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The β′-component, a major allergen found in fish roe, is synthesized in the liver of female fish as part of the precursor of the egg yolk protein vitellogenin (Vg). Vg is distributed through the bloodstream and contributes to ovary development. In the present study, β′-component, present in Vg fragments, was detected in the muscles and internal organs of mature female salmon, with concentrations exceeding the recommended labeling level under Japan's food allergy labeling system. Additionally, total protein extracted from tissues of female salmon reacted with immunoglobulin E antibody against the salmon roe β′-component. No β′-component was detected in the tissues of mature male fish in the absence of sex hormone stimulation from females nor in immature salmon without sexual differentiation, but excess stimulation of the female sex hormone induced Vg synthesis containing the β′-component in the male fish. These findings suggest that taking into account fish sex, maturity, and sexual isolation of mature male fish could improve the safety of salmon meat for individuals with salmon roe allergy. [ABSTRACT FROM AUTHOR]

To evaluate the safety of Terasi (Indonesian fermented shrimp paste), the product characteristics and allergenicity of 20 types of Indonesian commercial Terasi (ICT) that meet the Indonesian National Standard were evaluated, with a focus on the major shrimp allergen tropomyosin (TM). Marked protein hydrolysis of shrimp muscle occurred in all ICT samples, and no protein fragments or specific reaction of anti-TM immunoglobulin (Ig)G were observed in SDS-PAGE or immunoblot assays. In a competitive enzyme-linked immunosorbent assay using shrimp allergenic patient sera, we observed a markedly diminished specific IgE reaction of ICT compared with that of shrimp muscle, whereas the IgE-binding ability remained in all ICT samples. No clear correlation was found between the degree of protein hydrolysis and IgE reactivity. These results indicate that ICT could be defined as a low–allergenic processed seafood, but has the possibility to be a causative food for shrimp allergy. Direct immunological evaluation is required establishing the food safety of ICT, because assessments of protein profiles and hydrolysis are not useful for determining the safety of Terasi. [ABSTRACT FROM AUTHOR]

Summary: In Japan, national medical expenses are steadily increasing annually, and the financial burden on patients has followed a similar trend. This burden may contribute to frequent interrup-tions in prescribed therapeutic regimens. In particular, in patients with type 2 diabetes mellitus, it is important to evaluate regimen efficacy not only from the index of glycemic control but also psycho-logically, including satisfaction with their treatment. Herein, we examined the relationship between the burden of paying medical expenses and the degree of treatment satisfaction in patients with dia-betes mellitus type 2. As a result, more than 40% of patients felt burdened with paying medical ex-penses, this group being younger and paid more than those who did not feel burdened. In addition, the majority of the burdened cohort used injectable preparations and treatment satisfaction scores were also lower in this cohort. From the above findings, it was considered that several factors, such as age, dosage form used, and rate of out-of-pocket expenses were related to the feeling of burden of payment for medical expenses and treatment satisfaction. However, it is often difficult for med-ical institutions to intervene in these factors. Although the degree of treatment satisfaction can be increased by the attitudes and care of medical staff. The burden reduction associated with being able to pay medical expenses may lead to improvements in the degree of treatment satisfaction. [ABSTRACT FROM AUTHOR]

• Backslopping , improvement method in Terasi's' manufacture. • Isazaami (N. awatchensis) Terasi contained tropomyosin with high IgE-binding ability. • Starter improves the productivity of microorganisms during fermentation. • The IgE-binding ability of TM in Terasi was diminished in all the C-ELISA. • Backslopping effectively promoted the degradation of TM contained in Terasi. 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. Interestingly, Terasi added as a starter would have acted primarily as a nutrient source to promote microbial fermentation rather than as a source of fermenting microorganisms and endogenous proteases. The backslopping method is one of the improving methods for reduction of potential allergenicity of Terasi product. [ABSTRACT FROM AUTHOR]

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. Methods: Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population. Results: An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151–180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151–180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations. Conclusion: The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations. [ABSTRACT FROM AUTHOR]

Co/Cu multilayers deposited on an amorphous Si (a-Si) buffer layer revealed good crystallinity and lower resistivity than ones deposited on other buffer layers. The periodicity and the sharpness at the interface between each layer were not as good as those in the multilayer with a Ni–Fe buffer. Therefore, the multilayer with a Si buffer exhibited smaller resistivity ρ but slightly smaller change of resistivity Δρ. The annealing process improved the periodicity and the sharpness at the interface in the Co/Cu multilayer with a Si buffer, and the value of the magnetoresistance ratio in the multilayer with a Si buffer (17.1%) became larger than that with Ni–Fe (15.5%). © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The major allergenic protein in grey mullet roe was immunologically characterized using rabbit IgG against the β′-component, which is a vitellogenin fragment and the major allergen in chum salmon roe, and the IgE cross-reactivity between salmon and mullet roe was examined using chum salmon roe-allergic patients' sera. Grey mullet β′-component was identified in the yolk protein and consisted of 16 and 30 kDa proteins that showed marked reaction with the anti-β′-component IgG and shared N-terminal amino acid sequence similarity with vitellogenin. The grey mullet β′-component consisted of six different isoforms generated from vitellogenin A and vitellogenin B, and they inhibited the IgE-binding reaction between chum salmon β′-component and a chum salmon roe-allergic patient's serum. Thus, grey mullet roe may be an allergenic seafood capable of introducing IgE cross-reactivity to chum salmon roe through the β′-component. [ABSTRACT FROM AUTHOR]

[Display omitted] • Terasi, Indonesian fermented shrimp paste, was prepared on a laboratory scale. • Tropomyosin, shrimp major allergen, was degraded during Terasi manufacturing. • Allergenicity of processed shrimp would be diminished during the Terasi production. • The allergen degradation has no impact on the Terasi quality. • Terasi becomes a low allergenic seafood by producing under appropriate conditions. 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). Protein degradation and TM IgE-binding activity were examined by immunoblotting using anti-TM rabbit IgG and competitive enzyme-linked immunosorbent assays using shrimp-allergic patients' sera. The processing caused TM degradation, and the IgG-specific response in Akiami meat disappeared at the second fermentation step but remained in both Okiami and Isazaami Terasi. In contrast, TM IgE-binding in all meats decreased gradually during manufacturing and nearly completely disappeared in Akiami Terasi. Conclusively, Terasi production is an effective manufacturing process to reduce the IgE-binding ability of TM, and Terasi can be recognized as a low allergenic seafood when produced under an appropriate manufacturing condition. [ABSTRACT FROM AUTHOR]

Presents a study that investigated giant magnetoresistance properties of sputtered cobalt[sub66]-silver[sub34]/copper multilayered films. Relationship of giant magnetoresistance and magnetic properties to annealing temperature and copper thickness; Measurement of the magnetoreistivities of the samples; Determination of the magnetization curves of the samples.

A novel enzyme-linked immunosorbent assay (ELISA) system has been established for selective detection of chum salmon ( Oncorhynchus keta ) yolk protein (SYP). Rabbit and rat polyclonal Immunoglobulin G antibodies to β′-component (the major allergic protein in fish roe; anti-β) were applied for designing the ELISA system. The sandwich ELISA using rabbit anti-β for the capture antibody and horseradish peroxidase-labeled F(ab′) 2 fragment of rat anti-β for the detection antibody obtained high sensitivity and narrow specificity for SYP. Protein extraction using sodium dodecyl sulfate and 2-mercaptoethanol ensured strict specificity of the ELISA, and components of three popular processed foods had no effect on the ELISA response. The limits of determination and quantification of SYP were estimated to be 0.78 μg/g and 2.60 μg/g of food sample, respectively. In conclusion, the developed ELISA system has a probability to be applied for the detection of contaminated chum salmon roe in processed food. [ABSTRACT FROM AUTHOR]

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. As the CDR of bevacizumab is predicted to be highly positively charged under mildly acidic conditions and that DNA is negatively charged, the affinity of A14#1 to bevacizumab markedly increased at pH 4.7 (K D = 44 pM) than at pH 7.4 (K D = 12 nM). A14#1-based electrochemical detection method capable of detecting 31 pM of bevacizumab at pH 4.7 was thus developed. A14#1 could be potentially useful for therapeutic drug measurement as a novel ligand of bevacizumab. • A novel anti-idiotype aptamer specific for the therapeutic antibody, bevacizumab, was developed. • This paper also presents the first crystal structure of the aptamer-Fab region of antibody drug. • Based on structural analysis of the complex between the aptamer and the antibody, affinity improvement of the aptamer (K D = 44 pM) was achieved under mildly acidic condition. • By using the aptamer under mildly acidic condition, we detected 31–500 pM of bevacizumab electrochemically. [ABSTRACT FROM AUTHOR]

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. LUBAC is not only relevant for activation of nuclear factor-κB ( NF-κB) and mitogen-activated protein kinases ( MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases ( DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types. [ABSTRACT FROM AUTHOR]

Molecular characterization of a major allergen from salmon roeSalmon roe has a high allergic potency and often causes anaphylaxis in Japan. The major allergic protein of salmon roe is β′-component, which is a 35kDa vitellogenin fragment consisting of two subunits. To elucidate structural information and immunological characteristics, β′-component and the subunit components were purified from chum salmon (Onchorhincus keta) roe and vitellogenin-encoding mRNA was used to prepare β′-component subunit-encoding cDNA. This was PCR-amplified, cloned and sequenced and the deduced amino acid sequence compared with partial sequences of β′-component obtained by peptide mapping. The recombinant β′-component subunit was produced by bacterial expression in Escherichia coli and its IgE-binding ability was measured by ELISA using the sera of a patient allergic to salmon roe. This was then compared with that of the native β′-component with and without carboxymethylation. Following successful cloning of the cDNA encoding the β′-component subunit, 170 amino acid residues were deduced and matched with the amino acid sequences of 121 and 88 residues in the 16kDa and 18kDa subunits, respectively. The sequences of both β′-component subunits were almost identical, and the predicted secondary structure of the β′-component showed a high content of β-pleated sheets and no α-helices. There was no difference in IgE-binding ability between the native and recombinant β′-component subunits at the same protein concentration, regardless of carboxymethylation. In conclusion, β′-component is a homodimer protein composed of two isoform subunits having the same level of IgE-binding ability and, therefore, allergenic identity. [ABSTRACT FROM PUBLISHER]

Abstract: A fish yolk protein, β′-component (β′-c), is the major allergen in chum salmon roe. The effect of proteolysis on the allergenicity of β′-c was estimated. Changes in the IgE-binding ability of β′-c upon pepsin and trypsin digestion were investigated by monitoring the proteolytic cleavage. In the pepsin–trypsin digestion of chum salmon yolk protein, the β′-c contained therein was degraded in a manner similar to that of other yolk proteins, but digestion fragments with a molecular mass of >10kDa remained throughout the digestion process. Specifically, the peptide sequence between 31-Y and 119-Q (10kDa) was stable to pepsin–trypsin digestion and the portion showed high IgE-binding ability. As a result, pepsin–trypsin digestion had little effect on the IgE-binding ability of β′-c. These results suggest that β′-c reaches the small intestine in the form of high-molecular-mass components with IgE-binding ability in vivo. [Copyright &y& Elsevier]

Abstract: Prostaglandin E2 (PGE2) is a major mediator in the pathophysiology, and pathogenesis of gynecological diseases associated with abnormal endometrial disease with proliferation and inflammation, such as endometriosis. In this study, we investigated the effect of dienogest, a selective progesterone receptor agonist, on PGE2 production and the expression of aromatase, an estrogen synthase, in human immortalized endometrial epithelial cells. Compared with monolayer culture, the cells showed enhanced PGE2 production and expression of the PGE2 synthases cyclooxygenase-2 (COX-2), and microsomal prostaglandin E2 synthase-1 (mPGES-1) in a spheroid culture system. Dienogest inhibited PGE2 production and this effect was reversed by RU486, a progesterone receptor antagonist. Dienogest inhibited the PGE2 synthases mRNA and protein expression, and the nuclear factor-κB activation. Moreover, the suppressive effect of dienogest on PGE2 production was sustained 24h after the drug was withdrawn. Dienogest but not COX inhibitors inhibited aromatase expression. These results suggest that progesterone receptor activation reduces the gene expressions of COX-2, mPGES-1, and aromatase. Our findings suggest that the pharmacological mechanism of dienogest includes the direct inhibition of PGE2 synthase and aromatase expression and may contribute to the therapeutic effect on the progression of endometriosis. [Copyright &y& Elsevier]

Abstract: Dienogest was introduced as an oral progestin. Yet its strong oral potency on endometrial activity is not clearly explained. To circumvent this situation, steroid hormone receptor profiling using transactivation assay and endometrial activity test in rabbits were carried out with determination of plasma drug concentration. Agonistic/antagonistic activity on human progesterone receptor (PR), androgen receptor (AR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), estrogen receptor α (ERα), or estrogen receptor β (ERβ) were determined. Dienogest activate PR (EC50 =3.4 or 10.5nmol/l) with antagonistic activity on AR (EC50 =420.6 or 775.0nmol/l) but not agonistic nor antagonistic action on GR, MR (3000nmol/l). Dienogest activate neither ERα nor ERβ (3000nmol/l). Progesterone activated PR with antagonistic activity on AR and on MR. Dydrogesterone showed a similar profile to progesterone. Norethisterone activated PR, AR, and ERα. Medroxyprogesterone acetate activated PR, AR, and GR. Danazol activated PR and AR. Collectively, dienogest has a good specificity to PR compared with the other drugs. By oral treatment, dienogest showed the strongest endometrial activity (ED50 =0.0042mg/kg) in McPhail test among other progestins (ED50 values for MPA, DYG, NES were 0.074, 1.9, >0.05mg/kg, respectively). Dienogest showed higher plasma concentrations than those of the other progestins with higher doses. The estimated plasma concentration of dienogest at ED50 (3.66nmol/l) was close to its EC50 value to activate PR. Thus, the stronger oral activity of dienogest could be explained simply by its in vitro potency on PR and its oral pharmacokinetic profile. [Copyright &y& Elsevier]

Discusses a study that investigated the magnetoresistance properties of spin valves in the current-perpendicular-to-plane (CPP) mode. Schematic plane view of the CPP element structure; Conventional spin valve films in the CPP mode; Conditions of CPP heads simulation.

Deals with a study which examined the effectiveness of various presenting modes for computer-driven tactile displays. Method; Results of the study; Advantages of the relief mode for visually impaired persons.

Summary: Our previous study found that glycation with uronic acid‐type reducing sugar enhanced the anti‐inflammatory effect of fish myofibrillar protein (Mf) via the Maillard reaction, and the molecular mechanism of enhanced anti‐inflammatory effect was investigated in this study. Mf was glycated with various reducing sugars at 60 °C and 35% relative humidity. After pepsin‐trypsin digestion, the anti‐inflammatory effects were evaluated by assessing secretions of pro‐inflammatory cytokines and expressions of LPS‐stimulated signalling pathway‐related genes in RAW 264.7 macrophages. Mf glycated with uronic acid‐type reducing sugars: glucuronic acid, galacturonic acid and alginate oligosaccharide, suppressed expression of cd14 and further suppressed expressions of tlr4 and myd88 comparing with intact and glycated Mf with glucose and galactose. Furthermore, uronic acid‐glycated Mf significantly suppressed expressions and secretions of pro‐inflammatory cytokines. The results indicate that uronic acid‐type glycation enhances anti‐inflammatory effect of Mf by attenuating expression of cd14 and enhancing the Mf‐induced suppression in TLR4‐MyD88‐dependent inflammatory signalling pathway. [ABSTRACT FROM AUTHOR]

Describes a PC-NTSC Scan Converter System LSI that can handle several personal computer video signal formats. Input signal types; Display forms; Multimedia image conversion technology; Filter coefficient generation circuit; Field distortion free image processing algorithm.

Highlights • Salmon roe allergen (β′-c) orally administered to mice was detected by ELISA. • β′-c passed through the digestive tract without marked degradation. • β′-c was absorbed in the small intestine and circulated in blood stream. • The absorbed β′-c migrated through cytoplasm of the intestinal epithelial cells. Abstract 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. Immunohistochemical staining showed that orally administered β′-c was distributed from the apical side to the basal side of intestinal epithelial cells, suggesting that endocytosis may be involved in the intestinal absorption of β′-c. In conclusion, β′-c is absorbed along a large portion of the small intestine and circulates in the blood stream without significant digestion. The resistance of β′-c to gastrointestinal digestion seems to contribute to its strong allergenicity. [ABSTRACT FROM AUTHOR]

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 264.7 cells), and orally administered d -DWE mitigated acute inflammation in carrageenan-induced paw edema of mice. Mass spectrometry revealed d -DWE contained peptide LRDGEIILRY (derived from phycoerythrin β-chain) and chlorophyll a decomposition products, and they individually reduced the secretion of the proinflammatory mediators in LPS-stimulated RAW 264.7 cells. These results indicate the anti-inflammatory activity could be from a combined effect of phycobiliprotein and chlorophyll a decomposition products prepared from the water-extract of dulse. Thus, inexpensive and safe water-extraction method is effective for the extraction of anti-inflammatory components from dulse. [ABSTRACT FROM AUTHOR]

Introduces the psychophysical effect of apparent movement for tactile letter reading using an apparent-motion mode. Examination of temporal parameters for application to actual communication.

Objective: Dienogest (DNG), a selective P receptor (PR) agonist, is used to treat endometriosis. To investigate whether DNG affects nerve growth factor (NGF) expression, we stimulated human endometrial epithelial cells (hEECs) with inflammatory cytokines. Design: Prospective basic research study using immortalized hEEC lines. Setting: Development Research, Mochida Pharmaceutical Co., Ltd., Japan. Patient(s): None. Intervention(s): Not applicable. Main Outcome Measure(s): In immortalized hEECs, NGF production induced by tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β) was evaluated in the presence or absence of the synthetic progestin DNG or endogenous P. The NGF messenger RNA (mRNA) and protein were measured using real-time reverse transcriptase–polymerase chain reaction (PCR) and ELISA, respectively. The NGF bioactivity in the culture medium was measured by assaying neurite outgrowth of PC-12 cells. Result(s): Tumor necrosis factor-α and IL-1β induced NGF mRNA and protein and increased NGF bioactivity in the culture medium. These activities were inhibited by DNG in a hEEC line that stably expresses PR. In contrast, in an hEEC line that constitutively expresses faint levels of PR, no inhibitory effect of DNG on NGF mRNA was detected. The NGF mRNA was also inhibited in hEEC lines that express only PR-A or only PR-B. Conclusion(s): Nerve growth factor is one of the key mediators that generates the pain associated with endometriosis. Dienogest inhibits NGF expression through PR-A and PR-B in hEEC, which may contribute to the pharmacological mechanisms of how DNG relieves pain in endometriosis. [Copyright &y& Elsevier]

Objective: To investigate the effect of dienogest on the expression of Toll-like receptor (TLR) 4 in human endometrial epithelial cells. Design: Prospective basic research study. Setting: Pharmaceutical research center. Patient(s): None. Intervention(s): Not applicable. Main Outcome Measure(s): TLR4 in the immortalized progesterone receptor–expressing human endometrial epithelial cell line, EM-PR, was activated with lipopolysaccharide and high-mobility group box 1 (LPS/HMGB1) in the presence or absence of the synthetic progestin dienogest or endogenous progesterone. The production of interleukin (IL)-8, IL-6, and monocyte chemoattractant protein (MCP)-1 and the mRNA expression of TLR4 were measured with the use of ELISA and real-time reverse-transcription polymerase chain reaction respectively and nuclear factor (NF)-κB reporter gene assays were performed. The role of TLR4 was assayed with the use of TLR4-siRNA–transfected cells. Result(s): Coadministration of LPS/HMGB1 induced the production of IL-8, IL-6, and MCP-1, TLR4 mRNA expression, and NF-κB activity in EM-PR cells, and dienogest inhibited all of these parameters. TLR4 knockdown using TLR4 siRNA reduced IL-8 production. Conclusion(s): Dienogest inhibits TLR4 mRNA expression and subsequent IL-8 production induced by TLR4 agonists via an inhibitory effect on NF-κB activation in human endometrial epithelial cells. This pharmacologic effect of dienogest may contribute to its therapeutic effect on abnormal inflammation of endometrium. [Copyright &y& Elsevier]

Dienogest (DNG) is a selective progesterone receptor (PR) agonist and oral administration of DNG is used for the treatment of endometriosis. DNG is considered to act on PR to down-regulate pathophysiological factors associated with endometriosis. PR exists as two major isoforms, PR-A and PR-B, and their physiological functions are mostly distinct. It was suggested that PR isoform expression patterns are altered in endometriosis, but it is unknown whether the pharmacological effects of DNG are exerted through PR-A, PR-B or both. In the present study, we investigated the pharmacological effects of DNG through these PR isoforms on the expression of CYP19A1 which encodes aromatase and inflammatory and neuroangiogenesis factors associated with the pain and progression of endometriosis. We used immortalized human endometriotic epithelial cell lines that specifically express PR-A or PR-B in a spheroid cell culture system, and treated them with DNG. We evaluated messenger RNA (mRNA) expression of CYP19A1, prostaglandin (PG)E2 synthase (cyclooxygenase (COX)-2 and microsomal PGE2 synthase (mPGES)-1), inflammatory cytokines (interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1) and neuroangiogenesis factors (vascular endothelial growth factor (VEGF) and nerve growth factor (NGF)) using real-time polymerase chain reaction. In addition, PGE2 production was measured by enzyme immunoassay. We found that DNG down-regulated mRNA expression of CYP19A1, COX-2, mPGES-1, IL-6, IL-8, MCP-1, NGF and VEGF, and PGE2 production in human endometriotic epithelial cell lines that specifically express either PR-A or PR-B. These results demonstrate that DNG activates both PR-A and PR-B and down-regulates the expression of pathophysiological factors associated with pain and progression of endometriosis. Our results suggest that DNG exerts therapeutic efficacy against the pain and progression of endometriosis regardless of PR isoform expression patterns. [ABSTRACT FROM AUTHOR]

Chum salmon myofibrillar protein (Mf) digested by pepsin-trypsin (dMf) was conjugated to alginate oligosaccharide (AO) through the Maillard reaction between the lysine residues in the dMf and the reducing end-groups of AO. The dMf-AO conjugate strongly suppressed the production of inflammatory cytokines, particularly tumor necrosis factor-α and interleukin-6, in lipopolysaccharide-stimulated murine macrophages. The anti-inflammatory effect was enhanced with increasing amounts of AO bound to dMf through the Maillard reaction, and the subsequent process of the Maillard reaction was involved in the enhancement of the anti-inflammatory activity. AO-conjugated peptides, the major anti-inflammatory components contained in the dMf-AO conjugate, were successfully recovered using isoelectric focusing without the use of carrier ampholytes (autofocusing); they were effectively concentrated in acidic peptide fractions, with the negative charge of the carboxyl groups of AO contributing to this separation. In conclusion, the combined use of AO conjugation and autofocusing is a useful method for producing novel anti-inflammatory peptides from fish Mf. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In a flow microreactor, aryllithiums bearing a piperidylmethyl group were generated using nBuLi by precise residence time control and effective temperature control, and then selectively borylated with boronic esters such as 2‐isopropoxy‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane (BpinOiPr) and trimethyl borate B(OMe)3 by fast mixing. Moreover, the direct integration with Suzuki–Miyaura cross coupling were successfully achieved to obtain nitrogen‐containing biaryl compounds. The present method could be applied for the straightforward synthesis of the key intermediate of a bioactive component bearing a piperidylmethyl‐biphenyl framework. [ABSTRACT FROM AUTHOR]

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. Using aptamer affinity beads, bevacizumab was selectively purified and detected as a single peak in the chromatogram. HT-RPLC achieved good separation for bevacizumab with a sharp peak within 10 min. The calibration curves of the two monoclonal antibodies ranged from 1 to 50 μg/mL and showed good correlation coefficients (r2 > 0.999). The limit of detection (LOD) and lower limit of quantification (LLOQ) values for bevacizumab were 0.15 and 0.51 μg/mL, respectively. The proposed method was successfully applied to the bioanalysis of the plasma samples obtained from the patients with lung cancer and may be extended to plan optimal therapeutic programs and for the evaluation of biological equivalencies in the development of biosimilars. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fish myofibrillar protein (Mf) was glycated by the Maillard reaction. • Glycation with uronic acid enhanced the anti-inflammatory activity of Mf. • Glycation with neutral sugar had no effect on the anti-inflammatory activity. • The enhancement could be related to the number of carboxyl group introduced to Mf. • Alginate oligosaccharide is an excellent functional modified sugar for Mf. 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. The anti-inflammatory activity of Mf was not affected by glycation with glucose or galactose, whereas strongly enhanced by glycation with uronic acid-type reducing sugars: glucuronic acid, galacturonic acid, and alginate oligosaccharide. These results indicate that the presence of carboxyl group in reducing sugar is important for enhancing the anti-inflammatory activity of Mf. This study also shows that the enhanced effect could depend upon the number of carboxyl group in bound reducing sugar. [ABSTRACT FROM AUTHOR]

We present giant magnetoresistance measurements in the current-perpendicular-to-plane mode on single and dual spin valves whose areas are from 0.1 to 1.0 µm². Dependence on the magnetic layer thickness and the structure was investigated. It was revealed that magnetoresistance change increases 20% by insertion of a nonmagnetic spacer layer in the free layer. The results were analyzed within the framework of the two-current series-resistor model, and proved to be consistent with the theory. [ABSTRACT FROM AUTHOR]

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+).Results: Dienogest markedly inhibited interleukin 1β-stimulated C-C motif chemokine ligand 20 mRNA expression and protein secretion in EMosis-CC/TERT1/PRA-/PRB+, which was abrogated by the progesterone receptor antagonist RU486. In EMosis-CC/TERT1/PRA+, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA and protein. In EMosis-CC/TERT1, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA, but had no effect on C-C motif chemokine ligand 20 protein.Conclusion: Dienogest inhibited interleukin 1β-induced up-regulation of C-C motif chemokine ligand 20 in endometriotic epithelial cells, mainly mediated by progesterone receptor B. [ABSTRACT FROM AUTHOR]

The linear ubiquitin chain assembly complex ( LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo. 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. We identify RIPK1 and caspase-8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL-induced RIPK1-independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL-induced activation of NF-κB and, consequently, the production of cytokines, downstream of FADD, caspase-8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation. [ABSTRACT FROM AUTHOR]

Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions. [ABSTRACT FROM AUTHOR]

BSTRACT The textural degradation of threadfin-bream meat gel accompanying the breakdown of the myosin heavy chain was caused not by a heat-stable alkaline proteinase (HAP) but by a newly found gel degradation-inducing factor (GIF). GIF as well as HAP was recovered in the sarcoplasmic fraction, but GIF was separated from HAP by gel filtration on Ultrogel AcA 34. This factor showed strong proteolytic activity against the myosin heavy chain at pH 7.0 in the presence of 2.5% NaCl. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in human endometriotic stromal cells (ESCs). Design: Experimental study in vitro. Setting: University hospital. Patient(s): Seventeen patients with ovarian endometrioma. Intervention(s): ESCs from chocolate cyst linings of ovaries were treated with DNG. Main Outcome Measure(s): Expression of aromatase and COX-2 evaluated in spheroid cultures of human ESCs by real-time quantitative polymerase chain-reaction and immunocytochemistry, production of PGE2 quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-κB) DNA-binding examined by ELISA and immunocytochemistry. Result(s): The pharmaceutical actions of DNG on the expression of aromatase and COX-2 and the production of PGE2 were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE2 were expressed in spheroid cultures than in conventional ESCs monolayers. In the spheroid cultures, DNG (10−7 M) and progesterone (10−7 M) inhibited the expression of aromatase, COX-2, and PGE2. DNG also inhibited NF-κB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-κB p50 nuclear localization. Conclusion(s): Because DNG inhibits aromatase and COX-2 expression as well as PGE2 production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Nonalcoholic steatohepatitis (NASH) is associated with fat accumulation in the liver, and develops to cirrhosis with the progression of hepatic fibrosis. Eicosapentaenoic acid (EPA) is used to treat hyperlipidemia, and suppresses hepatic fat accumulation. As the effect of EPA on NASH remains unclear, we assessed the therapeutic effect of EPA and its mechanisms in an animal model of NASH.Methods: Wistar rats were fed a methionine- and choline-deficient (MCD) diet for 20 weeks, and given EPA ethyl ester (EPA-E, 1,000 mg/kg/day) or vehicle by gavage from week 12, at which hepatic fibrosis has already established. The liver was histologically analyzed for fibrosis and α-smooth muscle actin (αSMA) expression, and hepatic levels of transforming growth factor-β1 (TGF-β1), fibrogenic gene expression, reactive oxygen species (ROS), and triglyceride (TG) content were determined. Serum oxidative markers were also measured.Results: EPA-E treatment significantly suppressed the MCD-induced increase in fibrotic area of liver sections, with repressed macronodule formation. EPA-E also suppressed increases in hepatic fibrogenic factors, αSMA expression, TGF-β1 level, and messenger RNA (mRNA) levels of procollagens and connective tissue growth factor. EPA-E reduced MCD-induced increases in hepatic ROS level, serum oxidative markers, 8-isoprostane and ferritin, and hepatic TG content. Attenuation of hepatic fibrosis by EPA-E was significantly correlated with hepatic ROS level, but not TG content.Conclusions: EPA-E attenuates progression of hepatic fibrosis in developed steatohepatitis, and this effect is likely mediated by inhibition of ROS production. These actions may elicit the therapeutic effect of EPA-E against NASH. [ABSTRACT FROM AUTHOR]

BACKGROUND We aimed to establish an endometrial autograft model in rats that would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is an orally active progestin used for the treatment of endometriosis. We investigated whether DNG would affect angiogenesis of the ectopic endometrium in our model. METHODS Mechanically isolated endometrial fragments were transplanted into dorsal skinfold chambers in rats. We analyzed the effect of DNG on angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after transplantation using intravital fluorescence microscopy. RESULTS The DNG-administered group showed significant suppression of angiogenesis of endometrial autografts, as indicated by the reduced size of the microvascular network and decreased microvessel density compared with those of control animals. The newly formed microvessels of the DNG-administered group showed consistently elevated diameters and centerline red blood cell velocity was decreased. Immunohistochemistry revealed a significant reduction in the level of perivascular α-smooth muscle actin within endometrial grafts of the DNG-administered group. CONCLUSIONS DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels. [ABSTRACT FROM AUTHOR]

Abstract: We have observed a large specific magnetoresistance change (ΔRA, product of resistance change and element area) in metallic spin valves in the current-perpendicular-to-plane (CPP) mode by employing ferromagnetic Co–Fe–Al alloys as free and reference layers. The ΔRA is about five times larger than that for conventional materials. The results were analyzed with the semiclassical two-current theory, and the enhancement in ΔRA is ascribed to compatibility of relatively high resistivity and a large spin-asymmetry coefficient for the spin-dependent bulk scattering of the alloys. Since half-metallicity is not always necessary to realize such properties, this opens up new ways of developing CPP spin valve materials. The alloys show, respectively, low coercivity and high effective pinning field as the free and reference layers, which are eminently suitable for their practical application to a magnetic read sensor. Their applicability to the read heads for over 300Gbit/in2 recording density is also discussed. [Copyright &y& Elsevier]

Ultra high-energy (UHE) neutrino (1015 eV <) detection in natural huge rock salt formation has been studied. Radio wave is generated by Askar'yan effect in rock salt. That is caused by the number asymmetry of electrons and positrons (excess charge) in electromagnetic shower from an UHE neutrino. An Electromagnetic shower in rock salt is generated by a computer code of Geant4.5. A modified Greisen parameterization in longitudinal distribution of the shower and a modified Nishimura, Kamata, and Greisen function in lateral distribution of the shower (structure function) are fitted to a space distribution of the excess electrons. The structure function would assist to calculate radio wave emission without using an electromagnetic shower simulation. [ABSTRACT FROM AUTHOR]

Ultra high energy (UHE) neutrinos with the energy larger than 1015 eV, surely arrive at the earth with Greisen, Zatsepin, Kuz'min (GZK) effect, though the rate is very few. The rare call requires us to utilize a large mass (>10 Gton) of detection medium. UHE neutrino generates a huge number of unpaired electrons in rock salt. They would emit sensible radio wave by coherent Cherenkov (Askar'yan) effect. The longer attenuation length of radio wave in rock salt reduces the number of antennas required. Several rock salt samples including synthesized one are measured in attenuation length for radio wave transmission at 0.3 and 1.0 GHz. Some show attenuation length larger than 300 m, which indicate a possibility for constructing a salt neutrino detector. [ABSTRACT FROM AUTHOR]

Current-perpendicular-to-plane (CPP) spin valve (SV) films with nano-oxide layers have been developed. The enhancement of giant magnetoresistance by inserting the current confining layer between free and pinned layers was confirmed by the calculation of the current-flow distribution using a finite-element model. For the bottom-type spin valve films with the structure of PdPtMn/CoFeB/Ru/CoFeB/cu/oxidized CoFeB(t nm)/Cu/CoFeB, MR ratio of 5.0% and RA of 0.60 Ω m[SUP2] were obtained at t = 1.2 nm. The merged head using the CPP-SV film with a nano-oxide layer whose MR ratio was 3.2% was fabricated. The magnetic read core width was 130 nm when the physical free-layer width was 100 nm. 0.91 mV[SUBp-p] output voltage was obtained at the sense current of 4.8 mA which corresponds to the average current density of 19 MA/cm[SUP2]. [ABSTRACT FROM AUTHOR]