Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 6891 - 6891

Published: April 7, 2023

Iron is one of the essential mineral elements for human body and this nutrient deficiency a worldwide public health problem. in oxygen transport, participates many enzyme systems body, an important trace element maintaining basic cellular life activities. also plays role collagen synthesis vitamin D metabolism. Therefore, decrease intracellular iron can lead to disturbance activity function osteoblasts osteoclasts, resulting imbalance bone homeostasis ultimately loss. Indeed, deficiency, with or without anemia, leads osteopenia osteoporosis, which has been revealed by numerous clinical observations animal studies. This review presents current knowledge on metabolism under states diagnosis prevention anemia (IDA). With emphasis, studies related loss are discussed, potential mechanisms leading analyzed. Finally, several measures promote complete recovery listed improve quality life, including health.

Language: Английский

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Melatonin Ameliorates Hepatic Ferroptosis in NAFLD by Inhibiting ER Stress via the MT2/cAMP/PKA/IRE1 Signaling Pathway

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(12), P. 3937 - 3950

Published: Jan. 1, 2023

Ferroptosis, an iron-dependent cell death form, has recently been observed in the development of non-alcoholic fatty liver disease (NAFLD).Melatonin (Mel) shows potential benefits for preventing and treating diseases.Whether how Mel ameliorates hepatic ferroptosis NAFLD is not fully understood.Here we established a mouse model induced by long-term high-fat diet (HFD) feeding.We found that treatment ameliorated global metabolic abnormalities inhibited progression mice.Most importantly, supplementation significantly improved HFD-induced iron homeostasis disorders liver, including overload ferritin transport disorders.For another, lipid peroxidation.The recuperative role exogenous on hepatocyte was also PA-or Erastin-treated HepG2 cells.Mechanistically, MT2, but MT1, involved effect Mel.Furthermore, HFD or Erastin-activated ER stress activated PKA/IRE1 signaling pathway.Co-expression p-PKA p-IRE1 enhanced MT2 antagonist.Inhibitions PKA IRE1 respectively ferroptosis, activations cAMP/PKA reversed Mel's ferroptosis.Collectively, these findings suggest inhibits ameliorating through MT2/cAMP/PKA/IRE1 pathway, proving promising candidate drug NAFLD.

Language: Английский

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Exogenous melatonin ameliorates steroid-induced osteonecrosis of the femoral head by modulating ferroptosis through GDF15-mediated signaling

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 3, 2023

Abstract Background Ferroptosis is an iron-related form of programmed cell death. Accumulating evidence has identified the pathogenic role ferroptosis in multiple orthopedic disorders. However, relationship between and SONFH still unclear. In addition, despite being a common disease orthopedics, there no effective treatment for SONFH. Therefore, clarifying mechanism investigating pharmacologic inhibitors from approved clinical drugs strategy translation. Melatonin (MT), endocrine hormone that become popular dietary supplement because its excellent antioxidation, was supplemented external source to treat glucocorticoid-induced damage this study. Methods Methylprednisolone, commonly used glucocorticoid clinic, selected simulate injury current observed through detection ferroptosis-associated genes, lipid peroxidation mitochondrial function. Bioinformatics analysis performed explore melatonin receptor antagonist shGDF15 were applied block therapeutic effect MT further confirm mechanism. Finally, experiments rat model detect effects MT. Results alleviated bone loss rats by maintaining BMSC activity suppression ferroptosis. The results are verified MT2 can bioinformatic subsequent confirmed growth differentiation factor 15 (GDF15), stress response cytokine, downregulated process On contrary, increased expression GDF15 marrow mesenchymal stem cells. Lastly, rescue with plays key melatonin. Conclusions We proposed attenuated inhibiting regulation GDF15, supplementation exogenous might be promising method Graphical

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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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

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

Published: Feb. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

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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Therapeutic Effects of Melatonin in the Regulation of Ferroptosis: A Review of Current Evidence

Current Drug Targets, Journal Year: 2024, Volume and Issue: 25(8), P. 543 - 557

Published: May 6, 2024

Ferroptosis is implicated in the pathogenesis of multiple diseases, including neurodegenerative cardiovascular kidney pathologies, ischemia-reperfusion injury, and cancer. The current review article highlights involvement ferroptosis traumatic brain acute damage, ethanol-induced liver PM2.5-induced lung injury. Melatonin, a molecule produced by pineal gland many other organs, well known for its anti- aging, anti-inflammatory, anticancer properties used treatment different diseases. Melatonin's ability to activate anti-ferroptosis pathways sirtuin (SIRT)6/p- nuclear factor erythroid 2-related 2 (Nrf2), Nrf2/ antioxidant responsive element (ARE)/ heme oxygenase (HO-1)/SLC7A11/glutathione peroxidase (GPX4)/ prostaglandin-endoperoxide synthase (PTGS2), extracellular signal-regulated kinase (ERK)/Nrf2, ferroportin (FPN), Hippo/ Yes-associated protein (YAP), Phosphoinositide 3-kinase (PI3K)/ B (AKT)/ mammalian target rapamycin (mTOR) SIRT6/ receptor coactivator 4 (NCOA4)/ ferritin heavy chain 1 (FTH1) signaling suggests that it could serve as valuable therapeutic agent preventing cell death associated with various Further research needed fully understand precise mechanisms which melatonin regulates potential target.

Language: Английский

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Exogenous iron caused osteocyte apoptosis, increased RANKL production, and stimulated bone resorption through oxidative stress in a murine model

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 399, P. 111135 - 111135

Published: July 4, 2024

Language: Английский

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Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8740 - 8740

Published: May 14, 2023

(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process osteoarthritis (OA). Melatonin may be a new hope for the treatment OA because its antioxidant capacity. However, mechanism melatonin in still not completely clear, physiological characteristics articular cartilage make unable to play long-term role OA. (2) effects on ROS system chondrocytes therapeutic effect vivo were evaluated. Then, melatonin-loaded nano-delivery (MT@PLGA-COLBP) was prepared characterized. Finally, behavior MT@PLGA-COLPB mice (3) can inhibit activation by inhibiting TLR2/4-MyD88-NFκB signal pathway scavenging ROS, thus improving matrix metabolism delaying progression vivo. MT@PLGA-COLBP reach interior complete accumulation knee joints. At same time, it reduce number intra-articular injections improve utilization rate (4) This work provides idea osteoarthritis, updates highlights application prospect PLGA@MT-COLBP nanoparticles preventing

Language: Английский

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A ROS-responsive loaded desferoxamine (DFO) hydrogel system for traumatic brain injury therapy

Biomedical Materials, Journal Year: 2024, Volume and Issue: 19(2), P. 025016 - 025016

Published: Jan. 12, 2024

Traumatic brain injury (TBI) produces excess iron, and increased iron accumulation in the leads to lipid peroxidation reactive oxygen species (ROSs), which can exacerbate secondary damage lead disability death. Therefore, inhibition of overload oxidative stress has a significant role treatment TBI. Functionalized hydrogels with inhibiting ability will greatly contribute repair Herein, an injectable, post-traumatic microenvironment-responsive, ROS-responsive hydrogel encapsulated deferrioxamine mesylate (DFO) was developed. The is rapidly formed via dynamic covalent bonding between phenylboronic acid grafted hyaluronic (HA-PBA) polyvinyl alcohol (PVA), phenylboronate bonds are used respond reduce ROS levels damaged tissue promote neuronal recovery. release DFO from HA-PBA/PVA response further promotes regeneration recovery by relieving thus eradicating ROS. In Feeney model Sprague Dawley rats, HA-PBA/PVA/DFO significantly improved behavior TBI rats reduced area contusion rats. addition, could effectively Its effects were also explored, notably, as well ROS, protecting neurons Thus, this biocompatible drug-loaded great potential for This work suggests novel method after

Language: Английский

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