Search

The spin-lattice relaxation times T1 of an unstable nucleus 19O (T1/2 = 26.9 s, I = 5/2) implanted into Y2O3 stabilized ZrO2 (YSZ), which is a solid oxide fuel cell material, were measured at T = 278 − 333 K by means of the β-NMR technique, using a highly spin polarized 19O beam produced via the heavy ion reaction. The motional correlation times τc for oxygen motion derived from the T1 data are on the same straight line on the Arrhenius plot as those derived from the previous 17O-NMR data at above the room temperature. This indicates that 19O ions implanted into YSZ from outside seem to exhibit the same behavior as oxygen ions in the host YSZ material. [ABSTRACT FROM AUTHOR]

The nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome contributes to the development of inflammatory diseases. Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by NLRP3 gene mutations that results in excessive IL-1β production. We previously identified isoliquiritigenin (ILG), a component of Glycyrrhiza uralensis extracts, as a potent inhibitor of the NLRP3 inflammasome. Here, we aimed to investigate whether ILG inhibits the activation of NLRP3 inflammasome caused by NLRP3 gene mutations. We demonstrated that ILG significantly inhibited NLRP3 inflammasome-mediated lactate dehydrogenase (LDH) release and IL-1β production in two CAPS model THP-1 cell lines, NLRP3-D303N and NLRP3-L353P, in a dose-dependent manner. Interestingly, the NLRP3 inhibitor MCC950 inhibited LDH release and IL-1β production in NLRP3-D303N cells, but not in NLRP3-L353P cells. Western blotting and caspase-1 activity assays showed that ILG, as well as caspase inhibitors, including Z-VAD and YVAD, suppressed caspase-1 activation. Notably, ILG prevented cryo-sensitive foci formation of NLRP3 without affecting the levels of intracellular Ca 2+ . We concluded that ILG effectively prevents the constitutive activation of the inflammasome associated with NLRP3 gene mutations by inhibiting the aggregation of cryo-sensitive mutated NLRP3., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Interleukin-7 (IL-7) is a cytokine critical for the development and maintenance of group 2 innate lymphoid cells (ILC2s). ILC2s are resident in peripheral tissues such as the intestine and lung. However, whether IL-7 produced in the lung plays a role in the maintenance and function of lung ILC2s during airway inflammation remains unknown. IL-7 was expressed in bronchoalveolar epithelial cells and lymphatic endothelial cells (LECs). To investigate the role of local IL-7 in lung ILC2s, we generated two types of IL-7 conditional knockout (IL-7cKO) mice: Sftpc-Cre (SPC-Cre) IL-7cKO mice specific for bronchial epithelial cells and type 2 alveolar epithelial cells and Lyve1-Cre IL-7cKO mice specific for LECs. In steady state, ILC2s were located near airway epithelia, although lung ILC2s were unchanged in the two lines of IL-7cKO mice. In papain-induced airway inflammation dependent on innate immunity, lung ILC2s localized near bronchia via CCR4 expression, and eosinophil infiltration and type 2 cytokine production were reduced in SPC-Cre IL-7cKO mice. In contrast, in house dust mite (HDM)-induced airway inflammation dependent on adaptive immunity, lung ILC2s localized near lymphatic vessels via their CCR2 expression 2 weeks after the last challenge. Furthermore, lung ILC2s were decreased in Lyve1-Cre IL-7cKO mice in the HDM-induced inflammation because of decreased cell survival and proliferation. Finally, administration of anti-IL-7 antibody attenuated papain-induced inflammation by suppressing the activation of ILC2s. Thus, this study demonstrates that IL-7 produced by bronchoalveolar epithelial cells and LECs differentially controls the activation and maintenance of lung ILC2s, where they are localized in airway inflammation., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The potential roles of the gut microbiota in the pathogenesis of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), have attracted increased interest. We have investigated the links between gut microbiota and NASH development in Tsumura-Suzuki non-obese mice fed a high-fat/cholesterol/cholate-based (iHFC) diet that exhibit advanced liver fibrosis using antibiotic treatments. The administration of vancomycin, which targets Gram-positive organisms, exacerbated the progression of liver damage, steatohepatitis, and fibrosis in iHFC-fed mice, but not in mice fed a normal diet. F4/80 + -recruited macrophages were more abundant in the liver of vancomycin-treated iHFC-fed mice. The infiltration of CD11c + -recruited macrophages into the liver, forming hepatic crown-like structures, was enhanced by vancomycin treatment. The co-localization of this macrophage subset with collagen was greatly augmented in the liver of vancomycin-treated iHFC-fed mice. These changes were rarely seen with the administration of metronidazole, which targets anaerobic organisms, in iHFC-fed mice. Finally, the vancomycin treatment dramatically modulated the level and composition of bile acid in iHFC-fed mice. Thus, our data demonstrate that changes in inflammation and fibrosis in the liver by the iHFC diet can be modified by antibiotic-induced changes in gut microbiota and shed light on their roles in the pathogenesis of advanced liver fibrosis.

Gaussia luciferase (GLuc 18.2kDa; 168 residues) is a marine copepod luciferase that emits a bright blue light when oxidizing coelenterazine (CTZ). It is a helical protein where two homologous sequential repeats form two anti-parallel bundles, each made of four helices. We previously identified a hydrophobic cavity as a prime candidate for the catalytic site, but GLuc's fast bioluminescence reaction hampered a detailed analysis. Here, we used azacoelenterazine (Aza-CTZ), a non-oxidizable coelenterazine (CTZ) analog, as a probe to investigate its binding mode to GLuc. While analysing GLuc's activity, we unexpectedly found that salt and monovalent anions are absolutely required for Gluc's bioluminescence, which retrospectively appears reasonable for a sea-dwelling organism. The NMR-based investigation, using chemical shift perturbations monitored by 15 N- 1 H HSQC, suggested that Aza-CTZ (and thus unoxidized CTZ) binds to residues in or near the hydrophobic cavity. These NMR data are in line with a recent structural prediction of GLuc, hypothesizing that large structural changes occur in regions remote from the hydrophobic cavity upon the addition of CTZ. Interestingly, these results point toward a unique mode of catalysis to achieve CTZ oxidative decarboxylation., Competing Interests: No conflict of interest., (©2022TheAuthors.PublishedbyElsevierB.V.)

The mammalian immune system consists of two arms, innate and acquired immunity. When I was nominated in 2003 as editorial board members of B.B.R.C., it was in line with the paradigm shift in trends of immunology in the way of thinking from acquired immunity represented by peptide recognition by T-cell receptor to innate immunity represented by the recognition of pathogen-derived molecular pattern including lipid and carbohydrate. In this short perspective, I will introduce hot-spot of recent researches of inflammation, particularly inflammasome and immunometabolism. Here, particular attention is given to small molecule inhibitors of NLRP3 inflammasome activation., Competing Interests: Declaration of competing interest The author declares no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Climate warming imposes a serious threat, especially to freshwater ecosystems in temperate and (sub)polar regions, which are often dominated by cold-adapted ectotherms. Although relatively intense warming during winter is common across the climatic regions, comparably little focus has been put on the organismal impacts of winter warming. Embryonic development, which is exceptionally susceptible to ambient temperature, occurs during winter in various freshwater ectotherms. Yet, our knowledge of the effects of increased temperature during embryogenesis on later life stages is limited. Using brown trout ( Salmo trutta ), we examined how a 1.5°C temperature increase from fertilization to hatching affects various traits at the onset of the free-swimming stage (i.e. a comparison between 3.5 and 5.0°C treatments). Although all hatchlings were kept at the same temperature (7.0°C) from hatching to the onset of the free-swimming stage for about two months, the temperature increase during embryogenesis substantially reduced key ecological behaviours, i.e. activity and exploration levels, at the onset of the free-swimming stage despite only marginal temperature effects on morphological and physiological traits at this stage. Given the importance of behavioural traits in early growth and survival, our study suggests a likely pathway through which subtle changes in mean winter temperature affect early fitness.

Macrophages play critical roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is unclear which macrophage subsets are critically involved in the development of inflammation and fibrosis in NASH. In TSNO mice fed a high-fat/cholesterol/cholate-based diet, which exhibit advanced liver fibrosis that mimics human NASH, we found that Kupffer cells (KCs) were less abundant and recruited macrophages were more abundant, forming hepatic crown-like structures (hCLS) in the liver. The recruited macrophages comprised two subsets: CD11c + /Ly6C - and CD11c - /Ly6C + cells. CD11c + cells were present in a mesh-like pattern around the lipid droplets, constituting the hCLS. In addition, CD11c + cells colocalized with collagen fibers, suggesting that this subset of recruited macrophages might promote advanced liver fibrosis. In contrast, Ly6C + cells were present in doughnut-like inflammatory lesions, with a lipid droplet in the center. Finally, RNA sequence analysis indicates that CD11c + /Ly6C - cells promote liver fibrosis and hepatic stellate cell (HSC) activation, whereas CD11c - /Ly6C + cells are a macrophage subset that play an anti-inflammatory role and promote tissue repair in NASH. Taken together, our data revealed changes in liver macrophage subsets during the development of NASH and shed light on the roles of the recruited macrophages in the pathogenesis of advanced fibrosis in NASH.

Cannibalism among predators is a key intraspecific interaction affecting their density and foraging behavior, eventually modifying the strength of predation on heterospecific prey. Interestingly, previous studies showed that cannibalism among predators can increase or reduce predation on heterospecific prey; however, we know less about the factors that lead to these outcomes. Using a simple pond community consisting of Hynobius retardatus salamander larvae and their associated prey, I report empirical evidence that cannibalism among predators can increase predation on large heterospecific prey but reduce that on small heterospecific prey. In a field-enclosure experiment in which I manipulated the occurrence of salamander cannibalism, I found that salamander cannibalism increased predation on frog tadpoles but reduced that on aquatic insects simultaneously. The contrasting effects are most likely to be explained by prey body size. In the study system, frog tadpoles were too large for non-cannibal salamanders to consume, while aquatic insects were within the non-cannibals' consumable prey size range. However, when cannibalism occurred, a few individuals that succeeded in cannibalizing reached large enough size to consume frog tadpoles. Consequently, although cannibalism among salamanders reduced their density, salamander cannibalism increased predation on large prey frog tadpoles. Meanwhile, salamander cannibalism reduced predation on small prey aquatic insects probably because of a density reduction of non-cannibals primarily consuming aquatic insects. Body size is often correlated with various ecological traits, for instance, diet width, consumption, and excretion rates, and is thus considered a good indicator of species' effects on ecosystem function. All this considered, cannibalism among predators could eventually affect ecosystem function by shifting the size composition of the prey community., (© 2022 The Author. Ecology and Evolution published by John Wiley & Sons Ltd.)

Scope: Isoliquiritigenin (ILG) has been reported to attenuate adipose tissue inflammation and metabolic disorder; however, the underlying mechanisms remain to be elucidated. The aim of this study is to elucidate whether ILG shows the anti-inflammatory and antimetabolic syndrome effects through gut microbiota modification., Methods and Results: Mice are fed a high-fat diet (HFD) with or without ILG for up to 12 weeks. The effect of ILG on body weight, blood glucose level, adipose tissue inflammation, gut barrier function, and gut microbiota composition are investigated. ILG supplementation alleviates HFD-induced obesity, glucose tolerance, and insulin resistance and suppresses inflammatory gene expression in epididymal white adipose tissue (eWAT). Moreover, ILG supplementation modifies gut bacterial composition by increasing the abundance of antimetabolic disease-associated species (e.g., Parabacteroides goldsteinii and Akkemansia muciniphila) and up-regulated genes associated with gut barrier function. Fecal microbiome transplantation (FMT) from ILG-fed donors counteract HFD-induced body and eWAT weight changes, inflammation-related gene expression, glucose tolerance, and insulin resistance, thereby suggesting that ILG-responsive gut bacteria exerts anti-inflammatory and antimetabolic syndrome effects., Conclusion: Alterations in gut bacteria underly the beneficial effects of ILG against adipose tissue inflammation and metabolic disorders. ILG may be a promising prebiotic for the prevention and treatment of metabolic syndrome., (© 2022 Wiley-VCH GmbH.)

Osmium is defined in the international council for harmonization (ICH-Q3D) guidelines as an element whose concentration can be determined by validated methods including microwave-assisted nitric acid digestion and inductively coupled plasma mass spectrometry. However, microwave digestion using nitric acid is known to result in osmium recoveries higher than the theoretical values in spiked tests because of the formation of highly volatile osmium tetroxide in an oxidation reaction. To stabilize osmium, the addition of thiourea as a complexing agent has been tested and proved its utility. It remains unclear whether other compounds can prevent the over-recovery of osmium. In this study, we investigated four compounds, thiourea, ascorbic acid, sodium sulfite, and potassium metabisulfite, that could reduce the overestimation of osmium isotopes. The minimum amounts of thiourea, ascorbic acid, sodium sulfite, and potassium metabisulfite required to stabilize 10 ng/mL osmium in blank matrix were 1.0, 1.0, 2.5, and 2.5 g/L, respectively. The relative standard deviations obtained from 12 analyses for each stabilization solution were less than 3.3% in thiourea, 12.7% in ascorbic acid, 9.0% in sodium sulfite, and 10.6% in potassium metabisulfite. The stabilization solutions were investigated in a digested tablet matrix and were found to be effective. The impact of adding stabilization solutions on the determination of all ICH-Q3D element concentrations was also evaluated. As stabilization solutions had a small or significant impact on the determination of some elements, it was concluded that osmium determination should be conducted independently.

Transforming growth factor (TGF)-β1 and prostaglandin E 2 (PGE 2 ) are humoral factors critically involved in the induction of immunosuppression in the microenvironment of various types of tumors, including melanoma. In this study, we identified a natural compound that attenuated TGF-β1- and PGE 2 -induced immunosuppression and examined its effect on B16 melanoma growth in mice. By screening 502 natural compounds for attenuating activity against TGF-β1- or PGE 2 -induced suppression of cytolysis in poly(I:C)-stimulated murine splenocytes, we found that betulin was the most potent compound. Betulin also reduced TGF-β1- and PGE 2 -induced downregulation of perforin and granzyme B mRNA expression and cell surface expression of NKG2D and CD69 in natural killer (NK) cells. Cell depletion and coculture experiments showed that NK cells, dendritic cells, B cells, and T cells were necessary for the attenuating effects of betulin. Structure-activity relationship analysis revealed that two hydroxyl groups at positions C3 and C28 of betulin, their cis-configuration, and methyl group at C30 played crucial roles in its attenuating activity. In a subcutaneous implantation model of B16 melanoma in mice, intratumor administration of betulin and LY2157299, a TGF-β1 type I receptor kinase inhibitor, significantly retarded the growth of B16 melanoma. Notably, betulin increased significantly the number of CD69 positive NK cells in tumor sites at early stages of post-tumor cell injection. Our data suggest that betulin inhibits the growth of B16 melanoma by enhancing NK cell activity through attenuating the immunosuppressive tumor microenvironment.