Journal of Trace Elements in Medicine and Biology最新文献

Background

Selenium (Se) is an essential micronutrient, important for human health. The relationship of Se with cardiovascular risk factors is still inconclusive, especially regarding the role of different selenoproteins. The present study evaluated the relation of total serum Se as well as its distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3) and selenoprotein P (SelP) with cardiovascular risk factors in a sex-specific manner, in a healthy population with moderate levels of Se. Methods: A sub-sample from the ATTICA Study’s database, consisting of 398 participants (160 females and 238 males) with data on Se and selenoproteins levels, was considered. GPx3, SelP and the main non-specific serum selenium containing protein, selenoalbumin (SeAlb) were simultaneously determined in human plasma by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. Results: Participants that belong to the highest tertiles of GPx3 and SelP presented the lowest blood pressure. Homocysteine was inversely associated with SelP and its ratio SelP/TSe in both sexes. In males, the lowest tertile of GPx3 showed lower adiponectin levels (0.66 ± 0.21 μg/mL) in comparison to the 2nd tertile of GPx3 (p=0.002), SelP was inversely associated with visceral adipose index (VAI) (-2.29 ± 0.81, p=0.005). Particularly, in males, the middle tertile of SelP had the lowest VAI values. Regarding females, lower Lp(a) concentration by 11.96 ± 5.84 mg/dL was observed in low SelP levels while higher leptin concentration by 2.30 ± 0.73 μg/L and lower fibrinogen concentration by 27.32 ± 13.30 mg/dL was detected in low GPx3 levels. Conclusion: Circulating selenoproteins exert differentiated effects on cardiovascular risk factors, some of them in a sex-specific manner.

Background

Recent studies indicated that the liver is susceptible to Cu-induced stress as it stores and distributes the metal to other cellular organelles. To counteract the hepatocytic damage, a known polyphenol, quercetin, was employed for its remarkable antioxidant properties. Thus, the study aimed to assess quercetin’s potency against Cu-induced toxicity in HEPG2 cells.

Methods

The cellular viability of HEPG2 cells was carried out by MTT assay. All the cellular experiments were divided into control, Cu 100 µM, Cu 100 µM (with Q μM), Cu 300 µM, Cu 300 µM (with Q 50 nM), and only quercetin (50 nM). Following this, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in co-exposure studies. Moreover, rhodamine-123, Hoechst stain, monodansylcadaverine (MDC), and acridine orange (AO) stain were used to visualize the morphological changes under bright field and fluorescent microscopy. Subsequently, western blotting was adopted to determine the expression level of apoptotic and autophagic marker proteins.

Results

Copper increased intracellular ROS, resulted in morphological abnormalities, nuclear condensation, and disrupted MMP. Moreover, Cu caused apoptotic cell deaths characterized by overexpressed pro-apoptotic proteins such as poly (ADP-ribose) polymerase (PARP), cysteine-dependent aspartate-specific proteases 3 (Caspase 3), and Bcl-2-associated X protein (Bax) and downregulated anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), respectively. However, quercetin restored overexpressed pro-apoptotic proteins and induced autophagosome-bound microtubule-associated protein light chain-3 (LC3II) conversion from LC3I. Furthermore, Cu-modulated autophagy marker proteins, including sequestosome-1 (p62), heat shock cognate proteins (Hsc 70, Hsc 90), lysosome-associated membrane protein (LAMP-2A), and AMP-associated protein kinase (AMPK).

Conclusion

This study promotes the nutraceutical ability of quercetin to combat Cu-induced hepatotoxicity by understanding the intricate biological signaling pathways within cells.

Inorganic arsenic (iAs)-induced urothelial carcinoma (UC) develops into a poor-prognosis malignancy. Arsenic-induced oxidative stress contributes to circadian rhythm disruption altered metabolism. Glutamine anaplerosis is a common metabolic feature of rapidly proliferating malignant cells, in which glutaminase (GLS) is a key enzyme in this process. Therefore, this study intends to determine if arsenic-induced oxidative stress can alter circadian rhythms and promote glutamine anaplerosis. Exonic expression of core circadian molecules (CLOCK, ARNTL, and NR1D1) and GLS in varying grades of UC were assessed using 423 bladder cancer samples from the TCGA Urothelial Bladder Cancer (BLCA) dataset. The levels of circadian proteins and metabolic markers in 44 UC patients from non-black foot disease (BFD) and BFD areas were detected by immunohistochemistry. In vitro and in vivo experiments elucidated the regulatory mechanisms of arsenic-mediated circadian disturbance and metabolic alteration. Public database analysis showed that ARNTL, NR1D1, and GLS exhibited greater expression in more high-grade UC. Strong immunoreactivity for BMAL1, GLS, and low levels of NR1D1 were found in malignant urothelial lesions, especially in arsenic-exposed UC. Arsenic-induced overexpression of BMAL1 and GLS involves activation of NADH: quinone oxidoreductase 1 (NQO1), continuously altering the NADH oscillations to promote glutamate metabolism in SV-HUC-1, T24 and BFTC-905 cells. These phenomenon were also demonstrated in the urothelium of arsenic-exposed animals. The present findings highlight the potential clinical significance of BMAL1 and GLS in UC in the BFD region. Furthermore, these results suggest that arsenic interferes with circadian rhythm and glutamine anaplerosis by NADH oscillatory imbalance in urothelial cells and urothelial cancer cells, predisposing them to malignant development.

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.