Plasma NfL is associated with mild cognitive decline in patients with diabetes.

Background: Patients with diabetes are at a higher risk for cognitive decline. Thus, biomarkers that can provide early and simple detection of cognitive decline are required. Neurofilament light chain (NfL) is a cytoskeletal protein that constitutes neural axons.

Discovery of natural TRPA1 activators through pharmacophore-based virtual screening and a biological assay.

Transient receptor potential cation channel subfamily A member 1 (TRPA1), a member of the transient receptor potential family, detects a wide range of environmental stimuli, such as low temperature, abnormal pH, and reactive irritants. TRPA1 is of great interest as a target protein in fields related to pharmaceuticals and foods. In this study, a library of natural products was explored to identify TRPA1 activators by pharmacophore screening of known TRPA1 agonists and biological assays for agonist activity.

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.

Identification of a new class of non-electrophilic TRPA1 agonists by a structure-based virtual screening approach.

Recent work has gradually been clarifying the binding site of non-electrophilic agonists on the transient receptor potential A1 (TRPA1). This study searched for non-electrophilic TRPA1 agonists by means of in silico drug discovery techniques based on three-dimensional (3-D) protein structure. First, agonist-bound pocket structures were explored using an advanced molecular dynamics simulation starting from the cryo-electron microscopic structure of TRPA1, and several pocket structures suitable for virtual screening were extracted by structure evaluation using known non-electrophilic TRPA1 agonists.

Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands.

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.

Green Tea Intake and Risks for Dementia, Alzheimer's Disease, Mild Cognitive Impairment, and Cognitive Impairment: A Systematic Review.

Dementia has become a major issue that requires urgent measures. The prevention of dementia may be influenced by dietary factors. We focused on green tea and performed a systematic review of observational studies that examined the association between green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment.

Physical interactions among flavonoid enzymes in snapdragon and torenia reveal the diversity in the flavonoid metabolon organization of different plant species.

Flavonoid metabolons (weakly-bound multi-enzyme complexes of flavonoid enzymes) are believed to occur in diverse plant species. However, how flavonoid enzymes are organized to form a metabolon is unknown for most plant species. We analyzed the physical interaction partnerships of the flavonoid enzymes from two lamiales plants (snapdragon and torenia) that produce flavones and anthocyanins.

Generation of blue chrysanthemums by anthocyanin B-ring hydroxylation and glucosylation and its coloration mechanism.

Various colored cultivars of ornamental flowers have been bred by hybridization and mutation breeding; however, the generation of blue flowers for major cut flower plants, such as roses, chrysanthemums, and carnations, has not been achieved by conventional breeding or genetic engineering. Most blue-hued flowers contain delphinidin-based anthocyanins; therefore, delphinidin-producing carnation, rose, and chrysanthemum flowers have been generated by overexpression of the gene encoding flavonoid 3',5'-hydroxylase (F3'5'H), the key enzyme for delphinidin biosynthesis. Even so, the flowers are purple/violet rather than blue.

A flow cell for measuring X-ray Compton scattering of liquid at temperatures up to 623 K and pressures up to 20 MPa.

A flow-type cell was developed for measuring Compton scattering spectra of heat-sensitive aqueous solution. Compton scattering spectra of water and ethanol were measured in the region from ambient conditions to 623 K and 20 MPa. Compton profiles derived from measurement with the flow-type cell were comparable with those in the literature.

Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.

Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic.

Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men.

Background: The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels.

Methods: To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours.

Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum.

Aims: The importance of ethanol oxidation by intestinal aerobes and facultative anaerobes under aerobic conditions in the pathogenesis of ethanol-related colorectal cancer has been proposed. However, the role of obligate anaerobes therein remains to be established, and it is still unclear which bacterial species, if any, are most important in the production and/or elimination of carcinogenic acetaldehyde under such conditions. This study was undertaken to address these issues.

Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae.

Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7) and introducing the gene for a human sphingolipid desaturase (encoded by DES1).