Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis DOI Open Access

Wenya Bai,

Siying Huo,

Guilin Zhou

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115057 - 115057

Published: July 1, 2023

This study aimed to examine whether Biliverdin, which is a common metabolite of haem, can alleviate cerebral ischemia reperfusion injury (CIRI) by inhibiting pyroptosis. Here, CIRI was induced middle artery occlusion-reperfusion (MCAO/R) in C57BL/6 J mice and modelled oxygen glucose deprivation/reoxygenation (OGD/R) HT22 cells, it treated with or without Biliverdin. The spatiotemporal expression GSDMD-N infarction volumes were assessed immunofluorescence staining triphenyltetrazolium chloride (TTC), respectively. NLRP3/Caspase-1/GSDMD pathway, central the pyroptosis process, as well Nrf2, A20, eEF1A2 determined Western-blots. interactions verified using dual-luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation. Additionally, role Nrf2/A20/eEF1A2 axis modulating neuroprotective properties Biliverdin investigated A20 gene interference (overexpression and/or silencing). 40 mg/kg could significantly both vivo vitro, promoted activation elevated expression, but decreased expression. Nrf2 bind promoter thereby transcriptionally regulating A20. furthermore interacted through its ZnF4 domain ubiquitinate degrade it, leading downregulation eEF1A2. Our studies have also demonstrated that either knock-down over-expression blunted protective effect Rescue experiments further confirmed regulate NF-κB pathway via axis. In summary, our demonstrates ameliorates findings help identify novel therapeutic targets for treatment CIRI.

Language: Английский

Tetramethylpyrazine Confers Protection Against Oxidative Stress and NLRP3-Dependent Pyroptosis in Rats with Endometriosis DOI Creative Commons
Ke Xu, Mingzhe Zhang, Xiaofeng Zou

et al.

Organogenesis, Journal Year: 2025, Volume and Issue: 21(1)

Published: Feb. 18, 2025

Tetramethylpyrazine (TMP) has been confirmed to suppress inflammation in endometriosis (EMs). Herein, this study investigated whether and how TMP affected NLRP3 inflammasomes oxidative stress EMs. After establishment of an EMs rat model, rats were treated with different concentrations TMP. The size endometriotic lesions the latency frequency torsion recorded, followed by measurement relevant indicators (TNF-α, IL-6, IL-2, IL-10, MDA, SOD, GSH, CAT, ROS, NLRP3, ASC, GSDMD, caspase-1, Nrf2, HO-1). experimentally determined that treatment markedly decreased improved levels inflammatory proteins, markers, inflammasome, pyroptotic proteins elevated EMs, all which reversed upon treatment. Additionally, activities CAT lowered partly abrogated Furthermore, downregulation Nrf2 HO-1 was counteracted To sum up, represses excessive stress, inflammasome activation, pyroptosis may activate Nrf2/HO-1 pathway.

Language: Английский

Citations

1

Mitochondrial Dynamics and Metabolism in Macrophages for Cardiovascular Disease: a review DOI

Yi-lang Zhong,

Chenqin Xu,

Ji Li

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156620 - 156620

Published: March 7, 2025

Language: Английский

Citations

1

Pyroptosis in septic lung injury: Interactions with other types of cell death DOI Open Access
Yi Jiang,

Shenjia Gao,

Zhaoyuan Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115914 - 115914

Published: Nov. 24, 2023

Sepsis is a life-threatening systemic inflammatory response syndrome caused by the host imbalanced to infection. Lung injury most common complication of sepsis and one leading causes patient death. Pyroptosis specific programmed cell death characterized release cytokines. Appropriate pyroptosis can reduce tissue damage exert protective effect against infection during sepsis. However, overactivated results in massive death, septic shock, multiple organ dysfunction syndrome, even an increased risk secondary Recent studies suggest that interact with cross-regulate other types programs establish complex network which participates occurrence development lung injury. This review will focus on interactions between including apoptosis, necroptosis, PANoptosis, NETosis, autophagy, ferroptosis, summarize role sepsis-induced injury, discuss potential therapeutic strategies targeting treatment.

Language: Английский

Citations

18

Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota DOI Open Access
Jiaxi Chen,

Mengyue Pan,

Jingjie Wang

et al.

Toxicology and Applied Pharmacology, Journal Year: 2023, Volume and Issue: 467, P. 116494 - 116494

Published: March 29, 2023

Language: Английский

Citations

17

Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease DOI Creative Commons

Lingling Yuan,

Yingyi Wang, Na Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(8), P. 1012 - 1012

Published: Aug. 20, 2024

Oxidative stress (OS) is a key factor in the generation of various pathophysiological conditions. Nuclear erythroid 2 (NF-E2)-related (Nrf2) major transcriptional regulator antioxidant reactions. Heme oxygenase-1 (HO-1), gene regulated by Nrf2, one most critical cytoprotective molecules. In recent years, Nrf2/HO-1 has received widespread attention as regulatory pathway for intracellular defense against oxidative stress. It considered potential target treatment inflammatory bowel disease (IBD). This review highlights mechanism action and therapeutic significance IBD complications (intestinal fibrosis colorectal cancer (CRC)), well phytochemicals targeting IBD. The results suggest that effects on mainly involve following aspects: (1) Controlling to reduce intestinal inflammation injury; (2) Regulation flora repair mucosal barrier; (3) Prevention ferroptosis epithelial cells. However, due complex role Nrf2/HO-1, more nuanced understanding exact mechanisms involved way forward future.

Language: Английский

Citations

8

Melatonin alleviates septic ARDS by inhibiting NCOA4-mediated ferritinophagy in alveolar macrophages DOI Creative Commons
Wenting Xu,

Yutong Wu,

Sheng Wang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 24, 2024

Abstract Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play pivotal role the pathogenesis ARDS. Ferritinophagy process ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) releases large amounts iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects reduce However, it not clear whether MT’s protective effect related to inhibition ferritinophagy. Our vitro experiments demonstrated MT decreased intracellular malondialdehyde (MDA), Fe 2+ , lipid peroxidation levels, increased glutathione (GSH) levels proliferation, upregulated peroxidase (GPX4) heavy chain 1 (FTH1) protein LPS-treated macrophages. Mechanistically, antiferroptotic on macrophages was significantly compromised overexpression NCOA4. vivo alleviated expression NCOA4 FTH1 alveolar mice. Furthermore, improved mitigated damage tissue, ultimately increasing survival rates These findings indicate inhibit NCOA4-mediated ferritinophagy manner, thereby ameliorating

Language: Английский

Citations

7

Acute Lung Injury and the NLRP3 Inflammasome DOI Creative Commons

Wanjun Gu,

Qi Zeng,

Xin Wang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 3801 - 3813

Published: June 1, 2024

Abstract: Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading scattered interstitial alterations, pulmonary edema, subsequent acute hypoxic respiratory insufficiency. (ALI), along with its more serious counterpart, distress syndrome (ARDS), carry fatality rate that hovers around 30– 40%. Its principal pathological characteristic lies in unchecked inflammatory reaction. Currently, main strategies for treating ALI are alleviation inflammation prevention failure. Concerning etiology ALI, NLRP3 Inflammasome is essential body's innate immune response. The composition this inflammasome complex includes NLRP3, pyroptosis mediator ASC, pro-caspase-1. Recent research has reported response centered on inflammasomes plays key part may hence be prospective candidate therapeutic intervention. In review, we present an overview ailment characteristics constitution operation within framework. We also explore targeting combat injury. Keywords: injury, inflammasome, caspase-1, IL-1β, IL-18

Language: Английский

Citations

7

Kirenol inhibits inflammation challenged by lipopolysaccharide through the AMPK-mTOR-ULK1 autophagy pathway DOI Creative Commons
Juan Xiao, Xiaofang Shen,

Ruiming Kou

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 116, P. 109734 - 109734

Published: Jan. 25, 2023

Kirenol is a bioactive substance isolated from Herba Siegesbeckiae. Although the anti-inflammatory activity of kirenol has been well documented, its role in autophagy remains unknown. The present study aimed to investigate protective on inflammation challenged by lipopolysaccharide (LPS) acute lung injury (ALI) cell and mouse models unravel underlying mechanisms, with particular focus autophagy. For this purpose, an ALI were established, effects expression molecules related examined. results revealed that could significantly inhibit inflammatory cytokines secretion cells mice injured LPS; effect may be attributed enhanced as evidenced up-regulation LC3-II down-regulation p62 both vitro vivo. Phosphorylated AMPK ULK1 increased, while phosphorylated mTOR decreased kirenol-treated model. Moreover, inhibition using inhibitor or 3-MA chloroquine (CQ) reversed autophagy-enhancement exposure vitro, indicating enhance activating AMPK-mTOR-ULK1 pathway. RNA sequencing suggested was strongly biological functions response signaling Further vivo model studies demonstrated against inflammation, such improved histopathology, edema, leukocyte infiltration abolished 3-MA. These findings implicate can LPS-induced via

Language: Английский

Citations

15

Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases DOI Open Access

Yonghu Chen,

Yuqi Zhang, Ning Li

et al.

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(4), P. 829 - 846

Published: March 11, 2023

Language: Английский

Citations

13

Ficolin-A/2 Aggravates Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D–Induced Pyroptosis DOI

Li Huang,

Xiaowu Tan,

Weixia Xuan

et al.

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: 194(6), P. 989 - 1006

Published: March 3, 2024

Language: Английский

Citations

5