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Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 44-53页

作者： HUANG Hongmei yang maojun LI Ting WANG Dandan LI Ying TANG Xiaochi YUAN Lu GU Shi XU Yong Department of Endocrinology Chengdu Shuangliu District First People's Hospital(West China Airport of Sichuan University)Chengdu 610200China Department of Endocrinology Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation ***:A DN mouse model was constructed and treated with *** creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson *** tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney *** reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney ***,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and ***:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with ***2 is a post-transcriptional target of *** HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly ***,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMC

关键词： diabetic nephropathies neferine miR-17-5p NF-E2-related factor 2 oxidative stress

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Recent progress and challenges in the treatment of spinal cord injury

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Protein & Cell 2023年第9期14卷 635-652页

作者： Ting Tian Sensen Zhang maojun yang Ministry of Education Key Laboratory of Protein Science Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureSchool of Life SciencesTsinghua UniversityBeijing100084China Cryo-EMFacilityCenter SouthernUniversityof ScienceandTechnologyShenzhen518055China

Spinal cord injury(SCI)disrupts the structural and functional connectivity between the higher center and the spinal cord,resulting in severe motor,sensory,and autonomic dysfunction with a variety of *** pathophysiology of sci is complicated and multifaceted,and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after *** strategies targeting multiple aspects of scI pathology have achieved greater beneficial effects than individuai therapy *** many problems and challenges remain,the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat *** this review,we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following scI at both the acute and chronic *** addition,we analyze the current status,remaining problems,and realistic challenges towards clinical ***,we consider the future of scI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical *** forward,clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeuticbenefitinhumanswithscl.

关键词： spinal cord injury axon regeneration functional recovery therapeutic strategies clinical translation

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国外某油田玻璃钢管道失效原因分析

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山东化工 2024年第10期53卷 194-197页

作者：杨茂军张恺刘帅中海油石化工程有限公司工艺系统室山东青岛266101

国外某油田用于输送水源井水的玻璃钢管道频繁失效泄漏,对油田的正常生产造成严重影响。通过对玻璃钢管道施工安装质量、管道制造质量、水源井运行工况及流体介质组成等因素逐项分析,推断玻璃钢失效的主要原因是水源井水中含有的酸性物... 详细信息

国外某油田用于输送水源井水的玻璃钢管道频繁失效泄漏,对油田的正常生产造成严重影响。通过对玻璃钢管道施工安装质量、管道制造质量、水源井运行工况及流体介质组成等因素逐项分析,推断玻璃钢失效的主要原因是水源井水中含有的酸性物质对玻璃钢管材的环氧树脂具有腐蚀作用、井水的伴生气所含CO_(2)对玻璃钢发生化学及物理腐蚀造成的,同时,井水实际温度高于设计温度加速了玻璃钢的老化失效。结合以上原因,建议的解决措施为根据最新分析化验的水源井水的组分及运行参数,优化玻璃钢的原材料类型,开发出耐高温、耐酸及耐CO_(2)腐蚀的新型玻璃钢管道。

关键词：玻璃钢管道失效分析酸性环境 CO_(2) 操作温度

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When MAGE meets RING:insights into biological functions of MAGE proteins

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Protein & Cell 2011年第1期2卷 7-12页

作者： Yue Feng Jinlan Gao maojun yang MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China Center for Structural Biology School of Life SciencesTsinghua UniversityBeijing 100084China National Laboratory of Medical Molecular Biology Peking Union Medical CollegeTsinghua UniversityBeijing 100084China

The melanoma antigen(MAGE)family proteins are well known as tumor-specific antigens and comprise more than 60 genes,which share a conserved MAGE homology domain(MHD).Type I MAGEs are highly expressed cancer antigens,and they play an important role in tumorigenesis and cancer cell ***,several MAGE proteins were identified to interact with RING domain proteins,including a sub-family of E3 ubiquitin *** binding mode between MAGEs and RING proteins was investigated and one important structure of these MAGE-RING complexes was solved:the MAGE-G1-NSE1 *** and biochemical studies indicated that MAGE proteins could adjust the E3 ubiquitin ligase activity of its cognate RING partner both in vitro and in ***,the underlying mechanism was not fully ***,we review these exciting advances in the studies on MAGE family,suggest potential mechanisms by which MAGEs activate the E3 activity of their binding RING proteins and highlight the anticancer potential of this family proteins.

关键词： MAGE cancer testis antigen RING ubiquitin ligase TRIM28

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某油田水洗罐及低低压火炬系统运行问题的原因分析与解决方案

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当代化工研究 2024年第17期 134-136页

作者：张恺杨茂军王芙中海油石化工程有限公司山东266101

本文致力于解决某油田水洗罐及低压火炬系统运行中的问题。随着水洗罐操作温度提高,出现了低低压火炬产生黑烟、水洗罐操作压力升高等异常情况。通过现场调查和原因分析,发现问题主要源于火炬管线存在液袋和低点排凝设置不合理。文章描... 详细信息

本文致力于解决某油田水洗罐及低压火炬系统运行中的问题。随着水洗罐操作温度提高,出现了低低压火炬产生黑烟、水洗罐操作压力升高等异常情况。通过现场调查和原因分析,发现问题主要源于火炬管线存在液袋和低点排凝设置不合理。文章描述了现场流程,指出了操作温度升高导致的问题,并通过原因分析,揭示了问题的本质。为解决问题,提出了一系列措施,包括设置临时管线排空积液、增加压力平衡管线、提高管道保温效果。经过实施这些解决措施后,装置运行状况良好,水洗罐操作压力得以控制在正常范围内。本文为类似问题提供了实际有效的解决方案,为油田地面工程设施的在线优化和整改提供了有益的经验。

关键词：水洗罐低低压火炬黑烟操作压力升高

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Amazing structure of respirasome： unveiling the secrets of cell respiration

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Protein & Cell 2016年第12期7卷 854-865页

作者： Runyu Guo Jinke Gu Meng Wu maojun yang Ministry of Education Key Laboratory of Protein Science Tsinghua-Peking Joint Center for Life Sciences Beijing Advanced Innovation Center for Structural Biology School of Life Sciences Tsinghua University Beijing 100084 China

Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indis- pensable biological process in almost all living crea- tures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by yang＇s group from Tsinghua University （Gu et al. Nature 237（7622）：639-643, 2016） firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening. However, the study of cellular respiration went through a long history. Here, we briefly showed the detoured history of respiratory chain investigation, and then described the amazing structure of respirasome.

关键词： respirasome structure supercomplexesorganization cellular respiration respiratory complexes megacomplex

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Structures of SdrD from Staphylococcus aureus reveal the molecular mechanism of how the cell surface receptors recognize their ligands

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Protein & Cell 2013年第4期4卷 277-285页

作者： Xiao Wang Jingpeng Ge Bao Liu Yulin Hu maojun yang Key Laboratory for Protein Sciences of Ministry of Education Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Department of Vascular Surgery Peking Union Medical College HospitalBeijing 100005China Division of Hepatobiliary-Pancreatic The First Hospital of JiLlin UniversityChangchun 130021China

Staphylococcus aureus is the most important Gram-positive colonizer of human skin and nasal passage,causing high morbidity and ***-repeat containing protein D(SdrD),an MSCRAMM(Microbial Surface Components Recognizing Adhesive Matrix Molecules)family surface protein,plays an important role in *** adhesion and pathogenesis,while its binding target and molecular mechanism remain largely *** we solved the crystal structures of SdrD N2-N3 domain and N2-N3-B1 *** structural analysis and comparisons,we characterized the ligand binding site of SdrD,and proposed a featured sequence motif of its potential *** addition,the structures revealed for the first time the interactions between B1 domain and N2-N3 domain among B domain-containing *** results may help in understanding the roles SdrD plays in *** adhesion and shed light on the development of novel antibiotics.

关键词： SdrD adhesin MSCRAMM Staphylococcus aureus

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Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism

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Protein & Cell 2017年第11期8卷 834-847页

作者： Sensen Zhang Ningning Li Wenwen Zeng Ning Gao maojun yang Ministry of Education Key Laboratory of Protein Science Tsinghua-Peking Joint Center for Life Sciences Beijing Advanced Innovation Center for Structural Biology School of Life Sciences Tsinghua University Beijing 100084 China State Key Laboratory of Membrane Biology Peking-Tsinghua Center for Life Sciences School of Life Science Peking University Beijing 100871 China Institute for Immunology and School of Medicine Tsinghua-Peking Joint Center for Life Sciences Tsinghua University Beijing 100084. China

TRPML1 channel is a non-selective group-2 transient receptor potential （TRP） channel with Ca2＋ permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV （MLIV）. In the present study, we determined the cryo-electron microscopy （cryo-EM） structures of Mus musculus TRPML1 （mTRPMLI） in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain （PMD） may sense the luminal/extracellular stimuli and undergo a ＂move upward＂ motion during endocytosis, thus triggering the overall conformational change in TRPMLI. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca2＋, and phosphoinosi- tides in a combined manner so as to accommodate the dynamic endocytosis process.

关键词： mTRPML1 mucolipidosis type IV structualcomparisons combined regulation mechanism

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Research journey of respirasome

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Protein & Cell 2020年第5期11卷 318-338页

作者： Meng Wu Jinke Gu Shuai Zong Runyu Guo Tianya Liu maojun yang Ministry of Education Key Laboratory of Protein Science Tsinghua-Peking Joint Center for Life SciencesBeijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of *** research has been carried out on this lynchpin of *** the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1,scientists have gradually uncovered the mysterious veil of the electron transport chain(ETC).With the discovery of the mammalian respiratory mega complex I2III2IV2,a new perspective emerges in the research field of the *** these advances glitters the light of the revolution in both theory and ***,we give a short review about how scientists‘see’the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.

关键词： electron transport chain supercomplex organization cellular respiration structure of respirasome cryo-EM megacomplex

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Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen a

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Protein & Cell 2015年第10期6卷 757-766页

作者： Xinyue Zhang Meng Wu Wei Zhuo JinkeGu Sensen Zhang Jingpeng Ge maojun yang Key Laboratory for Protein Sciences of Ministry of Education Tsinghua-Peking Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China

Bone sialoprotein-binding protein （Bbp）, a MSCRAMMs （Microbial Surface Components Recognizing Adhesive Matrix Molecules） family protein expressed on the surface of Staphylococcus aureus （S. aureus）, mediates adherence to fibrinogen a （Fg a）, a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp273-598 and Bbp273-598-Fg a561-575 complex at a resolution of 2.03 A and 1.45 A, respectively. Apo-Bbp273-598 contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional DI strand in N2 domain and D1＇ and D2＇ strands in N3 domain. The peptide mapped to the Fg o561-575 bond to Bbp273-sgs on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G＂ covering the ligand upon ligand binding. BbpAla298-Gly301 in the N2 domain of the Bbp273-598-Fg a561-575 complex, which is a loop in the apo-form, formed a short a-helix to interact tightly with the peptide. In addition, Bbpser547-Glns61 in the N3 domain moved toward the binding groove to make contact directly with the peptide, while BbpAsp338-Gly355 and BbpThr365-Tyr387 in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.

关键词： bone sialoprotein-binding protein (Bbp),fibrinogen serine-aspartate repeat (Sdr) Microbial SurfaceComponents Recognizing Adhesive Matrix Molecules(MSCRAMM) Staphylococcus aureus

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