Raw and heat-treated quinoa protein protects against glucose metabolism disorders in high-fat diet (HFD)-induced mice by reshaping gut microbiota and fecal metabolic profiles.

Plant-based proteins have received considerable global attention due to their nutritional value and potential health effects. As a high-quality plant protein, the hypoglycemic effect of quinoa protein and its potential mechanism have not been fully elucidated. In the present study, we compared the hypoglycemic effects of raw quinoa protein (RP-quinoa) and heat-treated quinoa protein (HP-quinoa) and further explored their potential mechanisms using multi-omics analysis based on gut microbiota and fecal metabolic profiles in HFD-fed mice. Our results showed that both RP-quinoa and HP-quinoa effectively improved glucose metabolism and protected against alterations in gut microbiota induced by a chronic HFD. In addition, quinoa protein increased the relative abundance of beneficial bacteria such as the g__Lachnospiraceae_NK4A136_group, g__Eubacterium_xylanophilum_group, and g__Negativibacillus, followed by an increase in short-chain fatty acids and potentially beneficial metabolites such as L-phenylalanine and L-cysteine. Together, these findings provided the basis for linking gut microbiota and their metabolites to the hypoglycemic effect of quinoa protein.

Identification, screening and molecular mechanisms of natural stable angiotensin-converting enzyme (ACE) inhibitory peptides from foxtail millet protein hydrolysates: a combined in silico and in vitro study.

The stability of bioactive peptides under various food processing conditions is the basis for their use in industrial manufacturing. This study aimed to identify natural ACE inhibitors with excellent stability and investigate their physicochemical properties and putative molecular mechanisms. Five novel ACE inhibitory peptides (QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ) were isolated and identified using RP-HPLC and Nano LC-MS/MS with foxtail millet protein hydrolysates as the raw material. These peptides are non-toxic and exhibit strong ACE inhibitory activity in vitro (IC50 values between 0.13 mg mL-1 and 0.56 mg mL-1). In addition to QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ have excellent human intestinal absorption. Compared to FPGVSPF and SPAQLLPF, the stable helical structure of LVPYRP and WYWPQ allows them to maintain high stability under conditions that mimic gastrointestinal digestion and various food processing (temperatures, pH, sucrose, NaCl, citric acid, sodium benzoate, Cu2+, Zn2+, K+, Mg2+, Ca2+). The results of molecular docking and molecular dynamics simulation suggest that LVPYRP has greater stability and binding capacity to ACE than WYWPQ. LVPYRP might attach to the active pockets (S1, S2, and S1') of ACE via hydrogen bonds and hydrophobic interactions, then compete with Zn2+ in ACE to demonstrate its ACE inhibitory activity. The binding of LVPYRP to ACE enhances the rearrangement of ACE's active structural domains, with electrostatic and polar solvation energy contributing the most energy to the binding. Our findings suggested that LVPYRP derived from foxtail millet protein hydrolysates has the potential to be incorporated into functional foods to provide antihypertensive benefits.

Identification and molecular binding mechanism of novel pancreatic lipase and cholesterol esterase inhibitory peptides from heat-treated adzuki bean protein hydrolysates.

Heat-treated adzuki bean protein hydrolysates exhibit lipid-reducing properties; however, few studies have reported pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory effects and elucidated the underlying mechanisms. In this study, we accomplished the identification of antiobesity peptides through peptide sequencing, virtual screening, and in vitro experiments. Furthermore, the mechanisms were investigated via molecular docking. The findings reveal that the action of pepsin and pancreatin resulted in the transformation of intact adzuki bean protein into smaller peptide fragments. The < 3 kDa fraction exhibited a high proportion of hydrophobic amino acids and displayed superior inhibitory properties for both PL and CE. Five novel antiobesity peptides (LLGGLDSSLLPH, FDTGSSFYNKPAG, IWVGGSGMDM, YLQGFGKNIL, and IFNNDPNNHP) were identified as PL and CE inhibitors. Particularly, IFNNDPNNHP exhibited the most robust biological activity. These peptides exerted their inhibitory action on PL and CE by occupying catalytic or substrate-binding sites through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking.

Whole-Grain Highland Barley Attenuates Atherosclerosis Associated with NLRP3 Inflammasome Pathway and Gut Microbiota in ApoE-/- Mice.

The efficacy and mechanism of highland barley in the treatment of atherosclerosis have received little attention. Herein, we aimed to explore whether highland barley supplementation can prevent atherosclerosis progression and improve gut microbiota disorder in apolipoprotein E knockout (ApoE-/-) mice. Male ApoE-/- mice were fed a high-fat diet with whole-grain highland barley (WHB) or refined highland barley for 18 weeks. WHB substantially inhibited the formation of atherosclerotic plaques, reduced serum tumor necrosis factor-α, and downregulated the expression of NLRP3 in the aorta. Furthermore, the 16S rRNA analysis revealed that highland barley supplementation helped to restore the dysregulation of the gut microbiota, as evidenced by an increase in the relative abundance of specific beneficial bacteria known for their anti-inflammatory properties, such as Lachnospiraceae, Lactobacillus, Muribaculaceae, and Bifidobacterium. Highland barley supplementation might alleviate atherosclerotic plaque formation by modulating the NLRP3 inflammasome pathway and the synthesis of anti-inflammatory metabolites by the gut microbiota.

Comparison of the generation of α-glucosidase inhibitory peptides derived from prolamins of raw and cooked foxtail millet: In vitro activity, de novo sequencing, and in silico docking.

Foxtail millet prolamin has been demonstrated to have anti-diabetic effects. In this study, we compared the generation of anti-α-glucosidase peptides derived from prolamins of raw and cooked foxtail millet (PRFM and PCFM). PRFM and PCFM hydrolysates (PRFMH and PCFMH) both exhibited α-glucosidase inhibitory activity. After ultrafiltration according to molecular weight (Mw), the fraction with Mw < 3 kDa in PCFMH (PCFMH<3) showed higher α-glucosidase inhibitory activity than that in PRFMH (PRFMH<3). The composition of α-glucosidase inhibitory peptides identified by de novo sequencing in PCFMH<3 and PRFMH<3 was compared by virtual screening, combining biological activity, net charge, grand average of hydropathicity (GRAVY), and key hydrophobic amino acids (Met, Pro, Phe, and Leu). We found that the proportion of peptides with excellent α-glucosidase binding force in PCFMH<3 was higher than in PRFMH<3. Overall, cooking may positively affect the generation of peptides that perform well in inhibiting α-glucosidase derived from foxtail millet prolamin.

Deep learning drives efficient discovery of novel antihypertensive peptides from soybean protein isolate.

As a potential and effective substitute for the drugs of antihypertension, the food-derived antihypertensive peptides have arisen great interest in scholars recently. However, the traditional screening methods for antihypertensive peptides are at considerable expense and laborious, which blocks the exploration of available antihypertensive peptides. In our study, we reported the use of a protein-specific deep learning model called ProtBERT to screen for antihypertensive peptides. Compared to other deep learning models, ProrBERT reached the highest the area under the receiver operating characteristic curve (AUC) value of 0.9785. In addition, we used ProtBERT to screen candidate peptides in soybean protein isolate (SPI), followed by molecular docking and in vitro validation, and eventually found that peptides LVPFGW (IC50 = 20.63 µM), VSFPVL (2.57 µM), and VLPF (5.78 µM) demonstrated the good antihypertensive activity. Deep learning such as ProtBERT will be a useful tool for the rapid screening and identification of antihypertensive peptides.

Glycyrrhizin micellar nanocarriers for topical delivery of baicalin to the hair follicles: A targeted approach tailored for alopecia treatment.

Alopecia affected approximately 16.6% of all people in China, however, treatment options remain limited due to the side effects. Plant bioactive compound baicalin (BC) possesses hair growth-promotion activity, but poor water solubility and unsuitable log P value restrict its topical application, and natural Glycyrrhizin (GL) can exactly overcome these drawbacks. Here, BC was encapsulated in GL to form GL-BC micelles for alopecia treatment. Simultaneously, tween 80 (TW) as carriers was incorporated in the GL-BC to form GL-TW-BC micelles. The topical penetration, penetration pathways, cellular uptake and the underlying mechanisms behind the hair loss reconstruction of the GL micelles were investigated. We found the optimal GL-BC and GL-TW-BC formulations significantly improved the penetration and accumulation of BC in the porcine skin predominantly through the hair follicles pathways without causing skin irritation, which resulted in a targeted treatment. The proliferation of human dermal papilla cells (hDPCs) and effective cellular uptake was also enhanced. Moreover, the activation of the Wnt/ß-catenin pathway, up-expression of vascular endothelial growth factor (VEGF), α-melanocyte-stimulating hormone (α-MSH) and interleukin-10 (IL-10) were the mechanisms of micelles for the hair recovery. Interestingly, GL and BC exhibited a synergistic treatment of alopecia. Collectively, GL-BC and GL-TW-BC can be used as promising approaches for the treatment of alopecia.

Corrigendum: Effect of Different Processing Methods on the Millet Polyphenols and Their Anti-diabetic Potential.

[This corrects the article DOI: 10.3389/fnut.2022.780499.].

A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment.

The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by in-vitro and in-vivo studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.

Overview of the Composition of Whole Grains' Phenolic Acids and Dietary Fibre and Their Effect on Chronic Non-Communicable Diseases.

Chronic non-communicable diseases are the major cause of death globally. Whole grains are recommended in dietary guidelines worldwide due to increasing evidence that their consumption can improve health beyond just providing energy and nutrients. Epidemiological studies have suggested that the incorporation of whole grains, as part of a healthy diet, plays a key role in reducing one's risk for cardiovascular diseases (CVDs), obesity, type 2 diabetes (T2D) and cancer. Phenolic acids and dietary fibre are important components found in whole grains that are largely responsible for these health advantages. Both phenolic acids and dietary fibre, which are predominantly present in the bran layer, are abundant in whole-grain cereals and pseudo-cereals. Several studies indicate that whole grain dietary fibre and phenolic acids are linked to health regulation. The main focus of this study is two-fold. First, we provide an overview of phenolic acids and dietary fibres found in whole grains (wheat, barley, oats, rice and buckwheat). Second, we review existing literature on the linkages between the consumption of whole grains and the development of the following chronic non-communicable diseases: CVDs, obesity, T2D and cancer. Altogether, scientific evidence that the intake of whole grains reduces the risk of certain chronic non-communicable disease is encouraging but not convincing. Based on previous studies, the current review encourages further research to cover the gap between the emerging science of whole grains and human health.

Effect of Different Processing Methods on the Millet Polyphenols and Their Anti-diabetic Potential.

Interest in polyphenols has grown due to their beneficial effect on diabetes attenuation. Millets are ancient crops that are rich in polyphenols and used for both food and feed. They are grown worldwide and are adapted to production under dry, hot conditions. The polyphenols found in millets have anti-diabetic properties. However, millet is usually consumed after being processed by heating, germination, fermentation, and other processing methods, which may alter polyphenol content and thus affect their anti-diabetic potential. This mini-review profiles the effects of different processing methods on millet polyphenols and how changes in millet polyphenols affect the hypoglycemic effect of millet. Future studies are needed to compare the anti-diabetes potential of millet polyphenols before and after processing and to explore ways to minimize polyphenol losses and thus maintain their hypoglycemic effect in final products.

[The Clinical Features of Metabolic Syndrome in Receptors of Hematopoietic Stem Cells].

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.

Adzuki Bean Alleviates Obesity and Insulin Resistance Induced by a High-Fat Diet and Modulates Gut Microbiota in Mice.

Adzuki bean consumption has many health benefits, but its effects on obesity and regulating gut microbiota imbalances induced by a high-fat diet (HFD) have not been thoroughly studied. Mice were fed a low-fat diet, a HFD, and a HFD supplemented with 15% adzuki bean (HFD-AB) for 12 weeks. Adzuki bean supplementation significantly reduced obesity, lipid accumulation, and serum lipid and lipopolysaccharide (LPS) levels induced by HFD. It also mitigated liver function damage and hepatic steatosis. In particular, adzuki bean supplementation improved glucose homeostasis by increasing insulin sensitivity. In addition, it significantly reversed HFD-induced gut microbiota imbalances. Adzuki bean significantly reduced the ratio of Firmicutes/Bacteroidetes (F/B); enriched the occurrence of Bifidobacterium, Prevotellaceae, Ruminococcus_1, norank_f_Muribaculaceae, Alloprevotella, Muribaculum, Turicibacter, Lachnospiraceae_NK4A136_group, and Lachnoclostridium; and returned HFD-dependent taxa (Desulfovibrionaceae, Bilophila, Ruminiclostridium_9, Blautia, and Ruminiclostridium) back to normal status. PICRUSt2 analysis showed that the changes in gut microbiota induced by adzuki bean supplementation may be associated with the metabolism of carbohydrates, lipids, sulfur, and cysteine and methionine; and LPS biosynthesis; and valine, leucine, and isoleucine degradation.

Dietary supplementation with mung bean coat alleviates the disorders in serum glucose and lipid profile and modulates gut microbiota in high-fat diet and streptozotocin-induced prediabetic mice.

As amajor by-product of mung bean processing, mung bean coat (MBC), which is rich in polyphenols and dietary fiber, is deemed to be mainly responsible for the health benefits of mung bean. However, its beneficial effects on the hyperglycemia, hyperlipidemia, and gut microbiota composition in prediabetic mice is not fully understood. The objective of this study was to investigate the efficacy of MBC in alleviating high-fat diet and streptozotocin-induced prediabetes. Herein, compared with the model control, dietary supplementation with MBC (3%, w/w) for 12 weeks significantly decreased the fasting blood glucose (24.60%), total cholesterol (15.72%), triglyceride (14.41%), and low-density lipoprotein cholesterol (22.45%). Furthermore, the improvements in glucose tolerance were reflected in the reduction of the area under the curve (AUC) and incremental AUC by approximately 23.08% and 51.18%, respectively. 16S rRNA gene sequencing of fecal microbiota suggested that MBC promoted the enrichment of beneficial bacteria (Roseburia and Bifidobacterium) and the production of short-chain fatty acids. All of the results from this study provided a scientific reference for avoiding the functional ingredients waste of MBC and expanding its application value.

Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota.

Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We employed 16S rRNA and liver RNA sequencing technologies to identify the target gut microbes and signaling pathways involved in the hypoglycemic effect of FM supplementation. The results showed that FM supplementation significantly increased the relative abundance of Lactobacillus and Ruminococcus_2, which were significantly negatively correlated with FG and 2-h glucose. FM supplementation significantly reversed the trends of gene expression in diabetic rats. Specifically, FM supplementation inhibited gluconeogenesis, stimulated glycolysis, and restored fatty acid synthesis through activation of the PI3K/AKT signaling pathway. FM also reduced inflammation through inhibition of the NF-κB signaling pathway. Spearman's correlation analysis indicated a complicated set of interdependencies among the gut microbiota, signaling pathways, and metabolic parameters. Collectively, the above results suggest that the hypoglycemic effect of FM was at least partially mediated by the increased relative abundance of Lactobacillus, activation of the PI3K/AKT signaling pathway, and inhibition of the NF-κB signaling pathway.

Protein structural properties and proteomic analysis of rice during storage at different temperatures.

Rice quality changes during storage, but there have been few studies of how rice proteins changes during aging. The present study characterized the structural properties of protein in stored rice and identified the mechanism of quality deterioration using proteomics. Compared with protein from newly harvested rice, the free sulfhydryl content of protein from stored rice was significantly reduced and the disulfide bond content and surface hydrophobicity was higher. Storage resulted in a loss of α-helix and ß-sheet structures and increase in ß-turn and random coil structures. High-molecular-weight protein subunits decomposed to produce low-molecular-weight subunits at 30 °C, while protein aggregation occurred at 70 °C. At 30 ℃ 157 differential proteins were found and 70 ℃ 395 such proteins occurred. Redox homeostasis, response to oxidative stress, glutathione metabolism, tricarboxylic acid cycle, glycolysis/gluconeogenesis, starch and sucrose metabolism, and fatty acid biosynthesis and degradation led to the different quality of stored rice.

Protein Isolates from Raw and Cooked Foxtail Millet Attenuate Development of Type 2 Diabetes in Streptozotocin-Induced Diabetic Mice.

SCOPE: Millet protein has received much attention due to its beneficial role in alleviating metabolic disease symptoms. This study aims to investigate the role and molecular mechanism of foxtail millet protein isolates, including protein isolates from raw and cooked foxtail millet in alleviating diabetes, including gut microbiota and intracellular signal pathways. METHODS AND RESULTS: Protein isolates from raw and cooked foxtail millet are orally administered to streptozotocin (STZ)-induced diabetic mice for 5 weeks before hypoglycemic effect evaluation. The results show that foxtail millet protein isolates improve glucose intolerance and insulin resistance in diabetic mice. However, only the protein isolate from cooked foxtail millet reverse the weight loss trend and alleviate lipid disorders in diabetic mice. Besides, 16S rRNA sequencing show that both raw and cooked foxtail millet protein isolates altered diabetes-induced gut dysbiosis. In addition, western blotting analysis indicated that the protein isolate from cooked foxtail millet increases the expression levels of glucagon-like peptide-1 receptor (GLP-1R), phosphoinositide 3-kinase (PI3K), and phosphoinositide-protein kinase B (p-AKT)/AKT while the protein isolate from raw foxtail millet downregulates stearoyl-coenzyme A desaturase 1 (SCD1) level. CONCLUSION: Both raw and cooked foxtail millet protein isolates can exert hypoglycemic effects in diabetic mice through rewiring glucose homeostasis, mitigating diabetes-induced gut dysbiosis, and affecting the GLP-1R/PI3K/AKT pathway.

High-Molecular-Weight Glutenin Subunits: Genetics, Structures, and Relation to End Use Qualities.

High-molecular-weight glutenin subunits (HMW-GSs) are storage proteins present in the starchy endosperm cells of wheat grain. Encoding the synthesis of HMW-GS, the Glu-1 loci located on the long arms of group 1 chromosomes of the hexaploid wheat (1A, 1B, and 1D) present multiple allelism. In hexaploid wheat cultivars, almost all of them express 3 to 5 HMW-GSs and the 1Ay gene is always silent. Though HMW-GSs are the minor components in gluten, they are crucial for dough properties, and certain HMW-GSs make more positive contributions than others. The HMW-GS acts as a "chain extender" and provides a disulfide-bonded backbone in gluten network. Hydrogen bonds mediated by glutamine side chains are also crucial for stabilizing the gluten structure. In most cases, HMW-GSs with additional or less cysteines are related to the formation of relatively more or less interchain disulfide bonds and HMW-GSs also affect the gluten secondary structures, which in turn impact the end use qualities of dough.

Electromagnetized-Nanoparticle-Modulated Neural Plasticity and Recovery of Degenerative Dopaminergic Neurons in the Mid-Brain.

The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.

Folate-Modified Photoelectric Responsive Polymer Microarray as Bionic Artificial Retina to Restore Visual Function.

A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.