Determination of solute lipophilicity by reversed-phase high-performance liquid chromatography (RP-HPLC)

Lipophilicity was evaluated by the high-throughput RP-HPLC method. A set of 40 solutes with well-defined solvatochromic parameters were selected in this study. The chromatographic results show that, under the conditions of study, the lipophilicity index log kw was highly correlated with the experimental log Poct

Virtual screening models for finding novel antidepressants

Virtual screening was carried out against various biological targets related to depression by support vector machine classification using the atom-type descriptors. The models were effective as over 75 and 95% of the molecules in external test datasets could be correctly classified, depending on target. Antidepressant compounds had predicted activity against 2.3 targets, on average. An introduction is given to virtual screening and the results of classification experiments are presente

Approach to novel functional foods for stress control : 1. Toward structure-activity relationship and data mining of food compounds by chemoinformatics

Over the past several decades, thousands of natural organic compounds have been isolated from foods, and the information about their structures and biological activities has been accumulated. Despite the long research history of food products and their potential great promise as a medicine and functional food, the systematic research and development have not been carried out extensively. For understanding of the comprehensive structure-activity relationship, we have developed the database system of flavonoids, which are frequently found in vegetables and fruits. We also plan to execute a virtual screening of flavonoids with antidepressant activity by using the database and an advanced chemoinformatic tool. In this section, we will briefly describe (1) flavonoid database and (2) virtual screening of antidepressant compounds

Construction of a novel database for flavonoids

Flavonoids are polyphenolic compounds that exist ubiquitously in foods of plant origin. Flavonoids show various interesting biological activities, such as removal of oxygen radical, anti-cancer action, improvement of high blood pressure, antibacterial, antibiotic and anti-allergy actions. So far, over 4000 structurally unique flavonoids have been isolated from plant sources. Recently, databases of chemicals have been utilized in to help chemical and biological researches, however the comprehensive database of flavonoids with information about structural, biological and physicochemical properties not yet available. We have constructed the integrated database of flavonoids for nutrition research

Novel pH-dependent regulation of human cytosolic sialidase 2 (NEU2) activities by siastatin B and structural prediction of NEU2/siastatin B complex

Human cytosolic sialidase (Neuraminidase 2, NEU2) catalyzes the removal of terminal sialic acid residues from glycoconjugates. The effect of siastatin B, known as a sialidase inhibitor, has not been evaluated toward human NEU2 yet. We studied the regulation of NEU2 activity by siastatin B in vitro and predicted the interaction in silico. Inhibitory and stabilizing effects of siastatin B were analyzed in comparison with DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) toward 4-umbelliferyl N-acetylneuraminic acid (4-MU-NANA)- and α2,3-sialyllactose-degrading activities of recombinant NEU2 produced by E. coli GST-fusion gene expression. Siastatin B exhibited to have higher competitive inhibitory activity toward NEU2 than DANA at pH 4.0. We also revealed the stabilizing effect of siastatin B toward NEU2 activity at acidic pH. Docking model was constructed on the basis of the crystal structure of NEU2/DANA complex (PDB code: 1VCU). Molecular docking predicted that electrostatic neutralization of E111 and E218 residues of the active pocket should not prevent siastatin B from binding at pH 4.0. The imino group (1NH) of siastatin B can also interact with D46, neutralized at pH 4.0. Siastatin B was suggested to have higher affinity to the active pocket of NEU2 than DANA, although it has no C7–9 fragment corresponding to that of DANA. We demonstrated here the pH-dependent affinity of siastatin B toward NEU2 to exhibit potent inhibitory and stabilizing activities. Molecular interaction between siastatin B and NEU2 will be utilized to develop specific inhibitors and stabilizers (chemical chaperones) not only for NEU2 but also the other human sialidases, including NEU1, NEU3 and NEU4, based on homology modeling

Stress control and human nutrition

Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitaryadrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation

Risk factors for severity of colonic diverticular hemorrhage

Background/AimsColonic diverticular hemorrhage (DH) was a rare disease until the 1990s, and its incidence has increased rapidly since 2000 in Japan. In recent years, colonic DH has been the most frequent cause of lower gastrointestinal bleeding (LGIB). Nearly all cases of DH are mild, with the bleeding often stopping spontaneously. Some cases, however, require surgery or arterial embolization. In this study, using a cohort at Fukuoka University Chikushi Hospital, we investigated factors associated with severe colonic DH.MethodsAmong patients with LGIB who underwent colonoscopy at our hospital between 1995 and 2013, DH was identified in 273 patients. Among them, 62 patients (22.7%) were defined as having severe colonic DH according to recurrence of bleeding in a short period, and/or the necessity of transfusion, arterial embolization, or surgery. We then evaluated risk factors for severe DH among DH patients in this retrospective cohort.ResultsAmong the 273 patients with DH, use of non-steroidal anti-inflammatory drugs (NSAIDs) (odds ratio [OR], 2.801; 95% confidence interval [CI], 1.164–6.742), Charlson Risk Index (CRI) ≥2 (OR, 3.336; 95% CI, 1.154–7.353), right-sided colonic DH (OR, 3.873; 95% CI, 1.554–9.653), and symptoms of cerebral hypoperfusion (such as light-headedness, dizziness, or syncope) (OR, 2.926; 95% CI, 1.310–6.535) showed an increased risk of severe DH even after controlling for other factors.ConclusionsSevere DH occurred in 23% of DH patients, and NSAID use, CRI ≥2, right-sided colonic DH, and symptoms of cerebral hypoperfusion are suggested to be predictors of severe DH

A Structural Similarity Evaluation by SimScore in a Teratogenicity Information Sharing System

Many efforts have been devoted to the development of computer-aided prediction of drug toxicity over the decades, but at present, systems and programs available for predicting teratogenicity from chemical structures do not always give satisfactory answers yet, mainly because of the complex and unknown mechanism of reproductive and developmental toxicity. We developed a novel algorithm and implemented in the program “SimScore ” to evaluate quantitatively the structural similarity score of a target compound with the teratogenic drugs which are defined as serious human teratogens by the United States Food and Drug Administration. In SimScore, a molecular structure is divided into its skeletal and substituent parts in order to perform similarity comparison for these parts independently. This idea is based on that compounds with the same or similar skeleton show a similar biological activity, but their activity strengths depend on the variation of substituents. We demonstrated the usefulness of SimScore by applying it to an example. SimScore will be used in our web-based information system about teratogenicity to predict the potential risk of query compounds