MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-26
·
IF 6
Wei Xuehua,Xiong Xiangpeng,Wang Pingping,Zhang Shufang,Peng Dongxian
Background The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance.Methods High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues.Results High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein–protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC.Conclusion This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xi Chen,Di Wang,Xuejun Guo,Xiaoming Li,Wenjing Ye,Yang Qi,Wen Gu
The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin's effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
研究领域:
药理学
·
纳米技术
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·
IF 4.6
Honglin Jia,Qi Yang,Jiahui Hong,Rui Ding,Tao Liu,Qunfang Yang,Haiping Zheng,Qingshan Huang,Zhaowei Zhang,Xiaohong Chen,Renshan Sun,Yunlong Yu,Wenjun Shan
Maintaining the homeostasis of the skin's immune microenvironment is crucial for skin's health. In inflammatory skin conditions (like psoriasis), the immune microenvironment is dysregulated, including ROS accumulation and T cell overactivation. In addition to promoting inflammation and excessive keratinocyte proliferation, ROS upregulation in psoriasis also induces glucocorticoid resistance, which poses a significant challenge to the effectiveness of glucocorticoid treatment (e.g., dexamethasone) in psoriasis. To conquer this problem, we used epigallocatechin-3-gallate (EGCG) to eliminate ROS production in psoriasis. Application of EGCG reduced ROS levels and improved the anti-psoriasis effect of Dexamethasone (Dex) in vitro. Benefiting from the unique characteristics of microneedle for transdermal drug delivery, we construct a dissolvable microneedle (MN) patch containing EGCG and Dex (DEX/EGCG-MN), which can directly codelivery the two elements to the lesion area without stratum corneum barrier. Our MN alleviates psoriasis-like manifestations in imiquimod (IMQ)-induced psoriasis mouse model, indicated by epidermal thickness and dorsal skin signs. Besides, DEX/EGCG-MN corrected the disorder of immune cells, including innate and acquired immune cells. As a result, it mediates the balance in the skin's immune microenvironment. Meanwhile, our MN also ameliorated the hyperproliferation of keratinocytes in psoriatic lesions. We believe this approach may offer insights for further developing anti-psoriasis assays. This article is protected by copyright. All rights reserved
研究领域:
药理学
·
皮肤科
·
免疫学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）