E3 Ubiquitin Ligase CHIP Inhibits Haemocyte Proliferation and Differentiation via the Ubiquitination of Runx in the Pacific Oyster DOI Creative Commons

Miren Dong,

Ying Song, Weilin Wang

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1535 - 1535

Published: Sept. 13, 2024

Mollusca first evolve primitive immune cells (namely, haemocytes), which assemble a notable complex innate system, are continuously produced through proliferation and differentiation infused in the haemolymph. As typical E3 ligase, CHIP is critical for cell turnover homeostasis vertebrates. In this study, homolog (

Language: Английский

The Syvn1 inhibits neuronal cell ferroptosis by activating Stat3/Gpx4 axis in rat with spinal cord injury DOI Creative Commons
Shining Xiao, Yu Zhang, Shijiang Wang

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(10)

Published: May 27, 2024

Abstract Spinal cord injury (SCI) leads to secondary neuronal death, which severely impedes recovery of motor function. Therefore, prevention cell death after SCI is an important strategy. Ferroptosis, a new form discovered in recent years, has been shown be involved the regulation SCI. However, role and potential mechanisms ferroptosis are not fully understood. In this study, we report that E3 ubiquitin ligase Syvn1 suppresses promotes functional from vitro vivo. Mechanistically, screened with bioinformatics, immunoprecipitation, mass spectrometry, identified Stat3, transcription factor induces expression inhibitor Gpx4, as substrate Syvn1. Furthermore, neurons primary cellular source signalling. Moreover, determined binding domains Stat3 HEK 293 T cells using full‐length proteins series truncated Flag‐tagged Myc‐tagged fragments. created animal models silencing or overexpression found inhibits by stabilizing subsequently activates regulator Gpx4 summary, Syvn1‐mediated Stat3/Gpx4 signalling axis attenuates ferroptosis, reduces repair. our findings provide targets intervention strategies for treatment

Language: Английский

Citations

9

The Dual Roles of STAT3 in Ferroptosis: Mechanism, Regulation and Therapeutic Potential DOI Creative Commons

Jinghui Xie,

Dan Luo, Pengfei Xing

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4251 - 4266

Published: March 1, 2025

Ferroptosis, an iron-dependent programmed mechanism of cell death that is driven by lipid peroxidation, important pathogenic factor in oncological and non-oncological disorders. Dysregulation iron metabolism profoundly influences disease progression through ferroptosis modulation. Signal transducer activator transcription 3 (STAT3), a transcriptional regulator, regulates binding to promoters key molecules such as solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1). In this review, we described the role STAT3 supporting tumors survival suppressing malignancies, bidirectionally regulating non-tumors regulate development disease. We also reported emerging therapeutic strategies target STAT3-mediated ferroptosis, including natural phytochemicals, inhibitors, nanotechnology-enabled drug delivery systems. These advancements deepen mechanistic understanding regulation, provide new theoretical bases treat ferroptosis-related diseases.

Language: Английский

Citations

1

E3 ubiquitin ligase SYVN1 as a promising therapeutic target for diverse human diseases DOI Creative Commons
Li Zhu, Yongping Liu,

YuanWang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107603 - 107603

Published: Jan. 1, 2025

Numerous studies conducted in recent years indicate that mammalian E3 ubiquitin ligases serve as key regulators the maintenance of cellular homeostasis by targeting ubiquitination substrate proteins and activating downstream signaling pathways. SYVN1, an ligase, is characterized its significant functions regulating various biological processes, including molecular mechanisms related to gene expression, pathways, cell death, among others. Consequently, SYVN1 plays a crucial role both normal human physiology pathogenesis diseases, such oncogenesis, cardiovascular disorders, immune regulation, skeletal anomalies, neurological diseases. This review synthesizes findings regarding physiological pathophysiological roles offering new insights into potential strategies for prevention treatment well suggesting avenues future drug development. In this Review, we summarize latest elucidating which can regulate progression diseases humans. These important provide further investigation protein, prevent treat directions

Language: Английский

Citations

0

Puerarin Modulates the P62-Keap1-NRF2 Pathway and Enhances CA7 Function to Inhibit Ferroptosis in Ethanol-Induced Gastric Mucosal Injury DOI

Xin-Ran Liu,

Jiayi Ge,

Ximing J. Yang

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106127 - 106127

Published: Feb. 1, 2025

Language: Английский

Citations

0

JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases DOI Creative Commons

Yimeng Dai,

Chunguo Cui,

Dan Jiao

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 7, 2025

Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation JAK/STAT pathway implicated promoting or inhibiting ferroptosis, depending on context. JAK2 promotes activating STAT proteins, modulating expression key regulators like SLC7A11 GPX4, influencing iron homeostasis through pathways such as ferritinophagy hepcidin regulation. STAT1 activation primarily enhances suppression cystine-glutamate antiporter (System Xc-), leading to glutathione depletion contributing conditions Sjogren's syndrome age-related macular degeneration. In contrast, STAT3 plays protective upregulating which inhibits survival, particularly cancers hepatocellular carcinoma, prostate renal carcinoma. also discusses STAT6's involvement diseases asthma lung injury regulating antioxidant defenses. Furthermore, review explores potential therapeutic strategies targeting manipulate for disease treatment. cancer therapy, this can enhance effectiveness inducers, offering promising avenues overcome drug resistance. Additionally, interplay immune responses, oxidative stress, metabolism underscores significance progression intervention. By exploring these mechanisms, provides insights into development novel treatments modulation, with implications inflammatory neurodegenerative conditions.

Language: Английский

Citations

0

Long-Term Regulation of IL-17 Expression in Pacific Oyster Hemocytes by mGluR5 Through the Phosphoinositide Pathway DOI Creative Commons

Yiran Si,

Deliang Li, Wenjing Ren

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 438 - 438

Published: March 14, 2025

Metabotropic glutamate receptor 5 (mGluR5) is a critical regulator of immune responses within the neuroimmune system, influencing cytokine secretion and cell function. Although extensively studied in mammals, its role regulating IL-17 invertebrate immunity poorly understood. This study examines CgmGluR5 expression downstream signaling activation Pacific oyster (Crassostrea gigas) hemocytes following (Glu) Vibrio splendidus treatment. Glu treatment significantly induced key molecules, including PLC, DAG, IP3, Ca²⁺, PKC, while enhancing mRNA levels CgIL17-1, CgIL17-5, CgCaspase3. Elevated Ca²⁺ content CgIL17 were observed at 12 h post-Glu exposure, indicating CgmGluR5-mediated regulation through phosphoinositide pathway. A 1.14-fold increase apoptosis rate was found group compared to control group. Knockdown suppressed CgIL17-1 CgIL17-5 reduced granulocyte proportions, reflecting regulation. shows that mediates long-term oysters pathway, providing new theoretical insights for aquaculture management.

Language: Английский

Citations

0

Exploring the therapeutic mechanism of curcumin in spinal cord injury treatment based on network pharmacology, molecular dynamics simulation, and experimental validation DOI Creative Commons
Yongzhi He, Hongjun Zhao, Yang Luo

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: March 28, 2025

Curcumin, a natural active compound derived from plants, is widely used as pigment across the globe. Research has demonstrated that curcumin possesses neuroprotective properties in spinal cord injuries (SCIs); however, its specific mechanisms of action remain unclear. This study aimed to elucidate potential underlying curcumin's therapeutic effects SCI. We screened targets treatment injury using network pharmacology variety public databases. The interaction between and target was analyzed through bioinformatics analysis, molecular docking, dynamics simulation. Finally, prediction results were verified by simulating oxygen-glucose deprivation (OGD) PC12 cells. Initial screening indicated 13 core involved mitigating Curcumin may regulate HIF pathway, immune cells, inflammation, oxidative stress, other processes. Matrix metalloproteinase-9 (MMP9), tumor necrosis factor (TNF), interleukin-1β (IL-1β), signal transducer activator transcription 3 (STAT3), caspase (CASP3) identified key SCI regulation. Molecular docking exhibited favorable affinity with targets, MMP9 showing highest binding (-8.76 kcal/mol). Further studies confirmed stably binds MMP9, site located at residues 220-225. Cell counting kit-8 (CCK8) assay showed exerted good effect. Western blot inhibited expression protein but had no significant effect on TNF-α. exerts multiple pathways. Its involve inhibition prevention apoptosis ferroptosis, promotion neuronal repair. be mediating protective against These findings provide scientific evidence for further research development drugs.

Language: Английский

Citations

0

Differential changes in the microglial transcriptome between neonatal and adult mice after spinal cord injury DOI Creative Commons
Qi Jiang,

Shu-fang Xue,

Xiaojing Pan

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 21, 2025

Language: Английский

Citations

0

E3 Ubiquitin Ligase CHIP Inhibits Haemocyte Proliferation and Differentiation via the Ubiquitination of Runx in the Pacific Oyster DOI Creative Commons

Miren Dong,

Ying Song, Weilin Wang

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1535 - 1535

Published: Sept. 13, 2024

Mollusca first evolve primitive immune cells (namely, haemocytes), which assemble a notable complex innate system, are continuously produced through proliferation and differentiation infused in the haemolymph. As typical E3 ligase, CHIP is critical for cell turnover homeostasis vertebrates. In this study, homolog (

Language: Английский

Citations

1