Data_Sheet_1_Osteoporosis is associated with elevated baseline cerebrospinal fluid biomarkers and accelerated brain structural atrophy among older people.docx

ObjectiveThe aim of this study was to examine whether osteoporosis (OP) is associated with Alzheimer’s disease-related cerebrospinal fluid (CSF) biomarkers and brain structures among older people.MethodsFrom the Alzheimer’s disease Neuroimaging Initiative database, we grouped participants according to the OP status (OP+/OP−) and compared the Alzheimer’s disease (AD)-related CSF biomarker levels and the regional brain structural volumes between the two groups using multivariable models. These models were adjusted for covariates including age, education, gender, diagnosis of Alzheimer’s disease, and apolipoprotein E4 carrier status.ResultsIn the cross-sectional analyses at baseline, OP was related to higher CSF t-tau (total tau) and p-tau181 (tau phosphorylated at threonine-181) but not to CSF amyloid-beta (1–42) or the volumes of entorhinal cortex and hippocampus. In the longitudinal analyses, OP was not associated with the change in the three CSF biomarkers over time but was linked to a faster decline in the size of the entorhinal cortex and hippocampus.ConclusionOP was associated with elevated levels of CSF t-tau and p-tau181 at baseline, and accelerated entorhinal cortex and hippocampal atrophies over time among older people.</p

Presentation_1_A Chimeric Humanized Mouse Model by Engrafting the Human Induced Pluripotent Stem Cell-Derived Hepatocyte-Like Cell for the Chronic Hepatitis B Virus Infection.PDF

<p>Humanized mouse model generated by grafting primary human hepatocytes (PHHs) to immunodeficient mouse has contributed invaluably to understanding the pathogenesis of hepatitis B virus (HBV). However, the source of PHHs is limited, which necessitates the search for alternatives. Recently, hepatocyte-like cells (HLCs) generated from human induced pluripotent stem cells (hiPSCs) have been used for in vitro HBV infection. Herein, we developed a robust human liver chimeric animal model to study in vivo HBV infection by engrafting the hiPSC-HLCs to Fah^-/-Rag2^-/-IL-2Rγc^-/-SCID (FRGS) mice. After being optimized by a small molecule, XMU-MP-1, the hiPSC-HLCs engrafted FRGS (hHLC-FRGS) mice displayed approximately 40% liver chimerism at week 6 after engraftment and maintained at this level for at least 14 weeks. Viremia and HBV infection markers include antigens, RNA, DNA, and covalently closed circular DNA were detectable in HBV infected hHLC-FRGS mice. Furthermore, hiPSC-HLCs and hHLC-FRGS mice were successfully used to evaluate different antivirals. Therefore, we established a humanized mouse model for not only investigating HBV pathogenesis but also testing the effects of the anti-HBV drugs.</p><p>Highlights:</p><p>   (1) The implanted hiPSC-HLCs established a long-term chimerism in FRGS mice liver.</p><p>   (2) hHLC-FRGS mice are adequate to support chronic HBV infection with a full viral life cycle.</p><p>   (3) hiPSC-HLCs and hHLC-FRGS mice are useful tools for evaluation of antivirals against HBV infection in vitro and in vivo.</p><p>Research in Context </p><p>To overcome the disadvantages of using primary human hepatocytes, we induced human pluripotent stem cells to hepatocyte-like cells (hiPSC-HLCs) that developed the capability to express important liver functional markers and critical host factors for HBV infection. The hiPSC-HLCs were permissive for the HBV infection and supported a full HBV replication. The hiPSC-HLCs were then engrafted to immunodeficient mouse to establish a chimeric liver mouse model, which was capable of supporting HBV infection in vivo and evaluating the effects of antiviral drugs. Our results shed light into improving the cellular and animal models for studying HBV and other hepatotropic viruses.</p

Image_1_A Chimeric Humanized Mouse Model by Engrafting the Human Induced Pluripotent Stem Cell-Derived Hepatocyte-Like Cell for the Chronic Hepatitis B Virus Infection.PDF

<p>Humanized mouse model generated by grafting primary human hepatocytes (PHHs) to immunodeficient mouse has contributed invaluably to understanding the pathogenesis of hepatitis B virus (HBV). However, the source of PHHs is limited, which necessitates the search for alternatives. Recently, hepatocyte-like cells (HLCs) generated from human induced pluripotent stem cells (hiPSCs) have been used for in vitro HBV infection. Herein, we developed a robust human liver chimeric animal model to study in vivo HBV infection by engrafting the hiPSC-HLCs to Fah^-/-Rag2^-/-IL-2Rγc^-/-SCID (FRGS) mice. After being optimized by a small molecule, XMU-MP-1, the hiPSC-HLCs engrafted FRGS (hHLC-FRGS) mice displayed approximately 40% liver chimerism at week 6 after engraftment and maintained at this level for at least 14 weeks. Viremia and HBV infection markers include antigens, RNA, DNA, and covalently closed circular DNA were detectable in HBV infected hHLC-FRGS mice. Furthermore, hiPSC-HLCs and hHLC-FRGS mice were successfully used to evaluate different antivirals. Therefore, we established a humanized mouse model for not only investigating HBV pathogenesis but also testing the effects of the anti-HBV drugs.</p><p>Highlights:</p><p>   (1) The implanted hiPSC-HLCs established a long-term chimerism in FRGS mice liver.</p><p>   (2) hHLC-FRGS mice are adequate to support chronic HBV infection with a full viral life cycle.</p><p>   (3) hiPSC-HLCs and hHLC-FRGS mice are useful tools for evaluation of antivirals against HBV infection in vitro and in vivo.</p><p>Research in Context </p><p>To overcome the disadvantages of using primary human hepatocytes, we induced human pluripotent stem cells to hepatocyte-like cells (hiPSC-HLCs) that developed the capability to express important liver functional markers and critical host factors for HBV infection. The hiPSC-HLCs were permissive for the HBV infection and supported a full HBV replication. The hiPSC-HLCs were then engrafted to immunodeficient mouse to establish a chimeric liver mouse model, which was capable of supporting HBV infection in vivo and evaluating the effects of antiviral drugs. Our results shed light into improving the cellular and animal models for studying HBV and other hepatotropic viruses.</p