Automated Bowel Sound and Motility Analysis with CNN Using a Smartphone.

Bowel sound (BS) is receiving more attention as an indicator of gut health since it can be acquired non-invasively. Current gut health diagnostic tests require special devices that are limited to hospital settings. This study aimed to develop a prototype smartphone application that can record BS using built-in microphones and automatically analyze the sounds. Using smartphones, we collected BSs from 100 participants (age 37.6 ± 9.7). During screening and annotation, we obtained 5929 BS segments. Based on the annotated recordings, we developed and compared two BS recognition models: CNN and LSTM. Our CNN model could detect BSs with an accuracy of 88.9% andan F measure of 72.3% using cross evaluation, thus displaying better performance than the LSTM model (82.4% accuracy and 65.8% F measure using cross validation). Furthermore, the BS to sound interval, which indicates a bowel motility, predicted by the CNN model correlated to over 98% with manual labels. Using built-in smartphone microphones, we constructed a CNN model that can recognize BSs with moderate accuracy, thus providing a putative non-invasive tool for conveniently determining gut health and demonstrating the potential of automated BS research.

Hydrophobic interactions at subsite S1' of human dipeptidyl peptidase IV contribute significantly to the inhibitory effect of tripeptides.

Functional inhibitory peptides of human dipeptidyl peptidase 4 (hDPP4) have been highly anticipated as the active ingredient of functional food for type II diabetes; however, the molecular mechanism of hDPP4 inhibition remains unclear. In this study, we focused on dipeptides and tripeptides, which display structure-function correlations that are relatively easy to analyze, and examined their interactions with hDPP4 on an atomic level using a combination of docking studies and an hDPP4 inhibition assay. First, we performed comprehensive binding mode analysis of the dipeptide library and demonstrated that the formation of a tight interaction with the S1 subsite composing part of the substrate pocket is essential for dipeptides to compete with the substrate and strongly inhibit hDPP4. Next, we synthesized tripeptides by adding various amino acids to the C-terminus of Ile-Pro and Val-Pro, which have especially high inhibitory activity among compounds in the dipeptide library, and measured the hDPP4 inhibitory activity of the tripeptides. When hydrophobic amino acids (Ile, Met, Val, Trp) were added, the inhibitory activity increased several-fold. This phenomenon could be explained as follows: the C-terminal amino acid of the tripeptide formed hydrophobic interactions with Tyr547 and Trp629, which compose the S1' subsite located relatively outside the substrate pocket, thereby stabilizing the hDPP4-peptide binding. The structural information on the interaction between hDPP4 and peptide inhibitors attained in this study is anticipated to be useful in the development of a more potent hDPP4 competitive inhibitor.

Aromatic amino acid-leucine dipeptides exhibit anxiolytic-like activity in young mice.

We previously reported that Tyr-Leu (YL) exhibits potent anxiolytic-like activity comparable to diazepam in mice. In the current study, we revealed that aromatic amino acid-Leu, Phe-Leu and Trp-Leu (FL and WL, respectively), exhibited anxiolytic-like activity in the elevated plus-maze and open-field tests. FL and WL were orally active. Retro-sequence peptides of FL and WL were inactive. Similarly to YL, the anxiolytic-like activities of FL and WL were inhibited by WAY100135, SCH-23390 and bicuculline, antagonists of serotonin 5-HT1A, dopamine D1 and GABAA receptors, respectively, implying that FL and WL activate a common anxiolytic pathway to that of YL. Taken together, aromatic amino acid-Leu dipeptides such as YL, FL, and WL may exhibit anxiolytic-like activity in a manner dependent on the activation of 5-HT1A, D1 and GABAA receptors.

Soymorphin-5, a soy-derived µ-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPARα systems in diabetic KKAy mice.

Soymorphin-5 (YPFVV) derived from soybean ß-conglycinin ß-subunit is a µ-opioid agonist peptide having anxiolytic-like activity. Here, we show that soymorphin-5 improves glucose and lipid metabolism after long-term oral administration to KKAy mice, a type 2 diabetes model animal. Soymorphin-5 inhibited hyperglycemia without an increase in plasma insulin levels in KKAy mice. Soymorphin-5 also decreased plasma and liver triglyceride (TG) levels and liver weight, suggesting that soymorphin-5 improved lipid metabolism. Soymorphin-5 increased plasma adiponectin concentration and liver mRNA expression of AdipoR2, a subtype of adiponectin receptor that is involved in stimulating the peroxisome proliferator-activated receptor (PPAR)α pathway and fatty acid ß-oxidation. The expressions of the mRNA of PPARα and its target genes acyl-CoA oxidase, carnitine palmitoyltransferase 1 A, and uncoupling protein-2, in the liver were also increased after oral administration of soymorphin-5. Furthermore, des-Tyr-soymorphin-5 (PFVV) without µ-opioid and anxiolytic-like activities did not decrease blood glucose levels in KKAy mice. These results suggest that µ-opioid peptide soymorphin-5 improves glucose and lipid metabolism via activation of the adiponectin and PPARα system and subsequent increases of ß-oxidation and energy expenditure in KKAy mice.

ß-Lactotensin derived from bovine ß-lactoglobulin exhibits anxiolytic-like activity as an agonist for neurotensin NTS(2) receptor via activation of dopamine D(1) receptor in mice.

ß-Lactotensin (His-Ile-Arg-Leu) is a bioactive peptide derived from bovine milk ß-lactoglobulin, acting as a natural agonist for neurotensin receptors. We found that ß-lactotensin exhibited anxiolytic-like activity in an elevated plus-maze test after its intraperitoneal (i.p.) administration in mice. ß-Lactotensin was also orally active. The anxiolytic-like activity of ß-lactotensin after i.p. administration was blocked by levocabastine, an antagonist for the neurotensin NTS(2) receptor. ß-Lactotensin had anxiolytic-like activity in wild-type but not Ntsr2-knockout mice. ß-Lactotensin increased intracellular Ca(2+) flux in glial cells derived from wild-type mice but not Ntsr2 knockout mice. These results suggest that ß-lactotensin acts as an NTS(2) receptor agonist having anxiolytic-like activity. The anxiolytic-like activity of ß-lactotensin was also blocked by SCH23390 and SKF83566, antagonists for dopamine D(1) receptor, but not by raclopride, an antagonist for D(2) receptor. Taken together, ß-lactotensin may exhibit anxiolytic-like activity via NTS(2) receptor followed by D(1) receptor.

Dipeptide Tyr-Leu (YL) exhibits anxiolytic-like activity after oral administration via activating serotonin 5-HT1A, dopamine D1 and GABAA receptors in mice.

We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1-1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3-3mg/kg). A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT(1A), dopamine D(1) and GABA(A) receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT(1A), D(1) and GABA(A) receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT(1A), D(1) and GABA(A) receptors.