STINGing away the pain: the role of interferon-stimulated genes DOI Creative Commons
Erick J. Rodríguez‐Palma, Heather N. Allen, Rajesh Khanna

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(9)

Published: April 30, 2024

Pain and inflammation are biologically intertwined responses that warn the body of potential danger. In this issue JCI, Defaye, Bradaia, colleagues identified a functional link between pain, demonstrating inflammation-induced activation stimulator IFN genes (STING) in dorsal root ganglia nociceptors reduced pain-like behaviors rodent model inflammatory pain. Utilizing mice with gain-of-function STING mutation, type I regulation voltage-gated potassium channels as mechanism pain relief. Further investigation into mechanisms by which proinflammatory pathways can reduce may reveal druggable targets insights new approaches for treating persistent

Language: Английский

Decoding STING’s roles in cancer: immunity, pain, dormancy, and autophagy DOI
Huan‐Xin Lin, Ya‐ling Tang,

Xinhua Liang

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

0
MicroRNA-1985 enhances the redox capability of scallop (Patinopecten yessoensis) in response to poly(I:C) stimulation by targeting MNK1 DOI Creative Commons

Linghui Yu,

Huafeng Deng, Shaohua Liu

et al.

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

Published: May 8, 2025

To clarify the microRNA (miRNA)-target gene axis is involved in response to pathogen-associated molecular pattern (PAMP)-induced oxidative stress shellfish, full-length cDNA of a novel mitogen-activated protein kinase-interacting kinase 1 ( MNK1 ) homolog from scallop Patinopecten yessoensis PyMNK1 was cloned and characterized. The interaction between miR-1985 verified, then responses possible function miR-1985, , miR-1985/ poly(I:C) (a classic virus-related PAMP) stimulation P. were explored preliminarily dissected. results indicate: 1) 5354 bp, with high level sequence conservation across mollusks. 2) MiR-1985 bound 3’-UTR negatively regulated expression . 3) Py may repress relative superoxide dismutase SOD by binding its promoter. 4) Both silencing overexpression promoted enzymatic activity SOD. 5) be elevating SOD/catalase axis. summarize, all observations this study indicated that enhance redox capability via /SOD/CAT cascade thereby alleviate PAMP-induced stress.

Language: Английский

Citations

0
Suppressing Anaphase-Promoting Complex/Cyclosome–Cell Division Cycle 20 Activity to Enhance the Effectiveness of Anti-Cancer Drugs That Induce Multipolar Mitotic Spindles DOI Open Access
Scott C. Schuyler, Hsin-Yu Chen, Kai‐Ping Chang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6329 - 6329

Published: June 7, 2024

Paclitaxel induces multipolar spindles at clinically relevant doses but does not substantially increase mitotic indices. Paclitaxel's anti-cancer effects are hypothesized to occur by promoting chromosome mis-segregation on leading apoptosis, necrosis and cyclic-GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) pathway activation in daughter cells, secretion type I interferon (IFN) immunogenic cell death. Eribulin vinorelbine have also been reported cause increases cancer cells. Recently, suppression Anaphase-Promoting Complex/Cyclosome-Cell Division Cycle 20 (APC/C-CDC20) activity using CRISPR/Cas9 mutagenesis has sensitivity Kinesin Family 18a (KIF18a) inhibition, which functions suppress We propose that a way enhance the effectiveness agents is suppressing APC/C-CDC20 delay, block, anaphase entry. Delaying entry genomically unstable cells may spindle-induced In stable healthy human delayed level induced drugs lower cytotoxicity. outline specific combinations molecules investigate achieve goal enhancing agents.

Language: Английский

Citations

3
Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes DOI Creative Commons
Úrzula Franco‐Enzástiga,

Nikhil Nageshwar Inturi,

Keerthana Natarajan

et al.

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

Published: March 30, 2024

Abstract Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand gene regulation in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible technology followed sequencing (ATAC-seq). Using ATAC-seq, detected that females diverse differentially accessible regions (DARs) mapped X chromosome males autosomal genes. EGR1/3 SP1/4 transcription factor binding motifs were abundant within DARs females, JUN, FOS other AP-1 males. dissect open profile hDRG neurons, ATAC-seq. The neuron cluster showed higher accessibility GABAergic, glutamatergic, interferon-related genes Ca 2+ -signaling-related Sex differences sites neuron-proximal barcodes consistent with trends observed ATAC-seq data. We validated EGR1 biased female compared male. Strikingly, XIST , long-noncoding RNA responsible for inactivation, hybridization signal was found be highly dispersed neuronal but not non-neuronal nuclei suggesting weak inactivation neurons. Our findings point baseline epigenomic sex likely underlie divergent transcriptional responses determine mechanistic pain.

Language: Английский

Citations

2
STING recognition of viral dsDNA by nociceptors mediates pain in mice DOI Creative Commons
Sang Hoon Lee,

Fabio Bonifacio,

Arthur Silveira Prudente

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 121, P. 29 - 42

Published: July 22, 2024

Pain is often one of the initial indicators a viral infection, yet our understanding how viruses induce pain limited. Immune cells typically recognize nucleic acids, which activate receptors and signaling, leading to immunity. Interestingly, these signals are also present in nociceptors associated with pain. Here, we investigate response acids during infections, specifically focusing on role signal, Stimulator Interferon Genes (STING). Our research shows that cytosolic double-stranded DNA (dsDNA) from viruses, like herpes simplex virus 1 (HSV-1), triggers responses through STING expression nociceptors. In addition, agonists alone can elicit responses. Notably, involve direct activation TRPV1. We provided proof-of-concept showing TRPV1 significantly contribute mechanical hypersensitivity induced by HSV-1 infection. These findings suggest could be potential therapeutic target for relieving infections.

Language: Английский

Citations

2
Exploring blood transcriptomic signatures in patients with herpes zoster and postherpetic neuralgia DOI Creative Commons

Chunliang Wang,

Kaiyi Zhang,

Yuhan Bao

et al.

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

Published: Aug. 15, 2024

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN developed from herpes zoster (HZ), the developing mechanism unknown. A previous study investigated blood metabolomic proteomic profiling patients with HZ. The current aims to explore transcriptomic signature of compared HZ patients. Whole eight 15 was used for RNA-Seq analysis. There were 82 1,788 genes detected specifically groups, respectively. PHN-specific are involved viral infection, lipid carbohydrate metabolism, immune response. For coexpressed patients, there 407 differential expression (DEGs), including 205 upregulated (UP DEGs) 202 downregulated (DOWN groups. DEGs type I interferon (IFN), hemoglobin oxygen carrier activity. UP associated regulatory T cells (Tregs), activated NK cells, neutrophils, while DOWN Tregs, resting monocytes. results suggest that metabolism lipid, glycan, nucleotides, IFN signaling, altered neutrophil activation might contribute development It also suggested persistent or nonspecific immunity may

Language: Английский

Citations

2
STINGing away the pain: the role of interferon-stimulated genes DOI Creative Commons
Erick J. Rodríguez‐Palma, Heather N. Allen, Rajesh Khanna

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(9)

Published: April 30, 2024

Pain and inflammation are biologically intertwined responses that warn the body of potential danger. In this issue JCI, Defaye, Bradaia, colleagues identified a functional link between pain, demonstrating inflammation-induced activation stimulator IFN genes (STING) in dorsal root ganglia nociceptors reduced pain-like behaviors rodent model inflammatory pain. Utilizing mice with gain-of-function STING mutation, type I regulation voltage-gated potassium channels as mechanism pain relief. Further investigation into mechanisms by which proinflammatory pathways can reduce may reveal druggable targets insights new approaches for treating persistent

Language: Английский

Citations

0