Discovery of a Phosphodiesterase 7A Inhibitor of High Isozyme Selectivity Exhibiting Anti-Osteoporotic Effects.

Phosphodiesterases (PDEs) have drawn attention due to their critical roles in physiological and pathological conditions. Many research groups have studied these hydrolytic enzymes to develop new drugs, including apremilast as a PDE4 inhibitor and sildenafil as a PDE5 inhibitor. Targeting PDE7 has also been deemed a rational strategy to ameliorate autoimmune conditions.

Preferential sugar utilization by bifidobacterial species.

Bifidobacteria benefit host health and homeostasis by breaking down diet- and host-derived carbohydrates to produce organic acids in the intestine. However, the sugar utilization preference of bifidobacterial species is poorly understood. Thus, this study aimed to investigate the sugar utilization preference (i.

Macrophage polarization toward M1 phenotype in T cell transfer colitis model.

Background: T cell transfer colitis model is often used to study the CD4 T cell functions in the intestine. However, the specific roles of macrophages in colitis remain unclear. In this study, we aimed to evaluate the phenotype and functions of macrophages in the colonic lamina propria (LP) in a colitis model.

In Vitro Probiotic Characterization and Safety Assessment of Lactic Acid Bacteria Isolated from Raw Milk of Japanese-Saanen Goat ().

Two novel probiotic strains of lactic acid bacteria were successfully isolated from the raw milk of dairy Japanese-Saanen goats. Selection criteria for positive candidates were grown on de Man-Rogosa-Sharpe or M17 selective medium at 30, 35, or 42 °C anaerobically, and characterized based on Gram reaction, catalase test, and tolerance to low pH and bile salts. Among the 101 isolated positive candidates, two strains, YM2-1 and YM2-3, were selected and identified as using 16S rDNA sequence similarity.

Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides.

Bifidobacteria are among the first colonizers of the infant gut, and human milk oligosaccharides (HMOs) in breastmilk are instrumental for the formation of a bifidobacteria-rich microbiota. However, little is known about the assembly of bifidobacterial communities. Here, by applying assembly theory to a community of four representative infant-gut associated Bifidobacterium species that employ varied strategies for HMO consumption, we show that arrival order and sugar consumption phenotypes significantly affected community formation.

Diversification of a Fucosyllactose Transporter within the Genus .

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose [FL]), are associated with the formation of a -rich gut microbial community.

Evolution of milk oligosaccharides: Origin and selectivity of the ratio of milk oligosaccharides to lactose among mammals.

Background: The carbohydrate fraction of mammalian milk is constituted of lactose and oligosaccharides, most of which contain a lactose unit at their reducing ends. Although lactose is the predominant saccharide in the milk of most eutherians, oligosaccharides significantly predominate over lactose in the milk of monotremes and marsupials.

Scope Of Review: This review describes the most likely process by which lactose and milk oligosaccharides were acquired during the evolution of mammals and the mechanisms by which these saccharides are digested and absorbed by the suckling neonates.

Exploring Potential Bioactive Peptides in Fermented Bactrian Camel's Milk and Mare's Milk Made by Mongolian Nomads.

To date, bioactive proteins and peptides from minor livestock milks and their fermented products have been scarcely reported. In Mongolia, nomads are commonly rearing five livestock animal species (i.e.

Factors affecting decreasing viscosity of the culture medium during the stationary growth phase of exopolysaccharide-producing MTCC 25067.

MTCC 25067 produces a hetero-exopolysaccharide (HePS) when cultured which forms supramolecular networks in the culture medium, increasing the viscosity. In the present study, the viscosity of the bacterial culture reached its maximum at 48 hr of cultivation and then decreased during a stationary growth phase lasting for up to 144 hr. The monosaccharide composition did not change during the stationary growth phase, whereas degradation of HePS molecules was noticeable, leading to partial disintegration of their supramolecular networks.

Effects of low-dose milk protein supplementation following low-to-moderate intensity exercise training on muscle mass in healthy older adults: a randomized placebo-controlled trial.

Purpose: The purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate.

Methods: In a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60-84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry.

Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1.

Myocardial fibrosis is often associated with cardiac hypertrophy; indeed, fibrosis is one of the most critical factors affecting prognosis. We aimed to identify the molecules involved in promoting fibrosis under hypertrophic stimuli. We previously established a rat model of cardiac hypertrophy by pulmonary artery banding, in which approximately half of the animals developed fibrosis in the right ventricle.

Chemical structures of oligosaccharides in milks of the American black bear (Ursus americanus americanus) and cheetah (Acinonyx jubatus).

The milk oligosaccharides were studied for two species of the Carnivora: the American black bear (Ursus americanus, family Ursidae, Caniformia), and the cheetah, (Acinonyx jubatus, family Felidae, Feliformia). Lactose was the most dominant saccharide in cheetah milk, while this was a minor saccharide and milk oligosaccharides predominated over lactose in American black bear milk. The structures of 8 neutral saccharides from American black bear milk were found to be Gal(β1-4)Glc (lactose), Fuc(α1-2)Gal(β1-4)Glc (2'-fucosyllactose), Gal(α1-3)Gal(β1-4)Glc (isoglobotriose), Gal(α1-3)[Fuc(α1-2)]Gal(β1-4)Glc (B-tetrasaccharide), Gal(α1-3)[Fuc(α1-2)]Gal(β1-4)[Fuc(α1-3)]Glc (B-pentasaccharide), Fuc(α1-2)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (difucosyl lacto-N-neotetraose), Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (monogalactosyl monofucosyl lacto-N-neotetraose) and Gal(α1-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (Galili pentasaccharide).

Primary Prevention of Cow's Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow's Milk Formula at Birth: A Randomized Clinical Trial.

Importance: Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice.

Objective: To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.

Design, Setting, And Participants: The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan.

Rheological characteristics and supramolecular structure of the exopolysaccharide produced by Lactobacillus fermentum MTCC 25067.

Rheological properties and supramolecular structure of the exopolysaccharide (EPS) secreted by Lactobacillus fermentum MTCC 25067 were investigated. The critical concentration representing the lower-limit of the semi-dilute regime was estimated to be 0.71 g/L from the concentration dependence of zero-shear specific viscosity.

Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF-κB signaling.

Nuclear factor-κB (NF-κB) is a crucial transcription factor family involved in the regulation of immune and inflammatory responses and cell survival. The linear ubiquitin chain assembly complex (LUBAC), composed of the HOIL-1L, HOIP, and SHARPIN subunits, specifically generates Met1-linked linear ubiquitin chains through the ubiquitin ligase activity in HOIP, and activates the NF-κB pathway. We recently identified a chemical inhibitor of LUBAC, which we named HOIPIN-1 (HOIP inhibitor-1).

Purification, Rheological Characterization, and Visualization of Viscous, Neutral, Hetero-exopolysaccharide Produced by Lactic Acid Bacteria.

Viscous exopolysaccharide (EPS)-producing lactic acid bacteria (LAB) have received increasing interest in the dairy industry because of their capability to improve the texture and mouthfeel of fermented dairy products. To date, enormous efforts have been made to reveal the relationship between texture and EPS production in fermented milk products such as yogurt. However, the structure-rheology relationship of EPSs themselves is not yet well understood due to their low yields in general and their wide variety of chemical structures.

Sharing of human milk oligosaccharides degradants within bifidobacterial communities in faecal cultures supplemented with Bifidobacterium bifidum.

Gut microbiota of breast-fed infants are generally rich in bifidobacteria. Recent studies show that infant gut-associated bifidobacteria can assimilate human milk oligosaccharides (HMOs) specifically among the gut microbes. Nonetheless, little is known about how bifidobacterial-rich communities are shaped in the gut.

High-Throughput Screening for Linear Ubiquitin Chain Assembly Complex (LUBAC) Selective Inhibitors Using Homogenous Time-Resolved Fluorescence (HTRF)-Based Assay System.

The nuclear factor κB (NF-κB) pathway is critical for regulating immune and inflammatory responses, and uncontrolled NF-κB activation is closely associated with various inflammatory diseases and malignant tumors. The Met1-linked linear ubiquitin chain, which is generated by linear ubiquitin chain assembly complex (LUBAC), is important for regulating NF-κB activation. This process occurs through the linear ubiquitination of NF-κB essential modulator, a regulatory subunit of the canonical inhibitor of the NF-κB kinase complex.

Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults.

A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida⁻Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink.

Chemical structures of oligosaccharides in milk of the raccoon (Procyon lotor).

In this study on milk saccharides of the raccoon (Procyonidae: Carnivora), free lactose was found to be a minor constituent among a variety of neutral and acidic oligosaccharides, which predominated over lactose. The milk oligosaccharides were isolated from the carbohydrate fractions of each of four samples of raccoon milk and their chemical structures determined by H-NMR and MALDI-TOF mass spectroscopies. The structures of the four neutral milk oligosaccharides were Fuc(α1-2)Gal(β1-4)Glc (2'-fucosyllactose), Fuc(α1-2)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (lacto-N-fucopentaose IV), Fuc(α1-2)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (fucosyl para lacto-N-neohexaose) and Fuc(α1-2)Gal(β1-4)GlcNAc(β1-3)[Fuc(α1-2)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (difucosyl lacto-N-neohexaose).