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1.
J Fluoresc ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888658

RESUMO

Metal nanoparticles and their binary oxides are well-known for their interactions with biomolecules and their applications in the biomedical field. However, the potential of ternary oxide nanophosphors remains underexplored in these fields due to challenges associated with high-temperature synthesis procedures and the use of toxic chemicals. ZnAl2O4, a ternary oxide matrix, being recognized for its adjustable wide bandgap, impressive surface properties, mechanical strength, thermal stability, and high quantum yield, is chosen for the present work. This study aims to comprehensively investigate the structural, morphological, optical, and cytotoxic properties of zinc aluminate nano phosphors synthesized through a co-precipitation method followed by low-temperature calcination. Analysis using X-ray diffraction spectroscopy (XRD) and Fourier-transform infrared spectroscopy (FTIR) revealed that the formation of the ZnAl2O4 spinel phase initiates at 300 °C and completes at 750 °C.SEM-EDAX measurements provided further confirmation of the compositional integrity of the synthesized sample. The average crystallite size, determined to be 11.47 nm through a W-H plot, along with a higher bandgap value of 4.49 eV compared to bulk ZnAl2O4 from the diffuse reflectance spectra (DRS), attests to the success of the nanophosphor synthesis. The self-activated blue luminescent centers of ZnAl2O4 can be fine-tuned to emit light in the green and red regions of the electromagnetic spectrum through appropriate rare earth (RE) doping, utilizing Tb3+ and Eu3+ respectively. Furthermore, the particles underwent short-term in-vitro cytotoxicity testing using Dalton's Lymphoma Ascites cells (DLA) and normal cells, demonstrating high activity against DLA cells while maintaining compatibility with normal cells.

2.
Chem Biol Drug Des ; 103(1): e14374, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37994213

RESUMO

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors. The molecular and neural pathways linked to the regulation of schizophrenia have been extensively studied. Over 180 Schizophrenic risk loci have now been recognized due to several genome-wide association studies (GWAS). It has been observed that multiple transcription factors (TF) binding-disrupting single nucleotide polymorphisms (SNPs) have been related to gene expression responsible for the disease in cerebral complexes. Copy number variation, SNP defects, and epigenetic changes in chromosomes may cause overexpression or underexpression of certain genes responsible for the disease. Nowadays, gene therapy is being implemented for its treatment as several of these genetic defects have been identified. Scientists are trying to use viral vectors, miRNA, siRNA, and CRISPR technology. In addition, nanotechnology is also being applied to target such genes. The primary aim of such targeting was to either delete or silence such hyperactive genes or induce certain genes that inhibit the expression of these genes. There are challenges in delivering the gene/DNA to the site of action in the brain, and scientists are working to resolve the same. The present article describes the basics regarding the disease, its causes and factors responsible, and the gene therapy solutions available to treat this disease.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/terapia , Esquizofrenia/metabolismo , Estudo de Associação Genômica Ampla , Variações do Número de Cópias de DNA , Encéfalo/metabolismo , Epigênese Genética , Polimorfismo de Nucleotídeo Único
3.
J Alzheimers Dis ; 93(2): 705-726, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066913

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative dementia affecting people in their later years of life. The AD prevalence rate has significantly increased due to a lack of early detection technology and low therapeutic efficacy. Despite recent scientific advances, some aspects of AD pathological targets still require special attention. Certain traditionally consumed phytocompounds have been used for thousands of years to treat such pathologies. The standard extract of Gingko biloba (EGB761) is a combination of 13 macro phyto-compounds and various other micro phytocompounds that have shown greater therapeutic potential against the pathology of AD. OBJECTIVE: Strong physiological evidence of cognitive health preservation has been observed in elderly people who keep an active lifestyle. According to some theories, consuming certain medicinal extracts helps build cognitive reserve. We outline the research employing EGB761 as a dual target for AD. METHODS: This study investigates various inhibitory targets against AD using computational approaches such as molecular docking, network pharmacology, ADMET (full form), and bioactivity prediction of the selected compounds. RESULTS: After interaction studies were done for all the phytoconstituents of EGB761, it was concluded that all four of the phytocompounds (kaempferol, isorhamnetin, quercetin, and ginkgotoxin) showed the maximum inhibitory activity against acetylcholinesterase (AChE) and GSK3ß. CONCLUSION: The highly active phytocompounds of EGB761, especially quercetin, kaempferol, and isorhamnetin, have better activity against AChE and GSK3ß than its reported synthetic drug, according to molecular docking and network pharmacology research. These compounds may act on multiple targets in the protein network of AD. The AChE theory was primarily responsible for EGB761's therapeutic efficacy in treating AD.


Assuntos
Doença de Alzheimer , Ginkgo biloba , Humanos , Idoso , Ginkgo biloba/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Simulação de Acoplamento Molecular , Glicogênio Sintase Quinase 3 beta , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Quercetina/uso terapêutico , Acetilcolinesterase/metabolismo , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
4.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443598

RESUMO

Apocynin (APO) is a known multi-enzymatic complexed compound, employed as a viable NADPH oxidase (NOX) inhibitor, extensively used in both traditional and modern-day therapeutic strategies to combat neuronal disorders. However, its therapeutic efficacy is limited by lower solubility and lesser bioavailability; thus, a suitable nanocarrier system to overcome such limitations is needed. The present study is designed to fabricate APO-loaded polymeric nanoparticles (APO-NPs) to enhance its therapeutic efficacy and sustainability in the biological system. The optimized APO NPs in the study exhibited 103.6 ± 6.8 nm and -13.7 ± 0.43 mV of particle size and zeta potential, respectively, along with further confirmation by TEM. In addition, the antioxidant (AO) abilities quantified by DPPH and nitric oxide scavenging assays exhibited comparatively higher AO potential of APO-NPs than APO alone. An in-vitro release profile displayed a linear diffusion pattern of zero order kinetics for APO from the NPs, followed by its cytotoxicity evaluation on the PC12 cell line, which revealed minimal toxicity with higher cell viability, even after treatment with a stress inducer (H2O2). The stability of APO-NPs after six months showed minimal AO decline in comparison to APO only, indicating that the designed nano-formulation enhanced therapeutic efficacy for modulating NOX-mediated ROS generation.


Assuntos
Acetofenonas/química , Acetofenonas/farmacologia , Peróxido de Hidrogênio/farmacologia , NADPH Oxidases/metabolismo , Nanopartículas/química , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Neurônios/citologia , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos
5.
Int J Biol Macromol ; 151: 1240-1249, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751684

RESUMO

The emergence and spread of multidrug-resistant strains of Klebsiella pneumoniae is a major concern that necessitates the development of unique therapeutics. The essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery. In this study, as an initial step to structure-based drug discovery, CysE from K. pneumonia was structurally and biochemically characterized. Subsequently, blind docking of selected natural products into the X-ray crystallography determined 3D structure of the target was carried out. Experimental validation of the inhibitory potential of the top-scorers established quercetin as an uncompetitive inhibitor of Kpn CysE. Molecular dynamics simulations carried out to elucidate the binding mode of quercetin reveal that this small molecule binds at the trimer-trimer interface of hexameric CysE, a site physically distinct from the active site of the enzyme. Detailed analysis of conformational differences incurred in Kpn CysE structure on binding to quercetin provides mechanistic understanding of allosteric modulation. Binding of quercetin to CysE leads to conformation changes in the active site loops and proximal loops that affect its internal dynamics and consequently its affinity for substrate/co-factor binding, justifying the reduced enzyme activity.


Assuntos
Antibacterianos/química , Klebsiella pneumoniae/enzimologia , Serina O-Acetiltransferase/química , Regulação Alostérica/efeitos dos fármacos , Antibacterianos/farmacologia , Clonagem Molecular , Estabilidade Enzimática , Expressão Gênica , Humanos , Cinética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Desnaturação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Serina O-Acetiltransferase/antagonistas & inibidores , Serina O-Acetiltransferase/genética , Serina O-Acetiltransferase/isolamento & purificação , Relação Estrutura-Atividade
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