Selective Inhibitory Effect of Hesperetin on the Automaticity of the Guinea Pig Pulmonary Vein Myocardium.

The effect of a citrus-derived flavonoid, hesperetin, on the automaticity and contraction of isolated guinea pig myocardium was examined. Hesperetin inhibited the rate of ectopic action potential firing of the pulmonary vein myocardium; the slope of the diastolic depolarization was decreased with minimum change in the action potential waveform. The effect was dependent on the concentration; the EC value for firing rate was 56.

IL-5-producing group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils.

Intestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria.

Isoliquiritigenin inhibits NLRP3 inflammasome activation with CAPS mutations by suppressing caspase-1 activation and mutated NLRP3 aggregation.

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.

Lung group 2 innate lymphoid cells differentially depend on local IL-7 for their distribution, activation, and maintenance in innate and adaptive immunity-mediated airway inflammation.

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.

Biophysical analysis of luciferase bioluminescence mechanisms using a non-oxidizable coelenterazine.

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.

Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice.

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.

Temperature regime during embryogenesis alters subsequent behavioural phenotypes of juvenile brown trout.

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.

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis.

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 inflammasomes and immunometabolism: A small molecule inhibitor of the NLRP3 inflammasome.

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.

Study of X-ray topography using the super-Borrmann effect.

X-ray topography exerting the super-Borrmann effect has been performed using synchrotron radiation to display dislocation images with a high-speed and high-resolution CMOS camera. Forward-transmitted X-rays are positively employed instead of reflected X-rays to reveal dislocations in relatively thick crystals by simultaneously exciting a pair of adjacent {111} planes owing to the super-Borrmann effect. Before the experiment, minimum values of the attenuation coefficients A for σ and π polarizations of the incident X-rays in the three-beam case are calculated.

Predator cannibalism can shift prey community composition toward dominance by small prey species.

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 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.

Isoliquiritigenin Attenuates Adipose Tissue Inflammation and Metabolic Syndrome by Modifying Gut Bacteria Composition in Mice.

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.

Betulin Attenuates TGF-β1- and PGE-Mediated Inhibition of NK Cell Activity to Suppress Tumor Progression and Metastasis in Mice.

Transforming growth factor (TGF)-β1 and prostaglandin E (PGE) 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-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-induced suppression of cytolysis in poly(I:C)-stimulated murine splenocytes, we found that betulin was the most potent compound.

Stabilizers for Osmium Isotopes in Microwave-Irradiated Acid Digestion and Inductively Coupled Plasma Mass Spectrometry Analysis.

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.

The relationship between plant-eating and hair evacuation in snow leopards (Panthera uncia).

Although most felids have an exclusive carnivore diet, the presence of plant matter in scat has been reported among various species. This indicates that there may be an adaptive significance to the conservation of plant-eating behavior in felid evolution. Some studies have hypothesized that felids consume plants for self-medication or as a source of nutrition.

Enhanced recruitment of larger predators in the presence of large prey.

Most carnivores undergo diet shift from smaller to larger prey items during ontogeny. The trophic relationship between a growing carnivore and larger prey is representative of a size-structured predator-prey interaction. The strength of this interaction is, in part, determined by the recruitment of individuals from smaller predatory size classes into larger predatory size classes.

Development of a novel β-1,6-glucan-specific detection system using functionally-modified recombinant endo-β-1,6-glucanase.

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides.

Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD).

Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases.

Elimination of eosinophils using anti-IL-5 receptor alpha antibodies effectively suppresses IL-33-mediated pulmonary arterial hypertrophy.

Interleukin (IL)-5 is a critical regulator of eosinophils and a therapeutic target for asthma. The administration of anti-IL-5 or anti-IL-5 receptor (IL-5R) antibodies has been shown to reduce eosinophil counts and ameliorate asthmatic symptoms in studies on animal models of allergy as well as in human clinical trials. In order to explore other potential clinical uses of IL-5R antibodies, we used an animal model of IL-33-mediated pulmonary arterial hypertrophy.

Allergic diseases: From bench to clinic - Contribution of the discovery of interleukin-5.

T helper 2 cells produce a number of cytokines including inteleukin (IL)-5, IL-4 and IL-13. Group 2 innate lymphoid cells (ILC2s) also produce IL-5 under sterile conditions. IL-5 is interdigitating homodimeric glycoprotein and a member of the four α helical bundle motifs conserved among hematopoietic cytokines.

Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance.

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism.

CD206 M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors.

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFβ signaling pathway. We show that adipose tissue CD206 cells are primarily M2-like macrophages, and ablation of CD206 M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes.

Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.

The Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) complex is essential for LPS recognition and induces innate immune responses against Gram-negative bacteria. As activation of TLR4/MD-2 is also critical for the induction of adaptive immune responses, TLR4/MD-2 agonists have been developed as vaccine adjuvants, but their efficacy has not yet been ascertained. Here, we demonstrate that a funiculosin (FNC) variant, FNC-RED, and FNC-RED and FNC derivatives are agonists for both murine and human TLR4/MD-2.