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1.
NPJ Vaccines ; 7(1): 105, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36056015

RESUMEN

At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN®; a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN® is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN® induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2 × 108 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN® as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies.

2.
Asian Pac J Cancer Prev ; 20(1): 303-309, 2019 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-30678454

RESUMEN

Background: Drug delivery systems have been designed to achieve targeted delivery and control the release rate of the drugs. A serious challenge associated with drug delivery systems is the presence of the blood-brain barrier which limits drugs penetration. In the current study, the effects of cisplatin nanoparticles on A172 brain cancer cell line were investigated. Methods: Cisplatin nanoparticles were produced by miniemulsion polymerization technique and their properties were evaluated. Drug release assay was performed to characterize the nanoparticles' properties. Here, we examined the effects of cisplatin nanoparticles and free form of cisplatin on A172 cancer cell line. MTT assay was performed for different concentrations of the drug. To measure the apoptosis rate in A172 cell line in the presence of cisplatin nanoparticles or its free from, Annexin V staining method was used. Results: Our results indicated that loading type of cisplatin was physical loading and only 4.7% of cisplatin was released after 68 h. Furthermore, MTT assay showed that cisplatin nanoparticles in all concentrations had more cytotoxic effects on the cells comparing with the free form of cisplatin and control groups. We also showed that cisplatin nanoparticles could increase apoptosis in cancer cells more than the drug in the free form by using flow cytometry technique. Conclusion: Overall, these findings proved that cisplatin loaded on poly (Butylcyanoacrylate) nanoparticles, was more efficient than the free form of cisplatin in treating A172 cancer cell line.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/farmacología , Enbucrilato/química , Nanopartículas/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Cisplatino/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Enbucrilato/administración & dosificación , Humanos , Nanopartículas/química , Polímeros/administración & dosificación , Polímeros/química
3.
Mol Neurobiol ; 55(4): 3477-3489, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28502045

RESUMEN

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.


Asunto(s)
Familia , Mutación/genética , Trastornos Parkinsonianos/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Exones/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Monoéster Fosfórico Hidrolasas/genética , Proteínas Quinasas/genética , Ubiquitina-Proteína Ligasas/genética , Adulto Joven
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