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Factors associated with longitudinal changes in serum concentrations of Mac-2 binding protein: A prospective 3-year observational study.
Sugiura, T, Dohi, Y, Takase, H, Yamashita, S, Tsuzuki, Y, Ogawa, S, Tanaka, Y, Ohte, N
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(12):1337-1344
Abstract
BACKGROUND AND AIMS Mac-2 binding protein (M2BP) plays an important role in cell adhesion. In a recent cross-sectional study we reported that serum M2BP concentrations may reflect silent atherosclerosis. The aim of the present prospective follow-up study was to investigate possible relationships between changes in concentrations of M2BP and other factors over a >3-year period. METHODS AND RESULTS The present study enrolled subjects who visited Enshu hospital from 2014 to 2015 for a periodic physical check-up and then attended for another physical check-up after >3 years (n = 174). Factors affecting changes in M2BP concentrations were investigated at both baseline and follow-up. Subjects with liver dysfunction, a history of hepatic disease, malignant neoplasm, or cardiovascular events at baseline were excluded. Univariate and multivariate regression analyses showed that changes in serum M2BP concentrations during the follow-up period were significantly associated with changes in low-density lipoprotein cholesterol (LDL-C), triglyceride, and oxidative stress marker derivatives of reactive oxygen metabolites (d-ROM) concentrations. Moreover, the increase in LDL-C was significantly greater in subjects in whom M2BP concentrations increased during the follow-up period. Logistic regression analysis with an endpoint of increased M2BP revealed that increased LDL-C was an independent determinant of an increase in M2BP during the follow-up period. CONCLUSION During the observation period of >3 years, serum M2BP concentrations were increased in subjects who also exhibited increases in levels of metabolic parameters, especially LDL-C, and the oxidative stress marker d-ROM. These results support that serum M2BP reflects one of the contributors to the progression of silent atherosclerosis.
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Circulating microRNA-21 is an early predictor of ROS-mediated damage in subjects with high risk of developing diabetes and in drug-naïve T2D.
La Sala, L, Mrakic-Sposta, S, Tagliabue, E, Prattichizzo, F, Micheloni, S, Sangalli, E, Specchia, C, Uccellatore, AC, Lupini, S, Spinetti, G, et al
Cardiovascular diabetology. 2019;(1):18
Abstract
BACKGROUND Impaired glucose tolerance (IGT) is a risk factor for the development of diabetes and related complications that ensue. Early identification of at-risk individuals might be beneficial to reduce or delay the progression of diabetes and its related complications. Recently, microRNAs emerged as potential biomarkers of diseases. The aim of the present study was to evaluate microRNA-21 as a potential biomarker for the risk of developing diabetes in adults with IGT and to investigate its downstream effects as the generation of reactive oxygen species (ROS), the induction of manganese-superoxide dismutase-2 (SOD2), and the circulating levels of 4-HNE (4-hydroxynonenal). METHODS To evaluate the prognostic and predictive values of plasmatic microRNA-21 in identifying metabolic derangements, we tested a selected cohort (n = 115) of subjects enrolled in the DIAPASON Study, whom were selected on ADA criteria for 2hPG. Statistical analysis was performed using ANOVA or the Kruskal-Wallis test as appropriate. ROC curves were drawn for diagnostic accuracy of the tests; positive and negative predictive values were performed, and Youden's index was used to seek the cut-off optimum truncation point. ROS, SOD2 and 4-HNE were also evaluated. RESULTS We observed significant upregulation of microRNA-21 in IGT and in T2D subjects, and microRNA-21 was positively correlated with glycaemic parameters. Diagnostic performance of microRNA-21 was high and accurate. We detected significant overproduction of ROS by electron paramagnetic resonance (EPR), significant accumulation of the lipid peroxidation marker 4-HNE, and defective SOD2 antioxidant response in IGT and newly diagnosed, drug-naïve T2D subjects. In addition, ROC curves demonstrated the diagnostic accuracy of markers used. CONCLUSIONS our data demonstrate that microRNA-21 is associated with prediabetic status and exhibits predictive value for early detection of glucose imbalances. These data could provide novel clues for miR-based biomarkers to evaluate diabetes.
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Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.
Chen, H, Li, Y, Zhu, Y, Wu, L, Meng, J, Lin, N, Yang, D, Li, M, Ding, W, Tong, X, et al
Medicine. 2017;(33):e7456
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Abstract
The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.
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Serum oxygen radical activity and total antioxidation capacity are related with severities of surgical patient with sepsis: Prospective pilot study.
Jang, JY, Lee, SH, Shim, H, Lee, JG
Journal of critical care. 2017;:131-136
Abstract
PURPOSE The purpose of this pilot study was to evaluate the correlation between clinical severity and serum oxygen radical activity (ORA) and total antioxidation capacity (TAC) in critically ill surgical patients with sepsis. MATERIALS AND METHODS The prospective observational study was performed in surgical intensive care unit (SICU) patients with intra-abdominal sepsis. Serum ORA and TAC levels were measured using a spectrophotometry-based antioxidant assay machine. Serum selenium and zinc levels and plasma glutamine concentrations were also determined. Sequential organ failure assessment (SOFA) and multiple organ dysfunction (MOD) scores were calculated to evaluate the severity. Blood tests and severity scores were assessed on days 1, 3, and 7 in the SICU. RESULTS Twenty-seven patients were included. The mean APACHE II score was 22.4. The in-hospital mortality rate was 14.8%. Serum TAC levels correlated positively with SOFA and MOD scores on SICU days 1, 3 and 7, and serum ORA correlated negatively with SOFA and MOD scores on day 3. Serum zinc and selenium levels were lower than normal throughout the observation period. However, there was no significant relationship in clinical severity. CONCLUSIONS Serum TAC level may be a useful biomarker to predict severity of critically ill surgical patients with sepsis.
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Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.
Medeiros, MS, Schumacher-Schuh, A, Cardoso, AM, Bochi, GV, Baldissarelli, J, Kegler, A, Santana, D, Chaves, CM, Schetinger, MR, Moresco, RN, et al
PloS one. 2016;(1):e0146129
Abstract
Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.