Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences DOI Open Access
John Q. Yap, Azadeh Nikouee, Joseph T. F. Lau

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4211 - 4211

Published: April 29, 2025

Sepsis is a life-threatening condition that occurs when the body unable to effectively combat infection, leading systemic inflammation and multi-organ failure. Interestingly, females exhibit lower sepsis incidence improved clinical outcomes compared males. However, mechanisms underlying these sex-specific differences remain poorly understood. While sex hormones have been primary focus, emerging evidence suggests non-hormonal factors also play contributory roles. Despite in sepsis, management same for both males females, with treatment focused on combating infection using antibiotics hemodynamic support through fluid therapy. even interventions, mortality remains high, highlighting need more effective targeted therapeutic strategies. Sepsis-induced cardiomyopathy (SIC) key contributor failure characterized by left ventricular dilation impaired cardiac contractility. In this review, we explore SIC, particular focus mitochondrial metabolism. Mitochondria generate ATP required function fatty acid glucose oxidation, recent studies revealed distinct metabolic profiles between which can further differ context of SIC. Targeting pathways could provide new avenues treatment.

Language: Английский

“The NET effect”: Neutrophil extracellular traps—a potential key component of the dysregulated host immune response in sepsis DOI Creative Commons
Andrew Retter, Mervyn Singer, Djillali Annane

et al.

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: Feb. 4, 2025

Abstract Neutrophils release neutrophil extracellular traps (NETs) as part of a healthy host immune response. NETs physically trap and kill pathogens well activating facilitating crosstalk between cells complement. Excessive or inadequately resolved are implicated in the underlying pathophysiology sepsis other inflammatory diseases, including amplification response inducing thrombotic complications. Here, we review growing evidence implicating neutrophils central players dysregulated We discuss potential strategies for modifying to improve patient outcomes need careful selection.

Language: Английский

Citations

3
Inhibition of NETs prevents doxorubicin-induced cardiotoxicity by attenuating IL-18-IFN-γ-Cx43 axis induced cardiac conduction abnormalities DOI
Kun Li,

Kunmao Jiang,

Yu Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114016 - 114016

Published: Jan. 12, 2025

Language: Английский

Citations

1
An Artificial Piezoelectric-Conductive Integrated Peri-Implant Gingiva Enables Efficient Bacterial Inhibition and Soft-Tissue Integration DOI

Han Wen,

Zhiqing Liu, Hao Yu

et al.

Advanced Fiber Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

1
Lenvatinib-activated NDUFA4L2/IL33/PADI4 pathway induces neutrophil extracellular traps that inhibit cuproptosis in hepatocellular carcinoma DOI Creative Commons

Nan Yi,

Lingyun Zhang,

Xiangbo Huang

et al.

Cellular Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Lenvatinib is a potent first-line therapy for patients with hepatocellular carcinoma (HCC), but it also increased the number of neutrophils in HCC tumor microenvironment. CitH3, MPO-DNA, elastase and MPO activity were measured assessing neutrophil extracellular traps (NETs) vivo vitro. Cell cuproptosis was assessed by measurement copper content, FDX1, pyruvate. The functions lenvatinib, DNase I, interleukin 33 (IL33) neutralizing antibody GPX4 growth explored mice. induced NETs microenvironment via cells, not through direct stimulation neutrophils. In addition, NET clearance I improves efficacy lenvatinib mouse models. Mechanistically, promoted expression secretion IL33 cells that triggered formation. Moreover, knockdown Hepa1-6 improved Hepa1-6-bearing model mice reduced formation Subsequently, production increasing NDUFA4L2 cells. Furthermore, we found protein PADI4 Akt/mTOR signaling pathway. Rapamycin inhibition mTOR Consistently, selective PAD4 inhibitor GSK484 hydrochloride (GSK484) response to therapy. Importantly, contribute resistance inhibiting cuproptosis, apoptosis, pyroptosis, or ferroptosis Treatment reversed inhibitory effects on sensitized lenvatinib. Our study revealed lenvatinib-induced inhibited suggesting targeting IL33/PADI4/NET axis represents promising therapeutic strategy ameliorating HCC.

Language: Английский

Citations

4
Identification of potential targets regulating neutrophil extracellular traps in acute rejection of kidney transplantation based on transcriptomics and animal experiments DOI
Jun Pei,

Huali Weng,

Jinpu Peng

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114008 - 114008

Published: Jan. 5, 2025

Language: Английский

Citations

0
A Case Report of Systemic Capillary Leak Syndrome: When More Than One Inciting Factor Exists, the Question Is Who Pulls the Trigger? DOI Open Access

Vasileios Patriarcheas,

Eleftheria Ztriva,

Vasiliki Gougoula

et al.

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

Published: Jan. 10, 2025

Systemic capillary leak syndrome (SCLS) constitutes a rare clinical entity. It is characterized by spontaneous, recurrent episodes of increased permeability, leading to double clinico-biological paradox: diffuse pitting edema with hypovolemia or hypovolemic shock, and hemoconcentration hypoalbuminemia, in the absence secondary causes for such abnormalities. Even though several theories have been proposed, exact pathophysiology SCLS remains unclear. We report herein case idiopathic 38-year-old male patient history previous immunization, following COVID-19 infection, who was also diagnosed myeloproliferative neoplasm (MPN). To our knowledge, this first where coexists an MPN, legitimate question: Who pulls trigger?

Language: Английский

Citations

0
GNGT1 remodels the tumor microenvironment and promotes immune escape through enhancing tumor stemness and modulating the fibrinogen beta chain-neutrophil extracellular trap signaling axis in lung adenocarcinoma DOI Open Access

Linlin Fan,

Xiaowei Wang, Xiu‐Mei Zhang

et al.

Translational Lung Cancer Research, Journal Year: 2025, Volume and Issue: 14(1), P. 239 - 259

Published: Jan. 1, 2025

Despite the recent advancements in treatment of cancer, 5-year survival patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. Lung adenocarcinoma (LUAD) is NSCLC's most common subtype, and metastasis major cause death cancer. Therefore, identifying novel targets associated NSCLC crucial to improving treatment. This study aimed characterize expression GNGT1 LUAD clarify mechanism underlying association between higher level worse prognosis patients. The transcriptome datasets clinical information were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database. Bioinformatics analyses performed 515 who stratified into two groups (high- low-GNGT1 group) according level. Overall survival, DNA promotor methylation, immune infiltration, gene set enrichment analysis (GSEA), Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway elucidate functions identify related hub genes LUAD. Their verified using tissues transgenic mice overexpressing under control a lung-specific promoter (Scgb1a1-Cre). was overexpressed poor prognosis. significantly correlated alteration hypomethylated status. High advanced lymph node degree infiltration. Functional indicated that differentially expressed (DEGs) high-GNGT1 group participated replication, replication preinitiation, M phase, while adhesion molecules, apoptosis, natural killer cell-mediated cytotoxicity all downregulated. Messenger RNA protein levels correspondingly regulated human Scgb1a1-Cre; LSL-GNGT1 mouse model (GNGT1fl/+ mice). tumor proliferation via enhancement stemness interaction driver genes. Elevated promoted epithelial-mesenchymal transformation, remodeled microenvironment, led metastasis, ultimately worsening survival-related

Language: Английский

Citations

0
Pulmozyme Ameliorates LPS-Induced Lung Fibrosis but Provokes Residual Inflammation by Modulating Cell-Free DNA Composition and Controlling Neutrophil Phenotype DOI Creative Commons
Л. А. Алексеева,

Aleksandra V. Sen’kova,

Khetam Sounbuli

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 298 - 298

Published: Feb. 17, 2025

Pulmonary fibrosis, a chronic progressive lung disorder, can be the result of previous acute inflammation-associated injury and involves wide variety inflammatory cells, causing deposition extracellular matrix (ECM) components in lungs. Such is often associated with excessive neutrophil function formation DNA networks lungs, which are also some most important factors for fibrosis development. Acute subsequent was initiated C57Bl/6 mice by single intranasal (i.n.) administration LPS. Starting from day 14, human recombinant DNase I form Pulmozyme topical instilled i.n. twice week at dose 50 U/mouse. Cell-free (cfDNA), activity, cell content were analyzed blood serum bronchoalveolar lavage fluid (BALF). Inflammatory fibrotic changes tissue evaluated histological analysis. The gene expression profile spleen-derived neutrophils RT-qPCR. We demonstrated that significantly reduced connective expansion However, despite reliable antifibrotic effect, complete resolution inflammation respiratory system treated not achieved, possibly due to enhanced granulocyte recruitment nuclear/mitochondrial cfDNA balance BALF. Moreover, introduction caused enrichment population those an unusual phenotype, combining pro-inflammatory anti-inflammatory features, maintain inflammation. considered promising drug management; however, therapy may accompanied residual

Language: Английский

Citations

0
Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis DOI Creative Commons
Saugata Dutta, Saugata Dutta,

Payaningal R. Somanath

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 133 - 133

Published: Feb. 19, 2025

Cellular nucleosomes-the structural and functional units of chromatin-are inherently present in cells. During cellular damage or cell death, nucleosomes are released into circulation, either actively passively. Once released, can become immunogenic entities through various mechanisms. The nucleosomal proteins nucleosomes, called histones, play a pivotal role inducing immunogenicity. However, intact more than the histones alone, as double-stranded deoxyribonucleic acid (dsDNA) enhances its potential. Our recent study has shown that circulating predominantly rather free histones. Consequently, primarily function integral parts acting independently. Circulating their associated implicated pathogenesis wide array diseases. Notably, they critical lung injury sepsis. These diseases have high morbidity mortality rates lack early diagnostic biomarkers. Further investigation is required to fully elucidate disease processes. This review aims discuss current understanding sepsis, with focus on underlying

Language: Английский

Citations

0
Archaea-inspired deoxyribonuclease I liposomes prevent multiple organ dysfunction in sepsis DOI
Xinze Li, Fan Wu, Dedong Yu

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 1109 - 1126

Published: Feb. 26, 2025

Language: Английский

Citations

0