Comprehending toll-like receptors: pivotal element in the pathogenesis of sepsis and its complications DOI Creative Commons
Wei Wang,

Shengtian Mu,

Dongli Yan

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 2, 2025

Sepsis, a critical systemic inflammatory response syndrome elicited by pathogenic microorganisms, poses significant challenge in clinical practice due to its rapid progression and potential for multi-organ failure. This review delineates the intricate roles of Toll-like receptors (TLRs), essential components innate immune system, mediating host responses during sepsis. TLRs recognize pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs), thereby initiating signaling cascades that lead synthesis pro-inflammatory cytokines chemokines. However, dysregulation TLR can precipitate hyper-inflammatory state known as “cytokine storm,” characterized excessive tissue damage complications such Acute Respiratory Distress Syndrome (ARDS) acute kidney injury (AKI). Several therapeutic strategies targeting pathways are under exploration mitigate adverse effects Despite advancements, gaps remain, including need robust validation understanding expression variability among individuals. Future research should focus on elucidating precise mechanisms governing TLR-mediated developing human-specific interventions. aims consolidate current knowledge sepsis, highlighting their dual both defenders against infection contributors pathological conditions, informing future strategies.

Language: Английский

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

77
Current Perspectives of Mitochondria in Sepsis-Induced Cardiomyopathy DOI Open Access

Tatsuki Kuroshima,

Satoshi Kawaguchi, Motoi Okada

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4710 - 4710

Published: April 26, 2024

Sepsis-induced cardiomyopathy (SICM) is one of the leading indicators for poor prognosis associated with sepsis. Despite its reversibility, varies widely among patients. Mitochondria play a key role in cellular energy production by generating adenosine triphosphate (ATP), which vital myocardial metabolism. Over recent years, mounting evidence suggests that severe sepsis not only triggers mitochondrial structural abnormalities such as apoptosis, incomplete autophagy, and mitophagy cardiomyocytes but also compromises their function, to ATP depletion. This metabolic disruption recognized significant contributor SICM, yet effective treatment options remain elusive. Sepsis cannot be effectively treated inotropic drugs failing myocardium due excessive inflammatory factors blunt β-adrenergic receptors. review will share knowledge on cell death molecular mechanisms, focusing mitochondria an important regulator discuss potential developing therapies sepsis-induced injury.

Language: Английский

Citations

16
Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance DOI Creative Commons
Hongquan Wang, Joshua S. Fleishman,

Sihang Cheng

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 27, 2024

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, unique type regulated cell death, plays pivotal role inhibiting tumour growth, presenting new opportunities treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine vulnerability to ferroptosis. In this review, we first summarize the growth/development. Then, core molecular mechanisms ferroptosis, its upstream regulation, and downstream effects on Finally, review recent advances understanding how ncRNAs regulate ferroptosis from such modulate This aims enhance general ncRNA-mediated regulatory which highlighting ncRNA-ferroptosis axis as key druggable target overcoming

Language: Английский

Citations

15
Targeting novel regulated cell death：Ferroptosis, pyroptosis, and autophagy in sepsis-associated encephalopathy DOI Open Access

Jingjing Sun,

Joshua S. Fleishman, Xueyan Liu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116453 - 116453

Published: March 20, 2024

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is heterogenous complex clinical syndrome caused by the dysfunctional response host to infection. This leads excess mortality and morbidity worldwide. Despite relevance with high incidence, there lack understanding for its both acute/chronic pathogenesis therapeutic management. A better molecular mechanisms behind SAE may provide tools enhance efficacy. Mounting evidence indicates that some types non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, autophagy, contribute SAE. Targeting these RCD meaningful targets future treatments against review summarizes core mechanism which We focus on emerging compounds can inhibit delineate their beneficial pharmacological effects Within this we suggest inhibition serve potential strategy

Language: Английский

Citations

13
Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury DOI Open Access
V. V. Ryabov, Л. Н. Маслов,

Evgeniy V. Vyshlov

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 897 - 897

Published: Jan. 11, 2024

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased recent years. leading cause of death these ischemia/reperfusion (I/R) cardiac injury. It quite obvious that there an urgent need to create new drugs for the treatment STEMI based on knowledge pathogenesis I/R injury, particular, molecular mechanism ferroptosis. In this study, it was demonstrated ferroptosis involved development antitumor drug-induced cardiomyopathy, diabetic septic inflammation. There indirect evidence participates stress-induced activation AMPK, PKC, ERK1/2, PI3K, Akt prevents inhibition HO-1 alleviates roles GSK-3β NOS regulation require further study. stimulation Nrf2, STAT3 TLR4 NF-κB promotes cardiomyocytes. MiR-450b-5p miR-210-3p can increase tolerance cardiomyocytes hypoxia/reoxygenation through Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p miR-15a-5p aggravate

Language: Английский

Citations

12
FOXO1‐NCOA4 Axis Contributes to Cisplatin‐Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy DOI Creative Commons

Xue Wang,

Lei Xu, Yu Meng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(40)

Published: Aug. 29, 2024

Abstract Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs subsequent SNHL still under debate there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis triggered in following exposure cisplatin. Inhibiting protects against loss, inducing intensifies these effects. Furthermore, prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy SGNs, knocking down NCOA4 mitigates loss. Notably, upstream regulator of identified transcription factor forkhead box O1 (FOXO1) shown directly suppress expression SGNs. The FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases lipid peroxidation, disrupting interaction between knock out mice prevents SGN Collectively, highlights critical role FOXO1‐NCOA4 axis regulating damage, offering promising therapeutic targets mitigation.

Language: Английский

Citations

10
Exocarpium Citri Grandis ameliorates LPS-induced acute lung injury by suppressing inflammation, NLRP3 inflammasome, and ferroptosis DOI

Zaibin Xu,

Jiayu Li,

Kaili Zhou

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 329, P. 118162 - 118162

Published: April 7, 2024

Language: Английский

Citations

9
Induction of ferroptosis: A new strategy for the control of bacterial infections DOI
Rongxian Guo, Xin Fang, Ke Shang

et al.

Microbiological Research, Journal Year: 2024, Volume and Issue: 284, P. 127728 - 127728

Published: April 17, 2024

Language: Английский

Citations

9
Targeting Lcn2 to Inhibit Myocardial Cell Ferroptosis is a Potential Therapy for Alleviating Septic Cardiomyopathy DOI Creative Commons
Cheng Jiang, Ming‐Chih Hou, Shougang Sun

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Septic cardiomyopathy (SCM) represents a key feature of sepsis-associated cardiovascular failure, and ferroptosis is one the essential causes septic cardiac dysfunction. In this study, combined with omics analysis in vivo experiments, we verified damage on tissue mice mined target genes that can inhibit cardiomyocytes. Lipocalin-2 (Lcn2) was identified to be associated SCM progression via integrated transcriptomic proteomic analyses. Sepsis induced by cecal ligation perforation (CLP) mice. Ferroptosis dysfunction were detected pathological staining ELISA. However, after knockout Lcn2, cardiomyocyte significantly suppressed, inflammatory infiltrates reduced, reactive oxygen species (ROS) levels lowered, mitochondrial alleviated, function restored CLP summary, study found Lcn2 potential for inhibiting SCM. Targeting effectively inflammation, improve dysfunction, ferroptosis, alleviate

Language: Английский

Citations

1
Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies DOI Creative Commons
Dandan Guo, Songhua Cai,

Lvdan Deng

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 23, 2025

Ferroptosis is a distinct form of iron-dependent programmed cell death characterized primarily by intracellular iron accumulation and lipid peroxidation. Multiple cellular processes, including amino acid metabolism, various signaling pathways, autophagy, have been demonstrated to influence the induction progression ferroptosis. Recent investigations elucidated that ferroptosis plays crucial role in pathogenesis pulmonary disorders, lung injury, chronic obstructive disease, fibrosis, asthma. increasingly recognized as promising novel strategy for cancer treatment. Various immune cells within tumor microenvironment, CD8+ T cells, macrophages, regulatory natural killer dendritic shown induce modulate process through regulation metabolism pathways. Conversely, can reciprocally alter metabolic environment, leading activation or inhibition functions, thereby modulating responses. This paper reviews molecular mechanism describes discusses connection between microenvironment diseases, development prospect their interaction treatment diseases.

Language: Английский

Citations

1