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Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Gravedad del Paciente , SARS-CoV-2 , Anciano , China/epidemiología , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
In the late stages of its industrialization, China's economy still largely relies on energy. With increasing pressures to protect the environment and reduce carbon emissions, in 2013, the Chinese government officially issued four policies in succession to control total energy consumption. In this paper, we use the single difference model to estimate the average and dynamic economic impacts of such policies. We also introduce the energy dependence degree and divide all industrial sectors into two categories to estimate heterogeneous and dynamic policy effects based on the difference-in-differences (DID) model. Our empirical study shows that the implementation of energy consumption control policies results in a decrease in economic growth rates. Meanwhile, the negative dynamic economic effects of such policies decrease levels of volatility. Furthermore, such policies have heterogeneous economic effects on levels of energy dependence across sectors and have more significantly negative economic impacts on heavily energy-dependent industries but with hysteresis. Heterogeneous and dynamic economic effects on heavily energy-dependent industries are decreasing. We conclude with recommendations on ways to mitigate the negative effects observed.
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Dióxido de Carbono , Desarrollo Económico , Dióxido de Carbono/análisis , China , Desarrollo Industrial , Política PúblicaRESUMEN
BACKGROUND: The purpose of this study was to identify the consistency of invasive dynamic blood pressure (BP) monitoring between the superior mesenteric artery (SMA) and the common carotid artery (CCA). METHODS: Eight male Sprague-Dawley rats were cannulated in SMA and CCA simultaneously for BP monitoring, respectively. The abdominal aorta was prepared for the induction of BP change through clamping/de-clamping by a microvascular clip. The dynamic BP monitoring was performed by a polygraph system. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) values would be recorded during different time periods: the baseline (T1), the increasing period after clamping (T2), the platform period during clamping (T3), the decreasing period after de-clamping (T4), and the final platform period (T5). Three trials were performed on each rat with 15-minute intervals between consecutive monitoring. RESULTS: Systolic BP showed no significant differences between SMA and CCA. However, significant difference was found in diastolic blood pressure except at T5 (P=0.534). Mean arterial pressure of two arteries were significantly different only at T1 (P=0.015). The strength of association was significantly high between BP measurements through SMA and CCA (P<0.001). The Bland-Altman analyses showed that mean bias of MAP changed no more than 5 mmHg and standard deviation less than 8 mmHg during T2 and T4, respectively. CONCLUSION: The study indicates SMA might be an alternative site for invasive BP monitoring during abdominal aorta occlusion and release, especially in cerebrovascular-related research.
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Cytosolic phospholipase A2 (cPLA2) has been reported to be critical for infection-induced mitochondrial reactive oxygen species (ROS) production and diaphragm dysfunction (DD). In the present study, we aim to investigate whether cPLA2 was involved in ventilator-induced diaphragm dysfunction (VIDD). Our results showed that mechanical ventilation (MV) induced cPLA2 activation in the diaphragm with excessive mitochondrial ROS generation and muscle weakness. Specific inhibition of cPLA2 with CDIBA resulted in decreased mitochondrial ROS levels and improved diaphragm forces. In addition, mitochondria-targeted antioxidant MitoTEMPO attenuated ventilator-induced mitochondrial oxidative stress and downregulated cPLA2 activation in vivo. Both CDIBA and MitoTEMPO were able to attenuate protein degradation, muscle atrophy, and weakness following prolonged MV. Furthermore, laser Doppler imaging showed that MV decreased diaphragm tissue perfusion and induced subsequent hypoxia. An in vitro study also demonstrated a positive association between cPLA2 activation and mitochondrial ROS generation in C2C12 cells cultured under hypoxic condition. Collectively, our study showed that cPLA2 activation positively interacts with mitochondrial ROS generation in the development of VIDD, and ventilator-induced diaphragm hypoxia serves as a possible contributor to this positive feedback loop.
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Diafragma/fisiopatología , Fosfolipasas A2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Animales , Diafragma/enzimología , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Secondary brain injury is a major factor that affects the prognosis and outcome of traumatic brain injury (TBI) patients. Secondary brain edema is considered to be an initiating factor in secondary brain injury after TBI. A previous study has indicated that Notch signaling activation contributes to neuron death in mice affected by stroke; however, its role in neuronal oxidation stress for brain edema after TBI is not well established. Apparent diffusion coefficient (ADC) values can represent the brain edema after TBI. METHODS: We established a rat model of acute craniocerebral injury, using functional MRI to evaluate the ADC and cerebral blood flow values. The present study was designed to determine the effect of Notch inhibitor DAPT upon oxidation stress for brain edema after TBI. Rats were randomly distributed into five groups, control group, severe TBI group, severe TBI + vehicle group, severe TBI + DAPT group, and severe TBI + DPI group. All rats were sacrificed at 24 hours after TBI. RESULTS: Our data indicated that Notch signaling inhibitor DAPT significantly reduced the ADC values and improved the neurological function after TBI. In addition, DAPT decreased NOX2 levels and the ROS levels. Furthermore, DPI can decrease NOX2 levels and ROS levels. CONCLUSION: This study indicated that DAPT Notch signal inhibitors can inhibit NOX2-ROS generation, reduce the ADC values, relieve cerebral edema, and improve nerve function.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Diaminas/farmacología , Difusión , Regulación hacia Abajo/efectos de los fármacos , NADPH Oxidasa 2/antagonistas & inhibidores , Neuronas/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Receptores Notch/antagonistas & inhibidores , Tiazoles/farmacología , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Imagen por Resonancia Magnética , NADPH Oxidasa 2/metabolismo , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores Notch/metabolismoRESUMEN
Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.
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Traumatismos Craneocerebrales/prevención & control , Diaminas/farmacología , Fármacos Neuroprotectores/farmacología , Receptores Notch/antagonistas & inhibidores , Tiazoles/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/prevención & control , Traumatismos Craneocerebrales/patología , Traumatismos Craneocerebrales/fisiopatología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Notch/genética , Receptores Notch/metabolismo , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción HES-1/antagonistas & inhibidores , Factor de Transcripción HES-1/genética , Factor de Transcripción HES-1/metabolismoRESUMEN
Indirubin plays an important role in the treatment of many chronic diseases and exhibits strong anti-inflammatory activity. However, the molecular mode of action during mastitis prophylaxis remains poorly understood. In this study, a lipopolysaccharide (LPS)-induced mastitis mouse model showed that indirubin attenuated histopathological changes in the mammary gland, local tissue necrosis, and neutrophil infiltration. Moreover, indirubin significantly downregulated the production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α). We explored the mechanism whereby indirubin exerts protective effects against LPS-induced inflammation of mouse mammary epithelial cells (MMECs). The addition of different concentrations of indirubin before exposure of cells to LPS for 1 h significantly attenuated inflammation and reduced the concentrations of the three inflammatory cytokines in a dose-dependent manner. Indirubin downregulated LPS-induced cyclooxygenase-2 (COX-2) and Toll-like receptor 4 (TLR4) expression, inhibited phosphorylation of the LPS-induced nuclear transcription factor-kappa B (NF-kB) P65 protein and its inhibitor IkBα of the NF-kB signaling pathway. Furthermore, indirubin suppressed phosphorylation of P38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signal pathways. Thus, indirubin effectively suppressed LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways and may be useful for mastitis prophylaxis.
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Inflamación/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Receptor Toll-Like 4/fisiología , Animales , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Indoles/farmacología , Indoles/uso terapéutico , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Mastitis/tratamiento farmacológico , Ratones , Transducción de Señal/efectos de los fármacosRESUMEN
A new natural product named trolliamide was isolated from Trollius chinensis Bunge. Its structure was determined as 2-hydroxy-tetracosanoic acid(2,3-dihydroxy-1-hydroxymethyl-heptadec-7-enyl)-amide by spectroscopic methods, including UV, IR, MS and NMR. This is the first report of a ceramide isolated from Trollius chinensis.
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Ceramidas/análisis , Medicamentos Herbarios Chinos/química , Ranunculaceae/química , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Bioactivity-guided fractionation of an ethanol extract of the aerial parts of Dioscorea opposita afforded a new compound, 6,7-dihydroxy-2-methoxy-1,4-phenanthrenedione (1), and four known compounds, chrysoeriol 4'-O-beta-D-glucopyranoside (2), chrysoeriol 7-O-beta-D-glucopyranoside (3), alternanthin (4), and daucosterol. The structure of 1 was established on the basis of the interpretation of its 1D and 2D NMR spectrascopic data. Compounds 1-4 exhibited both promising neuroprotective effects and discernible to moderate antioxidant activities in vitro.