Homogeneous Polyporus polysaccharide exerts anti-bladder cancer effects via autophagy induction.

CONTEXT: Polyporus polysaccharide (PPS), the leading bioactive ingredient extracted from Polyporus umbellatus (Pers.) Fr. (Polyporaceae), has been demonstrated to exert anti-bladder cancer and immunomodulatory functions in macrophages. OBJECTIVE: To explore the effects of homogeneous Polyporus polysaccharide (HPP) on the proliferation and autophagy of bladder cancer cells co-cultured with macrophages. MATERIALS AND METHODS: MB49 bladder cancer cells and RAW264.7 macrophages were co-cultured with or without HPP intervention (50, 100, or 200 µg/mL) for 24 h. The cell counting kit-8 (CCK-8) assay and 5-ethynyl-2″-deoxyuridine (EdU) staining evaluated MB49 cell proliferation. Monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM) observed autophagosomes. Western blotting detected the expression levels of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins. RESULTS: HPP inhibited the proliferation of MB49 cells co-cultured with RAW264.7 cells but not MB49 cells alone. HPP altered the expression of autophagy-related proteins and promoted the formation of autophagosomes in MB49 cells in the co-culture system. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) not only antagonized HPP-induced autophagy but also attenuated the inhibitory effects of HPP on MB49 cell proliferation in the co-culture system. HPP or RAW264.7 alone was not sufficient to induce autophagy in MB49 cells. In addition, HPP suppressed the protein expression of the PI3K/Akt/mTOR pathway in MB49 cells in the co-culture system. DISCUSSION AND CONCLUSIONS: HPP induced bladder cancer cell autophagy by regulating macrophages in the co-culture system, resulting in the inhibition of cancer cell proliferation. The PI3K/Akt/mTOR pathway was involved in HPP-induced autophagy in the co-culture system.

Rapid screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Polyporus umbellatus and mechanism of action in the treatment of gout.

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.

S-o-(p-Methoxyphenylethynyl)benzyl (SMPEB) Glycosides for Catalytic Glycosylation and Their Application in the Synthesis of Polyporus Umbellatus Polysaccharides.

We herein reported a new type of S-o-(p-methoxyphenylethynyl)benzyl donor for a highly efficient glycosylation method. The donor was activated by 10% Tf2O and underwent glycosylation with various acceptors to provide the corresponding glycosides in excellent yield. Furthermore, two repetitive fragments of Polyporus umbellatus polysaccharides (PUPs), isolated from traditional Chinese medicine "Polyporus umbellatus", were prepared by combining the "single-catalyst one-pot" and "latent-active" strategies for the first time for future clear studies on the structure-activity relationship of PUPs.

Extraction, characterization, and anti-nonalcoholic steatohepatitis activity of a (1,3) (1,6)-ß-D-glucan from the Polyporus umbellatus (Pers.) Fries.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by inflammation and hepatic steatosis that may coincide with fibrotic activity. To date, no pharmacological agents have been approved for NASH treatment. Here, a homogeneous (1,3),(1,6)-ß-D-glucan (PUP-W-1, Mw: 41.07 kDa) was successfully purified from Polyporus umbellatus (Pers.) Fries sclerotia and characterized. The analysis showed that the PUP-W-1 backbone consisted of a repeating chain of eight →3)-ß-D-Glcp-(1 â†’ units, with branched chains of four ß-D-Glcp residues, joined by repeating 1,6-linkage units at the O-6 position of the backbone. The pharmacological effects of PUP-W-1 treatment in the context of NASH pathogenesis were explored using a methionine choline-deficient (MCD) diet-induced murine steatohepatitis model. The MCD model mice exhibited pronounced steatohepatitis, inflammatory activity, steatosis, stellate cell activation, and mild fibrotic activity. Treatment of the mice for three weeks with PUP-W-1 prevented the development of NASH due to the suppression of inflammation, lipid accumulation, and fibrosis. As suggested by these findings, PUP-W-1 may hold promise as a natural drug candidate or precursor for the treatment of NASH.

Phytochemistry and bioactivities of the main constituents of Polyporus umbellatus (Pers.) Fries.

BACKGROUND: Edible fungi resources have good application prospects in the research and development of food, medicine, and health products. Polyporus umbellatus (Pers.) Fries, as a precious edible and medicinal fungus, has long been used by Chinese medicine to treat urinary systems and related kidney diseases. PURPOSE: In recent years, researchers have discovered and isolated a variety of active compounds from P. umbellatus. Modern phytochemical and pharmacological experiments showed that the crude extract of P. umbellatus had many biological functions and could be widely used in the fields of food, pharmaceutical and cosmetics. This paper summarizes the active components of P. umbellatus, through elaborating its mechanism of action, further clarify the action substances, in order to improve the utilization rate of P. umbellatus, promote the development and application of P. umbellatus in food, pharmaceutical and cosmetics industry. METHODS: In this paper, the literatures related to P. umbellatus were summarized and classified by "China National Knowledge Instructure (CNKI)", "Google Scholar" and "Web of Science". Compared with other articles, this work systematically sorted out all the active substances with clear structures in P. umbellatus. On this basis, combined with the chemical composition of P. umbellatus, its functional efficacy was expounded, and the effects of different types of active substances in P. umbellatus were further presented. RESULTS: The main chemical constituents of P. umbellatus include polysaccharide and sterol, and the secondary compounds include fatty acids, phenols and other small molecules. These active substances endowed P. umbellatus anti-cancer, antibacterial, diuretic, antioxidant, enhance immune system, promote hair growth and other pharmacological activities, which has been verified many times in vivo and in vitro experiments. CONCLUSION: Modern in vitro or in vivo pharmacological experiments and clinical practice for the efficacy of P. umbellatus provides a strong support, and the separation of compounds in P. umbellatus has also deepened people's understanding of this traditional Chinese medicine, greatly promoted the development and application of P. umbellatus. However, the complex active substances of poring also hinder the research of P. umbellatus to some extent, and the mechanism of action and potential synergistic or antagonistic effect of the mixture of various active ingredients have not been clearly analyzed. How to use the bioactivity-guided separation strategy to identify more bioactive components and analyze the molecular mechanism of the main active components have become the main problems of P. umbellatus research, but also provides a direction for the further study of it.

Acetylome analysis of acetylation providing new insight into sclerotial generation in medicinal fungus Polyporus umbellatus.

Sclerotium-forming fungi are ecologically diverse and possess notable pathogenic or medicinal properties. The sclerotial generation mechanism is still elusive though Polyporus umbellatus sclerotia are typical Traditional Chinese Medicine with diuretic and antitumor effects. Protein acetylation displays a crucial role in several biological processes, but the functions of acetylation in this valuable fungus are unknown at present. In this study, acetylome of P. umbellatus was studied using nano LC-Triple TOF mass spectrometry system following immune-affinity-based enrichment. Totally, 648 acetylated sites in 342 proteins were identified and nine motifs were found to be conserved in P. umbellatus including KacY, KacA, KacL, KacG, MacS, MacA, RacA, RacL, and RacG. Acetylated proteins taken part in types of biological processes, particularly to those in biological processes associated with reactive oxygen species (ROS) metabolism. Inhibitors complement tests were carried out to verify the role of ROS in acetylation modification. It was concluded that oxidative stress regulated sclerotial generation via proteins acetylation in P. umbellatus. The present study presents new insight into the essential roles of acetylation in sclerotial formation, which may also be applicable for other sclerotium-forming fungi.

Homogeneous Polyporus Polysaccharide Inhibit Bladder Cancer by Resetting Tumor-Associated Macrophages Toward M1 Through NF-κB/NLRP3 Signaling.

Bladder cancer(BC)is one of the most common urinary system tumors, which characterized by a high incidence. Polyporus polysaccharide is the main active component of polyporus, which is clinically used in the treatment of bladder cancer, but the mechanism is not clear. In previous study, we isolated homogeneous polyporus polysaccharide(HPP) with high purity from polyporus. The goal of this study was to assess the polarization of macrophages induced by HPP in the bladder tumor microenvironment and explored its anti-bladder cancer mechanism through BBN bladder cancer rat model and Tumor associated macrophages(TAM). The results suggested that HPP regulates TAM polarization to improve the tumor inflammatory microenvironment, possibly through the NF-κB/NLRP3 signaling pathway. Our results suggested that HPP may be a potential therapeutic agent for bladder tumors.

Regiospecific 7-hydroxylation of ten-carbon monoterpenes by detoxifying CYP5035S7 monooxygenase of the white-rot fungus Polyporus arcularius.

In a previous study, we identified CYP5035S7 of the white-rot fungus Polyporus arcularius with a broad activity towards monoterpenes such as p-cymene. Therefore, in this study we aimed at further exploring the substrate scope of detoxifying CYP5035S7 towards terpenes and semi-preparatively isolating some of the products via whole-cell biotransformation, in order to obtain information about the enzyme's reactivity. We noticed a clear preference for the monoterpene skeleton and elucidated a distinct regioselectivity pattern based on key structural and electronic features of its substrates. This study illustrates how minimal characterisation effort may already suffice to provide vital information on enzymatic reactivity by the comparison of structural derivatives.

Late-Stage Functionalisation of Polycyclic (N-Hetero-) Aromatic Hydrocarbons by Detoxifying CYP5035S7 Monooxygenase of the White-Rot Fungus Polyporus arcularius.

Functionalisation of polycyclic aromatic hydrocarbons (PAHs) and their N-heteroarene analogues (NPAHs) is a tedious synthetic endeavour that requires diverse bottom-up approaches. Cytochrome P450 enzymes of white-rot fungi were shown to participate in the fungal detoxification of xenobiotics and environmental hazards via hydroxylation of PAH compounds. In this paper, the recently discovered activity of the monooxygenase CYP5035S7 towards (N)PAHs was investigated in detail, and products formed from the substrates azulene, acenaphthene, fluorene, anthracene, and phenanthrene by whole-cell biocatalysis were isolated and characterised. The observed regioselectivity of CYP5035S7 could be explained by a combination of the substrate's electron density and steric factors influencing the substrate orientation giving insight into the active-site geometry of the enzyme.

Taxonomy of the major rhizomorphic species of the "Melanopus group" within Polyporaceae in Yasuní National Park, Ecuador.

Yasuní National Park in Ecuador is one of the most biodiverse places on earth. The fungi in this tropical rainforest are also diverse but have received little research attention. This research paper focuses on an important group of fungi in the family Polyporaceae and examines the genera Polyporus, Atroporus, and Neodictyopus that form aerial melanized cord-like structures called rhizomorphs. Phylogenetic analyses, macro and micromorphological descriptions of basidiomata and rhizomorphs, as well as cultural characterization were completed to better understand these ecologically important fungi. Here we describe four new species: Atroporus yasuniensis, Atroporus tagaeri, Neodictyopus sylvaticus, and Polyporus taromenane, and a new variety Polyporus leprieurii var. yasuniensis. The information presented in this study adds important new knowledge about the unusual rhizomorph producing fungi found in Yasuní National Park, Ecuador and other tropical rainforests.

Polysaccharides from Polyporus umbellatus: A review on their extraction, modification, structure, and bioactivities.

Polyporus umbellatus (Pers.) Fries, a well-known medicinal fungus, has been reported to exhibit important functions of diuresis and dampness infiltration in traditional Chinese Medicine. Accumulating evidences have demonstrated that the P. umbellatus polysaccharides (PUPs) are the main and representative pharmacologically active ingredients and display multiple bioactivities both in vivo and in vitro methods, such as those of antioxidant, immunomodulatory, antitumor, anti-proliferative and hepatoprotective. Besides, many PUPs have been isolated from the different sources of P. umbellatus, including sclerotia, fruiting body, mycelia and fermentation liquid of this fungus. The purpose of the present review is to comprehensively and systematically reorganize the available information related to the extraction, purification, modification, structure characterization and to discuss diverse biological activities of PUPs to support their potential application value in pharmaceuticals field, functional foods and cosmetics areas. In addition, new invaluable insights on the future research with PUPs have also been proposed in the important areas of structural characterization and pharmacological activities.

Use of transcriptomic profiling to identify candidate genes involved in Polyporus umbellatus sclerotial formation affected by oxalic acid.

Polyporus umbellatus is a precious medicinal fungus. Oxalic acid was observed to affect sclerotial formation and sclerotia possessed more medicinal compounds than mycelia. In this study, the transcriptome of P. umbellatus was analysed after the fungus was exposed to various concentrations of oxalic acid. The differentially expressed genes (DEGs) encoding a series of oxidases were upregulated, and reductases were downregulated, in the low-oxalic-acid (Low OA) group compared to the control (No OA) group, while the opposite phenomenon was observed in the high-oxalic-acid (High OA) group. The detection of reactive oxygen species (ROS) in P. umbellatus mycelia was performed visually, and Ca2+ and H2O2 fluxes were measured using non-invasive micro-test technology (NMT). The sclerotial biomass in the Low OA group increased by 66%, however, no sclerotia formed in the High OA group. The ROS fluorescence intensity increased significantly in the Low OA group but decreased considerably in the High OA group. Ca2+ and H2O2 influx significantly increased in the Low OA group, while H2O2 exhibited efflux in the High OA group. A higher level of oxidative stress formed in the Low OA group. Different concentrations of oxalic acid were determined to affect P. umbellatus sclerotial formation in different ways.

Evolution and enrichment of CYP5035 in Polyporales: functionality of an understudied P450 family.

Bioprospecting for innovative basidiomycete cytochrome P450 enzymes (P450s) is highly desirable due to the fungi's enormous enzymatic repertoire and outstanding ability to degrade lignin and detoxify various xenobiotics. While fungal metagenomics is progressing rapidly, the biocatalytic potential of the majority of these annotated P450 sequences usually remains concealed, although functional profiling identified several P450 families with versatile substrate scopes towards various natural products. Functional knowledge about the CYP5035 family, for example, is largely insufficient. In this study, the families of the putative P450 sequences of the four white-rot fungi Polyporus arcularius, Polyporus brumalis, Polyporus squamosus and Lentinus tigrinus were assigned, and the CYPomes revealed an unusual enrichment of CYP5035, CYP5136 and CYP5150. By computational analysis of the phylogeny of the former two P450 families, the evolution of their enrichment could be traced back to the Ganoderma macrofungus, indicating their evolutionary benefit. In order to address the knowledge gap on CYP5035 functionality, a representative subgroup of this P450 family of P. arcularius was expressed and screened against a test set of substrates. Thereby, the multifunctional enzyme CYP5035S7 converting several plant natural product classes was discovered. Aligning CYP5035S7 to 102,000 putative P450 sequences of 36 fungal species from Joint Genome Institute-provided genomes located hundreds of further CYP5035 family members, which subfamilies were classified if possible. Exemplified by these specific enzyme analyses, this study gives valuable hints for future bioprospecting of such xenobiotic-detoxifying P450s and for the identification of their biocatalytic potential. KEY POINTS: • The P450 families CYP5035 and CYP5136 are unusually enriched in P. arcularius. • Functional screening shows CYP5035 assisting in the fungal detoxification mechanism. • Some Polyporales encompass an unusually large repertoire of detoxification P450s.

A new genus and two new species of melicharid mites (Acari: Mesostigmata) associated with wood-decaying fungi and mycophagous erotylid beetles (Coleoptera: Erotylidae) in Europe.

We describe a new genus in the mite family Melicharidae, Mycomelichares Masán Joharchi gen. nov., to accommodate two new species, Mycomelichares polypori Masán Joharchi sp. nov. and Mycomelichares reductus Masán Joharchi sp. nov. on the basis of specimens collected on wood-decaying fungi and/or mycophagous beetles of the genera Triplax Herbst and Tritoma Fabricius (Coleoptera: Erotylidae) in Slovakia and European part of Russia, respectively. Moreover, two previously described Proctolaelaps species-P. cyllodi Samsinák, 1960 and P. slovacus Masán, 1998 are transferred to the newly established genus. The new genus is characterized by specific characters in tritosternum (enlarged and brush-shaped, having their laciniae thickened, basaly fused and distally densely pilose), chelicerae (slightly dish-shaped digits with long, narrow and sharp denticles), ventral hypostome (setae h1 enlarged, thickened and distally flattened), setation (tendency towards placement of R series setae on soft integument, and reduction of some setae on idiosoma and legs), and unusual ecological specialisation on fungal substrates. Mycomelichares polypori sp. nov. is adapted to the life in sporophores of the basidiomycete bracket fungus, Polyporus squamosus (Polyporaceae). Mites of this species can be abundantly found on the lower fertile surface of the fungus, including large spore-bearing pores. Furthermore, keys to the melicharid genera reported from Palaearct, and the species of the genus are provided.

Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment.

BACKGROUND: Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of homogeneous polyporus polysaccharide (HPP) activated macrophages in the treatment of bladder cancer. METHODS: 100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Then macrophages derived from THP-1 were treated with different concentrations of HPP (1, 10 and 100 µg/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iß, iNOS mRNA. ELISA was used to test the change of IL-1ß and TNF-α in macrophage after the treatment with HPP. The conditioned medium from HPP-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein. RESULTS: HPP promoted the expression of pro-inflammatory factors, such as IL-Iß, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. Results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial-mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. CONCLUSION: The findings indicated that HPP inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.

An overview of Favolus from the Neotropics, including four new species.

Favolus is a monophyletic genus of polypores that causes white rot of various woody plants. The genus has a worldwide distribution and is ecologically and economically important. Several taxa have been described or reported from the Neotropics, and F. brasiliensis, described originally from Brazil, is the type species for the genus. Based on molecular investigations, F. brasiliensis is now known to represent a species complex. The species is morphologically and phylogenetically circumscribed and epitypified here, and F. rugulosus is proposed as a new related species. Favolus grammocephalus and Polyporus philippinensis, initially described from Asia, have also recently been recorded from the Neotropics, so these taxa were included in this investigation employing morphological and multigene (mitochondrial, ribosomal, and protein-coding regions) phylogenetic analyses. These latter two species do not occur in the Neotropics, but the misapplied names actually represent three new species: F. pseudogrammocephalus, F. radiatifibrillosus, and F. yanomami. Nine species of Favolus are documented now for the Neotropics. Detailed descriptions of F. brasiliensis and all new taxa are provided, along with comments, illustrations, a map of potential distribution, and a key for neotropical species of Favolus.

Structural studies of immunomodulatory (1 → 3)-, (1 → 4)-α glucan from an edible mushroom Polyporus grammocephalus.

A water soluble polysaccharide (PGPS) with molecular weight ~ 1.4 × 105 Da was isolated by alkali treatment from an edible mushroom Polyporus grammocephalus and purified by gel chromatography using sepharose-6B column. Monosaccharide analysis revealed that PGPS was made up of glucose only. PGPS contained (1 â†’ 3)-α-D-Glcp and (1 â†’ 4)-α-D-Glcp moieties in a molar ratio of nearly 1:2. Through a series of chemical and spectroscopic (1D/2D NMR) investigations, the repeating unit of the glucan was established as: →3)-α-D-Glcp(1 â†’ [4)-α-D-Glcp(1]2→ This α-glucan was observed to stimulate some prime components of immune system, namely, macrophages, splenocytes, and thymocytes.

Do the Main Components of the Sclerotia of Umbrella Polypore Mushroom, Polyporus umbellatus (Agaricomycetes), Correlate with Armillaria Associates?

Polyporus umbellatus is a traditional Chinese medicinal mushroom. The growth of P. umbellatus sclerotia requires the rhizomorphs of Armillaria spp. to supply nutrition. Whether the main components (MC) of sclerotia of P. umbellatus are related to the phylogeny of Armillaria associates or other environmental factors is largely unknown. In this study, we collected 17 sclerotia and soil samples from northeast to southwest China. In total, 17 Armillaria associates were isolated, and sclerotial MC contents and soil characteristics (total N, P, K, and organic matter) were determined. The analysis revealed that the MC content of P. umbellatus did not resemble a Brownian motion process in phylogeny of Armillaria associates, but were significantly influenced by the total N content of the soil. These results provide clear evidence that sclerotia of P. umbellatus associating with phylogenetic related Armillaria associates possess differing MC content. The mechanisms of nutrient exchange in P. umbellatus-Armillaria associations now require further elucidation.

Preparation, physicochemical characterization, and anti-proliferation of selenium nanoparticles stabilized by Polyporus umbellatus polysaccharide.

Selenium nanoparticles (SeNPs), a novel selenium form, have attracted worldwide attention due to their bioactivities and low toxicity. This study aimed to assess the physicochemical characterization, storage stability, and anti-proliferative activities of SeNPs stabilized by Polyporus umbellatus polysaccharide (PUP). Results showed that orange-red, zero-valent, amorphous and spherical SeNPs with mean diameter of approximately 82.5 nm were successfully prepared by using PUP as a capping agent. PUP-SeNPs solution stored at 4 °C in dark condition could be stable for at least 84 days. Moreover, PUP-SeNPs treatment inhibited four cancer cell lines proliferation in a dose-dependent manner, while no significant cytotoxicity towards three normal cell lines was observed. Comparing with the other cancer cell lines (HepG2, Hela, and HT29), PUP-SeNPs displayed the most sensitive towards MDA-MB-231 cells with an IC50 value of 6.27 µM. Furthermore, PUP-SeNPs significantly up-regulated Bax/Bcl-2 ratio, promoted cytochrome c release, increased caspase-9, -8 and -3 activities, and poly (ADP-ribose) polymerase cleavage, suggesting that mitochondria-mediated and death receptor-mediated apoptotic pathways were activated in MDA-MB-231 cells. Besides, PUP-SeNPs possessed better anti-proliferative activity than selenomethionine as well as lower cytotoxicity than sodium selenite. Taken together, PUP-SeNPs have strong potential as a dietary supplement for application in cancer chemoprevention, especially breast cancer.

Immunomodulatory Effect of Structurally Characterized Mushroom Sclerotial Polysaccharides Isolated from Polyporus rhinocerus on Bone Marrow Dendritic Cells.

This study evaluated the immunomodulatory effects of two high-molecular-weight and structurally different mushroom polysaccharides, an alkali-soluble polysaccharide (mPRSon) and a water-soluble polysaccharide-protein complex (PRW), isolated previously from the sclerotia of Pleurotus rhinocerus, on the maturation of murine bone-marrow-derived dendritic cells (BMDCs). The effects of mPRSon and PRW on the expression of morphological change, surface molecules, phagocytic activity, and cytokine release in BMDCs were determined by flow cytometry and a mouse cytokine array. The results showed that both mPRSon and PRW could induce phenotypic and functional maturation of BMDCs. At the same time, mPRSon upregulated the expression of membrane phenotypic marker CD86 and PRW markedly upregulated CD40, CD80, and CD86. In addition, mPRSon could bind to the dectin-1 receptor and stimulate the release of MIP-1α, MIP-2, and IL-2, while PRW could bind to complement receptor 3 and toll-like receptor 2 with an upregulation of the expression of IL-2, IL-6, MIP-1α, MIP-2, RANTES, IL-12p40p70, IL-12p70, TIMP-1, IFN-γ, KC, MCP-1, and GCSF. The study provides additional information on how structural differences in sclerotial polysaccharides influence their immunomodulatory activities on BMDCs involving different PAMP receptors. It is anticipated that more understanding of the interactions between the sclerotial polysaccharides and their receptors in immune cells can facilitate their future application for cancer immunotherapy.