Extracellular Histones Exacerbate Heat Stroke-Induced Liver Injury by Triggering Hepatocyte Pyroptosis and Liver Injury Via the Tlr9-Nlrp3 Pathway DOI
Yue Li, Huan Li,

Youqing Tang

et al.

Published: Jan. 1, 2023

Background: Severe heat stroke is often complicated by multiple organ failure, including liver injury. Recent evidence indicates that the underlying mechanism constitutes sterile inflammation triggered cell damage, in which hepatocyte NOD-like receptor family pyrin domain-containing 3 inflammasome activation and pyroptosis play key roles. As extracellular histones act as damage-associated molecular patterns mediate tissue toxicity inflammation, we aimed to investigate whether contribute inducing following stroke, promoting development of injury, elucidate potential mechanisms. Methods: Exogenous were administered AML-12 murine hepatocytes or male aged 8~12 week mice hyperthermic treatment (at 39°C a chamber with 60% relative humidity). Prior exposure, endogenous neutralized using neutralizing antibodies, inflammasomes inhibited RNA silencing, Toll-like 9 was modulated pharmacological agonist antagonist. Inflammasome assembly, caspase-1 activation, histological changes, enzyme levels measured. Statistical comparison more than two groups performed one-way ANOVA Tukey’s post-hoc testing. The correlations analyzed Pearson’s correlation test. All experiments repeated thrice. A p-value < 0.05 considered significant. Results: Heat induced histone release into space at correlating Moreover, augmented stroke-induced injury both vitro vivo dose- time-dependent manner, whereas conferred protection stroke. Histones mediated through signaling pathway, resulted inflammation. Conclusions: Our findings show are critical mediators aggravate setting. Therefore, suggest therapeutic targets limit death

Language: Английский

Luteolin enhanced antioxidant capability and induced pyroptosis through NF-κB/NLRP3/Caspase-1 in splenic lymphocytes exposure to ammonia DOI
Dechun Chen, F Shen, Jiahao Liu

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 919, P. 170699 - 170699

Published: Feb. 5, 2024

Language: Английский

Citations

24
Isoliquiritigenin alleviates the development of alcoholic liver fibrosis by inhibiting ANXA2 DOI Open Access
Na Liu, Min Liu,

Mengwei Jiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114173 - 114173

Published: Jan. 20, 2023

The study aimed to investigate the effect of isoliquiritigenin (ISL) on model alcoholic liver fibrosis (ALF). C57BL/6 mice were used establish animal ALF, HSC-T6 cells alcohol-activated cell model, and tandem mass tag (TMT) assays analyze proteome. results showed that ISL obviously alleviated hepatic in mice. visually improved area pathological stasis deposition fibrillar collagen (Sirius Red staining, Masson staining), inhibited mRNA expression levels interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) 1β (IL-1β) tissues. down-regulated IL-6 transforming growth factor-β1(TGF-β1) activated stellate (HSCs). And significantly reduced annexin A2 (ANXA2) vitro detected by TMT proteomics technology. Interestingly, it was found for first time could inhibit ANXA2 both vivo vitro, block sphingosine kinases (SPHKs)/sphingosine-1-phosphate (S1P)/interleukin 17 (IL-17) signaling pathway regulate α-smooth muscle actin (α-SMA) inhibiting phosphorylation signal transducer activator transcription 3 (STAT3) at downstream finally reverse HSCs activation fibrosis. Thus, we demonstrated is a drug monomer with notable anti-hepatic activity.

Language: Английский

Citations

16
Maternal Exposure to Polystyrene Nanoplastics Induces Sex-Specific Cardiotoxicity in Offspring Mice DOI Creative Commons
Xiuli Chen,

Shenzhen Huang,

Li Wang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(20), P. e39139 - e39139

Published: Oct. 1, 2024

Globally, plastic pollution threatens human health, particularly affecting the hearts of offspring exposed to maternal environmental factors early in development. Few studies have specifically addressed sex-specific cardiac injury resulting from exposure polystyrene nanoplastics (PS-NPs). This study investigates potential following 1 mg/L PS-NPs. Pregnant C57BL/6J mice were PS-NPs until 3 weeks postpartum establish a model. Heart tissues collected and weighed, transcriptomes sequenced analyzed using high-throughput RNA sequencing. Immunohistochemical staining was performed assess effects on immune infiltration, fibrosis, apoptosis offspring. caused significant reduction heart body weight female compared males. Additionally, induced transcriptional reprogramming metabolic disruptions also apoptosis, increased CD68

Language: Английский

Citations

4
Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway DOI Creative Commons
Qi Liu,

Bin-Bin Dong,

Zhenyu Ding

et al.

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

Published: Jan. 8, 2025

In patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed unphysiological strain (UPLS) in dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane receptor, senses signals. The Src/STAT3 pathway plays crucial role the mechanotransduction network, concurrently triggering pyroptosis related inflammatory responses. We hypothesized that stretch caused by UPLS can be sensed PECAM-1 lungs, leading VILI via and pathway. A model was established rats through UPLS. link between as well change activation of PECAM-1, Src/STAT3, firstly being explored. Then, inhibitors Src, STAT3 were adopted respectively, effect on VILI, inflammation, pathway, evaluated. vitro, human umbilical vein cells (HUVECs) used validate findings vivo. activated signaling rats, whereas inhibition or decreased injury, responses, pyroptosis. Inhibition also reduced mechanism validated HUVECs exposed overload cyclic stretch. This study suggests contributes activating PECAM-1/Src/STAT3 inducing responses aspyroptosis.

Language: Английский

Citations

0
COMPARATIVE ANALYSIS OF THE TOTAL PROTEOME IN NONALCOHOLIC STEATOHEPATITIS: IDENTIFICATION OF POTENTIAL BIOMARKERS DOI Creative Commons
Eda Ates, Hien Thi My Ong, Seung-Min Yu

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100921 - 100921

Published: Jan. 1, 2025

Nonalcoholic fatty liver disease (NAFLD) is a hepatic condition characterized excessive fat accumulation in the with advanced stage nonalcoholic steatohepatitis (NASH), potentially leading to fibrosis, cirrhosis, and cancer. Currently, identification classification of NASH require invasive biopsy, which has certain limitations. Mass spectrometry-based proteomics can detect crucial proteins pathways implicated development progression. We collected serum samples from choline-deficient, L-amino acid-defined high-fat diet fed C57BL/6J mice human examine proteomic alterations identify early biomarkers for diagnosis. In-depth targeted multiple reaction monitoring (MRM) scanning immunoblotting assays were used verify biomarker candidates mouse samples, enzyme-linked immunosorbent assay (ELISA) was employed analyze samples. The MRM analysis revealed 50 altered expression (18 up- 32 downregulated) that are involved biological processes such as detoxification, inflammation, acid metabolism. Ingenuity pathway identified impaired protein synthesis, cellular stress defense, communication, metabolism liver. Immunoblotting confirmed associated (Aldo B Fasn) urea cycle (Arg1, Cps1, Otc) serum. Further on using ELISA increased proteins, including Aldo B, Asl, Lgals3, demonstrating values 0.917, 0.979, 0.965 area under curve These findings offer valuable insights into molecular mechanisms possible diagnostic detection.

Language: Английский

Citations

0
Single cell analysis reveals that SPP1+ macrophages enhance tumor progression by triggering fibroblast extracellular vesicles DOI
Haocheng Wang, Bowen Qiu, Xinyu Li

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 55, P. 102347 - 102347

Published: March 13, 2025

Language: Английский

Citations

0
Evaluation of the efficacy of cell-penetrating monoclonal antibodies targeting intracellular p-NLRP3S295 in alleviating hepatotoxicant-induced NAFLD DOI

Jia‐Shen Wu,

Yu-Qiao He,

Yuandan Wei

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142696 - 142696

Published: March 1, 2025

Language: Английский

Citations

0
Research Progress on the Regulatory Role of Different Cell Death Pathways in Metabolic-dysfunction-associated Steatotic Liver Disease DOI
Congyue Zhang,

Mengjiao Sun,

Yanbing Ding

et al.

Clinics and Research in Hepatology and Gastroenterology, Journal Year: 2025, Volume and Issue: 49(6), P. 102578 - 102578

Published: April 2, 2025

Language: Английский

Citations

0
Annexin A: Cell Death, Inflammation, and Translational Medicine DOI Creative Commons
Z. Qian,

Z Q Li,

Xuebin Peng

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 5655 - 5672

Published: April 1, 2025

The annexin superfamily proteins, a family of calcium-dependent phospholipid-binding are involved in variety Ca²+-regulated membrane events. Annexin A, expressed vertebrates, has been implicated regulated cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and neutrophil extracellular trap-induced (NETosis). Given that inflammation is key driver death, the roles A have extensively studied. In this review, we discuss regulatory RCD inflammation, development related targeted therapies translational medicine, application animal models to study these processes. We also analyze current challenges future directions for improved diagnostic therapeutic strategies.

Language: Английский

Citations

0
The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD) DOI Creative Commons
Shujing Li,

An-Bu Liu,

Yuanyuan Yu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 3, 2024

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within cells, which can progress to end-stage in severe cases, posing threat life. Pyroptosis distinct, pro-inflammatory form cell death, differing from traditional apoptosis. In recent years, there has been growing research interest association between pyroptosis and NAFLD, encompassing mechanisms functions progression as well potential therapeutic targets. Controlled activate immune eliciting host responses shield body harm. However, undue activation may worsen inflammatory responses, induce cellular or tissue damage, disrupt potentially impact function. This review elucidates involvement key molecular players, including NOD-like receptor thermal protein domain associated 3(NLRP3) inflammasome, gasdermin D (GSDMD), caspase family, pathogenesis NAFLD. It emphasizes promising prospects targeting approach for NAFLD offers valuable insights into future directions field treatment.

Language: Английский

Citations

3