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1.
Neurosci Lett ; 715: 134611, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31698026

RESUMO

Continuous theta burst stimulation (cTBS) has been widely recognized as a therapeutic treatment for ischemic stroke, but the underlying mechanism is still elusive. Here, we investigated the protective effects of cTBS in the posterior parietal cortex during the chronic phase of stroke in the photothrombotic ischemic model. Infarction volume and neuron excitability in the peri-infarct area were assessed using immunohistochemistry and whole-cell patch-clamp. Spatial cognitive function was measured using the Morris water maze. Gamma-Amino butyric acid (GABA) interneurons were responsive to cTBS, and cTBS induced elevated phasic inhibition rather than tonic inhibition. Given that GABA-A-mediated phasic inhibition was elevated during the chronic phase of ischemic stroke for 30 days and was beneficial for stroke recovery, we investigated the therapeutic potential of cTBS in promoting functional recovery and found that the elevated phasic inhibition by cTBS improved spatial cognitive function in the photothrombotic stroke mouse model with induction in the posterior parietal cortex. Our study indicates the mechanism by which cTBS may modify the excitability of the brain cortex and provides novel insight into the potential of cTBS to protect against neuronal dysfunction in ischemic stroke.

2.
Front Cell Neurosci ; 12: 177, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997480

RESUMO

While increasing evidence demonstrated that voluntary wheel running promotes cognitive function, little is known on how different types of voluntary wheel running affect cognitive function in elderly populations. We investigated the effects of various voluntary wheel-running types on adult hippocampal neurogenesis and spatial cognition in middle-aged mice. Male C57BL6 and Thy1-green fluorescent protein (GFP) transgenic mice (13 months) were equally assigned to one of the following groups: (1) T1: no voluntary wheel running; (2) T2: intermittent voluntary wheel running; and (3) T3: continuous voluntary wheel running. The Thy1-GFP transgenic mice were used to specifically label granule cells, since Thy-1 is a promoter for neuronal expression. Behavioral evaluations suggested that intermittent voluntary wheel running improved Morris water maze performance in middle-aged mice. The number of BrdU-positive cells was significantly higher in both intermittent and continuous voluntary wheel running compared with no voluntary wheel running. However, only intermittent voluntary wheel running facilitated the newborn cells to differentiate into granule cells, while newborn cells tended to differentiate into astrocytes and repopulation of microglia was also enhanced in the continuous voluntary wheel-running group. These results indicated that intermittent voluntary exercise may be more beneficial for enhancing spatial memory. Effective improvement of hippocampal neurogenesis was also caused by intermittent voluntary wheel running in middle-aged mice.

3.
Mol Cancer ; 17(1): 29, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29455654

RESUMO

Acquired T790 M mutation is the commonest cause of resistance for advanced non-small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutant patients who had progressed after first line EGFR TKI (tyrosine kinase inhibitor). Several third generation EGFR TKIs which are EGFR mutant selective and wild-type (WT) sparing were developed to treat these patients with T790 M acquired resistant mutation. Osimertinib is one of the third generation EGFR TKIs and is currently the most advanced in clinical development. Unfortunately, despite good initial response, patients who was treated with third generation EGFR TKI would develop acquired resistance and several mechanisms had been identified and the commonest being C797S mutation at exon 20. Several novel treatment options were being developed for patients who had progressed on third generation EGFR TKI but they are still in the early phase of development. Osimertinib under FLAURA study had been shown to have better progression-free survival over first generation EGFR TKI in the first line setting and likely will become the new standard of care.


Assuntos
Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas , Compostos de Anilina , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Mutação/genética , Piperazinas/uso terapêutico
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 25(1): 128-32, 2005 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15852837

RESUMO

The simulation and fitting of the overlapped spectral lines with Voigt profile were presented in this paper. The relative errors epsilon of the fitted pressure-broadening linewidth when taking the overlapped spectral line as one spectrum were discussed in detail. The relationship between such error and the two spectral lines center distance deltav0, and theoretical pressure-broadening linewidth deltav(L)0 were analyzed. Epsilon is found to be very large and the relationship between epsilon and deltav0, deltav(L)0 is very complicated when the value of pressure-broadening linewidth is considerably less than that of Dopplerian one deltavD. When deltav(L)0 is comparative to deltaVD the relationship between epsilon and deltav0 is close to the smooth two-order polynomial curve. However, the slop of this curve is negative while deltav(L)0 is smaller than deltavD and is positive when larger. Generally, epsilon decreases with the increase of proportion of deltav(l)0 to the whole spectral linewidth. All the above conclusion and corresponding data are the significant reference to determine the precise pressure-broadening coefficient from the experimentally indistinguishable overlapped spectrum, as well as to correct the fitted pressure-broadening linewidth.


Assuntos
Algoritmos , Análise Espectral/instrumentação , Análise Espectral/métodos , Simulação por Computador , Pressão , Processamento de Sinais Assistido por Computador
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