Blocking copper transporter protein-dependent drug efflux with albumin-encapsulated Pt(IV) for synergistically enhanced chemo-immunotherapy DOI Creative Commons

Man Fang,

Lei Cao, Zhao Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract Non-small cell lung cancer (NSCLC) represents the most prevalent form of cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted interest. While numerous studies concentrate their functional modifications targeted delivery, tumor-induced frequently overlooked. Previous compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting to cisplatin. In order enhance efficacy potential applications in glutathione (GSH)-responsive albumin nanoquadrivalent (HSA@Pt) been constructed. light previous research into drug conjugation, this study was develop combined chemo-immunotherapy approach. The HSA@Pt high low toxicity, with tumor accumulation. Furthermore, tetrathiomolybdate (TM) has exert synergistic inhibitory effect Cu2+ Transporting Beta Polypeptide (ATP7B) Programmed Death Ligand 1 (PD-L1), impede efflux, induce cellular stress, activate immunity. findings suggest HSA@Pt's use strategy enhancing utility established drugs through sensitization.

Language: Английский

Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

et al.

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
Agonists and Inhibitors of the cGAS-STING Pathway DOI Creative Commons
Xiaoxuan Yu, Linxiang Cai,

Jingyue Yao

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3121 - 3121

Published: June 30, 2024

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is pivotal in immunotherapy. Several agonists and inhibitors the cGAS-STING have been developed evaluated for treatment various diseases. aim to activate STING, with dinucleotides (CDNs) being most common, while block enzymatic activity or DNA binding ability cGAS. Meanwhile, non-CDN compounds cGAS are also gaining attention. omnipresence vivo indicates that its overactivation could lead undesired inflammatory responses autoimmune diseases, which underscores necessity developing both pathway. This review describes molecular traits roles summarizes development inhibitors. information supposed be conducive design novel drugs targeting

Language: Английский

Citations

14
Relationship between the cGAS−STING and NF-κB pathways-role in neurotoxicity DOI Open Access

Shiyin Zhong,

Qiongli Zhou,

Jirui Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116698 - 116698

Published: May 6, 2024

Neurotoxicity can cause a range of symptoms and disorders in humans, including neurodegenerative diseases, neurodevelopmental disorders, nerve conduction abnormalities, neuroinflammation, autoimmune cognitive deficits. The cyclic guanosine-adenosine synthase (cGAS)-stimulator interferon genes (STING) pathway NF-κB are two important signaling pathways involved the innate immune response. cGAS-STING is activated by recognition intracellular DNA, which triggers production type I interferons pro-inflammatory cytokines, such as tumor necrosis factor, IL-1β, IL-6. These cytokines play role oxidative stress mitochondrial dysfunction neurons. various stimuli, bacterial lipopolysaccharide, viral particle components, neurotoxins. activation may lead to promote neuroinflammation neuronal damage. A potential interaction exists between pathways, blocks STING degradation inhibiting microtubule-mediated transport. This review examines progress research on roles these neurotoxicity their interrelationships. Understanding mechanisms will provide valuable therapeutic insights for preventing controlling neurotoxicity.

Language: Английский

Citations

10
The complexity of immune evasion mechanisms throughout the metastatic cascade DOI

Nicole M. Haynes,

Thomas B Chadwick, Belinda S. Parker

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1793 - 1808

Published: Sept. 16, 2024

Language: Английский

Citations

10
The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease DOI Creative Commons

Shuiyue Quan,

Xiaofeng Fu,

Huimin Cai

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 4, 2025

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing damage-associated molecular patterns (DAMPs), inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation this pathway culminates in AD-related neuroinflammation neurodegeneration. A substantial body mitochondria are involved critical pathogenic mechanisms AD, whose damage leads release mitochondrial (mtDNA) into extramitochondrial space. This leaked mtDNA serves DAMP, various pattern recognition receptors defense networks brain, including cGAS-STING pathway, ultimately leading an imbalance homeostasis. Therefore, modulation mtDNA-cGAS-STING restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In review, we focus on during stress activation pathway. Additionally, delve research progress further discuss primary directions potential hurdles developing targeted therapeutic drugs, gain deeper understanding pathogenesis provide new approaches its therapy.

Language: Английский

Citations

1
Interferonopathies: From concept to clinical practice DOI Creative Commons
Leonardo Oliveira Mendonça, Marie‐Louise Frémond

Best Practice & Research Clinical Rheumatology, Journal Year: 2024, Volume and Issue: unknown, P. 101975 - 101975

Published: Aug. 1, 2024

The horror autoinflammaticus derived from aberrant type I interferon secretion determines a special group of autoinflammatory diseases named interferonopathies. Diverse mechanisms involved in nucleic acids sensing, metabolizing or the lack signaling retro-control are responsible for phenotypes associated to Aicardi-Goutières Syndrome (AGS), Proteasome-Associated Autoinflammatory Diseases (PRAAS), STING-Associated Vasculopathy with Infancy Onset (SAVI) and certain forms monogenic Systemic lupus erythematosus (SLE). This review approaches interferonopathies basic immunogenetic concept diagnosis treatment.

Language: Английский

Citations

4
Anti‐Inflammatory Treatment of Subarachnoid Hemorrhage by Self‐Assembled Silymarin Nanoparticles DOI Creative Commons

Yong Li,

Youdong Zhou,

Yinqiu Tan

et al.

Small Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and mortality. Early brain injury (EBI) the main cause of mortality delayed neurological dysfunction in patients SAH. Neuroinflammation important pathological processes EBI.We prepared Silymarin nanoparticles (SIM NPs) through solvent precipitation method investigated their role combating EBI following SAH mice. We found that SIM NPs diameter 150 nm have strongest ability to cross blood‐brain barrier. are spherical contain irregular particles inside, which may be composed mainly silibinin assembled hydrogen bonding. Further vivo experiments showed improved short‐term mice, reduced cortical neural damage, inflammation Nrf2/STING pathway. Finally, water maze can improve long‐term memory learning Based on above results, we conclude silymarin reduce after by inhibiting pathway, neuroinflammation M1 polarization microglia.

Language: Английский

Citations

0
Advances in understanding the role and mechanism of the cGAS-STING signaling pathway in ocular diseases DOI Creative Commons
Mengdi Zhang, Jiayu Xu,

Wenjia Qu

et al.

Immunological Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: March 8, 2025

The cGAS-STING signaling pathway plays a critical role in the immune defense against DNA viruses and autoimmunity, coordinating cascade of events that enhance cytokine production, particularly type I interferons. This review summarizes recent advancements understanding pathway's impact on various ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy, uveitis. Activation this by cytoplasmic from either damaged retinal cells or external pathogens induces inflammatory responses may accelerate disease progression. Moreover, paper explores new therapeutic approaches target pathway, offering insights into how modulation could reduce inflammation improve clinical outcomes. emerging research area suggests potential for innovative treatments degenerative conditions.

Language: Английский

Citations

0
Blocking copper transporter protein-dependent drug efflux with albumin-encapsulated Pt(IV) for synergistically enhanced chemo-immunotherapy DOI Creative Commons

Man Fang,

Lei Cao, Zhao Zhang

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 18, 2025

Non-small cell lung cancer (NSCLC) represents the most prevalent form of cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted interest. While numerous studies concentrate their functional modifications targeted delivery, tumor-induced frequently overlooked. Previous compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting to cisplatin. In order enhance efficacy potential applications in glutathione (GSH)-responsive albumin nanoquadrivalent (HSA@Pt) been constructed. light previous research into drug conjugation, this study was develop combined chemo-immunotherapy approach. The HSA@Pt high low toxicity, with tumor accumulation. Furthermore, Ammonium Tetrathiomolybdate (TM) has exert synergistic inhibitory effect ATPase Copper Transporting Beta (ATP7B) Programmed Death Ligand 1 (PD-L1), impede efflux, induce cellular stress, activate immunity. findings suggest HSA@Pt's use strategy enhancing utility established drugs through sensitization.

Language: Английский

Citations

0
ALDH1A3 Regulates Cellular Senescence and Senescence-Associated Secretome in Prostate Cancer DOI Open Access
Sen Wang, Lin Wang, Yu Zhao

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1184 - 1184

Published: March 31, 2025

Background: Radiotherapy is a key treatment for cancer, effectively controlling local tumor growth through DNA damage that induces senescence or apoptosis in cancer cells. However, radiotherapy can trigger complex cellular reactions, such as cell senescence, which characterized by irreversible cycle arrest and the secretion of pro-inflammatory factors known senescent-associated secretory phenotype (SASP). Methods: This study investigates regulatory role ALDH1A3, enzyme implicated metabolism resistance, induction SASP. Using vitro models, we demonstrate ALDH1A3 knockdown accelerates senescent-like while regulating SASP cGAS-STING immune response pathway. Results: Our results indicate promotes it reduces via inhibition pathway, potentially mitigating SASP-related progression. Conclusions: These findings provide insights into molecular mechanisms underlying prostate suggest could be potential therapeutic target to enhance efficacy adverse effects

Language: Английский

Citations

0