Intracellular metal ion-based chemistry for programmed cell death DOI
Y You, Zhongying Guo, Tyler Wolter

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Intracellular metal ions play essential roles in multiple physiological processes, including catalytic action, diverse cellular intracellular signaling, and electron transfer. It is crucial to maintain ion homeostasis which achieved by the subtle balance of storage release intracellularly along with influx efflux at interface cell membrane. Dysregulation has been identified as a key mechanism triggering programmed death (PCD). Despite importance initiating PCD, molecular mechanisms within these processes are infrequently discussed. An in-depth understanding review role PCD may better uncover novel tools for cancer diagnosis therapy. Specifically, calcium (Ca

Language: Английский

The gasdermin family: emerging therapeutic targets in diseases DOI Creative Commons
Cheng‐long Zhu, Sheng Xu, Ruoyu Jiang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 7, 2024

Abstract The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player pyroptosis. This recently characterized class of pore-forming effector proteins is orchestrating processes such membrane permeabilization, pyroptosis, the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants infections. GSDMs have been implicated range diseases including, but not limited to, sepsis, viral infections, cancer, either through involvement pyroptosis or independently this process. regulation GSDM-mediated gaining recognition promising therapeutic strategy treatment various diseases. Current strategies inhibiting GSDMD primarily involve binding to GSDMD, blocking cleavage GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In review, we delve into cutting-edge understanding interplay between elucidate activation GSDMs, explore their associations diseases, discuss recent advancements potential developing inhibitors.

Language: Английский

Citations

26
Recognition and control of neutrophil extracellular trap formation by MICL DOI Creative Commons
Mariano Malamud,

Lauren Whitehead,

Alasdair McIntosh

et al.

Nature, Journal Year: 2024, Volume and Issue: 633(8029), P. 442 - 450

Published: Aug. 14, 2024

Regulation of neutrophil activation is critical for disease control. Neutrophil extracellular traps (NETs), which are web-like structures composed DNA and neutrophil-derived proteins, formed following pro-inflammatory signals; however, if this process uncontrolled, NETs contribute to pathogenesis, exacerbating inflammation host tissue damage

Language: Английский

Citations

19
Reactive Oxygen Species: Orchestrating the Delicate Dance of Platelet Life and Death DOI Creative Commons
Rui Liao, Long Wang, Jing Zeng

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 80, P. 103489 - 103489

Published: Jan. 5, 2025

Platelets, which are vital for blood clotting and immunity, need to maintain a delicately balanced relationship between generation destruction. Recent studies have highlighted that reactive oxygen species (ROS), act as second messengers in crucial signaling pathways, players this dance. This review explores the intricate connection ROS platelets, highlighting their dual nature. Moderate levels potent activators, promoting megakaryocyte (MK) differentiation, platelet production, function. They enhance binding collagen, increase coagulation, directly trigger cascades thrombus formation. However, role harbors double-edged sword. Excessive unleash its destructive potential, triggering apoptosis reducing lifespan of platelets. High can damage stem cells disrupt redox-dependent signaling, whereas uncontrolled activation promotes inappropriate clotting, leading thrombosis. Maintaining precise balance within hematopoietic microenvironment is paramount optimal homeostasis. While significant progress has been made, unanswered questions remain concerning specific pathways impact on disorders. Addressing these holds key unlocking full potential ROS-based therapies treating platelet-related diseases such thrombocytopenia aims contribute ongoing dialog inspire further exploration exciting field, paving way novel therapeutic strategies harness benefits while mitigating dangers.

Language: Английский

Citations

4
Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation DOI Creative Commons
Martina Colicchia, Gina Perrella, P. W. GANT

et al.

Research and Practice in Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 7(2), P. 100116 - 100116

Published: Feb. 1, 2023

Language: Английский

Citations

27
Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps DOI
Dongmei Lin, Yukun Zhang,

Saizhen Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 244, P. 125370 - 125370

Published: June 16, 2023

Language: Английский

Citations

23
NLRP3 exacerbates EAE severity through ROS-dependent NET formation in the mouse brain DOI Creative Commons

Da Jeong Byun,

Jaeho Lee,

Kyungryung Ko

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 2, 2024

Abstract Background Neutrophil extracellular trap (NET) has been implicated in the pathology of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, specific contributions NLRP3, a NET-associated molecule, to EAE pathogenesis its regulatory role NET formation remain unknown. Methods To investigate detrimental effect NETs supported by NLRP3 MS pathogenesis, we induced WT KO mice monitored disease severity. At peak disease, was assessed flow cytometry, immunoblotting, immunofluorescence staining. further identify propensity infiltrated neutrophils, NET-related chemokine receptors, degranulation, ROS production, PAD4 expression levels were evaluated cytometry. In some experiments, injected with DNase-1 eliminate formed NETs. Results Our data revealed that neutrophils significantly infiltrate brain spinal cord form during pathogenesis. elevates formation, primarily brain. also modulated phenotypes brain-infiltrated circulating augmenting CXCR2 CXCR4 expression, thereby potentially enhancing formation. facilitates ROS-dependent PAD4-independent manner neutrophils. Finally, NLRP3-supported exacerbates severity, triggering Th1 Th17 cells recruitment. Conclusions Collectively, our findings suggest may be an etiological factor This study provides evidence targeting could potential therapeutic strategy for MS, specifically attenuating

Language: Английский

Citations

14
Epigenetic regulation of innate immune dynamics during inflammation DOI
Blake A. Caldwell, Liwu Li

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: 115(4), P. 589 - 606

Published: Feb. 1, 2024

Innate immune cells play essential roles in modulating both defense and inflammation by expressing a diverse array of cytokines inflammatory mediators, phagocytizing pathogens to promote clearance, assisting with the adaptive processes through antigen presentation. Rudimentary innate "memory" states such as training, tolerance, exhaustion develop based on nature, strength, duration challenge, thereby enabling dynamic transcriptional reprogramming alter present future cell behavior. Underlying are broad changes epigenome, or chromatin alterations above level DNA sequence. These include direct modification cytosine methylation well indirect modifications histones that comprise protein core nucleosomes. In this review, we will discuss recent advances our understanding how these epigenetic influence behavior system during acute chronic inflammation, stable epigenome result long-term related pathophysiology.

Language: Английский

Citations

9
Neutrophil Extracellular DNA Traps in Response to Infection or Inflammation, and the Roles of Platelet Interactions DOI Open Access
William A. Chen, Danilo S. Boskovic

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3025 - 3025

Published: March 5, 2024

Neutrophils present the host’s first line of defense against bacterial infections. These immune effector cells are mobilized rapidly to destroy invading pathogens by (a) reactive oxygen species (ROS)-mediated oxidative bursts and (b) via phagocytosis. In addition, their antimicrobial service is capped a distinct cell death mechanism, release own decondensed nuclear DNA, supplemented with variety embedded proteins enzymes. The extracellular DNA meshwork ensnares pathogenic bacteria neutralizes them. Such neutrophil traps (NETs) have potential trigger hemostatic response web-like chromatin serves as prothrombotic scaffold for platelet adhesion activation. What less obvious that platelets can also be involved during initial NETs, forming heterotypic interactions neutrophils facilitating responses pathogens. Together, effectively localize an infection until it cleared. However, not all microbial infections easily Certain organisms may dysregulated platelet–neutrophil interactions, subsequently propagate thromboinflammatory processes. include some NETs. Therefore, in order make rational intervention easier, further elucidation platelet, neutrophil, pathogen still needed.

Language: Английский

Citations

9
Neutrophil extracellular traps in wound healing DOI
Zhanyong Zhu,

Shengzhi Zhou,

Sicheng Li

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(11), P. 1033 - 1045

Published: Oct. 16, 2024

Language: Английский

Citations

9
tRNA-derived small RNAs: their role in the mechanisms, biomarkers, and therapeutic strategies of colorectal cancer DOI Creative Commons
Bo Zhang, Yi Pan, Zhe Li

et al.

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

Published: Jan. 13, 2025

Colorectal cancer (CRC) is the third most prevalent malignancy and second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age onset. In recent years, there has been recognition significance tRNA-derived small RNAs (tsRNAs), encompassing fragments (tRFs) tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, epigenetics gradually come to light. Emerging research revealed dysregulation tsRNAs CRC, implicating their role CRC initiation progression, highlighting potential early diagnosis, prognosis, therapeutic strategies. Although clinical application still its stages, findings highlight a close relationship between biogenesis function tsRNAs, chemical modifications, tumor immune microenvironment (TIME). Additionally, similar other RNAs, can be effectively delivered via nanoparticles (NPs). Consequently, future should focus on elucidating concerning base TIME regulation, immunotherapy, NPs delivery systems facilitate translation.

Language: Английский

Citations

1