Qassim University

In this study, alpha-1-acid glycoprotein (AGP), a crucial biomarker associated with various diseases and physiological conditions, was selected for detection using the developed immunosensor. The immunosensor was fabricated by depositing a synthesized Nafion/silver nanoparticles (AgNPs) nanocomposite on the glassy carbon electrode as the substrate material. The changes in the physicochemical properties after Nafion/AgNPs nanocomposite deposition were analyzed through SEM and XPS measurements. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to analyze the immunosensor fabrication's electrochemical performance. AGP was detected through the immobilized anti-AGP on the electrode surface. The developed immunosensor exhibited a wide linear detection range from 0.05 to 3.2 mg/mL and a LOD of 0.17 mg/mL. The developed immunosensor showed excellent selectivity and repeatability when subjected to different kinds of interfering proteins. The recovery of AGP ranged from 101.7 to 103.7 % and RSD was <4 %, indicating high accuracy in real samples detection. The immunosensor developed for AGP detection showed a number of beneficial characteristics, including low cost and small volume sample requirements, making it highly suitable for point-of-care applications. This study provides new insights into the precise fabrication and affordable immunosensors for diverse clinical diagnostic applications.

Cardiotoxicity remains a major clinical challenge associated with various environmental and chemotherapeutic toxicants. Sunitinib (SNB) is a potent targeted cancer drug that is reported to induce severe organ damage including renal failure. Cirsiliol (CSL) is a natural flavone that exhibits marvelous pharmacological properties. In this investigation, we explored the potential cardioprotective nature of CSL to counter SNB induced cardiac impairments. Sprague Dawley rats (n = 36) were categorized into control, SNB (25 mgkg^-1), SNB (25 mgkg^-1) + CSL (10 mgkg^-1), and CSL (10 mgkg^-1) alone experimented group. SNB exposure led to a notable reduction in the expression of Endothelin Receptor Type B (EDNRB), Forkhead box O3a (FOXO3a), and sirtuin 1 (SIRT1) while exacerbating the expression of P21, P53, Endothelin-1 (EDN-1), Endothelin Receptor Type A (EDNRA). The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were promoted while the enzymatic activities of hemeoxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GSR), catalase (CAT), and glutathione (GSH) contents were reduced following the SNB exposure. Moreover, SNB intoxication led to a marked elevation in the concentrations of C-reactive protein, creatine kinase-myocardial band (CK-MB), Pro-B-Type natriuretic peptide (ProBNP), troponin-T, Lactate dehydrogenase (LDH), Creatine phosphokinase (CPK), troponin-I and Brain natriuretic peptide (BNP). Cardiac tissues showed sever immune-inflammatory responses after SNB intoxication as confirmed by augmented levels and expressions of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and total fraction of nuclear factor-kappa B (NF-κB). Furthermore, the SNB administration upregulated the concentrations of cysteine-aspartic proteases-9 (Caspase-9), cysteine-aspartic proteases-3 (Capase-3), and Bcl-2-associated X protein (Bax) while declining the concentration of B-cell lymphoma 2 (Bcl-2). SNB intoxication caused histological disarrays including myofibrillar degeneration, capillary dilation, wavy fibers, necrosis of focal regions, hypertrophy of cardiomyocytes, inflammation and interstitial edema. Nonetheless, CSL therapy notably reversed these pathological changes via upregulating SIRT1/FOXO3a and endothelin pathways while reducing cardiac inflammation, apoptosis and cardiac function markers. Our results are validated through in-silico which showed that CSL showed high binding affinity with key regulatory pathways.

Methoxychlor (MET) is a synthetic organo-chlorine insecticide that is known to exert deleterious effects on hepatic tissues. Homopterocarpin (HTP) isa bioactive compound that possess highly valuable pharmacological effects. Thirty-six male albino Sprague Dawley rats were categorized into control, MET (150 mgkg^-1), MET (150 mgkg^-1) + HTP (25 mgkg^-1), and HTP (25 mgkg^-1) alone administered group. MET intoxication suppressed the expressions of Sulfiredoxin-1 (SRXN1), Thioredoxin (TXN), Thioredoxin reductase 1 (TXNRD1) and Peroxiredoxin 1 (PRDX1) while augmenting the expressions of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), interleukin-6 (IL-6), toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α), TNF receptor-associated factor 6 (TRAF6), interleukin-6 beta (IL-6) receptor-associated kinase 1 (IRAK1), cyclooxygenase-2 (COX-2) & interleukin-1 beta (IL-1β). MET therapy led to the upregulation of reactive oxygen species (ROS) and malondialdehyde (MDA) while simultaneously inhibiting the catalytic activities of hem-oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione S-Transferase (GST), glutathione reductase (GSR), catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were reduced following the provision of MET. Besides, MET exposure exacerbated concentrations of gamma-glutamyl transferase (GGT), alanine transferase (ALT), hepcidin, alkaline phosphatase (ALP), and aspartate aminotransferase (AST) while lowering the concentrations of total proteins, hemojuvelin, and albumin in serum sample. Moreover, MET intoxication compromised apoptotic cascade via promoting the concentrations of cysteine-aspartic proteases-9 (Caspase-9), Bcl-2-associated X protein (Bax), and cysteine-aspartic proteases-3 (Caspase-3) while lowering the concentration of B-cell lymphoma (Bcl-2) in hepatic tissues. Severe histological disruptions were observed after MET administration. Nonetheless, HTP therapy alleviated hepatic damage via regulating redox profile, inflammatory and apoptotic indices, and histopathological alterations. Our findings were strengthened by computational analysis that revealed the strong binding affinity of HTP with key regulatory genes thereby showing its pivotal role in regulating gene expressions.