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| 1 | Astragaloside Ⅳ suppresses post-ischemic natural killer cell infiltration and activation in the brain:involvement of histone deacetylase inhibition显示文摘Natural killer(NK)cells,a type of cytotoxic lymphocytes,can infiltrate into ischemic brain and exacerbate neuronal cell death.Astragaloside Ⅳ(ASIV)is the major bioactive ingredient of Astragalus membranaceus,a Chinese herbal medicine,and possesses potent immunomodulatory and neuroprotective properties.This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells.ASIV reduced brain infarction and alleviated functional deficits in MCAO rats,and these beneficial effects persisted for at least 7 days.Abundant NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia,and this infiltration was suppressed by ASIV.Strikingly,ASIV reversed NK cell deficiency in the spleen and blood after brain ischemia.ASIV inhibited astrocyte-derived CCL2 upregulation and reduced CCR2+NK cell levels in the ischemic brain.Meanwhile,ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γproduction.ASIV restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain,suggesting inhibition of histone deacetylase(HDAC).Simultaneously,ASIV prevented p65 nuclear translocation.The effects of ASIV on reducing CCL2 production,restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate,an HDAC inhibitor,in astrocytes subjected to oxygen-glucose deprivation.Our findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery,which together contribute to the beneficial effects of ASIV against brain ischemia.Furthermore,ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition. | Baokai Dou Shichun Li Luyao Wei Lixin Wang Shiguo Zhu Zhengtao Wang Zunji Ke Kaixian Chen Zhifei Wang | 2021 | Frontiers of Medicine2021，15，1： | 3 |
| 2 | A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1βand IL-6显示文摘Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATPcompetitive inhibitor of PGK1 with an affinity of Kd= 99.08 nmol/L. DC-PGKI stabilizes PGK1in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition,DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages.Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2(nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium(DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease. | Liping Liao Wenzhen Dang Tingting Lin Jinghua Yu Tonghai Liu Wen Li Senhao Xiao Lei Feng Jing Huang Rong Fu Jiacheng Li Liping Liu Mingchen Wang Hongru Tao Hualiang Jiang Kaixian Chen Xingxing Diao Bing Zhou Xiaoyan Shen Cheng Luo | 2022 | Acta Pharmaceutica Sinica B2022，12，11： | 2 |
| 3 | Biological screening of natural products and drug innovation in China显示文摘 | Xiaojiang Hao Kaixian Chen | 2007 | Philos Trans R Soc Lond B Biol Sci2007，，： | 1 |
| 4 | Drug target inference by mining transcriptional data using a novel graph convolutional network framework显示文摘A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or offtarget effects.Recently,the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology.Here,we propose a novel Siamese spectral-based graph convolutional network(SSGCN)model for inferring the protein targets of chemical compounds from gene transcriptional profiles.Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets,and the biological networks under different experiment conditions further complicate the situation,the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles.On a benchmark set and a large time-split validation dataset,the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map.Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound,or reversely,in finding novel inhibitors of a given target of interest. | Feisheng Zhong Xiaolong Wu Ruirui Yang Xutong Li Dingyan Wang Zunyun Fu Xiaohong Liu XiaoZhe Wan Tianbiao Yang Zisheng Fan Yinghui Zhang Xiaomin Luo Kaixian Chen Sulin Zhang Hualiang Jiang Mingyue Zheng | 2022 | Protein & Cell2022，13，4： | 1 |
| 5 | Heat exposure promotes apoptosis and pyroptosis in Sertoli cells显示文摘Heat stress is an important influence on the male reproductive organs.Therefore,the effects of heat stress on genes or pathways related to the reproductive system of male mice were experimentally explored in this paper to further determine the effects of heat stimulation on mammals.Herein,models of heat-exposed mouse testicular tissue and heatexcited cells were successfully established.Many scorched vesicles were found after heat excitation of testis supporting cells,testicular mesenchymal(TM4)cells.Western blot,in situ terminal deoxynucleotide transferase dUTP Nick end labeling(TUNEL)and transmission electron microscopy showed that membrane rupture,mitochondrial damage and autophagic vesicles occurred in TM4 cells after thermal excitation.The N-segment fragment of the associated protein shear was increased,and the TUNEL result was positive.In conclusion,thermal excitation induced apoptosis and scorch death in TM4 cells.Thus,the Hippo pathway and apoptosis-related pathway were significantly enriched after heat stimulation in mouse testis,and the scorch death effect in TM4 cells was induced by heat excitation. | CHEN WANG CHAOFAN HE YUANYUAN GAO KAIXIAN WANG MENG LIANG | 2023 | BIOCELL2023，47，1： | 0 |
| 6 | Discovery of CECR2 Bromodomain Inhibitors with High Selectivities over BPTF Bromodomain显示文摘Cat's eye syndrome chromosome candidate 2 bromodomain(CECR2 BRD)and Bromodomain PHD transcription factor bromodomain(BPTF BRD)are the same subfamily proteins,both of which are highly conserved in sequence and binding pockets.Challenges remain in the development of small molecules to inhibit one of the two bromodomains(BRDs),in view of each subtype may possess unique physiological and pathological functions.There is still a lack of effective selective inhibitors of CECR2 BRD,which makes it difficult to fully understand the pathogenesis of CECR2-BRD in diseases,especially cancers.Herein,we report our efforts to discover a series of highly selective CECR2 BRD inhibitors over BPTF BRD based on TP-248.Structure-based molecular optimization led to the discovery of DC-CEi-26,whose IC_(50) for CECR2 BRD was 96.7±14.9 nmol/L and selectivity was up to 590×over BPTF BRD.DC-CEi-26 showed weak potencies for other classic BRDs in different subfamily,which may serve as a chemical probe for CECR2 BRD biological research. | Haibo Lu Shijia Zu Zhe Duan Yueyao Feng Jie Wang Jingyi Ma Qi Li Dongying Chen Bo Li Kaixian Chen Cheng Luo Jin Lin Tian Lu Hua Lin | 2022 | Chinese Journal of Chemistry2022，40，17： | 0 |
| 7 | αExtractor: a system for automatic extraction of chemical information from biomedical literature显示文摘Dear Editor,Great progress has been made using artificial intelligence(AI) techniques in learning knowledge from biomedical databases in recent years, revolutionizing the study of many fields, such as protein structure prediction and protein design(Madani et al., 2023). However, there is massive biomedical knowledge not curated in the form of structured data but hidden in primary scientific literature. | Jiacheng Xiong Xiaohong Liu Zhaojun Li Hongzhong Xiao Guangchao Wang Zhenjiang Niu Chaoyuan Fei Feisheng Zhong Gang Wang Wei Zhang Zunyun Fu Zhiguo Liu Kaixian Chen Hualiang Jiang Mingyue Zheng | 2024 | Science China(Life Sciences)2024，67，3： | 0 |
| 8 | Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3显示文摘The TEA domain(TEAD)family proteins(TEAD1-4)are essential transcription factors that control cell differentiation and organ size in the Hippo pathway.Although the sequences and structures of TEAD family proteins are highly conserved,each TEAD isoform has unique physiological and pathological functions.Therefore,the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases.Here,we identified a novel TEAD 1/3 covalent inhibitor(DC-TEADin1072)with biochemical IC50 values of 0.61±0.02 and 0.58±0.12μmol/L against TEAD1 and TEAD3,respectively.Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DCTEAD3 in03 with the IC_(50) value of 0.16±0.03μmol/L,which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling(ABPP)assays.In cells,DC-TEAD3 in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD(1-4)reporter assays with the IC50 value of1.15μmol/L.When administered to zebrafish juveniles,experiments showed that DC-TEAD3 in03 reduced the growth rate of zebrafish caudal fins,indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages. | Tian Lu Yong Li Wenchao Lu TWGM Spitters Xueyu Fang Jun Wang Simian Cai Jing Gao Yanting Zhou Zhe Duan Huan Xiong Liping Liu Qi Li Hualiang Jiang Kaixian Chen Hu Zhou Hua Lin Huijin Feng Bing Zhou Christopher L.Antos Cheng Luo | 2021 | Acta Pharmaceutica Sinica B2021，11，10： | 0 |
| 9 | Novel Sc-doped Bi_(3)TiNbO_(9) ferroelectric nanofibers prepared by electrospinning for visible-light photocatalysis显示文摘In this work,a novel Sc-doped Bi_(3)TiNbO_(9) ferroelectric nanofiber was first prepared by electrospinning.The nanofibers are approximately 100 nm level in diameter.The photocatalytic activity analysis reveals that the Bi_(3)TiNbO_(9) nanofibers synthesized by electrospinning are superior to powders prepared by the solid-state method,which is mainly attributed to the high specific surface area and high surface activity of the nanofibers.In addition,doping Sc can reduce the band gap of Bi_(3)TiNbO_(9) and further improve the photocatalytic efficiency.Bi_(3)TiNbO_(9) nanofibers containing 5 mol%Sc have the highest photocatalytic activity,which can degrade 98.55%of RhB under 405 nm light irradiation for 120 min.In addition,the catalytic mechanism of the catalyst was obtained by scavenger tests,active species capture tests and band structure analyses.After three cycles of photocatalytic experiment,the degradation rate is decreased by only 2.42%,proving that the nanofibers catalyst has excellent stability.This work provides good prospects for the practical application of electrospinning technology in the field of photocatalysis. | Zhixiong Song Shuwen Yu Kaixian Wang Zhengming Jiang Liyan Xue Fan Yang | 2023 | Journal of Rare Earths2023，41，3： | 0 |
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