mecha- nism is still elusive. In this study, we identified four Arabidopsis thaliana Nuclear Factor-YC homologs, NF- YCl, NF-YC3, NF-YC4, and NF-YC9 （NF-YCs）, which function redundantly as repressors of light-controlled hypocotyl elongation via histone deacetylation. Obvious etiolation phenotypes are observed in NF-YCs loss-of-function mutant seedlings grown under light conditions, including significant elongated hypocotyls and fewer opened cotyledons. We found that NF-YCs interact with histone deacetylase HDA15 in the light, co-target the promoters of a set of hypocotyl elongation-related genes, and modulate the levels of histone H4 acetylation on the associated chromatins, thus repressing gene expression. In contrast, NF-YC-HDA15 complex is dismissed from the target genes in the dark, resulting in increased level of H4 acetylation and consequent etiolated growth. Further analyses revealed that transcriptional repression activity of NF-YCs on the light-controlled hypocotyl elongation partially depends on the deacetylation activity of HDA15, and loss of HDA15 function could rescue the short-hypocotyl phenotype of NF-YCs overexpression plants. Taken together, our results indicate that NF-YCl, NF-YC3, NF-YC4, and NF-YC9 function as tran- scriptional co-repressors by interacting with HDA15 to inhibit hypocotyl elongation in photomorphogen- esis during the early seedling stage. Our findings highlight that NF-YCs can modulate plant development in response to environmental cues via epigenetic regulation.

关键词： photomorphogenesis hypocotyl elongation NF-YC histone deactylation

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