Browsing by Author "Li, Hui"

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    Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1
    (PLOS, 2009-05-29) Li, Hui; Wang, Dongmei; Singh, Lisam Shanjukumar; Berk, Michael; Tan, Haiyan; Zhao, Zhenwen; Steinmetz, Rosemary; Kirmani, Kashif; Wei, Gang; Xu, Yan; Obstetrics and Gynecology, School of Medicine
    Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK) activation and nitric oxide (NO) production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.
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    Chronic Voluntary Alcohol Drinking Causes Anxiety-like Behavior, Thiamine Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice
    (Frontiers Media, 2021-03-09) Xu, Hong; Li, Hui; Liu, Dexiang; Wen, Wen; Xu, Mei; Frank, Jacqueline A.; Chen, Jing; Zhu, Haining; Grahame, Nicholas J.; Luo, Jia; Psychology, School of Science
    The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water alone at the age of 60-day-old. The mice were exposed to alcohol for 7 months then subjected to neurobehavioral tests including open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Results from OF and EPM tests suggested that chronic voluntary drinking caused anxiety-like behaviors. After behavior tests, mice were sacrificed, and brain tissues were processed for biochemical analyses. Alcohol altered the levels of several neurotransmitters and neurotrophic factors in the brain including gamma-Aminobutyric acid (GABA), corticotropin-releasing factor, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor. Alcohol increased the expression of neuroinflammation markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor 2 (CCR2). Alcohol also induced cleaved caspase-3 and glial fibrillary acidic protein, indicative of neurodegeneration and gliosis. In addition, alcohol inhibited the expression of thiamine transporters in the brain and reduced thiamine levels in the blood. Alcohol also caused oxidative stress and endoplasmic reticulum (ER) stress, and stimulated neurogenesis.
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    Effects of Chronic Voluntary Alcohol Drinking on Thiamine Concentrations, Endoplasmic Reticulum Stress and Oxidative Stress in the Brain of Crossed High Alcohol Preferring Mice
    (Springer, 2019-11) Xu, Hong; Liu, Dexiang; Chen, Jing; Li, Hui; Xu, Mei; Wen, Wen; Frank, Jacqueline A.; Grahame, Nicholas J.; Zhu, Haining; Luo, Jia; Psychology, School of Science
    Chronic alcohol drinking can damage the central nervous system via many mechanisms. One of these may involve a deficiency of an essential nutrient, thiamine, as a result of chronic alcohol exposure. Although thiamine deficiency (TD) has often been linked to the neuropathology of alcohol-related brain damage, the underlying mechanisms remain to be investigated. The crossed High Alcohol Preferring (cHAP) mice prefer alcohol to water when they have free access. In this study, we used cHAP mice to determine the effect of chronic voluntary alcohol exposure on thiamine levels and neuropathological changes in the brain. The male cHAP mice were given free-choice access to 10% ethanol (EtOH) and water for 7 months, sacrificed, and thiamine concentrations in the blood plasma and brain were determined by liquid chromatography–mass spectrometry (LC-MS). The expression of thiamine transporters was examined by immunoblotting. In addition, oxidative stress, endoplasmic reticulum (ER) stress, active caspase-3 dependent apoptosis, and neurogenesis in the brain were evaluated. The results indicated that chronic alcohol exposure decreased thiamine levels and thiamine transporters, and increased oxidative stress, ER stress, and neuronal apoptosis in the brains. Interestingly, alcohol exposure also stimulated neurogenesis in the hippocampus which may serve as a compensatory mechanism in response to alcohol-induced brain damage. Our data have demonstrated that cHAP mice are a useful model to study the interaction between chronic alcohol consumption and TD, as well as TD’s contributions to the neuropathological processes resulting in alcohol-related brain damage.
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    Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats
    (Frontiers Media, 2020-05-01) Liu, Peifang; Li, Hui; Wang, Yueqiu; Su, Xiaolin; Li, Yang; Yan, Meiling; Ma, Lan; Che, Hui; Biochemistry and Molecular Biology, School of Medicine
    Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction.
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    A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults: a population-based study
    (Oxford, 2018-06) Li, Peiqin; Zhao, Jing; Kothapalli, Kumar S. D.; Li, Xiang; Li, Hui; Han, Yuxuan; Mi, Shengquan; Zhao, Wenhua; Li, Qizhai; Zhang, Hong; Song, Yiqing; Brenna, J. Thomas; Gao, Ying; Epidemiology, School of Public Health
    Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n–3) AA and n–3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n–6 AA and the ratio of AA to n–3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = −0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.
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    Society for Translational Medicine Expert consensus on the selection of surgical approaches in the management of thoracic esophageal carcinoma
    (AME Publishing Company, 2019-01) Mao, Yousheng; Yu, Zhentao; You, Bin; Fang, Wentao; Badgwell, Brian; Berry, Mark F.; Ceppa, DuyKhanh P.; Chen, Chun; Chen, Haiquan; Cuesta, Miguel A.; D’Journo, Xavier Benoit; Eslick, Guy D.; Fu, Jianhua; Fu, Xiangning; Gao, Shugeng; He, Jianxing; He, Jie; Huang, Yunchao; Jiang, Gening; Jiang, Zhongmin; Kim, Jae Y.; Li, Danqing; Li, Hui; Li, Shanqing; Liu, Deruo; Liu, Lunxu; Liu, Yongyu; Li, Xiaofei; Li, Yin; Mao, Weimin; Molena, Daniela; Morse, Christopher R.; Novoa, Nuria M.; Tan, Lijie; Tan, Qunyou; Toker, Alper; Tong, Ti; Wang, Qun; Weksler, Benny; Xu, Lin; Xu, Shidong; Yan, Tiansheng; Zhang, Lanjun; Zhang, Xingyi; Zhang, Xun; Zhang, Zhu; Zhi, Xiuyi; Zhou, Qinghua; Department of Surgery, Indiana University School of Medicine