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1.
Acta Pharmacol Sin ; 43(9): 2302-2312, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35190698

RESUMO

Rosiglitazone (RSG) is a synthetic agonist of peroxisome proliferator-activated receptor-γ (PPARγ), which plays a central role in the regulation of metabolism. Meta-analyses have suggested that RSG is associated with increased cardiovascular risk. However, the mechanisms underlying such adverse cardiac effects are still poorly understood. Here, we found that activation of PPARγ by RSG stimulated the endocannabinoid system (ECS), a membrane lipid signaling system, which induced cardiac hypertrophy. In neonatal rat cardiomyocytes, RSG increased the level of anandamide (AEA); upregulated the expression of N-acyl phosphatidylethanolamine phospholipase D (NapePLD), a key enzyme for AEA synthesis; and downregulated the expression of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of AEA. Importantly, PPARγ activation increased the expression of cannabinoid receptor type 1 (CB1) through an identified binding site for PPARγ in the CB1 promoter region. Moreover, both the in vitro and in vivo results showed that inhibition of the ECS by rimonabant, an antagonist of CB1, attenuated RSG-induced cardiac hypertrophy, as indicated by decreased expression of cardiac hypertrophy markers (ANP and BNP), deactivation of the mTOR pathway, and decreased cardiomyocyte size. Thus, these results demonstrated that the ECS functions as a novel target of PPARγ and that the AEA/CB1/mTOR axis mediates RSG-induced cardiac remodeling.


Assuntos
Endocanabinoides , PPAR gama , Animais , Cardiomegalia/induzido quimicamente , Miócitos Cardíacos/metabolismo , PPAR gama/metabolismo , Ratos , Receptor CB1 de Canabinoide , Rosiglitazona/farmacologia , Serina-Treonina Quinases TOR
2.
Artigo em Inglês | MEDLINE | ID: mdl-33044923

RESUMO

Acoustic pyrometer is expected to be a useful noninvasive method for monitoring gas temperature distribution inside a steel-making furnace. On the superficial layer above the burden of a blast furnace, most of the high-temperature gas is concentrated near the center, and tracking the position of the hotspot is critical for productivity. However, most of the existing acoustic temperature distribution reconstruction algorithms are developed with relatively uniform temperature distribution environments. Besides, their capabilities of tracking the pinnacle of temperature distribution in the region of interest (ROI) are rarely discussed. In this research, a reconstruction method of acoustic temperature tomography dedicated for highly centralized gas temperature distribution is proposed and demonstrated. The key metrics include the reproducibility of 2-D temperature distribution, the sensitivity of hotspot shift, and the accuracy of point-to-point (P2P)/peak temperature. To optimize the result of each metric, previous approaches of acoustic temperature tomography have been first evaluated. Then, the investigation of effects from the shape and size of meshes is proceeded to improve the performance. After that, a novel method to address convergence issues while using the iterative method is introduced. Consequently, the reconstruction method proposed in this article could effectively visualize the temperature map while hotspot moves to different locations. It could also sense the occurrence of a hotspot (2.56% of ROI) traveled from center to 1% of ROI's diameter. Moreover, a competitive accuracy with 5.89% and 1.46% error at P2P root-mean-square (rms) and peak temperature is achieved, respectively. Finally, a practical acoustic 2-D pyrometer consisted of 12 ultrasonic transducers arranged in a circular pattern with a 1-m width of ROI successfully detected the shift of a hotspot when the displacement of a heater reaches 5 cm.

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