Investigating immune-modulatory function of α-glucopyranose-rich compound polysaccharides by MC38-N4/OT-I co-culture system.

The potential antitumor function of polysaccharides is well accepted, it is unclear whether polysaccharides have immunoregulatory effect on CD8+ T lymphocyte cells to attack tumor cells. To evaluate the CD8+ T function enhancing role of polysaccharide compounds, the MC38-N4/OT-I co-culture system was established. The synergistic and complementary immune effect of α-glucopyranose-rich compound polysaccharides can be achieved by manipulating the antigen-specific T-cell expansion capacity and efficacy. This study was designed to investigate the antitumor-enhancement activity of a α-glucopyranose-rich compound polysaccharides by determining the activation of CD8+ T cells in a co-culture system. Compared to the control group (42.5 % ± 0.72 %), the specific α-glucopyranose-rich compound polysaccharides, comprising Agaricus blazei Murill, Grifola frondosa and Pericarpium Citri Reticulatae, demonstrated a significant decrease (20.4 % ± 1.23 %, p < 0.05) in the survival rate of MC38-N4 cells in the co-culture system. Additionally, the α-glucopyranose-rich compound polysaccharides resulted in a substantial increase (p < 0.01) in the proportion of CD8+ T cells and CD62L+ central memory T cells, which is a less differentiated T cell subset with high immune activity. Collectively, we reported that specific polysaccharide combination, which remodel the function of cytotoxic T cells and provided a basis for improving immune functions by using the specific types of polysaccharides.

Prognostic value of anthropometric- and biochemistry-based nutrition status indices on blood chemistry panel levels during cancer treatment.

Body weight, body mass index (BMI), Nutrition Risk Screening 2002 (NRS2002), and prognostic nutritional index (PNI) are among vital nutrition status indices employed during cancer treatment. These have also been associated with levels of blood chemistry panels (BCPs), which are touted as significant indicators of disease prognosis. However, it remains unclear which nutrition status index better predicts future trends in specific BCPs. Using the records of 407 cancer patients, we retrospectively examined the potential of nutritional status indices at baseline for predicting changes in specific BCPs over a 6-week period. Generally, both serum biochemical parameters and nutrition status indices fluctuated over the study period among study participants. PNI was often linearly associated with blood cell counts (white blood cells [WBCs] and hemoglobin) compared with anthropometric-based nutrition status indices. Increase in body weight was protective against having abnormal lymphocyte levels at 6 weeks (odds ratio [OR]: 0.960-0.974; CI: 0.935-0.997; P < 0.05), while increase in baseline PNI was associated with 0.865-0.941 and 0.675-0.915 odds of having future abnormal WBC and lymphocyte levels, respectively. Increases in PNI were also protective against having future abnormal albumin levels (OR: 0.734-0.886) and 8.5-12.5% decreases in the odds of having an abnormal C-reactive protein level in subsequent visits. Changes in NRS2002 tended to be associated with the odds of having future abnormal blood glucose levels. In conclusion, the serum biochemistry-derived nutrition status index, PNI, is a more consistent measure as an early indicator to track the trends of future changes in the BCPs of cancer patients. This implies that PNI could be targeted as an early-warning measure with relevant preventive interventions for patients at risk of malnutrition.

A Water Polysaccharide-Protein Complex from Grifola frondosa Inhibit the Growth of Subcutaneous but Not Peritoneal Colon Tumor under Fasting Condition.

SCOPE: Grifola frondosa has been shown to induce immune modulatory, modulate autophagy, and apoptosis in cancer cells. However, little is known about its potential for managing tumor progression as an adjunct to nutrient restriction. METHODS AND RESULTS: Water extract produces a G. frondosa polysaccharide-protein complex (G. frondosa PPC) of average molecular weight of 46.48 kDa, with glucose (54.8%) as the main constituent. Under serum-restricted conditions, G. frondosa PPC can significantly inhibit MC38 colorectal tumor cell migration in vitro. Under alternate-day fasting condition, G. frondosa PPC can only significantly inhibit the growth of subcutaneous (s.c.) tumor, but is feeble in halting its spread in the intraperitoneal (i.p.) cavity in tumor-bearing mice. Histopathological examination and Raman imaging show a significant increase in lipid content in the tumor microenvironment (TME) tissue of the s.c. tumor-bearing mice. G. frondosa PPC significantly increases C17:0 and C24:0 saturated fatty acids and significantly decreases C16:1 and C18:1 monounsaturated fatty acids in the TME of s.c. tumor-bearing mice compared with the i.p. cavity model. CONCLUSION: G. frondosa PPC significantly inhibits tumor growth in s.c. tumor-bearing mice under intermittent fasting conditions by altering the fatty acid composition of the TME.

Identification of the Wound Healing Activity Peptidome of Edible Bird's Nest Protein Hydrolysate and the In Silico Evaluation of Its Transport and Absorption Potential in Skin.

In this study, edible bird's nest (EBN) was proven to be a suitable source of bioactive peptides via enzymatic hydrolysis. The ultrafiltration component of the EBN peptides (EBNPs, Mw < 3 000 Da) could be responsible for moderate moisture retention and filaggrin synthesis. It was found that EBNP had a great capacity to protect HaCaT keratinocytes from DNA damage caused by UVB-irradiation and enhance wound healing by increasing the migratory and proliferative potential of cells. Furthermore, the external application of EBNP could effectively repair high glycolic acid concentration-induced skin burns in mice. A total of 1 188 peptides, predominantly the hydrophobic amino acids (e.g., Leu, Val, Tyr, Phe), were identified in the EBNP by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Molecular docking showed that hydrophobic tripeptides from EBNP had a good binding affinity to proton-dependent oligopeptide transporter PepT1. Our data indicated that the hydrophobic amino acid-rich EBNP plays an important role in skin wound healing.

Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype.

The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.

Soy Peptide Supplementation Mitigates Undernutrition through Reprogramming Hepatic Metabolism in a Novel Undernourished Non-Human Primate Model.

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

Interaction-based screening, Monte Carlo Bayesian inference-based de novo design and in vitro verification of adenine-binding peptide.

One of the main reasons for hyperuricemia is high purine intake. The primary strategy for treating hyperuricemia is blocking the purine metabolism enzyme. However, by binding the purine bases directly, we suggested a unique therapeutic strategy that might interfere with purine metabolism. There have been numerous reports of extensive interactions between proteins and purine bases. Adenine, constituting numerous protein co-factors, can interact with the adenine-binding motif. Using Bayesian Inference and Markov chain Monte Carlo sampling, we created a novel adenine-binding peptide Ile-Tyr-Val-Thr based on the structure of the adenine-binding motifs. Ile-Tyr-Val-Thr generates a semi-pocket that can clip the adenine within, as demonstrated by docking. Then, using thermodynamic techniques, the interaction between Ile-Tyr-Val-Thr and adenine was confirmed. The KD value is 1.50e-5 (ΔH = -20.2 kJ/mol and ΔG = -27.6 kJ/mol), indicating the high affinity. In brief, the adenine-binding peptide Ile-Tyr-Val-Thr may help lower uric acid level by blocking the absorption of food-derived adenine.

Oligomer-Aß42 suppress glioma progression via potentiating phagocytosis of microglia.

AIMS: Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid ß (Aß) leads to an active environment during the early stages of Alzheimer's disease (AD). Aß is also present in glioma tissues; however, the biological and translational implications of Aß in glioma are elusive. METHODS: Immunohistochemical (IHC) staining, Kaplan-Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between Aß and the malignancy of glioma. Subsequently, the potential of oligomer-Aß42 (OAß42) to inhibit glioma growth was investigated in vivo and in vitro. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. Finally, RNA-seq was utilized to identify the predominant signaling involved in this process and in vitro studies were performed to validate them. RESULTS: A positive correlation between Aß and a favorable prognosis was observed in glioma. Furthermore, OAß42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin-like growth factor 1 (IGF-1) secreted by OAß42-activated microglia was essential in the engulfment process. CONCLUSION: Our study proved an anti-glioma effect of Aß, and microglia could serve as a cellular target for treating glioma with OAß42.

Peptides with Charged Amino Acids Mitigate nZnO-Induced Growth Inhibition of Lactobacillus rhamnosus LRa05.

Growing concern is about the potential side effects of nanomaterials from food packaging, notably zinc oxide nanoparticles (nZnO). Previous research revealed that walnut-derived peptides could mitigate this inhibitory effect, but the mechanism involved is unclear. Here, we found that not all peptides have such an effect. Based on the growth inhibition model of Lactobacillus rhamnosus LRa05 induced by nZnO, we assessed the protective effects of various peptides. Notably, four peptides containing charged amino acids (PPKNW, WPPKN, ADIYTE, and WEREEQE) were found to effectively alleviate the growth inhibition phenomenon. We hypothesize that the peptide-nZnO interaction modifies this effect, as confirmed through infrared, Raman, and fluorescence spectroscopy. Our results highlight amide bonds, amino groups, carboxyl groups, and benzene rings as key peptide binding sites on nZnO, with static quenching primarily due to hydrogen bonds and van der Waals forces. This study elucidates peptide characteristics in nZnO interactions, facilitating a deeper exploration of food matrix-nanocomposite interactions.

The Evolution of Tumor Microenvironment in Gliomas and Its Implication for Target Therapy.

Gliomas develop in unique and complicated environments that nourish tumor cells. The tumor microenvironment (TME) of gliomas comprises heterogeneous cells, including brain-resident cells, immune cells, and vascular cells. Reciprocal interactions among these cells are involved in the evolution of the TME. Moreover, the study of attractive therapeutic strategies that target the TME is transitioning from basic research to the clinic. Mouse models are indispensable tools for dissecting the processes and mechanisms leading to TME evolution. In this review, we overview the paradoxical roles of the TME, as well as the recent progress of mouse models in TME research. Finally, we summarize recent advances in TME-targeting therapeutic strategies.

Walnut Protein: A Rising Source of High-Quality Protein and Its Updated Comprehensive Review.

Recently, plant protein as a necessary nutrient source for human beings, a common ingredient of traditional processed food, and an important element of new functional food has gained prominence due to the increasing demand for healthy food. Walnut protein (WP) is obtained from walnut kernels and walnut oil-pressing waste and has better nutritional, functional, and essential amino acids in comparison with other vegetable and grain proteins. WP can be conveniently obtained by various extraction techniques, including alkali-soluble acid precipitation, salting-out, and ultrasonic-assisted extraction, among others. The functional properties of WP can be modified for desired purposes by using some novel methods, including free radical oxidation, enzymatic modification, high hydrostatic pressure, etc. Moreover, walnut peptides play an important biological role both in vitro and in vivo. The main activities of the walnut peptides are antihypertensive, antioxidant, learning improvement, and anticancer, among others. Furthermore, WP could be applied in the development of functional foods or dietary supplements, such as delivery systems and food additives, among others. This review summarizes recent knowledge on the nutritional, functional, and bioactive peptide aspects of WP and possible future products, providing a theoretical reference for the utilization and development of oil crop waste.

Effects of casein phosphopeptides on thermal stability and sensory quality of whey protein emulsions containing calcium beta-hydroxy-beta-methylbutyrate.

This study aimed to elucidate the effect of casein phosphopeptides (CPP) on the thermal stability and sensory quality of whey protein emulsions containing calcium beta-hydroxy-beta-methylbutyrate (WPEs-HMB-Ca). The interaction mechanism among CPP, HMBCa, and WP in the emulsions before and after autoclaving (121 °C, 15 min) was systematically investigated from macroscopic external and microscopic molecular perspectives. It was found that WPEs-HMB-Ca treated by autoclaving resulted in an increase in droplet size (d4,3 = 24.09 µm) due to aggregation/flocculation of proteins, along with a stronger odor with higher viscosity, compared to those without autoclaving. When CPP:HMB-Ca = 1:25 (w/w) in the emulsion, the droplets exhibited a more uniform and consistent state in the emulsion. In addition, CPP was able to inhibit the formation of complex spatial network structures of proteins during autoclaving by binding with Ca2+, thus improving the thermal stability and storage stability of WPEs-HMB-Ca. This work might provide theoretical guidance for developing functional milk drinks with good thermal stability and flavor.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

A sensitive and economical method for simultaneous determination of D/L- amino acids profile in foods by HPLC-UV: Application in fermented and unfermented foods discrimination.

This work described a sensitive and economical HPLC-UV method with FDAA derivatization to simultaneously detect 36 D/l-amino acids, which provides higher sensitivity and lower cost than other HPLC-based methods. It was validated for linearity range (8-1000 µmol/L), limits of detection (2.68-62.44 pmol/L), limits of quantification (2.93 to 208.13 pmol/L), intraday precision (0.30 % - 5.31 %), interday precision (1.96 % - 8.04 %) and accuracy (86.53 % - 121.46 %). This method was then applied in the determination of D/L- amino acids abundance in fermented and unfermented food materials and showed the characteristics of each type of foods. The method also demonstrated good performance in another application case for the discrimination of different types of food materials based on D/L- amino acids profile. It emphasizes the ability of the method to study the characteristics, distribution and abundance of d-amino acids in foods and their potential application in food quality control.

Integrated evaluation the antioxidant activity of epicatechin from cell dynamics.

Oxidative damage has been implicated in the pathogenesis of numerous disorders by affecting the normal functions of several tissues. Further, oxidative stress acts within cells to influence cell morphology and the behavior of cell migration. The movement and migration of cells are crucial during the development of organisms as they transition from embryo to adult, and for the homeostasis of adult tissues. Epicatechin (EC) is a natural flavonoid derived mostly from tea, chocolate, and red wine. We investigated the protective impact of EC on D-galactose(D-gal)/rotenone-injured NIH3T3 cells and found alterations in cell dynamics throughout the procedure. The results reveal that D-gal/rotenone stimulation can cause the cell area to expand and the number of cellular protrusions to increase. EC intervention can considerably minimize the oxidative damage of rotenone on NIH3T3 cells (p < 0.05) but showed little influence on cell damage induced by D-gal. Furthermore, the corrective ability of EC as an antioxidant is reflected in a dose-dependent effect on cell movement, including variations in movement speed and distance. Overall, from the perspective of cell morphology and cell motility, EC has a good protective impact on cells harmed by rotenone induced oxidative damage, as well as corrective properties as an antioxidant to balance intracellular oxidative stress, which allowing for a more comprehensive evaluation of antioxidant performance of EC.

Intestinal absorptivity-increasing effects of sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate on food-derived bioactive peptide.

Delivering bioactive peptides orally is hampered by poor absorption across the gastrointestinal barrier. Using the walnut-derived peptide PW5, PPKNW, we explored whether coformulation of peptides with absorption enhancer sodium N-[8-(2-hydroxybenzoyl)aminocaprylate] (SNAC) could improve the intestinal absorption of orally-administered bioactive peptides. Herein, the application of SNAC enhanced the absorption efficiency of PW5 in a non-everted gut sac model. Particle size distribution (1 027.8 ± 6.74 nm) and zeta potential (-2.89 ± 0.07 mV) of the PW5-SNAC complex were significantly greater than that of individual PW5 and SNAC. Scanning electron microscopy revealed that SNAC application could aggravate the surface roughness and reduce the compact structure of PW5. It further showed that PW5 and SNAC binds through an endothermic process underpinned by hydrogen bond and van der Waals forces and that SNAC could bound primarily to the internal calyx of PW5. These findings are helpful for the effective delivery of bioactive peptides.

Hericium erinaceus mycelium-Derived Polysaccharide Alleviates Ulcerative Colitis and Modulates Gut Microbiota in Cynomolgus Monkeys.

SCOPE: Ulcerative colitis (UC) is rapidly increasing worldwide but prolong use of available corticosteroids treatment is associated with numerous adverse effects. There is the urgent need to develop novel therapeutic options. However, this requires the use of suitable disease models, but current models are generated with chemical agents mainly in rodents, which are unable to recapitulate the human occurrence. The aim of this study is to validate the occurrence of spontaneous UC in cynomolgus monkeys and explore the potential of Hericium erinaceus mycelium-derived polysaccharide in reversing UC pathologies. METHODS AND RESULTS: Postmortem bowel evaluation and biochemical analysis including inflammatory markers and fecal occult blood testing (FOBT) as well as nutrition status parameters, confirm the non-artificial induced spontaneous occurrence of UC in cynomolgus monkeys. Subsequently, H. erinaceus mycelium-derived polysaccharide supplementation significantly attenuates UC pathologies, improves nutritional status, reduces the incidence of diarrhea, and reduces inflammation in UC monkeys. Importantly, the polysaccharides administration enhances intestinal function and reshapes the gut microbiota. CONCLUSION: The study confirms the spontaneous UC monkeys can closely mimic the occurrence of UC in humans. Moreover, H. erinaceus mycelium-derived polysaccharide can effectively restore UC in monkeys, which show the prospects as precision nutritional supplement for the management of UC.

Bioactivity guided isolation and identification of phenolic compounds from Citrus aurantium L. with anti-colorectal cancer cells activity by UHPLC-Q-TOF/MS.

Natural plants are rich sources of various bioactive compounds. Consequently, the efficiently isolation of these bioactive components has always attracted considerable attention. Our work aims to demonstrate a framework for bioactivity guided isolation of potential effective compounds from the complex food materials. We demonstrated its application for isolation of phenolic compounds with anti-proliferative activity against colorectal cancer cells (CRCs) from Citrus aurantium L. Firstly, phenolic rich fraction was successfully identified as the main effective components that could simultaneously suppress the growth of CRCs and inhibit Wnt signaling. In order to obtain the bioactive phenolic constituents, a detailed study was performed by optimizing the purification conditions. Two phenolic rich fractions (40% and 60% ethanol elution fractions) were then obtained by AB-8 macroporous resins under optimized condition. Finally, the main components (65 compounds) were tentatively identified from the 40% ethanol eluant by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) analysis. Notably, there were five of the phytochemicals (Feruloylagmatine, Haploside C, Sagittatin A, Linderagalactone C and Koparin-2'-methyl ether) which were hitherto unidentified in Citrus aurantium L. fruit. In conclusion, this study showed that under the principle of bioactivity guided strategy, phenolic constituents with potential anti-CRCs activity were isolated from Citrus aurantium L.

Effects of Ilisha elongata protein, soy protein and whey protein on growth characteristics and adhesion of probiotics.

The effects of different food source proteins on the growth characteristics and intestinal adhesion of Lactobacillus plantarum 45 (LP45) were investigated by adding Ilisha elongata protein, soy protein and whey protein to the probiotic bacteria in vitro and using a probiotic adhesion model based on mouse intestinal tissues. Ilisha elongata protein and soy protein significantly reduced the growth time of LP45 and increased the total number of colonies fermented by LP45; whey protein only reduced the growth time of LP45; the effect of the three food source proteins on the acid production capacity of LP45 was small. These showed that the three food-derived proteins promoted the proliferation and adhesion of probiotics in the intestine, which were beneficial to the active role of intestinal probiotics and improved the intestinal microenvironment.