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Ginsenoside Rg5 alleviates radiation-induced acute lung vascular endothelium injury by reducing mitochondrial apoptosis via Sirt1

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Journal of Ginseng Research 2025年第3期49卷 260-270页

作者： Li, Churong Zhao, Biao Xiong, Jing Li, Linjie Pang, Dalong Unger, Keith Jung, Mira Lyu, Jiahua Kuang, Hao Liang, Long Li, Tao Chen, Long Bai, Hansong Radiotherapy Center Radiation Oncology Key Laboratory of Sichuan Province Sichuan Clinical Research Center for Cancer Sichuan Cancer Hospital & Institute Sichuan Cancer Center University of Electronic Science and Technology of China Chengdu China Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province School of Basic Medical Sciences Chengdu Medical College Chengdu China Department of Integrative Chinese and Western Medicine Sichuan Cancer Hospital & Institute Sichuan Cancer Center Affiliated Cancer Hospital of the University of Electronic Science and Technology of China Chengdu China Department of Immunology School of Basic Medical Sciences Chengdu Medical College Chengdu China Department of Radiation Medicine Lombardi Comprehensive Cancer Center Georgetown University Medical Center Washington DC United States Department of Oncology The Affiliated Hospital of Southwest Medical University Luzhou China School of Medicine University of Electronic Science and Technology of China Chengdu China

Background: Ginsenoside Rg5 possesses potent anti-oxidative, anti-inflammatory, and cytoprotective properties. This study explored the protective effects of ginsenoside Rg5 on radiation-induced pulmonary microvascular endothelial cells (PMECs) injury and the associated molecular mechanisms. Materials and methods: C57BL/6 mice were used for in vivo studies and primary human PMECs (PPMECs) were utilized as in vitro models. Mice with or without ginsenoside Rg5 pretreatment were irradiated by varying doses. Lung tissues were analyzed for histopathological changes and the expression of endothelial markers. In vitro, PPMECs were irradiated with or without ginsenoside Rg5 pretreatment and analyzed for apoptosis, oxidative stress, mitochondrial function, and endothelial barrier integrity. Results: Ginsenoside Rg5 pretreatment attenuated radiation-induced acute lung damage, preserved endothelial cell junction integrity, and maintained endothelial barrier function in vivo. In vitro, ginsenoside Rg5 significantly reduced IR-induced oxidative stress, apoptosis, and mitochondrial dysfunction in PPMECs. Ginsenoside Rg5 suppressed radiation-induced Mfn2 acetylation and proteasomal degradation via Sirt1-mediated deacetylation, thereby preserving mitochondrial dynamics and integrity. The protective effects of ginsenoside Rg5 on the integrity of mitochondrial and endothelial tight junction proteins and barrier function were also Sirt1-dependent. Conclusions: Ginsenoside Rg5 exerts a protective effect against radiation-induced endothelial injury by modulating mitochondrial dynamics and function, as well as maintaining endothelial barrier integrity, in a Sirt1-dependent manner. © 2025

关键词： Endothelial cell injury Ginsenoside Rg5 Mitochondrial dynamics Radiation Sirt1

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Transposon–host arms race: a saga of genome evolution

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Trends in Genetics 2025年第5期41卷 369-389页

作者： Iwasaki, Yuka W. Shoji, Keisuke Nakagwa, Shinichi Miyoshi, Tomoichiro Tomari, Yukihide Laboratory for Functional Non-coding Genomics RIKEN Center for Integrative Medical Sciences 1-7-22 Suehiro-cho Tsurumi-ku Kanagawa Yokohama 230-0045 Japan of Bio-Applications and Systems Engineering Tokyo University of Agriculture and Technology Tokyo Koganei-shi 184-8588 Japan Laboratory of RNA Function Institute for Quantitative Biosciences The University of Tokyo 1-1-1 Yayoi Tokyo Bunkyo-ku 113-0032 Japan RNA Biology Laboratory Faculty of Pharmaceutical Sciences Hokkaido University Kita 12-jo Nishi 6-chome Kita-ku Sapporo 060-0812 Japan Laboratory for Retrotransposon Dynamics RIKEN Center for Integrative Medical Sciences 1-7-22 Suehiro-cho Tsurumi-ku Kanagawa Yokohama 230-0045 Japan Department of Computational Biology and Medical Sciences of Frontier Sciences The University of Tokyo Tokyo Bunkyo-ku 113-0032 Japan

Once considered ‘junk DNA,’ transposons or transposable elements (TEs) are now recognized as key drivers of genome evolution, contributing to genetic diversity, gene regulation, and species diversification. However, their ability to move within the genome poses a potential threat to genome integrity, promoting the evolution of robust host defense systems such as Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KRAB-ZFPs), the human silencing hub (HUSH) complex, 4.5SH rnas, and PIWI-interacting rnas (pirnas). This ongoing evolutionary arms race between TEs and host defenses continuously reshapes genome architecture and function. This review outlines various host defense mechanisms and explores the dynamic coevolution of TEs and host defenses in animals, highlighting how the defense mechanisms not only safeguard the host genomes but also drive genetic innovation through the arms race. © 2025 Elsevier Ltd

关键词： evolutionary arms race genetic conflicts genome evolution host defense mechanisms transposable elements (TEs)

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Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes

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Science China Life Sciences 2025年第5期68卷 1423-1436页

作者： Hao Du Yao Zhang Xi Yu Xuanhe You Diwei Wu Ze Du Yongrui Cai Zhenyu Luo Hanpeng Lu Zhixin Liao Bi-Sen Ding Ya Zhao Yan Wang Ke Xiao Fan Yang Fangji Gan Ning Ning Jiancheng Zeng Peiliang Shi Zongke Zhou Shishu Huang Department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan University Rehabilitation Medicine Center West China HospitalSichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan University Institute of Translational Medicine Medical CollegeYangzhou University Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research College of Animal Science and Technology Sichuan Agricultural University Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province Sichuan Agricultural University Department of Lower Limb Surgery of Sichuan Province Orthopedic Hospital Central Laboratory of Sichuan Province Orthopedic Hospital Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions School of Mechanical Engineering Sichuan University Gem Pharmatech (Chengdu) Co. Ltd.

Osteoarthritis(OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression. Surprisingly, these genes were occupied by both H3K27me3 and H3K4me3 in normal chondrocytes, showing a poised bivalent state. Furthermore, we observed the derepression of similar bivalent genes in growth plate chondrocytes. Finally, a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model. Our results reveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy and contributes to a promising epigenetic therapy for OA.

关键词： osteoarthritis histone modifications H3K27me3 bivalency growth plate

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Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3

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Biomaterials 2025年 321卷 123350-123350页

作者： Meng, Nana Lu, Jiasheng Zhou, Jianfen Yang, Shengmin Zhang, Chen Jia, Ruiyi Ding, Yuan Bao, Yanning Wang, Jun Ma, Xiaopei Chen, Ruohan Jiang, Zhixuan Xie, Cao Lu, Linwei Lu, Weiyue Department of Pharmaceutics School of Pharmacy Fudan University & National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers Shanghai201203 China Department of Integrative Medicine Huashan Hospital Fudan University Shanghai200040 China Institutes of Integrative Medicine Fudan University Shanghai200040 China Shanghai Engineering Technology Research Center for Pharmaceutical Intelligent Equipment and Shanghai Frontiers Science Center for Druggability of Cardiovascular Non-coding RNA Institute for Frontier Medical Technology Shanghai University of Engineering Science Shanghai201620 China

One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin αvβ3. Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the in vivo immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines. © 2025 Elsevier Ltd

关键词： Ligands

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Quality Assessment of Domesticated Animal Genome Assemblies

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Bioinformatics and Biology Insights 2015年第Suppl 4期9S4卷 49-58页

作者： Seemann, Stefan E. Anthon, Christian Palasca, Oana Gorodkin, Jan Center for non-coding RNA in Technology and Health Department of Veterinary Clinical and Animal Sciences University of Copenhagen København Denmark

The era of high-throughput sequencing has made it relatively simple to sequence genomes and transcriptomes of individuals from many species. In order to analyze the resulting sequencing data, high-quality reference genome assemblies are required. However, this is still a major challenge, and many domesticated animal genomes still need to be sequenced deeper in order to produce high-quality assemblies. In the meanwhile, ironically, the extent to which rna seq and other next-generation data is produced frequently far exceeds that of the genomic sequence. Furthermore, basic comparative analysis is often affected by the lack of genomic sequence. Herein, we quantify the quality of the genome assemblies of 20 domesticated animals and related species by assessing a range of measurable parameters, and we show that there is a positive correlation between the fraction of mappable reads from rnaseq data and genome assembly quality. We rank the genomes by their assembly quality and discuss the implications for genotype analyses. © 2015, © 2015 SAGE Publications.

关键词： assembly quality domesticated animals genome assembly

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PTMD: A Database of Human Disease-associated Post-translational Modifications

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Genomics, Proteomics & Bioinformatics 2018年第4期16卷 244-251页

作者： Haodong Xu Yongbo Wang Shaofeng Lin Wankun Deng Di Peng Qinghua Cui Yu Xue Department of Bioinformatics & Systems Biology MOE Key Laboratory of Molecular Biophysics College of Life Science and Technology and the Collaborative Innovation Center for Biomedical Engineering Huazhong University of Science and Technology Department of Biomedical Informatics School of Basic Medical Sciences MOE Key Laboratory of Molecular Cardiovascular Sciences Center for Non-coding RNA Medicine Peking University

Various posttranslational modifications （PTMs） participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM–disease associations （PDAs）would be a great help for both academic research and clinical use. In this work, we reported PTMD,a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of diseaseassociated PTM events. By reconstructing a disease–gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http：//***.

关键词： Posttranslational modification Phosphorylation PTM-disease association Disease-gene network AKT1

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Computational strategies to search structured rnas in genomic sequence(and roads towards further analysis)

Computational strategies to search structured RNAs in genomi...

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2011国际基因组学大会

作者： Jan Gorodkin Center for non-coding RNA in Technology and Health IBHVUniversity of CopenhagenDenmark

A key application of early methods for computational rna folding was to aid interpretation of structure probing *** the years computational rna biology has developed in which improved energy models and the availability of multiple genomes have contributed substantially to the development of the *** methods that search for common rna structures in a set of co-regulated rnas have

关键词： rna and roads towards further analysis Computational strategies to search structured rnas in genomic sequence

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Using GPU to accelerate the pairwise structural rna alignment with base pair probabilities

Using GPU to accelerate the pairwise structural RNA alignmen...

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作者： Sundfeld, Daniel Teodoro, George Havgaard, Jakob H. Gorodkin, Jan Melo, Alba C. M. A. Information and Communication Technology Brasília Federal Institute Brasília Brazil Department of Computer Science University of Brasília Brasília Brazil Center for Non-Coding RNA in Technology and Health Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark

Structural alignments of Ribonucleic acid (rna) sequences solved by the Sankoff algorithm are computationally expensive and often require constraints to be used in practice. Modern Graphics Processing Units (GPUs) contain more than 1000 cores, which compute in parallel to speed up applications. Here, we present a GPU-based solution to the rna structural alignment problem that makes use of precalculated base pair probabilities on the individual sequences. We designed and developed an unconstrained version of the Sankoff algorithm, obtaining the optimal result and calculating the entire four-dimension dynamic programming matrix (4D DP). Our approach uses a two-level wavefront strategy to exploit parallelism. The 4D DP matrix is divided in one external matrix (EM) and several internal matrices (IM). We applied wavefront strategies on the EM and IMs in a two-level hierarchical way. At the first level, the wavefront is applied to the EM, calculating the cells that belong to the same diagonal in parallel. In the second level, since each cell in the EM is itself an IM matrix, the cells that belong to the same IM diagonal are calculated in parallel. The results obtained with real rna sequences show that our GPU version is capable of outperforming a multicore CPU version of the unconstrained version of the Sankoff algorithm. Compared with the CPU-based version running on 32 cores, our approach is able to achieve a speedup of 7.81x on the NVidia Tesla P100. In this case, the execution time was reduced from 6 hours and 18 minutes (32 cores) to 48 minutes and 20 seconds (GPU). © 2019 John Wiley & Sons, Ltd.

关键词： Graphics processing unit

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Computational Discovery of Conserved rna Structures and Functional Characterization of a Structured lncrna in Leishmania braziliensis

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non-coding rna Research 2025年

作者： Caroline R. Espada Christian Anthon Rubens D.M. Magalhães José Carlos Quilles Junior Natalia M.M. Teles Fabiano S. Pais Lissur A. Orsine Letícia de Almeida Tânia P.A. Defina Adam Dowle Jan Gorodkin Pegine B. Walrad Angela K. Cruz Department of Cell and Molecular Biology Ribeirão Preto Medical School University of São Paulo FMRP-USP Ribeirão Preto São Paulo Brasil Department of Biology York Biomedical Research Institute University of York York United Kingdom Center for non-coding RNA in Technology and Health Department of Animal and Veterinary Sciences Faculty for Health and Medical Sciences University of Copenhagen Copenhagen Denmark Data Science Lab Metabolomics and Proteomics Lab Bioscience Technology Facility Department of Biology University of York York United Kingdom

Leishmania parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical rna polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding rnas (ncrnas) have been identified in Leishmania transcriptomes, their functions remain unclear. Recognizing rna structure's importance, we performed a genome-wide alignment of L. braziliensis and related species, identifying conserved rna structures, 38 of which overlap with known ncrnas. One such ncrna, lncrna45 , was functionally characterized. Using a knockout cell line, we demonstrated that lncrna45 is crucial for parasite fitness. Reintroducing the wild type lncrna45 restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered rna-protein interactions. These findings suggest that lncrna45 's regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncrnas in Leishmania biology and their potential as therapeutic targets. Further research into these ncrnas could uncover new parasite regulation mechanisms and inspire novel treatment strategies.

关键词： non-coding rnas Leishmania braziliensis rna structure Gene expression regulation CRISPR- Cas9

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50 shades of rule composition from chemical reactions to higher levels of abstraction

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Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 2014年 8738卷 115-135页

作者： Andersen, Jakob Lykke Flamm, Christoph Merkle, Daniel Stadler, Peter F. Department of Mathematics and Computer Science University of Southern Denmark Denmark Institute for Theoretical Chemistry University of Vienna Austria Bioinformatics Group Department of Computer Science and Interdisciplinary Center for Bioinformatics Leipzig Germany Max Planck Institute for Mathematics in the Sciences Leipzig Germany Fraunhofer Institute for Cell Therapy and Immunology Leipzig Germany Center for Non-coding RNA in Technology and Health University of Copenhagen Denmark Santa Fe Institute United States

ISBN: (纸本)9783319103976

Graph rewriting has been applied quite successfully to model chemical and biological systems at different levels of abstraction. A particularly powerful feature of rule-based models that are rigorously grounded in category theory, is, that they admit a well-defined notion of rule composition, hence, provide their users with an intrinsic mechanism for compressing trajectories and coarse grained representations of dynamical aspects. The same formal framework, however, also allows the detailed analysis of transitions in which the final and initial states are known, but the detailed stepwise mechanism remains hidden. To demonstrate the general principle we consider here how rule composition is used to determine accurate atom maps for complex enzyme reactions. This problem not only exemplifies the paradigm but is also of considerable practical importance for many down-stream analyses of metabolic networks and it is a necessary prerequisite for predicting atom traces for the analysis of isotope labelling experiments. © Springer International Publishing Switzerland 2014.

关键词： Biological systems

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