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Drug Discov Today ; 24(7): 1332-1343, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30876845


Machine learning, especially deep learning, has the predictive power to predict adverse drug reactions, repurpose drugs and perform precision medicine. We provide a background of machine learning and propose a potential high-performance deep learning framework for its successful applications in these practices.

J Vis Exp ; (143)2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30663675


In this report, we present a method for the construction of a soluble lead flow battery (SLFB) with an extended cycle life. By supplying an adequate amount of sodium acetate (NaOAc) to the electrolyte, a cycle life extension of over 50% is demonstrated for SLFBs via long-term galvanostatic charge/discharge experiments. A higher quality of the PbO2 electrodeposit at the positive electrode is quantitatively validated for NaOAc-added electrolyte by throwing index (TI) measurements. Images acquired by scanning electron microscopy (SEM) also exhibit more integrated PbO2 surface morphology when the SLFB is operated with the NaOAc-added electrolyte. This work indicates that electrolyte modification can be a plausible route to economically enable SLFBs for large-scale energy storage.

PLoS One ; 9(11): e113397, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25415296


Tropomyosin-related kinase B (TrkB) signaling is critical for promoting neuronal survival following brain damage. The present study investigated the effects and underlying mechanisms of TrkB activation by the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) on traumatic brain injury (TBI). Mice subjected to controlled cortical impact received intraperitoneal 7,8-DHF or vehicle injection 10 min post-injury and subsequently daily for 3 days. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed. The protective effect of 7,8-DHF was also investigated in primary neurons subjected to stretch injury. Treatment with 20 mg/kg 7,8-DHF attenuated functional deficits and brain damage up to post-injury day 28. 7,8-DHF also reduced brain edema, neuronal death, and apoptosis at day 4. These changes were accompanied by a significant decrease in cleaved caspase-3 and increase in Bcl-2/Bax ratio. 7,8-DHF enhanced phosphorylation of TrkB, Akt (Ser473/Thr308), and Bad at day 4, but had no effect on Erk 1/2 phosphorylation. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels and promoted cAMP response element-binding protein (CREB) activation. This beneficial effect was attenuated by inhibition of TrkB or PI3K/Akt. 7,8-DHF also promoted survival and reduced apoptosis in cortical neurons subjected to stretch injury. Remarkably, delayed administration of 7,8-DHF at 3 h post-injury reduced brain tissue damage. Our study demonstrates that activation of TrkB signaling by 7,8-DHF protects against TBI via the PI3K/Akt but not Erk pathway, and this protective effect may be amplified via the PI3K/Akt-CREB cascades.

Lesões Encefálicas/prevenção & controle , Flavonas/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Receptor trkB/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Edema Encefálico/tratamento farmacológico , Lesões Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Flavonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Camundongos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia
PLoS One ; 7(1): e30294, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22272328


BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4)- and nuclear factor kappa B (NF-κB)-related signaling pathways in mice following TBI. METHODOLOGY/PRINCIPAL FINDINGS: Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg(-1)) or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB) permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg(-1) wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1ß, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2. CONCLUSIONS/SIGNIFICANCE: Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.

Lesões Encefálicas/tratamento farmacológico , Flavanonas/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiopatologia , Western Blotting , Edema Encefálico/prevenção & controle , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Fitoterapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa