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Background/Aims: Alterations in the blood-brain barrier (BBB) may play an important role in the pathogenesis and treatment of Alzheimer's disease (AD). We investigated BBB disturbance and its influence on the equilibrium of amyloid-beta protein (Abeta) between plasma and cerebrospinal fluid (CSF) in AD patients. Methods: We analyzed albumin ratio as a marker of the BBB permeability and correlated it with the severity of dementia, brain atrophy on MRI, apolipoprotein E isoform, CSF levels of total tau, CSF and plasma levels of Abeta 1-40 (Abeta(40)) and 1-42 (Abeta(42)), and CSF/plasma ratios of Abeta(40) and Abeta(42) in 42 AD patients. Results: The albumin ratio was positively correlated with the severity of medial temporal lobe atrophy but not with the other parameters including CSF/plasma ratios of Abeta(40) or Abeta(42). Conclusion: Our results suggest that progression of medial temporal lobe atrophy is associated with increased BBB permeability and that the transport of Abeta across the BBB is not influenced by the BBB alteration in AD. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

We developed a novel hepatitis B virus (HBV) infection-monitoring system using a luminescent, 11-amino acid reporter (HiBiT). We performed high-throughput antiviral screening using this system to identify anti-HBV compounds. After the infection of primary human hepatocytes with the recombinant virus HiBiT-HBV, which contains HiBiT at its preS1, 1262 compounds were tested in a first screening using extracellular HiBiT activity as an indicator of viral infection. Following a second screening, we focused on the compound skimmianine, which showed a potent antiviral effect. When skimmianine was added at the same time as HiBiT-HBV infection, skimmianine inhibited HiBiT activity with EC 50 of 0.36 pM, CC 50 of 1.67 μM and a selectivity index (CC 50 :EC 50 ratio) of 5,100,000. When skimmianine was added 72 h after HiBiT-HBV infection, the EC 50 , CC 50 and selectivity index were 0.19 μM, 1.87 μM and 8.79, respectively. Time-lapse fluorescence imaging analysis using another recombinant virus, ReAsH-TC155HBV, with the insertion of tetra-cysteine within viral capsid, revealed that skimmianine inhibited the accumulation of the capsid into hepatocytes. Furthermore, skimmianine did not inhibit either attachment or internalization. These results imply that skimmianine inhibits the retrograde trafficking of the virus after internalization. This study demonstrates the usefulness of the recombinant virus, HiBiT-HBV, for high-throughput screening to identify anti-HBV compounds.

Objective: It is a big problem that many older adults are physically inactive. Well-known benefits of physical exercise include a decrease in the risk of cognitive decline and physical frailty. Therefore, this study aims to examine whether our proposed exercise program can prevent cognitive decline and improve physical function in the elderly., Methods: This study will include nondemented older adults ( n  = 103) without regular exercise habits. The trial will include a physical exercise training program (once a week) and nutritional lectures (once a month) over 5 months and follow-up for ≥1 year. The primary endpoint is the program's efficacy in preventing cognitive decline, as assessed by changes in the memory performance index of the mild cognitive impairment (MCI) screen; the secondary endpoints are the incidence of MCI and dementia, physical testing, and frailty proportion. In the exploratory phase of the study, we will elucidate the underlying diseases causing MCI in community-dwelling older adults by neuroimaging., Discussion: This double-arm trial that aims to assess the impact of physical exercise on nondemented older adults' cognitive and physical function. Furthermore, our newly developed exercise program will be easy for older adults to undertake. Clinical Trial Registration : https://clinicaltrials.gov/, identifier [jRCT 1040220140]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Noguchi-Shinohara, Yokoyama, Komatsu, Masuda, Kouno, Yoshita and Ono.)