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| 1 | Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms显示文摘Iron homeostasis is essential for health;moreover,hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia.Here,we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells.We validated the results in C57BL/6J mice and a mouse model of hemochromatosis(Hfe^(−/−)mice).Our screen revealed that the anti-rheumatoid arthritis drug auranofin(AUR)potently upregulates hepcidin expression.Interestingly,we found that canonical signaling pathways that regulate iron,including the Bmp/Smad and IL-6/Jak2/Stat3 pathways,play indispensable roles in mediating AUR’s effects.In addition,AUR induces IL-6 via the NF-κB pathway.In C57BL/6J mice,acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation.Whereas chronically treating male Hfe^(−/−)mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling,decreasing systemic iron overload,but less effective in females.Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells,providing a mechanistic explanation for ineffectiveness of AUR in female Hfe^(−/−)mice.Notably,high-dose AUR(25 mg/kg)induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase(TXNRD)activity.We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by highdose AUR without comprising its beneficial effect on iron metabolism.In conclusion,our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis,and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms,suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders. | Lei Yang Hao Wang Xiang Yang Qian Wu Peng An Xi Jin Weiwei Liu Xin Huang Yuzhu Li Shiyu Yan Shuying Shen Tingbo Liang Junxia Min Fudi Wang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 5 |
| 2 | The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis显示文摘Dear Editor,Ferroptosis is an iron-dependent,non-apoptotic form of regulated cell death characterized by an accumulation of lipid.derived reactive oxygen species(ROS).The small-molecule compo und erastin in duces ferroptosis via in hibiti ng the cystineglutamate antiporter system x_(c).which consists of two subunits,namely the light chain xCT and the heavy chain 4F2hc(encoded by the SLC7A11 and SLC3A2 genes,respectively).^(1-4) | Renhong Yan Enjun Xie Yaning Li Jin Li Yuanyuan Zhang Ximin Chi Xueping Hu Lei xu Tingjun Hou Brent R.Stockwell Junxia Min Qiang Zhou Fudi Wang | 2022 | Cell Research2022，32，7： | 4 |
| 3 | Abnormal expression of TFIIIB subunits and RNA PolⅢgenes is associated with hepatocellular carcinoma显示文摘The levels of the products of RNA polymeraseⅢ-dependent genes(PolⅢgenes),including tRNAs and 5S rRNA,are elevated in transformed and tumor cells,which potentiate tumorigenesis.TFIIB-related factor 1(Brf1)is a key transcription factor and specifically regulates the transcription of PolⅢgenes.In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces PolⅢgene transcription and is sufficient for inhibiting cell transformation and tumor formation.Emerging evidence indicates that dysregulation of Brf1 and PolⅢgenes is linked to the development of hepatocellular carcinoma(HCC)in humans and animals.We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals.This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics.These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients. | Junxia Lei Songlin Chen Shuping Zhong | 2017 | Liver Research2017，1，2： | 3 |
| 4 | Col10a1 gene expression and chondrocyte hypertrophy during skeletal development and disease显示文摘类型 X 骨胶原基因, COL10A1,被 hypertrophic chondrocytes 明确地在 endochondral 期间表示骨化。Endochondral 骨化是包含软骨中介并且在 skeletogenesis 期间在脊椎动物导致大多数骨骼的形成的一个协调得好的过程。Chondrocyte 肥大是连接骨头和软骨开发的 endochondral 骨化的一个批评阶段。与 chondrocyte 肥大给它的特定的协会,在 endochondral 的类型 X 骨胶原戏必需品角色骨化。当变化和人的 COL10A1 的反常表示引起反常 chondrocyte 在许多骨胳的混乱被看见了的肥大时,有变异的类型 X 骨胶原的转基因的鼠标开发显示有缺点的 endochondral 骨化的可变骨骼造血的畸形,这以前被显示出当变化和人的 COL10A1 的反常表示引起反常 chondrocyte 在许多骨胳的混乱被看见了的肥大时。在这评论,我们与显示出生长板缺点的 COL10A1 基因变化总结了骨胳的 chondrodysplasia。我们也考察了相关的最近的研究有骨关节炎的类型 X 骨胶原基因表示和 chondrocyte 肥大。由于它的重要临床的关联,类型 X 骨胶原基因规定广泛地在过去的二十年被学习了。这里,我们集中于描绘 cis 提高元素和他们有约束力的因素的最近的进步一起授与 hypertrophic chondrocyte 特定的鼠科的类型 X 骨胶原基因(Col10a1 ) 表示。基于文学评论和我们的自己的研究,我们推测有多重因素,贡献 hypertrophic chondrocyte 特定的 Col10a1 表示。这些因素包括两 transactivators (例如 Runx2, MEF2C 等等) 并且抑压者(例如 AP1, NFATc1, Sox9 等等) ,当 Col10a1 表示的另外的余因子或 epigenetic 控制不能被排除时。 | Yaojuan LU Longwei QIAO Guanghua LEI Ranim R. MIRA Junxia GU Qiping ZHENG | 2014 | Frontiers in Biology2014，9，3： | 2 |
| 5 | hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human gli- oma cells显示文摘 | LEI S ZIHAO C JUNXIA Z | 2008 | Brain Research2008，1236，： | 1 |
| 6 | The Ce doping Cu/ZSM-5 as a new superior catalyst to remove NO from diesel engine exhaust显示文摘 | Lei Pang Chi Fan Lina Shao Kunpeng Song Junxia Yi Xing Cai Jian Wang Ming Kang Tao Li | 2014 | Chemical Engineering Journal2014，，： | 1 |
| 7 | MiR-125b is critical for the suppression of human U251 glioma stem cell profiferation 显示文摘 | Lei S Junxia Z Tianhong P | 2010 | Brain Research2010，1312，： | 1 |
| 8 | Ultrasound enhanced electrochemical oxidation of phenol and phthalic acid on boron-doped diamond electrode显示文摘 | Guohua Zhao Junxia Gao Shihao Shen Meichuan Liu Dongming Li Meifen Wu Yanzhu Lei | 2009 | Journal of Hazardous Materials2009，，2： | 1 |
| 9 | Experimental study on the effects of wetting-drying cycles of compacted loess 显示文摘 | Mao Yuncheng Li Guoyu Lei Junxia | 2014 | Advanced Materials Research2014，831，： | 1 |
| 10 | Wnt/beta-catenin signaling in glioma显示文摘 | Kailiang Zhang Junxia Zhang Lei Han | 2012 | Neuroimmune Pharmacol2012，7，4： | 1 |
| 11 | hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells显示文摘 | Lei Shi Zihao Cheng Junxia Zhang Rui Li Peng Zhao Zhen Fu Yongping You | 2008 | Brain Research2008，，： | 1 |
| 12 | Shape Classification of Cloud Particles Recorded by the 2D-S Imaging Probe Using a Convolutional Neural Network显示文摘The airborne two-dimensional stereo(2D-S) optical array probe has been operating for more than 10 yr, accumulating a large amount of cloud particle image data. However, due to the lack of reliable and unbiased classification tools,our ability to extract meaningful morphological information related to cloud microphysical processes is limited. To solve this issue, we propose a novel classification algorithm for 2D-S cloud particle images based on a convolutional neural network(CNN), named CNN-2DS. A 2D-S cloud particle shape dataset was established by using the 2D-S cloud particle images observed from 13 aircraft detection flights in 6 regions of China(Northeast, Northwest, North,East, Central, and South China). This dataset contains 33,300 cloud particle images with 8 types of cloud particle shape(linear, sphere, dendrite, aggregate, graupel, plate, donut, and irregular). The CNN-2DS model was trained and tested based on the established 2D-S dataset. Experimental results show that the CNN-2DS model can accurately identify cloud particles with an average classification accuracy of 97%. Compared with other common classification models [e.g., Vision Transformer(ViT) and Residual Neural Network(ResNet)], the CNN-2DS model is lightweight(few parameters) and fast in calculations, and has the highest classification accuracy. In a word, the proposed CNN-2DS model is effective and reliable for the classification of cloud particles detected by the 2D-S probe. | Rong ZHANG Haixia XIAO Yang GAO Haizhou SU Dongnan LI Lei WEI Junxia LI Hongyu LI | 2023 | Journal of Meteorological Research2023，37，4： | 0 |
| 13 | Linking Genetic Risks to Pathologicalα-Synuclein Transmission in Parkinson's Disease显示文摘Misfoldedα-synuclein(α-syn)hallmarks the neuropathological characteristics of Parkinson's disease(PD)and acts as a'pathological seed'that promotes the progression of the disease[1].About 15%of PD patients have a family history,5%-10%have a monogenic disorder with a Mendelian pattern of inheritance[2],and>90 independent risk signals identified by genome-wide association studies(GWASs)can be used to explain the non-monogenic risk of PD[3]. | Xiaoqing Mi Lei Chen Junxia Xie Ning Song | 2023 | Neuroscience Bulletin2023，39，7： | 0 |
| 14 | Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus显示文摘Divalent metal transporter 1(DMT1)is a ferrous iron import protein.The improper expression of DMT1 is involved in neurodegenerative diseases.In the present study,we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element(DMT1-IRE)and investigated its expression and function in the C6 glioma cell line.The DMT1-IRE gene,obtained by RT-PCR,was cloned into the shuttle plasmid-ing pAdTrack-CMV containing greenfluorescent protein(GFP)reporter gene.Linearized plasmid pAdTrack-CMV-DMT1-IRE was subsequently co-transformed into Escher-ichia coli(E.coli)BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with Pme I.Pac I-digested pAdEasy1-DMT1-IRE was then transfected into E1-transformed human embryonic kidney cells(HEK293 cells),in which recombinant adenoviruses were generated within 7 to 10 days.The results demon-strated that we obtained the DMT1-IRE gene.pAdEasy1-DMT1-IRE yielded a large fragment,plus a smaller fragment of 4.5 kb after digestion with Pac I.PCR confirmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE,indicating the successful construction of recombi-nant adenovirus plasmid containing DMT1-IRE.GFPfluorescence further confirmed the generation of recombi-nant AdDMT1-IRE adenovirus.AdDMT1-IRE could efficiently infect C6 glioma cells.And cell viability decreased in AdDMT1-IRE infected cells after iron overload compared to the control.These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron influx function. | Xixun DU Huamin XU Hong JIANG Jun WANG Lei WANG Junxia XIE | 2009 | Frontiers of Medicine2009，3，1： | 0 |
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