Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3024 - 3024

Published: March 5, 2024

The human skeleton is a metabolically active system that constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption formation. Emerging evidence reveals fascinating new insights into role sphingolipids, including sphingomyelin, sphingosine, ceramide, sphingosine-1-phosphate, in homeostasis. Sphingolipids are major class bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, kinases, thereby conferring cellular functions beyond energy metabolism. Lipids known contribute progression chronic inflammation, notably, an increase marrow adiposity parallel elevated loss observed most pathological conditions, aging, rheumatoid arthritis, osteoarthritis, osteomyelitis. Of numerous classes form, sphingolipids considered among deleterious. This review highlights important primary homeostasis how dysregulation these metabolites appears central many bone-related diseases. Further, their contribution invasion, virulence, colonization both viral bacterial host cell infections also discussed. Many unmet clinical needs remain, data date suggest future use sphingolipid-targeted therapy regulate dysfunction due variety diseases or infection promising. However, deciphering biochemical molecular mechanisms this diverse extremely complex sphingolipidome, terms health disease, next frontier field.

Language: Английский

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CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Aging, Journal Year: 2024, Volume and Issue: 16(10), P. 8965 - 8979

Published: May 22, 2024

Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing mechanisms underlying BMSCs will provide new candidate therapeutic targets for osteoporosis.

Language: Английский

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Molecular insights into the interplay between type 2 diabetes mellitus and osteoporosis: implications for endocrine health

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

Published: Jan. 17, 2025

Type 2 diabetes mellitus (T2DM) and osteoporosis are prevalent, interconnected chronic diseases that significantly impact global health. Understanding their complex biological relationship is crucial for improving patient outcomes treatment strategies. This review examines recent research on the mechanisms linking T2DM with osteoporosis. It focuses how abnormalities in bone metabolism, autophagy, ferroptosis, vitamin D receptor (VDR) gene polymorphisms contribute to patients. Our analysis indicates associated reduced formation increased resorption, which influenced by hormonal changes, inflammation, disrupted cellular signaling pathways. Additionally, perirenal fat thickness worsens through local inflammation altered adipokine levels. VDR provide new molecular insights into this connection. Addressing identified targeted management strategies may improve health individuals T2DM. Future should explore these associations greater detail develop more effective prevention

Language: Английский

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Cadmium exacerbates liver injury by remodeling ceramide metabolism: Multiomics and laboratory evidence

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 923, P. 171405 - 171405

Published: March 1, 2024

Language: Английский

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Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116571 - 116571

Published: April 26, 2024

Diabetes can lead to a disorder of bone-fat balance, significant cause osteoporosis due changes in environmental factors. Baicalin (Bai), an active ingredient Scutellaria baicalensis, has been confirmed possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, comprehensive understanding Bai's influence on diabetic (DOP), including its effects underlying mechanisms, remains elusive. This study investigated impact the equilibrium rats with DOP. The results indicated that Bai alleviated bone damage DOP by promoting osteogenesis inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested mechanism action might involve P38-MAPK pathway. In vitro, found enhance development marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation adipogenic lineages. It discovered promotion BMSC depends Additionally, synergistic effect mediated inhibitor suppressed differentiation. Our research indicates pathway play role osteogenic-adipogenic BMSCs, showcasing potential for treatment. highlights ability regulate between fat, presenting novel approach adressing

Language: Английский

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Lipid peroxidation inhibition by icaritin and its glycosides as a strategy to combat iron overload-induced osteoporosis in zebrafish

Food Research International, Journal Year: 2025, Volume and Issue: 203, P. 115900 - 115900

Published: Feb. 1, 2025

Language: Английский

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BMAL1-depletion remodels ceramide metabolism to regulate ferroptosis and sorafenib chemosensitivity in acute myeloid leukemia

iScience, Journal Year: 2025, Volume and Issue: 28(4), P. 112054 - 112054

Published: March 22, 2025

Language: Английский

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The Role of Ferroptosis in Osteoporosis and Advances in Chinese Herbal Interventions

Biology, Journal Year: 2025, Volume and Issue: 14(4), P. 367 - 367

Published: April 2, 2025

OP, a systemic bone disorder marked by reduced mass and heightened fracture risk, poses significant global health burden, particularly among aging populations. Current treatments, including bisphosphonates calcium supplementation, are limited adverse effects incomplete efficacy. Emerging research highlights ferroptosis—an iron-dependent cell death driven lipid peroxidation—as critical contributor to OP pathogenesis, characterized dysregulated iron metabolism, oxidative stress, peroxide accumulation, which disrupt remodeling impairing osteoblast function enhancing osteoclast activity. This review elucidates the mechanistic interplay between ferroptosis subtypes (diabetic osteoporosis (DOP), glucocorticoid-induced (GIOP), postmenopausal (PMOP)) evaluates efficacy of Chinese herbal interventions in mitigating ferroptosis-driven loss. Key findings reveal that excess exacerbates peroxidation via Fenton reaction, while glutathione peroxidase 4 (GPX4) inactivation system Xc- inhibition amplify damage. In DIOP, hyperglycemia-induced ROS advanced glycation end products suppress osteogenesis, countered melatonin naringenin nuclear factor -related 2 (Nrf2)/GPX4 activation. GIOP involves dexamethasone-mediated GPX4 downregulation, mitigated exosomes through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) signaling. PMOP estrogen deficiency-induced overload is alleviated aconitine icariin (ICA) kappa-light-chain-enhancer activated cells (NF-κB) signal transducer activator transcription 3 (STAT3) pathways. herbs, active compounds (quercetin, gastrodin, ICA, etc.) formulations (Bugu Shengsui Capsule, Erxian Decoction (EXD), etc.), regulate enhance antioxidant defenses (Nrf2/heme oxygenase 1(HO-1)), inhibit peroxidation, effectively restoring homeostasis. These underscore as pivotal mechanism progression highlight therapeutic promise herbs bridging traditional medicine with modern insights. Future should prioritize elucidating precise molecular targets, optimizing formulations, validating clinical address current gaps.

Language: Английский

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Activation of autophagy mediated by PI3K/Akt/mTOR signalling cascade alleviates impaired adipose‐derived stem cell osteogenesis in a diabetic microenvironment

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Advanced glycation end products (AGEs) contribute to the onset and advancement of diabetic osteoporosis (DOP). Adipose-derived stem cells (ASCs) have garnered attention in field bone renewal; mechanisms leading decreased osteogenesis within a environment are not fully understood. This study explores effects/molecular pathways AGEs on ASCs both vitro vivo. A DOP mouse model was used, were extracted from inguinal fat C57BL/6 mice. cultivated an osteogenic differentiation medium exposed AGEs, Torin1 (an autophagy activator), or ibandronate (IBAN), PI3K/Akt/mTOR signalling inhibitor. Osteogenesis activity measured. The expression markers, OPN RUNX2, decreased, ALP activities impaired, formation mineralised nodules reduced treated with AGEs. Additionally, autophagic flux blocked, there increase markers. After treatment Torin1, microenvironment restored by activating autophagy. Moreover, model, IBAN up-regulated rescued impaired microenvironment. cascade blocking flux. Autophagy induced could rescue negative influences provide potential therapeutic strategy for renewal individuals DOP.

Language: Английский

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