KRAS depletion suppresses ferroptosis and affects Hippo pathway in cataract

General Physiology and Biophysics, Год журнала: 2024, Номер 43(03), С. 243 - 253

Опубликована: Янв. 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

Язык: Английский

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A highly selective inhibitor of discoidin domain receptor‐1 (DDR1‐IN‐1) protects corneal epithelial cells from YAP/ACSL4‐mediated ferroptosis in dry eye

British Journal of Pharmacology, Год журнала: 2024, Номер 181(21), С. 4245 - 4261

Опубликована: Июль 8, 2024

This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed potential specific DDR inhibitors as a therapeutic strategy for by exploring underlying mechanism.

Язык: Английский

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Resveratrol Protects Müller Cells Against Ferroptosis in the Early Stage of Diabetic Retinopathy by Regulating the Nrf2/GPx4/PTGS2 Pathway

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Язык: Английский

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Association of autoimmune and allergic diseases with senile cataract: a bidirectional two-sample Mendelian randomization study

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 22, 2024

Background Many observational studies have been reported that patients with autoimmune or allergic diseases seem to a higher risk of developing senile cataract, but the views are not consistent. In order minimize influence reverse causality and potential confounding factors, we performed Mendelian Randomization (MR) analysis investigate genetic causal associations between autoimmune, cataract. Methods Single nucleotide polymorphisms associated ten common were obtained from IEU Open genome-wide association (GWAS) database. Summary-level GWAS statistics for clinically diagnosed cataract FinnGen research project GWAS, which consisted 59,522 individuals cataracts 312,864 control individuals. MR was conducted using mainly inverse variance weighted (IVW) method further sensitivity test robustness. Results As diseases, IVW results confirmed type 1 diabetes (OR = 1.06; 95% CI 1.05-1.08; p 2.24×10 -12 ), rheumatoid arthritis 1.05; 1.02-1.08; 1.83×10 -4 hypothyroidism 2.4; 1.42-4.06; 1.12×10 -3 systemic lupus erythematosus 1.02; 1.01-1.03; 2.27×10 asthma 1.2×10 ) rhinitis 1.07; 1.02-1.11; 2.15×10 correlated Celiac disease 1.04; 1.01-1.08; P 0.0437) atopic dermatitis 1.01-1.10; 0.0426) exhibited suggestive connection after Bonferroni correction. These consistent across median Egger methods, similar estimates in direction magnitude. Sensitivity proved these reliable. Conclusions The showed there relationships diabetes, arthritis, hypothyroidism, erythematosus, asthma, To clarify possible role allergy pathophysiology needed.

Язык: Английский

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Machine learning model for age-related macular degeneration based on heavy metals: The National Health and Nutrition Examination Survey 2005 to 2008

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 6, 2024

Age-related macular degeneration (AMD) is the leading cause of blindness in older people developed countries. It has been suggested that heavy metal exposure may be associated with development AMD, but most studies have focused on effects a single traditional methods. In this study, we analyzed relationship between 13 urinary concentrations and AMD using NHANES data 2005 2008. We constructed compared 11 machine learning models to identify best model for predicting risk. further interpreted by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, SHapley Additive exPlanations (SHAP) analysis. 216 patients out 2380 participants. The random forest (RF) performed optimally risk an AUC value 0.970. PFI analyses revealed age cadmium (Cd) were main factors influencing AMD. SHAP confirmed significance Cd concentration significant interaction race. Our study firstly explored levels based techniques, found had greatest impact superior predictive performance Furthermore, our provided new perspective early screening intervention

Язык: Английский

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Low levels of peroxiredoxins are associated with high iron content and lipid peroxidation in seminal plasma from asthenozoospermic infertile men

Endocrine and Metabolic Science, Год журнала: 2023, Номер 12, С. 100137 - 100137

Опубликована: Июнь 27, 2023

Asthenospermia is a common cause of male infertility refers to semen samples with spermatozoa that move slowly or immotile. Recent research has implicated oxidative stress-induced ferroptosis in asthenospermia's pathophysiology. Peroxiredoxins are important players the antioxidant defense protect cells against stress. However, some aspects response necessary for fertility not well understood. This case-control study aimed elucidate role peroxiredoxins regulating stress via their correlation ferroptosis. It included 90 fertile and asthenospermic subfertile males from Hilla City, Iraq. Total peroxiredoxin activity, peroxiredoxin-6 level, peroxiredoxin-4 level were measured alongside biomarkers glutathione peroxidase-4, malondialdehyde, reduced/oxidized protein thiol ratio. Infertile had significantly higher oxidized malondialdehyde levels than (p < 0.05). activities, levels, peroxidase-4 ratios lower infertile Therefore, activity correlate They inversely associated directly quality. These findings suggest crucial preventing have potential implications treating asthenospermia.

Язык: Английский

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Blue light induced ferroptosis in retinal damage via iron overload-associated oxidative stress

Journal of Environmental Sciences, Год журнала: 2024, Номер unknown

Опубликована: Апрель 1, 2024

Язык: Английский

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Identification and Verification of Ferroptosis-Related Genes in Keratoconus Using Bioinformatics Analysis

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 2383 - 2397

Опубликована: Апрель 1, 2024

Objective: Keratoconus is a commonly progressive and blinding corneal disorder.Iron metabolism oxidative stress play crucial roles in both keratoconus ferroptosis.However, the association between ferroptosis currently unclear.This study aimed to analyze verify role of ferroptosis-related genes (FRGs) pathogenesis through bioinformatics.Methods: We first obtained keratoconus-related datasets FRGs.Then, differentially expressed FRGs (DE-FRGs) associated with were screened analysis, followed by analysis their biological functions.Subsequently, LASSO SVM-RFE algorithms used screen for diagnostic biomarkers.GSEA was performed explore potential functions marker genes.Finally, associations these biomarkers immune cells analyzed.qRT-PCR detect expression tissues.Results: A total 39 DE-FRGs screened, functional enrichment revealed that closely related apoptosis, stress, response.Then, using multiple algorithms, 6 selected, ROC curve risk prediction ability.In addition, based on CIBERSORT alterations microenvironment patients might be H19, GCH1, CHAC1, CDKN1A.Finally, qRT-PCR confirmed H19 CHAC1 elevated group. Conclusion:This identified DE-FRGs, 4 which infiltrating cells, established model predictive value keratoconus.

Язык: Английский

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Cell loss in retinal ischemia is associated with increased necroptosis

Deleted Journal, Год журнала: 2024, Номер 121(8), С. 644 - 649

Опубликована: Июнь 26, 2024

Zusammenfassung Hintergrund Retinale Ischämie spielt bei zahlreichen Augenerkrankungen wie beispielsweise dem Glaukom eine zentrale pathophysiologische Rolle. Neben der Apoptose zählen Autophagie, Nekroptose und Ferroptose zu den Zelltodmechanismen, die nachgeschaltet sind. Ihre Rolle ist jedoch nicht eindeutig geklärt wird kontrovers diskutiert. Ziel Arbeit dieser Studie es, ein verbessertes Verständnis über alternativer Zelltodmechanismen Autophagie im Tiermodell Ischämie-Reperfusion erhalten. Diese Erkenntnisse könnten als Basis für einen autophagie- oder nekroptosebasierten Therapieansatz dienen. Material Methoden Die retinale wurde 6 bis 8 Wochen alten Ratten in einem Auge durch das vorrübergehende Erhöhen des Augeninnendrucks auf 140 mm Hg induziert (60 min), gefolgt von Reperfusion. Das unbehandelte kontralaterale diente Kontrolle. Retinae wurden 7 Tage nach immunhistochemisch mit Markern Ganglienzellen (RGZ), Makroglia (GFAP) sowie Autophagiemarker (LAMP1) Nekroptosemarker (RIPK3) untersucht ( n = 6/Gruppe). Ergebnisse führte Tagen sowohl signifikanten RGZ-Verlust p ≤ 0,001) auch einer Zunahme Astrozytenfläche 0,026). Interessanterweise war Anzahl autophagischer LAMP1-positiver Zellen unverändert 0,272), wohingegen nekroptotischer RIPK3-positiver signifikant erhöht vorlag 0,001). Diskussion Sieben scheinen nekroptotische Prozesse aktiviert sein so zum retinalen Zelltod zur Aktivierung Astrozyten beizutragen. Späte autophagische sind aktiviert. Nekroptose-assoziierte Parameter daher frühzeitiger therapeutischer Ansatz Betracht gezogen werden.

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Targeting ferroptosis: a novel therapeutic strategy for the treatment of retinal diseases

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 30, 2024

Ferroptosis plays a vital role in the progression of various retinal diseases. The analysis mechanism cell ferroptosis has brought new targeted strategies for treating vascular diseases, degeneration and nerve is also major scientific issue field ferroptosis. In this review, we summarized results from currently available

Язык: Английский

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