FSP1: a key regulator of ferroptosis

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764

Published: June 24, 2023

Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between

Language: Английский

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New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 30, 2024

Abstract Background Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes death in patients with sepsis. SCM’s pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, specific mechanisms their intricate interactions SCM remain unclear. This study employed bioinformatics analysis drug discovery approaches to identify regulatory molecules, distinct functions, underlying metabolism microenvironment, along potential interventional strategies SCM. Methods GSE79962, GSE171546, GSE167363 datasets were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) module identified using Limma Weighted Correlation Network Analysis (WGCNA), followed functional enrichment analysis. Machine learning algorithms, including support vector machine–recursive feature elimination (SVM–RFE), least absolute shrinkage selection operator (LASSO) regression, random forest, used screen mitochondria-related hub for early diagnosis Subsequently, nomogram was developed based on six genes. The immunological landscape evaluated single-sample gene set (ssGSEA). We also explored expression pattern distribution mitochondria/inflammation-related pathways UMAP plots single-cell dataset. Potential drugs Drug Signatures Database (DSigDB). In vivo vitro experiments performed validate pathogenetic mechanism therapeutic efficacy candidate drugs. Results Six DEGs [MitoDEGs; translocase inner membrane domain-containing 1 (TIMMDC1), ribosomal protein S31 (MRPS31), F-box only 7 (FBXO7), phosphatidylglycerophosphate synthase (PGS1), LYR motif containing (LYRM7), chaperone BCS1 (BCS1L)] identified. diagnostic model demonstrated high reliability validity both training validation sets. microenvironment differed between control groups. Spearman correlation revealed that MitoDEGs significantly associated cells. Upregulated showed remarkably naive/memory B cell, CD14 + monocyte, plasma cell subgroup, evidenced plot. varied across subgroups individuals. Metformin predicted be most promising highest combined score. Its restoring function suppressing inflammatory responses been validated. Conclusions presents comprehensive SCM, providing novel direction medical intervention

Language: Английский

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Melanin Nanoparticle-Modified Probiotics for Targeted Synergistic Therapy of Ulcerative Colitis

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(25), P. 31950 - 31965

Published: June 11, 2024

Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal and damaged barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, microecological imbalance. Oral probiotics living therapy for diseases, but their clinical application hindered poor bacterial biological activity insufficient retention. Here, we developed targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core modified melanin nanoparticles (MNPs) on its surface through click reaction of tricarboxyphenylboronic acid synergistic UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, inhibited apoptosis also significantly enhanced viability Lf in simulated gastrointestinal fluid. Fluorescence imaging vivo revealed high accumulation at site dextran sulfate sodium-induced UC mice. Moreover, results demonstrated effectively alleviated oxidative stress inflammatory response restored barrier. addition, 16S rRNA gene sequencing verified could increase abundance diversity microbial communities optimize composition to inhibit progression This work combines effective antioxidant anti-inflammatory strategies administration provide promising alternative treatment.

Language: Английский

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Astragaloside IV alleviates septic myocardial injury through DUSP1-Prohibitin 2 mediated mitochondrial quality control and ER-autophagy

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis. This study highlights the potential Astragaloside IV(AS) treatment septic and provides reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction. Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2CKO) /DUSP1 transgenic (DUSP1/PHB2TG) were used to generate LPS-induced sepsis models. The pathological mechanism by which AS-IV improves heart was detected using cardiac ultrasound, fluorescence staining, transmission electron microscopy, western blotting. After siRNA cardiomyocytes DUSP-1/PHB2, changes mitochondrial function morphology determined qPCR, blotting, ELISA, laser confocal targeted therapeutic effects further examined. SCM leads dysfunction. However, IV (AS) normalizes homeostasis ER function. Notably, protective effect blocked DUSP1/Prohibitin but remained unaffected DUSP1 (DUSP1/PHB2TG). AS DUSP1-PHB2 related

Language: Английский

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miRNA-541-5p regulates myocardial ischemia–reperfusion injury by targeting ferroptosis

Journal of Cardiothoracic Surgery, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 15, 2025

This article aims to use high-throughput sequencing identify miRNAs associated with ferroptosis in myocardial ischemia–reperfusion injury, select a target miRNA, and investigate its role H9C2 cells hypoxia-reoxygenation injury. SD rats were used as subjects. ELISA kits quantified MDA, SOD, GSH, LDH, ferritin levels. TTC staining evaluated infarction size. HE observed histopathological changes. DCFH-DA fluorescent probe detected ROS. CCK-8 kit measured cell viability. HiSeq 2000 performed differential expression analysis of miRNAs. qRT-PCR Western blots assessed the levels GPX-4, ACSL-4, HO-1, TFR-1 TFR-2. SPSS 21.0 software conducted statistical analysis. Myocardial injury resulted decreased SOD increased LDH up-regulation ferritin, TFR-2, down-regulation tissue damage, accumulation However, DFO treatment reversed these Subsequently, gene miRNA-541-5p was obtained by miRNA screening, further validation revealed that tissues I/R model group compared those NC group, P < 0.05. constructing lines overexpression inhibition, inversely correlated survival after led decrease an increase wb qRT-PCT demonstrated high up-regulated protein/mRNA TFR-1, but down-regulated GPX-4. In addition, ADAM 7, FNIP 2, HOXD 10, HCCS STK 3 preliminarily identified potential candidate genes for bioinformatics Among them, ADAM7 emerges most suitable based on selection criteria. summary, may be biomarker damage diseases can regulate oxidative stress iron death inhibiting miRNA-541-5p, thereby reducing mechanisms

Language: Английский

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Keap It in the Family: How to Fish out New Paradigms in Keap1‐Mediated Cell Signaling

Helvetica Chimica Acta, Journal Year: 2023, Volume and Issue: 106(12)

Published: Nov. 13, 2023

Abstract Keap1 is associated with cytoprotective signaling. These roles of typically focus on its role as a degrader the antioxidant response (AR) transcription factor, Nrf2, and inhibition this process upon labeling by electrophiles. However, work from several laboratories has reemphasized both important Nrf2 binding in negatively regulating AR, fact that electrophile modification dissociates Keap1. This model appears to be applicable other signaling modes regulated Here, we use recent data have derived using experiments zebrafish cultured cells discuss different models regulation.

Language: Английский

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Exploring STK3 in melanoma: a systematic review of signaling networks and therapeutic opportunities

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Nov. 22, 2024

Language: Английский

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MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway

Redox Report, Journal Year: 2024, Volume and Issue: 30(1)

Published: Dec. 31, 2024

Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role mechanism injury impairment remain unclear.

Language: Английский

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The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(4), P. 714 - 724

Published: Jan. 1, 2024

Sepsis-induced cardiomyopathy (SIC) represents a severe complication of systemic infection, characterized by significant cardiac dysfunction.This study examines the role DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Inverted Formin 2 (INF2) in pathogenesis SIC, focusing on their impact mitochondrial homeostasis dynamics.Our research demonstrates that silencing DNA-PKcs alleviates lipopolysaccharide (LPS)-induced cardiomyocyte death dysfunction.Using HL-1 cardiomyocytes treated with LPS, we observed knockdown notably reverses LPS-induced cytotoxicity, indicating protective against cellular damage.This effect is further substantiated reduction caspase-3 caspase-9 activation, key markers apoptosis, upon knockdown.Besides, our data reveal attenuates dysfunction, evidenced improved ATP production, enhanced activities respiratory complexes, preserved membrane potential.Moreover, deletion counteracts shifts towards fission, its regulatory influence dynamics.Conclusively, elucidates intricate interplay between INF2 modulation function dynamics during sepsis-induced cardiomyopathy.These findings offer new insights into molecular mechanisms underpinning SIC suggest potential therapeutic targets for mitigating dysfunction this critical condition.

Language: Английский

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Keap It in the Family: How to Fish Out New Paradigms in Keap1-Mediated Cell Signaling

Published: Oct. 2, 2023

Keap1 is associated with cytoprotective signaling. These roles of typically focus on its role as a degrader the antioxidant response (AR) transcription factor, Nrf2, and inhibition this process upon labeling by electrophiles. However, work from several laboratories has reemphasized both important Nrf2 binding in negatively regulating AR, fact that electrophile modification dissociates Keap1. This model appears to be applicable other signaling modes regulated Here we use recent data have derived using experiments zebrafish cultured cells discuss different models regulation.

Language: Английский

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