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Mikrochim Acta ; 188(4): 124, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712895


A sensitive and selective molecular imprinted polymeric network (MIP) electrochemical sensor is proposed for the determination of anti-cancer drug oxaliplatin (OXAL). The polymeric network [poly(pyrrole)] was electrodeposited on a glassy carbon electrode (GCE) modified with silver nanoparticles (Ag) functionalized Cu-metal organic framework (Cu-BDC) and nitrogen-doped carbon nanotubes (N-CNTs). The MIP-Ag@Cu-BDC /N-CNTs/GCE showed an observable reduction peak at -0.14 V, which corresponds to the Cu-BDC reduction. This peak increased and decreased by eluting and rebinding of OXAL, respectively. The binding constant between OXAL and Cu-BDC was calculated to be 3.5 ± 0.1 × 107 mol-1 L. The electrochemical signal (∆i) increased with increasing OXAL concentration in the range 0.056-200 ng mL-1 with a limit of detection (LOD, S/N = 3) of 0.016 ng mL-1. The combination of N-CNTs and Ag@Cu-BDC improves both the conductivity and the anchoring sites for binding the polymer film on the surface of the electrode. The MIP-based electrochemical sensor offered outstanding sensitivity, selectivity, reproducibility, and stability. The MIP-Ag@Cu-BDC /N-CNTs/GCE was applied to determine OXAL in pharmaceutical injections, human plasma, and urine samples with good recoveries (97.5-105%) and acceptable relative standard deviations (RSDs = 1.8-3.2%). Factors affecting fabrication of MIP and OXAL determination were optimized using standard orthogonal design using L25 (56) matrix. This MIP based electrochemical sensor opens a new venue for the fabrication of other similar  sensors and biosensors.

Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119516, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33561682


Herein, yellow emissive nitrogen doped graphene quantum dots (N@GQDs) were prepared by a novel advanced thermal driven oxidation. The N@GQDs was functionalized with ß-cyclodextrin (ß-CD) to improve its catalytic performance towards dopamine (DA) detection. The ß-CD/N@GQDs exhibited strong fluorescence at λem. = 550 nm after excitation at 460 nm with a quantum yield of 38.6%. The ß-CD/N@GQDs showed good peroxidase like activity via catalyzing the oxidation of tetramethylbenzidine (TMB) in presence of H2O2 to form blue colored product at λmax = 652 nm. In the colorimetric assay of DA, the detection based on the oxidation of TMB by H2O2 in presence of ß-CD/N@GQDs as a catalyst. Then, the color of the blue oxidized TMB (oxTMB) product was reduced by addition of DA. While the fluorometric detection of DA based on the "inner filter effect" of the overlapped emission spectrum of ß-CD/N@GQDs with the absorption spectrum of oxTMB, where, addition of DA reduces oxTMB to TMB and restores the fluorescence intensity of ß-CD/N@GQDs. Under the optimized conditions, the colorimetric method achieved linearity range of 0.12-7.5 µM and LOD (S/N = 3) of 0.04 µM, while the fluorometric method achieved linearity range of 0.028-1.5 µM and LOD (S/N = 3) of 0.009 µM. The peroxidase like activity of ß-CD/N@GQDs was used to detect DA in human plasma and serum samples with good % recoveries. The colorimetric and fluorometric methods exhibited good sensitivity and selectivity toward DA detection.

Neurotox Res ; 2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-33141427


Cadmium (Cd) is a heavy metal of considerable toxicity, inducing a number of hazardous effects to humans and animals including neurotoxicity. This experiment was aimed to investigate the potential effect of kaempferol (KPF) against Cd-induced cortical injury. Thirty-two adult Sprague-Dawley rats were divided equally into four groups. The control rats intraperitoneally (i.p.) injected with physiological saline (0.9% NaCl), the cadmium chloride (CdCl2)-treated rats were i.p. injected with 4.5 mg/kg of CdCl2, the KPF-treated rats were orally gavaged with 50 mg/kg of KPF, and the KPF + CdCl2-treated rats were administered orally 50 mg/kg of KPF 120 min before receiving i.p. injection of 4.5 mg/kg CdCl2. CdCl2 exposure for 30 days led to the accumulation of Cd in the cortical tissue, accompanied by a reduction in the content of monoamines and acetylcholinesterase activity. Additionally, CdCl2 induced a state of oxidative stress as evidenced by the elevation of lipid peroxidation and nitrate/nitrite levels, while glutathione content and the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase were decreased. Moreover, CdCl2 mediated inflammatory events in the cortical tissue through increasing tumor necrosis factor-alpha and interleukin-1 beta levels and upregulating the expression of inducible nitric oxide synthase. Furthermore, pro-apoptotic proteins (Bax and caspase-3) were elevated, while Bcl-2, the anti-apoptotic protein, was decreased. Also, histological alterations were observed obviously following CdCl2. However, KPF pretreatment restored significantly the examined markers to be near the normal values. Hence, the obtained data provide evidences that KPF pretreatment has the protective effect to preserve the cortical tissues in CdCl2-exposed rats by restraining oxidative stress, inflammatory response, apoptosis, neurochemical modulation, and improving the histological changes.

J Thromb Thrombolysis ; 50(2): 361-370, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32358665


Rivaroxaban (RIVA) inhibits factor Xa and exhibits antithrombotic and anti-inflammatory activities by inhibiting several cellular signaling molecules. Sunitinib (SUN) is FDA approved first-line drug for metastatic renal cancers and advanced cancerous states of gastrointestinal tract. Present hypothesis was aimed to examine the nephroprotective potential of RIVA in SUN-induced nephrotoxicity, mediated through the inhibition of oxidative stress-induced apoptosis and inflammation, via the TNF-α/NFk-B signaling pathways. Wistar rats 200-250 g were selected and divided randomely in 5 groups (n = 6): Group 1 kept as normal control; Group 2 as disease control and exposed to SUN 50 mg/kg thrice-weekly upto 21 days; Groups 3 and 4, were treatment groups and administered SUN 50 mg/kg thrice-weekly as of group 2 and treated with RIVA 5 and 10 mg/kg/daily for 21 days, respectively; and Group 5 fed with RIVA alone (10 mg/kg/daily for 21 days). Serum was separated from blood to estimate serum biochemical parameters and kidney tissues were collected to estimate antioxidant enzyme, mRNA and protein expression. SUN exposure significantly elevated levels of creatinine, urea, uric acid, blood urea nitrogen, albumin, and bilirubin, and decreased serum magnesium and iron levels. Malondialdehyde and catalase levels were significantly increased and glutathione and glutathione reductase levels were significantly decreased. Intracellular levels of caspase-3 and TNF-α were significantly increased; RIVA treatment restored the altered levels. In SUN-exposed animals, western blotting revealed significantly elevated NFk-B, IL-17, and MCP-1 expression, and IKBα levels were significantly downregulated; RIVA restored these levels to normal values.RIVA treatment significantly restored the apoptotic and inflammatory parameters in SUN-damaged renal tissues.

Cell Signal ; 66: 109435, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31706019


Overexpression of MDM2 oncoprotein has been detected in a large number of diverse human malignancies and has been shown to play both p53-dependent and p53-independent roles in oncogenesis. Our study was designed to explore the impact of MDM2 overexpression on the levels of various cell cycle regulatory proteins including Aurora kinase-B (AURK-B), CDC25C and CDK1, which are known to promote tumor progression and increase metastatic potential. Our data from human cell cycle RT2 profiler PCR array experiments revealed significant changes in the expression profile of genes that are involved in different phases of cell cycle regulation in LNCaP-MST (MDM2 transfected) prostate cancer cells. Our current study has demonstrated a significant increase in the expression level of AURK-B, CDC25C, Cyclin A2, Cyclin B and CDK1 in LNCaP-MST cells as compared with wild type LNCaP cells that were modulated by MDM2 specific inhibitor Nutlin-3. In fact, the expression levels of the above- mentioned proteins were significantly altered at both mRNA and protein levels after treating the cells with 20 µM Nutlin-3 for 24h. Additionally, the pro-apoptotic proteins including p53, p21, and Bax were elevated with the concomitant decrease in the key anti-apoptotic proteins following MDM2 inhibitor treatment. Also, Nutlin-3 treated cells demonstrated caspase-3 activation was observed with an in-vitro caspase-3 fluorescent assay performed with caspase 3/7 specific DEVD-amc substrate. Our results offer significant evidence towards the effectiveness of MDM2 inhibition in causing cell cycle arrest via blocking the transmission of signals through AURKB-CDK1 axis and inducing apoptosis in LNCaP-MST cancer cells. It is evident from our data that MDM2 overexpression probably is the primary cause for CDK1 up-regulation in the LNCaP-MST cells, which might have occurred possibly through activation of AURK-B. However, further studies in this direction should shed more light on the intracellular mechanisms involved in the regulation of Aurora kinase-B and CDK1 axis in MDM2 positive cancers.

Future Cardiol ; 13(1): 33-47, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27990840


There are many approaches to assessing platelet reactivity and many uses for such measurements. Initially, measurements were based on the ability of platelets separated from other blood cells to aggregate together following activation with an appropriate 'aggregating agent'. Later, measurements of platelet aggregation in blood itself were performed, and this led to a point-of-care approach to platelet function testing. Measurement of secretory activity through the appearance of the activation marker P-selectin on platelets now provides an alternative approach, which enables remote testing. Measurement of vasodilator-stimulated phosphoprotein phosphorylation is also moving toward application in situations remote from the testing laboratory. Here we provide an overview of the various approaches that are now available, assess their advantages and disadvantages, and describe some of the clinical situations in which they are being used.

Plaquetas/fisiología , Agregación Plaquetaria/fisiología , Pruebas de Función Plaquetaria , Adenosina Difosfato/farmacología , Plaquetas/efectos de los fármacos , Humanos , Selectina-P/metabolismo , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Vasodilatadores/farmacología