ObjectiveDeveloping a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs).DesignTransplantation of hBMSCs into Fah-/-Rag2-/-IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanised (hBMSC-FRGS) mouse. The generated hBMSC-FRGS mice were subjected to assessments of sustained viremia, specific immune and inflammatory responses and liver pathophysiological injury to characterise the progression of chronic hepatitis and cirrhosis after HBV infection.ResultsThe implantation of hBMSCs rescued FHF mice, as demonstrated by robust proliferation and transdifferentiation of functional human hepatocytes and multiple immune cell lineages, including B cells, T cells, natural killer cells, dendritic cells and macrophages. After HBV infection, the hBMSC-FRGS mice developed sustained viremia and specific immune and inflammatory responses and showed progression to chronic hepatitis and liver cirrhosis at a frequency of 55% after 54 weeks.ConclusionThis new humanised mouse model recapitulates the liver cirrhosis induced by human HBV infection, thus providing research opportunities for understanding viral immune pathophysiology and testing antiviral therapies in vivo.
Osteoarthritis (OA) is a chronic bone and joint disease characterized by articular cartilage degeneration and joint inflammation and is the most common form of arthritis. The clinical manifestations of OA are chronic pain and joint activity disorder, which severely affect the patient quality of life. Long non-coding RNA (lncRNA) is a class of RNA molecules >200 nucleotides long that are expressed in animals, plants, yeast, prokaryotes and viruses. lncRNA molecules lack an open reading frame and are not translated into protein. The present review collated the results of recent studies on the role of lncRNA in the pathogenesis of OA to provide information for the prevention, diagnosis and treatment of OA. Contents 1. Introduction 2. Biological functions of lncRNA 3. Relationship between lncRNAs and osteoarthritis 4. Conclusions and perspectives
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