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药理学与转录组学的综合分析预测白藜芦醇将通过靶向Ccl2和Esr1改善微塑料诱导的肺损伤。

Integrative Analysis of Pharmacology and Transcriptomics Predicts Resveratrol Will Ameliorate Microplastics-Induced Lung Damage by Targeting Ccl2 and Esr1.

作者信息

Zhang Yadong, Ren Jingyi, Zhu Siqi, Guo Zihao, Pei Huanting, Sun Xiaoya, Wu Jiarui, Yang Weijie, Zuo Jinshi, Ma Yuxia

机构信息

Hebei Key Laboratory of Environment and Human Health, Department of Nutrition and Food Hygiene, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China.

Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.

出版信息

Toxics. 2024 Dec 14;12(12):910. doi: 10.3390/toxics12120910.

DOI:10.3390/toxics12120910
PMID:39771125
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11728634/
Abstract

BACKGROUND

Microplastics (MPs) are ubiquitous on earth, posing a growing threat to human health. Previous studies have shown that the lung is a primary organ for MPs exposure. Resveratrol (RES) is a common dietary polyphenol that exhibits anti-inflammatory and antioxidant effects. However, whether RES exerts a protective effect against MPs-induced lung damage is still unknown.

METHODS

The targets of RES were retrieved from five databases. Differentially expressed genes (DEGs) were identified through comprehensive bioinformatic analysis. Multiple algorithms were employed to screen for the core targets. Ultimately, molecular docking analysis and molecular dynamics (MD) simulations were utilized to confirm the binding affinity between RES and the core targets.

RESULTS

In total, 1235 DEGs were identified in the transcriptomes. After removing duplicates, a total of 739 RES targets were obtained from five databases, and 66 of these targets intersected with DEGs. The potential core targets (Esr1, Ccl2) were further identified through topological analysis and machine learning. These findings were subsequently verified by molecular docking and MD simulations.

CONCLUSIONS

This study demonstrated that RES may mitigate lung injury induced by MPs by targeting Esr1 and Ccl2. Our research offers a novel perspective on the prevention and treatment of MPs-induced lung injury.

摘要

背景

微塑料在地球上广泛存在,对人类健康构成日益严重的威胁。先前的研究表明,肺是微塑料暴露的主要器官。白藜芦醇(RES)是一种常见的膳食多酚,具有抗炎和抗氧化作用。然而,RES是否对微塑料诱导的肺损伤具有保护作用仍不清楚。

方法

从五个数据库中检索RES的靶点。通过综合生物信息学分析鉴定差异表达基因(DEG)。采用多种算法筛选核心靶点。最终,利用分子对接分析和分子动力学(MD)模拟来确认RES与核心靶点之间的结合亲和力。

结果

在转录组中共鉴定出1235个DEG。去除重复项后,从五个数据库中总共获得739个RES靶点,其中66个靶点与DEG相交。通过拓扑分析和机器学习进一步鉴定了潜在的核心靶点(Esr1、Ccl2)。随后通过分子对接和MD模拟验证了这些发现。

结论

本研究表明,RES可能通过靶向Esr1和Ccl2减轻微塑料诱导的肺损伤。我们的研究为微塑料诱导的肺损伤的预防和治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/c0bf5dc06a63/toxics-12-00910-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/0e0c93c66a55/toxics-12-00910-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/6054b7ed226c/toxics-12-00910-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/aae00ed4d1d6/toxics-12-00910-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/7e0d99ec85ba/toxics-12-00910-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/a51b974c1aef/toxics-12-00910-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/395c9695eb9a/toxics-12-00910-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/383916f4c8cd/toxics-12-00910-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/9c644239fe65/toxics-12-00910-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/c0bf5dc06a63/toxics-12-00910-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/0e0c93c66a55/toxics-12-00910-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/6054b7ed226c/toxics-12-00910-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/aae00ed4d1d6/toxics-12-00910-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/7e0d99ec85ba/toxics-12-00910-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/a51b974c1aef/toxics-12-00910-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/395c9695eb9a/toxics-12-00910-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/383916f4c8cd/toxics-12-00910-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/9c644239fe65/toxics-12-00910-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64b5/11728634/c0bf5dc06a63/toxics-12-00910-g009.jpg

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本文引用的文献

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J Agric Food Chem. 2024 Jul 24;72(29):16250-16262. doi: 10.1021/acs.jafc.4c02040. Epub 2024 Jun 24.
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Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.白藜芦醇补充剂对老年人的影响和安全性:全面的系统评价。
Phytother Res. 2024 May;38(5):2448-2461. doi: 10.1002/ptr.8171. Epub 2024 Mar 3.
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Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling.
微塑料暴露通过诱导 ROS 信号导致人肺上皮细胞和小鼠肺部衰老。
Environ Int. 2024 Mar;185:108489. doi: 10.1016/j.envint.2024.108489. Epub 2024 Feb 8.
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Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies.揭示白藜芦醇在肺癌治疗中的潜在作用:机制和基于纳米粒子的药物传递策略。
Biomed Pharmacother. 2024 Mar;172:116207. doi: 10.1016/j.biopha.2024.116207. Epub 2024 Jan 31.
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Tissue accumulation of microplastics and potential health risks in human.微塑料在人体组织中的积累及其潜在健康风险
Sci Total Environ. 2024 Mar 10;915:170004. doi: 10.1016/j.scitotenv.2024.170004. Epub 2024 Jan 12.
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Microplastics and nanoplastics induced differential respiratory damages in tilapia fish Oreochromis niloticus.微塑料和纳米塑料诱导罗非鱼 Oreochromis niloticus 产生不同的呼吸损伤。
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