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Punicalagin alleviates hypercholesterolemia in mice through modulating farnesoid X receptor signaling and modulating gut microbiota

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Food Science and Human Wellness 2024年

作者： Huanhuan Liu Hongli Liu chunhong yan Jiaxiu Liu Yu Cao Guopeng Li Xiaodong Xia State Key Laboratory of Marine Food Processing and Safety Control National Engineering Research Center of Seafood School of Food Science and Technology Dalian Polytechnic University Beijing Advanced Innovation Center for Food Nutrition and Human Health College of Food Science and Nutritional Engineering China Agricultural University

Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties， but whether and how it could impact hypercholesterolemia remains not fully explored. The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms. After 6 weeks’ intervention， punicalagin significantly reduced serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels in mice fed a high-fat high-cholesterol (HFHC) diet. Meanwhile， punicalagin supplementation lowered hepatic cholesterol level， which corresponded to the down-regulation of cholesterol synthesis genes (Fdps， Cyp51) and up-regulated bile acid synthesis genes (Cyp7a1， Cyp27a1). In addition， bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter (ASBT). Furthermore， intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 (Fgf15) pathway was inhibited while hepatic FXR-small heterodimeric partner (SHP) pathway was activated in punicalagin group. Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase (BSH)-producing bacteria (Clostridiaceae and Bifidobacteriaceae) and the ratio of primary BAs to secondary BAs. In conclusion， the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism， which could be achieved by regulating gut microbiota， altering bile acid composition and modulating FXR signaling pathway. These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.

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以赛促教,建设附属医院优质“双师型”教学队伍——以浙江中医药大学附属第一医院为例

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中国高等医学教育 2024年第5期 31-32,35页

作者：严春红丁曦浙江中医药大学人文与管理学院浙江杭州310053 浙江中医药大学附属第一医院教学部浙江杭州310006

附属医院“双师型”教师的加入,有效缓解了学校的授课压力,但他们在教学技能方面也有待加强。学校联合附属第一医院从培训内容、指导团队、职能部门辅助、选拔与奖励等方面着手,构建全面综合的教学竞赛培训体系,不仅有助于参赛教师取得... 详细信息

附属医院“双师型”教师的加入,有效缓解了学校的授课压力,但他们在教学技能方面也有待加强。学校联合附属第一医院从培训内容、指导团队、职能部门辅助、选拔与奖励等方面着手,构建全面综合的教学竞赛培训体系,不仅有助于参赛教师取得佳绩,更重要的是以赛促教,通过培训成果的后续推广,对其他教师起到示范作用,整体提升“双师型”教师的教学水平,从而达成国家对于“医教协同”的期望。

关键词：附属医院双师型教学技能竞赛培训体系

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促肾上腺皮质激素释放因子2型受体参与慢性偏头痛小鼠痛觉敏化及焦虑的机制研究

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中华神经医学杂志 2024年第2期23卷 131-139页

作者：邹鲁宏阎春红武琳智张雪娟边疆攀枝花市中心医院麻醉科攀枝花617000 攀枝花市中心医院普外科攀枝花617000

目的探讨促肾上腺皮质激素释放因子2型受体(CRFR2)对慢性偏头痛小鼠痛觉敏化及焦虑的调控作用及潜在机制。方法将48只C57BL/6J小鼠按随机数字表法分为对照组、模型组、NBI35965组、K41498组,每组12只。后3组小鼠于第1、3、5、7、9天腹... 详细信息

目的探讨促肾上腺皮质激素释放因子2型受体(CRFR2)对慢性偏头痛小鼠痛觉敏化及焦虑的调控作用及潜在机制。方法将48只C57BL/6J小鼠按随机数字表法分为对照组、模型组、NBI35965组、K41498组,每组12只。后3组小鼠于第1、3、5、7、9天腹腔注射10 mg/kg硝酸甘油建立慢性偏头痛模型,NBI35965组及K41498组小鼠于第2、4、6、8天双侧三叉神经脊束尾核分别注射100 nL NBI35965、K41498溶液,对照组小鼠注射同体积生理盐水。第1、3、5、7、9天腹腔注射2 h后及第10天上午11时采用Von frey纤维丝检测小鼠眶额部机械痛阈值。于第11天上午11时采用高架十字迷宫实验检测小鼠的焦虑样行为。采用Western blotting实验检测小鼠三叉神经脊束尾核中促肾上腺皮质激素释放因子(CRF)、促肾上腺皮质激素释放因子1型受体(CRFR1)、CRFR2蛋白的表达。采用实时荧光定量聚合酶链式反应(RT-qPCR)检测小鼠三叉神经脊束尾核中CRFR1及CRFR2 mRNA的表达。采用免疫荧光染色检测小鼠三叉神经脊束尾核中降钙素基因相关肽(CGRP)、即刻早期基因(c-fos)、胶质纤维酸性蛋白(GFAP)及离子钙结合适配器分子1(Iba-1)蛋白的表达。结果 (1)与对照组比较,模型组、NBI35965组、K41498组小鼠第3、5、7、9、10天的眶额部机械痛阈值较低,差异均有统计学意义(P<0.05)。与模型组比较,K41498组小鼠第7、9、10天的眶额部机械痛阈值较高,差异均有统计学意义(P<0.05)。(2)与对照组比较,模型组、NBI35965组、K41498组小鼠的开臂进入次数较少,开臂停留时间较短,差异均有统计学意义(P<0.05)。与模型组比较,K41498组小鼠的开臂进入次数较多,开臂停留时间较长,差异均有统计学意义(P<0.05)。(3)与对照组比较,模型组、NBI35965组、K41498组小鼠三叉神经脊束尾核中CRF和CRFR2蛋白的表达较高,差异均有统计学意义(P<0.05)。与模型组比较,K41498组小鼠三叉神经脊束尾核中CRF蛋白的表达较低,差异有统计学意义(P<0.05)。(4)与对照组比较,模型组、NBI35965组、K41498组小鼠三叉神经脊束尾核中CRFR2 mRNA的表达较高,差异均有统计学意义(P<0.05)。(5)与对照组比较,模型组、NBI35965组、K41498组小鼠三叉神经脊束尾核中CGRP、c-fos、Iba-1、GFAP蛋白的表达均较高,差异均有统计学意义(P<0.05)。与模型组比较,K41498组小鼠三叉神经脊束尾核中CGRP及c-fos蛋白的表达较低,差异均有统计学意义(P<0.05)。结论 CRFR2通过调控三叉神经脊束尾核的神经元活化及CGRP释放而影响慢性偏头痛小鼠眶额部痛觉敏化及焦虑样行为的发生发展。

关键词：慢性偏头痛促肾上腺皮质激素释放因子三叉神经脊束尾核痛觉敏化焦虑

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Ferroptosis:An emerging therapeutic opportunity for cancer

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Genes & Diseases 2022年第2期9卷 334-346页

作者： Liyuan Wang Xiaoguang Chen chunhong yan Georgia Cancer Center Augusta UniversityAugustaGA 30912USA Department of Pharmacology Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China Department of Pharmacy Peking University Third HospitalBeijing 100191China Department of Biochemistry and Molecular Biology Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Ferroptosis,a new form of non-apoptotic,regulated cell death characterized by iron dependency and lipid peroxidation,is involved in many pathological conditions such as neurodegenerative diseases,heart ischemia/reperfusion injury,acute renal failure,and *** metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death,glutathione peroxidase 4(GPX4)resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation,thereby suppressing ***,RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in ***,erastin and other system Xc−inhibitors can deplete intracellular glutathione required for GPX4 function,leading to lipid peroxidation and *** therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens,the agents capable of inducing ferroptosis hold great promises to improve current cancer *** review will outline the molecular basis of ferroptosis,but focus on the strategies and the agents developed in recent years for therapeutic induction of *** potentials of these ferroptosis-inducing agents,which include system Xc−inhibitors,GPX4 inhibitors,and iron-based nanoparticles,in cancer therapy will be subsequently discussed.

关键词： Cancer therapy Erastin Ferroptosis GPX4 Lipid peroxidation Nanomedicine RSL3 System Xc-

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双向质量反馈护理模式在肝硬化合并上消化道出血患者中的应用效果

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临床医学研究与实践 2024年第20期9卷 148-151页

作者：沈蔚史亚非黄本卿闫春红联勤保障部队第九九〇医院河南驻马店463000

目的分析双向质量反馈护理模式在肝硬化合并上消化道出血患者中的应用效果。方法选取2021年1月至2023年12月我院收治的120例肝硬化合并上消化道出血患者为研究对象,随机将其分为常规组和观察组,各60例。常规组实施常规护理,观察组在常... 详细信息

目的分析双向质量反馈护理模式在肝硬化合并上消化道出血患者中的应用效果。方法选取2021年1月至2023年12月我院收治的120例肝硬化合并上消化道出血患者为研究对象,随机将其分为常规组和观察组,各60例。常规组实施常规护理,观察组在常规护理基础上实施双向质量反馈护理模式护理。比较两组的干预效果。结果观察组的大便潜血转阴时间、住院时长短于常规组,肝性脑病、继发性感染、便秘及再次出血发生率低于常规组(P<0.05)。干预后,两组的汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)及匹兹堡睡眠质量指数(PSQI)评分均降低,生活质量核心调查问卷(QLQ-C30)评分均升高,且观察组优于常规组(P<0.05)。干预后,两组的疾病诱因、疾病症状、疾病危害及自身治疗方案评分均升高,且观察组高于常规组(P<0.05)。观察组的护理满意度高于常规组(P<0.05)。结论双向质量反馈护理模式可缩短肝硬化合并上消化道出血患者的康复进程,降低不良事件发生率,减轻心理负担,改善睡眠障碍,提升生活质量及护理满意度,从而取得理想护理效果。

关键词：肝硬化上消化道出血双向质量反馈护理模式

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Cytoskeleton-associated protein tyrosine phosphorylation involved in induction of differentiation in mouse melanoma cells

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Chinese Science Bulletin 1999年第4期44卷 335-339页

作者： chunhong yan Rui Han Chinese Acad Med Sci Inst Mat Med Beijing 100050 Peoples R China Peking Union Med Coll Beijing 100050 Peoples R China

The malignancy of a cancer is due partly to its poor differentiation. Genistein, a protein tyrosine kinase inhibitor, is found to induce the highly malignant B16-BL6 mouse melanoma cells to differentiate to mature phenotypes. When Triton X-100 insoluble fraction of the differentiated cells is prepared and analyzed, tyrosine phosphorylation levels of three cytoskeleton-associated proteins (65, 60 and 53 ku respectively) are found to decrease dramatically. But no any change is found when phosphotyrosine contents of the cytosol fraction or the total cellular protein preparations are evaluated. It is concluded that cytoskeleton-associated protein tyrosine phosphorylation may be involved in the control of differentiation of cancer cells. The decrease of phosphotyrosine contents of cytoskeleton-associated proteins may be one of the important mechanisms underlying the differentiation induction of cancer cells by anticancer agents.

关键词： cytoskeleton-associated protein protein tyrosine phosphorylation cancer cell differentiation protein tyrosine ki-nase inhibitor.

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PCC0208017,a novel small-molecule inhibitor of MARK3/MARK4,suppresses glioma progression in vitro and in vivo

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Acta Pharmaceutica Sinica B 2020年第2期10卷 289-300页

作者： Fangfang Li Zongliang Liu Heyuan Sun Chunmei Li Wenyan Wang Liang Ye chunhong yan Jingwei Tian Hongbo Wang School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs inUniversities of ShandongYantai UniversityYantai 264005China Department of Clinical Medicine Binzhou Medical CollegeYantai 256603China GRU Cancer Center Augusta UniversityAugustaGA 30912USA

Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for ***,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as *** vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell *** compound attenuated glioma cell migration,glioma cell invasion,and *** mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle *** an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic *** docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and *** together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.

关键词： Glioma PCC0208017 MARK3 MARK4 Molecular docking

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Design,Synthesis and Biological Activities of Quinazoline Containing Sorafenib Analogs as Antitumor Agents

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Wuhan University Journal of Natural Sciences 2017年第3期22卷 239-246页

作者： ZHANG Jingwen WANG Ningning XIE Xiaoxia yan chunhong FU Fenghua YAO Jianwen WANG Hongbo School of Pharmacy Yantai University Yantai 264005Shandong China GRU Cancer Center Georgia Regents University AugustaGA 30912 USA

A series of novel sorafenib derivatives containing quinazoline moiety were designed and synthesized. Their anti-proliferative activities against HCT116 and HCT115 cell lines were evaluated using MTT assay. Most of the synthesized compounds showed significant cytotoxicity against the selected cell lines. These cytotoxicities were consistent with their inhibitory activity against the phosphorylation of c-Raf, MEK1/2 and ERK1/2. Compound GD-09 also showed much stronger anti-tumor activity than that of sorafenib in vivo by B16 melanoma xenograft model test.

关键词： sorafenib analogs synthesis quinazoline antitumor agents

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Lx2-32c,a novel semi-synthetic taxane,exerts antitumor activity against prostate cancer cells in vitro and in vivo

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Acta Pharmaceutica Sinica B 2017年第1期7卷 52-58页

作者： Guangyao Lv Dengjun Sun Jingwen Zhang Xiaoxia Xie Xiaoqiong Wu Weishuo Fang Jingwei Tian chunhong yan Hongbo Wang Fenghua Fu School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University)Ministry of EducationYantai University Departments of Medical Oncology Affiliated Yuhuangding HospitalMedical College of Qingdao University The Military Affiliated General Hospital of Beijing PLA State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College GRU Cancer Center Georgia Regents University

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32 c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32 c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32 c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32 c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly(ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32 c was shown by Western blotting assay. Xenograft implants of LNCa P and PC3-derived tumors in nude mice showed that Lx2-32 c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32 c as a candidate antitumor agent for the treatment of prostate cancer.

关键词： Lx2-32c Cephalomannine Prostate cancer Microtubule Cell cycle arrest Apoptosis

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新基建助推“双碳”目标达成的逻辑和建议

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价格理论与实践 2022年第4期 5-8,52页

作者：裴棕伟闫春红政信投资集团有限公司中国社会科学院技术创新与战略管理研究中心

实现“碳中和、碳达峰”是推动我国经济高质量发展的必由之路,而新型基础设施恰是当前经济高质量发展的重要驱动载体,厘清新基建助推“双碳”目标达成的逻辑具有一定理论意义和实践价值。本文从新基建助推“双碳”目标达成的现实背景出... 详细信息

实现“碳中和、碳达峰”是推动我国经济高质量发展的必由之路,而新型基础设施恰是当前经济高质量发展的重要驱动载体,厘清新基建助推“双碳”目标达成的逻辑具有一定理论意义和实践价值。本文从新基建助推“双碳”目标达成的现实背景出发,在明确“双碳”目标和新基建内涵的基础上,分析新基建助推“双碳”目标达成的必要性,并从科技创新助推节能减排、数字经济助推低碳发展、产业赋能助推绿色转型三个方面入手,构建新基建助推“双碳”目标达成的逻辑框架,建议未来加强顶层设计、强化目标协同、坚持科技减排、争取多元融资、打通政策壁垒,促进新基建成为“双碳”目标达成的新路径。

关键词：新型基础设施建设碳达峰碳中和数字经济低碳发展

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