Plant growth regulators and Axl and immune checkpoint inhibitors from the edible mushroom Leucopaxillus giganteus.

A novel compound, (R)-4-ethoxy-2-hydroxy-4-oxobutanoic acid (1), and six known compounds (2-7) were isolated from the fruiting bodies of the wild edible mushroom Leucopaxillus giganteus. The planar structure of 1 was determined by the interpretation of spectroscopic data analysis. The absolute configuration of 1 was determined by comparing specific rotation of the synthetic compounds. In the plant regulatory assay, the isolated compounds (1-7) and the chemically prepared compounds (8-10) were evaluated their biological activity against the lettuce (Lactuca sativa) growth. Compounds 1 and 3-10 showed the significant regulatory activity of lettuce growth. 1 showed the strongest inhibition activity among the all the compounds tested. In the lung cancer assay, all the compounds were assessed the mRNA expression of Axl and immune checkpoints (PD-L1, PD-L2) in the human A549 alveolar epithelial cell line by RT-PCR. Compounds 1-10 showed significant inhibition activity against Axl and/or immune checkpoint.

A mushroom-derived amino acid, ergothioneine, is a potential inhibitor of inflammation-related DNA halogenation.

Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2'-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms.

Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils.

Epithelial to mesenchymal transition (EMT) is a mechanism by which eosinophils can induce airway remodeling. Montelukast, an antagonist of the cysteinyl leukotriene receptor, can suppress airway remodeling in asthma. The purpose of this study was to evaluate whether montelukast can ameliorate airway remodeling by blocking EMT induced by eosinophils. EMT induced was assessed using a co-culture system of human bronchial epithelial cells and human eosinophils or the eosinophilic leukemia cell lines, Eol-1. Montelukast inhibited co-culture associated morphological changes of BEAS-2b cells, decreased the expression of vimentin and collagen I, and increased the expression of E-cadherin. Montelukast mitigated the rise of TGF-ß1 production and Smad3 phosphorylation. Co-culture of human eosinophils with BEAS-2B cells significantly enhanced the production of CysLTs compared with BEAS-2B cells or eosinophils alone. The increase of CysLTs was abolished by montelukast pre-treatment. Montelukast had similar effects when co-culture system of Eol-1 and BEAS-2B was used. This study showed that montelukast suppresses eosinophils-induced EMT of airway epithelial cells. This finding may explain the mechanism of montelukast-mediated amelioration of airway remodeling in bronchial asthma.

Novel cerebroside, termitomycesphin I, from the mushroom, Termitomyces titanicus.

The novel cerebroside, termitomycesphin I (1), and two known cerebrosides (2 and 3) were isolated from the edible mushroom, Termitomyces titanicus. The structures of 1-3 were determined and identified by interpreting the spectroscopic data.

Medicinal Mushroom, Grifola gargal (Agaricomycetes), Lowers Triglyceride in Animal Models of Obesity and Diabetes and in Adults with Prediabetes.

Grifola gargal is a medicinal mushroom with biological effects, such as antiatherogenic activity, and is used as a treatment for various chronic inflammatory diseases. The aim of this study is to investigate the antidiabetic and antiobesity effects of a low-molecular weight hot water extract from G. gargal (GGL) against diabetes type 2. In a human clinical trial, 10 subjects with prediabetes consumed 9.2 g of GGL daily for 4 weeks. The significant beneficial health effects observed were decreases in triglyceride levels. This is the first report of these results in humans. Moreover, in animal experiments, we investigated the influence of administered feed with 2% (w/w) GGL for 42 days by using KK-Ay and ob/ob mice as animal models of obesity and diabetes. Results showed that GGL reduces blood glucose and triglyceride levels and adipose tissue. GGL (2.0 mg/mL) significantly suppressed the expression of the cytokine interleukin-6 in 3T3-L1 cells compared with control cells. Thus, the results indicate that G. gargal may be used as a safe and healthy medicinal food to prevent and improve diabetes- and obesity-related metabolic syndrome.

Axl and immune checkpoints inhibitors from fruiting bodies of Pleurocybella porrigens.

A novel compound (1) and three known ones (2-4) were isolated from the fruiting bodies of Pleurocybella porrigens. The structure of the novel compound was determined by 1D and 2D NMR and HRESIMS data. The biological activity of 1-3 was evaluated using the A549 lung cancer cell line. The results showed the inhibitory activity of compounds 1-3 on the expression of Axl and immune checkpoint molecules.

The Medicinal Mushroom, Grifola gargal, Ameliorates Allergic Bronchial Asthma.

Grifola gargal Singer, a medicinal mushroom, has been found to be effective for the prevention and treatment of various chronic inflammatory diseases. However, the effects of G. gargal on allergic diseases are unknown. The present study investigated the effect of G. gargal extract on allergic bronchial asthma. Asthma was induced in mice by ovalbumin sensitization and inhalation. The grade of asthma was compared between mice fed with chow containing G. gargal extract and mice given standard chow. The human mast cell and eosinophilic cell lines were used for in vitro studies. G. gargal extract significantly reduced airway hyperresponsiveness, lung eosinophilic infiltration, lung interleukin (IL)-13 expression, and plasma IgE level and significantly increased IL-10 plasma levels compared to untreated control mice. Spleen regulatory T cells were significantly increased in mice treated with the G. gargal extract compared with untreated control mice. G. gargal extract significantly suppressed expression of cytokines in mast cells and eosinophils compared with control cells. Overall, these observations show that G. gargal extract augments the lung population of regulatory T cells and ameliorates allergic inflammation and airway hyperresponsiveness in mice with allergic bronchial asthma, suggesting the potential therapeutic benefit of G. gargal extract in allergic diseases.

Blood Glucose-Reducing and Fat-Reducing Effects of a Novel Medicinal Mushroom, Grifola gargal (Agaricomycetes).

Grifola gargal Singer is a medicinal mushroom with biological effects such as antiatherogenic and antiosteoporotic activities. The objective of this study was to examine a blood glucose-reducing effect and a fatreducing effect of G. gargal supplementation in vivo. The effects of G. gargal powder (GGP) in a high-molecular weight hot water extract (GGH) and a low-molecular weight hot water extract (GGL) on blood glucose were investigated in streptozotocin (STZ)-induced diabetic ICR mice (STZ diabetic mice). A significant decrease in blood glucose was observed after 5 weeks of GGL supplementation (fraction with a molecular weight ≤ 6000 Da) in STZ diabetic mice. In the next test, we examined the antihyperglycemic and fat-reducing effects of GGL in diet-induced obesity (DIO) mice fed a high-fat diet. GGL facilitated reductions in blood glucose and body fat. This study confirms, to our knowledge for the first time, that administration of G. gargal extract has antihyperglycemic and body fat-reducing effects in STZ diabetic mice and DIO mice. Therefore, G. gargal is a promising functional food to prevent and treat diabetes and lifestyle-related diseases.

Effect of the Medicinal Mushroom, Grifola gargal (Agaricomycetes), on Bone Turnover Markers and Serum Lipids in Middle-Aged and Elderly Japanese Women.

A clinical study was performed to examine the effect of the edible mushroom, Grifola gargal, on bone turnover markers and serum lipids in middle-aged and elderly Japanese women. Postmenopausal women aged 51-73 years (mean age, 61 years) received daily oral administration of 5 g G. gargal fruiting bodies (hot air-dried and powdered; G. gargal powder [GGP]). Serum levels of bone alkaline phosphatase (BAP) and lipids and urinary deoxypyridinoline (DPD) levels were measured before and 2 weeks after the start of GGP treatment. As a result, urinary DPD bone resorption marker levels in women treated with GGP decreased significantly. Serum levels of the BAP bone formation marker also tended to increase, but the difference was not significant. By contrast, the atherogenic index decreased and the high-density lipoprotein (HDL) ratio increased significantly. However, there were no statistically significant differences in serum lipids of total cholesterol, HDL cholesterol, and low-density lipoprotein cholesterol. In addition, this study demonstrated for the first time that G. gargal is safe for human consumption.

The Impact of Buttonhole Cannulation on Patients and Staff in Hemodialysis Facilities.

The two reasons that patients desire buttonhole cannulation are avoidance of puncture pain and extension of arteriovenous fistula life. Despite the desire to receive buttonhole cannulation by many patients, medical staff at most local hemodialysis facilities tend to hesitate to implement the cannulation method. This method is used on patients in the dialysis unit at Saitama Medical Center, but tends to be discontinued for those patients upon their transfer to local hemodialysis facilities. Medical staff members of one local hemodialysis facility report the percentage of patients on the buttonhole method was 53% in 2007, but that it sharply decreased to 17% in 2013. Hesitation by local hemodialysis facilities to adopt the buttonhole method is due to, but not limited to, several factors. These factors include the frequently occurring trampoline effect, the difficulty of removing scabs, formation of a false buttonhole track, and the pain from insertion of a dull needle. Perceived differences in the value of buttonhole cannulation may potentially affect communication between patients and staff in local hemodialysis facilities.

How to monitor vascular access in our hospital.

BACKGROUND: The number of dialysis patients in Japan has amounted to approximately 310,000. Most of the patients undergo hemodialysis. The reason why they can undergo hemodialysis is because maintaining and managing vascular access (VA) has improved. Recently, thanks to the progress of medical equipment, a variety of monitoring systems have been developed. It is important to make good use of these monitoring systems. RESULTS: In our hospital, we have been monitoring with an ultrasonic device and HD02. We measure blood flow of brachial artery with an ultrasonic device during nondialysis treatment. We examine real blood flow and blood recirculation with HD02 and evaluate the function of VA during dialysis. CONCLUSIONS: In order to provide good dialysis care, good use of monitoring devices of VA is significant.

Activated protein C modulates the proinflammatory activity of dendritic cells.

BACKGROUND: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. MATERIALS AND METHODS: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. RESULTS: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice. CONCLUSION: These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation.

Amelioration of Atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer.

The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-ß1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice.

[Interactive processes in video-mediated referential communication].

This study examined interactive processes that occurred in video-mediated referential communication task. Pairs of participants were assigned to one of four conditions; in a room with partition, or in separate rooms linked by telephone with three levels of noise interference (none, low, and high). In all conditions, a video-monitor link allowed the participants to see the upper body of their partner. Analyses of gestural and visual interaction revealed that participants in partition and no-interference conditions did not rely on the visual channel, while those in the others frequently looked at the monitor. Furthermore, gestural references appeared especially in high-noise condition. Qualitative analyses of conversations showed that participants in high-noise condition relied more on demonstrative references, and used more metaphoric expressions of a whole referent, based on the common ground shared by the pair. These results are discussed in terms of how people collaboratively interact and construct a shared context for communication between them.

Termitomycamides A to E, fatty acid amides isolated from the mushroom Termitomyces titanicus, suppress endoplasmic reticulum stress.

Five fatty acid amides, termitomycamides A to E (1 to 5), were isolated from the giant edible mushroom Termitomyces titanicus. The structures of 1-5 were determined by the interpretation of spectral data and/or synthesis. Compounds 2 and 5 showed protective activity against endoplasmic reticulum stress-dependent cell death.