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Fulin Tao,Yuanyuan Zhou,Mengwen Wang,Chongyang Wang,Wentao Zhu,Zhili Han,Nianxia Sun,Dianlei Wang 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.2
Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin- 8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance
Fulin Wang,Qi Tao,Luoqiong Xiao,Jiahao Hu,Leilei Xu 대한기계학회 2018 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.32 No.5
A realistic finite element model considering the ploughing effect of cutting edge fillet was developed in high speed machining. Taking the hardened tool steel AISI D2 as the object of research, the cutting force and chip morphology were reasonably analyzed and compared with the actual results of cutting experiments, which verified the correctness of the model. Then, based on the model, the formation process of single serrated tooth was analyzed, while the effects of cutting heat and temperature field, material hardness and cutting speed on chip formation were explored. The research results indicate that: (1) The ploughing-effect has a great impact on the feed force, and for hardened tool steel AISI D2, the stagnation angle of 30 o is more appropriate. (2) Also, stress concentration appears and shear slipping occurs along the shear plane in the process of serrated chip formation. The strain rate on the shear slipping surface is much greater than other places and the temperature gradient perpendicular to the shear plane is relatively higher. (3) The cutting force becomes larger with increasing the hardness value of workpieces, which causes the chip to more likely to produce serrated chips. (4) The fluctuation of cutting force is more significant as the cutting speed increases, which puts forward higher requirements for the tool and machine tool.