Frequency of <i>C</i>-Allylations on Oligoglycinates via <i>N</i>-Ylides

The highly selective mono-<i>C</i>-allylation of oligoglycinates such as a diethylenetriaminepentaacetate, an iminodiacetate, and an ethylenediaminetetraacetate via insertion of a vacuum operation between the <i>N</i>-allylation and C-migration steps is reported. It is contrastive that one-pot <i>N</i>-allylation–<i>C</i>-allylation procedure gave a mixture including multiallylated products. In the reaction with <i>N</i>-ylides, <i>gem-C</i>-diallylation and α,α′-<i>C</i>-diallylation of oligoglycinates are strongly inhibited even with the use of an excess of allyl bromide and base. A mechanism to explain this control of the frequency of <i>C</i>-allylation on oligoglycinates via <i>N</i>-ylides is also proposed

Accumulation of 8-PN in the GM. (a)–(e): HPLC chromatograms for quantitative analyses of 8-PN or naringenin in the GM.

<p>Chromatograms from mice fed an 8-PN-containing diet (a) and control diet (b). Chromatograms from mice fed a naringenin-containing diet (c) and control diet (d). (a) and (b) were obtained by the analytical condition for 8-PN. (c) and (d) were obtained by the analytical condition for naringenin. These analyses were undertaken by HPLC with electrochemical detection. (e) Contents of these flavonoids in the GM as determined by HPLC analysis. Data are the mean ± S.E (n = 4). Different letters indicate significant differences analyzed by the Tukey multiple comparison test with two-way ANOVA (<i>p</i> = 0.00043).</p

Preventive effect of <i>Humulus lupulus</i> on disuse muscle atrophy.

<p>Mice consumed a <i>Humulus lupulus</i>-mixed diet for 14 days, after which denervation was carried out. After 4 days, the weight of the GM was measured. The level of atrophy was calculated to be the ratio of the weight of denervated muscle to the weight of sham muscle in each mouse. Data are the mean ± S.E (n = 3). Asterisks indicate significant differences analyzed by the Student’s <i>t</i>-test (P = 0.0046).</p

Pharmacokinetic parameters of flavonoids after oral administration of 8-PN and naringenin (50 mg/kg body weight) in a single dose in mice.

<p>C_max: maximum concentration in plasma; AUC: area under the plasma concentration–time curve; Tmax: time to maximum plasma concentration; T_1/2: half-life of flavonoid in the elimination phase.</p><p>Each flavonoid (50 mg/kg bw) was administered to mice once by stomach intubation. Plasma concentration was analyzed by HPLC–UV. Data are the mean ± S.E (n = 4). Asterisks indicate significant differences between two groups (C_max: <i>p</i> = 0.026; AUC: <i>p</i> = 0.0039, Student’s <i>t-</i>test).</p

Accumulation of 8-PN and naringenin in the GM and plasma after their dietary intake for 22 days.

<p>Blood was collected from mice fed flavonoid (5.6 mmol flavonoid/kg diet) for 22 days, and then total body reflux was carried out. The GM was collected after the reflux. Plasma was prepared from the blood as described in the Materials and Methods section. Values of the total 8-PN and total naringenin indicate the sum of aglycone and conjugated metabolites obtained by the HPLC analysis with deconjugation treatment. Amount of flavonoids was determined by HPLC analyses as described in the Materials and Methods section. Data are the mean ± S.E. Different letters indicate significant differences upon analyses by the Tukey multiple comparison test with two-way ANOVA (<i>p</i> = 1.79×10^–9).</p

Protein and water content in the GM.

<p>Data are the mean ± S.E. There was no significant difference upon analyses by the Tukey multiple comparison test with one-way ANOVA (<i>p</i><0.05).</p

Cellular uptake of 8-PN in mouse C2C12 myotubes.

<p>Differentiated C2C12 cells seeded on 60-mm dishes were used. (a) 8-PN and (b) naringenin (10 µM) were administered to the cells for the indicated time. Cell homogenates were prepared and then each flavonoid was extracted. Amounts of flavonoids were determined by HPLC with UV detection. Data are the mean ± S.E (n = 3).</p

8-PN can prevent disuse muscle atrophy by enhancing Akt phosphorylation.

<p>(a) Muscle atrophy induced by denervation. The weight of the GM was measured after denervation for the indicated period. Open bar: sham leg (left); closed bar: denervated leg (right). Data are the mean ± S.E (n = 4). Asterisks indicate significant differences between sham and the denervated leg (Student’s <i>t</i>-test, <i>p</i><0.007). (b) Effect of dietary intake of 8-PN or naringenin on muscle atrophy. Mice consumed each flavonoid-mixed diet for 18 days, and denervation was then carried out. After 4 (black bar) or 6 (white bar) days, the level of atrophy in the GM was calculated as the ratio of the weight of denervated muscle to the weight of sham muscle in each mouse. Data are the mean ± S.E (n = 4). C: control-diet group, 8-PN: 8-PN-containing diet group. Asterisks indicate significant differences to the control diet, which was analyzed by the Tukey multiple comparison test with one-way ANOVA (day 4: <i>p</i> = 0.0034; day 6: <i>p</i> = 0.041). (c) Phosphorylation of Akt and atrogin-1 in the GM (which was collected on the 6th day after denervation) was detected by western blotting (upper) and the density of each image analyzed (bottom). The black bar and white bar in left graph denote phosphorylated Akt and total Akt, respectively. Data are the mean ± S.E (n = 4). C: control-diet group, 8-PN: 8-PN-containing diet group. *Significant differences to the control diet-denervation group (<i>p</i>0.05). #Significant differences to the control diet-sham group.</p

Conversion of xanthohumol to 8-prenylnaringenin (8-PN).

<p>Conversion of xanthohumol to 8-prenylnaringenin (8-PN).</p

Transient Elastography-Based Liver Profiles in a Hospital-Based Pediatric Population in Japan

<div><p>Background & Aims</p><p>The utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children.</p><p>Methods</p><p>FibroScan examinations were performed in pediatric patients (age, 1–18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥90%), non-obese healthy controls, and non-obese patients with liver disease.</p><p>Results</p><p>Among 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3–17.6 yr; 115 male). CAP values (mean±SD) were higher in the obese group (n = 52, 285±60 dB/m) compared with the liver disease (n = 40, 202±62, <i>P</i><0.001) and the control (n = 107, 179±41, <i>P</i><0.001) group. LSM values were significantly higher in the obese group (5.5±2.3 kPa) than in the control (3.9±0.9, <i>P</i><0.001), but there were no significant differences in LSM between the liver disease group (5.4±4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups.</p><p>Conclusions</p><p>Childhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children.</p></div