A Prospective Study of Long-term Outcomes in Female Patients with Nonalcoholic Steatohepatitis Using Age- and Body Mass Index-matched Cohorts

In patients with nonalcoholic steatohepatitis (NASH), the prevalence of cirrhosis is higher among women than men, and hepatocellular carcinoma (HCC) develops mainly in the cirrhotic stage among women. However, the long-term outcomes in female patients with NASH have not been fully elucidated, and age, gender and BMI were not simultaneously adjusted in previous studies on the prognosis of NASH. To elucidate the outcomes in female patients with NASH, we prospectively compared NASH patients with advanced fibrosis (advanced NASH) with hepatitis C virus-related advanced fibrosis (advanced CHC) patients and NASH patients with mild fibrosis (mild NASH) using study cohorts that were adjusted for body mass index (BMI) in addition to age. The median follow-up period was 92.5 months. Liver-related complication-free survival was significantly reduced in the advanced NASH group compared to the mild NASH group. No liver-related complications developed in the mild NASH group. The overall survival, liver-related complication- and cardiovascular/cerebrovascular disease-free survival were not significantly different between the advanced NASH and CHC groups. Female patients with NASH and advanced fibrosis may have a less favorable prognosis for liver-related complications than the matched cohorts with NASH and mild fibrosis, but may have a similar prognosis to the matched cohorts with CHC

Permanent Electric Dipole-Dipole Interactions in Lyotropic Polypeptide Liquid Crystals

The interaction energy between two adjacent α-helical molecules was calculated taking into account for permanent electric dipoles locating orl the helical core of a polymer mainchain in order to explain the cholesteric structure of lyotropic polypeptide liquid crystals. It was concluded that the dipole-dipole interactions were responsible for the formation of the cholesteric structure

Transforming growth factor α protects against Fas-mediated liver apoptosis in mice

AbstractThe Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors have recently been found to function in preventing apoptosis. In this study, we demonstrated that overexpression of transforming growth factor α (TGFα) has a dramatic protective effect on Fas-mediated hepatic apoptosis at the biochemical and histological levels. Moreover, 85.7% (six out of seven) of TGFα transgenic mice survived the lethal liver damage, whereas all wild-type mice died. Expression of Bcl-xL, an anti-apoptotic protein, was greatly increased in the transgenic mice. Taken together, our findings suggest that TGFα protects against Fas-mediated liver apoptosis in vivo and up-regulation of Bcl-xL may participate in protective effect of TGFα

Joint Degradation in a Monkey Model of Collagen-Induced Arthritis: Role of Cathepsin K Based on Biochemical Markers and Histological Evaluation

The role of cathepsin K in joint degradation in a model of collagen-induced arthritis (CIA) in cynomolgus monkey was examined using biochemical markers and histology. Joint swelling, urinary C-telopeptide of type II collagen (CTX-II), deoxypyridinoline (DPD), and N- and C-telopeptides of type I collagen (NTX and CTX-I, resp.) were analyzed. Immunohistochemistry of type II collagen, cathepsin K, and CTX-II were performed using joints. Joint swelling reached peak on day 42 and continued at this level. The CTX-II level peaked on day 28 and declined thereafter, while CTX-I, NTX, and DPD reached plateau on day 43. Joint swelling was positively correlated with CTX-II increases on days 20 and 42/43, with increases in CTX-I and NTX/Cr on days 42/43 and 84, and with DPD increases throughout the study period. Intense cathepsin K staining was observed in osteoclasts and in articular cartilage and synovial tissue in arthritic joints. CTX-II was present in the superficial layer of articular cartilage in CIA monkeys. Evidence from biochemical markers suggests that matrix degradation in the CIA model starts with degradation of cartilage, rather than bone resorption. Cathepsin K expressed in osteoclasts, articular cartilage, and synovial tissue may contribute to degradation of cartilage

Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo

AbstractThe effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF

TREM2 Expression in Schizophrenia

TREM2 and TYROBP are causal genes for Nasu–Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer’s disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia. Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia. Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P < 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients. Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders