Journal of Trace Elements in Medicine and Biology最新文献

Background

Acute myeloid leukemia (AML) is a hematological malignancy. The aim of this research was to develop a ferroptosis and cuproptosis related novel prognostic signature associated with AML.

Methods

The ferroptosis and cuproptosis related genes correlated with the prognosis of AML were identified by univariate Cox analysis. The consistent cluster analysis was performed for 150 AML patients in TCGA dataset. The key module genes associated with GSVA score of ferroptosis and cuproptosis were identified by WGCNA. univariate Cox and LASSO regression analysis were adopted to build a ferroptosis and cuproptosis AML prognostic signature. Finally, the expression of five prognostic genes in clinical tissue samples were verified by RT-qPCR.

Results

A grand total of 27 FCRGs associated with AML prognosis were identified.Then, two AML sub-types with significantly different survival were obtained. We found 3 significantly differential expressed immune cells (naive CD4 cells, regulatory T cells and resting mast cells) between two risk sub-groups. Meanwhile, ‘IL6 JAK STAT3 signaling’ and ‘P53 pathway’ were enriched in low-risk group. A ferroptosis and cuproptosis related prognostic signature was build based on 8 prognostic genes. RT-qPCR results indicated that there was no significant difference in the expression of OLFML2A and CD109 between AML and normal samples. However, compared to the control group, LGALS1, SOCS1, and RHOC showed significantly lower expression in the AML group.

Conclusion

The prognostic signature comprised of OLFML2A, LGALS1, ABCB11, SOCS1, RHOC, CD109, RD3L and PTPN13 based on ferroptosis and cuproptosis was established, which provided theoretical basis for the research of AML.

Background

Cadmium (Cd) is an environmental pollutant and a heavy metal known for its genotoxic effects, which can lead to cancer and other related diseases. Preventing Cd-induced genotoxicity is crucial; however, there is limited research on this topic. Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., is a popular medicinal compound with several health benefits. Nevertheless, its therapeutic effect on Cd-induced genotoxicity remains unexplored.

Methods

Human fetal lung fibroblasts were treated with 20 μM Cd²⁺ (CdCl₂) for 12 h and 5–20 μM SAL was used to test the anti-DNA damage effect. DNA damage was evaluated using γH2AX expression and the alkaline comet assay. Intracellular reactive oxygen species (ROS) levels were measured using flow cytometry.

Results

Exposure to 20 μM Cd²⁺ for 12 h induced significant DNA damage in human fetal lung fibroblasts, and this effect was notably attenuated by SAL treatment. SAL treatment did not decrease ROS levels in cells treated with Cd²⁺.

Conclusion

SAL effectively prevented Cd²⁺-induced DNA damage in human fetal lung fibroblasts. However, the underlying mechanism requires further investigation.

Background

Myocardial infarction (MI) is the result of reduced or stopped blood supply to a section of the myocardium. Regardless of its potential effectiveness in the treatment of several types of cancers, doxorubicin (DOX) capabilities are restricted because of its widespread cardiotoxic impact.

Aim

In this study, the protective effect of zinc oxide nanoparticles against doxorubicin-induced myocardial infarction in rats is examined.

Methods

Zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using X-ray diffraction, transmission electron microscope, and UV-Vis spectral analysis. A total cumulative dose of DOX (18 mg/kg body weight, i.p.) was injected once daily on days 2, 4, 6, 8, 10, and 12 (i.p.) to induce MI in rats. 24 rats were divided into 4 groups; control, MI, and MI treated with two doses of ZnO NPs (45 and 22.5 mg/kg).

Results

The treatment with ZnO NPs restored ST-segment near normal, ameliorated the changes in cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, total proteins, malondialdehyde, nitric oxide, reduced glutathione, and catalase.The histological investigation revealed that ZnO NPs treated group showed marked improvement in the examined cardiac muscle and liver in numerous sections.The lower dose of ZnO NPs (22.5 mg/kg) was significantly more effective than the higher dose (45 mg/kg).

Conclusion

The effect of ZnO NPs against doxorubicin-induced myocardial infarction in rats was assessed and the results revealed a successful cardioprotective potency through enhancing the antioxidant system and stimulating nitric oxide production in myocardial infarcted rats. This work implies that ZnO NPs could serve as promising agents for treating doxorubicin-induced cardiotoxicity.

Biomaterials intended for application in bone tissue engineering (BTE) ideally stimulate osteogenesis and angiogenesis simultaneously, as both mechanisms are of critical importance for successful bone regeneration. Mesoporous bioactive glass nanoparticles (MBGNs) can be tailored towards specific biological needs, for example by addition of ions like Molybdenum (Mo). While Mo has been shown to enhance osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as their ability to form and mature a primitive osseous extracellular matrix (ECM), there are contradictory findings regarding its impact on angiogenesis. In this study, the effects of Mo-MBGNs (mol%: 70 SiO₂, 25 CaO, 5 MoO₃) on viability, proliferation, osteogenic differentiation, ECM formation and angiogenic response of BMSCs were compared to undoped MBGNs (in mol%: 70 SiO₂, 30 CaO) and a control group of BMSCs. Furthermore, a human umbilical vein endothelial cells tube formation assay and a chorioallantoic membrane-assay using fertilized chicken eggs were used to analyze angiogenic properties. Mo-MBGNs were cytocompatible and promoted the proliferation of BMSCs. Furthermore, Mo-MBGNs showed promising osteogenic properties as they enhanced osteogenic differentiation, ECM formation and maturation as well as the gene expression and protein production of relevant osteogenic factors in BMSCs. However, despite the promising outcome on osteogenic properties, the addition of Mo to MBGNs resulted in anti-angiogenic effects. Due to the high relevance of vascularization in-vivo, the anti-angiogenic properties of Mo-MBGNs might hamper their osteogenic properties and therefore might restrict their performance in BTE applications. These limitations can be overcome by the addition of ions with distinct pro-angiogenic properties to the Mo-MBGNs-composition. Due to their promising osteogenic properties, Mo-MBGNs constitute a suitable basis for further research in the field of ionic (growth factor free) BTE.

Studies on essential trace elements in the context of Alzheimer’s disease (AD) concluded that Cu, Fe and Zn interact with amyloid-β, accelerating plaque formation in the brain. Additionally, Cu and Fe in the vicinity of plaques produce reactive oxygen species (ROS) resulting in oxidative stress, whereas Zn plays a role in the antioxidant defence as a co-factor for antioxidants. In this work, the Cu, Fe and Zn concentrations and isotope ratios were determined in whole blood, blood serum and cerebrospinal fluid of 10 patients diagnosed with AD and 8 control individuals, using tandem (ICP-MS/MS) and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), respectively. In whole blood and blood serum of AD patients, a heavier Cu isotopic composition was observed (significant for whole blood only) compared to controls. Albumin levels in cerebrospinal fluid tend to increase with age, which could indicate an increased leakiness of the blood-brain barrier. In cerebrospinal fluid, a large variability was observed for the Cu and Fe isotope ratios, potentially resulting from that leakiness at the blood-brain barrier. Therefore, potential effects of AD on the concentration and isotopic composition of essential elements in cerebrospinal fluid related to amyloid-β formation could be hidden. Finally, in blood serum, Zn, urea and creatinine concentrations showed an increase with age and showed a significant difference between sexes.

Background

We aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators.

Methods

We conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation.

Results

Subjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (> 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (< 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT.

Conclusions

Lower levels (< 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects.

Cadmium (Cd) is an environmental pollutant heavy metal with nephrotoxic effect. One of the primary constituents of essential oils is Linalool (Lin), a monoterpene having a variety of pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant effects. The purpose of this study was to ascertain how Lin affected endoplasmic reticulum stress (ERS) and pro-inflammatory mediators in Cd-induced nephrotoxicity. In the experiment, 28 male rats were randomly divided into four equal groups as control (no application), Cd (Cd at a dose of 3 mg/kg for the first 7 days), Cd+Lin (Cd at a dose of 3 mg/kg for the first 7 days and 100 mg/kg/day Lin) and Lin (100 mg/kg/day Lin) (n=7). The experiment was completed on the 15th day after all treatments were performed. Blood serum and kidney tissue samples were used for analyses. Cd-induced histopathological changes, inflammation, oxidative stress, and apoptosis were determined to increase in kidney tissue. However, it was observed that Cd-induced adverse effects in kidney tissue were mainly eliminated by Lin treatment. In conclusion, Lin demonstrated anti-inflammatory, anti-oxidant and anti-apoptotic effects in Cd-induced nephrotoxicity. Therefore, we believe that Lin may represent a high potential therapeutic strategy against renal tissue damage.

Summary

This study highlights the potential neurotoxic and impaired behavioral effects associated with high fluoride concentrations in drinking water.

Purpose

Fluoride is known to cause neurotoxicity, evinced by lower I.Q. levels in children from high-fluoride regions as compared to those in low-fluoride regions. Thus, the present study was designed to investigate the molecular mechanism behind the neurological and behavioural changes induced by sodium fluoride in Wistar rats.

Material and methods

A total of 24 female Wistar rats, aged six weeks and weighing approximately 150–220 g, were randomly divided into three groups: Group I (control) received reverse osmosis (R.O.) water, Group II received Sodium Fluoride (NaF) at 10 ppm, and Group III received NaF at 50 ppm in their drinking water for 60 days. The animals underwent behavioural tests including the Forced Swim Test (F.S.T.), Open Field Test (OFT), and Novel Object Recognition Test (N.O.R.T.), to assess any alterations in behaviour. After 60 days, the animals were euthanized, and their blood and brain samples were analysed to evaluate biochemical changes by Western Blot/I.H.C. analysis of B.A.X., Bcl2, LC3B, TLR4, PARP1, p53, Caspase, α-Synuclein, PARKIN, NeuN, KI67, DNM-1, and M.F.N. for assessing molecular pathways for toxicity.

Results

Impaired locomotion, memory impairment, and behaviour resembling depression in the animals were evinced by reduced mobility index in the F.S.T., discrimination index in the N.O.R.T., and reduced locomotor activity in the open field test results. Additionally, alterations in antioxidant levels and oxidative stress parameters were observed in the brain. The expression levels of various apoptotic and inflammatory biomarkers (B.A.X., Bcl2, TLR4, PARP1, p53, and Caspase) showed apoptosis in neurons. The confocal studies showed increased expression of inflammatory (α-Synuclein, PARKIN), apoptotic (LC3B, B.A.X., p53, KI67), and mitochondrial dysfunction (NeuN, DNM-1, M.F.N.) markers in fluoride-treated animals. Toxicity was more prominent in 50 ppm of fluoride-treated animals.

Conclusion

Fluoride showed potent neuronal toxicity as evidenced by alterations of various molecular markers.

Background

Cadmium, a metal implicated in environmental toxicity, is linked to tumor growth and cancer. On the other hand, zinc plays an essential function in oxidative stress and can counteract cadmium toxicity and carcinogenicity. This research aims to evaluate the urine and serum values of cadmium and zinc in breast cancer (BC) patients and their association with estrogen (ER) and HER-2 receptors, and redox status.

Methods

Forty BC patients and thirty healthy subjects participated in this study. Cadmium and zinc levels were measured in serum and urine samples by atomic absorption spectrophotometer. Redox status markers were determined by colorimetric methods.

Results

The amount of cadmium in the BC patients was substantially greater than in the healthy subjects. Zinc levels were significantly lower in patients with BC compared to controls. Breast cancer patients with ER-positive tumors had significantly higher urinary cadmium concentrations (U-Cd) compared to patients with ER-negative tumors. There was no significant difference between the parameters of redox status and the value of cadmium and zinc between patients with BC in the HER-2 subgroup. Malondialdehyde levels in the serum were substantially greater in BC patients than in healthy subjects. Total thiol level and catalase and superoxide dismutase activity in serum were considerably lower in BC patients than in healthy subjects.

Conclusions

The etiology of BC may be due to a disturbance in redox status and levels of elements. Increasing U-Cd and lowering zinc levels in the serum could be the risk factors for BC.