ALKBH5 modulation of ferroptosis in recurrent miscarriage: implications in cytotrophoblast dysfunction DOI Creative Commons
Chuanmei Qin, Jiayi Wu, Xiaowei Wei

et al.

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e18227 - e18227

Published: Oct. 18, 2024

Background As one of the most common and abundant internal modifications eukaryotic mRNA, N 6 -methyladenosine (m A) are closely related to placental development. Ferroptosis is a newly discovered form programmed cell death. During development, trophoblasts susceptible ferroptosis. However, interactions m A ferroptosis in trophoblast physiology injury unclear. Methods Recurrent miscarriage (RM) was selected as main gestational disease this study. Published data (GSE76862) were used analyze gene expression profiles patients with RM. The extent modification total RNA villous tissues between RM healthy controls (HC) compared. ALKBH5 (encoding AlkB homolog 5, demethylase) candidate for further research. Quantitative real-time reverse transcription PCR, western blotting, immunohistochemistry (IHC) confirmed elevated cytotrophoblasts Then, counting kit-8 assays, glutathione disulfide/glutathione quantification, 2′,7′-dichlorfluorescein-diacetate staining, malonaldehyde assays explore alterations ferroptosis-related characteristics following RAS-selective lethal (RSL3) stimulation after overexpression . Thereafter, we re-analyzed published sequencing upon knockdown , combined tissue RNA-seq data, FTL ferritin light chain) identified that regulated by ALKBH5. Finally, blotting IHC increased from Results Total levels decreased significant differentially A-related which In vitro experiments showed treatment RSL3 resulted death upregulated expression. Overexpression alleviated RSL3-induced HTR8 caused intracellular oxidation products. transcriptome revealed major Consistent ALKBH5, RSL3-induction Conclusion Elevated cytotrophoblast promoting Our results supported view an important regulator etiology suggested could be responsible epigenetic aberrations pathogenesis.

Language: Английский

Nature’s magic: how natural products work hand in hand with mitochondria to treat stroke DOI Creative Commons
Lin Cheng,

Shangbin Lv,

Wei Chen

et al.

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

Published: Jan. 7, 2025

Mitochondria, as the energy factories of cells, are involved in a wide range vital activities, including cell differentiation, signal transduction, cycle, and apoptosis, while also regulating growth. However, current pharmacological treatments for stroke challenged by issues such drug resistance side effects, necessitating exploration new therapeutic strategies. This review aims to summarize regulatory effects natural compounds targeting mitochondria on neuronal mitochondrial function metabolism, providing perspectives treatment. Numerous vitro vivo studies have shown that products berberine, ginsenosides, baicalein protect reduce stroke-induced damage through multiple mechanisms. These apoptosis modulating expression mitochondrial-associated apoptotic proteins. They inhibit activation permeability transition pore (mPTP), thereby decreasing ROS production cytochrome C release, which helps preserve function. Additionally, they regulate ferroptosis, fission, promote autophagy trafficking, further enhancing protection. As multi-target chemical agents, offer high efficacy with fewer present promising potential innovative therapies. Future research should investigate effectiveness safety these clinical applications, advancing their development strategy stroke.

Language: Английский

Citations

1
A Feedback Loop Driven by H4K12 Lactylation and HDAC3 in Macrophages Regulates Lactate‐Induced Collagen Synthesis in Fibroblasts Via the TGF‐β Signaling DOI Creative Commons
Ying Zou,

Mibu Cao,

Meiling Tai

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract The decrease in fibroblast collagen is a primary contributor to skin aging. Lactate can participate synthesis through lysine lactylation by regulating gene transcription. However, the precise mechanism which lactate influences requires further investigation. This study demonstrates that depletion of macrophages mitigates stimulating effect on fibroblasts. Through joint CUT&Tag and RNA‐sequencing analyses, feedback loop between H4K12 (H4K12la) histone deacetylase 3 (HDAC3) drives lactate‐induced are identified. Macrophages uptake extracellular via monocarboxylate transporter‐1 (MCT1), leading an up‐regulation H4K12la levels KAT5‐KAT8‐dependent response Poly‐L‐Lactic Acid (PLLA) stimulation, source low concentration persistent lactate, thereby promoting Furthermore, enriched at promoters TGF‐β1 TGF‐β3, enhancing their Hyperlactylation inhibits expression eraser HDAC3, while activation HDAC3 reduces suppresses In conclusion, this illustrates play critical role skin, targeting lactate‐H4K12la‐HDAC3‐TGF‐β axis may represent novel approach for production combat

Language: Английский

Citations

1
Lactate’s impact on immune cells in sepsis: unraveling the complex interplay DOI Creative Commons
Tao Zhang, Linjian Chen,

Gatkek Kueth

et al.

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

Published: Sept. 20, 2024

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate biomarker influence on dynamics, emphasizing critical modulating responses during sepsis. Mechanistically, key transporters like MCT1, MCT4, receptor GPR81 are crucial mediating these effects. HIF-1α also plays significant lactate-driven modulation. Additionally, affects through post-translational modifications such lactylation, acetylation, phosphorylation, which alter enzyme activities protein functions. These interactions between cells central to understanding sepsis-associated dysregulation, offering insights that can guide future research improve therapeutic strategies enhance patient outcomes.

Language: Английский

Citations

6
Utilizing integrated bioinformatics and machine learning approaches to elucidate biomarkers linking sepsis to purine metabolism-associated genes DOI Creative Commons
Feng Liang,

Man Zheng,

Junxia Lu

et al.

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

Published: Jan. 2, 2025

Language: Английский

Citations

0
TREM2 alleviates sepsis-induced acute lung injury by attenuating ferroptosis via the SHP1/STAT3 pathway DOI
Siyi Wu,

Yuanjie He,

Jiemei Li

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Investigation into the influence of mild hypothermia on regulating ferroptosis through the P53-SLC7A11/GPX4 signaling pathway in sepsis-induced acute lung injury DOI Creative Commons

Liujun Tao,

Jie Xu,

Liangyan Jiang

et al.

Intensive Care Medicine Experimental, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 15, 2025

Sepsis-induced acute lung injury (S-ALI) significantly contributes to unfavorable clinical outcomes. Emerging evidence suggests a novel role for ferroptosis in the pathophysiology of ALI, though precise mechanisms remain unclear. Mild hypothermia (32-34 °C) has been shown inhibit inflammatory responses, reduce oxidative stress, and regulate metabolic processes. P53 reported downregulate transcriptional activity solute carrier family 7 member 11 (SLC7A11), thereby limiting cystine uptake. This reduction availability compromises Glutathione peroxidase 4 (GPX4), cystine-dependent enzyme, ultimately increasing cellular susceptibility ferroptosis. However, it remains unclear whether mild exerts protective effects through P53-SLC7A11/GPX4 signaling pathway. study investigates influence on mediated by pathway S-ALI. utilized both vivo vitro models. In model, 64 Sprague-Dawley rats were employed, with 40 analyzed survival Sepsis was induced using cecum ligation puncture (CLP) method, after which subjected either normothermic (36-38 or hypothermic conditions duration 10 h. Twelve hours post-surgery, blood samples, bronchoalveolar lavage fluid, tissue samples harvested histological analysis, measurement markers, wet/dry ratios, gas assessment stress ferroptosis, Western blotting, RT-qPCR analysis. RLE-6TN cells exposed lipopolysaccharide (LPS) 24 h under conditions. These then evaluated cell viability, levels, as well blot analyses. CLP-induced sepsis led elevated levels increased scores, heightened markers. detrimental ameliorated hypothermia. Furthermore, reversed modified expression P53, SLC7A11, GPX4 molecules. Notably, also improved 5-day rate CLP rats. attenuates S-ALI modulates

Language: Английский

Citations

0
LncRNA FENDRR/ miR-424-5p serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes DOI Creative Commons

Xue Luo,

Xin Chen, Ying Gu

et al.

Immunobiology, Journal Year: 2025, Volume and Issue: 230(2), P. 152870 - 152870

Published: Jan. 18, 2025

Language: Английский

Citations

0
The Emerging Role of m6A and Programmed Cell Death in Cardiovascular Diseases DOI Creative Commons
Haixia Wang, Juanjuan Han, Hui Kong

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 247 - 247

Published: Feb. 8, 2025

N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, binding proteins. These regulate mRNA stability, splicing, nuclear export, translation, degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, plays crucial role maintaining cellular homeostasis, tissue development, function. Recently, m6A has emerged as significant research area due to regulating PCD implications cardiovascular diseases (CVDs). In this review, we delve into intricate relationship between various types modification, emphasizing their pivotal roles initiation progression of CVDs such myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), infarction (MI). Our findings underscore potential elucidating CVD pave new pathways for prevention treatment strategies.

Language: Английский

Citations

0
Biomimetic mineralized mesenchymal stem cell-derived exosomes for dual modulation of ferroptosis and lactic acid-driven inflammation in acute liver injury therapy DOI
Yiwei Tian, Jun Zhang,

Zengguang Jia

et al.

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Lactylation and regulated cell death DOI
Wenlong Zhang, Guangyao Shan, Guoshu Bi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: 1872(4), P. 119927 - 119927

Published: Feb. 28, 2025

Language: Английский

Citations

0