Targeting ferroptosis: opportunities and challenges of mesenchymal stem cell therapy for type 1 diabetes mellitus

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Abstract Type 1 diabetes mellitus (T1DM) is characterized by progressive β-cell death, leading to loss and insufficient insulin secretion. Mesenchymal stem cells (MSCs) transplantation currently one of the most promising methods for replacement therapy. However, recent studies have shown that ferroptosis not only key mechanisms but also reasons extensive cell death within a short period time after MSCs transplantation. Ferroptosis new type regulated (RCD) iron-dependent accumulation lipid peroxides. Due weak antioxidant capacity β-cells, they are susceptible cytotoxic stimuli such as oxidative stress (OS), therefore ferroptosis. Transplanted extremely perturbations in their microenvironment, especially OS, which can weaken induce through In pathophysiological process T1DM, large amount reactive oxygen species (ROS) produced, causing OS. Therefore, targeting may be way protect β-cells improve therapeutic effect This review reviews research related MSCs, summarizes developed strategies help inhibit study aims understand mechanism transplantation, emphasize importance protecting improving survival function transplanted provide direction therapy T1DM future.

Language: Английский

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MiR-370-3p regulate TLR4/SLC7A11/GPX4 to alleviate the progression of glucocorticoids-induced osteonecrosis of the femoral head by promoting osteogenesis and suppressing ferroptosis

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Melatonin and ferroptosis: Mechanisms and therapeutic implications

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 218, P. 115909 - 115909

Published: Nov. 4, 2023

Language: Английский

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Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 19, 2024

Abstract The unprecedented pandemic of COVID-19 swept millions lives in a short period, yet its menace continues among survivors the form post-COVID syndrome. An exponentially growing number suffer from cognitive impairment, with compelling evidence trajectory accelerated aging and neurodegeneration. novel enigmatic nature this yet-to-unfold pathology demands extensive research seeking answers for both molecular underpinnings potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is strongly proposed underlying mechanism post-COVID-19 neurodegeneration discourse. incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin (RAS) disruption, clock gene alteration. These events pave way ferroptosis, which shows signature COVID-19, premature aging, neurodegenerative disorders. In search treatment, melatonin shines as promising ferroptosis inhibitor repeatedly reported safety tolerability. According to various studies, has proven efficacy attenuating severity certain manifestations, validating reputation anti-viral compound. Melatonin well-documented anti-aging properties combating neurodegenerative-related pathologies. can block leading since it efficient anti-inflammatory, chelator, antioxidant, angiotensin II antagonist, regulator. Therefore, we propose culprit behind melatonin, well-fitting inhibitor, treatment.

Language: Английский

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GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 982, P. 176894 - 176894

Published: Aug. 13, 2024

Language: Английский

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HIF‐1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid‐induced osteonecrosis of the femoral head

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(5)

Published: March 13, 2024

With the prevalence of coronavirus disease 2019, administration glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety problems, which steroid-induced osteonecrosis femoral head (SONFH) is most concerning. Since hypoxia-inducible factor 1α (HIF-1α) key in cartilage development and homeostasis, it may play an important role SONFH. In this study, SONFH models were established using methylprednisolone (MPS) mouse its proliferating chondrocytes investigate HIF-1α differentiation, extracellular matrix (ECM) apoptosis glycolysis mice. The results showed that MPS successfully induced vivo vitro, MPS-treated demonstrated disturbed ECM significantly increased chondrocyte rate level. However, compared normal mice, not only expression genes related collagens glycolysis, but also did demonstrate significant differences mice co-treated inhibitor. And effects observed activator-treated similar those by MPS. degraded upregulating downstream target metalloproteinases. activator/inhibitor endoplasmic reticulum stress (ERS) pathway revealed high was ERS pathway, affected HIF-1α. Furthermore, glucose metabolism increasing glycolysis-related genes. conclusion, plays vital pathogenesis regulating apoptosis, glycolysis.

Language: Английский

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Exploring molecular disparities of H-type vasculature endothelial cells in osteonecrosis of the femoral head through single-cell analysis

BMC Musculoskeletal Disorders, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 6, 2025

Recent studies highlight the role of H-type vasculature in bone regeneration. This study, based on single-cell RNA sequencing (scRNA-seq), aims to explore changes endothelial cells (H_ECs) osteonecrosis femoral head (ONFH) and hip osteoarthritis (HOA), focusing death modes such as ferroptosis, pyroptosis, parthanatos. We re-analyzed scRNA-seq data samples publicly available 2022. study selected nine (3 each from HOA, ONFH stage 3 A, 4). CD31 + EMCN were classified H_ECs. Molecular differences assessed using Gene Ontology KEGG analysis. Hypoxia, parthanatos indices calculated, transcription factors predicted SENIC. Cell communication was analyzed with CellChat. After integrating 9 samples, 14 cell types identified: B cells, Mesenchymal stem Osteoblasts, Endothelial Monocytes, T NK Fibroblasts, Macrophages, Common myeloid progenitors, Chondrocytes, Myelocytes, Osteoclasts, Pericytes. The number H_ECs decreased necrosis severity. showed higher angiogenic capacity but lower stress resistance compared other cells. Angiogenic necrotic accompanied by an elevation inflammation levels. hypoxia index higher, ferroptosis increased A stages 4. No change observed pyroptosis. analysis revealed downregulation SLIT3-ROBO4 signaling during necrosis. show molecular Ferroptosis contribute demise ONFH, pericytes fibroblasts supporting H_EC angiogenesis.

Language: Английский

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Advances in Ferroptosis and Glucocorticoid-Induced Osteonecrosis of Femoral Head and Discussion of Related Ferroptosis Genes in Bone Metabolism or Oxidative Stress

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(01), P. 1717 - 1730

Published: Jan. 1, 2025

Language: Английский

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Melatonin affects trophoblast epithelial-to-mesenchymal transition and oxidative damage resistance by modulating GDF15 expression to promote embryo implantation

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 8, 2025

Melatonin is widely observed in the female reproductive system and regulates trophoblast cell functions, but its effects on embryo implantation underlying mechanisms are not well understood. By constructing an vitro culture model, we found that melatonin enhances migration human mouse cells. It also significantly promoted HTR-8/SVneo proliferation, inhibited apoptosis, enhanced migration, mitigated oxidative damage. Further investigation revealed increased rate of spheroids by promotes epithelial-mesenchymal transition (EMT) via growth differentiation factor 15 (GDF15)–mothers against decapentaplegic homolog 2/3 (SMAD2/3) pathway. Additionally, levels glutathione peroxidase 4 (GPX4) (GSH) cells upregulating expression GDF15, inhibiting reactive oxygen species (ROS) accumulation, increasing mitochondrial membrane potential, thus suppressing apoptosis during stress. In conclusion, EMT GDF15-SMAD2/3 pathway partially induces GPX4 through GDF15 to enhance damage resistance These findings highlight melatonin's regulatory role suggest new avenues for exploring biological reproduction clinical applications. GDF15-mediated activation SMAD2/3

Language: Английский

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Icariin promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by activating PI3K-AKT-UTX/EZH2 signaling in steroid-induced femoral head osteonecrosis

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

Published: March 18, 2025

Differentiation of bone marrow mesenchymal stem cells (BMSCs) is pivotal in the pathogenesis steroid-induced femoral head osteonecrosis. Icariin, an active ingredient Epimedii herba, has potential to regulate osteogenic differentiation BMSCs. Nevertheless, related mechanism still unclear. The study aimed explore whether icariin can affect by activating PI3K/AKT signaling alter UTX and EZH2 expression thus regulating osteogenesis-related genes BMSCs were collected from Sprague Dawley rats identified measuring positive ratios cell markers using flow cytometry. Cells treated with 1 μmol/L dexamethasone (DEX) for 24 h or without 0.1–10 μM treatment. Cell counting Kit-8 (CCK-8) assays cytometry analyses performed measure viability apoptosis. Western blotting was conducted measurement apoptotic markers, factors involved PI3K/AKT-UTX/EZH2 pathway, adipogenesis-related factors. Alizarin red S staining Oil-red O effect DEX, icariin, overexpression, knockdown on adipogenic Icariin ameliorated DEX-induced rat BMSC injury. activated signaling, thereby upregulating phosphorylated levels while inhibiting H3K27me3 expression. Additionally, promoted inhibited Importantly, overexpressing silencing exerted similar effects as did. promotes DEX-treated upregulate inhibit EZH2, finally inducing depletion.

Language: Английский

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