Background: and Purpose The objective of this study was to identify 2-year longitudinal changes in the muscle thickness (MT) and echo intensity (EI) of the abdominal, thigh, and lower limb muscles in chronic stroke survivors. Methods: This study included 15 chronic stroke survivors aged 74.1±9.9 years. The MT, EI, and subcutaneous fat thickness values of the following muscles on the paretic and nonparetic sides were assessed on transverse ultrasound images: rectus abdominis, external oblique, internal oblique, transversus abdominis, rectus femoris (RF), vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, gastrocnemius, and soleus. The ultrasound measurements were performed both at baseline and 2 years later. Results: After 2 years, the VL on the paretic side showed a significant decrease in MT (p= 0.031) and increase in EI (p=0.002), whereas the RF on the nonparetic side showed a significant decrease in EI (p=0.046). Correlation coefficient analyses showed that changes in MT (r= 0.668, p=0.012) and EI (r=0.597, p=0.018) of the VL on the paretic side were significantly associated with a change in the body mass index. Conclusions The findings of this longitudinal study suggest that the VL on the paretic side is subject to deteriorations in muscle quantity and quality, and conversely that the RF on the nonparetic side shows an improvement in muscle quality after 2 years in chronic stroke survivors

BACKGROUND: Ballooned hepatocytes (BH) are a key histological hallmark of nonalcoholic steatohepatitis (NASH), yet their consequences for liver-specific functions are unknown. METHODS: In our previous study, an experimental model of human induced-BHs (iBH) has been successfully developed based on cell sheet technology. This study aimed to determine the functions of iBHs in the primary human hepatocyte/ normal human dermal fibroblast (PHH/NHDF) co-culture cell sheets. Normal hepatocytes in the PHH/3T3-J2 co-culture cell sheets were set as a control, since 3T3-J2 murine embryonic fibroblasts have exhibited previously long term maintenance of PHH functions. RESULTS: It was found that, albumin secretion was not affected in iBHs, but urea synthesis as well as cytochrome P450 enzyme (CYP) activities including CYP1A2 and CYP3A4, were significantly reduced in iBHs. Besides, loss of bile canaliculi was observed in iBHs. These findings are consistent with clinical studies of human NASH. In addition, PHH/ NHDF cell sheets demonstrated two fold higher TGF-b1 secretion compared with PHH/3T3-J2 cell sheets. Furthermore, treatment with a TGF-b inhibitor and a semi-synthetic bile acid analogue (obeticholic acid, phase 3 trial of NASH therapy) ameliorated the histological appearance of established iBHs. CONCLUSION In summary, this study demonstrates the priority of iBHs in recapitulating not only histology but also clinically relevant hepatic dysfunctions in human NASH and suggests TGF-b and bile acid related signal pathway may play important roles in the formation of iBHs.

BACKGROUND: Ballooned hepatocytes (BH) are a key histological hallmark of nonalcoholic steatohepatitis (NASH), yet their consequences for liver-specific functions are unknown. METHODS: In our previous study, an experimental model of human induced-BHs (iBH) has been successfully developed based on cell sheet technology. This study aimed to determine the functions of iBHs in the primary human hepatocyte/ normal human dermal fibroblast (PHH/NHDF) co-culture cell sheets. Normal hepatocytes in the PHH/3T3-J2 co-culture cell sheets were set as a control, since 3T3-J2 murine embryonic fibroblasts have exhibited previously long term maintenance of PHH functions. RESULTS: It was found that, albumin secretion was not affected in iBHs, but urea synthesis as well as cytochrome P450 enzyme (CYP) activities including CYP1A2 and CYP3A4, were significantly reduced in iBHs. Besides, loss of bile canaliculi was observed in iBHs. These findings are consistent with clinical studies of human NASH. In addition, PHH/ NHDF cell sheets demonstrated two fold higher TGF-b1 secretion compared with PHH/3T3-J2 cell sheets. Furthermore, treatment with a TGF-b inhibitor and a semi-synthetic bile acid analogue (obeticholic acid, phase 3 trial of NASH therapy) ameliorated the histological appearance of established iBHs. CONCLUSION In summary, this study demonstrates the priority of iBHs in recapitulating not only histology but also clinically relevant hepatic dysfunctions in human NASH and suggests TGF-b and bile acid related signal pathway may play important roles in the formation of iBHs.