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AMPK-ChREBP axis mediates de novo milk fatty acid synthesis promoted by glucose in the mammary gland of lactating goats

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Animal Nutrition 2022年第3期10卷 234-242页

作者： Hengbo Shi Nannan jiang Ling Wei Jie Cai Wenying Zhang Qianming Jiang Juan JLoor Jianxin Liu Institute of Dairy Science College of Animal SciencesZhejiang UniversityHangzhou310058China College of Life Sciences and Medicine Zhejiang Sci-Tech UniversityHangzhou310018China Mammalian Nutrition Physiology Genomics Department of Animal Sciences and Division of Nutritional SciencesUniversity of IllinoisUrbanaIL61801USA

To investigate the role of glucose in regulating milk fatty acid synthesis,6 lactating Guanzhong dairy goats were infused with 0,60,or 100 g/d glucose via the external pubic artery in a 33 repeated Latin square experiment.A concomitant in vitro experiment was conducted to investigate possible mechanisms whereby glucose regulates milk fatty acid synthesis.RNA sequencing was used for cellular transcriptome analysis.Drugs,MK-2206,rapamycin,and dorsomorphin were used to block cellular mammalian AMP-activated protein kinase(AMPK),AKT serine/threonine kinase 1,and mechanistic target of rapamycin kinase signaling pathways,respectively.Carbohydrate response element binding protein(ChREBP)was knockdown and overexpressed to investigate its role in regulating milk fatty acid synthesis in mammary epithelial cells.Glucose infusion linearly elevated the concentration of C8:0(P=0.039)and C10:0(P=0.041)in milk fat while it linearly decreased(P=0.049)that of C16:0.This result was in agreement with the upregulation of genes related to de novo synthesis of fatty acids and lipid droplet formation,including adipose differentiation-related protein,butyrophilin subfamily 1 member A1,fatty acid synthase(FASN)and ChREBP.Their expression increased(P<0.05)linearly in the lactating goat mammary gland.In vitro,glucose linearly stimulated the expression of genes related to de novo synthesis of fatty acids and cellular triacylglycerol in cultured mammary epithelial cells.RNA sequencing and inhibition studies revealed that glucose induced transcriptomic changes increasing lipogenic pathways,with AMPK responding to glucose by controlling ChREBP and FASN.Knockdown and overexpression of ChREBP highlighted its essential role in lipogenesis.The knockdown and overexpression of ChREBP protein also revealed an essential role in regulating the de novo synthesis of fatty acids.Collectively,our data highlight that glucose supplementation promotes de novo fatty acid synthesis via the AMPK-ChREBP axis,hence increasing milk fat yield in the goat mammary gla

关键词： Milk fat Glucose infusion Mammary gland Carbohydrate response element binding protein De novo synthesis

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Comparison of fatty acid profile of three adipose tissues in Ningxiang pigs

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Animal Nutrition 2018年第3期4卷 256-259页

作者： Qianming Jiang Chenyan Li Yuannian Yu Yueteng Xing Dingfu Xiao Bin Zhang Hunan Co-Innovation Center of Animal Production Safety College of Animal Science and Technology Hunan Agricultural University

The present study is conducted to determinate fatty acids(FA) composition in 3 adipose tissues. Subcutaneous and perirenal adipose tissues were prepared from 24 Ningxiang castrated boars and 24 castrated gilts fattened by a traditional diet for 56 d, respectively. The results showed that the FA profile in the 3 adipose tissues(dorsal subcutaneous adipose [DSA], abdominal subcutaneous adipose [ASA], and perirenal adipose [PA]) differed greatly. In boars, the proportions of oleic acid(c18:1 n9 c)(P < 0.05), cis-11-20 c acid(c20:1)(P < 0.05), and a-linolenic acid(c18:3 n3)(P < 0.05) in DSA were the highest among 3 adipose tissues, whereas palmitic acid(c16:0)(P < 0.05) and stearic acid(c18:0)(P < 0.05) in DSA had the lowest proportion. In gilts, cis-11-20 c acid(c20:1)(P < 0.05) in DSA was the highest, while stearic acid(c18:0)(P < 0.05) in subcutaneous adipose was the lowest among these deposits. Overall, the results indicate that from external to inner carcass of boars, the sum of saturated fatty acids(SFA) increase, but the sum of monounsaturated fatty acids(MUFA) decrease, while ASA of gilts have the greatest proportion of MUFA and the lowest SFA. Sex and adipose locations as significant effects on the FA profile are interaction.

关键词： Fatty acid Dorsal subcutaneous adipose Abdominal subcutaneous adipose Perirenal adipose Ningxiang pig

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Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids

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Journal of Animal Science and Biotechnology 2022年第5期13卷 1458-1468页

作者： Renxu Chang Xudong Sun Hongdou Jia Qiushi Xu Zhihao Dong Yan Tang Shengbin Luo Qianming Jiang Juan J.Loor Chuang Xu College of Veterinary Medicine China Agricultural UniversityYuan Ming Yuan West Road No.2Haidian DistrictBeijing 100193China College of Veterinary Medicine Hunan Agricultural UniversityChangsha 410128China Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases College of Animal Science and Veterinary MedicineHeilongjiang Bayi Agricultural UniversityNo.5 Xinyang RoadDaqing 163319Heilongjiang ProvinceChina Mammalian NutriPhysioGenomics Department of Animal Sciences and Division of Nutritional SciencesUniversity of IllinoisUrbana 61801USA

Background:In early lactation,bovine mammary epithelial cells undergo serious metabolic challenges and oxidative stress both of which could be alleviated by activation of autophagy.Nuclear factor erythroid 2 related factor 2(NFE2L2),a master regulator of cellular redox homeostasis,plays an important role in the regulation of autophagy and oxidative stress.Thus,the objective of this study was to investigate the role of NFE2L2-mediated autophagy on oxidative stress of bovine mammary epithelial cells in response to exogenous free fatty acids(FFA).Results:Exogenous FFA induced linear and quadratic decreases in activities of glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD),and increases in the contents of reactive oxygen species(ROS)and malondialdehyde(MDA).Protein abundance of LC3-phosphatidylethanolamine conjugate(LC3-Ⅱ)and the number of autophagosomes and autolysosomes decreased in a dose-dependent manner,while protein abundance of p62 increased in cells challenged with FFA.Activation of autophagy via pre-treatment with Rap attenuated the FFAinduced ROS accumulation.Importantly,FFA inhibited protein abundance of NFE2L2 and the translocation of NFE2L2 into the nucleus.Knockdown of NFE2L2 by siRNA decreased protein abundance of LC3-Ⅱ,while it increased protein abundance of p62.Furthermore,sulforaphane(SFN)pre-treatment attenuated the FFA-induced oxidative stress by activating NFE2L2-mediated autophagy.Conclusions:The data suggested that NFE2L2-mediated autophagy is an important antioxidant mechanism in bovine mammary epithelial cells experiencing increased FFA loads.

关键词： Autophagy Bovine mammary epithelial cells NFE2L2 Oxidative stress

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SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation

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International Journal of Oral Science 2021年第1期13卷 62-70页

作者： Xuemei Qiu Sheng jiang Yanxuan Xiao Yumin He Tao Ren Lu jiang Rui Liu qianming Chen State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management West China Hospital of StomatologySichuan UniversityChengduChina Ministry of science and technology The Second Affiliated Hospital of Chengdu Medical College(China National Nuclear Corporation 416 Hospital)ChengduChina Oncology Department Clinical Medical College and The First Affiliated Hospital of Chengdu Medical CollegeChengduChina

Oral squamous cell carcinoma(OSCC)become a heavy burden of public health,with approximately 300000 newly diagnosed cases and 145000 deaths worldwide per year.Nucleotide metabolism fuel DNA replication and RNA synthesis,which is indispensable for cell proliferation.But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown.Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase(DHODH)is upregulated in OSCC tissues,compared to non-cancerous adjacent tissues.Enhanced expression of DHODH is correlated with a shortened patient survival time.Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft.Further,loss of functional DHODH imped de novo pyrimidine synthesis,and disrupt mitochondrial respiration probably through destabilizing the MICOS complex.Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC.Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth,and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.

关键词： SOX2 metabolism squamous

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1例表现为非典型性血管增生的放射性口腔黏膜炎

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华西口腔医学杂志 2022年第6期40卷 721-726页

作者：王显文陈谦明江潞口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心四川大学华西口腔医院口腔黏膜病科成都610041

放射性口腔黏膜炎是因放射线电离辐射引起的口腔黏膜损伤,常表现为口腔黏膜充血、糜烂和溃疡,表现为非典型性血管增生的情况国内外未见报道。本文首次报道1例颌面部恶性肿瘤放疗后发生口腔黏膜非典型性血管增生改变的病例,结合该病例的... 详细信息

放射性口腔黏膜炎是因放射线电离辐射引起的口腔黏膜损伤,常表现为口腔黏膜充血、糜烂和溃疡,表现为非典型性血管增生的情况国内外未见报道。本文首次报道1例颌面部恶性肿瘤放疗后发生口腔黏膜非典型性血管增生改变的病例,结合该病例的诊治情况及既往文献报道,讨论了颌面部放射治疗导致口腔黏膜出现非典型性血管增生的发生机制及其治疗方案。

关键词：放射性口腔黏膜炎非典型性血管增生口腔放射治疗

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协同育人模式下高职本科专业课程体系构建研究与实践--以广东食品药品职业学院药学专业为例

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职业技术教育 2020年第11期41卷 28-32页

作者：张谦明江永南广东食品药品职业学院广州510520 广东食品药品职业学院药学院

高职本科协同育人试点改革成为当前本科层次职业教育最为主要的途径。开展高职本科协同育人试点,开展高职本科专业课程体系构建研究与实践,是培养高素质技术技能人才,提升人才培养质量的现实需要。调研表明,我国执业药师数量短缺,传统... 详细信息

高职本科协同育人试点改革成为当前本科层次职业教育最为主要的途径。开展高职本科协同育人试点,开展高职本科专业课程体系构建研究与实践,是培养高素质技术技能人才,提升人才培养质量的现实需要。调研表明,我国执业药师数量短缺,传统专业毕业生所掌握的知识与技能不能很好地满足社会的需求。因此,高职本科协同育人试点专业应该对普通本科与高职教育的课程体系进行改革,推动基础理论知识学习与实践教学有机结合,适当增加实践教学课时,促进学生设计与研发能力和职业岗位技能的有效提升。

关键词：协同育人模式高职本科课程体系药学专业

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Controllable microfluidic strategies for fabricating microparticles using emulsions as templates

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Particuology 2016年第1期14卷 18-31页

作者： Maojie Zhang Wei Wang Rui Xie Xiaojie Ju Zhuang Liu Lu jiang qianming Chen Liangyin Chu School of Chemical Engineering Sichuan University Chengdu 610065 China State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610065 China State Key Laboratory of Oral Diseases Sichuan University Chengdu 610041 China

Microfluidic techniques provide flexible strategies for fabrication of uniform advanced microparticles with well-tailored sizes, shapes, structures, and functions from controllable emulsion templates. This review highlights recent progress on controllable synthesis of microparticles using versatile microfluidic emulsions as templates, First, highly controllable and scalable microfluidic techniques for the generation of defined emulsions are introduced. Versatile microfluidic strategies for fabricating microparticles from diverse controllable emulsion templates are then summarized, including solid microparticles with spher- ical, non-spherical, and Janus configurations, porous microparticles with flexible pore structures, and compartmental microparticles with controlled internals. Finally, the future development of microfluidic techniques for microparticle fabrication is briefly discussed.

关键词： Microfluidics Microparticle Microreactor Emulsion Template synthesis

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毒蕈碱受体通过Yes相关蛋白信号对口腔鳞状细胞癌生物学行为的实验研究

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国际口腔医学杂志 2022年第2期49卷 138-143页

作者：江涵神应强陈谦明口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心口腔黏膜病国家临床重点专科中国医学科学院口腔黏膜癌变与防治创新单元四川大学华西口腔医院口腔黏膜病科成都610041

目的研究毒蕈碱(m)受体在口腔鳞状细胞癌(OSCC)中发挥的作用及机制。方法分析癌症基因图谱(TCGA)数据库,并利用实时定量聚合酶链式反应(RT-qPCR)荧光定量查询和检测m受体基因在头颈部肿瘤和OSCC细胞中的表达水平,再采用m受体激动剂卡巴... 详细信息

目的研究毒蕈碱(m)受体在口腔鳞状细胞癌(OSCC)中发挥的作用及机制。方法分析癌症基因图谱(TCGA)数据库,并利用实时定量聚合酶链式反应(RT-qPCR)荧光定量查询和检测m受体基因在头颈部肿瘤和OSCC细胞中的表达水平,再采用m受体激动剂卡巴胆碱进一步研究其对OSCC细胞增殖和侵袭的影响,最终利用免疫荧光探究激活m受体对OSCC细胞内Yes相关蛋白(YAP)核转位的影响。结果m受体基因在头颈部肿瘤中有表达差异:在5种OSCC细胞系中HN4和HN12的m3受体基因高表达(P<0.05)。激活m受体具有促进OSCC细胞增殖和侵袭的潜能,促进YAP的核转位可能是m受体的作用机制。结论m受体在OSCC发生发展中发挥重要作用,靶向m受体可能是未来治疗OSCC的新策略。

关键词：毒蕈碱受体口腔鳞状细胞癌卡巴胆碱

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减毒5-氟尿嘧啶乳糖苷衍生物的合成及抗口腔鳞状细胞癌活性的实验研究

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华西口腔医学杂志 2022年第1期40卷 32-38页

作者：张羽婷刘江赵行何杨陈谦明口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心中国医学科学院口腔黏膜癌变与防治创新单元四川大学华西口腔医院口腔黏膜病科成都610041 呼吸健康研究所靶向示踪研究室疾病分子网络前沿科学中心四川大学华西医院呼吸与重症医学科成都610041

目的为降低5-氟尿嘧啶(5-FU)毒性,设计并合成了5-FU乳糖苷衍生物,并初步探究其抗肿瘤活性。方法采用Vorbrüggen法合成5-FU乳糖苷衍生物,通过高分辨质谱(HRMS)、核磁共振氢谱(^(1)HNMR)、核磁共振碳谱(^(13)CNMR)、异核多量子相干谱(HM... 详细信息

目的为降低5-氟尿嘧啶(5-FU)毒性,设计并合成了5-FU乳糖苷衍生物,并初步探究其抗肿瘤活性。方法采用Vorbrüggen法合成5-FU乳糖苷衍生物,通过高分辨质谱(HRMS)、核磁共振氢谱(^(1)HNMR)、核磁共振碳谱(^(13)CNMR)、异核多量子相干谱(HMQC)及异核多键相关谱(HMBC)表征其结构,并用细胞计数试剂盒8(CCK-8)研究其体外毒性及抗肿瘤活性。结果用简单高效的方法合成了目标化合物Ⅰa、Ⅰb,并通过HRMS、^(1)HNMR、^(13)CNMR、HMQC及HMBC证实了Ⅰa、Ⅰb分别为N-1位及N-3位乳糖基取代的5-FU核苷衍生物;经CCK-8法验证较高浓度(0.7μmol·mL^(-1))Ⅰa、Ⅰb处理24 h对正常口腔角质形成细胞NOK生长的抑制率分别为30.28%及50.68%,均较5-FU的抑制作用弱(68.22%,P<0.05),其中Ⅰb对2种口腔鳞状细胞癌细胞的生长均有较显著的抑制作用,0.7μmol·mL^(-1)浓度下处理Cal-27细胞及UM SCC-47细胞24 h后抑制率分别为81.20%、80.19%。结论目标化合物Ⅰa、Ⅰb较5-FU具有较低毒性,且Ⅰb较Ⅰa具有更明显的抗口腔鳞状细胞癌细胞增殖活性。

关键词： 5-氟尿嘧啶乳糖苷衍生物减毒抗肿瘤口腔鳞状细胞癌

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RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair

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Bone Research 2022年第2期10卷 367-377页

作者： Yanxuan Xiao Jingyi Li Xiaoyu Liao Yumin He Tao He Cuiping Yang Lu jiang So Mi Jeon Jong-Ho Lee Yongbin Chen Rui Liu qianming Chen State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and ManagementWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China The Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 HospitalChengduSichuan 610051China School of Biological Sciences and Technology Chengdu Medical CollegeChengdu 610599China Department of Cardio-thoracic Surgery the Second Affiliated Hospital of Chengdu Medical CollegeChina National Nuclear Corporation 416 HospitalChengduSichuan 610051China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences Yunnan Province Kunming Institute of ZoologyKunmingYunnan 650223China Department of Health Sciences The Graduate School of Dong-A UniversityBusan 49315Republic of Korea Department of Biological Sciences Dong-A UniversityBusan 49315Republic of Korea Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China

Exposure to radiation causes DNA damage;hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1(RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination(HR) repair but not nonhomologous endjoining(NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase(c GAS) to release c GAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29(SGF29), which subsequently enables c GAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1(PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains c GAS K491 me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of c GAS that is essential for the regulation of ionizing radiation-elicited HR repair.

关键词： thereby repair remove

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