Biometals最新文献

Structural and quantitative changes in lipid and osmolyte profiles can serve as markers of technogenic stress caused by heavy metal pollution. This study investigates the biochemical responses of common soil filamentous fungi (Alternaria septospora, Cladosporium halotolerans, Fusarium equiseti, Trichoderma harzianum, and Clonostachys farinosa) to copper (Cu) exposure, focusing on changes in lipids (membrane and storage lipids) and specific osmolytes (polyols and certain carbohydrates). Based on effective concentration values, A. septospora and C. farinosa proved to be the most Cu-resistant species. Under Cu stress, we observed an increased phosphatidylcholines/phosphatidylethanolamines (PC/PE) ratio in the melanized A. septospora, C. halotolerans, and the resistant C. farinosa. Conversely, Cu exposure led to an increased proportion of phosphatidic acids in T. harzianum. Changes in osmolyte composition included elevated mannitol levels, alongside reduced levels of low molecular weight polyols (arabitol, erythritol) and carbohydrates, primarily trehalose. The increased PC/PE ratio, elevated mannitol, and reduced low molecular weight polyols may serve as reliable indicators of Cu-induced stress. These findings underscore the pivotal role of lipid and osmolyte remodeling in fungal tolerance to copper stress and suggest their potential utility as biochemical markers for assessing environmental heavy metal contamination and guiding bioremediation strategies.

With aging and environmental pollution, heavy metal exposure has become a growing concern for age-related eye diseases. However, the relationship between heavy metals and age-related macular degeneration (AMD), cataracts, glaucoma, and diabetic retinopathy (DR) remains unclear. This study investigates the association between urinary heavy metals and these eye diseases, focusing on the molecular mechanisms of cadmium (Cd) in driving AMD. Data from the 2005-2008 NHANES (n = 1865) were analyzed using multivariable logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS) modeling, and sensitivity analyses. Potential molecular mechanisms of Cd in AMD were explored via intersection gene screening, protein-protein interaction network construction, and GO/KEGG enrichment analyses. In single-metal exposure models, Cd was significantly associated with AMD (OR = 1.563, 95% CI: 1.177-2.077, P = 0.00205), Co with cataract (OR = 1.386), U with glaucoma (OR = 1.300), and As with DR (OR = 1.214). In the WQS model, only AMD remained significantly associated with the overall metal mixture (OR = 1.89, 95% CI: 1.22-2.91, P = 0.0041). BKMR identified Cd as the most influential contributor to AMD (PIP = 0.523). The exposure-response curve for Cd and AMD demonstrated an upward trend, with the risk of AMD increasing as Cd exposure levels rose. Additionally, the overall metal mixture was positively associated with AMD risk. Subgroup and RCS analyses confirmed the stability of results, with no significant interaction across demographic subgroups. Sensitivity analyses further validated the findings: the highest quartile of Cd exposure was associated with increased AMD risk (OR = 2.45), and a significant dose-response trend was observed (P for trend = 0.0187). The association remained robust after excluding outliers (OR = 1.31, P = 0.0483).Mechanistically, Cd may induce retinal pigment epithelium damage via oxidative stress (SIRT1/TP53 axis), inflammation (TLR4/NF-κB pathway and pro-inflammatory cytokines), dysregulated apoptosis (BCL2/BAX imbalance), and hypoxia-induced metabolic disruption (HIF-1 signaling). Cd is an independent risk factor for AMD, likely acting through multiple toxic pathways. The effects of U, Co, and As may depend on exposure thresholds or confounders. These findings highlight the need for stricter Cd control and targeted antioxidant or anti-inflammatory strategies for age-related eye disease prevention and treatment.

The formation and maintenance of a biological seal between the peri-implant soft tissue and the titanium (Ti) abutment are critical for preventing peri-implant disease and ensuring implant longevity. However, this seal is fragile and prone to breakdown, particularly under inflammatory conditions. This study aimed to investigate the potential of a polyethylene glycol (PEG) coating associated to a bioactive flavonoid naringenin (NA) to enhance human gingival fibroblast (HGF) functions related to biological sealing on Ti surfaces. Initially, the effects of NA (10 µg/mL) on HGF proliferation, adhesion, and collagen synthesis were assessed under tumor necrosis factor alpha (TNF-α)-induced inflammatory challenge. Subsequently, Ti discs were coated with PEG or PEG incorporated with 10 µg/mL (v/v) of NA, and their surface morphology, chemical composition, and NA release profiles were evaluated. HGF responses, including viability, adhesion/spreading, matrix metalloproteinases (MMPs) and collagen production, were analyzed on the coated discs in the presence or absence of TNF-α-challenge. The results demonstrated that NA enhanced critical cellular processes underlying biological seal formation, including cell proliferation, adhesion, and collagen synthesis, while Ti discs were successfully coated with PEG-NA, which enabled rapid NA release. Moreover, the Ti/PEG-NA coating improved HGF viability and collagen synthesis while reducing TNF-α-induced MMP-2 and MMP-9 production. These in vitro findings underscore the potential of the PEG-NA coating to modulate HGF adhesion and metabolism, representing a promising strategy to enhance soft tissue integration and, consequently, long-term implant stability.

Manganese is an essential trace element for the human body, yet its role in heart function remains inadequately understood, this study aimed to reveal the influence of Mn deficiency on the heart, and uncover underlying mechanisms involved. A manganese-deficient diet was provided to weaned mice, to which manganese chloride (MnCl₂) was administered intraperitoneally to correct Mn deficiency. The pathological changes in the heart were evaluated through histological examination. Cardiac oxidative stress levels were assessed using flow cytometry and biochemical assay kits. The adenosine triphosphate (ATP) content and the levels of mitochondrial respiratory chain (MRC) complexes I-IV were measured with biochemical assay kits. Real-time PCR and Western blotting were performed to determine protein expression related to the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Mn deficiency induced significant cardiac structural damage and elevated serum levels of cardiac injury markers. It also promoted oxidative stress and compromised antioxidant defenses. Mitochondrially, Mn deficiency impaired function, evidenced by reduced ATP levels and suppressed activities of MRC complexes I-IV. Crucially, Mn deficiency inhibited the Nrf2 pathway, demonstrated by decreased Nrf2, HO-1, and NQO1 expression and increased Keap1 expression. However, MnCl₂ supplementation significantly improved these alterations. Research results indicated the association of myocardial damage caused by Mn deficiency with mitochondrial dysfunction and oxidative damage, both of which show close correlations with the Nrf2 signaling pathway.

Major depressive disorder (MDD) is a prevalent psychiatric condition associated with increased oxidative stress, which may contribute to its pathophysiology. Elevated malondialdehyde (MDA) levels and reduced total antioxidant capacity (TAC) and glutathione peroxidase (GPX) activity have been observed in individuals with MDD. Nano-selenium, a novel formulation with enhanced bioavailability and antioxidant potency compared to conventional selenium, may help modulate these oxidative stress biomarkers. In this randomized, triple-blind, placebo-controlled trial, 50 adults newly diagnosed with MDD received either nano-selenium (55 µg/day) or placebo, both alongside sertraline (50 mg/day), over a 12-week period. A total of 42 participants (21 per group) completed the study. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HDRS), and serum levels of GPX, TAC, and MDA were assessed at baseline and post-intervention. Compared to placebo, nano-selenium significantly reduced depressive symptoms (mean change: -5.09 ± 4.94; P < 0.001) and increased TAC (mean change: 0.03 ± 0.04 mmol/L; P = 0.003) and GPX levels (median change: 9.56 U/L; IQR: -7.86 to 30.31; P = 0.044). While MDA levels decreased significantly in both groups, between-group differences were not statistically significant. These findings suggest that nano-selenium may serve as a safe and effective adjunctive therapy for reducing depressive symptoms and improving antioxidant status in MDD. However, the short duration and modest sample size of this study limit generalizability. Larger, multicenter trials with extended follow-up are recommended to confirm and expand upon these results. This study was approved by the Research Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1402.206; June 13, 2023) and registered with the Iranian Registry of Clinical Trials (IRCT20091114002709N62; July 29, 2023). Written informed consent was obtained from all participants.

Wilson's disease (WD) is a rare autosomal recessive disorder caused by mutations in ATP7B, which is marked by defective copper metabolism that leads to toxic copper buildup in organs such as the liver and brain, ultimately causing hepatocellular injury and liver fibrosis. This review systematically examined the multifaceted mechanisms through which copper overload drives liver fibrosis. In short, copper ions generate reactive oxygen species via the Fenton reaction, thereby directly impairing the mitochondrial structure and function and inducing hepatocyte apoptosis, necrosis, and cuproptosis. Copper ions also activate signaling pathways such as the TGF-β1/Smad and NF-κB pathways, which stimulate hepatic stellate cells and promote their transdifferentiation into collagen-secreting myofibroblasts, which then accelerate extracellular matrix deposition. Moreover, abnormal lipoylation of the copper-dependent proteins metal-binding domain of ferredoxin 1 and dihydrolipoamide transacetylase causes mitochondrial protein oligomer buildup and tricarboxylic acid cycle dysfunction, reinforcing an "oxidative damage-inflammation-fibrosis" vicious cycle. The disruption of copper chaperones and lysosomal copper accumulation further intensifies oxidative stress and dysregulates the immune microenvironment. Current therapies focus mainly on copper chelation but exhibit limited ability to reverse established fibrosis. Meanwhile, emerging gene therapies face the challenges of delivery efficiency and immunogenicity. Future research should therefore elucidate the dynamic interplay between copper metabolism and the liver microenvironment, identify key regulatory nodes across different disease stages, and shift treatment paradigms from narrow "symptomatic copper chelation" to integrated strategies aimed at restoring copper homeostasis. Such advances could yield novel approaches toward the prevention and treatment of WD liver fibrosis.