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Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression,elucidating the curative mechanism of Danzhi Xiaoyao powder

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Journal of Traditional Chinese Medical Sciences 2024年第1期11卷 3-20页

作者： Kunyu Li Leiming You Jianhua Zhen Guangrui Huang Ting Wang Yanan Cai Yunan Zhang anlong xu School of Life Sciences Bejing University of Chinese MedicineBeijing 102488China School of Life Sciences Sun Yat-Sen UniversityGuangzhou 510006Chin

Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in ***:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of *** also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis *** Connectivity Map database was retrieved to screen candidate drugs for *** on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of ***:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with *** DEGs,including hub genes,were primarily involved in immune and inflammatory response-related *** factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune *** Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and *** the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other ***:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for *** curative mechanisms of DZXY in SD are also partially elucidated.

关键词： Subthreshold depression Leukocyte mRNAbiomarker CTRA Transcription factor activity CMap Danzhi Xiaoyaopowder Networkpharmacology

Suppressing FXR promotes antiviral effects of bile acids via enhancing the interferon transcription

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3513-3527页

作者： xue Liang Kunpeng Liu Xin Jia Cuiqin Cheng Meiqi Zhang Lingdong Kong Qiqi Li Zhe Liu Min Li Junliang Li Yao Wang anlong xu School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China Guangxi Key Laboratory of Special Biomedicine School of MedicineGuangxi UniversityNanning 530004China Beijing Academy of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Beijing Research Institute of Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral ***,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical *** this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus *** deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus ***,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through *** IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA *** FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus ***,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon *** FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

关键词： Bile acids FXR IRF3 Interferon transcription RNA virus Z-guggulsterone Broad-spectrum antiviral activity Synergistic inhibitory effect

Fangchinoline induces antiviral response by suppressing STING degradation

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Journal of Pharmaceutical Analysis 2024年第6期14卷 902-913页

作者： Jinyong Wang Fang Xie Xin Jia xuejiao Wang Lingdong Kong Yiying Li b xue Liang Meiqi Zhang Yuting He Wandi Feng Tong Luo Yao Wang anlong xu School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing100029China School of Life Science Beijing University of Chinese MedicineBeijing100029China Beijing Key Laboratory of Drug Target Identification and New Drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against ***,it presents a valuable therapeutic target for infectious diseases and *** observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1N1),and herpes simplex virus-1(HSV-1)in *** treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse ***,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(IFN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in ***,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral ***,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degradation,as a promising candidate for antiviral therapy.

关键词： Fangchinoline Virus Type I interferons Stimulator of interferon genes Protein degradation

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu anlong xu State Key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

The RAG key to vertebrate adaptive immunity descended directly from a bacterial ancestor

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National Science Review 2022年第8期9卷 18-21页

作者： Xin Tao Ziwen Huang Fan Chen Xinli Wang Tingting Zheng Shaochun Yuan anlong xu State Key Laboratory of Biocontrol Guangdong Key Laboratory of Pharmaceutical Functional GenesSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai)School of Life SciencesSun Yat-sen University Center for Infection and Immunity School of MedicineSun Yat-sen University Shanghai Institute of Immunology College of Basic Medical SciencesShanghai Jiao Tong University School of Medicine Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology School of Life Sciences Beijing University of Chinese Medicine

The emergence of RAG recombinase to mediate V(D)J recombination has been considered an important milestone in the evolution of adaptive immunity in jawed vertebrates. In past decades,hypotheses, including the invasion of viral or bacterial genes and the transposition of mobile elements, have been proposed to shed light on the origin and evolution of the RAG genes and V(D)J recombination.

关键词： TRANSPOSON

Functional requirement of terminal inverted repeats for efficient ProtoRAG activity reveals the early evolution of V(D)J recombination

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National Science Review 2020年第2期7卷 403-417页

作者： Xin Tao Shaochun Yuan Fan Chen Xiaoman Gao Xinli Wang Wenjuan Yu Song Liu Ziwen Huang Shangwu Chen anlong xu State Key Laboratory of Biocontrol Guangdong Key Laboratory of Pharmaceutical Functional Genes School of Life Sciences Sun Yat-sen University Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology School of Life Sciences Beijing University of Chinese Medicine

The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats(TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23 RSS and recombination mediated by Proto RAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23 RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5 TIR and 3 TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences(RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate Proto RAG-but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in Bb RAG1 L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT?domain, which facilitates the specific TIR recognition of the Bb RAGL complex, and the other is NBD?, which is responsible for DNA binding and the protein stabilization of the Bb RAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.

关键词： ProtoRAG transposon terminal inverted repeat V(D)J recombination recombination signal sequence evolution

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千金藤素抗病毒作用的免疫学机制研究

药物评价研究 2024年第6期47卷 1232-1239页

作者：王靳勇何昱廷谢芳成翠芹张美琦初英杰罗政李俊良徐安龙王遥北京中医药大学中药学院北京102488 北京中医药大学生命科学学院北京102488

目的探索千金藤素体内外的抗病毒作用,并基于抗病毒天然免疫通路探究其抗病毒作用的分子机制。方法CCK-8法检测千金藤素(0.0625~64.0000μmol·L^(-1))对A549细胞活力的影响;利用表达绿色荧光蛋白的水疱性口炎病毒(VSV-GFP)感染A549细... 详细信息

目的探索千金藤素体内外的抗病毒作用,并基于抗病毒天然免疫通路探究其抗病毒作用的分子机制。方法CCK-8法检测千金藤素(0.0625~64.0000μmol·L^(-1))对A549细胞活力的影响;利用表达绿色荧光蛋白的水疱性口炎病毒(VSV-GFP)感染A549细胞模型,结合流式细胞术检测千金藤素对病毒复制的影响并探究预处理、吸附过程及吸附后加药对VSV-GFP病毒复制的影响;实时荧光定量PCR(qRT-PCR)检测千金藤素对甲型流感病毒(H1N1)、脑心肌炎病毒(EMCV)和单纯疱疹病毒I型(HSV-1)复制的影响;构建VSV感染小鼠模型探究千金藤素的体内抗病毒作用;A549细胞中利用生物信息学方法探究其抗病毒机制;qRT-PCR检测药物处理A549和原代胚胎成纤维细胞(MEF)后IFNB1及干扰素刺激基因(ISGs)表达变化;免疫印迹法(Immunoblotting)检测人源单核细胞白血病细胞(THP-1)中TBK1和STAT1的磷酸化水平。结果与模型组相比,千金藤素在A549细胞中显著抑制VSV、H1N1、EMCV和HSV-1复制;千金藤素不影响VSV的吸附过程,而预处理或吸附后给药可以显著抑制病毒复制;千金藤素提高VSV感染小鼠的存活率;千金藤素激活基于IFN-I通路的抗病毒天然免疫应答。结论千金藤素通过激活基于IFN-I通路的抗病毒天然免疫发挥体内外抗病毒作用。

关键词：千金藤素抗病毒天然免疫 I型干扰素通路干扰素刺激基因抗病毒

The development of traditional Chinese medicine

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Journal of Traditional Chinese Medical Sciences 2021年第S01期8卷 1-9页

作者： Danning Ma Shanshan Wang Yu Shi Shenglou Ni Minke Tang anlong xu National Center for TCM International Communication Beijing University of Chinese MedicineBeijing100029China International Exchange and Cooperation Department Beijing University of Chinese MedicineBeijing100029China Periodical Center Beijing University of Chinese MedicineBeijing102488China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing102488China School of Life Sciences Beijing University of Chinese MedicineBeijing102488China

Similar to other medicines,traditional Chinese medicine(TCM)originated from the need for various practical solutions to treat *** is a knowledge system summarized and condensed by the Chinese nation in the health care practice for thousands of *** continues to serve the health care *** study summarized the history,health concept,main treatment strategies and methods,current development,and future perspectives of *** may provide a more comprehensive image of the overall TCM system.

关键词： Traditional Chinese medicine Correspondence between universe and man Image thinking History Prospect

Identification and expression of amphioxus AmphiSmad1/5/8 and AmphiSmad4

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Science China(Life Sciences) 2011年第3期54卷 220-226页

作者： YU xueSong LI JianWei LIU Hui LI XiaoDan CHEN ShangWu ZHANG HongWei xu anlong State Key Laboratory of Biocontrol Open Laboratory for Marine Functional Genomics of State High- Tech Development Program Guangdong Key Laboratory of Pharmaceutical Functional Genes College of Life Sciences Sun Yat-Sen University Guangzhou 510275 China Institute of Developmental Biology College of Life Sciences Shandong University Jinan 250100 China

Smad family proteins are identified as intracellular signal mediators of the TGF-β *** this study,we identified two novel members of the Smad family,termed as AmphiSmad1/5/8 and AmphiSmad4,from Chinese *** AmphiSmad1/5/8 and AmphiSmad4 showed a typical domain structure of Smad proteins consisting of conserved MH1 and MH2 *** analysis placed AmphiSmad1/5/8 in the Smad1,5 and 8 subgroup of the R-Smad subfamily,and AmphiSmad4 in the Co-Smad *** spatial and temporal gene expression patterns of AmphiSmad1/5/8 and AmphiSmad4 showed that they may be involved in the embryonic development of notochord,myotome and alimentary canal,and may help to establish the specification of dorsal-ventral axis of ***,AmphiSmad1/5/8 and AmphiSmad4 showed extensive distribution in all adult tissues examined,suggesting that these two genes may play important roles in the morphogenesis of a variety of tissues especially notochord and gonad.

关键词： amphioxus Smad AmphiSmad1/5/8 AmphiSmad4 expression patterns organogenesis dorsal-ventral patterning