PMID: 

Biomed Res Int. 2019 ;2019:7528609. Epub 2019 Apr 16. PMID: 31139649

Abstract Title: 

Structural Elucidation and Immune-Enhancing Effects of Novel Polysaccharide from.

Abstract: 

Beta-glucan (-glucan) is a macromolecule structure where glucose unit has bonded through-glycosidic bond at 1 and 3 positions. It is well known as a natural immunomodulator without exhibiting any side effects via enhancing immunity. Mushroom contains a large amount of-glucan and it has anticancerous and antioxidant efficacy. Structure and physical properties of-glucan are highly influenced by the types of mushroom. In particular,has-1, 3 and-1, 6 bonds in their structure. It has been noted that-glucan content also depends upon the size of mushroom particles. The exact content of-glucan and their immunological activity by a particle size ofhave yet to be fully elucidated. Herein,-glucan contents were analyzed according to the particle size of leaf mushroom followed by cell activation and immunoactivity analysis. The highest-glucan content was observed at a particle size of 20-30m (27.65± 0.30 w/w). All samples showed ~ 103% cell activation compared to the control and greater cell activity was observed at higher concentration. The significant increase in cytokines secretion was observed in the presence of 20-30m particle size ofcompared to the control. This study suggested that 20-30m size is the suitable size ofthat can be used as a health supplement and food additive to act as an immune booster, hypotensive agent, and hypoglycemic agent.

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PMID: 

Biosci Biotechnol Biochem. 2019 Dec ;83(12):2280-2287. Epub 2019 Aug 14. PMID: 31412751

Abstract Title: 

extract and ergosterol reduce allergic reactions in an allergy mouse model by suppressing the degranulation of mast cells.

Abstract: 

The increasing number of patients suffering from allergic diseases is a global health problem.is an edible mushroom consumed as a health food in Asia, and has recently been reported to have anti-allergic effects. We previously reported thatextract (GFE) and its active components, ergosterol and its derivatives, inhibited the antigen-induced activation of RBL-2H3 cells. Here, we demonstrated that GFE and ergosterol also had an inhibitory effect on the degranulation of bone marrow-derived mast cells (BMMCs) and alleviated anaphylactic cutaneous responses in mice. Using an air pouch-type allergic inflammation mouse model, we confirmed that oral administration of GFE and ergosterol suppressed the degranulation of mast cells. Our findings suggest that, including ergosterol as its active component, reduces type I allergic reactions by suppressing mast cell degranulation in mice, and might be a novel functional food that prevents allergic diseases.

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PMID: 

Int J Mol Sci. 2019 Oct 24 ;20(21). Epub 2019 Oct 24. PMID: 31653116

Abstract Title: 

The Positive Effects ofHeteropolysaccharide on NAFLD and Regulation of the Gut Microbiota.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. In this study, the ability ofheteropolysaccharide (GFP) to ameliorate NAFLD was investigated in rats fed a high-fat diet (HFD). The molecular mechanisms modulating the expression of specific gene members related to lipid synthesis and conversion, cholesterol metabolism, and inflammation pathways were determined. The components of the intestinal microflora in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Supplementation with GFP significantly increased the proportions of,, andand decreased the proportions of,,,, and. In addition,,, andwere shown to be significant cecal microbiota according to the Spearman's correlation test between the gut microbiota and biomedical assays (|r|>0.7). Histological analysis and biomedical assays showed that GFP treatments could significantly protect against NAFLD. In addition,,andmay play vital roles in the prevention of NAFLD. These results suggest that GFP could be used as a functional material to regulate the gut microbiota of NAFLD individuals.

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PMID: 

PLoS One. 2019 ;14(11):e0224740. Epub 2019 Nov 7. PMID: 31697749

Abstract Title: 

Synergistic immuno-modulatory activity in human macrophages of a medicinal mushroom formulation consisting of Reishi, Shiitake and Maitake.

Abstract: 

A key characteristic of mushroom polysaccharides that elicit an immunomodulatory response is that they are rich inβ-glucans and low in α-glucans. In this study we analysed nine commercially available preparations from three mushroom species, Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes) and Maitake (Grifola frondosa), for β- and α-glucan content. Based on β- and α-glucan content we selected three extracts to combine into a formula and evaluated the ability of the individual extracts and formula to impact on the expression of cytokines IL-1α, IL-6, IL-10 and TNF-α in human macrophages with and without LPS stimulation. The majority of mushroom extracts and the formula were found to be highly potent immuno-stimulators possessing EC50 values lower than 100 μg/mL. Interestingly the mushroom formula had lower EC50 values in TNF-α expression from LPS stimulated macrophages compared to the individual extracts, suggesting a potential synergistic effect of the mushroom formula. A responseadditivity graph and curve-shift analysis illustrated that indeed the mushroom formula exhibited an immuno-stimulatory synergistic effect on the expression of the majority of cytokines evaluated in both LPS stimulated and non-stimulated human macrophages, with IL-10 having an antagonistic response.This study represents the first report of a synergistic immuno-modulatory response in human macrophages elicited from a mushroom formula rationally derived from β- and α-glucan content.

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PMID: 

Int J Biol Macromol. 2019 Nov 20. Epub 2019 Nov 20. PMID: 31759027

Abstract Title: 

Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin.

Abstract: 

This study aimed to investigate the hypoglycemic and hypolipidemic activities of polysaccharides from Grifola frondosa (GFP) in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ). Results showed that oral administration of GFP markedly reduced the serum levels of fasting blood glucose (FBG), oral glucose tolerance (OGT), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and significantly decreased the hepatic levels of TC, TG and free fatty acids (FFA). Meanwhile, high-dose of GFP supplementation (900 mg/kg day) also showed powerful effects on moderating the composition of intestinal microflora in diabetic mice, especially altering the functionally relevant intestinal microbial phylotypes. Spearman's correlation network analysis revealed that key microbial phylotypes responding to GFP intervention were strongly correlated with the glucose and lipid metabolic disorders associated parameters. Moreover, GFP treatment regulated mRNA expression levels of the genes responsible for hepatic glucose and lipid metabolism. It is noteworthy that GFP treatment markedly increased mRNA expressionof cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acids (BAs) synthesis and excretion in liver. These findings demonstrated that GFP could prevent hyperglycemia and hyperlipidemia in diabetic mice by altering gut microbiota and regulating hepatic glycolipid metabolism related genes, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

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PMID: 

Int J Biol Macromol. 2020 Mar 15 ;147:79-88. Epub 2020 Jan 8. PMID: 31923503

Abstract Title: 

A polysaccharide from Grifola frondosa fruit body induces HT-29 cells apoptosis by PI3K/AKT-MAPKs and NF-κB-pathway.

Abstract: 

BACKGROUND: A neutral polysaccharide was isolated from the fruiting body of a mushroom Grifola frondosa (GFP-A). The tumor suppressive activity of GFP-A on protein expressions of PI3K/AKT, MAPKs, nuclear factorκB and caspase pathways in HT-29 cells were investigated.METHODS: The inhibitory effect and mechanism of GFP-A on the HT-29 cells were investigated. The cell viability was examined by MTT. Scanning electron microscopy analysis and flow cytometry were conducted to examine the apoptosis of cells. The protein expressions of PI3K/AKT, MAPKs, nuclear factorκB and caspase pathways were analyzed using western blot.RESULTS: The results of MTT assay showed that GFP-A of 180 μg/mL could significantly inhibit the proliferation of HT-29 cells. Western blotting results showed that GFP-A decreased the protein expression of PI3K and AKT, enhanced the phosphorylation of c-Jun N-terminal kinase (JNK), p38 MAPK and inhibited the phosphorylation of ERK1/2 and the translocation of nuclear factor-κB (NF-κB) into the nucleus. In the meanwhile, GFP-A could up-regulate the ratio of Bax to Bcl-2, increase the release of cytochrome C to cytoplasm, ultimately lead to the activation of caspase-9.CONCLUSIONS: The above results confirmed that GFP-A promoted the apoptosis of HT-29 cells through PI3K/AKT-MAPKs-NF-κB and caspase signaling pathways.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2019 Dec ;44(23):5174-5183. PMID: 32237355

Abstract Title: 

[Meta-analysis on effect of Grifola frondosa polysaccharide in regulating in vivo immunoregulatory function on animal disease models].

Abstract: 

The study aimed to explore the in vivo immunoregulatory function of Grifola frondosa polysaccharide( GFP) on animal disease models. Databases of PubMed,Embase,Web of Scinece,CNKI,CBM and Wan Fang Data were searched from the date of their establishment to February 2018. Two reviewers independently screened included studies and evaluated their quality by using SYRCLE's risk of bias tool. R software was used to analyze the data. Finally,20 animal experiment studies were included. According to Metaanalysis. For cellular immunity,GFP could effectively enhance the proliferation of effect or T cells,natural killer cells and macrophages in mice. The percentage of CD4+T cells( MD = 1. 89,95% CI [0. 94,2. 83],P< 0. 000 1),CD8+T cells( MD = 8. 46,95% CI[5. 93,11. 00],P<0. 000 1),NK cells( MD= 2. 67,95% CI [0. 23,5. 11],P= 0. 03),and macrophages( MD= 14. 09,95% CI[0. 84,27. 34],P= 0. 04) were all higher than those in control group. For humoral immunity,GFP could increase the secretion of TNF-α and INF-γ． The secretion of TNF-α( SMD = 15. 92,95% CI [9. 07,22. 76],P<0. 000 1) and INF-γ( SMD = 5. 34,95% CI[3. 42,7. 26],P<0. 000 1) were all higher than those in control group. In conclusion,GFP could regulate immunologic function by enhancing the proliferation activity of immune cells( CD4+T cells,CD8+T cells,NK cells and macrophages) and the secretion of immune factors( TNF-α and INF-γ) ． However,it is necessary to further standardize the selection of specific surface markers of immune cells and the administration of GFP,in order to reduce the heterogeneity among the studies. At the same time,more attention shall be paid to experimental design,implementation and full report,especially to the establishment and implementation of animal experimental registration system,so as to improve the transparency and quality of the whole process of animal experimental research,enhance the value of basic research ultimately,and provide a reliable theoretical basis for the transformation of basic research into clinical research.

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PMID: 

Virus Res. 2020 Apr 2 ;279:197885. Epub 2020 Jan 22. PMID: 31981772

Abstract Title: 

Host microRNAs and exosomes that modulate influenza virus infection.

Abstract: 

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate over half of human protein-coding genes and play a vital role in cellular development, proliferation, metabolism, and homeostasis. Exosomes are rounded or cup-like extracellular vesicles that carry proteins, mRNAs, miRNAs, and lipids for release and exchange messages between cells involved in various cellular processes. Influenza virus is a substantial public health challenge. The expression of host miRNAs is altered in response to stimulation by influenza virus. These dysregulated miRNAs directly or indirectly target viral genes to regulate viral replication and stimulate or suppress innate immune responses and cell apoptosis during viral infection. Exosomes released by infected cells are associated with the transfer of antigens and key molecules that activate and modulate immune function. Dysregulation of miRNAs and secretion of exosomes are associated with pathogenicity and immune regulation during influenza infection. This review provides a comprehensive summary of the information available regarding host miRNAs and exosomes that are involved in the modulation of influenza virus infection and will facilitate the development of preventative or therapeutic strategies against influenza virus.

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PMID: 

J Virol. 2020 Apr 16 ;94(9). Epub 2020 Apr 16. PMID: 32051269

Abstract Title: 

Human Immunodeficiency Virus-Associated Exosomes Promote Kaposi's Sarcoma-Associated Herpesvirus Infection via the Epidermal Growth Factor Receptor.

Abstract: 

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi's sarcoma (KS), the most common malignancy in people living with human immunodeficiency virus (HIV)/AIDS. The oral cavity is a major route for KSHV infection and transmission. However, how KSHV breaches the oral epithelial barrier for spreading to the body is not clear. Here, we show that exosomes purified from either the saliva of HIV-positive individuals or the culture supernatants of HIV-1-infected T-cell lines promote KSHV infectivity in immortalized and primary human oral epithelial cells. HIV-associated saliva exosomes contain the HIV-activation response element (TAR), Tat, and Nef RNAs but do not express Tat and Nef proteins. The TAR RNA in HIV-associated exosomes contributes to enhancing KSHV infectivity through the epidermal growth factor receptor (EGFR). An inhibitory aptamer against TAR RNA reduces KSHV infection facilitated by the synthetic TAR RNA in oral epithelial cells. Cetuximab, a monoclonal neutralizing antibody against EGFR, blocks HIV-associated exosome-enhanced KSHV infection. Our findings reveal that saliva containing HIV-associated exosomes is a risk factor for the enhancement of KSHV infection and that the inhibition of EGFR serves as a novel strategy for preventing KSHV infection and transmission in the oral cavity.Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi's sarcoma (KS), the most common malignancy in HIV/AIDS patients. Oral transmission through saliva is considered the most common route for spreading the virus among HIV/AIDS patients. However, the role of HIV-specific components in the cotransfection of KSHV is unclear. We demonstrate that exosomes purified from the saliva of HIV-positive patients and secreted by HIV-infected T-cell lines promote KSHV infectivity in immortalized and primary oral epithelial cells. HIV-associated exosomes promote KSHV infection, which depends on HIV-activation response element (TAR) RNA and EGFR of oral epithelial cells, which can be targeted for reducing KSHV infection. These results reveal that HIV-associated exosomes are a risk factor for KSHV infection in the HIV-infected population.

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PMID: 

FEMS Microbiol Lett. 2020 Feb 1 ;367(4). PMID: 32108899

Abstract Title: 

Astragaloside IV attenuates IL-1β secretion by enhancing autophagy in H1N1 infection.

Abstract: 

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1β) and pro-IL-1β protein level, but significantly decreased secretion of IL-1β, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1β in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1β secretion.

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