Selenium modulates AR/IGF-1R/EGFR and TROP2 signaling pathways and improves anticancer efficacy in murine mammary carcinoma 4T1.

The micronutrient selenium (Se) has been shown to exert potential anticancer properties. This study aimed to evaluate the effects of Se (in Se yeast form) on the selenoproteins (SELENO), AR/IGF-1R/EGFR, PI3K/Akt/mTOR and Ras/Raf/ERK cascades, and immune checkpoint blockade in TNBC murine 4T1 cells. We also assessed the effects of combination treatment with chemotherapeutic doxorubicin and Se on trophoblast cell surface antigen 2 (TROP2) levels. Compared with the control groups, cells incubated with Se (0.25, 0.5, 0.75, 1.0, 1.5 µg Se/mL) have lower viability, raised intracellular Se concentrations and SELENO expression, and higher malondialdehyde products in a dose-dependent manner. Se induced the inactivation of AR/IGF-1R/EGFR and downregulation of the PI3K/Akt/mTOR and Ras/Raf/ERK signaling molecules. Se-treated cells also exhibited decreased mitochondrial membrane potential, reduced levels of the cell cycle regulatory protein cyclin D1, cancer stemness, metastatic and EMT-related markers, and increased apoptosis. Subsequently, Se treatment significantly suppressed PD-1/PD-L1 and CTLA-4 mRNA levels and proteins. Doxorubicin decreased 4T1 cell viability and TROP2 expression levels, but the addition of Se to doxorubicin contributed to further reductions. Similar responses to Se treatment were also observed in the human MDA-MB-231 and MCF-7 breast cancer cells. These results show that Se upregulates SELENO and anti-AR/IGF-1R/EGFR signaling in TNBC cells, thus inducing oxidative stress-dependent apoptosis and cell cycle arrest, stemness, EMT, and metastasis, as well as blocking the immune checkpoint molecules. TROP2 down-regulation with Se is also a potential anti-TNBC therapeutic target.

Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors.

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model.

Selenium (Se) and fish oil (FO) exert anti-epidermal growth factor receptor (EGFR) action on tumors. This study aimed to compare the anti-cancer efficacy of EGFR inhibitors (gefitinib and erlotinib) alone and in combination with nutritional supplements of Se/FO in treating lung cancer. Lewis LLC1 tumor-bearing mice were treated with a vehicle or Se/FO, gefitinib or gefitinib plus Se/FO, and erlotinib or erlotinib plus Se/FO. The tumors were assessed for mRNA and protein expressions of relevant signaling molecules. Untreated tumor-bearing mice had the lowest body weight and highest tumor weight and volume of all the mice. Mice receiving the combination treatment with Se/FO and gefitinib or erlotinib had a lower tumor volume and weight and fewer metastases than did those treated with gefitinib or erlotinib alone. The combination treatment exhibited greater alterations in receptor signaling molecules (lower EGFR/TGF-ß/TßR/AXL/Wnt3a/Wnt5a/FZD7/ß-catenin; higher GSK-3ß) and immune checkpoint molecules (lower PD-1/PD-L1/CD80/CTLA-4/IL-6; higher NKp46/CD16/CD28/IL-2). These mouse tumors also had lower angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastases, and proliferation of Ki-67, as well as higher cell cycle arrest and apoptosis. These preliminary results showed the Se/FO treatment enhanced the therapeutic efficacies of gefitinib and erlotinib via modulating multiple signaling pathways in an LLC1-bearing mouse model.

Denoising Autoencoder-Based Feature Extraction to Robust SSVEP-Based BCIs.

For subjects with amyotrophic lateral sclerosis (ALS), the verbal and nonverbal communication is greatly impaired. Steady state visually evoked potential (SSVEP)-based brain computer interfaces (BCIs) is one of successful alternative augmentative communications to help subjects with ALS communicate with others or devices. For practical applications, the performance of SSVEP-based BCIs is severely reduced by the effects of noises. Therefore, developing robust SSVEP-based BCIs is very important to help subjects communicate with others or devices. In this study, a noise suppression-based feature extraction and deep neural network are proposed to develop a robust SSVEP-based BCI. To suppress the effects of noises, a denoising autoencoder is proposed to extract the denoising features. To obtain an acceptable recognition result for practical applications, the deep neural network is used to find the decision results of SSVEP-based BCIs. The experimental results showed that the proposed approaches can effectively suppress the effects of noises and the performance of SSVEP-based BCIs can be greatly improved. Besides, the deep neural network outperforms other approaches. Therefore, the proposed robust SSVEP-based BCI is very useful for practical applications.

Combination of Fish Oil and Selenium Enhances Anticancer Efficacy and Targets Multiple Signaling Pathways in Anti-VEGF Agent Treated-TNBC Tumor-Bearing Mice.

Fish oil (FO) and selenium (Se) possess antiangiogenic potential in malignant tumors. This study aimed to determine whether combination of FO and Se enhanced treatment efficacy of low-dose antiangiogenic agent Avastin (bevacizumab) in a dose-dependent manner and targeted multiple signaling pathways in triple-negative breast cancer (TNBC)-bearing mice. Randomized into five groups, mice received treatment with either physiological saline (control), Avastin alone, or Avastin in combination with low, medium, and high doses of FO/Se. The target signaling molecules for anticancer were determined either by measuring protein or mRNA expression. Avastin-treated mice receiving FO/Se showed lower tumor growth and metastasis than did mice treated with Avastin alone. Combination-treated mice exhibited lower expressions in multiple proangiogenic (growth) factors and their membrane receptors, and altered cytoplasmic signaling molecules (PI3K-PTEN-AKT-TSC-mTOR-p70S6K-4EBP1, Ras-Raf-MEK-ERK, c-Src-JAK2-STAT3-TMEPAI-Smad, LKB1-AMPK, and GSK3ß/ß-catenin). Dose-dependent inhibition of down-stream targets including epithelial-to-mesenchymal transition transcription factors, nuclear cyclin and cyclin-dependent kinases, cancer stem cell markers, heat shock protein (HSP-90), hypoxia-inducible factors (HIF-1α/-2α), matrix metalloprotease (MMP-9), and increased apoptosis were observed. These results suggest that combination treatment with FO and Se increases the therapeutic efficacy of Avastin against TNBC in a dose-dependent manner through multiple signaling pathways in membrane, cytoplasmic, and nucleic targets.

Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer.

The potential anti-cancer properties of selenium (Se) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) have been documented. However, few studies have been conducted examining anti-tumor effects of nutritional supplements (NS) containing Se and EPA/DHA in combination with anti-cancer agents, such as taxol (Tax), adriamycin (Adr), and avastin (Ava). Compared with triple-negative breast cancer (TNBC)-bearing positive control (TB) mice, a low dose of Tax, Adr, and Ava decreased tumor size and the incidence of metastasis in TB-Tax, TB-Adr, and TB-Ava groups. Combination treatment with anti-cancer agent and NS (2.7 µg Se and 5.1 mg EPA/3.7 mg DHA/g) induced additional decreases in TB-Tax-NS, TB-Adr-NS, and TB-Ava-NS groups. Th1-associated cytokines were increased, and Th2-type cytokines were decreased significantly in TB mice with combination treatment than that of anti-cancer agent treatment alone. Combination treatment with anti-cancer agents and NS has also been shown to further increased tumor malondialdehyde (MDA) levels, lowered hypoxia-inducible factor (HIF)-1α, angiogenic markers (vascular endothelial growth factor [VEGF] and CD31) and metastatic potential, as well as reduced heat shock proteins, receptor tyrosine kinase AXL, and surface markers of cancer stem cells, and increased apoptotic proteins. For immune checkpoint molecules, combination treatment was associated with a greater decrease in programmed cell death ligand-1 (PD-L1) in both tumors and mammary glands, but PD-1 level in primary tumors was increased. Our results suggest that combination treatment with low-dose anti-cancer agents (Tax, Adr, and Ava) and oral supplementation of Se/ EPA/DHA significantly decreased tumor growth and metastatic progression in TNBC mice through multiple anti-tumor mechanisms.

Effects of C/N ratio on nitrate removal and floc morphology of autohydrogenotrophic bacteria in a nitrate-containing wastewater treatment process.

The effects of C/N ratio of a nitrate-containing wastewater on nitrate removal performed by autohydrogenotrophic bacteria as well as on the morphological parameters of floc such as floc morphology, floc number distribution, mean particle size (MPS), aspect ratio and transparency were examined in this study. The results showed that the nitrate reduction rate increased with increasing C/N ratio from 0.5 to 10 and that the nitrogen removal of up to 95% was found at the C/N ratios of higher than 5 (between 0.5-10). Besides, high C/N ratio values reflected a corresponding high nitrite accumulation after 12-hr operation, and a fast decreasing rate of nitrite in the rest of operational time. The final pH values increased with the C/N ratio increasing from 0.5 to 2.5, but decreased with the C/N ratio increasing from 2.5 to 10. There were no significant changes in floc morphology with the MPSs ranging from 35 to 40µm. Small and medium-sized flocs were dominant in the sludge suspension, and the number of flocs increased with the increasing C/N ratios. Furthermore, the highest apparent frequency of 10% was observed at aspect ratios of 0.5 and 0.6, while the transparency of flocs changed from 0.1 to 0.7.

Uptake of BDE-209 on zebrafish embryos as affected by SiO2 nanoparticles.

It was hypothesized that interactions between emerging contaminants such as decabromodiphenyl ether (BDE-209) and nanoparticles (NPs) such as nano-SiO2 (nSiO2), can affect contaminant transport in the aquatic environment and its ecotoxicity. This study assessed the influence of nSiO2 on the uptake of BDE-209 by zebrafish embryo. The distribution of BDE-209 and nSiO2 on the external chorion and the internal embryo mass (i.e., dechorionated embryo) was measured. For single exposure of nSiO2 to zebrafish embryo, separately, results showed that nSiO2 accumulation on the chorion surface was higher than that in the dechorionated embryo. The nSiO2 accumulation on the chorion surface was 129-200 mg-nSiO2/g-chorion at 48 h post fertilization, hpf, of exposure time, whereas the equilibrium adsorption of nSiO2 on the dechorionated embryo was ca. 0.42-0.54 mg-nSiO2/g-embryo at 6 hpf. Results showed that the formation of nSiO2-BDE-209 associates promoted both extracellular and intracellular uptake of BDE-209 by zebrafish embryo, thereby increasing the bioconcentration of BDE-209 on the chorion surface and in embryo. The results also revealed that the accumulation of BDE-209 on the chorion was remarkably greater than that on the dechorionated embryo at 48 hpf. The uptake of BDE-209 was 17.2 ±â€¯0.45 mg/g-chorion (or 86 ng-BDE-209/chorionated embryo) and 0.37 ±â€¯0.01 mg/g-embryo (or 18.6 ng-BDE-209/dechorionated embryo), respectively, when co-exposure of zebrafish embryos to BDE-209 and nSiO2. Results from the SEM and EDS analysis revealed that nSiO2 already passed through the chorion and adhered to the embryo surface/mass.

Nitrate removal and extracellular polymeric substances of autohydrogenotrophic bacteria under various pH and hydrogen flow rates.

In recent years there has been an increasing interest in the use of autohydrogenotrophic bacteria to treat nitrate from wastewater. However, our knowledge about the characteristics of extracellular polymeric substances (EPS) releasing by these activities is not yet very advanced. This study aimed to investigate the change in EPS compositions under various pH values and hydrogen flow rates, taking into consideration nitrogen removal. Results showed that pH7.5 and a hydrogen flow rate of 90mL/min were the optimal operating conditions, resulting in 100% nitrogen removal after 6hr of operation. Soluble and bound polysaccharides decreased, while bound proteins increased with increasing pH. Polysaccharides increased with increasing hydrogen flow rate. No significant change of bound proteins was observed at various hydrogen flow rates.

Optical properties of algogenic organic matter within the growth period of Chlorella sp. and predicting their disinfection by-product formation.

Algogenic organic matter (AOM) in eutrophic waters is a well-known precursor to disinfection by-product (DBP) formation in drinking water. This purpose of this study is (i) to characterize the optical properties of AOM origins, including intra- (IOM) and extra-cellular organic matter (EOM), derived from Chlorella sp. growth as precursors to two major carbonaceous DBPs (C-DBPs), trihalomethanes (THMs) and haloacetic acids (HAAs) and (ii) to correlate these optical properties with THM and HAA formation potential (FP) in order to predict DBP formation. The results show that both EOM and IOM had low UV254 and UV280 absorbance during their entire growth phase. While IOM chiefly comprised of aromatic proteins and soluble microbial products-like substances (80% of average fluorescent intensity-AFI), EOM spectra were rich in humic- and fulvic-like substances (60% AFI). However, its chemical nature likely differed from terrestrial humics. In DBPFP tests, IOM was a higher-yielding precursor of THMs and HAAs compared to EOM, regardless its growth status. Consequently, C-DBPFP of IOM was always higher than EOM during four growth phases. Results from DBP tests also showed insignificant variation of EOM-derived THMFP and HAAFP during the algal growth phase, while the algal growth status strongly influenced the yields of IOM-derived THMFP and HAAFP. From correlation analysis, our results showed no correlation between UV absorbance with THMFP and HAAFP. Conversely, the regional AFI showed a good correlation with HAAFP and C-DBPFP. Predicting models based on AFI for the formation of HAAs and C-DBPs consequently yielded great predictability for laboratory AOM-containing water samples, with a coefficient of determination R2=0.879, p<0.01 and R2=0.846, p<0.01. This study indicates a promising application of fluorescent spectra for predicting DBPs derived from algae-rich water sources.

Teratogenic responses of zebrafish embryos to decabromodiphenyl ether (BDE-209) in the presence of nano-SiO2 particles.

This study investigated the influence of nano-SiO2 particles (nSiO2) on the teratogenic responses of zebrafish embryos to decabromodiphenyl ether (BDE-209). Zebrafish embryos were exposed to BDE-209 in the absence and presence of nSiO2 for 96 h post fertilization (hpf). Results showed that formation of nSiO2-BDE-209 associates promoted both extracellular and intracellular uptake of BDE-209 by zebrafish embryos, thereby increasing the bioconcentration of BDE-209 on the chorion surface and the embryos. Results also showed embryos delay hatching temporarily when co-exposure to BDE-209 and nSiO2 at 60 hpf. Furthermore, there was heartbeat decline (28.3 beats/10s) and increase in irregular heartbeat (45.8%) in zebrafish larvae at 96 hpf, compared to the sole exposure to BDE-209 (32.7 beats/10s and 0%). Malformation in terms of spinal curvature (SC), pericardial edema (PE) and yolk sac edema (YSE) were observed on zebrafish larvae at 33.9, 23.4, and 18%, respectively. Overall, abnormal development of zebrafish was apparent when co-exposure to BDE-209 and nSiO2. All relevant evidence considered, nSiO2 could facilitate the transport of BDE-209 towards zebrafish embryos and negatively impact the development of zebrafish.

Supplementation with Selenium yeast on the prooxidant-antioxidant activities and anti-tumor effects in breast tumor xenograft-bearing mice.

Selenium (Se) is essential for antioxidant activity involved in immune function and anti-carcinogenic action, whereas at higher concentrations, Se may have pro-oxidant properties. The present study was aimed at determining the effects of Se supplementation, as Se yeast, on oxidative stress in non-tumor/tumor tissues, as well as regulation of the apoptotic process, and immune responses in mice-bearing breast tumor xenografts. Female BALB/cByJNarl mice were divided into control (CNL and CNL-con), Se-supplemented control (CNL-HS, given as a single oral dose of 912 ng Se daily), breast tumor-bearing (TB and TB-con), TB-LS (228 ng Se), TB-MS (456 ng Se) and TB-HS (912 ng Se) groups. All mice were treated with/without Se for 14 days. A number of variables were further measured. Compared with the TB groups, tumor bearing mice with Se supplement had increased plasma Se concentrations, reduced erythrocyte Se-dependent glutathione peroxidase (GPx) activity and malondialdehyde (MDA) products and inhibited tumor growth. They have also higher Se concentrations in non-tumor and tumor tissues. Significantly elevated concentrations of MDA and reduced GPx activities, as well as increased anti-apoptotic bcl-2 and tumor suppressor p53 concentrations in tumor tissues were observed as Se accumulated in tumor, whereas lower MDA products were found in various non-tumor tissues than did the corresponding values. Further, there were elevated concentrations of Th1-derived cytokines and decreased Th2-type interleukin (IL)-4 in tumor-bearing mice with the treatment of Se. In conclusion, accumulation of Se in tumors may induce oxidative stress and p53-dependent pro-oxidative apoptosis, thus inhibiting the growth of breast tumor.

Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition, and Apoptosis in Human Breast Cancer Cells.

Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells.

A stabilization device that promotes the efficiency of cardiopulmonary resuscitation during ambulance transportation to the level as under non-moving conditions.

BACKGROUND: The survival rate of patients with out-of-hospital cardiac arrest is low, and measures to improve the quality of cardiopulmonary resuscitation (CPR) during ambulance transportation are desirable. We designed a stabilization device, and in a randomized crossover trial we found performing CPR in a moving ambulance with the device (MD) could achieve better efficiency than that without the device (MND), but the efficiency was lower than that in a non-moving ambulance (NM). PURPOSE: To evaluate whether a modified version of the stabilization device, can promote further the quality of CPR during ambulance transportation. METHODS: Participants of the previous study were recruited, and they performed CPR for 10 minutes in a moving ambulance with the modified version of the stabilization device (MVSD). The primary outcomes were effective chest compressions and no-flow fraction recorded by a skill-reporter manikin. The secondary outcomes included back pain, physiological parameters, and the participants' rating about the device after performing CPR. RESULTS: The overall effective compressions in 10 minutes were 86.4±17.5% for NM, 60.9±14.6% for MND, 69.7±22.4% for MD, and 86.6%±13.2% for MVSD (p<0.001). Whereas changes in back pain severity and physiology parameters were similar under all conditions, MVSD had the lowest no-flow fraction. Differences in effective compressions and the no-flow fraction between MVSD and NM did not reach statistical significance. CONCLUSIONS: The use of the modified device can improve quality of CPR in a moving ambulance to a level similar to that in a non-moving condition without increasing the severity of back pain.

Arsenic, cadmium, lead, and aluminium concentrations in human milk at early stages of lactation.

BACKGROUND: Human milk is considered to be the best nutrition for all infants because it provides the optimal source of nutritional, immunological, developmental, psychological, economic, practical, and environmental benefits in both the short and long terms. To the best of our knowledge, few studies in Taiwan have examined the toxicant levels in breast milk and associated factors. METHODS: The research was carried out over a 6-month period. Forty-five healthy lactating women, who delivered full-term newborns at our maternity ward, were recruited, and all participants had been living in coastal urban areas of mid-Taiwan for at least 3 years. One hundred and eighty human milk samples were collected on four occasions, which were classified into four lactation stages as follows: colostrums, transitional milk, early mature milk, and mature milk. RESULTS: We found that lead, cadmium, aluminium, and arsenic concentrations were the highest in colostrums: 13.22 ± 3.58 ng/mL, 1.37 ± 0.94 ng/mL, 56.45 ± 22.77 ng/mL, and 1.50 ± 1.50 ng/mL, respectively. The results of lead, cadmium, aluminium, and arsenic determination in human milk samples demonstrated a trend of decline of microelement concentrations with advancing stages of lactation. We found that the infants of smoking mothers were exposed to more cadmium than infants of nonsmoking mothers (p < 0.05). CONCLUSION: According to our findings, frequent routine sampling of breast milk is worthwhile. Prevention strategies including behavior modification and education on proper nutrition should be provided to women who are at high risk of toxicant exposure. In summary, breastfeeding is still generally encouraged and recommended.

A stabilization device to improve the quality of cardiopulmonary resuscitation during ambulance transportation: a randomized crossover trial.

BACKGROUND: The quality of cardiopulmonary resuscitation (CPR) during ambulance transportation is suboptimal, and therefore measures that can improve the quality are desirable. PURPOSE: To evaluate whether the use of a stabilization device can improve the quality of CPR during ambulance transportation. METHODS: This randomized controlled crossover trial enrolled 22 experienced ambulance officers. Each participant performed CPR in an ambulance under three conditions with 72 h apart, each condition for 10 min: non-moving (NM), moving without device (MND), and moving with device (MD). The sequences of conditions were randomized. The primary outcomes were effective chest compressions recorded by the Laerdal Resusci-Anne Skill-reporter manikin. The secondary outcomes included the severity of back pain scored using the Brief Pain Inventory short-form, the physiology parameter before and after CPR, and the changes in postural stability which was represented by the sway index (SI) of lower back measured using a goniometer. RESULTS: The overall effective compressions in 10 min were 87.0±17% for NM, 59.0±19% for MND, and 69.0±23% for MD (p<0.001). Compared to MND, MD had a lower no-flow fraction while driving on curved sections (0.04 vs. 0.29, p<0.001). Whereas the pain severity and social interference scores were similar under all conditions, MND had a higher SI than MD and NM. CONCLUSIONS: The use of a stabilization device can improve the quality of CPR and posture stability during ambulance transportation, although the effects on the severity of back pain were not significant.

Status of essential trace minerals and oxidative stress in viral hepatitis C patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may be an important factor leading to altered trace mineral homeostasis, thereby accelerating the progression of hepatitis C virus (HCV) infection. Our aim was to determine whether NAFLD influenced the status of certain essential trace minerals and oxidative stress in chronic HCV-infected patients. DESIGN AND METHODS: Blood biochemical parameters were determined in a group of 30 healthy, non-obese, non-diabetic participants (CNL group), and hepatitis C patients without NAFLD (HCV group, n = 30) and with NAFLD (HCV-NAFLD group, n = 32). RESULTS: Concentrations of thiobarbituric acid reactive substances (TBARS; a measure of oxidative stress), C-reactive protein (CRP), ferritin, aminotransferases, lipid profiles, and insulin metabolism were markedly abnormal in both patient groups than in CNL subjects. Compared to patients in the HCV group, those with HCV-NAFLD group had lower high-density lipoprotein concentrations, higher low-density lipoprotein and homeostasis model assessment-insulin resistance (HOMA-IR) values, disrupted antioxidant enzyme activities, and elevated TBARS concentrations, as well as decreased plasma concentrations of trace minerals zinc (Zn) and selenium (Se) and increased copper (Cu). The alterations in mineral homeostasis were also linked to TBARS, CRP, ferritin, lipoproteins, and HOMA-IR values in the HCV-NAFLD group. CONCLUSIONS: There is a progressive deterioration in the homeostasis of minerals (Zn, Se, and Cu) in HCV-NAFLD patients, which may reflect greater oxidative stress and inflammation. These results suggest that the disturbance in mineral metabolism by NAFLD has an impact on the effectiveness of treatment for chronic HCV infection.

Zinc supplementation alters plasma aluminum and selenium status of patients undergoing dialysis: a pilot study.

End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentrations of certain essential and non-essential trace metals and high oxidative stress. We evaluated the effects of zinc (Zn) supplementation on plasma aluminum (Al) and selenium (Se) concentrations and oxidative stress in chronic dialysis patients. Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentrations (HA group, Al > 50 g/L; and MA group, Al > 30 to ≤ 50 g/L). All patients received daily oral Zn supplements for two months. Age- and gender-matched healthy individuals did not receive Zn supplement. Clinical variables were assessed before, at one month, and after the supplementation period. Compared with healthy subjects, patients had significantly lower baseline plasma Se concentrations and higher oxidative stress status. After two-month Zn treatment, these patients had higher plasma Zn and Se concentrations, reduced plasma Al concentrations and oxidative stress. Furthermore, increased plasma Zn concentrations were related to the concentrations of Al, Se, oxidative product malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase activities. In conclusion, Zn supplementation ameliorates abnormally high plasma Al concentrations and oxidative stress and improves Se status in long-term dialysis patients.

Distribution of selenium and oxidative stress in breast tumor-bearing mice.

The present study investigated the effects of breast tumors on the blood and tissue distribution of essential trace mineral selenium (Se), and oxidative stress status of mice. Female 10-week-old BALB/cByJNarl mice were randomly assigned into control (CNL) and breast tumor-bearing (TB) groups. TB mice were injected subcutaneously into the right hind thigh with 5 × 10(6) EMT6 mouse mammary tumor cells. After 22 days, we measured Se concentrations, Se-dependent glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) products (indicator of oxidative stress) in plasma, various tissues, and plasma vascular endothelial growth factor (VEGF) concentrations. There were no significant differences in body weights and daily intake between both groups. Compared with the CNL group, TB mice have decreases in plasma Se concentrations and GPx activities, as well as higher plasma VEGF and MDA concentrations. Plasma Se concentrations were also negatively correlated with plasma MDA and VEGF concentrations. Furthermore, tissue Se concentrations and GPx activities in TB animals were lower; whereas the MDA concentrations higher in various tissues including liver, kidney, brain, lung, spleen, and thymic tissues. In conclusion, disruption of Se homeostasis critically reflects oxidative stress in target tissues, thus may increase the risk for progression of breast cancer and metastasis.

The relationship of plasma aluminum to oxidant-antioxidant and inflammation status in asthma patients.

Aluminum (Al) is a non-essential mineral which human beings are exposed to on day-to-day life. The purpose of this study was to assess the concentrations of plasma Al and the relationship of those levels with risk factors for asthma. In total, 27 allergic asthmatics and 30 healthy volunteers were enrolled. Plasma Al and selected blood parameters were measured, and a pulmonary function test was performed. Higher Al concentrations were found in the asthmatics than the healthy controls. Increased immunoglobulin E, high-sensitivity C-reactive protein, lipid peroxidation products, and pro-inflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-4) were observed, but IL-10 and overall antioxidant and enzyme activities were lower. Associations between oxidative-antioxidant status and inflammatory markers with plasma Al levels in asthmatics were noted. Al status was also linked to cytokine concentrations and pulmonary function. In conclusion, abnormal Al distribution may further precipitate oxidative stress and inflammation, alter Th1/Th2 lymphocyte balance, and therefore contribute to the development of asthma.