Bisphenol A accelerates the vascular complications in patients with Type 2 diabetes mellitus through vascular calcification-a molecular approach.

PURPOSE: Environmental pollutant Bisphenol A (BPA) strongly interacts with insulin resistance, which leads to type 2 diabetes mellitus (T2DM). Uncontrolled glucose levels in both blood and urine develops vascular complications in T2DM patients. However, glucose-controlled diabetic patients are also affected by vascular complications due to vascular calcification, and there is a lack of clinically relevant data on BPA levels available in patients with T2DM-associated vascular complications due to vascular calcification. Therefore, we measured BPA levels in T2DM-associated vascular complications and correlated systemic BPA levels with vascular calcification-related gene expression. METHODS: This study included 120 participants with T2DM and its associated vascular complications. Serum and urinary BPA were estimated using an ELISA kit, and gene expression of the study participants in peripheral blood mononuclear cells (PBMCs) was studied with quantitative real-time PCR. RESULTS: Serum and urinary BPA levels were higher in T2DM and its associated vascular complications with CVD and DN patients compared to control. Both Serum and urinary BPA had higher significance with Sirt1 (p < 0.001, p < 0.001), Runx2 (p < 0.01, p < 0.001) and IL-1beta (p < 0.001, p < 0.02) gene expression in the study groups, but, TNF-alpha significant with Serum BPA (p < 0.04), not urinary BPA (p < 0.31). CONCLUSION: BPA levels were positively correlated with lower Sirt1 and increased Runx2 in T2DM-associated vascular complications patients. Also, higher expression of IL-1beta and TNF-alpha was observed in T2DM-associated vascular complications patients. Our study is the first to associate BPA levels with vascular calcification in patients with T2DM and its associated vascular complications.

Correlation between abnormal GSK3ß, ß Amyloid, total Tau, p-Tau 181 levels and neuropsychological assessment total scores in CKD patients with cognitive dysfunction: Impact of rHuEPO therapy.

BACKGROUND: Cognitive dysfunction potentially affecting up to 60% of CKD patients. GSK-3ß plays a key role in the pathogenesis of AD and Cognitive dysfunction, contributing to Aß production and Aß-mediated neuronal death by phosphorylating tau inducing hyperphosphorylation in paired helical filaments. However, studies have shown that plasma p-Tau181 is more specific for AD and cognitive dysfunction. Anemia is a vital risk factor for cognitive dysfunction in CKD patients. EPO is usually to treat anemia in CKD and also improved in cognitive function. The aim of the study is to correlate between the impacts of rHuEPO therapy on platelet GSK3ß expression, plasma Aß, total Tau, p-Tau 181 levels and neuropsychological assessments total scores in CKD patients with Cognitive dysfunction. METHODS: The subjects, 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction patients. To correlate abnormal proteins with neuropsychological tests scoring in CKD with cognitive dysfunction subjects after the six months rHuEPO therapy. RESULTS: The p < 0.05 is considered as statistically significant. Pearson and Spearman correlation coefficient was used to determine the potential relationship between abnormal proteins with neuropsychological tests scoring in respective experimental groups. CONCLUSIONS: The use of abnormal protein levels, preferably in association with neuropsychological assessment total scores, appears to be a potential tool that can improve the CKD with cognitive dysfunction diagnosis. In post rHuEPO treatment, the altered protein abnormalities and neuropsychological assessment scores were retrieved significantly compared to pre treatment determined the clinical usefulness of rHuEpo as supplemental therapeutic agent in cognitive dysfunction in CKD.

Cerium Phosphate-Cerium Oxide Heterogeneous Composite Nanozymes with Enhanced Peroxidase-Like Biomimetic Activity for Glucose and Hydrogen Peroxide Sensing.

In the present work, we focus on the development of CePO4-CeO2 composite nanorods with peroxidase mimetic activity for the sensitive detection of hydrogen peroxide and glucose. The Ce3+/PO43- molar ratio (CP10:1, CP5:1, CP2:1) in the hydrothermal reaction controlled the formation of pure CePO4, CePO4-CeO2 composite nanozymes with different percentages of CeO2, and its crystal structure. A higher Ce3+/PO43- molar ratio (CP10:1 or CP5:1) was required to obtain CePO4-CeO2 composite nanostructure, while a lower Ce3+/PO43- molar (CP2:1) ratio was sufficient to fabricate pure CePO4 nanorods. In the presence of hydrogen peroxide, the prepared nanozymes catalyze the oxidation of chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Steady state kinetic analysis based on the Michaelis-Menten model revealed that CP10:1 showed excellent affinity toward the TMB ( Km = 0.236 mM and Vmax = 8.78 × 10-8 M s-1) in comparison to the catalytic activity of CP5:1 and CP2:1 and horseradish peroxidase ( Km = 0.434 mM and Vmax = 10.0 × 10-8 M s-1). The superior peroxidase activity of CePO4-CeO2 composite nanozymes can be ascribed to the enhanced redox switching between Ce3+ ↔ Ce4+ sites from the CePO4 and CeO2 lattice, respectively. The colorimetric detection of hydrogen peroxide and glucose showed a linear response around 150 µM concentration with the limits of detection (LOD) of 2.9 and 4.1 µM, respectively.

Structure dependent luminescence, peroxidase mimetic and hydrogen peroxide sensing of samarium doped cerium phosphate nanorods.

Rare earth phosphates have been used extensively in luminescent phosphors, bio-imaging, catalysis, and sensors. However, there is a need to correlate the structural-chemical changes associated with stability and performance. In the present work, hydrothermally synthesized CePO4:Smx (x = 0, 5 and 10 mol%) nanorods were annealed at different temperatures to understand the modulations in structure as well as optical and enzyme mimetic properties. As prepared samarium doped cerium phosphate (SCP) nanorods crystallized in a hydrated hexagonal structure transformed into an anhydrous hexagonal and a monoclinic structure on annealing at 400 °C and 800 °C, respectively. Though temperature did not affect the rod-like morphology of the SCP, the lattice strain changed from compressive to tensile. Monoclinic SCP exhibited excellent emission until 5% Sm3+ doping while the quenching effect dominated at 10% Sm3+. Monoclinic SCP samples demonstrated higher peroxidase-like enzymatic activity in comparison to natural enzyme HRP and hexagonal SCP. A mechanism for the enhanced peroxidase-like activity of the monoclinic structure was proposed based on the fluorescence property of terephthalic acid and the surface peroxo complex using Raman spectroscopy. Fluorimetric detection based on the luminescent quenching effect of the monoclinic SCP nanorods treated with different concentrations of hydrogen peroxide showed a linear response from 0 to150 µM concentration with a detection limit (LOD) of 3.17 µM H2O2. Our results demonstrate the importance of structure for enzyme mimetic activity.

Abnormal amyloid ß42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease.

BACKGROUND: Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid ß (Aß) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aß has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aß production. The aim of this study is to assess the antioxidant status and Aß42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction. METHODS: A total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aß42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aß level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects. RESULTS: Like AD subjects, significantly increased Aß and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects. CONCLUSION: Results suggest that elevated plasma oxidative stress and Aß were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.