Biometals最新文献

Iron overload diseases (IOD) are harmful conditions that may lead to a significant decrease in quality of life. The only three IOD approved chelators have significant adverse effects that hinder therapeutic adherence. The search for new chelators may benefit from drug repositioning (DR), a strategy that aims to identify new applications for approved drugs. Antiresorptives (AR) are drugs that inhibit bone resorption. Here, the iron binding and antioxidant effects of four bisphosphonates (etidronate, alendronate, tiludronate, and zoledronate) and strontium ranelate AR were studied in buffer and cell models, in order to verify their potential as alternative treatments of IOD in the absence of bone disease. Competition equilibrium tests between the bisphosphonates and ferric calcein or ferric transferrin showed a moderate ability to scavenge iron. Bisphosphonates showed antioxidant activity against iron-induced reactive species generation in the presence of ascorbate. Etidronate and tiludronate helped to prevent cell death by iron-dependent oxidative stress. Although measurable, the effect of physiological levels of calcium did not prevent the desired chelating and antioxidant effects of the bisphosphonates. Our results show that etidronate and tiludronate have valuable physicochemical properties that could be employed in a DR strategy for the treatment of IOD.

As coral reefs continue to decline globally, a toolbox of new interventions such as nutritional supplementation are being considered. Low level supplementation of the trace element manganese (Mn) has increasingly been shown to enhance the resilience of photosynthetic Cnidarians to thermal stress, however, questions around the timing of Mn delivery relative to a thermal stress event remain unanswered. Here we explore how the timing of Mn additions influences the response of the common reef building coral Acropora millipora to thermal stress. Coral health was assessed using a variety of different metrics including photochemical efficiency, oxygen dynamics, elementomics and symbiont densities. A. millepora displayed significantly improved thermal tolerance when exposed to either intermittent pulse (19.34 µg L^-1 every second day) dosing or constant (4.24 µg L^-1) supply of dissolved Mn from 7 days before heat stress exposure (32 °C). Pulse dosed corals maintained higher photosynthetic efficiency and photosynthesis to respiration rates, as well as increased Symbiodiniaceae densities compared to thermally stressed corals without Mn supplementation. Elemental analysis revealed that both coral tissue and Symbiodiniaceae in Mn-treated corals accumulated significantly more Mn than non-Mn treated corals. Collectively, our results suggest that intermittent (pulse) Mn exposure prior to the onset of thermal stress may provide the greatest support for thermal resilience in corals. This study advances understanding on how essential elements like Mn could be strategically delivered as an active intervention to enhance coral tolerance during periods of thermal stress.

Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality and its rising incidence underscores the urgent need to explore novel therapeutic targets. Cancer is often characterized by dysregulated copper metabolism, which plays a crucial role in modulating tumor cell properties like cell proliferation, angiogenesis and metastasis. Therefore, exploiting their metabolic vulnerability using copper overload-based anticancer strategies has emerged as a novel approach. Despite the significant therapeutic potential of copper, its application in anticancer therapy has been limited due to systemic toxicity and non-target localization. In the present study we report targeted delivery of copper to the tumor site and its anticancer therapeutic potential of copper conjugated aminated arabinogalactan (Cu-aAG) in HCC. The synthesized compound was characterized using FT-IR, NMR, Mass spectroscopy and assessed for its anti-cancer therapeutic potential against the Wistar rat model of N-nitrosodiethylamine-induced hepatocellular carcinoma. The chemical characterization of Cu-aAG revealed successful copper complexation as evidenced by characteristic FT-IR peaks and elemental analysis showing 1.19% copper content. The involvement of amine and hydroxyl groups in the complexation was further confirmed by NMR and mass spectral analysis thus ensuring formation of stable, copper-centered co-ordination complexes. Cu-aAG treatment to tumor bearing Wistar rats significantly decreased tumor burden and tumor multiplicity (3.92 ± 2.9) as compared to untreated Tumor group (18.90 ± 3.02). Further, Cu-aAG treatment induced apoptotic cell death, cell cycle arrest, and inhibited angiogenesis. These findings highlight the potential of targeted delivery of copper overload-mediated anticancer therapy for inhibiting tumor growth and progression in HCC.

This study aimed to assess metal exposure in the fingernails of men with nasopharyngeal cancer. Fingernail samples were analyzed using total reflection X-ray fluorescence technique. A multivariable logistic regression model was used to predict metal exposure levels, and Spearman correlations were used to identify variables associated with increased cancer risk. The results showed that the concentrations of 11 metals significantly differed between patients and healthy controls. Adjusted odds ratios (adj.OR) of metal exposure indicated significant positive associations with increased risk of cancer: Fe (adj.OR = 1.04), Cr (adj.OR = 3.70), Ni (adj.OR = 1.87), Cd (adj.OR = 2.93), As (adj.OR = 3.95), and Pb (adj.OR = 3.65). In contrast, significantly lower levels of Ca and Zn were associated with increased risk of cancer: Ca (adj.OR = 0.9976) and Zn (adj.OR = 0.96). Among smoking patients, adj.ORs followed a similar trend but at higher levels, with an increasing risk for Fe (adj.OR = 1.02) < Mn (adj.OR = 1.96) < Cr (adj.OR = 2.31) < Ni (adj.OR = 2.72) < Cd (adj.OR = 5.57) < Pb (adj.OR = 5.61) < As (adj.OR = 6.96) and a decreasing risk for Zn (adj.OR = 0.93) > Ca (adj.OR = 0.9968). Furthermore, Spearman correlations showed that significantly higher levels of Ni and Cd and lower levels of Cu were associated with patients' living environments. Meanwhile, higher levels of Cr, Mn, Fe, Ni, As, and Pb and lower levels of Ca and Zn were significantly associated with smoking habits. In conclusion, significant alterations in fingernail metal concentrations were associated with an increased risk of nasopharyngeal cancer. Exposure to toxic metals, mainly through smoking and living environments, may contribute to disease development. These findings highlight the importance of public health strategies to mitigate metal-related cancer risks.