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Shijiazhuang, China

Sun Y.,Hebei Medical University | Tian T.,Affiliated Hospital of Chengde Medical College | Gao J.,Hebei University | Liu X.,Hebei Medical University | And 8 more authors.
Journal of Neuroimmunology | Year: 2016

Immoderate immunoreaction of antigen-specific Th17 and Treg cell dysfunction play critical roles in the pathogenesis of multiple sclerosis. We examined Th17/Treg immune responses and the underlying mechanisms in response to metformin in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Metformin reduced Th17 and increased Treg cell percentages along with the levels of associated cytokines. Molecules involved in cellular metabolism were altered in mice with EAE. Suppressed activation of mTOR and its downstream target, HIF-1α, likely mediated the protective effects of metformin. Our findings demonstrate that regulation of T cell metabolism represents a new therapeutic target for CNS autoimmune disorders. © 2016 Elsevier B.V.. Source


Zhen C.,Hebei Medical University | Feng X.,Hebei Medical University | Li Z.,Hebei General Hospital | Wang Y.,Hebei Medical University | And 7 more authors.
Journal of Neuroimmunology | Year: 2015

Multiple sclerosis (MS) has been associated with a history of sub-optimal exposure to ultraviolet light, implicating vitamin D3 as a possible protective agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of experimental autoimmune encephalomyelitis (EAE), and explored its potential mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression. Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in the spinal cord. The protective effect of 1,25(OH)2D3 was associated with significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS treatment. © 2015 Elsevier B.V. Source


Guo Y.,Hebei Medical University | Guo Y.,Key Laboratory of Hebei Neurology | Guo Y.,Hebei Institute of Cardiocerebrovascular Disease | Zhang Y.,Roswell Park Cancer Institute | And 14 more authors.
Laboratory Investigation | Year: 2013

Oxidative stress is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the major cellular defense mechanisms against oxidative stress. However, the role of Nrf2-mediated neuroprotection (antioxidant defense) in the disease development of ALS remains unclear. To further investigate the role of Nrf2 in ALS, we genetically eliminate the Nrf2 gene from SOD1-G93A mice, a commonly used ALS mouse model, by generating a double mutant (Nrf2-/-SOD1-G93A mice). We found that it only had a modest impact on the course of disease by knocking out Nrf2 gene in these mice. Further studies demonstrated that, among previously known Nrf2-regulated phase II enzymes, only NAD(P)H: quinone oxidoreductase 1 induction was significantly affected by the elimination of Nrf2 gene in SOD1-G93A mice. Taken together, our data suggested that Nrf2 is not the sole mediator for the induction of antioxidant genes in SOD1-G93A mice, and Nrf2-mediated neuroprotection is not the key protective mechanism against neurodegeneration in those mice. © 2013 USCAP, Inc. All rights reserved. Source


An T.,Hebei Medical University | An T.,Beijing Shunyi Hospital of China Medical University | Shi P.,Hebei Medical University | Duan W.,Hebei Medical University | And 15 more authors.
Molecular Neurobiology | Year: 2014

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease involving both upper and lower motor neurons. The mechanism of motor neuron degeneration is still unknown. Although many studies have been performed on spinal motor neurons, few have been reported on brainstem and its motor nuclei. The aim of this study was to investigate oxidative stress and autophagic changes in the brainstem and representative motor nuclei of superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. The expression levels of cluster of differentiation molecule 11b (CD11b), glial fibrillary acidic protein, glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, voltage-dependent anion-selective channel protein 1, Sequestosome 1/p62 (p62), microtubule-associated protein 1 light chain 3B (LC3), and SOD1 proteins in brainstem were examined by Western blot analysis. Immunohistochemistry and immunofluorescence were performed to identify the cellular localization of SOD1, p62, and LC3B, respectively. The results showed that there were progressive asctrocytic proliferation and microglial activation, induction of antioxidant proteins, and increased p62 and LC3II expression in brainstem of SOD1-G93A mice. Additionally, SOD1 and p62 accumulated in hypoglossal, facial, and red nuclei, but not in oculomotor nucleus. Furthermore, electron microscope showed increased autophagic vacuoles in affected brainstem motor nuclei. Our results indicate that brainstem share similar gliosis, oxidative stress, and autophagic changes as the spinal cord in SOD1-G93A mice. Thus, SOD1 accumulation in astrocytes and neurons, oxidative stress, and altered autophagy are involved in motor neuron degeneration in the brainstem, similar to the motor neurons in spinal cord. Therefore, therapeutic trials in the SOD1G93A mice need to target the brainstem in addition to the spinal cord. © 2014 Springer Science+Business Media. Source


Zhang K.,Hebei Medical University | Shi P.,Hebei Medical University | An T.,Hebei Medical University | Wang Q.,Hebei Medical University | And 12 more authors.
Brain Research | Year: 2013

Autophagy dysregulation has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). The expression of LC3II and sequestosome 1 (P62) was progressively increased in the lumbar spinal cord of ALS mice. However, whether autophagy is activated or inhibited is still unclear. By treating mice with food restriction, a well-recognized way to induce autophagy, we found that 48 h of food restriction significantly reduced p62 and mutated SOD1 expressions at onset stage but not at pre-end stage in the spinal cord of SOD1-G93A mice. These data indicate that activating autophagy at a certain disease stage may have potential protective effects on ALS. © 2013 Elsevier B.V. Source

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