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2.
J Neurochem ; 168(2): 142-160, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38169121

RESUMEN

White matter injury (WMI) is one of the most serious complications associated with preterm births. Damage to oligodendrocytes, which are the key cells involved in WMI pathogenesis, can directly lead to myelin abnormalities. L-ascorbyl-2-phosphate (AS-2P) is a stable form of vitamin C. This study aimed to explore the protective effects of AS-2P against chronic hypoxia-induced WMI, and elucidate the underlying mechanisms. An in vivo chronic hypoxia model and in vitro oxygen-glucose deprivation (OGD) model were established to explore the effects of AS-2P on WMI using immunofluorescence, immunohistochemistry, western blotting, real-time quantitative polymerase chain reaction, Morris water maze test, novel object recognition test, beaming-walking test, electron microscopy, and flow cytometry. The results showed that AS-2P resulted in the increased expression of MBP, Olig2, PDGFRα and CC1, improved thickness and density of the myelin sheath, and reduced TNF-α expression and microglial cell infiltration to alleviate inflammation in the brain after chronic hypoxia. Moreover, AS-2P improved the memory, learning and motor abilities of the mice with WMI. These protective effects of AS-2P may involve the upregulation of protein arginine methyltransferase 5 (PRMT5) and downregulation of P53 and NF-κB. In conclusion, our study demonstrated that AS-2P attenuated chronic hypoxia-induced WMI in vivo and OGD-induced oligodendrocyte injury in vitro possibly by regulating the PRMT5/P53/NF-κB pathway, suggesting that AS-2P may be a potential therapeutic option for WMI.


Asunto(s)
Lesiones Encefálicas , Sustancia Blanca , Animales , Ratones , FN-kappa B/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales Recién Nacidos , Sustancia Blanca/patología , Hipoxia/metabolismo , Lesiones Encefálicas/patología , Ácido Ascórbico/metabolismo , Oxígeno/metabolismo
3.
Front Pharmacol ; 14: 1134464, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969871

RESUMEN

Introduction: Hypoxic-ischemic encephalopathy (HIE) is a crucial cause of neonatal death and neurological sequelae, but currently there is no effective therapy drug for HIE. Both oxidative stress and apoptosis play critical roles in the pathological development of HIE. Myricetin, a naturally extracted flavonol compound, exerts remarkable effects against oxidative stress, apoptosis, and inflammation. However, the role and underlying molecular mechanism of myricetin on HIE remain unclear. Methods: In this study, we established the neonatal rats hypoxic-ischemic (HI) brain damage model in vivo and CoCl2 induced PC12 cell model in vitro to explore the neuroprotective effects of myricetin on HI injury, and illuminate the potential mechanism. Results: Our results showed that myricetin intervention could significantly reduce brain infarction volume, glia activation, apoptosis, and oxidative stress marker levels through activating NRF2 (Nuclear factor-E2-related factor 2) and increase the expressions of NRF2 downstream proteins NQO-1 and HO-1. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of myricetin. Conclusion: This study found that myricetin might alleviate oxidative stress and apoptosis through NRF2 signaling pathway to exert the protective role for HI injury, which suggested that myricetin might be a promising therapeutic agent for HIE.

4.
Entropy (Basel) ; 20(6)2018 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-33265536

RESUMEN

One important element of military supply transportation is concealment, especially during war preparations and warfare periods. By introducing entropy to calculate the transportation concealment degree, we investigate the issue about concealed military supply transportation on the whole road network and propose an optimal flow distribution model. This model's objective function is to maximize the concealment of military supply transportation. After analyzing the road network, classifying different nodes, summarizing the constraint conditions based on the properties and assumptions in the transportation process, and combining the general parameter limits, the optimal flow distribution model is further transformed into a calculable non-linear programming model. Thus, based on this non-linear programming model, we can obtain the optimal distribution scheme of military supply transportation from the perspectives of network analysis and concealment measurement. Lastly, an example of military supply transportation in Jiangsu province, China is illustrated to prove the feasibility of the proposed model. The managerial implication is that by utilizing the proposed flow distribution model, military supplies can be efficiently transported to the required destinations based on maximizing the concealment degree. Not only this model can be utilized in the real military supply transportation, it can be also applied in other transportation fields which require time efficiency and concealment.

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