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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： xiu ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

Amplifying protection against acute lung injury:Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

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Chinese Herbal Medicines 2024年第3期16卷 422-434页

作者： Junjie Li Ming Dong Qing Yao Xu Dong Yuanyuan Chen Jincai Wen Yingjie Xu Zhixin Wu Xiaomei Zhao ye xiu Xiaoyan Zhan Zhaofang Bai Xiaohe Xiao Chengde Medical University Chengde 067000China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China National Key Laboratory of Kidney Diseases The Fifth Medical Center of PLA General HospitalBeijing 100039China School of Stomatology Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application&Experimental Center for Stomatology EngineeringJiamusi UniversityJiamusi 154007China Southern Medical University Guangzhou 510515China

Objective:Acute lung injury(ALI)is characterized by inflammation and currently lacks an efficacious pharmacological *** medicine combination of Lonicerae Japonicae Flos(LJF)and Forsythiae Fructus(FF)demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory *** previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ***,there have been no reports of LJF and FF pairing for lung *** aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF)with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism ***:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury *** exudate cells(AECs)were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow ***(MPO)activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and *** effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1βproteins in bone marrow derived macrophages(BMDMs)supernatant was assessed using Western blot method under various inflammasome activation *** addition,the concentration of IL-1βand changes in lactatedehydrogenase(LDH)release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ***,the effects of LJF,FF and LF on STING and IRF3 phosphor

关键词： acute lung injury BMDMS inflammasomes Lonicerae Japonicae Flos-Forsythia Fructus drug pair STING

Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 159-170页

作者： Xiao-Mei Zhao Zhi-Xin Wu Yan Wang Ying-Jie Xu ye xiu Xu Dong Jun-Jie Li Gui-Ji Lv Si-Hao Wang Yu-Rong Li Zhao-Fang Bai Xiao-He Xiao Department of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of Military Patient Management The Fifth Medical Center of PLA General HospitalBeijingChina Department of Hepatology China Military Institute of Chinese Materia The Fifth Medical Center of PLA General HospitalBeijingChina Departmentof Hepatology National Key Laboratory of Kidney DiseasesBeijingChina

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

关键词： Epimedii Folium Fructus Ligustri Lucidi idiosyncratic drug-induced liver injury NOD-like receptor family pyrin domain containing 3 inflammasome traditional Chinese medicine

综合保税区改善城市企业绿色技术创新效应实证研究

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中央财经大学学报 2024年第3期 118-128页

作者：叶修群胡璐蒋嘉云刘长进江西师范大学商学院南京师范大学商学院南昌航空大学经济管理学院

综合保税区在以其扩大对外开放政策平台功能推动经济外向型转型的同时,改善城市企业绿色技术创新效应。笔者以2005—2021年中国内地地级市及以上城市的面板数据,运用双重差分法实证检验了设立综合保税区与城市企业绿色技术创新效应二者... 详细信息

综合保税区在以其扩大对外开放政策平台功能推动经济外向型转型的同时,改善城市企业绿色技术创新效应。笔者以2005—2021年中国内地地级市及以上城市的面板数据,运用双重差分法实证检验了设立综合保税区与城市企业绿色技术创新效应二者之间的关联。检验结果证实:设立综合保税区促进了所在城市企业绿色技术创新效应的提高;综合保税区的制度示范效应和产业结构升级效应与所在城市企业绿色技术创新效应正相关,综合保税区的FDI技术溢出效应与所在城市企业绿色技术创新效应负相关;综合保税区与城市企业绿色技术创新效应的关联性因设立综合保税区城市的地理位置、行政等级和城市规模等不同而表现出异质性;设立综合保税区对城市企业绿色技术创新效应的影响存在某种程度的负空间外部性。本研究将综合保税区通过整合各类海关特殊监管区所具有的多种功能聚焦于如何影响城市企业绿色技术创新效应上,通过实证检验揭示了设立综合保税区与城市企业绿色技术创新效应之间的影响机制,所得研究结论有助于为国家批准、设立综合保税区以及相关部门制定综合保税区具体政策和城市企业充分利用综合保税区改善绿色技术创新效应提供理论依据。

关键词：综合保税区绿色技术创新制度示范 FDI技术溢出产业结构升级

Constructing Order Two Superconvergent WG Finite Elements on Rectangular Meshes

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Numerical Mathematics(Theory,Methods and Applications) 2023年第1期16卷 230-241页

作者： xiu ye Shangyou Zhang Department of Mathematics University of Arkansas at Little RockLittle RockAR 72204USA Department of Mathematical Sciences University of DelawareNewarkDE 19716USA

In this paper,we introduce a stabilizer free weak Galerkin(SFWG)finite element method for second order elliptic problems on rectangular *** a special weak Gradient space,an order two superconvergence for the SFWG finite element solution is obtained,in both L 2 and H1 norms.A local post-process lifts such a Pk weak Galerkin solution to an optimal order Pk+2 *** numerical results confirm the theory.

关键词： Finite element weak Galerkin method stabilizer free rectangular mesh

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牡荆素对慢性阻塞性肺疾病大鼠的作用

中国临床药理学杂志 2024年第2期40卷 210-214页

作者：赖立英刘笑静雷聪云叶秀春丽水市中医院康复科浙江丽水323000 丽水市中医院呼吸科浙江丽水323000 丽水市中医院呼吸与危重症医学科浙江丽水323000

目的研究牡荆素抑制Ras同源类似物C(RhoC)/Rho激酶(ROCK)信号对慢性阻塞性肺疾病大鼠肺组织炎症和气道重塑的影响。方法SD大鼠分成对照组、模型组(慢性阻塞性肺疾病模型)、低剂量实验组(建模后给予1.5 mg·kg^(-1)的牡荆素治疗)、中剂... 详细信息

目的研究牡荆素抑制Ras同源类似物C(RhoC)/Rho激酶(ROCK)信号对慢性阻塞性肺疾病大鼠肺组织炎症和气道重塑的影响。方法SD大鼠分成对照组、模型组(慢性阻塞性肺疾病模型)、低剂量实验组(建模后给予1.5 mg·kg^(-1)的牡荆素治疗)、中剂量实验组(建模后给予3.0 mg·kg^(-1)的牡荆素治疗)、高剂量实验组(建模后给予6.0 mg·kg^(-1)的牡荆素治疗)、高剂量+溶血磷脂酸(LPA)实验组(建模后给予6.0 mg·kg^(-1)的牡荆素和LPA 1 mg治疗)。用蛋白质印迹法检测RhoC蛋白表达,检测大鼠肺功能指标,用苏木精-伊红染色观察肺组织病理学,评价大鼠气道炎症评分、气道平滑肌厚度,用酶联免疫吸附试验法检测肺泡灌洗液中白细胞介素-6(IL-6)含量,用免疫组化检测肺组织中碱性成纤维细胞生长因子(bFGF)表达。结果对照组、模型组、高剂量实验组、高剂量+LPA实验组的RhoC蛋白表达水平分别为0.25±0.02、0.71±0.09、0.31±0.03和0.47±0.04,用力肺活量(FVC)分别为(8.25±0.62)、(4.12±0.24)、(7.21±0.54)和(6.44±0.52)mL,炎症评分分别为0.52±0.04、2.54±0.15、1.23±0.11和1.79±0.32,平滑肌厚度分别为(19.28±1.52)、(28.43±1.74)、(19.45±1.18)和(25.85±1.57)μm,IL-6含量分别为(2.40±0.08)、(5.67±0.44)、(2.85±0.23)和(4.01±0.29)ng·L^(-1),bFGF蛋白表达水平分别为0.19±0.02、0.52±0.05、0.24±0.02和0.43±0.05。模型组的上述指标与对照组比较,高剂量实验组的上述指标与模型组比较,高剂量+LPA实验组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论牡荆素抑制RhoC/Rock信号改善慢性阻塞性肺疾病大鼠肺组织炎症和气道重塑。

关键词：牡荆素慢性阻塞性肺疾病 Ras同源类似物C/Rho激酶信号气道重塑炎症

Four-Order Superconvergent Weak Galerkin Methods for the Biharmonic Equation on Triangular Meshes

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Communications on Applied Mathematics and Computation 2023年第4期5卷 1323-1338页

作者： xiu ye Shangyou Zhang Department of Mathematics University of Arkansas at Little RockLittle RockAR72204USA Department of Mathematical Sciences University of DelawareNewarkDE19716USA

A stabilizer-free weak Galerkin(SFWG)finite element method was introduced and analyzed in ye and Zhang(SIAM ***.58:2572–2588,2020)for the biharmonic equation,which has an ultra simple finite element *** work is a continuation of our investigation of the SFWG method for the biharmonic *** new SFWG method is highly accurate with a convergence rate of four orders higher than the optimal order of convergence in both the energy norm and the L^(2)norm on triangular *** new method also keeps the formulation that is symmetric,positive definite,and ***-order superconvergence error estimates are proved for the corresponding SFWG finite element solutions in a discrete H^(2)*** of four orders in the L^(2)norm is also derived for k≥3,where k is the degree of the approximation *** postprocessing is proved to lift a P_(k)SFWG solution to a P_(k+4)solution elementwise which converges at the optimal *** examples are tested to verify the theor ies.

关键词： Finite element Weak Hessian Weak Galerkin(WG) Biharmonic equation Triangular mesh

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气体检测管在药用气体中的应用研究

药物分析杂志 2024年第3期44卷 475-481页

作者：叶秀金王彩媚王淼胡淑君陈英广东省药品检验所国家药品监督管理局药用辅料质量控制与评价重点实验室广州510663

目的:建立一种药用气体中杂质气体的测定方法。方法:本研究介绍了气体检测管的原理和装置,考察了其准确性、精密度和影响因素等,并用于药用气体中气体杂质的检测。结果:A、B 2个厂家生产的压缩气体检测管受压力影响较大;A、C 2个厂家生... 详细信息

目的:建立一种药用气体中杂质气体的测定方法。方法:本研究介绍了气体检测管的原理和装置,考察了其准确性、精密度和影响因素等,并用于药用气体中气体杂质的检测。结果:A、B 2个厂家生产的压缩气体检测管受压力影响较大;A、C 2个厂家生产的压缩气体检测管及各厂家环境气体检测管受流速影响较大;气体检测管受测定时间影响;环境温度和湿度均可影响H_(2)O检测管的检测,环境湿度对B厂家生产的CO_(2)环境气体检测管也有影响;不同厂家的检测管在同一检测条件下差异性较小,压缩气体检测管在恒流装置下能准确测定气体杂质含量,而部分环境气体检测管不能准确测定;不同原理的检测管杂质干扰不同。提示在气体检测管使用时关注影响因素,选择合适的检测管和方法。结论:本法准确性和精密度较好,可用于药用气体的检测中,为药用气体中杂质气体的检测提供参考。

关键词：气体检测管应用杂质影响因素

超高效液相色谱-离子淌度飞行时间质谱法测定辅料中22种真菌毒素

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药物分析杂志 2024年第3期44卷 434-441页

作者：胡佳哲刘亚雄赖宇红叶秀金王淼杨志业广东省药品检验所国家药监局药用辅料质量控制与评价重点实验室广州510663

目的:建立超高效液相色谱-离子淌度飞行时间质谱法同时检测药用辅料中22种真菌毒素的分析方法。方法:采用Waters CORTECS^(■)UPLC^(■)C_(18)(100 mm×2.1 mm,1.6μm)色谱柱,以0.1%甲酸水溶液-乙腈甲醇混合溶液(60∶40)为流动相,梯度洗... 详细信息

目的:建立超高效液相色谱-离子淌度飞行时间质谱法同时检测药用辅料中22种真菌毒素的分析方法。方法:采用Waters CORTECS^(■)UPLC^(■)C_(18)(100 mm×2.1 mm,1.6μm)色谱柱,以0.1%甲酸水溶液-乙腈甲醇混合溶液(60∶40)为流动相,梯度洗脱,流速0.25 mL·min^(-1),柱温35℃。采用电喷雾离子源,MSe数据采集模式,正、负离子扫描模式,外标法定量。结果:22种真菌毒素在质量浓度为0.2~500μg·L^(-1)范围内,线性关系良好(r均大于0.9985);检测限为0.1~2.0μg·kg^(-1);平均回收率为80.4%~118.2%,RSD为0.20%~8.8%;22种真菌毒素的基质效应不明显。应用该方法检测了32批次玉米淀粉和167批次糊精,其中一些批次检出黄曲霉毒素B1、伏马毒素B1、伏马毒素B2和玉米赤霉烯酮。结论:该方法准确、高效和稳定,可为药用辅料中真菌毒素风险评估提供方法参考。

关键词：药用辅料真菌毒素糊精玉米淀粉玉米赤霉烯酮伏马毒素黄曲霉毒素超高效液相色谱-离子淌度飞行时间质谱有毒有害污染物