We aimed to identify the glucose metabolism statuses of nondiabetic Japanese adults using a machine learning model with a questionnaire. In this cross-sectional study, Japanese adults (aged 20–64 years) from Tokyo and surrounding areas were recruited. Participants underwent an oral glucose tolerance test (OGTT) and completed a questionnaire regarding lifestyle and physical characteristics. They were classified into four glycometabolic categories based on the OGTT results: category 1: best glucose metabolism, category 2: low insulin sensitivity, category 3: low insulin secretion, and category 4: combined characteristics of categories 2 and 3. A total of 977 individuals were included; the ratios of participants in categories 1, 2, 3, and 4 were 46%, 21%, 14%, and 19%, respectively. Machine learning models (decision tree, support vector machine, random forest, and XGBoost) were developed for identifying the glycometabolic category using questionnaire responses. Then, the top 10 most important variables in the random forest model were selected, and another random forest model was developed using these variables. Its areas under the receiver operating characteristic curve (AUCs) to classify category 1 and the others, category 2 and the others, category 3 and the others, and category 4 and the others were 0.68 (95% confidence intervals: 0.62–0.75), 0.66 (0.58–0.73), 0.61 (0.51–0.70), and 0.70 (0.62–0.77). For external validation of the model, the same dataset of 452 Japanese adults in Hokkaido was obtained. The AUCs to classify categories 1, 2, 3, and 4 and the others were 0.66 (0.61–0.71), 0.57 (0.51–0.62), 0.60 (0.50–0.69), and 0.64 (0.57–0.71). In conclusion, our model could identify the glucose metabolism status using only 10 factors of lifestyle and physical characteristics. This model may help the larger general population without diabetes to understand their glucose metabolism status and encourage lifestyle improvement to prevent diabetes.

The van der Waals ferromagnet Cr$_2$Ge$_2$Te$_6$ (CGT) has a two-dimensional crystal structure where each layer is stacked through van der Waals force. We have investigated the nature of the ferromagnetism and the weak perpendicular magnetic anisotropy (PMA) of CGT by means of X-ray absorption spectroscopy and X-ray magnetic circular dichroism (XMCD) studies of CGT single crystals. The XMCD spectra at the Cr $L_{2,3}$ edge for different magnetic field directions were analyzed on the basis of the cluster-model multiplet calculation. The Cr valence is confirmed to be 3+ and the orbital magnetic moment is found to be nearly quenched, as expected for the high-spin $t_{2g}$$^3$ configuration of the Cr$^{3+}$ ion. A large ($\sim 0.2$ eV) trigonal crystal-field splitting of the $t_{2g}$ level caused by the distortion of the CrTe$_6$ octahedron has been revealed, while the single-ion anisotropy (SIA) of the Cr atom is found to have a sign {\it opposite} to the observed PMA and too weak compared to the reported anisotropy energy. The present result suggests that anisotropic exchange coupling between the Cr atoms through the ligand Te $5p$ orbitals having strong spin-orbit coupling has to be invoked to explain the weak PMA of CGT, as in the case of the strong PMA of CrI$_3$.

Carnosic acid (CA), carnosol (CL) and rosmarinic acid (RA), components of the herb rosemary, reportedly exert favorable metabolic actions. This study showed that both CA and CL, but not RA, induce significant phosphorylation of AMP-dependent kinase (AMPK) and its downstream acetyl-CoA carboxylase 1 (ACC1) in HepG2 hepatoma cells. Glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), rate-limiting enzymes of hepatic gluconeogenesis, are upregulated by forskolin stimulation, and this upregulation was suppressed when incubated with CA or CL. Similarly, a forskolin-induced increase in CRE transcriptional activity involved in G6PC and PCK1 regulations was also stymied when incubated with CA or CL. In addition, mRNA levels of ACC1, fatty acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP-1c) were significantly reduced when incubated with CA or CL. Finally, it was shown that CA and CL suppressed cell proliferation and reduced cell viability, possibly as a result of AMPK activation. These findings raise the possibility that CA and CL exert a protective effect against diabetes and fatty liver disease, as well as subsequent cases of hepatoma.

Xerostomia, also known as dry mouth, is caused by a reduction in salivary secretion and by changes in the composition of saliva associated with the malfunction of salivary glands. Xerostomia decreases quality of life. In the present study, we investigated the effects of peptides derived from β-lactoglobulin C on age-dependent atrophy, gene expression profiles, and the dysfunction of salivary glands. Long-term oral administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK) and His59-Lys60 (HK) peptides induced salivary secretion and prevented and/or reversed the age-dependent atrophy of salivary glands in older rats. The transcripts of 78 genes were upregulated and those of 81 genes were downregulated by more than 2.0-fold (p ≤ 0.05) after LHK treatment. LHK upregulated major salivary protein genes such as proline-rich proteins (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatins (Cst5, Cyss, Vegp2), amylases (Amy1a, Amy2a3), and lysozyme (Lyzl1), suggesting that LLHK, LHK, and HK restored normal salivary function. The AP-2 transcription factor gene (Tcfap2b) was also induced significantly by LHK treatment. These results suggest that LLHK, LHK, and HK-administration may prevent and/or reverse the age-dependent atrophy and functional decline of salivary glands by affecting gene expression.

We examined whether oral administration of a hop-derived prenylflavonoid isoxanthohumol (IX) would show anti-obesity activity and the underlying mechanism of the potential activity using a high-fat diet (HFD)-induced obese mouse model. Oral administration of 180 mg/kg IX for 8 weeks suppressed HFD-induced accumulation of visceral fat and body weight gain in mice. Simultaneously, IX changed the composition of the microbiome, as determined by a significant increase in the relative abundances of Akkermansia muciniphila, Blautia, and Escherichia coli. A. muciniphila accounted for 23% and 24% of the total microbiome in the HFD+60 mg/kg and 180 mg/kg IX groups, respectively, while it was undetectable in the normal diet (ND) and HFD groups. Similarly, Blautia accounted for 8% and 10% of the total microbiome in the HFD+60 mg/kg and 180 mg/kg IX groups, respectively, while it accounted for less than 1% in the ND and HFD groups. In contrast, a significant decrease in the relative abundance of Oscillospira was observed in the HFD+60 mg/kg and 180 mg/kg IX groups compared with the HFD group. We further examined the anti-obesity effect of IX using a germ-free (GF) mouse model to clarify the relationship between the microbiome and the effect of IX. IX showed no significant anti-obesity effect on fat accumulation and weight gain in GF mice. These results suggest that the anti-obesity effect of IX may involve microbial changes.

The aim of this study was to verify the effect of treatment with isoxanthohumol (IX) on the metabolomics profile of mouse feces to explore the host-intestinal bacterial interactions at the molecular level. The fecal contents of several amino acids in the high-fat diet (HFD) + 0.1% IX group (treated with IX mixed in diets for 12 weeks) were significantly lower than in the HFD group. The fecal contents of the secondary bile acid deoxycholic acid (DCA) in the HFD + 180 mg/kg IX group (orally treated with IX for 8 weeks) were significantly lower than in the HFD group; the values in the HFD group were higher than those in the normal diet (ND) group. Administration of IX changed the fecal metabolomics profile. For some metabolites, IX normalized HFD-induced fluctuations.

This study, following Japanese Registry of NeuroEndovascular Treatment 1 and 2 (JR-NET 1 & 2), shows an annual trend of cases including adverse events and clinical outcomes at 30 days after NET. JR-NET3 was registered by 749 cumulative total number of physicians, certified by the Japanese Society of Neuroendovascular Therapy in 166 centers, between 2010 and 2014. Medical information about the patients was anonymized and retrospectively registered through a website. A total of 40,177 patients were recruited, 632 patients were excluded because data of preprocedural status were not available. So we analyzed 39,545 patients retrospectively. The proportion of octogenarians is increasing year-by-year and 14.7% in 2014 compared with 10.4% in 2010. Most frequent target disease is intracranial aneurysm. For the proportion of the treatment of intracranial aneurysm, 50.0% in 2010, but that has decreased to 44.8% in 2014. However, number of procedures were increased from 3150 in 2010 to 3419 in 2014. Although before the positive clinical evidence of mechanical thrombectomy for acute ischemic stroke (AIS) was established, the proportion of endovascular treatment for AIS increased 13.8% in 2014 compared with 6.3% in 2010. The number of patients requiring neuroendovascular treatment in Japan is increasing since 2010-2013, but that declined a little in 2014 caused by study operation suspended at the end of 2013. The outcomes of such therapy are clinically acceptable. Details of each type of treatment will be investigated in sub-analyses of the database.

We investigated if the orally administered Lactobacillus pentosus strain S-PT84 (S-PT84) might show anti-stress activity and ameliorate stress-induced immune suppression in mice. Stress of mice induced an increase in serum corticosterone and a decrease in splenic natural killer activity and in the number of splenocytes versus control mice. However, these changes were not observed in stressed mice that had been administered S-PT84. Furthermore, interleukin (IL)-12 and IL-10 production, which was downregulated in lipopolysaccharide-activated macrophages from stressed mice, was maintained at control levels in the macrophages of stressed mice that had been fed S-PT84. Interferon-γ production, which was downregulated in concanavalin A-activated splenocytes from stressed mice, tended to be maintained at control levels in stressed mice that had been fed S-PT84, although IL-4 production by these cells was not influenced by S-PT84 administration. Additionally, reduced glutathione (GSH) levels were decreased in serum and peritoneal macrophages from stressed mice versus controls, but these GSH levels were significantly higher in stressed animals that had been administered S-PT84 compared with those that had not. These results suggest that S-PT84 exerts anti-stress activity through immune modulation and/or antioxidative activity.

Curcumin has various biological activities including antioxidant and antiinflammatory actions, and alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to realize its bioactivities. We have generated capsules and tablets containing Theracurmin, a highly absorptive curcumin. In addition, we recently created a drinkable preparation of Theracurmin. To evaluate the absorption efficiency of this type of curcumin, we performed a single-dose, double-blind, 4-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin beverage and 3 other drinkable types of curcumin sold in Japan. Twenty-four healthy subjects (male/female=13/11, age: 23-32) were administered with these 4 drinkable preparations of curcumin. The area under the blood concentration-time curve at 0-8 h was found to be 1.5 to 4.0-fold higher with Theracurmin than with the other 3 kinds of curcumin beverage. Moreover, maximal plasma curcumin concentrations (0-8 h) of Theracurmin were 1.8 to 3.8 times higher than those of the other 3 curcumin beverages. These data indicate that our newly prepared Theracurmin beverage exhibits a much better absorption efficiency than other kinds of curcumin beverage sold in Japan.