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In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 µg/mL, with a limit of detection (LOD) of 0.01 µg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.
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Técnicas Biosensibles , Carbono , Electrodos , Oro , Nanopartículas del Metal , Receptores de Transferrina , Oro/química , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , Carbono/química , Humanos , Inmunoensayo/métodos , Límite de Detección , Técnicas Electroquímicas/métodos , Reproducibilidad de los ResultadosRESUMEN
Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC50 values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC50 against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.
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In the original publication [...].
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Cancer is the most prevalent disease globally, which presents a significant challenge to the healthcare industry, with breast and lung cancer being predominant malignancies. This study used RNA-seq data from the TCGA database to identify potential biomarkers for lung and breast cancer. Tumor Necrosis Factor (TNFAIP8) and Sulfite Oxidase (SUOX) showed significant expression variation and were selected for further study using structure-based drug discovery (SBDD). Compounds derived from the Euphorbia ammak plant were selected for in-silico study with both TNFAIP8 and SUOX. Stigmasterol had the greatest binding scores (normalized scores of -8.53â¯kcal/mol and -9.69â¯kcal/mol) with both proteins, indicating strong stability in their binding pockets throughout the molecular dynamics' simulation. Although Stigmasterol first changed its initial conformation (RMSD = 0.5â¯nm with the starting conformation) in SUOX, it eventually reached a stable conformation (RMSD of 1.5â¯nm). The compound on TNFAIP8 showed a persistent shape (RMSD of 0.35â¯nm), indicating strong protein stability. The binding free energy of the complex was calculated using the MM/GBSA technique; TNFAIP8 had a ΔGTOTAL of -24.98â¯kcal/mol, with TYR160 being the most significant residue, contributing -2.52â¯kcal/mol. On the other hand, the SUOX complex had a binding free energy of -16.87â¯kcal/mol, with LEU151 being the primary contributor (-1.17â¯kcal/mol). Analysis of the complexes' free energy landscape unveiled several states with minimum free energy, indicating robust interactions between the protein and ligand. In its conclusion, this work emphasises the favourable ability of Stigmasterol to bind with prospective targets for lung and breast cancer, indicating the need for more experimental study.
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Neoplasias de la Mama , Euphorbia , Neoplasias Pulmonares , Estigmasterol , Euphorbia/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Estigmasterol/química , Estigmasterol/farmacología , Estigmasterol/análogos & derivados , Estigmasterol/aislamiento & purificación , Femenino , Simulación de Dinámica Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Estructura Molecular , Termodinámica , Simulación del Acoplamiento MolecularRESUMEN
Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.
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Técnicas Biosensibles , Nanopartículas del Metal , Carbono/química , Oro/química , Transcortina , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , Inmunoensayo , Técnicas Electroquímicas/métodos , Electrodos , Biomarcadores , Límite de DetecciónRESUMEN
An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was â¼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration.
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The efficient detection of the foodborne pathogen Salmonella typhimurium has historically been hampered by the constraints of traditional methods, characterized by protracted culture periods and intricate DNA extraction processes for PCR. To address this, our research innovatively focuses on the crucial and relatively uncharted virulence factor, the Outer Membrane Protein D (OmpD) in Salmonella typhimurium. By harmoniously integrating the power of virtual screening and site-directed mutagenesis, we unveiled aptamers exhibiting marked specificity for OmpD. Among these, aptamer 7ZQS stands out with its heightened binding affinity. Capitalizing on this foundation, we further engineered a repertoire of mutant aptamers, wherein APT6 distinguished itself, reflecting unmatched stability and specificity. Our rigorous validation, underpinned by cutting-edge bioinformatics tools, amplifies the prowess of APT6 in discerning and binding OmpD across an array of Salmonella typhimurium strains. This study illuminates a transformative approach to the prompt and accurate detection of Salmonella typhimurium, potentially redefining boundaries in applied analytical chemistry and bolstering diagnostic precision across diverse research and clinical domains.Communicated by Ramaswamy H. Sarma.
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The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (-)-EGCG, effectively bound within the ATP-binding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (-)-CG (-)-GCG (+)-CG, and (-)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (-)-CG and the widely investigated catechin (-)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs.