bims-nastce Biomed News
on NASH and T cells
Issue of 2022‒01‒09
four papers selected by
Petra Hirsova
Mayo Clinic College of Medicine


  1. Cancer Discov. 2022 Jan 07.
      Integrated single-cell analysis of T cells reveals landscapes of T-cell states in different cancers.
    DOI:  https://doi.org/10.1158/2159-8290.CD-RW2022-002
  2. Curr Dev Nutr. 2021 Dec;5(12): nzab138
      Nonalcoholic fatty liver disease (NAFLD) is intricately linked to metabolic disease (including obesity, glucose intolerance, and insulin resistance) and encompasses a spectrum of disorders including steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis. Rodents consuming high-fat (HF; ∼40 kcal% fat including fats containing higher concentrations of saturated and trans fats), high-fructose (HFr), and high-cholesterol (HC) diets display many clinically relevant characteristics of NASH, along with other metabolic disorders. C57BL/6 mice are the most commonly used animal model because they can develop significant metabolic disorders including severe NASH with fibrosis after months of feeding, but other models also are susceptible. The significant number of diets that contain these different factors (i.e., HF, HFr, and HC), either alone or in combination, makes the choice of diet difficult. This methodology review describes the efficacy of these nutrient manipulations on the NAFLD phenotype in mice, rats, guinea pigs, hamsters, and nonhuman primates.
    Keywords:  NAFLD; diet; guinea pigs; hamsters; high-cholesterol; high-fat; high-fructose; mice; nonhuman primates; rats
    DOI:  https://doi.org/10.1093/cdn/nzab138
  3. Metabolism. 2021 Dec 30. pii: S0026-0495(21)00415-7. [Epub ahead of print] 155115
      BACKGROUND: Due to its extremely high prevalence and severity, non-alcoholic fatty liver disease (NALFD) is a serious health and economic concern worldwide. Developing effective methods of diagnosis and therapy demands a deeper understanding of its molecular basis. One of the strategies in such an endeavor is the analysis of alterations in the morphology of liver cells. Such alterations, widely reported in NAFLD patients and disease models, are related to the cytoskeleton. Therefore, the fate of the cytoskeleton components is useful to uncover the molecular basis of NAFLD, to further design innovative approaches for its diagnosis and therapy.MAIN FINDINGS: Several cytoskeleton proteins are up-regulated in liver cells of NAFLD patients. Under pathological conditions, keratin 18 is released from hepatocytes and its detection in the blood emerges as a non-invasive diagnosis tool. α-smooth muscle actin is up-regulated in hepatic stellate cells and its down-regulation has been widely tested as a potential NALFD therapeutic approach. Other cytoskeleton proteins, such as vimentin, are also up-regulated.
    CONCLUSIONS: NAFLD progression involves alterations in expression levels of proteins that build the liver cytoskeleton or associate with it. These findings provide a timely opportunity of developing novel approaches for NAFLD diagnosis and therapy.
    Keywords:  Cytoskeleton; Hepatic stellate cells; Hepatocytes; Keratin 18; Non-alcoholic fatty liver disease; α-Smooth muscle actin
    DOI:  https://doi.org/10.1016/j.metabol.2021.155115
  4. J Vis Exp. 2021 Dec 16.
      With the increase of incidence, inflammatory bowel diseases (IBD), which are chronic diseases affecting the gastrointestinal tract, impose a considerable health and financial burden on individuals and society. Therefore, it is critical to investigate the mechanisms underlying the pathogenesis and development of IBD. Here, a gut microbiota antigen-specific T cell transfer colitis model is described. CBir1 flagellin has been recognized as the immunodominant gut bacterial antigen in experimental colitis and patients with Crohn's disease. CBir1 TCR transgenic naϊve CD4+ T cells, specific to CBir1 flagellin, can induce chronic colitis after adoptive transfer into immune-deficient Rag1-/- mice. The disease severity is assessed by histopathology. The CD4+ T cell phenotypes in colonic lamina propria are also determined. This model closely resembles the development of IBD, which provides an ideal murine model for investigating the mechanisms driving the pathogenesis of IBD and testing the potential drugs for treating IBD.
    DOI:  https://doi.org/10.3791/63293