Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 289, С. 117645 - 117645

Опубликована: Янв. 1, 2025

Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked various inflammatory diseases, including bowel disease (IBD). In this study, we elucidate novel regulatory mechanism involving proteins (RPs) RPL13A RPS3, which mediate proinflammatory chemokine production in DON-exposed gut epithelial cells. Through combination of transcriptomic analysis experimental models, demonstrate that while negatively regulates inflammation enhancing anti-inflammatory transcription factor ATF3, RPS3 acts as driver, promoting via activation MAPK pathways, transcriptional upregulation EGR-1, stabilization mRNA through cytosolic translocation HuR. Our findings reveal dynamic interplay between wherein counteracts effects offering finely tuned axis response environmental toxins. These insights provide potential molecular targets for therapeutic intervention toxin-induced diseases gut, highlighting non-canonical roles modulating immune stressors.

Язык: Английский

Deciphering the Host-Pathogen Interface in COVID-19: The precision molecular insight into epitranscriptomic modifications of high-impact transcripts

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

ABSTRACT The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact since its emergence in late 2019. Characterized wide spectrum of clinical manifestations, ranging from asymptomatic infection to distress and death, necessitated extensive research into host-pathogen interactions that drive disease progression. Understanding molecular mechanisms underlying host response SARS-CoV-2 is crucial for development effective therapeutic interventions preventative strategies. This study employed multi-omic approach combined direct RNA sequencing (DRS) Illumina cDNA investigate whole blood transcriptomic profiles patients. By leveraging unique capabilities Nanopore DRS, which provides long-read data, we were able capture not only gene expression levels but also modifications, including poly(A) tail length, non-adenine residue (non-A), pseudouridylation (psU), 5-methylcytosine (m5C) methylation. comprehensive analysis allowed us identify differentially expressed genes (DEGs) explore these modifications on function within context COVID-19. Our findings reveal significant alterations patterns, lengths, non-A prevalence psU m5C patients compared healthy controls. These results provide valuable insights complex interplay between viral infection, immune response, processing, contributing deeper understanding pathogenesis.

Язык: Английский

Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern

Vaccines, Год журнала: 2025, Номер 13(4), С. 424 - 424

Опубликована: Апрель 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Язык: Английский