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The mtDNA-cGAS-STING Axis in Acute Kidney Injury and Maladaptive Repair: Preclinical Evidence for Traditional Chinese Medicine and Natural Product-Based Interventions.

Acute kidney injury (AKI) is a heterogeneous syndrome characterized by substantial variation in etiology, clinical course, and recovery. Persistent tubular stress, mitochondrial dysfunction, and dysregulated inflammatory and immune responses can prolong tissue injury and lead to incomplete kidney recovery and maladaptive repair. When released into the cytosol, mitochondrial DNA (mtDNA) can activate cyclic GMP-AMP synthase (cGAS), which generates 2',3'-cGAMP and activates stimulator of interferon genes (STING). Downstream TBK1-IRF3 and NF-κB signaling programs amplify inflammation, regulated ce…

Host Genetic Susceptibility and Antiviral Immunity Shape the Pathogenesis and Outcomes of Herpes Simplex Encephalitis.

Herpes simplex encephalitis (HSE), predominantly caused by herpes simplex virus type 1 (HSV-1), is the most common sporadic viral encephalit … LR3), retinoic-acid-inducible gene-I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), which compromise type I interferon (IFN) production in central nervous system (CNS) resident cells; disrupted neuron intrinsic antiviral mechanisms represented by mutations in specific gene …

Virulence regulation in the fish pathogen Pseudomonas plecoglossicida: an integrated overview.

The genomes of pathogenic bacteria typically encode a diverse array of virulence factors, which constitute the fundamental basis for resisting host immunity and establishing infection. Given the high energetic cost of virulence gene expression, pathogens must precisely orchestrate the activation and silencing of these genes in accordance with the infection process, thereby flexibly executing diverse biological functions within the constraints of their energy budget. To sustain efficient infection, pathogens have evolved multiple mechanisms governing gene expression, enabling them to maintain c

Emerging Challenges and Advances in Porcine Circovirus: A Decade in Review.

Over the past decade, porcine circoviruses (PCVs) have continued to pose a significant threat to global swine health, and pivotal discoverie … r active investigation. Recent studies have revealed that PCVs evade host defenses by targeting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-type I interferon (IFN-I) pathway and modulating regulated cell death pathways, thereby fostering viral persistence and immune dysregulation. PCV-induced immunosuppression not only exacerbat …

STING activation promotes intestinal mucin secretion in IBD.

BACKGROUND & AIMS: Goblet cells produce mucus protecting the intestinal epithelium. Depleted goblet cells and a disrupted mucus layer are observed in inflammatory bowel diseases (IBD). Remarkably, both deficiency and overactivation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway lead to goblet cell depletion in mice. Here, we analyzed the role of cGAS-STING in goblet cell mucus regulation in IBD patients and human crypt-derived colonic organoids (HCO). METHODS: MUC and cGAS-STING pathway gene expression was analyzed in inflamed and non-inflamed mucosa (n = 8…

cGAS/STING is associated with brain-gut-liver axis disturbance and systemic inflammation in cerebral ischemia.

Cerebral ischemia triggers a cascade of systemic inflammatory responses closely associated with brain-gut-liver axis disturbance, yet the underlying molecular mechanism remains incompletely understood. This study aimed to elucidate the mechanistic role of the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling pathway in disrupting gut-liver axis homeostasis following cerebral ischemia. Using a middle cerebral artery occlusion (MCAO) rat model, we employed a multidisciplinary approach combining behavioral, histological, molecular, and biochemical assays. We demonstrat…

Barrier-to-Autointegration Factor 1: a key regulator of nuclear envelope integrity, genome stability, and disease progression.

Barrier-to-Autointegration Factor 1 (BANF1) is a self-associating protein encoded within the q13.1 locus of chromosome 11. It is integral to … ted, with cancer cells leveraging its functions to preserve NE integrity, inhibit activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) immune pathway, and facilitate epithelial-mesenchymal transition (EMT). These activities contribute to enhanced genomic stability and promote tumor cell proliferation and migration, thereby co …

Discovery of STING antagonists targeting cGAS-STING pathway to alleviate IMQ-induced psoriasis-like dermatitis.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is pivotal in the immune defense against infections and cancer. However, aberrant activation of this pathway can trigger autoimmune and inflammatory diseases by inducing excessive production of type I interferon (IFN) and pro-inflammatory cytokines. Inhibition of the aberrant activation of the cGAS-STING signaling pathway by targeting STING represents a novel therapeutic strategy for these autoimmune and inflammatory disorders. In this study, we discovered three novel STING antagonists based on surface …

Coumarins as natural aphrodisiacs: Mechanistic insights and future perspectives in male sexual health.

BACKGROUND: Male sexual dysfunction, particularly erectile dysfunction and reduced libido, affects a significant portion of the global male … exual health through several mechanisms: enhancing testosterone levels, modulating nitric oxide and cyclic GMP signaling, promoting vasodilation, stimulating neurotransmitters like oxytocin and dopamine, and improving sperm quality and motility. Preclinical studies show improvements in sexual behavior, erectile response, and hormone regulation. A clinical tr …

Unveiling the anti-inflammatory and antinociceptive effects of limonene in two models of carrageenan-induced inflammation and formalin-induced pain: role of l -arginine/nitric oxide/cGMP/K ATP channel signaling pathways, opioidergic, and benzodiazepine receptors.

Pain and inflammation are critical and complex biological responses to tissue damage or disease, which significantly impair life quality. Th … ntinociceptive and anti-inflammatory properties, mediated through the l -arginine/nitric oxide (NO)/cyclic GMP (cGMP)/ATP-sensitive potassium channel (K ATP ) signaling pathways, opioidergic, and benzodiazepine receptors.

Engineered mesenchymal stem cells for targeted delivery of H2S to suppress cGAS-STING inflammation and enhance cardioprotection in myocardial ischemia-reperfusion.

Myocardial ischemia-reperfusion (MI/R) injury remains a significant clinical challenge, primarily attributed to excessive oxidative stress and sterile inflammation resulting from dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Therapeutic strategies that target single pathological factors demonstrate limited efficacy, highlighting a critical need for integrative approaches targeting the complex ischemic microenvironment. Herein, this study develops a therapeutic platform termed "Hydro-guarder", integrating mesenchymal stem cells (MSCs…

Genomic and functional analysis of Pseudomonas protegens CS11 reveals multifaceted biocontrol mechanisms against Sclerotinia sclerotiorum via antifungal metabolites, root colonisation and plant defence induction in tomato.

Sclerotinia sclerotiorum is one of many fungal pathogens that threaten global crop production. Antagonistic rhizobacteria have emerged as promising eco-friendly alternatives to synthetic pesticides that can be deployed for effective and sustainable management of the fungal disease. From 60 rhizobacterial strains isolated in this study, eight were able to inhibit the in vitro growth of S. sclerotiorum. Among these, strain CS11 exhibited complete (100 %) inhibition and demonstrated multiple plant growth-promoting traits, including siderophore production, nitrogen assimilation, phosphate solubili

Молекулярные механизмы и терапевтические стратегии, используемые для лечения заболеваний печени в рамках CGAS-STING: поиск продолжается.

Синтаз-стимулятор интерферональных генов (cGAS-STING) стал центральным регулятором гомеостаза и патологии печени, регулирующим врожденный иммунитет, воспаление, фиброгенез и восстановление тканей. Дисрегуляция сигнала CGAS-STING, часто обусловленная цитосолическим зондированием ДНК, клеточным стрессом или перекрестной активацией с другими иммунными путями, приводит к чрезмерным интерферонам типа I и провоспалительному производству цитокина, усугубляя травму печени. Эта аберрантная активация связана с хроническим воспалением печени, фиброзом и канцерогенеза, что подчеркивает ее дуалистическую р

Совпадение в аннотации оригинала
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as a central regulator of liver homeostasis and pathology, governing innate immunity, inflammation, fibrogenesis, and tissue repair. Dysregulated cGAS-STING signaling, often driven by cytosolic DNA sensing, cellular stress, or cross-activation with other immune pathwa…

Human papillomavirus-related oropharyngeal squamous cell carcinoma exhibits enhanced radiosensitivity despite limited activation of cytosolic DNA sensing pathways and innate immune responses.

BACKGROUND: Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key ro … sors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cyclic GMP-AMP synthase (cGAS) and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infilt …

cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective.

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD) share key pathological features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, autophagic dysfunction, and DNA damage. By identifying cytosolic DNA and triggering the type I interferon response, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates neuroinflammation. Dysregulated cGAS-STING signaling has been linked to neu…

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination.

BACKGROUND: Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. METHODS: By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO…

Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke.

Ischemic stroke is one of the leading causes of death and disability. Dual transcranial direct current stimulation (dual-tDCS) is a promising intervention to treat ischemic stroke, but its efficacy and underlying mechanism remain to be verified. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a key mediator in cerebral injury. However, little is known about the effect of cGAS-STING on neuronal damage in ischemic stroke, and it remains to be studied whether the cGAS-STING pathway is involved in tDCS intervention for ischemic stroke. Therefor…

6-Shogaol attenuates cisplatin induced emesis by inhibiting the mtDNA-cGAS-STING signaling pathway in a rat pica model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger (Zingiber officinale Rosc.) is a traditional anti-emetic herb. 6-shogaol, the main active compound of … were determined by IHC. The levels of 8-oxo G DNA glycosylase 1 (OGG1), flap endonuclease 1 (FEN1), cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), phospho-STING (p-STING), TANK binding kinase 1 (TBK1), phospho-TBK1 (pTBK1), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB) in gastric antrum and ileum were assayed by western …

Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations.

Sepsis, characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection, remains a significant challenge in clinical practice. Despite advancements in understanding host-bacterial interactions, molecular responses, and therapeutic approaches, the mortality rate associated with sepsis has consistently ranged between 10 and 16%. This elevated mortality highlights critical gaps in our comprehension of sepsis etiology. Traditionally linked to bacterial and fungal pathogens, recent outbreaks of acute viral infections, including Middle East respiratory syn

Protective role of cGAS in NASH is related to the maintenance of intestinal homeostasis.

BACKGROUND & AIMS: Various intracellular pathways regulate inflammation in NASH. Cyclic GMP-AMP synthase (cGAS) is a DNA sensor that activates STING and plays a role in inflammatory diseases. Here, we explored the role of cGAS in hepatic damage, steatosis, inflammation, and liver fibrosis in mouse models of NASH. METHODS: cGAS deficient (cGAS-KO) and STING deficient (STING-KO) mice received high fat-high cholesterol-high sugar diet (HF-HC-HSD) or relevant control diets. Livers were evaluated after 16 or 30 weeks. RESULTS: HF-HC-HSD diet, both at 16 and 30 weeks, resulted in increased cGAS pr…