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Bioinformatics analysis of ferroptosis in spinal cord injury

Neural Regeneration Research 2023年第3期18卷 626-633页

作者： Jin-Ze Li Bao-You Fan Tao Sun Xiao-Xiong Wang Jun-Jin Li Jian-Ping Zhang Guang-Jin Gu Wen-Yuan Shen De-Rong Liu Zhi-Jian Wei Shi-Qing Feng International Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina Shandong University Centre for Orthopedics Advanced Medical Research InstituteCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina

Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

关键词： bioinformatics drug ferroptosis Gene Ontology enrichment analysis gene-miRNA network Kyoto Encyclopedia of Genes and Genomes pathway mRNA-miRNA-lncRNA network progression spinal cord injury

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Global Profiles of Acetylated Proteins in Brains of Scrapie Agents 139A- and ME7-Infected Mice Collected at Mid-Early, Mid-Late, and Terminal Stages

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Biomedical and Environmental Sciences 2022年第8期35卷 722-734页

作者： SHI Qi CHEN Dong Dong ADALATI Maimaitiming XIAO Kang GAO Li Ping YANG Xue Hua WU Yue Zhang CHEN Cao DONG Xiao Ping State Key Laboratory of Infectious Disease Prevention and Control NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102200China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang UniversityHangzhou 310014ZhejiangChina China Academy of Chinese Medical Sciences Bejing 10000China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan 43000HubeiChina Shanghai Institute of lnfectious Disease and Biosafety Shanghai 201318China

Objective To describe the global profiles of acetylated proteins in the brains of scrapie agents 139Aand ME7-infected mice collected at mid-early,mid-late,and terminal stages.Methods The acetylated proteins from the cortex regions of scrapie agent(139A-and ME7)-infected mice collected at mid-early(80 days postinfection,dpi),mid-late(120 dpi),and terminal(180 dpi) stages were extracted,and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry.The proteins in the infected mice showing 1.5-fold higher or lower levels than that of agematched normal controls were considered as differentially expressed acetylated peptides(DEAPs).Results A total of 118,42,and 51 DEAPs were found in the brains of 139A-80,139A-120,and 139A-180dpi mice,respectively.Meanwhile,390,227,and 75 DEAPs were detected in the brains of ME7-80,ME7-120,and ME7-180 dpi mice,respectively.The overwhelming majority of DEAPs in the mid-early stage were down-regulated,and more portions of DEAPs in the mid-late and late stages were up-regulated.Approximately 22.1%(328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated.Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39(80dpi),13(120 dpi),and 10(180 dpi) significantly changed pathways in 139A-infected mice.Meanwhile,55,25,and 18 significantly changed pathways were observed in the 80,120,and 180 dpi samples of139A-and ME7-infected mice(P pathways were commonly involved in all tested samples.Moreover,many steps in the citrate cycle(tricarboxylic acid cycle) were affected,represented by down-regulated acetylation for relevant enzymes in the mid-early stage and upregulated acetylation in the mid-late and late stages.Conclusion Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection,showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.

关键词： Prion Scrapie-infected mouse Acetylation Proteomics Kyoto Encyclopedia of Genes and Genomes pathway

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Bioinformatic analysis of cytokine expression in the proximal and distal nerve stumps after peripheral nerve injury

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Neural Regeneration Research 2021年第5期16卷 878-884页

作者： Xiao-Qing Cheng Wen-Jing Xu Xiao Ding Gong-Hai Han Shuai Wei Ping Liu Hao-Ye Meng Ai-Jia Shang Yu Wang Ai-Yuan Wang Institute of Orthopedics Chinese PLA General HospitalBeijingChina Beijing Key Laboratory of Regenerative Medicine in Orthopedics Chinese PLA General HospitalBeijingChina Key Lab of Musculoskeletal Trauma&War Injuries Chinese PLA General HospitalBeijingChina Department of Neurosurgery Chinese PLA General HospitalBeijingChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In our previous study,we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis,which can characterize the dynamic expression of proteins.In the present study,we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1,7,14 and 28 days after injury using protein microarray analysis.Interleukins were increased in the distal nerve stumps at 1–14 days post nerve transection.However,growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps.The P-values of the inflammatory response,apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps,but the opposite was observed for angiogenesis.The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps,while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps.Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps.Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury.Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7,2016(approval No.2016-x9-07).

关键词： cytokine distal stumps Gene Ontology Kyoto Encyclopedia of Genes and Genomes pathway microarray microenvironment peripheral nerve injury proximal stumps

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The antioxidant activity,c-glucosidase and acetylcholinesterase inhibition activity,and chemical composition of Paeonia delavayi petal

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Food Quality and Safety 2022年第2期6卷 318-329页

作者：宋静张怀璧王振兴王娟 College of Landscape Architecture and Horticulture Sciences Southwest Forestry UniversityKunmingChina New Zealand Institute for Plant&Food Research Limited Palmerston NorthNew Zealand College of Life Science Southwest Forestry UniversityKunmingChina Eco-Development Academy Southwest Forestry UniversityKunmingChina.

Objectives:This study aimed to evaluate the functional activity and phytochemical composition in the flower petals of Paeonia delavayi(P delavay)in different colors.Materials and Methods:P delavayi petal extracts were prepared by maceration in methanol,including purple petal extract(PPE),red petal extract(RPE),and yellow petal extract(YPE),and their antioxidant activity and x-glucosidase and acetylcholinesterase inhibition activities were evaluated.To correlate these measured activities to phytochemicals in the petals,an ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)-based metabolomics method was applied to profile the compositions in the petals of different colors.Finally,the kyoto encyclopedia of genes and genomes(KEGG)metabolic pathways database was used to identify the related metabolic pathways that are responsible for the production of these polyphenolic phytochermicals in the petals.Results:The results showed that PPE had the highest total phenolic content,total flavonoid content,and the strongest 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt(ABTS)radical scavenging ability,ferric reducing antioxidant power,and acetylcholin-esterase inhibition ability in all three samples,while YPE showed the strongest 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging activity and x-glucosidase inhibition ability.A total of 232 metabolites were detected in the metabolomic analysis,198 of which were flavonoids,chalcones,flavonols,and anthocyanins.Correlation analysis indicated that peonidin-3-O-arabinoside and cyanidin-3-O-arabinoside were the major contribu-tors to the antioxidant activity.Principal component analysis showed a clear separation among these three petals.In addition,a total of 38,98,and 96 differential metabolites were identified in PPE,RPE,and YPE,respectively.pathway enrichment revealed 6 KEGG pathways that displayed significant enrichment differences,of which the anthocyanin biosynthesis,flavone and flavonol biosynthesis were the most enriched signaling path

关键词： Paeonia delavayi,antioxidant activity a-glucosidase acetylcholinesterase metabolomics Kyoto Encyclopedia of Genes and Genomes pathway

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