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.

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.

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.

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.

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.

Comparison of 3 hyperuricemia mouse models and evaluation of food-derived anti-hyperuricemia compound with spontaneous hyperuricemia mouse model.

Hyperuricemia animal models have long been used for evaluating food-derived anti-hyperuricemia compounds. Fructose and potassium oxonate are commonly used for developing hyperuricemia mouse model. Recent research also developed spontaneous hyperuricemia model by uricase knockout (Uox-/-). In this work, we evaluated 3 kinds of models with the same gene background to illustrate the differences between the treatments. Unlike the uric acid levels in potassium oxonate (224.79 ± 33.62 µmol/L) and Uox-/- groups (458.39 ± 38.29 µmol/L), fructose treatment did not lead to higher serum uric acid level (174.93 ± 30.46 µmol/L) comparing to the control group (153.53 ± 40.96 µmol/L). However, abnormal glycometabolism only developed in the fructose and the Uox-/- group. In addition, anemia, inflammasome and severe renal injury occurred in the Uox-/- group. The Uox-/- mice were then treated with puerarin and allopurinol, and found that puerarin could reduce serum uric acid and alleviated the serious renal damage associated with high uric acid. Thus, the Uox-/- mice could be a suitable model for screening and evaluating anti-hyperuricemia compounds.

A modified xanthine oxidase cell model for screening of antihyperuricemic functional compounds.

Hyperuricemia is a purine metabolism disorder, with increasing prevalence worldwide. Here, a high throughput cell model for screening of antihyperuricemic compounds was set up. Human kidney cells (HK2 cells) were stimulated with adenosine and the resulting supernatant and lysate were then analyzed using high performance liquid chromatography (HPLC). The results showed that hypoxanthine content was increased in both HK2 cells supernatant and xanthine oxidase (XO)-overexpressing HK2 cells lysate, but no uric acid was detected due to lower endogenous XO content in these cells. Exogenous XO was added to the supernatant, and then used to evaluate the antihyperuricemic activity of Febuxostat and two the previously identified peptides, Pro-Gly-Ala-Cys-Ser-Asn (PGACSN) and Trp-Met-Leu (WML). By adding exogenous XO, this combined-adenosine-XO-induced hyperuricemia model was optimized and established, and the Febuxostat and peptides were confirmed to significantly reduce uric acid production in the HK2 cells supernatant (p < 0.05). Therefore, this cell model could be recommended for screening potential bioactive antihyperuricemic compounds.

Physicochemical, functional, and digestive characteristics of tea seed cake protein obtained by ultrafiltration.

To make full use of tea seed cake protein (TSCP), this study investigated the physicochemical and functional properties of TSCP, including the TSCP extract and three ultrafiltration fractions TSCP-1 (Mw > 10 kDa), TSCP-2 (3.5 kDa < Mw < 10 kDa), and TSCP-3 (Mw < 3.5 kDa). After ultrafiltration, the content, thermal stability, and surface hydrophobicity of TSCP were increased, and the molecular weight distribution and structure of TSCP showed significant differences. In terms of functionality, each fraction showed its advantages. Specifically, compared with the others, TSCP had better solubility and foaming properties, and TSCP-1 had significantly higher oil absorption capacity, and TSCP-2 had better water absorption capacity and emulsifying properties, and TSCP-3 can flow more easily (p < 0.05). In terms of nutritional value, the content of essential amino acids in all samples was sufficient. The degree of hydrolysis of TSCP was highest (80.98 ± 1.50%), and ultrafiltration decreased digestibility. These results indicated that ultrafiltration effectively improved the structure and functional properties of TSCP, and the obtained fractions can be applied to different scenarios. Practical Application: Tea seed cakes are rich in protein and usually regarded as byproducts during oil processing. Because of its good functional properties, tea seed cake proteins obtained by ultrafiltration have the potential to be used as ingredients for food.

Pickering Emulsion Stabilized by Tea Seed Cake Protein Nanoparticles as Lutein Carrier.

To effectively deliver lutein, hydrothermally prepared tea seed cake protein nanoparticles (TSCPN) were used to fabricate Pickering emulsion, and the bioaccessibility of lutein encapsulated by Pickering emulsion and the conventional emulsion was evaluated in vitro. The results indicated that the average size and absolute value of zeta potential of TSCPN increased along with the increase in the protein concentration, and 2% protein concentration was adopted to prepare TSCPN. With the increase in the concentration of TSCPN, the size of Pickering emulsion decreased from 337.02 µm to 89.36 µm, and when the TSCPN concentration was greater than 0.6%, all emulsions exhibited good stability during the 14 days storage. Combined with the microstructure result, 1.2% TSCPN was used to stabilize Pickering emulsion. With the increase in ionic concentration (0-400 mM), the particle size of the emulsions increased while the absolute value of zeta potential decreased. TSCPN-based Pickering emulsion was superior to the conventional emulsion for both lutein encapsulation (96.6 ± 1.0% vs. 82.1 ± 1.4%) and bioaccessibility (56.0 ± 1.1% vs. 35.2 ± 1.2%). Thus, TSCPN-based Pickering emulsion in this study have the potential as an effective carrier for lutein.

Subcritical Water Enhanced with Deep Eutectic Solvent for Extracting Polysaccharides from Lentinus edodes and Their Antioxidant Activities.

In the present study, subcritical water extraction (SWE) assisted with deep eutectic solvent (DES) is used to extract Lentinus edodes polysaccharides (LEP). In addition, the antioxidant activity of the polysaccharide samples was also investigated. Based on a single factor test and response surface test, the optimal extraction factors were a liquid-solid solvent of 40:1 mL/g, extraction temperature of 147.23 °C, water content of 39.76% and extraction time of 17.58 min. Under these extraction conditions, the yield of LEP was 6.26 ± 0.08%. Compared with the SWE and hot water extraction (HWE), it improved by 19.24% and 17.01%, respectively. In addition, the results of monosaccharide composition, molecular weight, FT-IR, UV and SEM confirmed that the extracts had the features of polysaccharides. Interestingly, the polysaccharides obtained with the SWE assisted with the DES procedure showed a higher DPPH scavenging activity, hydroxyl radical scavenging activity and hydrogen peroxide scavenging activity, which indicated that the polysaccharides with this method had a stronger antioxidant activity. These findings demonstrated that the SWE-assisted DES is a strong method to obtain polysaccharides from Lentinus edodes for food, biopharmaceutical and other industrial production.