Biometals最新文献

The iron(III) binding properties of citrate and rhizoferrin, a citrate containing siderophore, are compared. Citrate forms many oligonuclear complexes, whereas rhizoferrin forms a single mononuclear complex. The α-hydroxycarboxylate functional group, which is present in both citrate, and rhizoferrin, has a high affinity and selectivity for iron(III) under most biological conditions. The nature of the toxic form of iron found in the blood of patients suffering from many haemoglobinopathies and haemochromatosis is identified as a mixture of iron(III)citrate complexes. The significance of the presence of this iron pool to patients suffering from systemic iron overload is discussed. The wide utilisation of the α-hydroxycarboxylate functional group in siderophore structures is described, as is their photo-induced decarboxylation leading to the release of iron(II) ions. The importance of this facile dissociation to algal iron uptake is discussed.

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work.

Under normal physiological conditions, the endogenous Labile Iron Pool (LIP) constitutes a ubiquitous, dynamic, tightly regulated reservoir of cellular ferrous iron. Furthermore, LIP is loaded into new apo-iron proteins, a process akin to the activity of metallochaperones. Despite such importance on iron metabolism, the LIP identity and binding properties have remained elusive. We hypothesized that LIP binds to cell constituents (generically denoted C) and forms an iron complex termed CLIP. Combining this binding model with the established Calcein (CA) methodology for assessing cytosolic LIP, we have formulated an equation featuring two experimentally quantifiable parameters (the concentrations of the cytosolic free CA and CA and LIP complex termed CALIP) and three unknown parameters (the total concentrations of LIP and C and their thermodynamic affinity constant Kd). The fittings of cytosolic CALIP × CA concentrations data encompassing a few cellular models to this equation with floating unknown parameters were successful. The computed adjusted total LIP (LIP_T) and C (C_T) concentrations fall within the sub-to-low micromolar range while the computed Kd was in the 10⁻² µM range for all cell types. Thus, LIP binds and has high affinity to cellular constituents found in low concentrations and has remarkably similar properties across different cell types, shedding fresh light on the properties of endogenous LIP within cells.

Background

In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population.

Methods

In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass.

Results

The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters.

Discussion

and Conclusions.

Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Cadmium (Cd) is a widely distributed pollutant that adversely affects plants’ metabolism and productivity. Phytohormones play a vital role in the acclimation of plants to metal stress. On the other hand, phytohormones trigger systemic resistances, including systemic acquired resistance (SAR) and induced systemic resistance (ISR), in plants in response to biotic interactions. The present study aimed to investigate the possible induction of SAR and ISR pathways in relation to the hormonal alteration of barley seedlings in response to Cd stress. Barley seedlings were exposed to 1.5 mg g⁻¹ Cd in the soil for three days. The nutrient content, oxidative status, phytohormones profile, and expression of genes involved in SAR and ISR pathways of barley seedlings were examined. Cd accumulation resulted in a reduction in the nutrient content of barley seedlings. The specific activity of superoxide dismutase and the hydrogen peroxide content significantly increased in response to Cd toxicity. Abscisic acid, jasmonic acid, and ethylene content increased under Cd exposure. Cd treatment resulted in the upregulation of NPR1, PR3, and PR13 genes in SAR pathways. The transcripts of PAL1 and LOX2.2 genes in the ISR pathway were also significantly increased in response to Cd treatment. These findings suggest that hormonal-activated systemic resistances are involved in the response of barley to Cd stress.

Schiff base complexes play a crucial role in bioinorganic chemistry. A novel curcumin/phenylalanine tridentate Schiff base ligand and its palladium (II) complex were synthesized so that they were stable in aqueous buffer. The structure of the complex was investigated using a variety of methods, including DFT, NBO analysis, FMOs, and MESP. The interaction of the complex with a plasmid (pUC19) and CT-DNA was studied. The anticancer, antibacterial, and antioxidant activities of the complex were examined. The statistical analysis of the MTT assay was compared using the 1-way ANOVA and Tukey test. Results showed that the complexes were stable in aqueous buffer, pH 8. The extrinsic fluorescence emission of the plasmid and CT-DNA was quenched while interacting with the complex. The complex had an IC₅₀ of 72.47 µM against MCF-7 cells. The ANOVA and Tukey analysis of MTT data demonstrated a statistically significant difference between groups (P < 0.0001). The minimum inhibitory concentrations (MIC) of the complex for E. coli and S. aureus were 300 and 200 µg/mL, with 96.3 and 95.2% biofilm growth inhibition at 250 µg/mL, respectively. The sample concentrations contributing to 50% radical inhibition in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test for curcumin, ligand, and palladium (II) complex were 33.62, 21.27, and 51.26 µM, respectively. The results suggest that the complex interaction with DNA is one of the potential mechanisms for eliminating cancer cells and bacteria in the planktonic and biofilm. On the other hand, while stability in an aqueous buffer at pH 8 increases, the modified curcumin antioxidant effect decreases.

Independent trials indicate that either oral Zn²⁺ or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn²⁺ deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn²⁺ is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn²⁺ bioavailability and active absorption by cation transporters known to transport metformin. Intracellular Zn²⁺ provides a natural buffer of many protease reactions; the variable “set point” is determined by Zn²⁺ regulation or availability. A Zn²⁺-interactive protease network is suggested here. The two viral cysteine proteases are therapeutic targets against COVID-19. Viral and many host proteases are submaximally inhibited by exchangeable cell Zn²⁺. Inhibition of cysteine proteases can improve COVID-19 outcomes and non-infectious inflammation. Metformin reportedly enhances the natural moderating effect of Zn²⁺ on bioassayed proteome degradation. Firstly, the dissociable metformin–Zn²⁺ complex could be actively transported by intestinal cation transporters; thereby creating artificial pathways of absorption and increased body Zn²⁺ content. Secondly, metformin Zn²⁺ coordination can create a non-natural protease inhibitor independent of cell Zn²⁺ content. Moderation of peptidolytic reactions by either or both mechanisms could slow (a) viral multiplication (b) viral invasion and (c) the pathogenic host inflammatory response. These combined actions could allow development of acquired immunity to clear the infection before life-threatening inflammation. Nirmatrelvir (Paxlovid®) opposes COVID-19 by selective inhibition the viral main protease by a Zn²⁺-independent mechanism. Pending safety evaluation, predictable synergistic benefits of metformin and Zn²⁺, and perhaps metformin/Zn²⁺/Paxlovid® co-administration should be investigated.

Arsenic (As) is a widespread environmental metalloid and human carcinogen, and its exposure is associated with a wide range of toxic effects, leading to serious health hazards. As poisoning is a complex systemic multi-organ and multi-system damage disease. In this study, a rat model of As poisoning was established to investigate the levels of trace elements in the blood of rats and sex differences in the effect of As on every trace elements in rat blood. Twenty 6-week-old SD (Sprague Dawley) rats were randomly divided into the control group and the As-exposed group. After 3 months, the contents of 19 elements including As in the blood were detected in these two groups by inductively coupled plasma mass spectrometry (ICP-MS). As levels in the blood of As-exposed rats were significantly higher than those in the control group, with increased levels of Rb, Sr, Cs and Ce, and decreased levels of Pd. As showed a significant positive correlation with Rb. There were significant sex differences in blood Se, Pd, Eu, Dy, Ho, and Au levels in the As-exposed group. The results showed that As exposure can lead to an increase of As content in blood and an imbalance of some elements. There were sex differences in the concentration and the correlation between elements of some elements. Elemental imbalances may affect the toxic effects of As and play a synergistic or antagonistic role in As toxicity.

Graphical abstract

Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)₂phen(H₂O).5H₂O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 μg/mL and MFCs from 15.62 to 62.5 μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 μg/mL for 5 days. After 24 h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600 μg/mL), with the 50% cytotoxic concentration calculated as 776.2 μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.