Supercomputer-Based Virtual Screening for Deoxyribonucleic Acid Methyltransferase 1 Inhibitors as Novel Anticancer Agents DOI Open Access
Lara Johanna Friedrich,

Axel Guthart,

Min Zhou

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11870 - 11870

Published: Nov. 5, 2024

Targeting epigenetics is a new strategy to treat cancer and develop novel epigenetic drugs with anti-tumor activity. DNA methyltransferases transfer the methyl group from

Language: Английский

Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1 DOI Creative Commons
Jiaxing Chen, Xinyu Yang, Qiaochu Li

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 139 - 153

Published: May 3, 2024

Epigenetic changes are important considerations for degenerative diseases. DNA methylation regulates crucial genes by epigenetic mechanism, impacting cell function and fate. presents hypermethylation in degenerated nucleus pulposus (NP) tissue, but its role intervertebral disc degeneration (IVDD) remains elusive. This study aimed to demonstrate that methyltransferase mediated was responsible IVDD integrative bioinformatics experimental verification. Methyltransferase DNMT3B highly expressed severely NP tissue (involving human rats) in-vitro cells (NPCs). Bioinformatics elucidated hypermethylated were enriched oxidative stress ferroptosis, the ferroptosis suppressor gene SLC40A1 identified with lower expression higher tissue. Cell culture using NPCs showed induced downregulating SLC40A1, promoting a phenotype. An in-vivo rat model inhibitor 5-AZA alleviated puncture-induced IVDD. Taken together, aggravates via regulating SLC40A1. mechanism within is promising therapeutic biomarker

Language: Английский

Citations

7
Strategies for in Silico Drug Discovery to Modulate Macromolecular Interactions Altered by Mutations DOI Creative Commons
Pitambar Poudel, Maria A. Miteva, Emil Alexov

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(4)

Published: April 16, 2025

Most human diseases have genetic components, frequently single nucleotide variants (SNVs), which alter the wild type characteristics of macromolecules and their interactions. A straightforward approach for correcting such SNVs-related alterations is to seek small molecules, potential drugs, that can eliminate disease-causing effects. Certain disorders are caused by altered protein-protein interactions, example, Snyder-Robinson syndrome, therapy focuses on development molecules restore homodimerization spermine synthase. Other originate from protein-nucleic acid as in case cancer; these cases, elimination effects requires effect mutation p53-DNA affinity. Overall, especially complex diseases, pathogenic mutations macromolecular This be direct, i.e., alteration affinity specificity, or indirect via concentration binding partners. Here, we outline progress made methods strategies computationally identify capable altering interactions a desired manner, reducing increasing affinity, eliminating effect. When applicable, provide examples outlined general strategy. Successful cases presented at end work.

Language: Английский

Citations

1
Ferroptosis in Cancer: Epigenetic Control and Therapeutic Opportunities DOI Creative Commons

Roberta Veglia Tranchese,

Sabrina Battista, Laura Cerchia

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1443 - 1443

Published: Nov. 13, 2024

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathway in cancer biology. This review delves into the epigenetic mechanisms that modulate ferroptosis cells, focusing on how DNA methylation, histone modifications, and non-coding RNAs influence expression function essential genes involved this process. By unraveling complex interplay between these ferroptosis, article sheds light novel gene targets functional insights could pave way for innovative treatments to enhance therapeutic efficacy overcome resistance therapy.

Language: Английский

Citations

6
Research progress and applications of epigenetic biomarkers in cancer DOI Creative Commons
Jianjun Gao, Wujiang Shi,

Jiangang Wang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Epigenetic changes are heritable in gene expression without the nucleotide sequence of genes. play an important role development cancer and process malignancy metastasis. Previous studies have shown that abnormal epigenetic can be used as biomarkers for disease status prediction. The reversibility controllability modification also provide new strategies early prevention treatment. In addition, corresponding drug has reached clinical stage. this paper, we will discuss recent progress application tumor from three perspectives: DNA methylation, non-coding RNA, histone modification, order to opportunities additional research applications.

Language: Английский

Citations

5
Identification of 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids as promising DNMT1 inhibitors DOI
Jingyi Liu,

Minli Ruan,

Yueqin Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 274, P. 116538 - 116538

Published: May 27, 2024

Language: Английский

Citations

4
Chemical diversity and antimelanoma potential of rosemary essential oils: Unveiling mechanistic insights through quantitative proteomics DOI

Yeqin Huang,

Mengting Ding, Di Wang

et al.

Industrial Crops and Products, Journal Year: 2024, Volume and Issue: 215, P. 118652 - 118652

Published: May 3, 2024

Language: Английский

Citations

3
DNMT inhibitor, 5-aza-2′-deoxycytidine mitigates di(2-ethylhexyl) phthalate-induced aggravation of psoriasiform inflammation in mice via reduction in global DNA methylation in dermal and peripheral compartments DOI

Ali S. Alfardan,

Ahmed Nadeem,

Sheikh F Ahmad

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 137, P. 112503 - 112503

Published: June 20, 2024

Language: Английский

Citations

3
The Advances in the Development of Epigenetic Modifications Therapeutic Drugs Delivery Systems DOI Creative Commons

Tingyi Li,

Yanwei Chen, Shuai Li

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 10623 - 10637

Published: Oct. 1, 2024

Epigenetic dysregulation can significantly trigger the onset and progression of various diseases, epigenetic therapy is a new treatment strategy by changing DNA methylation, histone modification, N6-methyladenosine, chromatin modification other modifications to regulate gene expression levels for therapeutic purposes. However, small-molecule drugs face challenges in disease treatment, such as lack selectivity, limited efficacy, insufficient safety. Nanomedicine delivery systems offer significant advantages addressing these issues enhancing drug targeting, improving bioavailability, reducing nonspecific distribution. This help minimize side effects while increasing both effectiveness safety drugs. In this review, we focus on mechanism role regulatory factors well faced small molecule inhibitors strategies, especially research advancements systems, review discuss potential using nanotechnology develop systems.

Language: Английский

Citations

3
N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1 DOI

Renjie Xiao,

Tianjiao Wang, Depei Wu

et al.

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(3)

Published: Jan. 20, 2025

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes. N6-methyladenosine (m6A)-related epigenetic regulation widely involved the pathogenesis of diabetes complications. However, function m6A methyltransferase Wilms tumor 1-associated protein (WTAP) diabetic healing remains elusive. AIM To investigate potential regulatory mechanism WTAP during healing. METHODS Human umbilical vein endothelial cells (HUVECs) were induced high glucose (HG) to establish vitro cell model. Male BALB/c mice intraperitoneally injected streptozotocin mimic diabetes, full-thickness excision was made HG-induced HUVECs mouse models treated siRNAs DNA 1 (DNMT1) overexpression vectors. Cell viability migration ability detected by counting kit-8 Transwell assays. In angiogenesis measured using tube formation experiment. The images wounds captured, re-epithelialization collagen deposition skin tissues analyzed hematoxylin eosin staining Masson’s trichrome staining. RESULTS expression several methyltransferases, including METTL3, METTL14, METTL16, KIAA1429, WTAP, RBM15, measured. exhibited most elevation compared normal control. depletion notably restored enhanced suppressed HG. unclosed area smaller knockdown-treated than control at nine days post-wounding, along rate deposition. levels on DNMT1 mRNA repressed knockdown HUVECs. inhibited Overexpression reversed effects CONCLUSION elevated epigenetically regulates modification impair

Language: Английский

Citations

0
Novel Epitranscriptomic and Epigenetic Therapeutic Strategies and Targets for Ferroptosis in Liver Fibrosis DOI
Minghui Li, Yang Yang,

Qi-Qi Dong

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 996, P. 177344 - 177344

Published: Feb. 25, 2025

Language: Английский

Citations

0