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Directly targeting BAX for drug discovery:Therapeutic opportunities and challenges

Acta Pharmaceutica Sinica B 2024年第6期14卷 2378-2401页

作者： Zhenwei Zhang Linghui Hou Dan Liu Shenglin Luan Min Huang Linxiang Zhao Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China China Resources Sanjiu Medical&pharmaceutical Co. Ltd.Shenzhen 518000China

For over two decades,the development of B-cell lymphoma-2(Bcl-2)family therapeutics has primarily focused on anti-apoptotic proteins,resulting in the first-in-class drugs called BH3 mimetics,especially for Bcl-2 inhibitor *** pro-apoptotic protein Bcl-2-associated X protein(BAX)plays a crucial role as the executioner protein of the mitochondrial regulated cell death,contributing to organismal development,tissue homeostasis,and *** dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death,such as cancer,neurodegeneration,and heart *** addition to conducting thorough investigations into the physiological modulation of BAX,research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX,as well as diverse all-molecule BAX *** review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on ***,it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX,offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.

关键词： Apoptosis Pro-apoptotic protein BAX Dynamic conformational activation Small-molecule apoptosis modulators

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Light quality regulates plant biomass and fruit quality through a photoreceptor-dependent HY5-LHC/CYCB module in tomato

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Horticulture Research 2023年第12期10卷 93-107页

作者： Jiarong Yan Juan Liu Shengdie Yang Chenghao Jiang Yanan Liu Nan Zhang Xin Sun Ying Zhang Kangyou Zhu Yinxia Peng Xin Bu Xiujie Wang Golam Jalal Ahammed Sida Meng Changhua Tan Yufeng Liu Zhouping Sun Mingfang Qi Feng Wang Tianlai Li College of Horticulture Shenyang Agricultural UniversityShenyang 110866China College of Land and Environment Shenyang Agricultural UniversityShenyang 110866China College of Horticulture and Plant Protection Henan University of Science and TechnologyLuoyang 471023China Henan International Joint Laboratory of Stress Resistance Regulation and Safe Production of Protected Vegetables Luoyang471023China Key Laboratory of Protected Horticulture Ministry of EducationShenyang 110866China

Increasing photosynthesis and light capture offers possibilities for improving crop yield and provides a sustainable way to meet the increasing global demand for ***,the poor light transmittance of transparent plastic films and shade avoidance at high planting density seriously reduce photosynthesis and alter fruit quality in vegetable crops,and therefore it is important to investigate the mechanisms of light signaling regulation of photosynthesis and metabolism in tomato(Solanum lycopersicum).Here,a combination of red,blue,and white(R1W1B0.5)light promoted the accumulation of chlorophyll,carotenoid,and anthocyanin,and enhanced photosynthesis and electron transport rates by increasing the density of active reaction centers and the expression of the genes LIGHT-HARVESTING COMPLEX B(SlLHCB)and A(SlLHCA),resulting in increased plant *** addition,R1W1B0.5 light induced carotenoid accumulation and fruit ripening by decreasing the expression of LYCOPENEβ-CYCLASE(SlCYCB).Disruption of SlCYCB largely induced fruit lycopene accumulation,and reduced chlorophyll content and photosynthesis in leaves under red,blue,and white *** studies showed that ELONGATED HYPOCOTYL 5(SlHY5)directly activated SlCYCB,SlLHCB,and SlLHCA expression to enhance chlorophyll accumulation and ***,R1W1B0.5 light-induced chlorophyll accumulation,photosynthesis,and SlHY5 expression were largely decreased in the slphyb1cry1 ***,R1W1B0.5 light noticeably promoted photosynthesis,biomass,and fruit quality through the photoreceptor(SlPHYB1 and SlCRY1)-SlHY5-SlLHCA/B/SlCYCB module in ***,the manipulation of light environments in protected agriculture is a crucial tool to regulate the two vital agronomic traits related to crop production efficiency and fruit nutritional quality in tomato.

关键词： crops metabolism quality

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Exploration of anti-cardiac fi brosis active ingredients of Eucalyptus globulus Labill. fruit and their mechanism of action based on chromatography-mass spectrometry and network pharmacology

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Journal of Polyphenols 2023年第1期5卷 1-14页

作者： Minjie Li Xiaoli Wang Tianyu Cheng Weizhuo Tang Xiaoshu Zhang Faculty of Functional Food and Wine Shenyang Pharmaceutical UniversityShenyang 110016China College of Biological and Chemical Engineering Changsha UniversityChangsha 410022China

The fruit of Eucalyptus globulus Labill.,also known as“Yikouzhong(YKZ)”in China,belongs to the myrtaceae *** aim of this study was to characterize the chemical composition of YKZ extract by GC-MS combined with LC-MS/MS.A total of 34 compounds were initially identified by GC-MS and 54 compounds were identified by LC-MS/MS positive and negative total ion flow *** total phenols and flavonoid-like substances were quantified using an enzyme standardization method to determine the presence of phenolic substances in *** the same time,a network pharmacology approach based on LC-MS/MS was used to construct a“drug-component-target”network for myocardial protection,and 696 potential anti-myocardial fibrosis targets were *** PPI analysis identified 72 core targets,and the enrichment analysis revealed that the core targets may exert anti-myocardial fibrosis effects by regulating Lipid and atherosclerosis and Proteoglycans signaling *** together,these results suggest that YKZ anti-cardiac fibrosis may act through multiple components and targets,and this study provides a scientific basis for the functional development and application of YKZ against myocardial fibrosis.

关键词： GC-MS LC-MS/MS total polyphenols myocardial fibrosis network pharmacology

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