Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Сен. 5, 2023

Much recent attention has been directed toward the spatial organization of cell nucleus and manner in which three-dimensional topologically associated domains transcription factories are epigenetically coordinated to precisely bring enhancers into close proximity with promoters control gene expression. Twenty lines evidence robustly implicate cannabinoid exposure accelerated organismal cellular aging. Aging recently shown be caused by increased DNA breaks. These breaks rearrange maldistribute epigenomic machinery weaken reverse differentiation, cause genome-wide demethylation, reduce transcription, lead inhibition developmental pathways, contribute progressive loss function chronic immune stimulation that characterize Both lineage-defining superenhancers superanchors them weakened. Cannabis phenocopies elements this process reproduces chromatin breakages, reduces DNA, RNA protein histone synthesis, interferes controlling both modifications, induces general hypomethylation, epigenomically disrupts critical boundary cohesin motors create loops. This pattern widespread interference programs relative dedifferentiation (which is pro-oncogenic) reinforced impairment intermediate metabolism locks stem cell-like hyper-replicative state) perpetuates increases aging senescence programs, damage, genomic instability, oncogenesis), together account for diverse teratologic carcinogenic outcomes reported large epidemiologic studies Europe, USA, elsewhere. It also accounts prominent phenotype observed clinically long-term cannabis use disorder 20 characteristics it manifests. Increasing daily use, increasing pregnancy, exponential dose-response effects heighten clinical urgency these findings. Together, findings indicate genotoxicity epigenotoxicity features dependence strongly multiomics investigations genome-epigenome-transcriptome-metabolome, conformation, 3D nuclear architecture. Considering well-established relationships, diversity cannabinoids, multigenerational nature implications, great caution warranted community penetration.

Язык: Английский

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New role for the anandamide metabolite prostaglandin F2α ethanolamide: Rolling preadipocyte proliferation

Journal of Lipid Research, Год журнала: 2023, Номер 64(11), С. 100444 - 100444

Опубликована: Сен. 19, 2023

White adipose tissue regulation is key to metabolic health, yet still perplexing. The chief endocannabinoid anandamide metabolite, prostaglandin F

Язык: Английский

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Do Delta-9-Tetrahydrocannabinol and Cannabidiol have Opposed Effects on Male Fertility?

Toxicology Letters, Год журнала: 2024, Номер 403, С. 94 - 104

Опубликована: Дек. 8, 2024

Язык: Английский

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Probiotics supplementation to adult human small intestinal stoma microbiota causes dynamic increase in the community resistance to perturbations and nutrient utilization

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 30, 2023

Abstract The gut microbiota plays a pivotal role in health and disease. use of probiotics as microbiota-targeted therapies is promising strategy to improve host health. However, dynamic molecular mechanisms are often not elucidated, especially when targeting the small intestinal microbiota. Here, we show that supplementation probiotic formula (Ecologic®825) adult human ileostoma counteracts growth Enterococcaceae Enterobacteriaceae reduces ethanol production, leading major changes nutrient utilization resistance perturbations. observed alterations coincided with an initial increase lactate production decrease pH by probiotics, followed sharp levels butyrate propionate. Additionally, increased multiple N -acyl amino acids was detected stoma samples supplemented formula. Overall, this study shows how network theory can be used current or identify novel therapies. outcome may help further understand reported effects these on host.

Язык: Английский

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Cannabis medicinal en el tratamiento del dolor crónico visceral

Revista de la Sociedad Española del Dolor, Год журнала: 2022, Номер unknown

Опубликована: Янв. 1, 2022

a la corrección de estilo final, composición y revisión prueba resultante antes que se publique en su forma final.Tenga cuenta durante el proceso producción pueden dar errores lo podría afectar contenido final.El copyright todos los derechos legales aplican al artículo pertenecen Revista Sociedad Española Dolor.

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