Environmental cadmium exposure perturbs systemic iron homeostasis via hemolysis and inflammation, leading to hepatic ferroptosis in common carp (Cyprinus carpio L.)

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 275, P. 116246 - 116246

Published: March 26, 2024

Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, still largely unknown whether how at environmentally relevant concentrations affects iron metabolism. Here, we studied the of environmental exposure (5 50 μg/L) homeostasis possible mechanisms in common carp. The data revealed elevated serum iron, transferrin saturation deposition livers spleens, leading disruption systemic homeostasis. Mechanistic investigations substantiated drove hemolysis by compromising osmotic fragility inducing defective morphology erythrocytes. concurrently exacerbated hepatic inflammatory responses, resulting activation IL6-Stat3 signaling subsequent hepcidin transcription. Notably, elicited ferroptosis through increased burden oxidative stress livers. Taken together, our findings provide evidence mechanistic insight could undermine via erythrotoxicity hepatotoxicity. Further investigation ecological risk assessment other pollutants metabolism-related warranted, especially under realistic scenarios.

Language: Английский

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Application of 4D printing and bioprinting in cardiovascular tissue engineering

Biomaterials Science, Journal Year: 2023, Volume and Issue: 11(19), P. 6403 - 6420

Published: Jan. 1, 2023

Cardiovascular diseases have remained the leading cause of death worldwide for past 20 years. The current clinical therapeutic measures, including bypass surgery, stent implantation and pharmacotherapy, are not enough to repair massive loss cardiomyocytes after myocardial ischemia. Timely replenishment with functional tissue via biomedical engineering is most direct effective means improve prognosis survival rate patients. It widely recognized that 4D printing technology introduces an additional dimension time in comparison traditional 3D printing. Additionally, context bioprinting, both printed material resulting product designed be biocompatible, which will mainstream bioprinting future. Thus, this review focuses on application cardiovascular diseases, discusses bottleneck development finally looks forward future direction prospect revolutionary technology.

Language: Английский

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Diminishing Hepcidin via Reducing IL-6/STAT3 Pathway by Utilizing Ferulic Acid: An In Vitro Study

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 923 - 923

Published: April 9, 2025

Background/Objectives: Hepcidin is a negative regulator of iron absorption that released by hepatocytes. It one the main contributors to hypoferremia and anemia in inflammatory oncological disorders are mediated proinflammatory cytokine IL-6/STAT3 pathway. Ferulic acid (FA) phenolic compound with pleiotropic biological activities, including anti-inflammatory activity. However, its effect on hepcidin secretion still unknown. Thus, this study aimed explore impact FA levels underlying mechanism. Methods: HepG2 cells were treated different log percentages FA, their viability was determined via MTT assay. The relative expression IL-6 HAMP untreated measured qRT-PCR, protein hepcidin, STAT3 using ELISA. Results: test showed an inverse relationship between concentrations cell proliferation; FA’s IC50 value 0.07669%. significantly increased following 24 h culture 4 μg/mL LPS. Meanwhile, addition decreased these two genes IL-6, compared LPS alone. Conclusions: Overall, findings show modifies pathways, affecting suggests as potential therapeutic agent against developed due dysregulated diseases such disorders.

Language: Английский

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The interplay between the myeloperoxidase-hypochlorous acid system, heme oxygenase, and free iron in inflammatory diseases

Journal of Inorganic Biochemistry, Journal Year: 2025, Volume and Issue: 270, P. 112927 - 112927

Published: April 17, 2025

Language: Английский

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Iron Deficiency Treatment in Heart Failure—Challenges and Therapeutic Solutions

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(9), P. 2934 - 2934

Published: April 24, 2025

Iron deficiency (ID) is a common comorbidity in heart failure (HF), affecting nearly 50% of patients and worsening symptoms, exercise capacity, prognosis. This review summarizes recent evidence from meta-analyses, clinical trials, guidelines on the pathophysiology, diagnosis, treatment ID HF. HF results chronic inflammation, intestinal congestion, impaired iron metabolism. Diagnosis based serum ferritin transferrin saturation (TSAT) levels. While oral therapy has limited efficacy, intravenous iron, particularly ferric carboxymaltose derisomaltose, improves symptoms tolerance reduces hospitalizations. Timely diagnosis are essential. Intravenous preferred therapeutic approach, but further research needed to optimize long-term management.

Language: Английский

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Transferrin Receptor 2 in Canine Testicular Tumors: An Emerging Key Role in Seminomas

Animals, Journal Year: 2025, Volume and Issue: 15(2), P. 264 - 264

Published: Jan. 18, 2025

Transferrin Receptor 2 (TfR2) is a homolog of 1 (TfR1), involved in regulating intra and extracellular iron levels. Altered pathways have been associated with cancer onset progression; however, their role canine tumors remains poorly explored. This study investigated TfR2 immunohistochemical expression non-neoplastic testis for the first time most common types testicular tumors: intratubular seminomas (ITSEMs), diffuse (DSEMs), Leydig cell (LCTs), Sertoli (SCTs). Immunohistochemical analysis revealed differential pattern according to tumor type, high observed ITSEMs DSEMs, occasional LCTs, absence SCTs. These results suggest that may play relevant seminoma development. Furthermore, specific highlights its potential as therapeutic target, where regulation possible compensatory mechanisms warrant further investigation.

Language: Английский

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Impact of plant-derived antioxidants on heart aging: a mechanistic outlook

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Heart aging involves a complex interplay of genetic and environmental influences, leading to gradual deterioration cardiovascular integrity function. Age-related physiological changes, including ventricular hypertrophy, diastolic dysfunction, myocardial fibrosis, increased arterial stiffness, endothelial are influenced by key mechanisms like autophagy, inflammation, oxidative stress. This review aims explore the therapeutic potential plant-derived bioactive antioxidants in mitigating heart aging. These compounds, often rich polyphenols, flavonoids, other phytochemicals, exhibit notable antioxidant, anti-inflammatory, cardioprotective properties. substances have intricate properties, ability scavenge ROS, enhance endogenous antioxidant defenses, regulate signaling pathways, impede fibrosis inflammation-promoting processes. By focusing on molecular linked cardiac aging, produced from plants provide significant promise reduce age-related decline improve general health. Through comprehensive analysis preclinical clinical studies, this work highlights associated with promising effects antioxidants. The findings may helpful for researchers identifying specific molecules preventive heart.

Language: Английский

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Ferritinophagy: a possible new iron-related metabolic target in canine osteoblastic osteosarcoma

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: March 24, 2025

Canine osteosarcomas (COS) are the most common bone tumors in dogs, characterized by high metastatic rates, poor prognosis, and responsiveness to routine therapies, which highlights need for new treatment targets. In this context, metabolism of neoplastic cells represents an increasingly studied element, as cancer depend on particular metabolic pathways that also elements vulnerability. Among these, tumor (TCs) show higher iron requirements sustain proliferation (so-called addiction), achieved increasing uptake and/or activating ferritinophagy, a process mediated Nuclear receptor Co-Activator 4 (NCOA4) leading mobilization from ferritin (Ft) deposits. Previous studies have shown COS overexpress Transferrin Receptor 1 (TfR1) increase uptake. study we evaluated immunohistochemical expression ferritinophagy-related proteins, namely Ferritin Heavy chain (FTH1) NCOA4, proliferating cell nuclear antigen (PCNA) canine normal osteoblastic osteosarcoma (COOS) samples. Normal samples revealed negative/weak immunoreactivity FTH1, NCOA4 PCNA <10% osteocytes. COOS majority showed PCNA. Our data suggest activation ferritinophagy responds feed their “iron addiction.” These data, though preliminary, further targeting potential strategy worthy be transferred into clinical practice.

Language: Английский

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Calcium and IL-6 regulate the anterograde trafficking and plasma membrane residence of the iron exporter ferroportin to modulate iron efflux

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(6), P. 107348 - 107348

Published: May 6, 2024

Language: Английский

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Role of Nutraceuticals in Counteracting Inflammation in In Vitro Macrophages Obtained from Childhood Cancer Survivors

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 714 - 714

Published: Feb. 8, 2024

The advancement of anti-cancer therapies has markedly improved the survival rate children with cancer, making them long-term childhood cancer survivors (CCS). Nevertheless, these treatments cause a low-grade inflammatory state, determining inflamm-aging and, thus, favoring early onset chronic diseases normally associated old age. Identification novel and safer therapeutic strategies is needed to counteract prevent inflamm-aging. Macrophages are cells involved in immune responses, pivotal role iron metabolism, which related inflammation. We obtained macrophages from CCS patients evaluated their phenotype markers, states, metabolism by Western blotting, ELISA, assays. observed strong increase classically activated markers (M1) alteration CCS, an intracellular concentration markers. These results suggest that prevalence M1 could be worsening inflammation CCS. Therefore, we propose as targets To avoid toxic regimens, tested some nutraceuticals (resveratrol, curcumin, oil-enriched lycopene), already known exert anti-inflammatory properties. After administration, macrophage switch towards M2, well reductions pro-inflammatory cytokines concentration. suggest—for first time—that reduce through mechanism action, modulating metabolism.

Language: Английский

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