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2.
Heliyon ; 7(10): e08124, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34632131

RESUMO

The rapid development of safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a necessary response to coronavirus outbreak. Here, we developed PRAK-03202, the world's first triple antigen virus-like particle vaccine candidate, by cloning and transforming SARS-CoV-2 gene segments into a highly characterized S. cerevisiae-based D-Crypt™ platform, which induced SARS CoV-2 specific neutralizing antibodies in BALB/c mice. Immunization using three different doses of PRAK-03202 induced an antigen-specific (spike, envelope, and membrane proteins) humoral response and neutralizing potential. Peripheral blood mononuclear cells from convalescent patients showed lymphocyte proliferation and elevated interferon levels suggestive of epitope conservation and induction of T helper 1-biased cellular immune response when exposed to PRAK-03202. These data support further clinical development and testing of PRAK-03202 for use in humans.

3.
Mol Biol Rep ; 45(6): 1897-1911, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30194562

RESUMO

Breast cancer is the most common cancer worldwide that costs lives of millions of people every year. Plant products with potential anticancer activities have become a vital source of novel agents in treating cancer. Adiantum capillus veneris (ACV) and Pteris Quadriureta (PQ) are such traditional herbs with potential pharmacological properties. In this study, both crude methanol extract and gold nanoparticles of ACV and PQ were tested for their anticancer activities in MCF7 and BT47 cell lines. By using GC-MS, we have identified 23 and 28 bioactive compounds in ACV and PQ respectively. We analysed the effects of ACV and PQ nanoparticles on various proteins involved in cell cycle and apoptosis using western blotting and PCR. With the help of flow cytometry, we measured number of cells undergoing apoptosis. We found that both the crude extract and nanoparticles have anti-proliferative and apoptosis inducing properties against MCF7 and BT47 cell lines. We also performed molecular docking to check whether there were any interactions between proteins involved in apoptosis and cell cycle and bioactive compounds present in the plant extracts. By using docking analysis, we also showed that phytol and eicosapentaenoic acid present in ACV and PQ interact with Bcl2 and cyclin D1. These findings demonstrate that ACV and PQ possess anticancer activities by modulating proteins involved in cell cycle and apoptosis. ACV and PQ that effectively modulate various oncogenic molecules can be used as promising agent for cancer therapy.


Assuntos
Adiantum/metabolismo , Neoplasias da Mama/tratamento farmacológico , Pteris/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Ouro , Humanos , Células MCF-7/efeitos dos fármacos , Nanopartículas Metálicas , Simulação de Acoplamento Molecular/métodos , Fitoterapia/métodos , Extratos Vegetais/farmacologia
4.
Sci Rep ; 7(1): 2045, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28515436

RESUMO

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent inhibitor of matrix metalloproteinases (MMPs) is a common negative target of oncogenic signals and a potential therapeutic target for novel drug development. Here, we show that sequential RECKlessness stimulates angiogenesis and Notch signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and chemointervention. We also report the chemotherapeutic effect of nimbolide, a limonoid from the neem tree (Azadirachta indica) based on the upregulation of RECK as well as modulation of the expression of key molecules involved in invasion and angiogenesis. We demonstrate that nimbolide upregulates RECK by targeting miR-21, and HIF-1α resulting in reduced MMP activity and blockade of VEGF and Notch signalling. Nimbolide reduced microvascular density, confirming its anti-angiogenic potential. Molecular docking analysis revealed interaction of nimbolide with HIF-1α. Additionally, we demonstrate that nimbolide upregulates RECK expression via downregulation of HIF-1α and miR-21 by overexpression and knockdown experiments in SCC4 and EAhy926 cell lines. Taken together, these findings provide compelling evidence that targeting RECK, a keystone protein that regulates mediators of invasion and angiogenesis with phytochemicals such as nimbolide may be a robust therapeutic approach to prevent oral cancer progression.


Assuntos
Transformação Celular Neoplásica/genética , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Limoninas/farmacologia , MicroRNAs/genética , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Cricetinae , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Limoninas/química , Masculino , MicroRNAs/química , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos
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