HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury DOI Creative Commons
Li Zhu, Qiang Zheng, Xiaodong Liu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Acute kidney injury (AKI) is a clinical syndrome associated with multitude of conditions. Although renal replacement therapy (RRT) remains the cornerstone treatment for advanced AKI, its implementation can potentially pose risks and may not be readily accessible across all healthcare settings regions. Elevated lactate levels are implicated in sepsis-induced AKI; however, it unclear whether increased directly induces AKI or elucidates underlying mechanisms. For human, measurement arterial blood gas performed using direct determination L-lactate through an electrode oxidation method by analyzer. mice, enzyme-linked immunosorbent assay (ELISA) kits were employed to quantify concentrations biomarkers cell supernatant. The mouse model was single intraperitoneal (i.p.) administration (30 mg/kg) low-dose LPS (2 24 h. Proteomic analysis conducted identify lactylated proteins tissues. Techniques such as, immunoprecipitation, western blotting immunofluorescence used evaluate HMGB1 lactylation, neutrophil extracellular traps (NETs)and assess related molecular signaling pathways. Our findings indicate that serves as independent predictor patients acute decompensated heart failure (ADHF). We observed co-administration lipopolysaccharide (LPS) resulted overproduction, which subsequently elevated serum creatinine (Cre) urea nitrogen (BUN). Furthermore, combined application shown provoke lactylation within Notably, pretreatment small interfering RNA (siRNA) effectively diminished lactate-mediated alleviated severity AKI. Additionally, accumulation found enhance expression NETs bloodstream, circulating positively correlating lactylation. Importantly, pre-administration inhibitors (glycyrrhizin) dehydrogenase A (LDH-A) (oxamate) reversed upregulation induced both polymorphonuclear neutrophils (PMNs) supernatant, thereby ameliorating accumulation. These illuminate role inducing mice activation HMGB1-NETs pathway.

Language: Английский

Molecular mechanisms and therapeutic target of NETosis in diseases DOI Creative Commons
Jiayu Huang, Weiqi Hong, Meihua Wan

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(3)

Published: Aug. 19, 2022

Abstract Evidence shows that neutrophils can protect the host against pathogens in multiple ways, including formation and release of neutrophil extracellular traps (NETs). NETs are web‐like structures composed fibers, DNA, histones, various granule proteins. capture kill pathogens, bacteria, viruses, fungi, protozoa. The process NET is called NETosis. According to whether they depend on nicotinamide adenine dinucleotide phosphate (NADPH), NETosis be divided into two categories: “suicidal” “vital” However, components, elastase, myeloperoxidase, cell‐free cause a proinflammatory response potentially severe diseases. Compelling evidence indicates link between pathogenesis number diseases, sepsis, systemic lupus erythematosus, rheumatoid arthritis, small‐vessel vasculitis, inflammatory bowel disease, cancer, COVID‐19, others. Therefore, targeting products critical for treating diseases linked with Researchers have discovered several inhibitors, such as toll‐like receptor inhibitors reactive oxygen species scavengers, prevent uncontrolled development. This review summarizes mechanism NETosis, receptors associated pathology NETosis‐induced NETosis‐targeted therapy.

Language: Английский

Citations

105
Neutrophil intrinsic and extrinsic regulation of NETosis in health and disease DOI
Valentina Poli, Ivan Zanoni

Trends in Microbiology, Journal Year: 2022, Volume and Issue: 31(3), P. 280 - 293

Published: Nov. 5, 2022

Language: Английский

Citations

95
Pathophysiology of systemic sclerosis (scleroderma) DOI Creative Commons
Ann-Helen Rosendahl, Katrin Schönborn, Thomas Krieg

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2022, Volume and Issue: 38(3), P. 187 - 195

Published: March 1, 2022

Systemic sclerosis (scleroderma) is an autoimmune-triggered chronic fibrosing disease that affects the skin and many other organs. Its pathophysiology complex involves early endothelial damage, inflammatory infiltrate a resulting fibrotic reaction. Based on predisposing genetic background, altered balance of acquired innate immune system leads to release cytokines chemokines as well autoantibodies, which induce activation fibroblasts with formation myofibroblasts deposition stiff rigid connective tissue. A curative treatment still not available but remarkable progress has been made in management organ complications. In addition, several breakthroughs have led new therapeutic concepts. these, compounds developed during last years, target these different pathways offer specific approaches.

Language: Английский

Citations

92
Neutrophils in COVID-19: Not Innocent Bystanders DOI Creative Commons
Ellen McKenna,

Richard Wubben,

Johana M. Isaza-Correa

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 1, 2022

Unusually for a viral infection, the immunological phenotype of severe COVID-19 is characterised by depleted lymphocyte and elevated neutrophil count, with neutrophil-to-lymphocyte ratio correlating disease severity. Neutrophils are most abundant immune cell in bloodstream comprise different subpopulations pleiotropic actions that vital host immunity. Unique vary their capacity to mount antimicrobial responses, including NETosis (the generation extracellular traps), degranulation de novo production cytokines chemokines. These processes play role antiviral immunity, but may also contribute local systemic tissue damage seen acute SARS-CoV-2 infection. complications such as thrombosis, respiratory distress syndrome multisystem inflammatory children. In this Progress review, we discuss anti-viral pathological roles neutrophils potential therapeutic strategies target neutrophil-mediated responses.

Language: Английский

Citations

88
Ferroptosis in health and disease DOI Creative Commons
Carsten Berndt, Hamed Alborzinia,

Vera Skafar Amen

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

Citations

79
Paraptosis: a unique cell death mode for targeting cancer DOI Creative Commons

Sweata Hanson,

Aiswarya Dharan,

P. V. Jinsha

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: June 15, 2023

Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems' development, health disease. Out of all, apoptosis one major PCDs was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire ability escape apoptotic death, thereby increasing their resistance towards current therapies. This issue has led need search for alternate forms programmed mechanisms. Paraptosis an alternative pathway characterized by vacuolation damage endoplasmic reticulum mitochondria. Many natural compounds metallic complexes have been reported induce paraptosis lines. Since morphological biochemical features are much different from other PCDs, it understand modulators governing it. In this review, we highlighted factors trigger specific mediating pathway. Recent findings include inducing anti-tumour T-cell immunity immunogenic responses against A significant played also scaled its importance knowing mechanism. study xenograft mice, zebrafish model, 3D cultures, novel paraptosis-based prognostic model low-grade glioma patients broad aspect potential involvement field therapy. co-occurrence modes with photodynamic therapy combinatorial treatments tumour microenvironment summarized here. Finally, growth, challenges, future perspectives research discussed review. Understanding unique PCD would help develop combat chemo-resistance various

Language: Английский

Citations

59
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death DOI Open Access

Lan-Lan Bu,

Huanhuan Yuan,

Lingli Xie

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15160 - 15160

Published: Oct. 13, 2023

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals metabolites in circulatory system. The senescence death ECs not only adverse outcomes, but also causal contributors endothelial dysfunction, an early risk marker atherosclerosis. pathophysiological process EC involves both structural functional changes has been linked various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, aberrant metabolite sensing signaling. Multiple forms have documented atherosclerosis, autophagic death, apoptosis, pyroptosis, NETosis, necroptosis, ferroptosis. Despite this, molecular mechanisms underlying or atherogenesis fully understood. To provide a comprehensive update on subject, this review examines historic latest findings alterations associated with different stages

Language: Английский

Citations

44
Different types of cell death in diabetic endothelial dysfunction DOI Open Access
Jieru Shen,

Wenqing San,

Yangyang Zheng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115802 - 115802

Published: Oct. 31, 2023

Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, resistance, glucose lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction key feature diabetic complications such as nephropathy, retinopathy, neuropathy, atherosclerosis. Importantly, death thought to be factor contributing injury. Morphologically, can divided into three forms: type I apoptosis, II autophagy, III necrosis. According the difference in function, accidental (ACD) regulated (RCD). RCD controlled process involving numerous proteins precise signaling cascades. Multiple subroutines covered may involved dysfunction, including necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic death, lysosome-dependent alkaliptosis, oxeiptosis, cuproptosis, PANoptosis. This article briefly reviews mechanism significance associated with which will help deepen understanding provide new therapeutic ideas.

Language: Английский

Citations

44
Neutrophil extracellular traps in homeostasis and disease DOI Creative Commons

Han Wang,

Susan J. Kim,

Lei Yu

et al.

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

Published: Sept. 20, 2024

Language: Английский

Citations

38
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

29