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lKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies liudi Yao Yilu Zhou Juanjuan li Aiman Alzetani Ben G.Marshall David Hancock tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(lKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39l,a key subunit within the lKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between lKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by lKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39l Crosstalk EMT lKB1 Pulmonary fibrosis

舒芬太尼调节Fas/Fasl信号通路对卵巢癌增殖、迁移和侵袭的影响

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中国优生与遗传杂志 2024年第8期32卷 1587-1592页

作者：王向阳刘安军李波中国人民解放军联勤保障部队第九六〇医院麻醉科山东济南250031 山东大学附属生殖医院麻醉科山东济南250031

目的探讨舒芬太尼对卵巢癌细胞增殖、迁移和侵袭的影响,分析其机制是否与脂肪酸合成酶(Fas)/脂肪酸合成酶配体(Fasl)信号通路有关。方法使用0.001~100μmol/l的舒芬太尼处理卵巢癌细胞SKOV3,筛选最佳药物浓度;将SKOV3细胞分为对照组、... 详细信息

目的探讨舒芬太尼对卵巢癌细胞增殖、迁移和侵袭的影响,分析其机制是否与脂肪酸合成酶(Fas)/脂肪酸合成酶配体(Fasl)信号通路有关。方法使用0.001~100μmol/l的舒芬太尼处理卵巢癌细胞SKOV3,筛选最佳药物浓度;将SKOV3细胞分为对照组、低浓度舒芬太尼组(舒芬太尼-l组,0.01μmol/l舒芬太尼)、中浓度舒芬太尼组(舒芬太尼-M组,0.1μmol/l舒芬太尼)、高浓度舒芬太尼组(舒芬太尼-H组,1μmol/l舒芬太尼)、舒芬太尼-H+sh-NC组、舒芬太尼-H+sh-Fas组。检测各组SKOV3细胞增殖、凋亡、迁移、侵袭能力;Western blot检测E-cadherin、N-cadherin、Snail、Fas、Fasl蛋白表达情况。结果使用0.001~100μmol/l的舒芬太尼处理卵巢癌细胞,细胞存活率显著降低,呈浓度依赖性,选择浓度为0.01、0.1、1μmol/l的舒芬太尼进行后续实验;与对照组相比,舒芬太尼-l组、舒芬太尼-M组、舒芬太尼-H组细胞增殖、迁移、侵袭数,N-cadherin、Snail蛋白水平均降低,细胞凋亡率,E-cadherin、Fas、Fasl蛋白水平均升高(Pl信号通路抑制卵巢癌细胞增殖、迁移和侵袭,促进卵巢癌细胞凋亡。

关键词：舒芬太尼脂肪酸合成酶/脂肪酸合成酶配体信号通路卵巢癌增殖迁移侵袭

浓香型白酒酿造过程中黄浆水理化指标和风味物质的变化规律

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中国酿造 2024年第7期43卷 104-109页

作者：梅漫莉王艳丽何宏魁曹润洁马金同李静心李安军安徽瑞思威尔科技有限公司安徽亳州236820 安徽古井贡酒股份有限公司安徽亳州236820

该研究在浓香型白酒发酵过程中(28周)持续对黄浆水进行取样,探究其主要理化指标和风味物质的变化规律。结果表明,发酵前期黄浆水的酸度快速上升,pH快速降低,发酵2~28周,酸度维持在3.45~4.71 ml/g,pH在3.47~3.91;淀粉含量在发酵开始时急... 详细信息

该研究在浓香型白酒发酵过程中(28周)持续对黄浆水进行取样,探究其主要理化指标和风味物质的变化规律。结果表明,发酵前期黄浆水的酸度快速上升,pH快速降低,发酵2~28周,酸度维持在3.45~4.71 ml/g,pH在3.47~3.91;淀粉含量在发酵开始时急剧减少,之后缓慢减少,最终接近于0;酒精度在发酵前期增加,发酵第6周时达到最高(13.99%vol),发酵中期降低,后期增加并稳定在9.08%vol~9.36%vol。主要风味物质的总含量在发酵前期增多,中后期降低,后期增加并稳定在50240.69~60561.74 mg/l之间;酸类物质发酵前期增加,到第9周时增加到54160.75 mg/l,之后含量降低,最后在43811.51~57237.04 mg/l范围内波动;醇类、酯类物质的含量在发酵前期增长,在发酵9~11周达到最高值并有所波动,后趋于稳定,醇类物质含量稳定在707.50~790.26 mg/l之间,酯类物质含量稳定在1990.90~2266.28 mg/l之间;酚类物质含量前期基本保持不变,中期增长,后期稳定并达到最高(12652μg/l)。

关键词：浓香型白酒黄浆水理化指标风味物质变化规律

典型岩溶矿区突水成因研究——以龙宝煤矿为例

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矿业工程研究 2024年第1期39卷 57-65页

作者：焦安军李继红林华颖田世祥苏谦毕节市能源发展技术中心贵州毕节551799 贵州大学矿业学院贵州贵阳550025 贵州乌江水电开发有限责任公司乌江渡发电厂贵州遵义563100 贵州省矿山安全科学研究院有限公司贵州贵阳550025 贵州华达地质工程有限公司贵州贵阳550000

为研究岩溶地区煤矿采面突水成因,以贵州黔北地区龙宝煤矿为试验地点,采用可控源音频大地电磁法确定水源及导水通道,并结合COMSOl建立突水模型,分析突水过程裂隙水压和突水量变化.采用可控源音频大地电磁法探明突水点附近T_(1)y^(2)地... 详细信息

为研究岩溶地区煤矿采面突水成因,以贵州黔北地区龙宝煤矿为试验地点,采用可控源音频大地电磁法确定水源及导水通道,并结合COMSOl建立突水模型,分析突水过程裂隙水压和突水量变化.采用可控源音频大地电磁法探明突水点附近T_(1)y^(2)地层形成2条导水通道,P_(3)c地层形成5条导水通道,P_(3)l地层形成4条导水通道,煤层采动导致应力场和地下水的天然流场发生变化,在上部地层形成岩体裂隙并贯穿T_(1)y^(1)和T_(1)y^(3)隔水层.通过模拟不同裂隙与工作面导通后的突水量,并结合现场实测突水量综合分析可知,突水前,采空区的冒落带已经导通了Ⅰ号导水通道,使涌水量一直保持在20 m^(3)/h左右;推采过程中,顶板受到采动影响冒落,使采面与Ⅱ号导水通道贯通,导致含水层T_(1)y^(2)中的承压水通过Ⅱ号导水通道瞬间涌入工作面,使涌水量突然增大至100 m^(3)/h.

关键词：突水岩溶地区龙宝煤矿地球物理勘探数值模拟

Development of pharmacological immunoregulatory anticancer therapeutics:current mechanistic studies and clinical opportunities

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2477-2526页

作者： Nanhao Yin Xintong li Xuanwei Zhang Shaolong Xue Yu Cao Gabriele Niedermann You lu Jianxin Xue Division of Thoracic Tumor Multimodality Treatment Cancer Center&State Key Laboratory of Biotherapyand The National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Department of Gynecology and Obstetrics West China Second University HospitalSichuan UniversityNo.20Section 3South Renmin RoadChengdu 610041 SichuanPR China Department of Emergency Medicine Laboratory of Emergency MedicineWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Institute of Disaster Medicine&Institute of Emergency Medicine Sichuan UniversityNo.17Gaopeng AvenueChengdu 610041 SichuanPR China Department of Radiation Oncology Medical Center—University of FreiburgFaculty of MedicineUniversity of FreiburgGerman Cancer Consortium(DKTK)Partner Site DKTK-FreiburgRobert-Koch-Strasse 379106 FreiburgGermany laboratory of Clinical Cell Therapy West China HospitalSichuan UniversityNo.2222Xinchuan RoadChengdu 610041 SichuanPR China

Immunotherapy represented by anti-PD-(l)1 and anti-CTlA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still *** to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable ***,comprehending the larger picture is *** this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint *** with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including lAG-3,tim-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(l)1 and anti-CTlA-4 agents and agonists of co-stimulatory molecules of T *** by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical ***-generation agents also include immune epigenetic drugs and cytokine-based *** therapies,cancer vaccines,and oncolytic viruses are not covered in this *** comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

关键词： clinical immuno landscape

The protective effects of peptides from Chinese baijiu on AAPH-induced oxidative stress in HepG2 cells via Nrf2 signaling pathway

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Food Science and Human Wellness 2022年第6期11卷 1527-1538页

作者： Jiaying Huo Yuezhang Ming Huifeng li anjun li Jiwen Zhao Mingquan Huang Weizheng Sun Jihong Wu Jinglin Zhang Key laboratory of Brewing Molecular Engineering of China light Industry Beijing Technology and Business UniversityBeijing 100048China School of Food Science and Engineering South China University of TechnologyGuangzhou 510640China Inner Mongolia Taibusiqi Grassland King Wine Co. Ltd.Inner Mongolia 027000China Anhui Gujing Distillery Co. Ltd.Anhui 236000China Shandong Bandaojing Co. Ltd.Shandong 256300China

Antioxidant peptides have been widely ***,only a few reports have been published examining the antioxidant peptides derived from Chinese *** this study,6 novel peptides derived from Chinese baijiu were identified successfully using high-performance liquid chromatography-quadrupoletime-of-flight mass spectrometry(HPlC-QTOF-MS)with a concentration of 0.835–24.540μg/*** underlying molecular mechanisms were investigated,and their cytoprotective effects were examined against 2,2’-azobis(2-methylpropanimidamidine)dihydrochloride(AAPH)-induced oxidative stress in Hep G2 *** results showed that these peptides exerted protective effects by suppressing reactive oxygen species(ROS)generation,preventing malondialdehyde(MDA)formation,and upregulating cellular antioxidant enzyme activities(SOD,CAT,and GSH-Px)in a dose-dependent *** experiments proved that these peptides exerted antioxidant effects via Nrf2/ARE-mediated signaling pathway by promoting Nrf2 nuclear translocation,inhibiting ubiquitination,and enhancing transcription capacity of Nrf2 in Hep G2 *** findings provide the molecular basis for the effects of antioxidant peptides derived from Chinese baijiu,which is important for a deeper understanding of the relationship between human health and moderate drinking.

关键词： Chinese baijiu High-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry Antioxidant peptides HepG2 cells Nrf2 signaling pathway

萝卜硫素通过p-mTOR/p-S6信号通路增强CD8^+记忆细胞前体细胞的分化

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中国肿瘤生物治疗杂志 2018年第9期25卷 920-927页

作者：李红张震周斌吕全军张毅郑州大学公共卫生学院河南郑州450052 郑州大学第一附属医院生物细胞治疗中心河南郑州450052

目的:检测萝卜硫素(sulforaphane, SFN)对CD8^+T细胞分化、表型及胞内因子分泌的影响并探讨其可能的调控机制。方法:在体外培养实验中,按照SFN处理的剂量分为对照(0 mmol/l)组、SFN 10 mmol/l组、SFN 20 mmol/l组。采用流式细胞术检测SF... 详细信息

目的:检测萝卜硫素(sulforaphane, SFN)对CD8^+T细胞分化、表型及胞内因子分泌的影响并探讨其可能的调控机制。方法:在体外培养实验中,按照SFN处理的剂量分为对照(0 mmol/l)组、SFN 10 mmol/l组、SFN 20 mmol/l组。采用流式细胞术检测SFN对CD8^+T细胞分化、表型及胞内因子分泌的影响以及mTOR siRNA对CD8^+T细胞CD127和lKRG1表达的影响;采用q RT-PCR检测抗凋亡因子Bcl-2和Bcl-6的表达水平,Annexin-V/PI双染法检测SFN对CD8^+T细胞凋亡的影响,Western blotting检测信号通路蛋白p-mTOR、p-S6以及内参b-actin蛋白的表达。结果:SFN促进CD8^+记忆细胞前体细胞的形成、显著降低CD8^+T细胞PD-1和tim-3的表达水平(Pl-2和Bcl-6的表达显著增加、CD8^+T细胞的凋亡受到显著抑制,p-mTOR和p-S6蛋白表达水平也显著降低(Pl-2、IFN-g、TNF-a的分泌(P27表达及降低lKRG1表达水平(均P<0.01)。结论:SFN可能通过抑制pmTOR信号通路促进CD8^+记忆细胞前体细胞的形成,获得更多年轻化的T细胞,为临床免疫细胞治疗提供新的思路。

关键词：萝卜硫素 p-mTOR/p-S6信号通路 CD8^+记忆细胞前体细胞

Three new lignan glucosides from the roots of Scutellaria baicalensis

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Acta Pharmaceutica Sinica B 2016年第3期6卷 229-233页

作者： Hailin long Haijing Zhang anjun Deng lin Ma lianqiu Wu Zhihong li Zhihui Zhang Wenjie Wang Jiandong Jiang Hailin Qin State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

Three new lignan glucosides, baicalensinosides A-C (1-3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofuran-type lignan glycoside with a mono-hydroxyl substitution at the 7'-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin (OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 mu mol/l, compounds 1-3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Scutellaria baicalensis Roots labiatae lignan glycoside Baicalensinosides A-C 3,4-Dibenzyltetrahydrofuran Osteoprotegenn-activating activity Anti-osteoporotic activity

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人参发根的诱导及其适宜培养条件的研究

生物工程学报 2004年第2期20卷 215-220页

作者：赵寿经李昌禹钱延春骆晓佩张昕王雪松康波愈吉林大学生物与农业工程学院长春130022 中国农业科学院特产研究所吉林132109

利用发根农杆菌A4 菌株在人参根外植体上直接诱导产生发根。在 1 2MS固体培养基上建立起发根离体培养系 ,经连续多代的培养 ,发根仍保持旺盛生长状态。PCR扩增结果表明 ,发根农杆菌Ri 质粒的rolC基因已在人参发根基因组中整合并得到表... 详细信息

利用发根农杆菌A4 菌株在人参根外植体上直接诱导产生发根。在 1 2MS固体培养基上建立起发根离体培养系 ,经连续多代的培养 ,发根仍保持旺盛生长状态。PCR扩增结果表明 ,发根农杆菌Ri 质粒的rolC基因已在人参发根基因组中整合并得到表达。液体培养基中发根生长速度约为固体培养的 2倍。经对发根中人参皂苷含量及比生长速率的测定 ,筛选出高产发根系R992 3。利用HPlC法测定了R992 3发根系中单体皂苷Rg1、Re、Rf、Rb1、Rc、Rb2和Rd的含量 ,人参总皂苷含量达 15 2mg g。确定 1 2MS培养液 (3 0g l蔗糖 )、摇床转速 110r min、每 2周更换一次培养液、继代培养时间 4周 ,为人参发根生长适宜条件。探讨了培养容积。

关键词：发根农杆菌人参根外植体诱导固体培养基质粒基因整合表达人参皂苷