Inhibition of phospholipase D promotes neurological function recovery and reduces neuroinflammation after spinal cord injury in mice DOI Creative Commons

Han Ke,

Fan Bai, Zihan Li

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 20, 2024

Introduction Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation one the main pathophysiological features secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), critical lipid-signaling molecule, known to be involved various physiological processes, including regulation Despite this knowledge, specific PLD SCI remains unclear. Methods In study, we constructed mouse models and administered inhibitor (FIPI) treatment investigate efficacy PLD. Additionally, transcriptome sequencing protein microarray analysis spinal tissues were conducted further elucidate its mechanism action. Results The results showed that expression increased after inhibition significantly improved locomotor ability, reduced glial scarring, decreased damage mice SCI. Transcriptome altered gene inflammation regulation. Subsequently, revealed variations numerous inflammatory factors. Biosignature pointed association immunity, thus confirming obtained from sequencing. Discussion Collectively, these observations furnish compelling evidence supporting anti-inflammatory effect FIPI context while also offering insights into function which may potential therapeutic target for

Language: Английский

Targeting ferroptosis regulators by natural products in colorectal cancer DOI Creative Commons
Yiping Zhang, Jun Xie

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 27, 2024

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed and second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such delayed diagnosis, multidrug resistance, limited therapeutic effectiveness persist, emphasizing need for innovative approaches. This review explores potential natural products, nutraceuticals, phytochemicals targeting ferroptosis-related regulators novel strategy CRC. Ferroptosis, form regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance CRC progression therapy resistance. Natural known their diverse bioactive effects favorable safety profiles, emerge promising candidates to induce ferroptosis cells. Exploring amino acid, iron, metabolism regulators, oxidative stress reveals avenues inducing comprehensive provides insights into multifaceted products on proteins integral regulation, including GPX4, SLC7A11, ACSL4, NCOA4, HO-1. By elucidating intricate mechanisms through which modulate these proteins, this lays foundation

Language: Английский

Citations

7
Brosimine B and the biphasic dose-response: insights into hormesis and retinal neuroprotection DOI Creative Commons
Susanne Suely Santos da Fonseca, Natacha Medeiros de Souza Port’s, Gisele Priscila Soares de Aguiar

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

The biphasic dose-response behavior, also known as hormesis, is a characteristic feature of numerous natural products. It defined by beneficial effects at low concentrations and toxicity higher doses. This study investigates the hormetic Brosimine B, flavonoid derived from Brosimum acutifolium, on retinal cell viability under oxidative stress. To simulate ischemic conditions, we used an oxygen-glucose deprivation (OGD) model. Retinal cells were treated with varying analyses viability, reactive oxygen species (ROS) production, antioxidant enzyme activity performed. B 10 µM significantly enhanced reduced ROS likely through modulation stress-protective enzymes such catalase. However, (>10 µM) induced cytotoxic effects. A computational modeling approach using (inverted U-shaped) model revealed biologically interpretable parameters, including peak response 10.2 zone width (σ = 6.5 (R2 0.984). These results confirm that exhibits neuroprotective within well-defined concentration window, supporting its potential therapeutic agent for stress-related damage. highlights value in optimizing analyses, offering framework refining product therapies predicting toxicological thresholds pharmacological applications.

Language: Английский

Citations

0
Integrating untargeted and pseudotargeted metabolomics and network analysis reveals the interventional effects of red yeast rice on rat serum metabolites DOI

Ge Xun,

Yingxuan Li,

Yifan Zhang

et al.

Food Bioscience, Journal Year: 2024, Volume and Issue: 59, P. 104051 - 104051

Published: April 8, 2024

Language: Английский

Citations

3
KRAS depletion suppresses ferroptosis and affects Hippo pathway in cataract DOI Open Access

Hongda Jiang,

Yinggui Yu, Yu Yan

et al.

General Physiology and Biophysics, Journal Year: 2024, Volume and Issue: 43(03), P. 243 - 253

Published: Jan. 1, 2024

Cataract, a painless and progressive disorder is manifested as the opacification of lens that represents most significant cause blindness worldwide. The objective this study to unveil function Kirsten rat sarcoma (KRAS) potential action mechanisms against cataract. ferroptosis-associated differentially expressed genes (DEGs) pivot were extracted through comprehensive bioinformatics methods. Erastin was applied for inducing ferroptosis in hydrogen peroxide (H2O2)-treated SRA01/04 cells, validated by detecting content intracellular iron, glutathione (GSH), malondialdehyde (MDA). Additionally, effects KRAS deficiency on determined functional assays. proteins expression related Hippo pathway Western blotting. A total 73 ferroptosis-related DEGs discovered, 6 critical core confirmed upregulation cataract cell model. H2O2-treated cells exhibited decrease viability proliferation, iron accumulation, MDA increase, GSH consumption, rise COX2 decline GPX4, with further aggravated under erastin treatment, while phenomena improved knockdown. involved signalling activation. Downregulation might restrain affect

Language: Английский

Citations

2
Inhibition of phospholipase D promotes neurological function recovery and reduces neuroinflammation after spinal cord injury in mice DOI Creative Commons

Han Ke,

Fan Bai, Zihan Li

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 20, 2024

Introduction Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation one the main pathophysiological features secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), critical lipid-signaling molecule, known to be involved various physiological processes, including regulation Despite this knowledge, specific PLD SCI remains unclear. Methods In study, we constructed mouse models and administered inhibitor (FIPI) treatment investigate efficacy PLD. Additionally, transcriptome sequencing protein microarray analysis spinal tissues were conducted further elucidate its mechanism action. Results The results showed that expression increased after inhibition significantly improved locomotor ability, reduced glial scarring, decreased damage mice SCI. Transcriptome altered gene inflammation regulation. Subsequently, revealed variations numerous inflammatory factors. Biosignature pointed association immunity, thus confirming obtained from sequencing. Discussion Collectively, these observations furnish compelling evidence supporting anti-inflammatory effect FIPI context while also offering insights into function which may potential therapeutic target for

Language: Английский

Citations

1