p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy DOI

Francisco Triana-Martinez,

Alessandra Pierantoni,

Daisy Graça

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 15, 2024

The ability of an organism to overcome infectious diseases has traditionally been linked killing invading pathogens. Accumulating evidence, however, indicates that, apart from restricting pathogen loads, organismal survival is coupled additional yet poorly understood mechanism called disease tolerance. Here we report that p16 High immune cells play a key role in establishing We found the FDA-approved BNT162b2 mRNA COVID-19 vaccine potent and rapid inducer subsets both mice humans. In turn, were indispensable for counteracting different lethal conditions, including LPS-induced sepsis, acute SARS-CoV-2 infection ionizing irradiation. Mechanistically, propose activation TLR7 or low physiological activity STING sufficient induce subset establishes adenosine environment Furthermore, containing these signals within beneficial range by deleting MDA5 appeared maintain STING, induces delays organ deterioration upon aging with improved healthspan. Our data highlight

Language: Английский

Nuclear Overexpression of SAMHD1 Induces M Phase Stalling in Hepatoma Cells and Suppresses HCC Progression by Interacting with the Cohesin Complex DOI Creative Commons
Juntang Shao, Wei Wang, Shiyu Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Emerging evidence suggests that the sterile alpha‐motif (SAM) and histidine‐aspartate (HD) domain‐containing protein 1 (SAMHD1) is implicated in various cancers, including hepatocellular carcinoma (HCC). However, its precise role tumor cells underlying mechanisms remain unclear. This study aimed to investigate expression patterns, prognostic values, functional of SAMHD1 HCC progression. We constructed liver tissue microarrays using paired paratumor specimens from 187 patients with primary HCC. Our findings indicate nuclear levels are increased tumors compared tissues. Moreover, decline advanced stages, higher staining correlating favorable outcomes. Hepatocyte‐specific knockout mice, generated by crossing fl/fl mice Alb‐cre showed accelerated progression a diethylnitrosamine (DEN)‐induced model. In hepatoma cell lines, overexpression inhibited proliferation stalling mitosis, independent deoxynucleotide triphosphohydrolase (dNTPase) function. Mechanistically, interacts cohesin complex nucleus, enhancing sister chromatid cohesion during division, which delays metaphase suggest plays critical slowing regulating highlighting potential as therapeutic target manipulating dynamics.

Language: Английский

Citations

0
Mouse models of type I interferonopathies DOI Creative Commons
Domnica Luca, Hiroki Kato

Human Molecular Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Type I interferonopathies are severe monogenic diseases caused by mutations that result in chronically upregulated production of type interferon. They present with a broad variety symptoms, the mechanisms which being extensively studied. Mouse models an important resource for this purpose, and context, we review several key molecular phenotypic findings advancing our understanding respective diseases. We focus on genotypes related to nucleic acid metabolism, sensing cytosolic receptors downstream signalling.

Language: Английский

Citations

0
p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy DOI

Francisco Triana-Martinez,

Alessandra Pierantoni,

Daisy Graça

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 15, 2024

The ability of an organism to overcome infectious diseases has traditionally been linked killing invading pathogens. Accumulating evidence, however, indicates that, apart from restricting pathogen loads, organismal survival is coupled additional yet poorly understood mechanism called disease tolerance. Here we report that p16 High immune cells play a key role in establishing We found the FDA-approved BNT162b2 mRNA COVID-19 vaccine potent and rapid inducer subsets both mice humans. In turn, were indispensable for counteracting different lethal conditions, including LPS-induced sepsis, acute SARS-CoV-2 infection ionizing irradiation. Mechanistically, propose activation TLR7 or low physiological activity STING sufficient induce subset establishes adenosine environment Furthermore, containing these signals within beneficial range by deleting MDA5 appeared maintain STING, induces delays organ deterioration upon aging with improved healthspan. Our data highlight

Language: Английский

Citations

0