Enhanced anti-inflammatory effect of fish myofibrillar protein by introducing pectin oligosaccharide and its molecular mechanisms.

This study investigated the efficacy of glycation with edible uronic acid-containing oligosaccharides via the Maillard reaction to enhance the anti-inflammatory effect of fish myofibrillar protein (Mf). Lyophilized Mf was reacted with pectin oligosaccharide (PO, half of the total protein weight) at 60 °C and 35 % relative humidity for up to 12 h to produce glycated Mf (Mf-PO). After pepsin and trypsin digestion, the anti-inflammatory effect was assessed by measuring the secretions of proinflammatory cytokines in LPS-stimulated RAW 264.

Convergent approach for direct cross-coupling enabled by flash irreversible generation of cationic and anionic species.

In biosynthesis multiple kinds of reactive intermediates are generated, transported, and reacted across different parts of organisms, enabling highly sophisticated synthetic reactions. Herein we report a convergent synthetic approach, which utilizes dual intermediates of cationic and carbanionic species in a single step, hinted at by the ideal reaction conditions. By reactions of unsaturated precursors, such as enamines, with a superacid in a flow microreactor, cationic species, such as iminium ions, are generated rapidly and irreversibly, and before decomposition, they are transported to react with rapidly and independently generated carbanions, enabling direct C-C bond formation.

Analysis of the Medication Persistence Rate for and Adherence to Oral 5-Aminosalicylic Acid Preparations in Japanese Patients with Ulcerative Colitis: Study Using a Nationwide Claims Database.

Introduction: 5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date.

Maillard-type glycated collagen with alginate oligosaccharide suppresses inflammation and oxidative stress by attenuating the expression of LPS receptors and in macrophages.

Inflammation and oxidative stress contribute to noncommunicable diseases (NCDs), with macrophages playing pivotal roles. Glycated collagen through Maillard-type glycation holds promise for enhancing anti-inflammatory properties, but its mechanism remains unclear. This study investigates the cellular mechanism and aims to contribute to expanding collagen utilization.

Impact of backslopping in TERASI manufacture, as an improving method to reduce shrimp allergenicity.

The backslopping method was applied to the manufacture of Terasi (fermented shrimp paste) as countermeasures against the technical issue depending on the raw material, and its contribution to reduction of the potential allergenicity of Terasi was examined. Three kinds of starters, the low allergenic Indonesian commercial Terasi (CT), Akiami (Acetes japonicus) Terasi produced in laboratory scale (AT) and heated AT (HAT) were added to the manufacturing process of the Isazaami (Neomysis awatchensis) Terasi which contained tropomyosin (TM) with high IgE-binding ability. Addition of the starter effectively promoting the degradation of the shrimp protein and the reduction of the IgE-binding ability of TM.

Development of a liquid chromatography-based versatile bioanalysis for bevacizumab based on pretreatment combining aptamer affinity purification and centrifugal ultrafiltration concentration.

We report on the development of a versatile and accurate bioanalytical method for bevacizumab using a pretreatment method combining affinity purification with anti-idiotypic DNA aptamers and centrifugal ultrafiltration concentration, followed by liquid chromatography (LC)-fluorescence analysis. An affinity purification method using Sepharose beads as an affinity support removed immunoglobulin G and a large amount of coexisting substances in the serum sample. Purified bevacizumab was separated as a single peak by conventional LC and detected fluorometrically, showing good linearity (R = 0.

Glycation with uronic acid-type reducing sugar enhances the anti-inflammatory activity of fish myofibrillar protein via the Maillard reaction.

The role of carboxyl group in uronic acid in enhancing the anti-inflammatory activity of fish myofibrillar protein (Mf) was investigated, when lyophilized Mf was reacted with various reducing sugars at 60 °C and 35% relative humidity through the Maillard reaction. After pepsin and trypsin digestion, the anti-inflammatory activity was evaluated by measuring the secretions of tumor necrosis factor-α, interleukin-6, interleukin-1β, and nitric oxide in lipopolysaccharide-stimulated RAW 264.7 macrophage.

Efficacy of Low-Dose Estrogen-Progestins and Progestins in Japanese Women with Dysmenorrhea: A Systematic Review and Network Meta-analysis.

Introduction: Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.

Methods: We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).

Variation in shrimp tropomyosin allergenicity during the production of Terasi, an Indonesian fermented shrimp paste.

Terasi is a fermented shrimp paste in Indonesia. We examined the effect of the Terasi manufacturing process on the abundance of the allergen tropomyosin (TM) and its IgG/IgE-binding ability. Terasi was produced from three shrimps, Akiami (Acetes japonicus), Okiami (Euphausia pacifica), and Isazaami (Neomysis awatchensis).

Comparison of Maillard-Type Glycated Collagen with Alginate Oligosaccharide and Glucose: Its Characterization, Antioxidant Activity, and Cytoprotective Activity on HO-Induced Cell Oxidative Damage.

To improve the antioxidant activity of collagen molecules using Maillard-type glycation, the relation between antioxidant activity and progress indexes for the Maillard reaction must be understood. In this study, lyophilized tilapia scale collagen was mixed with a half weight of alginate oligosaccharide (AO) or glucose and incubated at 60 °C and 35% relative humidity for up to 18 h to produce the Maillard-type glycated collagen (C-AO and C-Glu, respectively). As glycation progressed, the amount of conjugated sugar coupled with UV-vis absorbance at 294 nm and 420 nm increased more rapidly in C-Glu than in C-AO, and the available lysine decreased rapidly in C-Glu compared with C-AO.

Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation.

Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, a detailed mapping of transient cellular states during in vitro differentiation has not been performed. Here, we conduct single-cell transcriptomic profiling of an hESC-RPE differentiation protocol that has been developed for clinical use.

Development of a DNA aptamer that binds to the complementarity-determining region of therapeutic monoclonal antibody and affinity improvement induced by pH-change for sensitive detection.

Therapeutic monoclonal antibodies (mAbs) are successful biomedicines; however, evaluation of their pharmacokinetics and pharmacodynamics demands highly specific discrimination from human immunoglobulin G naturally present in the blood. Here, we developed a novel anti-idiotype aptamer (termed A14#1) with extraordinary specificity against the anti-vascular endothelial growth factor therapeutic mAb, bevacizumab. Structural analysis of the antibody-aptamer complex showed that several bases of A14#1 recognized only the complementarity determining region (CDR) of bevacizumab, thereby contributing to its extraordinary specificity.

Insight into the Ferrier Rearrangement by Combining Flash Chemistry and Superacids.

The transformation of glycals into 2,3-unsaturated glycosyl derivatives, reported by Ferrier in 1962, is supposed to involve an α,β unsaturated glycosyl cation, an elusive ionic species that has still to be observed experimentally. Herein, while combination of TfOH and flow conditions failed to observe this ionic species, its extended lifetime in superacid solutions allowed its characterization by NMR-based structural analysis supported by DFT calculations. This allyloxycarbenium ion was further exploited in the Ferrier rearrangement to afford unsaturated nitrogen-containing C-aryl glycosides and C-alkyl glycosides under superacid and flow conditions, respectively.

Digestibility in the gastrointestinal tract and migration to blood of β'-component (Onk k 5), a major salmon roe IgE-binding protein.

The major allergen of chum salmon (Oncorhynchus keta) roe is the β'-component (Onc k 5, β'-c), which is a yolk protein and a fragment of vitellogenin. When yolk content containing β'-c was orally administered to mice, β'-c passed through the gastrointestinal tract and was excreted in feces without marked degradation. The direct administration of β'-c to ligated jejunal and ileal loops showed that β'-c was absorbed through the small intestine and transferred into the blood.

Anti-Idiotype DNA Aptamer Affinity Purification⁻High-Temperature Reversed-Phase Liquid Chromatography: A Simple, Accurate, and Selective Bioanalysis of Bevacizumab.

This study presents a simple, accurate, and selective bioanalytical method of bevacizumab detection from plasma samples based on aptamer affinity purification⁻high-temperature reversed-phased liquid chromatography (HT-RPLC) with fluorescence detection. Bevacizumab in plasma samples was purified using magnetic beads immobilized with an anti-idiotype DNA aptamer for bevacizumab. The purified bevacizumab was separated with HT-RPLC and detected with its native fluorescence.

High-Throughput Bioanalysis of Bevacizumab in Human Plasma Based on Enzyme-Linked Aptamer Assay Using Anti-Idiotype DNA Aptamer.

We propose a highly selective, sensitive, accurate, and high-throughput bioanalysis method for bevacizumab utilizing an anti-idiotype DNA aptamer. With this method, bevacizumab in a plasma sample was reacted in a 96-well plate immobilized with the aptamer and further reacted with a protein A-HRP conjugate. The resulting HRP activity was colorimetrically detected using a microplate reader.

LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis.

The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death. In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype.

A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development.

Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur.

Anti-inflammatory effects of dulse (Palmaria palmata) resulting from the simultaneous water-extraction of phycobiliproteins and chlorophyll a.

The use of dulse (Palmaria palmata) as a source of edible anti-inflammatory products was evaluated in this study. Phycobiliproteins and chlorophyll a were simultaneously extracted from lyophilized dulse leaves via water-extraction, and subjected to thermolysin digestion to produce thermolysin-digested water-extract (d-DWE). d-DWE significantly reduced tumor necrosis factor-α, interleukin-6, and nitric oxide in LPS-stimulated murine macrophages (RAW 264.

Dienogest inhibits C-C motif chemokine ligand 20 expression in human endometriotic epithelial cells.

Objective: C-C motif chemokine ligand 20 is thought to contribute to the development of endometriosis by recruiting Th17 lymphocytes into endometriotic foci. The present study investigated the effects of dienogest, a progesterone receptor agonist used to treat endometriosis, on C-C motif chemokine ligand 20 expression by endometriotic cells.

Study Design: Effects of dienogest on mRNA expression and protein secretion of C-C motif chemokine ligand 20 induced by interleukin 1β were assessed in three immortalized endometriotic epithelial cell lines, parental cells (EMosis-CC/TERT1), and stably expressing human progesterone receptor isoform A (EMosis-CC/TERT1/PRA+) or isoform B (EMosis-CC/TERT1/PRA-/PRB+).

The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II In both of these complexes, HOIP limits caspase-8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase-8-dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL-containing complex, LUBAC also restricts TRAIL-induced necroptosis.

The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis.

Unlabelled: Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catalytic core component is heme-oxidized iron regulatory protein 2 ubiquitin ligase-1-interacting protein (HOIP). To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, we investigated the physiological role of HOIP in the liver parenchyma.

Linear ubiquitination in immunity.

Linear ubiquitination is a post-translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo.

In vitro and in vivo anti-inflammatory activity of digested peptides derived from salmon myofibrillar protein conjugated with a small quantity of alginate oligosaccharide.

Salmon myofibrillar protein (Mf) was investigated as a source of edible anti-inflammatory products. Peptides produced by stepwise digestion of Mf (without carbohydrate) with pepsin and trypsin had little effect on the secretion of inflammation-related compounds from lipopolysaccharide-stimulated RAW 264.7 macrophage cells.