APOPTOSIS, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 20, 2024
Language: Английский
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: Feb. 7, 2025
Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.
Language: Английский
Citations
3
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 9, 2025
The innate immune system promptly detects and responds to invading pathogens, with a key role played by the recognition of bacterial-derived DNA through pattern receptors. Z-DNA binding protein 1 (ZBP1) functions as sensor inducing type I interferon (IFN) production, responses also inflammatory cell death. ZBP1 interacts cytosolic via its DNA-binding domains, crucial for activation. Brucella abortus is etiologic agent brucellosis in livestock humans, leading significant economic losses public health impact. Despite other sensors that recognize B. DNA, including Toll-like receptor 9 Stimulator genes (STING), here we evaluated participation sensing infection. Using macrophages derived from knockout (KO) mice demonstrated partially contributes IFN-β expression upon infection or transfection. knockdown STING siRNA decreased residual signal elicited infection, demonstrating presence redundant DNA-sensing mechanism driving IFN production. Furthermore, involved signaling IRF-1 expression. Additionally, Unfolded Protein Response (UPR) activation during However, does not influence production proinflammatory mediators, inflammasome it dispensable control bacterial replication macrophages. This study highlights complex interactions components receptors identifies DNA-induced response.
Language: Английский
Citations
1
Pathogens, Journal Year: 2024, Volume and Issue: 13(7), P. 561 - 561
Published: July 3, 2024
Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. causes acute respiratory disease, commonly known as the "flu" in humans. In some individuals, flu can lead to pneumonia distress syndrome. A (IAV) is most significant because it recurring seasonal epidemics, occasional pandemics, zoonotic outbreaks human populations, globally. The host innate immune response IAV infection plays a critical role sensing, preventing, clearing well disease pathology. Host cells sense through multiple receptors mechanisms, which culminate induction concerted antiviral creation state, inhibits clears from cells. However, antagonizes escapes many steps by different mechanisms. Herein, we review those viral This covers aspects response, i.e., (1) sensing incoming particles, (2) activation downstream signaling pathways, (3) expression interferon-stimulated genes, (4) antagonism escape.
Language: Английский
Citations
7
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: March 19, 2025
Abstract Nucleic acids from both self- and non-self-sources act as vital danger signals that trigger immune responses. Critical illnesses such acute respiratory distress syndrome, sepsis, trauma ischemia lead to the aberrant cytosolic accumulation massive release of nucleic are detected by antiviral innate receptors in endosome or cytosol. Activation for deoxyribonucleic ribonucleic triggers inflammation, a major contributor morbidity mortality critically ill patients. In past decade, there has been growing recognition therapeutic potential targeting acid sensing critical care. This review summarizes current knowledge ischemia. Given extensive research on common pathological conditions like cancer, autoimmune disorders, metabolic disorders aging, we provide comprehensive summary beyond illness offer insights may inform its role conditions. Additionally, discuss strategies specifically target sensing. By examining sources, sensor activation function, well impact regulating these pathways across various diseases, highlight driving illness.
Language: Английский
Citations
0
Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 966 - 966
Published: June 16, 2024
Innate immunity, the first line of host defense against viral infections, recognizes components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing absent in melanoma 2-like and cytosolic DNA sensors (e.g., Z-DNA-binding protein 1 cyclic GMP-AMP synthase). Different types nucleic acid can recognize specific due to their unique structures. PANoptosis is a form inflammatory cell death pathway that triggered innate immune driven caspases receptor-interacting serine/threonine kinases PANoptosome complexes. 2) not only detect viruses, but also mediate providing scaffold for assembly PANoptosomes. This review summarizes structures sensors, discusses roles infections driving PANoptosis, highlights crosstalk between sensors. It underscores promising prospect manipulating as therapeutic approach infections.
Language: Английский
Citations
3
Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15
Published: May 24, 2024
Introduction With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need to discover effective therapeutic targets for this complex condition. Coding and non-coding RNAs, with traditional biochemical parameters, have shown promise as viable therapy. Machine learning (ML) techniques emerged powerful tools predicting drug responses. Method In study, we developed ML-based model identify most influential features response in treatment using three medicinal plant-based drugs (Rosavin, Caffeic acid, Isorhamnetin), a probiotics (Z-biotic), at different doses. A hundred rats were randomly assigned ten groups, including normal group, streptozotocin-induced diabetic eight treated groups. Serum samples collected analysis, while liver tissues (L) adipose (A) underwent histopathological examination molecular biomarker extraction quantitative PCR. Utilizing five machine algorithms, integrated 32 12 select predictive each combined model. Results discussion Our results indicated that high doses selected effectively mitigated inflammation, reduced insulin resistance, improved lipid profiles renal function biomarkers. The identified 13 features, 10 20 accuracy 80% AUC (0.894, 0.93, 0.896), respectively. This study presents ML accurately identifies implicated pathways associated T2DM pathogenesis.
Language: Английский
Citations
1
mBio, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 30, 2024
ABSTRACT The interaction between Z-DNA binding protein 1 (ZBP1) and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been uncovered in several viral infections. However, role of this molecular pathway during infection with alpha-herpesvirus pseudorabies virus (PRV) remains largely elusive. Here, we report that PRV infection, ZBP1-mediated NLRP3 activation is inhibited by tegument VP22, thereby facilitating infection. Through a combination RNA sequencing genetic studies, demonstrate VP22 functions as virus-encoded virulence factor evading inhibitory effects ZBP1 on Importantly, replication pathogenicity recombinant lacking are significantly increased ZBP1-deficient cells mice. Mechanistically, interacts ZBP1, impeding recruitment receptor-interacting kinase Caspase-8, inhibiting activation. Furthermore, show N-terminal 1–50 amino acid domain dominantly destabilizes function. Taken together, these findings identify functional link inflammatory response, providing novel insights into pathogenesis other herpesviruses. IMPORTANCE pivotal innate immune sensor regulates cell death its unknown. serves restrictive triggering inflammasome, process counteracted PRV-encoded VP22. interferes 3/Caspase-8, particularly through acids. deficiency enhances viruses or These reveal how escapes responses potentially informing rational design therapeutic interventions.
Language: Английский
Citations
1
Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 19, 2024
Abstract Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become critical strategy for treatment. PANoptosis, newly discovered form of regulated death, integrates key molecular components pyroptosis, apoptosis, and necroptosis, activating these three pathways simultaneously achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits growth resistance activates strong anti‐tumor immune response, making tumor‐specific induction potential therapeutic strategy. Currently, treatment research related is focused mainly on the development small molecules cytokines. However, approaches still face limitations terms metabolic stability tumor specificity. The unique physicochemical properties biological activities nanomaterials hold promise optimizing strategies. This review summarizes concept mechanisms highlights latest applications nanoagents PANoptosis‐based anti‐cancer therapy, discusses challenges future directions clinical translation. It hoped that this will inspire further exploration treatments, providing new perspectives researchers field.
Language: Английский
Citations
1
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 19, 2024
Abstract Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become critical strategy for treatment. PANoptosis, newly discovered form of regulated death, integrates key molecular components pyroptosis, apoptosis, and necroptosis, activating these three pathways simultaneously achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits growth resistance activates strong anti‐tumor immune response, making tumor‐specific induction potential therapeutic strategy. Currently, treatment research related is focused mainly on the development small molecules cytokines. However, approaches still face limitations terms metabolic stability tumor specificity. The unique physicochemical properties biological activities nanomaterials hold promise optimizing strategies. This review summarizes concept mechanisms highlights latest applications nanoagents PANoptosis‐based anti‐cancer therapy, discusses challenges future directions clinical translation. It hoped that this will inspire further exploration treatments, providing new perspectives researchers field.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5226 - 5226
Published: May 10, 2024
Nucleic acids are not only static carriers of genetic information but also play vital roles in controlling cellular lifecycles through their fascinating structural diversity [...].
Language: Английский
Citations
0