Biometals最新文献

Therapy resistance is a major challenge in cancer treatment, with multidrug resistance (MDR) being a well-characterized phenomenon wherein cancer cells develop resistance not only to the administered drug but also to structurally diverse compounds. Metal chelators, including quinolines and thiosemicarbazones, have shown broad antitumor activity and potential in overcoming MDR by modulating metal metabolism. However, predicting whether chelators increase or decrease toxicity in MDR cells remains complex, especially as chelator-metal complexes may become substrates for ATP-binding cassette (ABC) transporters, leading to resistance or hypersensitivity. In this study, we developed cell lines with comparable expression levels of the three major MDR ABC transporters (ABCB1, ABCC1, and ABCG2). Our findings demonstrated distinct transporter-specific influences on chelator toxicity. Cells expressing ABCC1 displayed significant resistance to thiosemicarbazones (Dp44mT, COTI-2, DpC) in both their metal-free and metal-bound forms. Vesicular transport assays further demonstrated that ABCC1 actively transports the Fe-GSH complex, formed under physiological glutathione levels, indicating its role in regulating the labile iron pool and reducing intracellular iron toxicity. These findings underscore the importance of transporter-chelator interactions in shaping drug resistance and sensitivity and highlight the intricate roles of ABC transporters in modulating chelator activity.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus (DM). Evidence suggests that trace element imbalances may contribute to the development and progression of DR. This study aimed to evaluate the levels of selected trace elements in Iraqi patients with DM, with and without retinopathy, to identify potential biomarkers associated with disease progression. A total of 120 participants were involved and divided into three groups: healthy controls (n = 60), DM patients (n = 30), and DR patients (n = 30). Blood samples were analyzed for the concentrations of Cu, Zn, Mg, Pb, Cd, Ni, Cr, Co, Mn, and Al using flame and flameless atomic absorption spectrophotometry. DR patients showed elevated levels of Cu, Pb, Cd, Ni, and Al, and decreased levels of Zn, Mg, Cr, Co, and Mn compared to both DM and control groups (p < 0.05 or p < 0.01). Correlation analyses revealed distinct element interactions within DM and DR groups, particularly antagonistic relationships such as Cu–Zn and Zn–Co in DR patients. The study demonstrates a strong association between trace element dysregulation and diabetic retinopathy, suggesting that specific elements such as Cu, Zn, Mg and Co may serve as valuable indicators for monitoring disease progression. These findings strongly support further investigation into trace elements for the prevention and management of DR.

Chagas disease remains a major public health challenge, and there is a need for new therapeutic agents. N-heterocyclic carbene (NHC) complexes, particularly those linked to silver or gold, have shown significant anticancer, antimicrobial, and antiparasitic activities. This study aimed to evaluate the efficacy of four NHC compounds (QMT3, QMT4, QMT7, and QMT8) against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro assays revealed that QMT3 and QMT8 exhibited the strongest antiparasitic effects, with QMT3 showing the highest potency and stability over time (IC₅₀ = 10.3 µg/mL at 24 h). Both compounds induced rapid, irreversible cell death in epimastigotes, primarily through late apoptotic-like and necrotic pathways, as evidenced by Annexin V/PI labeling. Additionally, treatment with QMT3 and QMT8 led to significant increases in intracellular reactive oxygen species (ROS), particularly superoxide (SO). Notably, both compounds displayed high specificity for the parasite with low cytotoxicity towards mammalian cells, although QMT8 was less toxic to host cells than QMT3 at short exposure times. Molecular modeling studies revealed that QMT3, and QMT8 bind to the active site of TryR, a crucial player in maintaining redox homeostasis in trypanosomatids, potentially competing with its natural ligand and disrupting its enzymatic function. These findings suggest that QMT3 and QMT8, silver- and gold-based NHC complexes, act through redox system disruption and TryR inhibition, positioning them as promising candidates for the development of new treatments for Chagas disease.

Chromium in its hexavalent form (Cr(VI)) is a highly toxic environmental pollutant that poses severe risks to human health and ecosystems. Staphylococcus aureus can play a role in the removal of Cr(VI) from aqueous solutions, primarily through a process of reduction and subsequent biosorption. While it’s not as widely studied for this purpose as some other bacterial species, it has been shown to reduce and bind Cr(VI), potentially offering a way to remediate contaminated environments. This study assessed the biosorption potential of the bacterial strain Staphylococcus aureus CC1956, which tolerates Cr(VI) levels up to 700 mg/L. The strain demonstrated significant Cr(VI) removal across various conditions, including pH values from 5.0 to 9.0, temperatures ranging from 25 to 45 °C, and initial Cr(VI) concentrations between 50 and 300 mg/L. Competing anions exerted minimal influence on biosorption efficiency, whereas adding glucose significantly enhanced Cr(VI) removal. The adsorption data were best described by the Langmuir isotherm model, indicating a monolayer binding of Cr(VI) onto the bacterial surface. The main functional groups involved in the biosorption process revealed by FTIR analysis are hydroxyl, phosphoryl, carboxyl, and amine groups in the binding of Cr(VI). SEM–EDX analysis also confirmed the association of chromium with the cell surface. These findings highlight the potential of S. aureus CC1956 as an effective biosorbent for Cr(VI) and its promising application in the bioremediation of contaminated wastewater.

Selenium biofortification of staple foods is a strategy for ameliorating Selenium deficiency among populations. The aim of this study is to investigate the effect of Selenium biofortification on some phytochemicals present in Gboma (Solanum macrocarpon L.) leaves and to assess the effect of its dietary inclusions on some antioxidant molecules, immunoglobulins and inflammatory cytokines in the serum of Wistar rats. Gboma, also called African Eggplant was cultivated on soil enriched with Selenium biofortified fertilizer and harvested at maturity. The phytochemicals present were assessed via HPLC. The samples were also included into the diet of Wistar rats (4% and 8% inclusions) for fourteen days. The serum was then collected and assayed for glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase activities. Imuunoglobulins M, G, A and E as well as the inflammatory makers-tumor necrosis factor-α and interleukin-10 were also assayed for. The results showed that Selenium bioaccumulation increased the concentration of some phytochemicals such as chlorogenic acid, 4- hydroxybenzoic acid and delphinidin. An increase in the activity of the antioxidant enzymes was also observed in rats fed with Selenium biofortified Gboma leaves (4% and 8%), compared to control and rats fed diets supplemented with Gboma leaves without Selenium biofortification. In addition, IgG, IgM and IgA levels increased in the serum of treated rats, coupled with an increase in IL-10 levels. This study therefore, shows that Selenium biofortification enhanced the antioxidant and immunomodulatory properties of Gboma leaves.

Iron is an essential micronutrient required for normal growth and development. However, excessive iron intake can exert toxic effects, particularly during sensitive developmental windows such as pregnancy. In this study, pregnant female mice were supplemented with varying concentrations of iron until day 21 post-delivery. On postnatal days 0 and 21, we assessed the body weight, liver index, hepatic iron content, antioxidant capacity, and expression of ferroptosis-related proteins in the offspring. Excessive maternal iron supplementation significantly decreased both body and liver weights of offspring and induced histopathological abnormalities in hepatic tissue. Liver iron levels were markedly elevated, accompanied by significant reductions in the activities of antioxidant enzymes including T-AOC, CAT, GSH-Px, and SOD, as well as decreased hepatic GSH content. Moreover, iron overload increased the protein expression levels of p-AMPKα/AMPKα, p-ULK1/ULK1, Beclin1, FTH1, and COX2, while decreasing the levels of SLC7A11, GPX4, and NCOA4. Collectively, these findings suggest that excessive iron supplementation during pregnancy leads to hepatic iron accumulation, oxidative stress, and ferroptosis in offspring mice.

Mental health disorders (MHD) are conditions marked by disturbances in thinking, mood, or behavior that can cause significant distress or impair daily functioning. Diagnosis remains challenging, particularly in precision medicine, due to the scarcity of reliable biomarkers as objective diagnostic tools and external validators. This study investigates essential trace metals, cofactors in vital enzymes, as potential biomarkers for MHD. A total of 168 patients with mood spectrum disorders (MSD), schizophrenia spectrum disorders (SSD), and personality disorders (PD) and 61 healthy controls (HC) were evaluated for serum levels of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), as well as transferrin (TF), transferrin saturation (% TF-sat), ferritin (F), and Cu/Zn, Cu/Mg, Fe/Cu ratios. Principal Component Analysis (PCA) and regression models assessed the relationship between these biological variables and MHD. Zn levels were lower in patients, particularly in the PD group. Fe, TF, and % TF-sat were also lower in patients, with the SSD group showing the greatest decrease. Mg levels were similarly lower in patients than in controls. Zn, Fe, Fe/Cu, and TF showed protective effects against MHD, with odds ratios ranging from 0.22 to 0.50. The Cu/Zn ratio was higher in all patients’ groups. The Cu component, including Cu, Cu/Zn, and Cu/Mg levels, was linked to an 84% increase in the odds of having an MHD. This study highlights the potential of trace metals as adjunctive biomarkers in psychiatry, supporting clinical diagnosis and offering new insights into psychiatric pathophysiology.

Garlic (Allium sativum) is a key culinary ingredient and agricultural product that releases its pungent aroma when cut or crushed due to the presence of volatile organosulfur compounds. These compounds, specifically allicin and ajoene, rapidly modify human metallothioneins (MTs), leading to the dissociation of Zn(II) ions. This study employed a top-down protein MS analysis to identify the most reactive cysteine sites in MT2, confirming that both compounds induce S-thioallylation and alter Zn(II) binding. Spectrophotometric studies indicated that both compounds mobilized nearly six molar equivalents of Zn(II) from MT2 after one hour, with ajoene demonstrating slightly higher dissociation efficiency than allicin. Moreover, allicin mobilized Zn(II) from all human isoforms of MT (MT1-MT4), with the lowest efficiency observed for MT4. Mass spectrometry analysis revealed a diverse array of modified complexes, with ajoene resulting in more complex formations than allicin. Reduced glutathione interacts with both untreated and allicin- or ajoene-treated MTs, forming mixed and partially oxidized complexes, highlighting the relationship between these compounds depending on the cell’s redox state. The use of reducing agents demonstrated that MTs’ S-thioallylation is reversible, allowing the protein to rebind Zn(II) after reduction, thereby maintaining its role in zinc homeostasis and rendering the effects of allicin temporary. The health implications of the modifications are significant, given the established role of Zn(II) in inhibiting pro-inflammatory pathways and enhancing antioxidant responses. Zn(II) ions were shown to inhibit the activation of the NF-κB pathway, which regulates pro-inflammatory cytokines. Our findings indicate that the modification of metallothioneins (MTs) by garlic-derived organosulfur compounds may play a crucial role in zinc homeostasis, with implications for immune regulation in humans, and warrant further investigation into their potential therapeutic applications.

Graphical Abstract

Heavy metals-mediated environmental pollution and global warming are two emerging threats to plant and human health worldwide. Several anthropogenic and natural activities with a preference for industrialization and heavy transportation have accelerated heavy metals and CO₂ emissions into aerial and soil environments. For a few decades, woody trees have been considered an effective bioaccumulator or bioindicator tool for pollution assessment processes of air-born pollutants. The present study aimed to reveal the carbon sequestration and phytoremediation potential of commonly grown tree species at industrial and residential sites of Multan City, Pakistan, during the summer (2022) and winter seasons (2023). For this purpose, Cd, Cr, Cu, Fe, Pb, Mn, and Zn were assessed from bark and leaves samples of S.cuminii, F.religiosa, C.fistula, C. erectus, and M. azedarach for phytoremediation assessment and above- and below-ground biomass, width, height, and chlorophyll contents were used to access the carbon sequestration potential. Results showed that the phytoremediation potential of tree species based on heavy metal accumulation and translocation (BAF, CBCI, MAI) followed the overall trend S.cuminii > F.religiosa > C.fistula > C. erectus > M. azedarach, while the carbon sequestration trend based on biomass production (AGB, BGB, TB) and chlorophyll pigments (Chla, Chlb, TChl, and carotenoids) followed by the overall trend S.cuminii > F.religiosa > C.erectus > M.azedarach > C.fistua. PCA analysis, mental and Pearson correlation, and PLS-SEM analysis emphasized our conclusion where F. religiosa and S. cumini showed a significantly positive correlation with carbon sequestrant (CS) and heavy metal deposition in leaf and bark samples with preference at industrial sites and summer season. In conclusion, BCF for all tree species was more than 1, which emphasized their phytoremediation potential against heavy metals and should be preferred for biomonitoring and bioremediation, but F. religiosa and S. cumini were more viable options for carbon sequestration and phytoremediation, each with unique strengths for different contexts. Finally, tree species selection should account for factors like local climate, soil conditions, land use objectives, and desired ecosystem services.

The research of Bombyx mori mainly focuses on the overall brewing of Bombyx mori, there are few studies on Bombyx mori protein and by-products after processing. In order to improving the utilization rate of Bombyx mori, Bombyx mori polypeptide was chelated with inorganic zinc to prepare Bombyx mori polypeptide chelated zinc in this study. Bombyx mori polypeptide was used as the raw material to prepared Bombyx mori polypeptide chelated zinc. Characterization and analysis of Bombyx mori polypeptide chelated zinc used UV spectroscopy, infrared spectroscopy and scanning electron microscopy. It detected the zinc ion absorption rate of polypeptide chelated zinc by constructing an in vitro Caco-2 cell absorption model. The results suggested that the transport amounts of ZnSO₄, glycine chelated zinc were lower than Bombyx mori polypeptide chelated zinc. A total of 5 monomeric peptide chelated zinc were identified by Bombyx mori polypeptide chelated zinc mass spectrometry analysis and named M1–M5. Based on M1–M5 and network pharmacology, verified whether Bombyx mori polypeptide chelated zinc had anti-inflammatory effects. In order to analysed the anti-inflammatory effect of network pharmacology and molecular docking calculation results, RAW264.7 inflammation model was constructed in vitro and the effects of different concentrations of polypeptide chelated zinc on the release of TNF-α, IL-6, and IL-1β were studied. The results demonstrated that Bombyx mori polypeptide chelated zinc had inhibitory effects to the all inflammatory factors. This work provided a data foundation for the development of a new type of zinc ion nutritional enhancer.