Journal of Trace Elements in Medicine and Biology最新文献

Aim

This review presents specific insights on the molecular underpinnings of the connection between fluorosis, type 2 diabetes, and microvascular complications, along with the novel biomarkers that are available for early detection.

Summary

Fluoride is an essential trace element for the mineralization of teeth and bones in humans. Exposure to higher concentrations of fluoride has harmful effects that significantly outweigh its advantageous ones. Dental fluorosis and skeletal fluorosis are the common side effects of exposure to fluoride, which affect millions of individuals globally. Alongside, it also causes non-skeletal fluorosis, which affects the population suffering from non-communicable diseases like diabetes by impacting the soft tissues and causing diabetic microvascular complications. Previous studies reported the prevalence range of these diabetic complications of neuropathy (3–65 %), nephropathy (1–63 %), and retinopathy (2–33 %). Fluoride contributes to the development of these complications by causing oxidative stress, cellular damage, degrading the functioning capability of mitochondria, and thickening the retinal vein basement.

Conclusion

Early diagnosis is a prompt way of prevention, and for that, biomarkers have emerged as an innovative and useful technique. This allows healthcare practitioners and policymakers in endemic areas to comprehend the molecular complexities involved in the advancement of diabetic microvascular problems in the context of high fluoride exposure.

Background

Bromhexine (BHX) is a mucolytic drug used in treatment the respiratory disorders which are associated with excessive or viscid mucus. Transition metal complexes have made tremendous progress in the treatment of a variety of human ailments, according to reported articles. Transition metal complexes are being developed as medications with a lot of effort. Metal complexes can form a variety of coordination geometries, giving them distinct forms. So, binary metal complexes of bromhexine drug have been prepared to enhance the biological activity and stability of the free drug.

Methods

A new series of binary complexes with bromhexine drug (BHX) has been prepared with some transition metal ions namely Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II). Elemental analyses, FT-IR, mass spectrometry, thermal studies and UV-Vis spectra have been used to characterize and structurally elucidate the produced metal complexes. Antibacterial activity has been tested for the ligand and metal complexes against a variety of pathogenic bacterial species (Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus). In addition, the ligand has been tested for anticancer efficacy against the MCF-7 breast cancer cell line, as opposed to binary metal complexes. The binding orientation or conformation of the free BHX ligand and Co(II) complex in the active region of the protein of crystal structure of Escherichia coli (PDB ID: 3T88) and Pseudomonas aeruginosa (PDB ID: 6NE0) has been performed using molecular docking studies.

Results

The BHX ligand coupled in neutral bidentate mode to the metal ions, according to FT-IR and ¹H-NMR spectral results. The molar conductivity measurements of the complexes in DMF proved the electrolytic nature of all binary complexes. Co(II) complex showed the highest inhibition zone diameter against S. aureus, E. coli and P. aeruginosa. Zn(II) complex had the greatest inhibitory effect against P. aeruginosa and B. subtilis. Also, Cd(II) chelate appeared high efficacy as antibacterial agent against Pseudomonas aeruginosa and Staphylococcus aureus.

Conclusion

All the output data conjugated to confirm the octahedral geometry of the metal complexes. The biological findings revealed that metal complexes can be more active than the free BHX ligand. Against MCF-7 cell line, Cd(II)-L complex is highly active complex (4.95 µg/mL) but BHX free drug is the most active compound (3.96 µg/mL).

Background

Sodium Benzoate (SB) is used in daily products such as drinks, juices, sauces, oils, ketchup, toothpaste, mouthwashes, cosmetics, dentifrices, and pharmaceutical products. However, SB has been implicated in gonadotoxicity even at a dosage within the safe limit. Zinc (Zn), on the other hand, has been shown to improve various fertility indices. Hence, this study was designed to explore the possible ameliorative effect of Zn on SB-induced testicular toxicity. METHODS: Animals were randomly divided into control, SB, Zn, and SB+Zn. All treatment lasted for 28 days. RESULTS: SB treatment caused a derangement in reproductive hormone levels, sperm function, and kinematics and a down-regulation of the Androgen receptor (ANDR). Also, a decrease in testicular levels of SOD, CAT, GSH, Nrf2, and HO- 1 activity and an increase in IL-1β, TNF-α, Nf-κB, and Caspase 3 were observed. These SB-induced distortions were ameliorated in SB-treated rats exposed to Zn. CONCLUSION: Our study suggests that zinc abates SB-induced testicular toxicity by modulating Nrf2/HO-1/ Nf-κB signaling and ANDR upregulation.

Purpose

While copper (Cu) is essential for biological organisms, excessive Cu can be harmful. Ferroptosis is a programmed cell death pathway, but the role of ferroptosis in renal injury induced by Cu is limited. The aim of this study was to investigate the role of ferroptosis in kidney injury in chickens and the molecular mechanism by which Cu promotes renal ferroptosis.

Materials and methods

Chicken were subjected to Cu treatment by artificially adding excess Cu to the basal diet (the Cu concentration in the diet was supplemented to 110–330 mg/kg), and the impact on kidney fibrosis, tissue structure, and ferroptosis-related molecular markers was studied. Then, the expression levels of genes and proteins related to ferroptosis, iron metabolism and ferroautophagy were detected to explore the promoting effect of Cu on ferroptosis in chicken kidney.

Main findings

Cu treatment resulted in significant fibrosis and tissue structure damage in chicken kidneys. Molecular analysis revealed a significant upregulation of LC3Ⅱ, P62, ATG5, and NCOA4, along with a decrease in FTH1 and FTL protein levels. Additionally, crucial markers of ferroptosis, including the loss of GPX4, SLC7A11, and FSP1, and an increase in PTGS2 and ACSL4 protein levels, were observed in chicken kidneys after Cu exposure.

Conclusion

Our study showed that dietary Cu excess caused kidney injury in brochickens and exhibited ferroptosis-related features, including lipid peroxidation, reduction of ferritin, and downregulation of FSP1 and GPX4. These results indicate that excess Cu can induce renal ferroptosis and lead to kidney injury in chickens. This study highlights the complex interplay between Cu ions and ferroptosis in the context of renal injury and provides a new perspective for understanding the mechanism of Cu-induced renal injury.

Background

Zinc transport proteins (ZIP and ZnT), metallothioneins (MT) and protein kinase CK2 are involved in dysregulation of zinc homeostasis in breast and prostate cancer cells. Following up our previous research, we targeted ZIP12, ZnT1, MT2A and CK2 in this study by investigating their expression levels and protein localisation.

Methods

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence confocal microscopy were employed to quantify the expression of ZIP12, ZnT1, MT2A and CK2 subunits in a panel of breast and prostate cell lines without or with extracellular zinc exposure. The cellular localisations of these target proteins were also examined by immunofluorescence confocal microscopy.

Results

In response to the extracellular zinc exposure, the gene expression was elevated for SLC39A12 (ZIP12), SLC30A1 (ZnT1) and MT2A (MT2A) in normal prostate epithelial cells (RWPE-1) in contrast to their cancerous counterparts (PC3 and DU145), whilst the gene expression was higher for SLC39A12 (ZIP12) and SLC30A1 (ZnT1) in both normal (MCF10A) and basal breast cancer cells (MDA-MB-231) compared to luminal breast cancer cells (MCF-7). At the protein level, the expression for both ZIP12 and ZnT1 was trending lower in the time course for the breast cancer cells whilst their expression was remained constant in the normal breast epithelial cells. The expression of ZIP12 in prostate cancer cells was higher than the normal prostate cells. The protein expression for CK2 α/αꞌ and CK2β was markedly higher in prostate cancer cells than the normal prostate cells. Upon extracellular zinc exposure, ZIP12 was, for the first time, conspicuously localised in the plasma membrane of breast cancer cells but not in normal breast epithelial cells and prostate cells. ZnT1 is only localised in the plasma membrane of breast cancer cells. MT2A is distinctively seen close to the plasma membrane in breast cancer cells. CK2 is also for the first time shown to be localised in proximity to the plasma membrane of breast cancer cells.

Conclusion

The findings, particularly the localisation of ZIP12 and CK2, are novel and significant for our understanding of zinc homeostasis in breast and prostate cancer cells.

Introduction

Chronic low-grade inflammation and oxidative stress are pivotal contributors to the metabolic complications associated with obesity. Selenoprotein P (SELENOP) and glutathione peroxidase 1 (GPx1) are selenoproteins involved in the reduction of reactive oxygen species and pro-inflammatory cytokines levels. Nutritional epigenomics revealed the interaction of microRNAs and nutrients with an important impact on metabolic pathways involved in obesity. However, the knowledge regarding the influence of microRNA on selenium biomarkers and its impact on metabolic pathways related to obesity remains scarce. Thus, the aim of this study was to investigate the association of plasma miR‐7‐5p expression with selenium and inflammatory biomarkers in women with overweight/obesity.

Material and methods

Anthropometric evaluations were performed and blood samples were collected for the analysis of fasting glucose, insulin, inflammatory and selenium biomarkers, and miR-7–5p expression in 54 women with overweight/obesity. Gene expression of SELENOP and GPX1 were evaluated in peripheral mononuclear blood cells.

Results

This study observed a negative correlation between SELENOP levels and miR-7–5p (rho = −0.350; p = 0.018). Additionally, it was observed that body fat (OR = 0.737; p = 0.011), age (OR = 1.214; p = 0.007), and miR‐7‐5p (OR = 0.990; p = 0.015) emerged as significant predictors of SELENOP levels.

Conclusions

In conclusion, we observed a significant inverse association between miR‐7‐5p expression and SELENOP concentration in overweight/obese women, suggesting that age and percentage of body fat are also associated.

Trial registration number

Brazilian Registry of Clinical Trials (ReBEC) number RBR-2nfy5q

Aim

The primary aim of this study was to determine the selenium (Se) and iodine (I) food concentrations and dietary intake of the population living in the Kurdish controlled region of northern Iraq. We also assessed the extent to which iodised salt contributes to dietary iodine intake.

Methodology

Foods and samples of salt and drinking water were analysed, including 300 crops samples from 40 local farms. The results, supplemented by food composition data, were used to assess dietary Se and I intake for 410 volunteers using a semi-quantitative food questionnaire. To directly investigate the nutritional status of individuals, urine samples were also collected from participants.

Results

Selenium intake was mainly supplied by protein and cereal sources. Calculated median dietary intake of Se was 62.7 µg d⁻¹ (mean = 66.3 µg d⁻¹) with c. 72 % of participants meeting or exceeding dietary reference intake recommendations for age. Median dietary intake of I, excluding salt consumption, was 94.6 µg d⁻¹ (mean 100.2 µg d⁻¹), increasing to 607.2 µg d⁻¹ when salt (of which >90 % was iodized) was included. Salt intake was estimated to be c.13.5 g d⁻¹ (5400 mg Na d⁻¹) which greatly exceeds WHO recommended intake (< 2000 mg d⁻¹ of Na). Urine iodine concentrations indicated that 98 % of school aged children had excessive iodine intake (≥300 µg L⁻¹) and 80–90 % of all study participants had above average or excessive iodine intake (≥200 µg L⁻¹).

Conclusions

Poultry and rice are the main sources of dietary Se to this population but around a third of children receive an inadequate Se intake. Fresh fruit and vegetables are the main sources of dietary I, but consumption of local foods cannot supply adequate I without iodised salt supplementation. Consumption of iodized salt well above recommended amounts is supplying this population with substantial iodine intake. Interventions to reduce salt intake would help to limit excessive iodine intake whilst also reducing cardio-vascular risks from Na consumption.

AIM:to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns.METHOD:A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression.RESULTS:A reduction of 19 % was found between each km distance from the residence and the Steel company and P₅₀ concentration of Cd, Al, and Pb (OR_P50=0.81; 95 %CI:0.67–0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (OR_P50=0.84; 95 %CI:0.70–1.01; OR_P75=1.10; 95 %CI:0.91–1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(OR_P50=1.10; 95 %CI:0.91–1.33; OR_P75=1.03; 95 %CI:0.84–1.26), in the adjusted analysis.CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.