Molecular weight (MW) is a key determinant of polysaccharide functionality, but its role in regulating microencapsulation efficiency and delivery performance remains insufficiently defined. In this study, enzymatically hydrolyzed Agaricus bisporus polysaccharides (ABP) were microencapsulated after MW modulation to construct a predominantly amorphous maltodextrin matrix and address the high hygroscopicity and limited thermal stability of ABP. Fractions with different MW ranges showed that chain length strongly affected spatial entanglement and encapsulation performance. The 10-50 kDa fraction (Group M), prepared at a 1:2 core-to-wall ratio, showed the best processing adaptability, with a powder yield of 91.78% and an encapsulation efficiency of 75.35%. SEM, FTIR, XRD, DSC, and TGA analyses indicated the formation of a stable, predominantly amorphous polymer matrix with a suitable peak phase transition temperature (178.5°C), which reduced thermoplastic adhesion during spray drying. Microencapsulation also reduced moisture absorption. The moderate chain length improved chain flexibility and reduced steric hindrance, thereby affecting antioxidant performance and release kinetics. The optimized system retained in vitro antioxidant activity and produced sustained release during simulated gastrointestinal digestion. These findings provide a practical framework for stabilizing and delivering bioactive mushroom polysaccharides for functional food applications.

Background Ganoderma lucidum spore oil (GLSO) contains small molecules that are efficiently absorbed into the bloodstream upon oral administration. Previous studies suggest potential cardio-protective roles of GLSO, relevant for myocardial infarction (MI) patients. Purpose To evaluate the effects of GLSO on cardiac function in MI patients residing at high altitudes (above 3500 meters), we focused on the improvements of ventricular function, alterations in energy metabolism, and modulation of gut microbiota. Study Design A single-arm clinical trial was performed involving 38 Tibetan MI patients to assess the efficacy of GLSO over eight-week treatment. Methods Patients received GLSO orally for eight weeks, followed by cardiac assessment, metabolomic analysis, and gut microbiota analysis. Results Cardiac functional improvements were observed with enhanced left ventricular diastolic performance and reduced cardiac regurgitation in 47.06% patients. A decrease in electrocardiographic abnormalities was detected in 77.78% of the patients. Metabolomic profiling revealed significant reductions in fatty acids and acylcarnitines, with concurrent increases in bile acids and β-alanine levels. Gut microbiota analysis indicated increased microbial diversity and a notable rise in Akkermansia populations. Conclusion The GLSO oral preparation appears to improve cardiac function in high-altitude MI patients. These benefits may be mediated through enhanced β-oxidation of fatty acids and favorable modulation of gut microbiota. Our study suggests a promising therapeutic role for GLSO in this patient population.

Grifola frondosa is a valued edible and medicinal fungus whose polysaccharides are key bioactive components, yet the identification of specific homogeneous effectors and their detailed immunomodulatory mechanisms remains a critical focus of research. In this study, polysaccharide fractions were isolated from G. frondosa fruiting bodies via systematic purification, and the principal bioactive polysaccharide responsible for breast cancer inhibition was identified. A novel homogeneous polysaccharide, GFI-21α, was determined as the primary effector. Structural characterization defined GFI-21α as a high-molecular-weight α-(1 → 4)-D-glucan backbone featuring →3,6)- and →4,6)-linked branch points substituted at the O-6 position with short →3)-α-D-Glcp-(1 → side chains. None of the isolated polysaccharide fractions exhibited direct cytotoxicity in vitro. However, in vivo experiments demonstrated that GFI-21α elicited substantial tumor growth suppression. This efficacy significantly exceeded that of the clinical β-glucan comparator, lentinan, without causing overt toxicity. Mechanistically, distinct from the innate immune modulation typically associated with β-glucans, GFI-21α was associated with enhanced intratumoral CD8+ T cell responses and IFN-γ-associated cytotoxic effector activity. These findings establish GFI-21α as a structurally distinct α-glucan with potent antitumor efficacy, supporting its potential as a candidate for cancer immunotherapy.

[This corrects the article DOI: 10.3389/fphar.2017.00219.].

[This corrects the article DOI: 10.3389/fneur.2018.00412.].

Background/Objectives: Our lab has previously reported that Grifola frondosa (maitake mushroom) GF5000 has antidiabetic potential owing to its ability to improve insulin resistance. This study aimed to gain insight into the system-level hypoglycemic mechanisms of GF5000 using transcriptomics, proteomics, and network pharmacology. This study provides new insights into the hypoglycemic mechanisms of GF5000, identifying key molecular targets involved in mitigating insulin resistance in T2DM. Methods: Liver protein and gene expression in normal control (NC), diabetic control (DC), and GF5000-treated (GF5000) rats were analyzed via iTRAQ and RNA-seq. The relationships between differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and type 2 diabetes (T2DM) disease targets were studied using Metascape and the Cytoscape GeneMANIA plug-in. Results: One hundred and fifty-two DEGs and sixty-two DEPs were identified; twenty DEGs/DEPs exhibited the same trend in mRNA and protein expression levels when comparing the GF5000 vs. DC groups. The Metascape analysis revealed that the T2DM disease targets included four DEGs—Gck, Scd, Abcb4, and Cyp3a9—and two DEPs—glucokinase and acetyl-CoA carboxylase 2. A Cytoscape–GeneMANIA analysis of thirteen DEGs/DEPs related to T2DM showed that Apoa1/Apolipoprotein A-I, Gckr/glucokinase regulatory protein, and Gck/glucokinase had the highest connectivity and centrality in the topological network. The qPCR results confirmed that GF5000 increased the mRNA expression of GCK in GCK-knockdown HepG2 cells. Conclusions: These results provide theoretical evidence for the use of GF5000 as a potential active nutritional ingredient for the prevention and treatment of T2DM. Our findings suggest that GF5000 targets multiple pathways implicated in T2DM, offering a multi-faceted approach to disease management and prevention.

[This corrects the article DOI: 10.3389/fnagi.2017.00403.].

Breast cancer represents a persistent global health challenge, with multidrug resistance (MDR) posing a significant obstacle to effective treatment. In this study, we investigate the potential of Ganoderma lucidum extract (GLE) in reversing MDR in breast cancer and delve into the underlying mechanisms. We establish a robust in vitro 3D model of breast cancer with acquired MDR induced by paclitaxel. Utilizing the CCK-8 method, we assess the impact of GLE on cytotoxic drug sensitivity to determine its in vitro MDR reversal activity.Our results reveal that GLE enhances the toxicity of paclitaxel in breast cancer cells by inhibiting the ATPase activity of P-glycoprotein (P-gp) and increasing the intracellular and extracellular excretion of P-gp substrates, all without significantly altering P-gp protein expression. Additionally, GLE inhibits the phosphorylation of ERK1/2, suggesting that the enhanced sensitivity of breast cancer cells to paclitaxel by GLE is associated with the MAPK pathway. These findings indicate that GLE may inhibit P-gp-mediated drug efflux via the MAPK pathway, thus effectively overcoming paclitaxel resistance in breast cancer.This study provides valuable insights into the potential clinical applications of GLE in reversing multidrug resistance, offering hope for improved breast cancer treatment strategies.

Summary Grifola frondosa is an edible and medicinal fungus with various biological activities. Previously, we reported Gaylussacia frondosa polysaccharide F2 can improve insulin resistance in diabetic rats. In the present study, our aim was to identify its prebiotic function. The structure of polysaccharide F2 was obtained from gel permeation chromatography (GPC), Infrared (IR) spectroscopy and saccharide mapping. Simulated digestion and fecal bacteria fermentation of F2 in vitro was performed to investigate its digestion and fermentation characteristic. Dynamic changes of molecular weight and composition of F2 during digestion and fermentation were monitored by HPLC. The effects of F2 on intestinal microbiota were studied by 16S rDNA sequencing and bioinformatics analysis. The results of simulated digestion in vitro showed that F2 was not digested in saliva, but minor degraded in stomach and intestine. It was worth noting that the content of polysaccharide F2 decreased and short-chain fatty acids (SCFAs) content increased during the fermentation process with fecal. 16S rDNA sequencing results showed that F2 may reshape the structure of gut microbiota, and enrich microbial communities of Bacteriodes spp., Phascolarctobacterium spp., Enterococcus spp. and Veillonella spp. Data suggested F2 could be utilized by intestinal bacteria to produce hypoglycemic components, which was a promising prebiotic. The hypoglycemic mechanism of F2 may be associated with enhancement of SCFAs-producing bacteria (Enterococcus spp.) and BSH (Bile salt hydrolase)-producing bacteria (Bacteriodes spp. and Enterococcus spp.), acceleration the bile acids metabolism and SCFAs production.

Grifola frondosa is an edible and medicinal fungus with various biological activities. Previously, we reported that G. frondosa polysaccharide F2 improved insulin resistance in diabetic rats. In this study, our aim was to identify its prebiotic function. Simulated digestion and faecal bacteria fermentation of F2 in vitro were performed to investigate its digestion and fermentation characteristic. The effects of F2 on intestinal microbiota were studied by 16S rDNA sequencing and bioinformatics analysis. Results showed that F2 was not digested in saliva but was minorly degraded in the stomach and intestine. 16S rDNA sequencing results showed that the hypoglycaemic mechanism of F2 may be associated with enhancement of short-chain fatty acids (SCFAs)-producing bacteria (Enterococcus spp.) and bile salt hydrolase-producing bacteria (Bacteroides spp. and Enterococcus spp.), acceleration the bile acids metabolism and SCFAs production. Data suggested that F2 could be utilised by intestinal bacteria to produce hypoglycaemic components, which was a promising prebiotic.

The Ascomycete genus Cordyceps affects plant crops significantly, filling an important ecological niche. Cordyceps militaris (L.) Fr. presents many health benefits for humans, but its population history has not been reported. The objective of this research was to report the collection, population structure, demographic history, diversity, and cytosine deaminases of 43 wild strains of C. militaris in China through resequencing using an Illumina HiseqTM platform. All strains were assigned to the warm, subtropical, and middle temperate zone populations, confirmed by ADMIXTURE-1.3.0, PCA, and phylogenic analysis. Their population sizes declined historically, suggesting that this species suffered from bottlenecks in the wild. LD decays (r2) revealed a north-to-south migration pattern of wild C. militaris, consistent with the MSMC2-v2.1.4 analysis. The regions of high Pi were aggregating at the chromosomes CP023325.1 (51) and CP023323.1 (9), playing a key role in adaptation, especially for the sites on cytosine deaminase. Within the species, genetic differentiation was relatively high among the three populations (Fst = 0.083, 0.092, and even 0.109). According to the artificial intelligence-assisted (RoseTTAFold) predicted structures of the cytosine deaminases, they were classified into eight clades with unique, distinct, and structurally conserved domains, offering a potential suite of single- and double-stranded deaminases of great promise as tunable base editors for therapeutic and agricultural breeding applications. These provided new insights for mining novel proteins from macrofungi, structurally and functionally.

Background:Cognitive function declines with increasing age and maintaining high cognitive functioning especially at late life remains a challenging question to be addressed. Emerging evidence in the role of mushroom in promoting cognition has been produced from limited observational studies but there is a lack of definitive evidence on both longitudinal relationships from prospective cohort studies and clinical efficacy from clinical trials. Objectives:To explore the definitive evidence of mushroom on cognitive functions among at-risk middle-aged and young-olds. Design:The first study is a 10-year cognitive assessment follow-up on an existing cohort, the Diet and Healthy Aging (DaHA), which recruited over 1,000 older adults from the year 2010 to the year 2016. The second is a carefully designed randomized controlled trial (RCT) to assess the role of mushrooms in promoting cognitive functioning among around 600 middle-aged adults and young-olds. Participants:Participants were selected based on specific inclusion criteria, such as being community-living adults aged 45-74 years with a family history of dementia, APOE ε4 allele, or subjective cognitive decline, while consuming mushrooms no more than once a week and having no dementia, along with the exclusion of individuals with neurological or psychiatric disorders and significant sensory or motor impairments. Intervention:Participants in the intervention group will consume Pleurotus citrinopileatus mushroom powder daily for 24 months, with compliance monitored using electronic diary apps. The powder contains 7.0 mg/g of ergothioneine (dry weight). Measurements:Cognitive function including Mini Mental State Examination, Rey Auditory Verbal Learning Test, Symbol Digit Modality test, Clinical Dementia Rating etc. along with mental health and biological markers will be measured at baseline, 1 year, and 2 years after baseline.

Prediabetes (pre-DM) is the buffer period before developing overt type 2 diabetes (T2DM), and the search for novel food agents to protect against pre-DM is in high demand. Our team previously reported that the Grifola frondosa (maitake mushroom) polysaccharide F2 reduced insulin resistance in T2DM rats induced by streptozocin (STZ) combined with a high-fat diet (HFD). This study aimed to evaluate the effects of G. frondosa polysaccharide F2 on disordered lipid and glucose metabolism and to investigate its mechanisms in pre-DM mice. F2 (30 and 60 mg/kg/d) was administered (i.g.) for 5 weeks to pre-DM mice. The results showed that F2 decreased the fasting blood glucose and lipid profile index of pre-DM mice (p < 0.05 or 0.0001). An untargeted metabolomics analysis of feces from pre-DM mice showed that F2 reduced the content of conjugated bile acids, including taurochenodeoxycholic acid and taurocholic acid, and increased the free bile acids of lithocholic acid. The results of 16S rDNA sequencing of feces from pre-DM mice showed that bile salt hydrolase (BSH)-producing bacteria, including Bacillus, Bifidobacterium, and Lactococcus, may be the therapy targets of F2 in pre-DM mice. Through the integrated analysis of untargeted metabolomics and 16S rDNA sequencing, it was found that F2 may ameliorate glucose and lipid metabolism disorders by promoting bile acid metabolism while regulating the abundance of BSH-producing bacteria (Lactococcus spp.), suggesting its potential as a functional food ingredient for the prevention of T2DM.

Myeloid derived suppressor cells (MDSCs) are known to accumulate in cancer patients and tumor-bearing mice, playing a significant role in promoting tumor growth. Depleting MDSCs has emerged as a potential therapeutic strategy for cancer. Here, we demonstrated that a fungal polysaccharide, extracted from Grifola frondosa, can effectively suppress breast tumorigenesis in mice by reducing the accumulation of MDSCs. Treatment with Grifola frondosa polysaccharide (GFI) leads to a substantial decrease in MDSCs in the blood and tumor tissue, and a potent inhibition of tumor growth. GFI treatment significantly reduces the number and proportion of MDSCs in the spleen, although this effect is not observed in the bone marrow. Further analysis reveals that GFI treatment primarily targets PMN-MDSCs, sparing M-MDSCs. Our research also highlights that GFI treatment has the dual effect of restoring and activating CD8+T cells, achieved through the downregulation of TIGIT expression and the upregulation of Granzyme B. Taken together, our findings suggest that GFI treatment effectively eliminates PMN-MDSCs in the spleen, leading to a reduction in MDSC numbers in circulation and tumor tissues, ultimately enhancing the antitumor immune response of CD8+T cells and inhibiting tumor growth. This study introduces a promising therapeutic agent for breast cancer.

Russula griseocarnosa, an edible and medicinal mushroom abundant in nutrients and notable bioactivities, is predominantly grown in the broad-leaved forest with trees of the family Fagaceae in southern China. This species forms ectomycorrhizal associations with plant roots and cannot be artificially cultivated currently. Previous research indicates a strong correlation between the growth of R. griseocarnosa and factors such as the host plant, climate variables (specifically mean temperature and precipitation from June to October), and the rhizosphere microbiota of its habitat. However, comprehensive studies on the fundamental biology of this species are lacking. The interaction between R. griseocarnosa and its host plant, as well as the mechanisms underlying the microbial community dynamics within its habitat, remain ambiguous. The limited repertoire and diversity of carbohydrate-active enzymes (CAZymes) in R. griseocarnosa relative to saprophytic fungi may contribute to its recalcitrance to cultivation on synthetic media. The specific core enzyme and the substances provided by the host plant to facilitate growth are yet to be elucidated, posing a significant challenge in the artificial cultivation of R. griseocarnosa. The habitat of R. griseocarnosa harbours unique microbial communities, indicating the presence of potentially beneficial microorganisms that could be exploited for artificial propagation and conservation efforts. However, the lack of definitive functional verification experiments hinders the realization of this promising prospect. This review offers a comprehensive overview of the nutritional profile and health benefits of R. griseocarnosa, emphasizing recent developments in its isolation, molecular ecology, and artificial cultivation. Additionally, it explores prospective advancements in R. griseocarnosa research, aiming to enrich our foundational understanding for applied purposes and fostering progress in the realm of ectomycorrhizal edible mushrooms.

Selenopeptides may be a valuable bioactive compound to promote gut microbiota-targeted therapeutic methods for intestinal disease and hepatopathy. However, limited information is available on the utilization of selenopeptides by gut microbiota, especially Selenium(Se) function. For this purpose, the present study aimed to investigate the protective effect of selenopeptide(RYNA(Se)MNDYT, Se-P2, purity of ≥ 95%) and its original peptide(RYNAMNDYT, P2, purity of ≥ 95%) in vivo by the microbiota-metabolite axis and further analyze the potential contribution of Se biofortification to Se-P2 bioactivity. The results showed that Se-P2 exhibits a higher protective effect on lipopolysaccharide(LPS)-induced inflammation than P2, including pathology of the colon and liver, which suggested that the bioactivity of P2 was promoted by the organic combination of Se. Notably, gut microbiota composition tended to be a healthy structure by Se-P2 pretreatment in LPS-injured mice, which had a positive effect on LPS-induced gut microbiota dysbacteriosis. Additionally, only Se-P2 promoted an increase in the relative abundance of Lactobacillus, Alistipes, and Roseburia and a decrease in the relative abundance of Akkermansia, Erysipelatoclostridium, and Bacteroides in LPS-injured mice. The changes in gut microbiota were obviously correlated with the changes in metabolites and affected the metabolic pathways of valine, leucine, isoleucine, phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism. This may be one of the key reasons for Se-P2 to exert bioactivity through the microbiota-metabolite axis. Furthermore, Se-biofortification in Se-enriched Cordyceps militaris affected the parental proteins of Se-P2 to modulate mitogen-activated protein kinase, GPI anchored protein, and carbohydrate metabolism, translation, folding, sorting and degradation, which may contribute to the bioactivity of Se-P2. Our study provides information on the effect of Se on selenopeptides in vivo, which further promotes the prospective applications of selenopeptides as dietary supplements.

Natural polysaccharides interact with gut microbes to enhance human well-being. Grifola frondosa is a polysaccharides-rich edible and medicinal mushroom. The prebiotic potential of G. frondosa polysaccharides has been explored in recent years, however, the relationship between their various structural features and prebiotic activities is poorly understood. In this study, three homogenous polysaccharides GFP10, GFP21 and GFP22 having different molecular weights (Mw), monosaccharide compositions and glycosidic linkages were purified from G. frondosa, and their effects on intestinal microbial composition were compared. GFP10 was a fucomannogalactan with an Mw of 23.0 kDa, and it selectively inhibited Enterobacter, while GFP21 was a fucomannogalactoglucan with an Mw of 18.6 kDa, and it stimulated Catenibacterium. GFP22 was a 4.9 kDa mannoglucan that selectively inhibited Klebsiella and boosted Bifidobacterium, Catenibacterium and Phascolarctobacterium, and prominently promoted the production of short-chain fatty acids (SCFAs). The selective modulation of gut microbiota by polysaccharides was structure-dependent. A relatively lower Mw and a high proportion of glycosidic linkages like T-Glcp, 1,3-Glcp, 1,3,6-Glcp and 1,4-Glcp might be more easily utilized to produce SCFAs and beneficial for the proliferation of Catenibacterium and Phascolarctobacterium. This research provided a valuable resource for further exploring the structure-activity relationship and prebiotic activity of G. frondosa polysaccharides.

Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

Breast cancer patients undergoing chemotherapy often experience muscle wasting and weakness, which impact their quality of life. A potential solution lies in customizing amino acid compositions based on exome-derived formulations (ExAAs). The study hypothesized that tailoring dietary amino acids using ExAAs could enhance muscle health. Theoretical amino acid requirements were calculated from the genome's exome region, and a breast cancer mouse model undergoing paclitaxel treatment was established. The mice were supplemented with a cancer-specific nutritional formula (QJS), and the effects of QJS and amino acid-adjusted QJS (adjQJS) were compared. Both formulations improved the nutritional status without compromising tumor growth. Notably, adjQJS significantly enhanced muscle strength compared to QJS (1.51 ± 0.25 vs. 1.30 ± 0.08 fold change, p < 0.05). Transcriptome analysis revealed alterations in complement and coagulation cascades, with an observed upregulation of C3 gene expression in adjQJS. Immune regulation also changed, showing a decrease in B cells and an increase in monocytes in skeletal muscle with adjQJS. Importantly, adjQJS resulted in a notable increase in Alistipes abundance compared to QJS (10.19 ± 0.04% vs. 5.03 ± 1.75%). This study highlights the potential of ExAAs as valuable guide for optimizing amino acid composition in diets for breast cancer patients undergoing chemotherapy.

This study aimed to compare the nutritive value and anti-obesity effect of ordinary Cordyceps militaris (CM) and selenium-enriched CM (SeCM). The results indicated that Se enrichment significantly increased the total carbohydrate and soluble dietary fiber content, while the protein and insoluble dietary fiber content decreased. Although the fat content was not affected, the medium and long-chain fatty acids content significantly changed. Moreover, Se enrichment significantly elevated the phytochemicals belonging to terpenoids and alkaloids, which are linked with the enhanced biosynthesis of secondary metabolites. Both CM and SeCM reduced body weight, adipose accumulation, impaired glucose tolerance, and lipid levels in high-fat diet (HFD)-fed mice, and there was no significant difference between them. Network pharmacological analysis revealed that dietary CM and SeCM prevented HFD-induced obesity and associated metabolic diseases with multi-ingredients acting on multi-targets. Overall, Se enrichment improved the nutritive value of CM without altering its anti-obesity effects.