Epigenetics-targeted drugs: current paradigms and future challenges

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Language: Английский

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Bidirectional Drive Reverse-Phase Enhanced Fluorescence Lateral Flow Immunoassay with Spectral Overlap and Quantitative Balance for the Analysis of Deoxynivalenol

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

The capacity of the reverse-phase enhanced fluorescence (turn-on mode) to sensitively alter intensity from "zero" "one" has drawn increasing interest and investigation in competitive lateral flow immunoassay (LFIA). During this process, three important considerations must be made: designing an effective quenching agent, choosing a suitable donor, building mode. In work, we employed Au@MnO2 nanoparticles as highly quenchers AuNCs donors achieve overlap absorption emission spectra. Furthermore, have effectively created immunological network-based LFIA balance quantitative relationship for quick accurate detection deoxynivalenol (DON) toxin (Au@MnO2-GAB-CFLFIA). Notably, our proposed fluorescent turn-on mode demonstrated 11.65-fold sensitivity enhancement (0.0509 ng/mL) compared colorimetric (0.593 ng/mL). network shows 5.08-fold non-network (0.259 Moreover, satisfactory recoveries 93.33–109.02% are obtained real samples (maize, wheat, oat). DON detection, spectral offer more novel efficient strategies LFIA.

Language: Английский

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SIRT1 Regulates Fumonisin B1-Induced LMH Cell PANoptosis and Antagonism of Lycopene

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Mycotoxin contamination is a universal agricultural problem and critical health issue. Fumonisin B1 (FB1) one of the most toxic extensive fumonisins that exist in various agro-products foods. Lycopene (LYC), as natural carotenoid, becoming increasingly favored owing to its oxidation resistance. Here, we aim explore mechanism FB1-induced hepatotoxicity antagonism LYC. In this study, our findings indicated FB1 induced mitochondrial structure damage loss function chicken hepatocytes. Furthermore, upregulated expression PANoptosis-related signal molecules. also reduced levels SIRT1 Ac-FOXO1 protein expression, which then inhibited mitophagy. However, LYC relieved these alterations. Most importantly, knockdown protective effects PANoptosis. Our study provides evidence for role mycotoxin-induced hepatocyte injury points potential target liver protection.

Language: Английский

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Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(25), P. 14349 - 14363

Published: June 13, 2024

Deoxynivalenol (DON) is a common agricultural mycotoxin that chemically stable and not easily removed from cereal foods. When organisms consume food made contaminated crops, it can be hazardous to their health. Numerous studies in recent years have found hesperidin (HDN) has hepatoprotective effects on wide range of toxins. However, few scholars explored the potential HDN attenuating DON-induced liver injury. In this study, we established low-dose DON exposure model intervened with three doses HDN, acting male C57 BL/6 mice AML12 cells, which served as vivo vitro models, respectively, investigate protective mechanism against exposure-induced The results suggested disrupted hepatic autophagic fluxes, thereby impairing structure function, significantly attenuated these changes. Further revealed alleviated excessive autophagy through mTOR pathway lysosomal dysfunction AKT/GSK3β/TFEB pathway. Overall, our study could ameliorate flux disorders via pathway, reducing

Language: Английский

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Deoxynivalenol-Induced Pyroptosis and Autophagy Inhibition Collectively Promote Inflammatory Injury in the Glandular Stomach of Chicken Embryos

Poultry Science, Journal Year: 2025, Volume and Issue: unknown, P. 105052 - 105052

Published: March 1, 2025

Language: Английский

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Natural Phenolic Compounds against Trichothecenes: From Protective Mechanisms to Future Perspectives

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Trichothecenes (TCNs), Fusarium-derived mycotoxins exemplified by deoxynivalenol and T-2 toxin, threaten global health through multisystem toxicity widespread contamination. Natural phenolic compounds (NPCs), leveraging their intrinsic safety natural abundance, demonstrate multimechanistic efficacy in counteracting TCN toxicity. This article reviews both domestic international research on the protective mechanisms of NPCs against TCN-induced exert effects multitiered mechanisms: (1) molecular regulation via Nrf2-centric antioxidant activation MAPK/NF-κB inflammatory axis suppression, coupled with coordinated inhibition programmed cell death pathways (apoptosis/ferroptosis/pyroptosis) autophagy modulation, where GPX4 emerges as a critical ferroptosis regulator; (2) restoring microbiome balance, enhancing intestinal barrier function, optimizing nutrient transport. Gut microflora may also serve an additional target for mitigating TCNs. further inhibit Fusarium proliferation mycotoxin biosynthesis. While there is demonstrated potential food sustainable feed development, challenges persist bioavailability optimization, pharmacokinetic profiling, microbiota-metabolite crosstalk. analysis advances NPC-based strategies detoxification agriculture.

Language: Английский

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Hesperidin mitigated deoxynivalenol-induced liver injury by inhibiting ROS/ P53/ PGC-1α-mediated disruption of mitochondrial dynamics and PANoptosis

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156747 - 156747

Published: April 1, 2025

Language: Английский

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Low-dose deoxynivalenol exposure triggers hepatic excessive ferritinophagy and mitophagy mitigated by hesperidin modulated O-GlcNAcylation

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 135952 - 135952

Published: Sept. 24, 2024

Language: Английский

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Chronic dietary deoxynivalenol exposure interferes the intestinal microbial community structure and antibiotic resistome in laying hens

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 286, P. 117213 - 117213

Published: Oct. 19, 2024

Language: Английский

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