An Endogenous Tachykinergic NK2/NK3 Receptor Cascade System Controlling the Release of Serotonin from Colonic Mucosa

5-Hydroxytryptamine (5-HT) released from colonic mucosal enterochromaffin (EC) cells is a major signaling molecule, which participates in the pathophysiological regulation of colonic functions in gut disorder including irritable bowel syndrome (IBS), but the endogenous modulator system for the 5-HT release is not yet well elucidated. Our in vitro studies in guinea-pig colon have indicated that the cascade pathway of neuronal tachykinergic NK₃ receptors and NK₂ receptors on peptide YY (PYY)-containing endocrine L cells represents an endogenous modulator system for 5-HT release from EC cells and that melatonin, endogenous tachykinins and PYY play important roles in modulation of the release of 5-HT from EC cells via the endogenous NK₂/NK₃ receptor cascade system. This review aims at examining the potential role of the endogenous tachykinergic NK2/NK3 receptor cascade system controlling the release of 5-HT from EC cells, with special attention being paid to the pathophysiology of gut disorders including IBS.     

Combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1′-oxybis-, tetrapropylene derivs. in rats

We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1′-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000?mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42–53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods. Increases in prothrombin time and activated partial thromboplastin time values were observed only in males at 200 and 1000?mg/kg/day. Hypertrophy of centrilobular hepatocytes was observed with increased liver weight in both sexes at 200 and 1000?mg/kg/day, but there was no histologic evidence of hepatotoxicity. Diffuse hypertrophy of follicular cells in thyroid glands was observed in females at 200?mg/kg/day and in both sexes at 1000?mg/kg/day, with an increased blood cholesterol level in females at 1000?mg/kg/day. The conception index was decreased for females at 1000?mg/kg/day; and no abnormalities were detected in the reproductive indices of implantation, delivery, or pups’ condition, although a slight increase in the pups’ body weight was noted at birth. Our data indicate a no-observed-adverse-effect level of 40?mg/kg/day for repeated-dose toxicity on the basis of the prolongation of blood coagulating time, and of 200?mg/kg/day for reproductive/developmental toxicity on the basis of the decreased conception index.     

In silico analysis‐based identification of the target residue of integrin α6 for metastasis inhibition of basal‐like breast cancer

Metastasis causes death in breast cancer patients. To inhibit breast cancer metastasis, we focused on integrin α6, a membrane protein that contributes to cell migration and metastasis. According to in silico analysis, we identified Asp‐358 as an integrin α6‐specific vertebrate‐conserved residue and consequently as a potential therapeutic target. Because Asp‐358 is located on the surface of the β propeller domain that interacts with other molecules for integrin α6 function, we hypothesized that a peptide with the sequence around Asp‐358 competitively inhibits integrin α6 complex formation. We treated basal‐like breast cancer cells with the peptide and observed reductions in cell migration and metastasis. The result of the immunoprecipitation assay showed that the peptide inhibited integrin α6 complex formation. Our immunofluorescence for phosphorylated paxillin, a marker of integrin‐regulated focal adhesion, showed that the peptide reduced the number of focal adhesions. These results indicate that the peptide inhibits integrin α6 function. This study identified the functional residue of integrin α6 and designed the inhibitory peptide. For breast cancer patients, metastasis inhibition therapy may be developed in the future based on this study.     

The utility of longitudinal slicing method for rectal specimen: pathological analysis of circumferential resection margin of intersphincteric resection for low‐lying rectal cancer

The pathological assessment of the resection margin of rectal cancer is important to predict clinical outcome. The transverse slicing method of rectal specimens is recommended in Western countries. However, in Japan the longitudinal slicing method is traditionally advocated. The aim of this study was to assess the advantages of the longitudinal slicing method. The subjects were 197 consecutive patients with primary rectal cancer who underwent curative intersphincteric resection from 2000 to 2013. The resected rectal specimens were cut into 12 slices in the direction of the long axis. Resection margin was considered positive when it was less than or equal to 1 mm. Resection margin was positive in 23 patients (12%). They were classified into two groups, namely the DEEP group (n = 16, 70%), when the resection margin corresponded to the deepest tumor invasion area, and the ENTRY group (n = 7, 30%), when resection margin was around the initial cutting point of the anal canal. It was shown that resection margin tends to be positive not only in the deepest tumor invasion area but also in the entry area of the anal canal. The longitudinal slicing method may have some advantages for accurate assessment of resection margin especially in low‐lying rectal cancer.     

Quick and Simple FRAIL Scale Predicts Incident Activities of Daily Living (ADL) and Instrumental ADL (IADL) Disabilities: A Systematic Review and Meta-analysis

Objectives

To quantitatively examine frailty defined by FRAIL scale as a predictor of incident disability risks by conducting a systematic review and meta-analysis.

A searchable database for proteomes of oral microorganisms

An online database of proteomes for two-dimensional electrophoresis (2DE) gel data was constructed and it is now freely accessible through a web-based interface. Proteins from three oral bacteria, Streptococcus mutans UA159, Actinobacillus actinomycetemcomitans HK1651, and Porphyromonas gingivalis W83, whose genome databases are freely available, were separated by 2DE, and protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and identified. About 1000 spots from the gels of P. gingivalis W83 were extracted and analyzed by MALDI-TOF, and 330 proteins were identified. In addition, 160 of 240 spots of A. actinomycetemcomitans and 158 of 356 spots of S. mutans were identified. Information such as spot coordinates on the gels, protein names (predicted functions), molecular weights, isoelectroric points, and links to online databases, including Oral Pathogen Sequence Databases of the Los Alamos National Laboratory Bioscience Division (ORALGEN) and National Center for Biotechnology Information (NCBI) or The Institute Genomic Research (TIGR), were stored in tables accessible through the relational database management system MySQL on an Apache web server. To test for functionality of this database system, responses of S. mutans to environmental changes were analyzed using the database and 21 spots on the gel were identified as proteins whose expression had been increased or decreased by environmental pH change without in-gel trypsin digestion, protein extraction, or MALDI-TOF/TOF-MS (mass spectrometer) analysis. The identified proteins are agreement with those reported in previous papers on acid tolerance of S. mutans, demonstrating the usefulness of the system. This database is available at http://www.myamagu.dent.kyushu-u.ac.jp/~bioinformatics/index.html or http://www.bipos.mascat.nihon-u.ac.jp/index.html.