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1.
Clin J Gastroenterol ; 13(5): 635-649, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32495144

RESUMO

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett's oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett's oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett's oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett's oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett's oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Adenocarcinoma/diagnóstico por imagem , Esôfago de Barrett/diagnóstico por imagem , Diagnóstico por Imagem , Humanos
2.
J Med Chem ; 62(22): 10402-10422, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31647659

RESUMO

Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.


Assuntos
Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/química , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Relação Estrutura-Atividade , Aminas/química , Humanos , Isoenzimas/química , Isoenzimas/metabolismo , Metilação , Nitrogênio/química , Fosfatidilinositol 3-Quinases/química , Inibidores de Fosfoinositídeo-3 Quinase/síntese química , Pirimidinas/química , Albumina Sérica Humana/metabolismo
3.
Anal Chem ; 89(7): 3909-3918, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28256129

RESUMO

Alkanes are one of the most widespread contaminants in the natural environment, primarily as a consequence of biological synthesis and oil spills. Many indigenous microbes metabolize alkanes, and the chemotaxis and accumulation in some strains has been identified. For the first time, we apply Raman microspectroscopy to identify such chemotaxis-related affinity, and quantify the alkane concentrations via spectral alterations. Raman spectral alterations were only found for the alkane chemo-attractant bacteria Acinetobacter baylyi ADP1, not for Pseudomonas fluorescence, which exhibits limited chemotaxis toward alkane. The significant alterations were attributed to the strong chemotactic ability of A. baylyi enhancing the affinity and accumulation of alkane molecules on cell membranes or cellular internalization. Spectral fingerprints of A. baylyi significantly altered after 1-h exposure to pure alkanes (dodecane or tetradecane) and alkane mixtures (mineral oil or crude oil), but not monocyclic aromatic hydrocarbons (MAHs) or polycyclic aromatic hydrocarbons (PAHs). A semilog linear regression relationship between Raman spectral alterations and alkane concentrations showed its feasibility in quantifying alkane concentration in environmental samples. Pure alkanes or alkane mixtures exhibited different limits of detection and regression slopes, indicating that the chemotaxis-related alkane accumulation in A. baylyi is dependent on the carbon chain length. This work provides a novel biospectroscopy approach to characterize the chemotaxis-related alkane bioaccumulation, and has immense potential for fast and high-throughput screening bacterial chemotaxis.


Assuntos
Acinetobacter/química , Alcanos/análise , Quimiotaxia , Acinetobacter/metabolismo , Alcanos/metabolismo , Análise Espectral Raman
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