作者: Li, Jiao ; Xu, Guo-Tong ; Shi, Si ; Jin, Caixia ; Sun, Wan ; Liu, Caiying ; Lu, Lixia ; Zhu, Tong ; Xu, Jing-Ying ; Ou, Qingjian ; Wang, Juan ; Zhang, Jieping ; Gao, Furong ; Zhang, Jingfa ; Tian, Haibin

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world, and timely prevention and treatment are very important. Previously, we found that a neurodegenerative factor, Glia maturation factor-β (GMFB), was upregulated in the vitreous at a very early stage of diabetes, which may play an important role in pathogenesis. Here, we found that in a high glucose environment, large amounts of GMFB protein can be secreted in the vitreous, which translocates the ATPase ATP6V1A from the lysosome, preventing its assembly and alkalinizing the lysosome in the retinal pigment epithelial (RPE) cells. ACSL4 protein can be recognized by HSC70, the receptor for chaperone-mediated autophagy, and finally digested in the lysosome. Abnormalities in the autophagy-lysosome degradation process lead to its accumulation, which catalyzes the production of lethal lipid species and finally induces ferroptosis in RPE cells. GMFB antibody, lysosome activator NKH477, CMA activator QX77, and ferroptosis inhibitor Liproxstatin-1 were all effective in preventing early diabetic retinopathy and maintaining normal visual function, which has powerful clinical application value. Our research broadens the understanding of the relationship between autophagy and ferroptosis and provides a new therapeutic target for the treatment of DR.

2020-09-01·European review for medical and pharmacological sciences

MicroRNA-362 inhibits cell growth and metastasis in glioblastoma by targeting MAPK1.

Article

作者: Shi, H-Z ; Ma, L-N ; Zhu, H ; Wang, D-N

OBJECTIVEGlioblastoma (GBM) is a deadly brain cancer that seriously threatens the lives of patients. Moreover, various microRNAs (miRNAs) have been found to be involved in the progression of GBM. The purpose of this study is to preliminarily elucidate the regulatory mechanism of miR-362 in GBM.PATIENTS AND METHODSThe abnormal expression of miR-362 and MAPK1 was detected by RT-qPCR or Western blot analysis in GBM tissues and cells. CCK-8 and transwell assays were performed to measure cell proliferation, migration and invasion. The relationship between miR-362 and MAPK1 was confirmed by luciferase reporter assay.RESULTSMiR-362 expression was reduced in GBM tissues and cells. The decreased expression of miR-362 predicted poor prognosis in GBM patients. Functionally, overexpression of miR-362 inhibited the proliferation and metastasis of GBM cells. In addition, miR-362 directly targets MAPK1. MAPK1 was negatively correlated with miR-362 expression in GBM. Moreover, MAPK1 was upregulated and served as a tumor promoter in GBM. More importantly, the upregulation of MAPK1 weakened the inhibitory effect of miR-362 on cell proliferation and metastasis in GBM.CONCLUSIONSMiR-362 restrains cell proliferation and metastasis in GBM by targeting MAPK1, indicating that miR-362 functions as a tumor suppressor in GBM.

2020-07-01·Journal of Insect Physiology3区 · 农林科学

Role of adenosine in functional recovery following anoxic coma in Locusta migratoria

3区 · 农林科学

Article

作者: Lanz, Christopher ; Robertson, R Meldrum ; Van Dusen, Rachel A

When exposed to prolonged anoxia insects enter a reversible coma during which neural and muscular systems temporarily shut down. Nervous system shut down is a result of spreading depolarization throughout neurons and glial cells. Upon return to normoxia, recovery occurs following the restoration of ion gradients. However, there is a delay in the functional recovery of synaptic transmission following membrane repolarization. In mammals, the build-up of extracellular adenosine following spreading depolarization contributes to this delay. Adenosine accumulation is a marker of metabolic stress and it has many downstream effects through the activation of adenosine receptors, including the inhibition of cAMP production. Here we demonstrate that adenosine lengthens the time to functional recovery following anoxic coma in locusts. Caffeine, used as an adenosine receptor antagonist, decreased the time to recovery in intact animals and lengthened the time to recovery in semi-intact animals. A cAMP inhibitor, NKH 477, delayed recovery time in male animals. Our results show that the rate of recovery in insect systems is affected by the presence of adenosine.

100 项与考福新达普酸盐酸盐相关的药物交易

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