A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases.

In the field of rare and intractable diseases, new drug development is difficult and drug repositioning (DR) is a key method to improve this situation. In this study, we present a new method for finding DR candidates utilizing virtual screening, which integrates amino acid interaction mapping into scaffold-hopping (AI-AAM). At first, we used a spleen associated tyrosine kinase inhibitor as a reference to evaluate the technique, and succeeded in scaffold-hopping maintaining the pharmacological activity.

Molecular Design of Cyclic Peptides with Cell Membrane Permeability and Development of MDMX-p53 Inhibitor.

Cyclic peptides have been expected to be one of the modalities of intracellular protein-protein interaction (PPI) inhibitors, but they are generally known to have low cell membrane permeability. In this study, we focused on the conformation of cyclic peptides in the cell membrane to determine the requirement for their cell membrane permeability through passive diffusion. Utilizing the requirement, we searched for structures with high affinity for MDMX via computational chemistry and acquired cyclic peptide ( = 0.

[Inter-laboratory Study on the Modified Methods for Analyzing Bisphenol A Content for Migration Tests from Polycarbonate Food Apparatuses, Containers, and Packaging].

An inter-laboratory study involving 24 laboratories was conducted to validate the modified analytical method for the migration solution of heptane for the determination of bisphenol A migrating from polycarbonate food processing materials. In this study, two concentrations of samples were blindly coded. Each laboratory determined the analyte (bisphenol A, phenol and p-tert-butylphenol) concentration in each sample according to the established protocol.

Time-domain Brillouin imaging of sound velocity and refractive index using automated angle scanning.

We present a picosecond optoacoustic technique for mapping both the longitudinal sound velocity and the refractive index in solids by automated measurement at multiple probe incidence angles in time-domain Brillouin scattering. Using a fused silica sample with a deposited titanium film as an optoacoustic transducer, we map and in the depth direction. Applications include the imaging of sound velocity and refractive index distributions in three dimensions in inhomogeneous samples such as biological cells.

Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging.

Pathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samples is lost in the samples. Infrared laser-scanning large-area surface-enhanced Raman spectroscopy (SERS) equipped with gold-nanoparticle-based SERS substrate enables us to visualize metabolites in fresh-frozen needle-biopsied samples with spatial matching between SERS and HE staining images with pathological annotations. DCIS ( = 14) and IBC ( = 32) samples generated many different SERS peaks in finger-print regions of SERS spectra among pathologically annotated lesions including cancer cell nests and the surrounding stroma.

Simple method to measure rheological properties of soft surfaces by a micro-needle contact.

We developed a simple method to investigate rheological properties of soft surfaces, such as polymeric liquids and colloidal suspensions, by capturing the images of a metal micro-needle inserted into the surface. At contact, a meniscus-like deformation is formed on the surface. By relating the shape of the deformation to the balance of applied forces, local elasticity and viscosity just inside the surface are obtained.

Adjustable biodegradability of low-swelling hydrogels prepared from recombinant peptides based on human collagen type 1.

An ideal hydrogel for tissue engineering and regenerative therapy is cytocompatible, biocompatible, and has low-swelling characteristics. Recently, a novel low-swelling hydrogel with a homogenous structure was developed by crosslinking a recombinant peptide, modeled on human collagen type 1 (RCPhC1), with a four-arm polyethylene glycol (tetra-PEG). Here, we hypothesized that the biodegradability of the RCPhC1 hydrogel was adjustable by altering its initial polymer concentration.

Visualizing fluid transport inside orally disintegrating tablets and changes in tablets using real-time X-ray radiography and X-ray computed tomography.

Objective: To investigate the disintegration of wet- and dry-compressed orally disintegrating (OD) tablets, with synchrotron radiation as the X-ray source.

Significance: Pharmaceutical tablets are vital for the treatment of various diseases. Therefore, they are constantly developed to ensure desirable characteristics.

Linear imaging theory for differential phase contrast and other phase imaging modes in scanning transmission electron microscopy.

We propose a linear imaging theory for differential phase contrast under the weak-phase-weak-amplitude object approximation. Contrast transfer functions are defined for thin and thick weak objects, and they successfully describe several imaging characteristics of differential phase contrast. We discuss the defocus dependence of the contrast for several examples: atomic resolution, a p-n junction, a heterointerface, and grain boundaries.

[Validation Study on Migration Test for Plastic Food Utensils, Containers, and Packaging].

Migration test of food utensils, containers, and packaging is an important test method for confirming the safety and their compliance to the standards. However, there is little report on inter-laboratory study which was performed to evaluate the entire migration test, including migration operations and quantification. An interlaboratory study was performed participating 22 laboratories using 8 types of model synthetic resin samples containing 10 substances with a wide range of Log P values to evaluate the accuracy of the entire migration test.

The Irreversible FLT3 Inhibitor FF-10101 Is Active Against a Diversity of FLT3 Inhibitor Resistance Mechanisms.

Small-molecule FLT3 inhibitors have recently improved clinical outcomes for patients with FLT3-mutant acute myeloid leukemia (AML) after many years of development, but resistance remains an important clinical problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 which has previously shown activity against FLT3 tyrosine kinase inhibitor resistance-causing FLT3 F691L and D835 mutations. We report that FF-10101 is also active against an expanded panel of clinically identified FLT3 mutations associated with resistance to other FLT3 inhibitors.

Accurate molecular orientation at interfaces determined by multimode polarization-dependent heterodyne-detected sum-frequency generation spectroscopy via multidimensional orientational distribution function.

Many essential processes occur at soft interfaces, from chemical reactions on aqueous aerosols in the atmosphere to biochemical recognition and binding at the surface of cell membranes. The spatial arrangement of molecules specifically at these interfaces is crucial for many of such processes. The accurate determination of the interfacial molecular orientation has been challenging due to the low number of molecules at interfaces and the ambiguity of their orientational distribution.

Substituent and Solvent Effects on the Photoisomerization of Cinnamate Derivatives: An XMS-CASPT2 Study.

Cinnamate derivatives show a variety of photo-induced reactions. Among them is trans-cis photoisomerization, which may involve the nonradiative decay (NRD) process. The extended multistate complete active space second-order perturbation (XMS-CASPT2) method was used in this study as a suitable theory for treating multireference electronic nature, which was frequently manifested in the photoisomerization process.

Cause Clarification of Cysteine Oxidation by Active Species Generated during the Oxidation Process of Cinnamaldehyde and Impact on an In Chemico Alternative Method for Skin Sensitization Using a Nucleophilic Reagent Containing Cysteine.

Aldehydes comprise a major portion of skin sensitizers because they can react with both cysteine and lysine. Moreover, cinnamaldehyde (CA) is a typical moderate sensitizer and is often used in an alternative test method for skin sensitization. The amino acid derivative reactivity assay (ADRA) is an in chemico test method that evaluates the reactivity of cysteine derivatives (-(2-(1-naphthyl)acetyl)-l-cysteine, NAC) and lysine derivatives with the test chemicals and uses CA as a proficiency substance.

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models.

Purpose: The clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832.

Methods: Antitumor activity was assessed in xenograft mouse models of human pancreatic cancer.

Thermally Controlled Construction of Fe-N Active Sites on the Edge of a Graphene Nanoribbon for an Electrocatalytic Oxygen Reduction Reaction.

Pyrolytically prepared iron and nitrogen codoped carbon (Fe/N/C) catalysts are promising nonprecious metal electrocatalysts for the oxygen reduction reaction (ORR) in fuel cell applications. Fabrication of the Fe/N/C catalysts with Fe-N active sites having precise structures is now required. We developed a strategy for thermally controlled construction of the Fe-N structure in Fe/N/C catalysts by applying a bottom-up synthetic methodology based on a N-doped graphene nanoribbon (N-GNR).

A label-free, direct solid-phase fluorimetric analysis of ochratoxin A in agricultural products with monoclonal antibody-immobilized monolith.

We established a method for directly measuring mycotoxin ochratoxin A (OTA) in foods by solid-phase fluorescence of monolith-immobilized antibodies. The antibody was introduced onto only one side of an 8 mm-diameter, 3 mm-thick monolith via covalently immobilized protein G. 4 μg (2.

[Surveillance of Chromium (VI) Concentrations in Mineral Water Products in 2018].

We used ion chromatography with post column derivatization to measure chromium (VI) concentrations in 155 mineral water (MW) products purchased from markets in Japan in 2018. Chromium (VI) recovery in spiked samples of the 155 MW products ranged from 95 to 106%, suggesting that this method is well suited for ensuring that MW products meet the requisite health and food safety standards. Chromium (VI) levels were above detection limits in 54 of the MW products, giving a total detection rate of 35%.

Determination of sterigmatocystin in foods in Japan: method validation and occurrence data.

A survey of the contamination of foods by sterigmatocystin (STC) was performed by an analytical method based on LC-MS/MS. STC was extracted from samples with acetonitrile/water (85/15, v/v) and then purified with immunoaffinity columns. The method was validated by a small-scale inter-laboratory study using spiked wheat samples.

Cause of and countermeasures for oxidation of the cysteine-derived reagent used in the amino acid derivative reactivity assay.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing for skin sensitization that solves certain problems found in the use of the direct peptide reactivity assay (DPRA). During a recent validation study conducted at multiple laboratories as part of the process to include ADRA in an existing OECD test guideline, one of the nucleophilic reagents used in ADRA-N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC)-was found to be susceptible to oxidation in much the same manner that the cysteine peptide used in DPRA was. Owing to this, we undertook a study to clarify the cause of the promotion of NAC oxidation.

Topical treatments with acylceramide dispersions restored stratum corneum lipid lamellar structures in a reconstructed human epidermis model.

Long-periodicity phase (LPP) lamellar structures in intercellular lipid matrixes of the stratum corneum (SC) are considered important for maintenance of skin permeability barriers. Acylceramides are essential components of LPP structures, and their absence influences skin barriers under physiological and pathological conditions, such as atopic dermatitis and dry skin. Although topical applications of acylceramide have been shown to facilitate maintenance of the skin barrier, it is unknown whether topically applied acylceramides are incorporated into intercellular lipids to form LPP structures.

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 2)].

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using heptane as a food-simulating solvent for oily or fatty foods, based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. In the official method, heating for evaporation was done with a water bath.

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 1)].

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using three food-simulating solvents (water, 4% acetic acid and 20% ethanol), based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. For evaporation, a water bath was used in the official method, and a hot plate in the modified method.

Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival.

Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues.