Browsing by Author "Ding, Fei"

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    Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
    (Journal of the American Heart Association, 2018-09) Shen, Yuntian; Yan, Baihui; Zhao, Qiang; Wang, Zhuoran; Wu, Jiangbo; Ren, Jiafa; Wang, Wei; Yu, Shu; Sheng, Huaxin; Crowley, Steven D; Ding, Fei; Paschen, Wulf; Yang, Wei
    Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood. Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA . Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ). Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level. CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord. Thiamet-G was used to increase O-linked β-N-acetylglucosamine modification. After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice. Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice. Finally, pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA improved outcome. Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia. Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
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    Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.
    (Oncotarget, 2016-05) Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; Chang, Jianhua; Wei, Qingyi
    The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.
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    Ultra-broadband microwave metamaterial absorber
    (Applied Physics Letters, 2012-03-05) Ding, Fei; Cui, Yanxia; Ge, Xiaochen; Jin, Yi; He, Sailing
    A microwave ultra-broadband polarization-independent metamaterial absorber is demonstrated. It is composed of a periodic array of metal-dielectric multilayered quadrangular frustum pyramids. These pyramids possess resonant absorption modes at multi-frequencies, of which the overlapping leads to the total absorption of the incident wave over an ultra-wide spectral band. The experimental absorption at normal incidence is above 90% in the frequency range of 7.8-14.7GHz, and the absorption is kept large when the incident angle is smaller than 60 degrees. The experimental results agree well with the numerical simulation.