Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 275, P. 116278 - 116278

Published: April 1, 2024

Due to the rise in temperature and sea level caused by climate change, detection rate of aflatoxin B1 (AFB1) food crops has increased dramatically, frequency severity aflatoxicosis humans animals are also increasing. AFB1 strong hepatotoxicity, causing severe liver damage even cancer. However, mechanism hepatotoxicity remains unclear. By integrating network toxicology, molecular docking vivo experiments, this research was designed explore potential mechanisms AFB1. Thirty-three intersection targets for AFB1-induced were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, apoptosis significantly enriched. In addition, proteins ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, IGF1 exhibited good affinity with significant pathological changes occurred mice. induction expression levels ERK, decreased levsls PI3K AKT1. Moreover, treatment an increase Caspase3 expression, a decrease Bcl2/Bax ratio. combining toxicology study confirms first time that promotes pathway inactivating PI3K/AKT1 activating EGFR/ERK hence aggravating hepatocyte apoptosis. This provides new strategies studying toxicity environmental pollutants possible development hepatoprotective drugs.

Language: Английский

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Evidence for a Functional Link Between the Nrf2 Signalling Pathway and Cytoprotective Effect of S-Petasin in Human Retinal Pigment Epithelium Cells Exposed to Oxidative Stress

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 180 - 180

Published: Feb. 4, 2025

The retinal pigment epithelium (RPE) is a highly specialised monolayer subjected to constant oxidative stress, which, in the long term, favours development of complex pathological process that underlying cause macular damage. Therefore, counteracting overproduction ROS best-researched approach preserve functional integrity RPE. S-Petasin, secondary metabolite extracted from plant Petasites hybridus, has numerous biological effects, which highlight its anti-inflammatory and antioxidative properties. aim our study investigate whether S-Petasin exerts cytoprotective effects by protecting RPE pretreatment with were assessed determination cell viability, intracellular levels, activation Nrf2 pathway resulting post-transcriptional antioxidant/antiapoptotic response. Our results show (1) reduces improving viability exposed damage; (2) activates signalling pathway, modulating response antioxidant chemical biomarkers; (3) Bax an increase those Bcl-2, concomitant downregulation Bax/Bc-2 ratio. Overall, provide first evidence able protect

Language: Английский

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Peroxiredoxin 6 in Stress Orchestration and Disease Interplay

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 379 - 379

Published: March 23, 2025

As a moonlighting protein with multiple enzymatic activities, peroxiredoxin 6 (PRDX6) maintains redox homeostasis, regulates phospholipid metabolism, and mediates intra- inter-cellular signaling transduction. Its expression activity can be regulated by diverse stressors. However, the roles relevant mechanisms of these regulators in various conditions have yet to comprehensively reviewed. In this study, stressors were systematically reviewed both vivo vitro classified into chemical, physical, biological categories. We found that regulatory effects on PRDX6 primarily mediated via key transcriptional factors (e.g., NRF2, HIF-1α, SP1, NF-κB), micro-RNAs, receptor- or kinase-dependent pathways. Additionally, certain stressors, including reactive oxygen species, pH fluctuations, post-translational modifications, induced structure-based functional switches enzyme. further altered under disease conditions, particular focus neuropsychiatric disorders cancers, proposed concept PRDX6-related (PRD), which refers spectrum diseases associated dysregulated expression. Finally, we an exogenous supplementation provided preventive therapeutic potentials for oxidative stress-related injuries models. Taken together, review underscores critical role as cellular orchestrator response highlighting its clinical potential monitoring development strategies.

Language: Английский

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Therapeutic prospects and potential mechanisms of Prdx6: as a novel target in musculoskeletal disorders

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

With the global population aging, musculoskeletal disorders (MSDs) have posed significant physical and psychological health challenges for patients as well a substantial economic burden on society. The advancements in conservative surgical interventions MSDs been remarkable recent years; however, current treatment modalities still fall short of meeting optimal requirements patients. Recently, peroxiredoxin 6 (Prdx6) has gained considerable attention from researchers due to its antioxidative, anti-inflammatory, anti-apoptotic properties. It found that Prdx6 is involved multiple system diseases, including MSDs; exact role lacking. This study aimed summarize structure, regulatory mechanism, potential function Prdx6. These findings may demonstrate novel target inhibiting advancement MSDs.

Language: Английский

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Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

International Journal of Ophthalmology, Journal Year: 2024, Volume and Issue: 17(6), P. 1018 - 1027

Published: May 24, 2024

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on (EGF)-induced activation retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated 100 ng/mL EGF. Erlotinib were used to intervene EGF treatment. Cellular viability, proliferation, migration detected methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay wound healing respectively. EGFR/protein kinase B (AKT) pathway proteins N-cadherin, α-smooth muscle actin (α-SMA), vimentin tested Western blot assay. also determined immunofluorescence staining. RESULTS: treatment for 24h induced a significant increase ARPE-19 cells’ proliferation migration, phosphorylation EGFR/AKT proteins, decreased total expression. suppressed through down regulating AKT protein expressions. inhibited EGF-induced an proliferative migrative ability in cells clearly expression α-SMA, proteins. Similarly, significantly affected up-regulation CONCLUSION: EGFR-knockdown suppress via may be possible therapeutic approach vitreoretinopathy (PVR).

Language: Английский

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Three-Dimensional Bioprinting for Retinal Tissue Engineering

Biomimetics, Journal Year: 2024, Volume and Issue: 9(12), P. 733 - 733

Published: Dec. 1, 2024

Three-dimensional bioprinting (3DP) is transforming the field of regenerative medicine by enabling precise fabrication complex tissues, including retina, a highly specialized and anatomically tissue. This review provides an overview 3DP’s principles, its multi-step process, various techniques, such as extrusion-, droplet-, laser-based methods. Within scope biomimicry biomimetics, emphasis placed on how 3DP potentially enables recreation retina’s natural cellular environment, structural complexity, biomechanical properties. Focusing retinal tissue engineering, we discuss unique challenges posed layered structure, vascularization needs, interplay between numerous cell types. Emphasis recent advancements in bioink formulations, designed to emulate characteristics improve viability, printability, mechanical stability. In-depth analyses bioinks, scaffold materials, emerging technologies, microfluidics organ-on-a-chip, highlight potential bioprinted models replicate disease states, facilitating drug development testing. While remain achieving clinical translation—particularly immune compatibility long-term integration—continued innovations bioinks scaffolding are paving way toward functional constructs. We conclude with insights into future research directions, aiming refine for personalized therapies transformative applications vision restoration.

Language: Английский

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Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32887 - e32887

Published: June 1, 2024

Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and number cases increasing yearly. However, effective treatments are unavailable, arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, anti-aging effects other diseases. whether ARB can be used treat dry AMD remains unknown. To explore therapeutic potential molecular mechanism treatment AMD. MTT assays, reactive oxygen species (ROS) production flow cytometry qPCR western blotting were assess impact on human RPECs induced by H

Language: Английский

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