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1.
J Biotechnol ; 394: 34-47, 2024 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-39128505

RESUMO

Salinity stress is a major concern in regions where irrigation relies on saline water. This study aimed to investigate the relative water content (RWC), electrolytic leakage (EL), total chlorophyll content, free amino acid content, and total soluble sugar content were analyzed in different groundnut species subjected to various salinity treatments. The results showed that salinity stress significantly reduced the RWC in groundnut leaves, with A. duranensis (wild type) exhibiting higher RWC values compared to the Arachis hypogaea species. RNA sequencing was performed to identify differentially expressed genes (DEGs) during salt stress. A total of 9079 DEGs were identified, with 1372 genes upregulated and 2509 genes downregulated. Genes belonging to transcription factor families, such as WRKY, MYB, bHLH, E2F, and Auxin efflux carrier proteins, were induced under salt stress in the tolerant genotype. Conversely, genes encoding NADH dehydrogenase, glutathione S-transferase, protein kinases, UDP-glycosyltransferase, and peroxidase were downregulated. Gene ontology and pathway analyses revealed several enriched categories and metabolic pathways associated with salt stress response, including catalytic activity, response to salt stress, ATP-dependent activity, and oxidative phosphorylation. The findings of this study provide insights into the physiological and molecular responses of groundnut to salinity stress. A. duranensis exhibited better salinity tolerance than Arachis hypogaea, as indicated by higher RWC values, lower electrolytic leakage, and differential gene expression patterns. These results contribute to our understanding of the mechanisms underlying salt stress tolerance in groundnut and may guide future efforts to develop salinity-tolerant groundnut species, ultimately improving crop yield in saline-affected regions.


Assuntos
Arachis , Regulação da Expressão Gênica de Plantas , Estresse Salino , Transcriptoma , Arachis/genética , Arachis/metabolismo , Estresse Salino/genética , Salinidade , Perfilação da Expressão Gênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Estresse Fisiológico/genética , Tolerância ao Sal/genética
2.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670524

RESUMO

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Imunoconjugados/uso terapêutico , Neoplasias/terapia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Humanos , Imunoterapia/métodos , Imunoterapia/estatística & dados numéricos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/estatística & dados numéricos , Oncologia/tendências , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/estatística & dados numéricos , Terapia de Alvo Molecular/tendências , Neoplasias/classificação
3.
Peptides ; 134: 170402, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32889022

RESUMO

Viral infectious diseases have resulted in millions of deaths throughout history and have created a significant public healthcare burden. Tremendous efforts have been placed by the scientific communities, health officials and government organizations to detect, treat, and prevent viral infection. However, the complicated life cycle and rapid genetic mutations of viruses demand continuous development of novel medicines with high efficacy and safety profiles. Peptides provide a promising outlook as a tool to combat the spread and re-emergence of viral infection. This article provides an overview of five viral infectious diseases with high global prevalence: influenza, chronic hepatitis B, acquired immunodeficiency syndrome, severe acute respiratory syndrome, and coronavirus disease 2019. The current and potential peptide-based therapies, vaccines, and diagnostics for each disease are discussed.


Assuntos
Antivirais/farmacologia , Peptídeos/farmacologia , Vacinas Virais/farmacologia , Viroses/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Animais , COVID-19/prevenção & controle , Vacinas contra COVID-19/farmacologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Vacinas contra Influenza/farmacologia , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Viroses/prevenção & controle , Tratamento Farmacológico da COVID-19
4.
Amino Acids ; 52(9): 1207-1226, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32945974

RESUMO

With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.


Assuntos
Aminoácidos/química , Desenvolvimento de Medicamentos , Descoberta de Drogas , Fragmentos de Peptídeos/uso terapêutico , Animais , Humanos , Fragmentos de Peptídeos/química
5.
PLoS One ; 15(6): e0233961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479512

RESUMO

Hundreds of target specific peptides are routinely discovered by peptide display platforms. However, due to the high cost of peptide synthesis only a limited number of peptides are chemically made for further analysis. Here we describe an accurate and cost effective method to bin peptides on-phage based on binding region(s), without any requirement for peptide or protein synthesis. This approach, which integrates phage and yeast display platforms, requires display of target and its alanine variants on yeast. Flow cytometry was used to detect binding of peptides on-phage to the target on yeast. Once hits were identified, they were synthesized to confirm their binding region(s) by HDX (Hydrogen deuterium exchange) and crystallography. Moreover, we have successfully shown that this approach can be implemented as part of a panning process to deplete non-functional peptides. This technique can be applied to any target that can be successfully displayed on yeast; it narrows down the number of peptides requiring synthesis; and its utilization during selection results in enrichment of peptide population against defined binding regions on the target.


Assuntos
Técnicas de Visualização da Superfície Celular/métodos , Biblioteca de Peptídeos , Alanina/genética , Alanina/metabolismo , Bacteriófagos/genética , Bacteriófagos/metabolismo , Técnicas de Visualização da Superfície Celular/economia , Análise Custo-Benefício , Citometria de Fluxo/economia , Citometria de Fluxo/métodos , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/metabolismo , Mutação , Ligação Proteica/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
6.
Int J Sports Physiol Perform ; 9(6): 966-72, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24622942

RESUMO

PURPOSE: To assess changes in body composition, lumbar-spine bone mineral density (BMD), and rowing performance in college-level rowers over a competition season. METHODS: Eleven Division I college rowers (mean ± SD 21.4 ± 3.7 y) completed 6 testing sessions throughout the course of their competition season. Testing included measurements of fat mass, bone-free lean mass (BFLM), body fat (%BF), lumbar-spine BMD, and 2000-m time-trial performance. After preseason testing, rowers participated in a periodized training program, with the addition of resistance training to the traditional aerobic-training program. RESULTS: Significant (P < .05) improvements in %BF, total mass, and BFLM were observed at midseason and postseason compared with preseason. Neither lumbar-spine BMD nor BMC significantly changed over the competitive season (P > .05). Finally, rowing performance (as measured by 2000-m time and average watts achieved) significantly improved at midseason and postseason compared with preseason. CONCLUSION: Our results highlight the efficacy of a seasonal concurrent training program serving to improve body composition and rowing performance, as measured by 2000-m times and average watts, among college-level rowers. Our findings offer practical applications for coaches and athletes looking to design a concurrent strength and aerobic training program to improve rowing performance across a season.


Assuntos
Composição Corporal , Densidade Óssea , Educação Física e Treinamento/métodos , Esportes/fisiologia , Adolescente , Feminino , Humanos , Vértebras Lombares , Masculino , Força Muscular/fisiologia , Resistência Física/fisiologia , Treinamento Resistido , Adulto Jovem
7.
AAPS PharmSciTech ; 9(4): 1247-52, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19115110

RESUMO

A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer hydroxypropyl methylcellulose (HPMC K(3)LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of HPMC K(3)LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitro-in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/química , Sinvastatina/química , Solventes/química , Animais , Varredura Diferencial de Calorimetria , Colesterol/sangue , Avaliação Pré-Clínica de Medicamentos , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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