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1.
J Biomol Struct Dyn ; : 1-12, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393679

RESUMEN

Amyloidosis is an extraordinarily vigorous and heterogeneous group of disorders that causes numerous organ failures due to the precipitation of misfolded proteins. Many of these damaged proteins are discarded before causing any fatal diseases due to the contribution of the protein quality control (PQC) system and its chaperons, including glucose-regulated protein (GRP78). One of the most important enzymatic proteins inside the body is lysozyme, which is reported to have many mutated variants that may cause amyloid fibrils. This study used structural bioinformatics and molecular dynamics simulations to test and suggest binding sites for the human lysozyme protein with GRP78. Multiple sequence alignment (MSA) shows that part of the lysozyme envelope protein (C65-C81 cyclic region) has high similarities (30.77% identity) with the cyclic Pep42. Additionally, the binding between the lysozyme cyclic region (C65-C81) and GRP78 substrate binding domain (SBD) is found favorable. The number and types of interactions vary between each of the mutant isoforms of lysozyme. The more significant the conformational changes in the mutation, the greater its probability of aggregation and the formation of amyloid fibrils. Each mutation leads to different interactions and binding patterns with GRP78. The present computational study suggests a lysozyme-GRP78 binding site, thus paving the way for drug designers to construct suitable carriers that can collect misfolded lysozyme proteins and eliminate them from the body, preventing their aggregation and amyloidogenesis.Communicated by Ramaswamy H. Sarma.

2.
Sci Rep ; 13(1): 2749, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36797452

RESUMEN

Both gallic and citrate are well-established antioxidants that show promise as new selective anti-cancer drugs. Gold nanoparticles (AuNPs) as well can be developed as flexible and nontoxic nano-carriers for anti-cancer drugs. This article evaluating the efficiency and biocompatibility of gallic acid and citrate capping gold nanoparticles to be used as anti-cancer drug. The biosafety and therapeutic efficiency of prepared nano-formulations were tested on Hela and normal BHK cell line. Gold nanospheres coated with citrate and gallate were synthesized via wet chemical reduction method. The prepared nano-formulations, citrate and gallate coated gold nanospheres (Cit-AuNPs and Ga-AuNPs), were characterized with respect to their morphology, FTIR spectra, and physical properties. In addition, to assess their cytotoxicity, cell cycle arrest and flow cytometry to measure biological response were performed. Cit-Au NPs and Ga-Au NPs were shown to significantly reduce the viability of Hela cancer cells. Both G0/G cell cycle arrest and comet assay results showed that genotoxic effect was induced in Hela cells by Cit-Au NPs and Ga-Au NPs. The results of this study showed that Cit-Au NPs and Ga-AuNPs inhibit the growth of metastatic cervical cancer cells, which could have therapeutic implications.


Asunto(s)
Antineoplásicos , Nanopartículas del Metal , Nanosferas , Humanos , Ácido Cítrico/química , Células HeLa , Oro/farmacología , Oro/química , Nanopartículas del Metal/química , Citratos , Antineoplásicos/farmacología , Antineoplásicos/química
3.
Molecules ; 26(21)2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34770863

RESUMEN

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.


Asunto(s)
Coronavirus/metabolismo , Interacciones Microbiota-Huesped/fisiología , Receptores de Coronavirus/metabolismo , Anticuerpos Neutralizantes , Antivirales/farmacología , COVID-19 , Coronavirus/patogenicidad , Humanos , Receptores de Coronavirus/fisiología , Receptores Virales/metabolismo , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus/efectos de los fármacos
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