Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors

Biomechanics and Modeling in Mechanobiology - Recent experimental evidence points to the possibility that cell surface-associated caveolae may participate in mechanotransduction. The particular...     

Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors

Background: D-serine, the enantiomer of L-serine, was identified in mammals 20?years ago. Although a close relationship between D-serine and renal dysfunction has been shown, the clinical implications of urinary D- and L-serine in humans are poorly understood. The aim of this study was to evaluate the relationship between urinary D- and L-serine with well-known renal biomarkers, and clarify the prognostic value of D- and L-serine for renal events.

Methods: This cross-sectional, prospective study included 65 patients with atherosclerotic risk factors, who were followed up for a median of 16?months. The primary endpoint was a composite of end-stage renal disease and a decline in estimated glomerular filtration rate (eGFR)?≥?25% from baseline.

Results: Urinary D-serine concentrations showed a better correlation with eGFR than did urinary L-serine, whereas neither urinary D- nor L-serine correlated with tubular markers such as urinary liver-type fatty acid-binding protein and N-acetyl-beta-D-glucosaminidase. A Cox regression analysis revealed that low urinary D-serine levels were significantly associated with the primary endpoint after adjusting for confounding factors (hazard ratio 12.60; 95% confidence interval, 3.49–45.51).

Conclusions: Urinary D-serine is associated with glomerular filtration and can be a prognostic biomarker of renal dysfunction in patients with atherosclerotic risk factors.     

Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

On the basis of deguelin, a series of the B,C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1α inhibition. Among them, compound 57 showed potent HIF-1α inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 C-terminal inhibitor.     

Evaluation of the feasibility and preference of Nox-A1 type 2 ambulatory device for unattended home sleep test: a randomized crossover study

Sleep and Biological Rhythms - There is an increasing need for portable sleep monitoring in clinical practice, but there is no comparative study that used the same device for home and in-laboratory...     

Effective tempo of the step test for dynamic balance ability in the elderly

This study aimed to examine the reliability and sex- and age-related differences of step tests with stipulated tempos as well as to clarify useful test parameters and tempos. One hundred forty elderly people and fifty young adults conducted tapping and stepping tests, matching the tempo provided by a metronome. Both tests involve movements where the subject touches a sheet with both the right and left hands or right and left legs at a designated spot. Evaluation parameters were the time difference between the beep sound and the time at which the sheet was touched in both tests as well as two-leg support and one-leg support times in the step test. The trial-to-trial reliability of the parameters in both tests was high. The time differences of both 40 bpm tests in the elderly were larger in males than in females. In the step test, the time difference and two-leg support times of the elderly were larger, in the order of 40, 60, and 120 bpm, and the one-leg support time was less in 40 bpm than 60 bpm or 120 bpm. The one-leg support time of the young subjects was larger, in the order of 40, 60, and 120 bpm. A significant age-related difference was found in the 40 bpm and 60 bpm test, and the time difference and two-leg support time were larger in the elderly while the one-leg support time was larger in the young subjects. The time difference at 40 bpm in the elderly was larger in the step test than in the tap test. There was no significant difference between both tests in the young subjects. In conclusion, the step test with the slow tempo, because it requires a long one-leg support phase, is effective for evaluating dynamic balance in the elderly. The time difference and two-leg and one-leg support times are effective evaluation parameters of the step test.     

High Performance Proteomics: 7th HUPO Brain Proteome Project Workshop March 7-9, 2007 Wellcome Trust Conference Centre, Hinxton, UK

The Wellcome Trust Conference Centre at Hinxton, UK, was the meeting place of the 7th HUPO Brain Proteome Project Workshop entitled "High Performance Proteomics". It started on Wednesday, March 7, 2007 with a steering committee meeting followed by a two days series of talks dealing with the standardization and handling of tissues, body fluids as well as of proteomics data. The presentation and accompanying vivid discussions created a picture of actual strategies and standards in recent proteomics.     

Laurus nobilis leaf extract controls inflammation by suppressing NLRP3 inflammasome activation

Laurus nobilis Linn. (Lauraceae), commonly known as Bay, has been used as a traditional medicine in the Mediterranean and Europe to treat diverse immunological disorders. Although the effects of L. nobilis on immunosuppression have been reported, the detailed underlying mechanism remains unclear. In this study, to elucidate the anti-inflammatory mechanism of L. nobilis, we examined the effect of L. nobilis leaf extract on inflammasome activation in mouse bone marrow-derived macrophages. L. nobilis leaf extract inhibited NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation, which was associated with caspase-1 activation, interleukin-1β secretion, and apoptosis-associated speck-like protein containing a CARD (ASC) pyroptosome complex formation. We also observed that 1,8-cineole, the major component of L. nobilis extract, consistently suppressed NLRP3 inflammasome activation. Furthermore, L. nobilis leaf extract attenuated the in vivo expression of proinflammatory cytokines in an acute lung injury mouse model. Our results provide the first evidence that L. nobilis leaf extract modulates inflammatory signaling by suppressing inflammasome activation.