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Dual Roles of SIRT7 Inhibition by Oroxylin A Reprogram HSCs Fate: PRMT5 Succinylation-Driven Senescence and Ecto-Calreticulin-Dependent NK Cell Immune Clearance in Liver Fibrosis.

Activation of hepatic stellate cells (HSCs) represents a central pathological event in liver fibrogenesis, and targeted clearance of activat … of protein arginine methyltransferase 5 (PRMT5). This cascade attenuated symmetric dimethylation of cyclic GMP-AMP synthase (cGAS), thereby activating the cGAS-stimulator of interferon genes (STING) signaling and promoting HSC senescence. Concurrently, OA-elicited SIRT7 inhibition promotes externalized calreticulin (ecto-CRT) expression, thereby enhancing na …

Mitochondrial p32-mediated regulation of p-TBK1 affects the radiosensitivity of colorectal cancer.

PURPOSE: Many colorectal cancer (CRC) patients respond poorly to radiotherapy due to radioresistance. Understanding the molecular mechanisms … rmore, depletion of p32 induced the DNA damage response (DDR) by activating cytoplasmic DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1), which was reversed by p32/TBK1 double knockout. Depletion of p32 also induced the mitochondrial fragmentation, induced mtDNA leakage through the mitochondrial p …

Shaoyao Gancao decoction promotes splenic immune homeostasis mediating cGAS-STING signaling pathway to delay autoimmune hepatitis progression.

ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao Gancao Decoction (SGD), a classic Chinese herbal formula from the "Treatise on Cold Damage (Shang Ha … pleen and liver. Additionally, SGD reduced HSC proliferation and activation. Further, SGD decreased cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), nuclear factor kappa-B (NF-κB), and transforming growth factor-β1 (TGF-β1) expression in the liver and HSCs. CONCLUSIONS: SGD promoted splenic immune homeostasis, which inhibited the hepa …

The ability of SAMHD1-deficient monocytes to trigger the Type I IFN response depends on cGAS and mitochondrial DNA.

In humans, mutations in sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) lead to the development of a type I int … tions revealed that chronic activation of type I IFN signaling in SAMHD1-knockout (KO) monocytes is cyclic GMP-AMP synthase (cGAS)-dependent. Analysis of other nucleic acid sensors showed that type I IFN signaling in SAMHD1-KO cells is not dependent on melanoma differentiation-associated protein 5 (MDA5) or retinoic acid-inducible gene I (RIG-I). In agreemen …

Photoaging: UV radiation-induced cGAS-STING signaling promotes the aging process in skin by remodeling the immune network.

Excessive exposure of the skin to UV radiaton (UVR) accelerates the aging process and leads to a photoaging state which involves similar pat … danger signal which stimulates cytoplasmic DNA sensors. The activation of the signaling through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) is a major defence and survival mechanism combatting against tissue injuries. There is abundant evidence that UVR exposure of skin stimulates cGAS-STING signaling which promotes cellular sen …

STING aggravates ferroptosis-dependent myocardial ischemia-reperfusion injury by targeting GPX4 for autophagic degradation.

Despite advancements in interventional coronary reperfusion technologies following myocardial infarction, a notable portion of patients continue to experience elevated mortality rates as a result of myocardial ischemia-reperfusion (MI/R) injury. An in-depth understanding of the mechanisms underlying MI/R injury is crucial for devising strategies to minimize myocardial damage and enhance patient survival. Here, it is discovered that during MI/R, double-stranded DNA (dsDNA)-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signal accumulates, accompanied by high rates of myoc…

Crosstalk between oxidative stress, mitochondrial dysfunction, chromosome instability, and the activation of the cGAS-STING/IFN pathway in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis, vascular dysfunction, and immune dysregulation. Recent studies have highlighted the crucial role of cellular stress responses and their connection to innate immunity in SSc pathogenesis, particularly the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, which has emerged as a pivotal mediator. In SSc, cGAS detects cytosolic DNA and activates STING, triggering type I interferon production and proinflammatory responses. Errors in chromosome segregation, leading to chromosomal instab…

Podocyte Metabolic Reprogramming and Targeted Therapy.

Podocytes, highly specialized glomerular epithelial cells, are essential for maintaining the filtration barrier integrity, yet they are part … nsors (nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 and cyclic GMP-AMP synthase-stimulator of IFN genes), and metabolic enzymes (ceramide synthase 6, glutaminase-2, and ornithine decarboxylase-1) in orchestrating this reprogramming. Emerging evidence supports the therapeutic potential of modulating podocyte metabol …

Mitochondria-dependent innate immunity: A potential therapeutic target in Flavivirus infection.

Mitochondria, known as the powerhouse of cells, play a crucial role in host innate immunity during flavivirus infections such as Dengue, Zik … m, which serves as a damage-associated molecular pattern (DAMP). Cytosolic mtDNA is sensed by cGAS (cyclic GMP-AMP synthase), leading to the activation of the STING (Stimulator of Interferon Genes) pathway to increase IFN production and expand inflammation. Flaviviral proteins control mitochondrial morphology by controlling mitochondrial fission (MF) and fus …

Engineered Salmonella Enteritidis vector targeting innate immune molecules provides protection against Salmonella Enteritidis and Salmonella Typhimurium.

Targeting the innate immune response is a critical factor in vaccine success. There are numerous serotypes of Salmonella, and cross-reactivi … or (SIRV) system. The rSC0163 strain, enhanced by the SIRV system, targets the host's innate immune cyclic GMP-AMP synthase (cGAS) molecule, triggering downstream immune pathways and significantly increasing levels of antibodies (IgA and IgY) and cytokines (IFN-γ and IL-4) in the peripheral blood of immunized chickens. Compared with the control strain rSC016 …

Двойная целеопределённость тротуаров TLR9 и CGAS-STING Translates Attenuates Astrocyte Inflamitation: потенциальные последствия при множественном склерозе.

Цель этого исследования заключается в изучении роли 9-го рецептора Toll (TLR9), датчика деоксирибозы нуклеиновой кислоты (DNA), в активации астроцитов и его вклада в многочисленные патогенез склероза (MS). Кроме того, мы изучили, действуют ли TLR9 и циклический GMP-AMP синтазы-стимулятор интерфероновых генов (cGAS-STING) синергетически для содействия воспалительной активации астроцитов и дает ли комбинированное ингибирование обоих путей более высокий защитный эффект. Человеческие астроциты обрабатывались неметилированным цитосином-фосфоротиоатом-гуанином (CpG) олигододоксинуклеотидом при разли

Совпадение в аннотации оригинала
This study aims to investigate the role of Toll-like receptor 9 (TLR9), a deoxyribose nucleic acid (DNA) sensor, in astrocyte activation and its contribution to multiple sclerosis (MS) pathogenesis. Additionally, we examined whether TLR9 and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathways act synergistically to promote astroc…

Tumor microenvironment-responsive manganese-based nano-modulator activate the cGAS-STING pathway to enhance innate immune system response.

BACKGROUND: Manganese ions (Mn2+) combined with adjuvants capable of damaging and lysing tumor cells form an antitumor nano-modulator that enhances the immune efficacy of cancer therapy through the cascade activation of the cyclic GMP-AMP interferon gene synthase-stimulator (cGAS-STING) pathway, which underscores the importance of developing antitumor nano-modulators, which induce DNA damage and augment cGAS-STING activity, as a critical future research direction. METHODS AND RESULTS: We have successfully synthesized an antitumor nano-modulator, which exhibits good dispersibility and biosafety…

Secondary messenger signalling influences Pseudomonas aeruginosa adaptation to sinus and lung environments.

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemic

Paraxanthine enhances memory and neuroplasticity more than caffeine in rats.

Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, r … oline, dopamine, and gamma-aminobutyric acid), and neurochemicals (BDNF, catalase, glutathione, and cyclic GMP) were analyzed from whole brain samples in young (8 weeks old) and aged (16 months old) rats. Compared to the control group, escape latency improved in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.05) in young animals, and in PXN HIGH and CAF HIGH in …

Metal coordination nanotheranostics mediated by nucleoside metabolic inhibitors potentiate STING pathway activation for cancer metalloimmunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an effective way to initiate an immune response against tumors, and the research on agonists targeting STING has become a new hotspot in the development of antitumor drugs. However, as a novel STING agonist, the limited bioavailability and activation routes of manganese ions (Mn2+) significantly hinder its antitumor effects. To address these challenges, we have designed a metal-coordinated nucleoside metabolic inhibitor (gemcitabine, Gem)-induced metal nanotheranostic (MGP) with PEGylation. This fo…

DNA corona on nanoparticles leads to an enhanced immunostimulatory effect with implications for autoimmune diseases.

Autoimmune and inflammatory diseases are highly complex, limiting treatment and the development of new therapies. Recent work has shown that … rleukin 6 (IL-6). We probed two intracellular DNA sensing pathways, toll-like receptor 9 (TLR9) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), to determine how cells sense the DNA-nanoparticle complexes. We found that the cGAS-STING pathway is the primary route for the interaction between DNA-nanoparticles and macrophages. These s …

Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway.

BACKGROUND AND PURPOSE: Stimulator of interferon response cGAMP interactor 1 (STING), a central hub protein of cyclic GMP-AMP synthase (cGAS)-STING signalling pathway, has a crucial role in regulating type I interferons (IFNs) production and response. Recent studies indicate that excessive activation of STING is strongly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Searching immunomodulators that negatively regulate STING might greatly contribute to the suppression of autoimmunity. EXPERIMENTAL APPROACH: The peripheral blood mononuclear cells (PBMCs) of S…

Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population … in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocaliza …

Atractylenolide III suppresses senescence-associated secretome via inhibiting cGAS/NF-κB pathway in hepatic stellate cells.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent … on of SASP factors (interleukin [IL]-1α, IL-1β, IL6 and IL-8) in senescent cells. ATR III regulated cyclic GMP-AMP synthase (cGAS)/nuclear factor κ (NF-κB) signalling to affect SASP expression in senescent cells. The addition of 2'3' cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could aff …

Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a … . The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.