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1.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
2.
Phys Rev E ; 100(3-1): 032405, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31639915

RESUMO

Absence epilepsy is characterized by a sudden paroxysmal loss of consciousness accompanied by oscillatory activity propagating over many brain areas. Although primary generalized absence seizures are supported by the global corticothalamic system, converging experimental evidence supports a focal theory of absence epilepsy. Here a physiology-based corticothalamic model is investigated with spatial heterogeneity due to focal epilepsy to unify global and focal aspects of absence epilepsy. Numeric and analytic calculations are employed to investigate the emergent spatiotemporal dynamics as well as their underlying dynamical mechanisms. They can be categorized into three scenarios: suppressed epilepsy, focal seizures, or generalized seizures, as summarized from a phase diagram vs focal width and characteristic axon range. The corresponding temporal frequencies and spatial extents of cortical waves in generalized seizures and focal seizures agree well with experimental observations of global and focal aspects of absence epilepsy, respectively. The emergence of the spatiotemporal dynamics corresponding to focal seizures provides a biophysical explanation of the temporally higher frequency but spatially more localized cortical waves observed in genetic rat models that display characteristics of human absence epilepsy. Predictions are also presented for further experimental test.


Assuntos
Córtex Cerebral/patologia , Epilepsia Tipo Ausência/patologia , Modelos Neurológicos , Tálamo/patologia , Animais , Humanos , Ratos
3.
Phys Rev E ; 95(4-1): 042410, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28505725

RESUMO

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.


Assuntos
Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Modelos Neurológicos , Tálamo/fisiologia , Simulação por Computador , Epilepsia/fisiopatologia , Humanos , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Dinâmica não Linear , Convulsões/fisiopatologia , Tálamo/fisiopatologia
4.
PLoS Comput Biol ; 13(2): e1005384, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28192429

RESUMO

The brain is highly energy consuming, therefore is under strong selective pressure to achieve cost-efficiency in both cortical connectivities and activities. However, cost-efficiency as a design principle for cortical activities has been rarely studied. Especially it is not clear how cost-efficiency is related to ubiquitously observed multi-scale properties: irregular firing, oscillations and neuronal avalanches. Here we demonstrate that these prominent properties can be simultaneously observed in a generic, biologically plausible neural circuit model that captures excitation-inhibition balance and realistic dynamics of synaptic conductance. Their co-emergence achieves minimal energy cost as well as maximal energy efficiency on information capacity, when neuronal firing are coordinated and shaped by moderate synchrony to reduce otherwise redundant spikes, and the dynamical clusterings are maintained in the form of neuronal avalanches. Such cost-efficient neural dynamics can be employed as a foundation for further efficient information processing under energy constraint.


Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Encéfalo/fisiologia , Cognição/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Animais , Simulação por Computador , Metabolismo Energético/fisiologia , Humanos , Armazenamento e Recuperação da Informação/métodos , Modelos Estatísticos
5.
Phys Rev E ; 94(2-1): 022412, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27627340

RESUMO

A recent physiologically based model of the ascending arousal system is used to analyze the dynamics near the transition from wake to sleep, which corresponds to a saddle-node bifurcation at a critical point. A normal form is derived by approximating the dynamics by those of a particle in a parabolic potential well with dissipation. This mechanical analog is used to calculate the power spectrum of fluctuations in response to a white noise drive, and the scalings of fluctuation variance and spectral width are derived versus distance from the critical point. The predicted scalings are quantitatively confirmed by numerical simulations, which show that the variance increases and the spectrum undergoes critical slowing, both in accord with theory. These signals can thus serve as potential precursors to indicate imminent wake-sleep transition, with potential application to safety-critical occupations in transport, air-traffic control, medicine, and heavy industry.


Assuntos
Sono , Vigília , Ritmo Circadiano , Simulação por Computador , Humanos , Saúde do Trabalhador
6.
Front Comput Neurosci ; 10: 42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242499

RESUMO

Neurons communicate and transmit information predominantly through spikes. Given that experimentally observed neural spike trains in a variety of brain areas can be highly correlated, it is important to investigate how neurons process correlated inputs. Most previous work in this area studied the problem of correlation transfer analytically by making significant simplifications on neural dynamics. Temporal correlation between inputs that arises from synaptic filtering, for instance, is often ignored when assuming that an input spike can at most generate one output spike. Through numerical simulations of a pair of leaky integrate-and-fire (LIF) neurons receiving correlated inputs, we demonstrate that neurons in the presence of synaptic filtering by slow synapses exhibit strong output correlations. We then show that burst firing plays a central role in enhancing output correlations, which can explain the above-mentioned observation because synaptic filtering induces bursting. The observed changes of correlations are mostly on a long time scale. Our results suggest that other features affecting the prevalence of neural burst firing in biological neurons, e.g., adaptive spiking mechanisms, may play an important role in modulating the overall level of correlations in neural networks.

7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 37(2): 119-20, 2003 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12839665

RESUMO

OBJECTIVE: To evaluate their genotoxic risk in nurses occupationally exposed to antineoplastic drugs with chromosomal aberration test and cytokinesis-block micronucleus (CBMN) test. METHODS: Sixteen nurses in the exposure group were selected from the oncology department of the same hospital, with an average length of exposure of 5.5 years and daily making 8.25 chemotherapeutic preparations in average. The controls were students from a nursing school. Peripheral blood from both groups was cultured at 37 degrees C for 48 h and 72 h, respectively, and then slides were prepared for conventional chromosomal aberration test and CBMN test. One hundred blood cells in metaphase and 1 000 binuclear lymphocytes in each sample were observed under microscope. RESULTS: The results showed that the mean chromosomal aberration rate in the exposure group was (6.38 +/- 3.30)%, significantly higher than that in the controls (1.25 +/- 0.93)% (P < 0.01). And, the mean micronucleated cell rate in the exposure group was (15.06 +/- 5.30) per thousand, very significantly higher than that in the controls (4.56 +/- 1.67) per thousand (P < 0.01). CONCLUSIONS: The investigation indicated that chromosome damage rate in the nurses from oncology department was higher than that in the controls, which may be related to their occupational exposure to antineoplastic drugs.


Assuntos
Antineoplásicos/efeitos adversos , Aberrações Cromossômicas/induzido quimicamente , Enfermeiras e Enfermeiros , Exposição Ocupacional/efeitos adversos , Adulto , Feminino , Humanos , Testes para Micronúcleos , Mutagênicos/efeitos adversos
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