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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu qiuyun tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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BoMyrosinase plays an essential role in sulforaphane accumulation in response to selenite treatment in broccoli

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Horticultural Plant Journal 2024年第2期10卷 488-502页

作者： qiuyun Wu Qi Wu Yuxiao tian Chunyan Zhou Shuxiang Mao Junwei Wang Ke Huang College of Horticulture Hunan Agricultural UniversityChangshaHunan 410128China Engineering Research Center for Horticultural Crop Germplasm Creation and New Variety Breeding Ministry of EducationChangshaHunan 410128China Key Laboratory for Vegetable Biology of Hunan Province ChangshaHunan 410128China Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops Ministry of Agriculture and Rural Affairs of ChinaChangshaHunan 410128China

Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase(MY) is a key gene responsible for the catalysis of sulforaphane formation, but the molecular mechanisms through which MY regulates sulforaphane biosynthesis in plants remains largely unknown. Here, we discovered that the change of sulforaphane content in broccoli sprouts caused by exogenous selenite treatments is positively related to BoMY expression. BoMY overexpression in the Arabidopsis thaliana tgg1 mutants could dramatically increase myrosinase activity and sulforaphane content in the rosette leaves of 35S::BoMY/tgg1 and rescue its phenotypes.Moreover, an obvious increase of myrosinase activity and sulforaphane content was displayed in transgenic BoMY-overexpressed broccoli lines.In addition, a 2 033 bp promoter fragment of BoMY was isolated. Yeast one-hybrid(Y1H) library screening experiment uncovered that one bHLH transcription factor, BoFAMA, could directly bind to BoMY promoter to activate its expression, which was further evidenced by Y1H assay and dual-luciferase reporter assay. BoFAMA is a selenite-responsive transcription factor that is highly expressed in broccoli leaves;its protein is solely localized to nucleus. Additionally, genetic evidence suggested that the knockdown of FAMA gene in Arabidopsis thaliana could significantly decrease sulforaphane yield by inhibiting the expression of myrosinase genes. Interestingly, exogenous selenite supply could partially restore the low level of sulforaphane content in transgenic Arabidopsis FAMA-silencing plants. Our findings uncover a novel function of FAMAMY module in the regulation of selenite-mediated sulforaphane synthesis and provide a new insights into the molecular mechanism by which selenite regulates the accumulation of sulforaphane in plants.

关键词： Brassica oleracea var.italica Myrosinase BoMY Sulforaphane Selenite treatment

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Stock assessment for Atlantic yellowfin tuna based on extended surplus production model considering life history

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Acta Oceanologica Sinica 2022年第8期41卷 41-51页

作者： Zhipan tian Fei Wang Siquan tian qiuyun Ma College of Marine Sciences Shanghai Ocean UniversityShanghai 201306China National Distant-water Fisheries Engineering Research Center Shanghai 201306China Key Laboratory of Sustainable Exploitation of Oceanic Fisheries Resources Ministry of EducationShanghai 201306China Fisheries College Zhejiang Ocean UniversityZhoushan 316022China

The modern fishery stock assessment could be conducted by various models,such as Stock Synthesis model with high data requirement and complicated model structure,and the basic surplus production model,which fails to incorporate individual growth,maturity,and fishery selectivity,etc.In this study,the Just Another Bayesian Biomass Assessment(JABBA)Select which is relatively balanced between complex and simple models,was used to conduct stock assessment for yellowfin tuna(Thunnus albacares)in the Atlantic Ocean.Its population dynamics was evaluated,considering the influence of selectivity patterns and different catch per unit effort(CPUE)indices on the stock assessment results.The model with three joint longline standardized CPUE indices and logistic selectivity pattern performed well,without significant retrospective pattern.The results indicated that the stock is not overfished and not subject to overfishing in 2018.Sensitivity analyses indicated that stock assessment results are robust to natural mortality but sensitive to steepness of the stock-recruitment relationship and fishing selectivity.High steepness was revealed to be more appropriate for this stock,while the fishing selectivity has greater influence to the assessment results than life history parameters.Overall,JABBA-Select is suitable for the stock assessment of Atlantic yellowfin tuna with different selectivity patterns,and the assumptions of natural mortality and selectivity pattern should be improved to reduce uncertainties.

关键词： population dynamics selectivity tropical tuna fishery management

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SOCS2对山羊鼻甲骨细胞增殖、周期及凋亡的影响

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畜牧兽医学报 2024年第5期55卷 2226-2240页

作者：李秋云田芯源廖文圣张焕容任玉鹏杨发龙朱江江向华西南民族大学动物医学四川省高等学校重点实验室成都610041 青藏高原动物遗传资源保护与利用四川省重点实验室成都610041

细胞因子信号转导抑制因子2 (suppressor of cytokine signaling 2,SOCS2)在动物体内参与调节多种生理和病理过程,如细胞凋亡、细胞增殖、细胞周期、肿瘤和炎症反应等。本研究在首次克隆山羊SOCS2基因的基础上,研究过表达和干扰SOCS2表... 详细信息

细胞因子信号转导抑制因子2 (suppressor of cytokine signaling 2,SOCS2)在动物体内参与调节多种生理和病理过程,如细胞凋亡、细胞增殖、细胞周期、肿瘤和炎症反应等。本研究在首次克隆山羊SOCS2基因的基础上,研究过表达和干扰SOCS2表达对山羊鼻甲骨细胞增殖、周期及凋亡的影响。以1周岁的健康简州大耳羊(6只)的心、肝、脾、肺、肾、瘤胃、大肠、小肠和山羊鼻甲骨细胞共9个样本为模板,采用反转录PCR技术克隆山羊SOCS2基因CDS区序列,并进行序列分析。利用RT-qPCR技术检测SOCS2基因在不同组织中的表达。将克隆得到的SOCS2基因CDS区连接载体构建真核表达载体pcDNA3.1-SOCS2。根据山羊SOCS2基因序列设计合成并筛选有效siRNA。利用Lipofectamine^(TM) 3000试剂将pcDNA3.1-SOCS2和siRNA片段分别转染至鼻甲骨细胞,采用蛋白免疫印迹技术检测SOCS2蛋白表达,MTT法检测SOCS2对细胞增殖的影响,流式细胞术检测SOCS2对细胞周期和凋亡的影响,并利用RT-qPCR技术检测细胞周期相关基因p21、CDK2和凋亡相关基因Caspase3、Caspase7、PARP1、p53、Bax、BCL2L11和Bcl-2的转录水平。结果显示,成功扩增山羊SOCS2基因序列,总长为1 065 bp, CDS区长为597 bp,编码198个氨基酸残基。SOCS2基因在肝中表达水平最高;SOCS2可以抑制细胞增殖。成功构建真核表达载体pcDNA3.1-SOCS2,且该基因在鼻甲骨细胞内成功表达。SOCS2过表达可导致G2/M+S期细胞数量显著增加,且下调CDK2和p21基因的mRNA表达;促进细胞凋亡,且上调Caspase3、Caspase7、Bax、p53、BCL2L11、Bcl-2基因的mRNA表达,PARP1表达水平无显著变化。而干扰SOCS2表达后,G0/G1期细胞数量显著升高,且CDK2和p21基因的mRNA表达上调;细胞凋亡被抑制,且Caspase3、Bax、p53、PARP1基因的mRNA表达下调,Caspase7、BCL2L11、Bcl-2基因表达水平无显著变化。综上所述,SOCS2可将细胞周期阻滞在G2/M+S期,促进细胞凋亡,抑制细胞增殖。研究结果为全面揭示山羊SOCS2功能提供试验数据。

关键词：山羊 SOCS2 细胞增殖细胞周期细胞凋亡

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中医药调节炎症因子治疗肠易激综合征研究进展

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实用中医内科杂志 2024年第5期38卷 25-28页

作者：周丽洁黄适田维方威龙覃秋云广西中医药大学广西南宁530001 广西中医药大学附属瑞康医院广西南宁530011

肠易激综合征(irritable bowel syndrome,IBS)是一种常见的功能性胃肠疾病,因其病程长、反复发作、难以根治的特点,给患者带来了许多困扰。肠易激综合征的发病机制尚不明确,目前认为持续性低度炎症与肠易激综合征发生有密切联系,炎症因... 详细信息

肠易激综合征(irritable bowel syndrome,IBS)是一种常见的功能性胃肠疾病,因其病程长、反复发作、难以根治的特点,给患者带来了许多困扰。肠易激综合征的发病机制尚不明确,目前认为持续性低度炎症与肠易激综合征发生有密切联系,炎症因子水平影响炎性反应的发生。西医治疗肠易激综合征长期疗效不佳、容易复发。许多研究表明,中医药可以调控炎症因子,降低炎性反应,减轻内脏敏感性,改善IBS症状,不良反应小、疗效高、复发率低。文章旨在探讨炎症因子与IBS发生的相关性以及中医药调节炎症因子治疗IBS的研究进展。

关键词：肠易激综合征炎症因子中医药研究进展

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电感耦合等离子体原子发射光谱(ICP-AES)法测定真空精炼镁合金物料中铁、铜、镍

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中国无机分析化学 2024年第4期14卷 464-472页

作者：孙洪飞王立鹏李蕊唐飞龙杨柒梅伍秋云田阳吴鉴昆明理工大学云南省有色金属真空冶金重点实验室昆明650093 昆明理工大学省部共建复杂有色金属资源清洁利用国家重点实验室昆明650093 昆明理工大学真空冶金国家工程研究中心昆明650093 昆明理工大学冶金与能源工程学院昆明650093

真空精炼是目前镁金属提纯的重要工艺,工艺原料及真空精炼提纯镁金属过程残留物中Fe、Cu、Ni含量的准确测定对工艺参数的优化及调整具有重要的指导作用。传统测定方法中以邻二氮杂菲分光光度法、新亚铜灵分光光度法、丁二酮肟分光光度... 详细信息

真空精炼是目前镁金属提纯的重要工艺,工艺原料及真空精炼提纯镁金属过程残留物中Fe、Cu、Ni含量的准确测定对工艺参数的优化及调整具有重要的指导作用。传统测定方法中以邻二氮杂菲分光光度法、新亚铜灵分光光度法、丁二酮肟分光光度法测定三种元素含量,结果准确,但操作繁琐,周期较长,难以满足工业生产中高效、快速测定的需要,且方法中所需的有机萃取剂对环境污染较大。选择电感耦合等离子体发射光谱(ICP-AES)法测定真空蒸馏精炼镁合金物料中Fe、Cu、Ni,系统探究溶解酸、溶解温度、溶解时间对物料溶解和测定的影响,选择盐酸(1+1)和过氧化氢溶解体系,200℃加热条件下反应20 min为最佳消解镁合金原料条件;选择王水溶解体系,200℃加热条件下反应25 min为真空精炼残留物最佳溶解条件。并探讨ICP-AES测定过程中各元素的检出限和测定下限以及共存元素的干扰情况,建立了ICP-AES法测定真空精炼提纯镁合金物料的方法。测定结果的相对标准偏差(RSD,n=11)为Fe 5.9%~11.5%、Cu 2.6%~11.8%、Ni 3.4%~11.5%,各元素加标回收率为Fe 96.4%~102%、Cu 101%~108%、Ni 103%~105%;按照建立的方法测定镁合金原料、真空精炼残留物中的铁、铜、镍,并与国家标准方法测定结果进行对比,结果相一致。实现了ICP-AES法快速、准确测定真空蒸馏精炼镁合金物料中铁、铜、镍含量,对及时、高效、准确评估真空精炼提纯镁工艺及产品具有重要意义。

关键词：电感耦合等离子体发射光谱法(ICP-AES) 真空精炼残留物铁铜镍

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基于方元的《伤寒论》用药规律研究

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世界中医药 2024年第5期19卷 706-711页

作者：马重阳徐甜蒋欣妤陈佳慧殷秀敏程发峰王雪茜王庆国张秋云首都医科大学中医药学院北京100069 北京中医药大学中医学院北京100029 北京市通州区玉桥街道社区卫生服务中心北京101101

目的:方元被定义为组成《伤寒论》中方剂有规律可循的最小方剂单元,既体现了方剂的组方特色,又便于临床灵活化裁。本研究拟通过数据挖掘方法,从方元的角度分析《伤寒论》的用药规律。方法:本研究运用R语言计算不同方剂之间Jaccard相似... 详细信息

目的:方元被定义为组成《伤寒论》中方剂有规律可循的最小方剂单元,既体现了方剂的组方特色,又便于临床灵活化裁。本研究拟通过数据挖掘方法,从方元的角度分析《伤寒论》的用药规律。方法:本研究运用R语言计算不同方剂之间Jaccard相似系数及不同中药之间的关联规则,并使用网络社团结构分析,进行《伤寒论》中方元的识别。结果:《伤寒论》中所有方剂的相似性明显高于《方剂学》教材中方剂的相似性,表明方剂中存在更小的方剂单元。关联规则及社团分析能够识别方元,如2味药方元石膏-甘草、桂枝-当归、栀子-香豉等,以及3味药方元干姜-黄连-人参、当归-细辛-通草、麻黄-桂枝-杏仁等。结论:《伤寒论》中存在2味或3味药构成的方元,未来需要对这些方元进行临床或实验上的验证,以明确方元的功效,指导临床应用。

关键词：经方方元方剂结构方剂相似性关联规则社团结构伤寒论数据挖掘

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Effects of genetic polymorphisms on methotrexate levels and toxicity in Chinese patients with acute lymphoblastic leukemia

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Blood Science 2023年第1期5卷 32-38页

作者： Qishan Hao Yang Song qiuyun Fang Yani Lin Long Chen Xiaodan Wang Ping Zhang Zhe Wang Xiaoyuan Gong Kaiqi Liu Qinghua Li Zheng tian Min Wang Jianxiang Wang Yingchang Mi State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina SINO-US Diagnostics Lab TianjinChina

Methotrexate(MTX)has an antitumor effect when used for the treatment of acute lymphoblastic leukemia(ALL).This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX.Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay.The serum MTX concentration was determined using homogeneous enzyme immunoassay.MTX-related toxicities were also evaluated.Renal toxicity was significantly associated with higher serum MTX concentrations at 24,48,and 72 hours,and MTX elimination delay(P=0.001,P<0.001,P<0.001,and P<0.001,respectively),whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours,and MTX elimination delay in candidate polymorphisms(P=0.014,P=0.019,and P=0.007,respectively).SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours(P=0.016,P=0.043,respectively).MTRR rs1801394 was associated with serum MTX concentrations at 72 hours(P=0.045).Neutropenia was related to SLC19A1 rs4149056(odds ratio[OR]:3.172,95%confidence interval[CI]:1.310–7.681,P=0.011).Hepatotoxicity was associated with ABCC2 rs2273697(OR:3.494,95%CI:1.236–9.873,P=0.018)and MTRR rs1801394(OR:0.231,95%CI:0.084–0.632,P=0.004).Polymorphisms of SLCO1B1,SLC19A1,ABCC2,and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.

关键词： Acute lymphoblastic leukemia Concentration Methotrexate Polymorphism Toxicity

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艾灸联合非营养性吸吮及低位灌肠对改善小儿肠造口还纳术后胃肠功能的研究

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中外医学研究 2024年第10期22卷 139-143页

作者：谢舒婷黄鑫鑫王瑶顾祖锐赵文飘谢秋云廖文秀何秀莉曾甜广西壮族自治区妇幼保健院广西南宁530012

目的:探讨艾灸联合非营养性吸吮及低位灌肠在小儿肠造口还纳术后对胃肠功能的影响。方法:选取2022年7月—2023年6月在广西壮族自治区妇幼保健院新生儿外科住院的140例肠造口还纳术后患儿,按随机数表法将入组患儿分为四组,各35例。对照... 详细信息

目的:探讨艾灸联合非营养性吸吮及低位灌肠在小儿肠造口还纳术后对胃肠功能的影响。方法:选取2022年7月—2023年6月在广西壮族自治区妇幼保健院新生儿外科住院的140例肠造口还纳术后患儿,按随机数表法将入组患儿分为四组,各35例。对照组给予低位灌肠+非营养性吸吮,干预1组给予艾灸+非营养性吸吮,干预2组给予艾灸+低位灌肠,干预3组给予艾灸+低位灌肠+非营养性吸吮。比较各组术后胃肠功能指标、肠内外营养相关指标、腹围变化及并发症发生率。结果:干预3组胃液颜色转归时间、肠鸣音恢复时间、腹围恢复时间均早于对照组、干预1组、干预2组,首次排便时间早于对照组、干预1组,差异有统计学意义(P0.05)。结论:艾灸联合非营养性吸吮及低位灌肠在小儿肠造口还纳术后可促进胃肠功能恢复,减少早期并发症发生率。

关键词：肠造口艾灸非营养性吸吮低位灌肠术后胃肠功能

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Resveratrol ameliorates lipopolysaccharide-induced anxiety-like behavior by attenuating YAP-mediated neuroinflammation and promoting hippocampal autophagy in mice

Resveratrol ameliorates lipopolysaccharide-induced anxiety-l...

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2019中国生理学会学术年会暨张锡钧基金第十五届全国青...

作者： Xiaofang Fan qiuyun tian Fukun Zhang Xiaoqiong Shan Junming Fan 龚永生 Institute of Hypoxia Medicine School of Basic Medical SciencesWenzhou Medical University

＜正＞[Objective]:Resveratrol （RSV） has been well documented to protect against inflammatory responses and exert neuroprotective effects.Yes-associated protein （YAP） is a major downstream effector of hippo signaling pathway that plays critical roles in inflammation.However, little is known about the role of RSV on YAP-mediated neuroinflammation associated with mental disorders.The present study was sought to explore whether the anxiolytic effect of RSV was in relation to suppression of YAP pathway and identify its potential mechanism.

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