Biometals最新文献

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.

Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC—CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC₅₀) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.

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

Effects of arsenic exposure on trace elements in blood of SD rats, there were sex differences in the blood concentrations of some elements in the As-exposed group. Blood concentrations of some elements changed in the As-exposed group, while correlations were found between some elements. ↑: increased in the As-exposed group. ↓: decreased in the As-exposed group

The diorganotin(IV) complexes (5–20) were synthesized in the present research from 4-fluorophenoxyacetic hydrazide and salicylaldehyde derivatives-based hydrazone ligands (1–4) to get an effective biological agent to combat microbial and oxidant deformities. Numerous spectral techniques such as (¹H, ¹³C, ¹¹⁹Sn) NMR, UV–Vis, IR, and mass spectrometry were executed to illuminate the composition of complexes. These techniques ascertained tridentate chelation of hydrazone ligands with tin metal through enolic, phenolic oxygens and imine nitrogen, revealing pentacoordinated geometry of the complexes. The single crystal XRD of complex (5) confirmed distorted trigonal bipyramidal geometry. The TGA studies showed thermal stability up to 180 °C of the complexes, whereas the low conductance observed pointed to the non-electrolytic nature of the compounds. Furthermore, serial dilution assay was implemented to uncover the microbial inhibition efficacy (against six strains) of the compounds using ciprofloxacin and fluconazole. Among the synthesized compounds, (1, 8) exhibited comparable MIC value to standard. The compound (8) was reported as four times more potent than the fluconazole against C. albicans. Using DPPH assay, the antioxidant efficiency was examined which advocates enhanced efficacy of complexes than the ligands. The potency of complex (8) against C. albicans makes it a point of interest for molecular docking investigation, so, complex (8) and its ligand (1) were studied against protein of C. albicans (5TZ1), revealing the more efficacy of complex (binding energy-11.6 kcal/mol) than ligand. Further, the compounds were analysed for ADME prediction which concluded the efficacy of compounds as orally efficient pharmaceuticals.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

Over recent years, we have been living under a pandemic, caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). One of the major virulence factors of Coronaviruses is the Non-structural protein 1 (Nsp1), known to suppress the host cells protein translation machinery, allowing the virus to produce its own proteins, propagate and invade new cells. To unveil the molecular mechanisms of SARS-CoV2 Nsp1, we have addressed its biochemical and biophysical properties in the presence of calcium, magnesium and manganese. Our findings indicate that the protein in solution is a monomer and binds to both manganese and calcium, with high affinity. Surprisingly, our results show that SARS-CoV2 Nsp1 alone displays metal-dependent endonucleolytic activity towards both RNA and DNA, regardless of the presence of host ribosome. These results show Nsp1 as new nuclease within the coronavirus family. Furthermore, the Nsp1 double variant R124A/K125A presents no nuclease activity for RNA, although it retains activity for DNA, suggesting distinct binding sites for DNA and RNA. Thus, we present for the first time, evidence that the activities of Nsp1 are modulated by the presence of different metals, which are proposed to play an important role during viral infection. This research contributes significantly to our understanding of the mechanisms of action of Coronaviruses.