Single-cell transcriptome analysis reveals mechanism of phosphodiesterase inhibitor in neonatal mouse infection-associated liver injury treatment

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication

Egyptian Liver Journal, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 12, 2024

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is unique characteristic of hepatocytes. This has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose review explores the molecular mechanisms underlying hepatocyte polyploidization its potential role in promoting resilience against aging-related decline function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, adaptation, highlighting their relevance aging. Main body Hepatocyte occurs through such cytokinesis failure endoreplication, leading binuclear or mononuclear cells. Polyploid exhibit enhanced repair capacity, which helps mitigate accumulation age-related damage. The increased gene dosage facilitates better responses, particularly oxidative genotoxic insults. Metabolic adaptations, including xenobiotic metabolism lipid regulation, further support liver’s ability maintain homeostasis Additionally, demonstrate altered epigenetic landscapes proteostasis mechanisms, contributing improved reduced susceptibility senescence. These adaptations collectively enhance structural challenges. Conclusion represents critical protective that safeguard instability, dysfunction, stress. Understanding pathways driving could pave way novel therapeutic strategies combat disorders health span. Graphical

Language: Английский

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The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models

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

Published: June 14, 2024

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid represent a promising approach concurrently studying neurotoxicity and providing insights into complex interplay between drugs Herein, we have examined molecular mechanisms underlying drug-induced reprotoxicity discussed experimental findings from case studies. Additionally, explore utility organoid in elucidating complications neurodrug exposure. Have principles models, ability recapitulate neurodevelopmental processes simulate toxicity controlled environment. Challenges future perspectives field been addressed with focus advancing technologies improve assessment enhance drug safety screening. This review underscores importance unraveling relationship

Language: Английский

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HiTIP-seq profiles epigenomic reprogramming of patient-derived diffuse midline glioma stem cells to epigenetic therapy

hLife, Journal Year: 2024, Volume and Issue: 2(9), P. 471 - 487

Published: July 14, 2024

Diffuse midline glioma (DMG), H3K27-altered, is lethal pediatric-type, high-grade, localized to the region of central nervous system. Effective treatment guidelines are absent, and clinical trials preferred for primary or recurrent DMG patients. Recently, epigenetic agent-based immunotherapy has exhibited promising therapeutic effects in setting. However, underlying mechanisms remain a mystery. The rare tumor samples from biopsy resection largely impede basic research, by using patient-derived cells which better recapitulate parental tumor's heterogeneity compared established cell lines. As an reprogramming disease, exhibits global loss H3K27 trimethylation (H3K27me3) gain acetylation (H3K27ac). Analysis multiple marks fundamentally necessary. traditional techniques cannot allow ultra-low input high-throughput. Herein we have developed new method called high-throughput situ tagged immunoprecipitation sequencing (HiTIP-seq), uses integrated superhydrophobic microwell array technology (InSMART). We were able perform 100 parallel assays as few per on single chip. applied profile alterations three-dimensional (3D) cultures derived Our HiTIP-seq with RNA (RNA-seq) analysis revealed that combination agents (panobinostat tazemetostat), reprogrammed histone modifications drove transcriptome changes. Among them, Wnt inhibitory factor 1 (WIF1) H3K27ac H3K27me3, leads upregulated expression. Altogether, versatile modifications, suitable both research studying 3D models.

Language: Английский

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Specific cell subclusters of dental pulp stem cells respond to distinct pathogens through the ROS pathway

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 12, 2024

Microbial pathogens invade various human organs, including the oral cavity.

Language: Английский

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