Modulating pro-fibrotic macrophages using yeast beta-glucan microparticles prepared by Pressurized Gas eXpanded liquid (PGX) Technology®.

Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.

ß-glucans, SAM, and GSH fluctuations in barley anther tissue culture conditions affect regenerants' DNA methylation and GPRE.

BACKGROUND: Microspore embryogenesis is a process that produces doubled haploids in tissue culture environments and is widely used in cereal plants. The efficient production of green regenerants requires stresses that could be sensed at the level of glycolysis, followed by the Krebs cycle and electron transfer chain. The latter can be affected by Cu(II) ion concentration in the induction media acting as cofactors of biochemical reactions, indirectly influencing the production of glutathione (GSH) and S-adenosyl-L-methionine (SAM) and thereby affecting epigenetic mechanisms involving DNA methylation (demethylation-DM, de novo methylation-DNM). The conclusions mentioned were acquired from research on triticale regenerants, but there is no similar research on barley. In this way, the study looks at how DNM, DM, Cu(II), SAM, GSH, and ß-glucan affect the ability of green plant regeneration efficiency (GPRE). RESULTS: The experiment involved spring barley regenerants obtained through anther culture. Nine variants (trials) of induction media were created by adding copper (CuSO4: 0.1; 5; 10 µM) and silver salts (AgNO3: 0; 10; 60 µM), with varying incubation times for the anthers (21, 28, and 35 days). Changes in DNA methylation were estimated using the DArTseqMet molecular marker method, which also detects cytosine methylation. Phenotype variability in ß-glucans, SAM and GSH induced by the nutrient treatments was assessed using tentative assignments based on the Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The effectiveness of green plant regeneration ranged from 0.1 to 2.91 plants per 100 plated anthers. The level of demethylation ranged from 7.61 to 32.29, while de novo methylation reached values ranging from 6.83 to 32.27. The paper demonstrates that the samples from specific in vitro conditions (trials) formed tight groups linked to the factors contributing to the two main components responsible for 55.05% of the variance (to the first component DNM, DM, to the second component GSH, ß-glucans, Cu(II), GPRE). CONCLUSIONS: We can conclude that in vitro tissue culture conditions affect biochemical levels, DNA methylation changes, and GPRE. Increasing Cu(II) concentration in the IM impacts the metabolism and DNA methylation, elevating GPRE. Thus, changing Cu(II) concentration in the IM is fair to expect to boost GPRE.

Epicatechin and ß-Glucan from Whole Highland Barley Grain Synergistic Benefit on Attenuating Hyperglycemia via Improving Hepatic Glucose Metabolism in Diabetic C57BL/6J Mice.

Our previous study proved that epicatechin (EC) and ß-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3ß (GSK-3ß) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.

Comparative Analysis of the Aspergillus fumigatus Cell Wall Modification and Ensuing Human Dendritic Cell Responses by ß-(1,3)-Glucan Synthase Inhibitors-Caspofungin and Enfumafungin.

Caspofungin, a lipopeptide, is an antifungal drug that belong to the class of echinocandin. It inhibits fungal cell wall ß-(1,3)-glucan synthase activity and is the second-line of drug for invasive aspergillosis, a fatal infection caused mainly by Aspergillus fumigatus. On the other hand, Enfumafungin is a natural triterpene glycoside also with a ß-(1,3)-glucan synthase inhibitory activity and reported to have antifungal potential. In the present study, we compared the growth as well as modifications in the A. fumigatus cell wall upon treatment with Caspofungin or Enfumafungin, consequentially their immunomodulatory capacity on human dendritic cells. Caspofungin initially inhibited the growth of A. fumigatus, but the effect was lost over time. By contrast, Enfumafungin inhibited this fungal growth for the duration investigated. Both Caspofungin and Enfumafungin caused a decrease in the cell wall ß-(1,3)-glucan content with a compensatory increase in the chitin, and to a minor extent they also affected cell wall galactose content. Treatment with these two antifungals did not result in the exposure of ß-(1,3)-glucan on A. fumigatus mycelial surface. Enzymatic digestion suggested a modification of ß-(1,3)-glucan structure, specifically its branching, upon Enfumafungin treatment. While there was no difference in the immunostimulatory capacity of antifungal treated A. fumigatus conidia, alkali soluble-fractions from Caspofungin treated mycelia weakly stimulated the dendritic cells, possibly due to an increased content of immunosuppressive polysaccharide galactosaminogalactan. Overall, we demonstrate a novel mechanism that Enfumafungin not only inhibits ß-(1,3)-glucan synthase activity, but also causes modifications in the structure of ß-(1,3)-glucan in the A. fumigatus cell wall.

Identifying optimal serum 1,3-ß-D-Glucan cut-off for diagnosing Pneumocystis Jirovecii Pneumonia in non-HIV patients in the intensive care unit.

BACKGROUND: Serum (1,3)-ß-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. METHODS: This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden's index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. RESULTS: Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG's area under the receiver operating characteristic curve was 0.90 (0.87-0.93). At manufacturer's 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09-20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10-9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03-93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden's index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV. CONCLUSIONS: Tailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG's diagnostic performance in the ICU settings.

ß-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). ß-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received ß-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. RESULTS: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. CONCLUSION: ß-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

Bacteroides uniformis degrades ß-glucan to promote Lactobacillus johnsonii improving indole-3-lactic acid levels in alleviating colitis.

BACKGROUND: Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. ß-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. RESULTS: BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. CONCLUSIONS: These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract.

An exploratory clinical study of ß-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma.

Background: ß-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of ß-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods: This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received ß-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. Results: A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. Conclusions: This preliminary study demonstrates that ß-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100044088.

Adaptative responses of Neurospora crassa by histidine kinases upon the attack of the arthropod Sinella curviseta.

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of ß-glucan, ergothioneine, ergosterol, and carotenoids. ß-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli.

Anti-tumor and anti-metastasis of water-soluble sulfated ß-glucan derivatives from Saccharomyces cerevisiae.

Traditional fungi ß-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble ß-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as ß-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural ß-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural ß-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-α, TNF-α, and IL-1ß levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer research.

Oat ß-(1 → 3, 1 → 4)-d-glucan alleviates food allergy-induced colonic injury in mice by increasing Lachnospiraceae abundance and butyrate production.

Oat ß-(1 â†’ 3, 1 â†’ 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.

The Function and Mechanism of Laminaripentaose Prepared from Curdlan for the Amelioration of the Cognitive Dysfunctions in Obese Mice.

Functional oligosaccharides induce specific alterations in gut microbiota, potentially providing physiological benefits. However, the effects of laminaripentaose (LPA) on metabolic syndrome and the mechanism underlying it have not been intensively investigated yet. This study aimed to determine the effects of LPA on obesity and obesity-induced cognition impairment in mice. C57BL/6N mice fed with a high-fat diet received an LPA treatment for 12 weeks. An antibiotic intervention was further applied to evaluate the effects of the gut microbiota on cognitive functions. LPA treatment (500 mg/kg) reduced the weight gain by 32.4%. Furthermore, LPA improved memory functions and reduced hippocampal insulin resistance and neuronal injury. LPA markedly reduced systemic low-grade inflammation and intestinal barrier injury. Moreover, LPA increased gut beneficial bacteria, and Butyricimonas and Bifidobacterium were increased by 94.0 and 422.7%, respectively, accompanied by increased fecal short-chain fatty acids. Interestingly, antibiotic cocktail treatment abrogated the beneficial effects of LPA on cognition, which further suggests that LPA may attenuate obesity-induced cognition impairment via the gut-brain axis. Our findings provide the first evidence for the potential of dietary LPA to prevent obesity and obesity-associated complications.

Antifungal characterizations of a novel endo-ß-1,6-glucanase from Flavobacterium sp. NAU1659.

ß-1,6-Glucan plays a crucial role in fungal cell walls by linking the outer layer of mannoproteins and the inner layer of ß-1,3-glucan, contributing significantly to the maintenance of cell wall rigidity. Therefore, the hydrolysis of ß-1,6-glucan by ß-1,6-glucanase directly leads to the disintegration of the fungal cell wall. Here, a novel ß-1,6-glucanase FlGlu30 was identified from the endophytic Flavobacterium sp. NAU1659 and heterologously expressed in Escherichia coli BL21 (DE3). The optimal reaction conditions of purified FlGlu30 were 50℃ and pH 6.0, resulting in a specific activity of 173.1 U/mg using pustulan as the substrate. The hydrolyzed products of FlGlu30 to pustulan were mainly gentianose within 1 h of reaction. With the extension of reaction time, gentianose was gradually hydrolyzed to glucose, indicating that FlGlu30 is an endo-ß-1,6-glucanase. The germination of Magnaporthe oryzae Guy11 spores could not be inhibited by FlGlu30, but the appressorium formation of spores was completely inhibited under the concentration of 250.0 U/mL FlGlu30. The disruptions of cell wall and accumulation of intracellular reactive oxide species (ROS) were observed in FlGlu30-treated M. oryzae Guy11 cells, suggesting the significant importance of ß-1,6-glucan as a potential antifungal target and the potential application of FlGlu30. KEY POINTS: • ß-1,6-Glucan is a key component maintaining the rigid structure of fungal cell wall. • ß-1,6-Glucanase is an antifungal protein with significant potential applications. • FlGlu30 is the first reported ß-1, 6-glucanase derived from Flavobacterium.

Regulatory effect of ß-glucan secreted by Rhizobium pusense on triglyceride metabolism and their relationships with the modulation of intestinal microbiota in mice fed a high-fat diet.

The present study investigated the regulatory effects of ß-glucan secreted by Rhizobium pusense (RPG) on triglyceride metabolism and gut microbiota in mice fed a high-fat diet. The results indicated that supplementation with RPG significantly reduced body weight gain, blood glucose levels, and the tissue index of epididymal white adipose tissue (eWAT) and subcutaneous adipose tissue (SAT). Conversely, it increased the tissue index of brown adipose tissue (BAT). Furthermore, RPG supplementation effectively decreased the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum. Regarding its influence on the triglyceride (TG) mechanism, RPG decreased TG levels in both serum and liver, while elevating TG levels in feces. Moreover, it moderated the composition of gut microbiota in mice fed a high-fat diet, particularly altering functionally relevant intestinal microbial phylotypes, leading to enhanced levels of short-chain fatty acids (SCFAs) in feces. Additionally, RPG treatment regulated the mRNA and protein levels of genes responsible for TG metabolism in the AMPK pathway, indicating an impact on TG synthesis and excretion in the liver. Pearson's correlation network analysis demonstrated strong correlations between key microbial phylotypes responsive to RPG intervention and parameters associated with TG metabolic disorders. SCFA levels were also found to correlate with the mRNA expression levels of genes involved in TG metabolism. Finally, lipidomics analyses were performed to investigate the underlying mechanisms of RPG intervention (glycerophospholipid metabolic pathway) and to identify potential lipid biomarkers, such as TG (18:2/20:4/22:6), TG (18:1/20:4/22:6), TG (20:1/18:1/22:4), PC (17:0/20:4), TG (18:1/20:4/22:5), PC (22:4/22:6), PC (20:0/22:6), PC (20:0e/20:4), DG (18:3e/18:2), DG (10:0/18:2), DG (18:2/14:2), TG (10:0/18:2/20:4), TG (16:1/14:3/18:2) and TG (16:0/14:2/22:6). Overall, our results suggest that RPG could activate the hepatic AMPK signaling pathway by regulating gut microbiota and metabolites through gut-liver crosstalk to exert a lipid-lowering effect in mice fed a high-fat diet and improve obesity.

ß-Glucan-binding proteins are key modulators of immunity and symbiosis in mutualistic plant-microbe interactions.

In order to discriminate between detrimental, commensal, and beneficial microbes, plants rely on polysaccharides such as ß-glucans, which are integral components of microbial and plant cell walls. The conversion of cell wall-associated ß-glucan polymers into a specific outcome that affects plant-microbe interactions is mediated by hydrolytic and non-hydrolytic ß-glucan-binding proteins. These proteins play crucial roles during microbial colonization: they influence the composition and resilience of host and microbial cell walls, regulate the homeostasis of apoplastic concentrations of ß-glucan oligomers, and mediate ß-glucan perception and signaling. This review outlines the dual roles of ß-glucans and their binding proteins in plant immunity and symbiosis, highlighting recent discoveries on the role of ß-glucan-binding proteins as modulators of immunity and as symbiosis receptors involved in the fine-tuning of microbial accommodation.

Baker's yeast beta glucan supplementation was associated with an improved innate immune mRNA expression response after exercise.

Beta glucans are found in many natural sources, however, only Baker's Yeast Beta Glucan (BYBG) has been well documented to have structure-function effects that are associated with improved innate immune response to stressors (e.g., exercise, infection, etc.). The purpose was to identify a BYBG-associated mRNA expression pattern following exercise. Participants gave IRB-approved consent and were randomized to BYBG (Wellmune®; N=9) or Placebo (maltodextrin; N=10) for 6-weeks prior to performing 90 min of whole-body exercise. Paxgene blood samples were collected prior to exercise (PRE), after exercise (POST), two hours after exercise (2H), and four hours after exercise (4H). Total RNA was isolated and analyzed for the expression of 770 innate immune response mRNA (730 mRNA targets; 40 housekeepers/controls; Nanostring nCounter). The raw data were normalized against housekeeping controls and expressed as Log2 fold change from PRE for a given condition. Significance was set at p < 0.05 with adjustments for multiple comparisons and false discovery rate. We identified 47 mRNA whose expression was changed after exercise with BYBG and classified them to four functional pathways: 1) Immune Cell Maturation (8 mRNA), 2) Immune Response and Function (5 mRNA), 3) Pattern Recognition Receptors and DAMP or PAMP Detection (25 mRNA), and 4) Detection and Resolution of Tissue Damage (9 mRNA). The identified mRNA whose expression was altered after exercise with BYBG may represent an innate immune response pattern and supports previous conclusions that BYBG improves immune response to a future sterile inflammation or infection.

Fabrication of folic acid-conjugated pyrimidine-2(5H)-thione-encapsulated curdlan gum-PEGamine nanoparticles for folate receptor targeting breast cancer cells.

In this study 5-((2-((3-methoxy benzylidene)-amino)-phenyl)-diazenyl)-4,6-diphenyl pyrimidine-2(5H)-thione was synthesized. The pharmacological applications of pyrimidine analogs are restricted due to their poor pharmacokinetic properties. As a solution, a microbial exopolysaccharide (curdlan gum) was used to synthesize folic acid-conjugated pyrimidine-2(5H)-thione-encapsulated curdlan gum-PEGamine nanoparticles (FA-Py-CG-PEGamine NPs). The results of physicochemical properties revealed that the fabricated FA-Py-CG-PEGamine NPs were between 100 and 400 nm in size with a majorly spherical shaped, crystalline nature, and the encapsulation efficiency and loading capacity were 79.04 ± 0.79 %, and 8.12 ± 0.39 % respectively. The drug release rate was significantly higher at pH 5.4 (80.14 ± 0.79 %) compared to pH 7.2. The cytotoxic potential of FA-Py-CG-PEGamine NPs against MCF-7 cells potentially reduced the number of cells after 24 h with 42.27 µg × mL-1 as IC50 value. The higher intracellular accumulation of pyrimidine-2(5H)-thione in MCF-7 cells leads to apoptosis, observed by AO/EBr staining and flow cytometry analysis. The highest pyrimidine-2(5H)-thione internalization in MCF-7 cells may be due to folate conjugated on the surface of curdlan gum nanoparticles. Further, internalized pyrimidine-2(5H)-thione increases the intracellular ROS level, leading to apoptosis and inducing the decalin in mitochondrial membrane potential. These outcomes demonstrated that the FA-Py-CG-PEGamine NPs were specificity-targeting folate receptors on the plasma membranes of MCF-7 Cells.

Proanthocyanidins and ß-Glucan Synergistically Regulate Intestinal Inflammation in Dextran Sulfate Sodium-Induced Colitis Mice.

Proanthocyanidins (PA) have been proven to have an anti-inflammation effect in multiple models by regulating oxidative stress. ß-glucan (BG) could alleviate colitis from the perspectives of intestinal permeability and gut microbiota. In the present study, the synergistic anti-inflammatory function of PA and BG was explored from multiple aspects including immune response, intestinal barrier, gut microbiota, and differential metabolites. The results showed that the supplementation of PA and BG improved the colitis symptoms including atrophy of the colon, body weight loss, and organ index increase. Additionally, inflammatory cytokine levels and oxidative stress status were significantly regulated with the intake of PA and BG. Moreover, PA and BG intervention improved intestinal permeability and promoted the expression of barrier proteins. The microbiome and metabolic profile of cecal contents showed that PA and BG supplementation increased the abundance of anti-inflammatory bacteria and decreased the abundance of pro-inflammatory bacteria. Furthermore, some beneficial metabolites involved in amino acid metabolism, carbohydrate metabolism, and biosynthesis of other secondary metabolite pathways were increased. Overall, these findings have demonstrated the regulation of the inflammatory response and remodel of metabolite profiles by PA and BG complexes, indicating that it may serve as a new strategy for inflammatory bowel disease treatment in the future.

Valorization of barley (Hordeum vulgare L.) brans from the sustainable perspective: A comprehensive review of bioactive compounds and health benefits with emphasis on their potential applications.

Barley is an important source of sustainable diets for humans, while its brans is commonly disposed as wastes. The recycling of barley brans has become a key for facilitating the valorization of barley as a whole to achieve its sustainable development. This review summarized the value of barley brans as an excellent source of multiple functional components (phenolic compounds, ß-glucan, and arabinoxylan), which conferred extensive health benefits to barley brans mainly including antioxidant, anti-obesity and lipid-lowering, anti-diabetic, and hepatoprotective properties. The utilization of barley brans reflected a great potential for sustainable development. Exploiting of food products and edible films containing barley brans or their bioactive compounds and non-food applications (preparation of bioactive substances, laccase enzymes, and biosorbents) have been attempted for supporting the zero-waste concept and circular economy. Considering their diverse applications, effective extraction techniques of bioactive compounds from barley brans and their safety are the priority of future research.

Assessing the influences of ß-glucan on highland barley starch: Insights into gelatinization and molecular interactions.

Developing highland barley products is complex, possibly due to the presence of ß-glucan in highland barley. This study aims to investigate the impact of ß-glucan on the physicochemical properties, microstructure, and molecular interactions of highland barley starch (HBS) during gelatinization and aging. Increasing the ß-glucan content significantly reduced peak viscosity, setback viscosity, and breakdown viscosity, indicating altered gelatinization behavior. The ß-glucan content increase caused a significant drop in peak viscosity. With 20% ß-glucan addition, it reduced by 883 mPa·s, nearly 38%. Rheological analysis showed a transition from a solid-like to a liquid-like texture or quality, ultimately leading to a shear-thinning behavior. Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) confirmed the interaction between HBS and ß-glucan via intermolecular hydrogen bonding, promoting the formation of double helical structures in starch. These findings provide a deeper understanding of the role of ß-glucan in the processing of highland barley, highlighting its influence on the starch's properties.