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Dysregulation of the HIF-1α/BNIP3 axis links defective mitophagy to glycolytic reprogramming in a rat model of gastric precancerogenesis 认领 引用
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作者 Xin-Fang Zhang Guan-Hua Lv +4 位作者 Shu-Jian An Xi-Ran Yang Wen-Zhao Guo Chen-Yang Yu Cheng-Hui Zhu 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第4期244-258,共15页
BACKGROUND Chronic atrophic gastritis is a common gastric disorder frequently accompanied by precancerous lesions,including intestinal metaplasia and dysplasia.Progression of these lesions represents a critical stage ... BACKGROUND Chronic atrophic gastritis is a common gastric disorder frequently accompanied by precancerous lesions,including intestinal metaplasia and dysplasia.Progression of these lesions represents a critical stage in gastric carcinogenesis.Hypoxia-inducible factor 1-alpha(HIF-1α)and BCL2/adenovirus E1B 19 kDa interacting protein 3(BNIP3)are key regulators of cellular hypoxia responses and mitophagy,while metabolic reprogramming toward glycolysis is closely associated with gastric mucosal transformation.We hypothesized that dysregulation of HIF-1α/BNIP3 signaling promotes precancerous lesions of gastric cancer(PLGC)development through coordinated alterations in mitophagy and glycolytic metabolism.AIM To determine dynamic changes in HIF-1α/BNIP3 signaling and investigate mitophagy-glycolysis interactions during PLGC development in rats.METHODS Eighty male Sprague-Dawley rats were randomly assigned to normal and model groups.A PLGC model was established using a comprehensive induction method.Eight rats per group were sacrificed at weeks 4,10,16,22,and 28.Gastric histopathology was evaluated by hematoxylin and eosin staining.Immunofluorescence assessed HIF-1αand BNIP3 expression in gastric antrum tissue.Quantitative real-time polymerase chain reaction and western blotting were used to assess the expression of mitophagy-related and glycolysis-related genes and proteins.RESULTS As time progressed,gastric mucosa in the model group gradually developed inflammation,atrophy,intestinal metaplasia,and dysplasia.In gastric antrum tissue,HIF-1αprotein and mRNA expression continuously increased.The expression of mitophagy-related markers,including BNIP3,Beclin1,and microtubule-associated protein 1 light chain 3,initially increased but subsequently declined,whereas sequestosome 1 expression showed an opposite trend.Regarding metabolic alterations,cytochrome C oxidase subunit 4 expression exhibited a mild decrease from week 16,while hexokinase 2 and lactate dehydrogenase A protein and mRNA expression significantly increased from week 22 onward.CONCLUSION HIF-1α/BNIP3 signaling dynamically regulates mitophagy and glycolysis during PLGC progression;appropriate HIF-1αis protective,whereas sustained overexpression induces autophagy dysfunction and metabolic imbalance. 展开更多
关键词 Hypoxia-inducible factor 1-alpha BCL2/adenovirus E1B 19 kDa interacting protein 3 Precancerous lesions of gastric cancer Mitophagy Glycolysis
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Cucurbit[n]urils(n=7,8)can strongly bind neutral hydrophilic molecules in water 认领 引用 被引量：3
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作者 Ming-Shuang Li Mao Quan +1 位作者 Xi-Ran Yang Wei Jiang 《Science China Chemistry》 SCIE EI CAS CSCD 2022年第9期1733-1740,共8页
It is challenging to recognize neutral hydrophilic molecules in water.Effective use of hydrogen bonds in water is generally accepted to be the key to success.In contrast,hydrophobic cavity is usually considered to pla... It is challenging to recognize neutral hydrophilic molecules in water.Effective use of hydrogen bonds in water is generally accepted to be the key to success.In contrast,hydrophobic cavity is usually considered to play an insignificant role or only to provide a nonpolar microenvironment for hydrogen bonds.Herein,we report that hydrophobic cavity alone can also strongly bind neutral,highly hydrophilic molecules in water.We found that cucurbit[n]urils(n=7,8)bind 1,4-dioxane,crown ethers and monosaccharides in water with remarkable affinities.The best binding constant reaches 107 M−1 for cucurbit[8]uril,which is higher than its binding affinities to common organic cations.Density functional theory(DFT)calculations and control experiments reveal that the hydrophobic effect is the major contributor to the binding through releasing the cavity water and/or properly occupying the weakly hydrated cavity.However,hydrophobic cavity still prefers nonpolar guests over polar guests with similar size and shape. 展开更多
关键词 molecular recognition the hydrophobic effect hydrophilic molecules cucurbit[n]uril naphthotube
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Biomimetic Recognition of Organic Drug Molecules in Water by Amide Naphthotubes 认领 引用 被引量：3
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作者 Yan-Long Ma Mao Quan +8 位作者 Xiu-Lian Lin Qian Cheng Huan Yao Xi-Ran Yang Ming-Shuang Li Wei-Er Liu Lin-Ming Bai Ruibing Wang Wei Jiang 《CCS Chemistry》 CSCD 2021年第4期1078-1092,共15页
Molecular recognition in water is the basis of numerous biological functions.The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups.This is achieved b... Molecular recognition in water is the basis of numerous biological functions.The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups.This is achieved by bioreceptors for which specific noncovalent interactions are efficiently used in a hydrophobic pocket.In contrast,most synthetic receptors cannot efficiently bind the neutral,polar groups of drug molecules and,thus,often exhibit poor binding selectivity and affinity.In this research,we report a systematic study on the binding behaviors of three types of macrocyclic hosts(amide naphthotubes,cucurbit[7]uril,andβ-cyclodextrin)to 18 model compounds and 13 drug molecules.Our results show that the high desolvation penalty of polar groups of guests is the reason for the relatively low binding affinity of cucurbit[7]uril andβ-cyclodextrin.However,amide naphthotubes with a biomimetic cavity bind efficiently and selectively to organic guests through hydrophobic effects and hydrogen bonding.Drug molecules with multiple polar groups can be better accommodated by these naphthotubes.The anti-configured naphthotube show good biocompatibility according to preliminary cell experiments and is capable of enhancing the water solubility of two poorly soluble drug molecules.Therefore,they may have practical applications in pharmaceutical sciences. 展开更多
关键词 molecular recognition drug excipient supramolecular chemistry β-cyclodextrin uril
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