Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

Elucidating salt-reduction mechanisms of aroma-active compounds from yeast extracts through sensomics approaches and electroencephalography.

This study investigated the savory intensity of aroma-active compounds derived from yeast extract Maillard reaction models. Sensory evaluation results revealed that beef flavoring model (28.00 g) exhibited the highest savory perception intensity when the yeast extract FA34 (0.50 g) the added. Eleven aroma-active compounds associated with saltiness perception were identified via solid-phase microextraction and extraction combined with gas chromatography-mass spectrometry/olfactory. The odorant-NaCl mixture model and saltiness intensity evaluation results revealed that thiazole and 4-methylpentanoic acid could significantly (p < 0.05) enhance the saltiness perception of salt solution (5.00 g/L), 2-methylpyrazine, 2-methyl-3-furanthiol, 2,6-dimethylpyrazine, furfuryl mercaptan, and methyl 2-methyl-3-furyl disulfide could significantly (p < 0.01) enhance the saltiness perception of a salt solution (5.00 g/L). Electroencephalography revealed that the main mechanisms underlying aroma-induced saltiness perception enhancement included the strengthening of the saltiness perception signal and prolonging signal stimulation time in the frontal regions of the cerebral cortex.

Characteristics of saltiness-enhancing peptides derived from yeast proteins and elucidation of their mechanism of action by molecular docking.

This study aimed to identify saltiness-enhancing peptides from yeast protein and elucidate their mechanisms by molecular docking. Yeast protein hydrolysates with optimal saltiness-enhancing effects were prepared under conditions determined using an orthogonal test. Ten saltiness-enhancing peptide candidates were screened using an integrated virtual screening strategy. Sensory evaluation demonstrated that these peptides exhibited diverse taste characteristics (detection thresholds: 0.13-0.50 mmol/L). Peptides NKF, LGLR, WDL, NMKF, FDSL and FDGK synergistically or additively enhanced the saltiness of a 0.30% NaCl solution. Molecular docking revealed that these peptides predominantly interacted with TMC4 by hydrogen bonding, with hydrophilic amino acids from both peptides and TMC4 playing a pivotal role in their binding. Furthermore, Leu217, Gln377, Glu378, Pro474 and Cys475 were postulated as the key binding sites of TMC4. These findings establish a robust theoretical foundation for salt reduction strategies in food and provide novel insights into the potential applications of yeast proteins.

Effects of Wheat Oligopeptide on the Baking and Retrogradation Properties of Bread Rolls: Evaluation of Crumb Hardness, Moisture Content, and Starch Crystallization.

Delaying the deterioration of bakery goods is necessary in the food industry. The objective of this study was to determine the effects of wheat oligopeptide (WOP) on the qualities of bread rolls. The effects of WOP on the baking properties, moisture content, and starch crystallization of rolls during the storage process were investigated in this study. The results showed that WOP effectively improved the degree of gluten cross-linking, thereby improving the specific volume and the internal structure of rolls. The FTIR and XRD results showed that the addition of WOP hindered the formation of the starch double helix structure and decreased its relative crystallinity. The DSC results revealed a decrease in the enthalpy change (ΔH) from 0.812 to 0.608 J/g after 7 days of storage with 1.0% WOP addition, further indicating that WOP reduced the availability of water for crystal lattice formation and hindered the rearrangement of starch molecules. The addition of WOP also improved the microstructure of the rolls that were observed using SEM analysis. In summary, WOP is expected to be an effective natural additive to inhibit starch staling and provide new insights into starchy food products.

The Effects of Yeast Protein on Gut Microbiota in Mice When Compared with Soybean Protein and Whey Protein Isolates.

Different protein sources can impact gut microbiota composition and abundance, and also participate in health regulation. In this study, mice were gavaged with yeast protein (YP), soybean protein isolate (SPI), and whey protein isolate (WPI) for 28 days. Body weights showed similar patterns across different protein administration groups. The ileum in YP-supplemented mice exhibited good morphology, and tight-junction (TJ) proteins were slightly upregulated. Immunoglobulin (Ig)A, IgM, and IgG levels in the ileum of different protein groups were significantly increased (p < 0.05). Interleukin (IL)-10 levels were significantly increased, whereas IL-6 levels were significantly reduced in the YP group when compared with the control (C) (p < 0.05). Glutathione peroxidase (GSH-Px) levels in the ileum were significantly increased in the YP group (p < 0.05). These results indicate that YP potentially improved intestinal immunity and inflammatory profiles. The relative abundances of Parabacteroides, Prevotella, and Pseudobutyrivibrio in the YP group were more enriched when compared with the C and SPI groups, and Parabacteroides was significantly upregulated when compared with the WPI group (p < 0.05). Overall, the results indicate that YP upregulates the beneficial bacteria and improves ileal immunity and anti-inflammatory capabilities.

Characterization and sweetness-enhancing effect of peptides from yeast extract based on sensory evaluation and molecular docking approaches.

Yeast extract (YE) is derived from the soluble component in yeast cells, which is rich in peptides and has been used as a sweet-enhancing agent. It has the potential to be utilized to produce natural sweet-flavored peptides or sweet-enhancing peptides. To study the synergistic effect and mechanism of sweetness-enhancing peptides derived from YE, ultrafiltration fraction with molecular weight less than 1 kDa was screened according to sensory analysis, which showed a synergistic sweetening effect in stevioside and mogroside solution. Twenty potential taste peptides were identified from the screened fractions, among which EV, AM, AVDNIPVGPN and VDNIPVGPN showed sweetness-enhancing effects on both stevioside and mogroside. The sweetener-receptor-peptide complex was constructed to investigate the interaction of stevioside and mogroside to taste receptor type 1 member 2 accompanied by these peptides. The results of the molecular docking indicated that new hydrophobic interactions (Leu 279, Pro 308, Val 309, etc.) and hydrogen bonds (Ser 40, Ala 43, Asp 278, etc.) were formed between sweeteners and active sites in the venus flytrap domain. In conclusion, the presence of sweetness-enhancing peptides from YE improved the binding stability of sweeteners and receptors by increasing the binding interaction, especially the hydrophobic interactions, which contribute to the synergistic effect of sweetness-enhancing peptides.

Ultrasound assisted fabrication of the yeast protein-chitooligosaccharide-betanin composite for stabilization of betanin.

Betanin, a water-soluble colorant, is sensitive to light and temperature and is easily faded and inactivated. This study investigated the formation of yeast protein-chitooligosaccharide-betanin complex (YCB) induced by ultrasound treatment, and evaluated its protective effect on the colorant betanin. Ultrasound (200-600 W) increased the surface hydrophobicity and solubility of yeast protein, and influenced the protein's secondary structure by decreasing the α-helix content and increasing the contents of ß-sheet and random coil. The ultrasound treatment (200 W, 15 min) facilitated binding of chitooligosaccharide and betanin to the protein, with the binding numbers of 4.26 ± 0.51 and 0.61 ± 0.06, and the binding constant of (2.73 ± 0.25) × 105 M-1 and (3.92 ± 0.10) × 104 M-1, respectively. YCB could remain the typical color of betanin, and led to a smaller and disordered granule morphology. Moreover, YCB exhibited enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract. This study extends the potential application of the fungal proteins for stabilizing bioactive molecules.

Empagliflozin Induces Vascular Relaxation in Rat Coronary Artery Due to Activation of BK Channels.

Purpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function. Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms. Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 µmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ± 28.51, 78.06 ± 40.98, respectively (p < 0.01 vs Ctrl, n = 3-7; p < 0.001 vs DM+L-EMPA, n = 5-7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-ß1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor. Conclusion: Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism.

Nutritional Values and Bio-Functional Properties of Fungal Proteins: Applications in Foods as a Sustainable Source.

From the preparation of bread, cheese, beer, and condiments to vegetarian meat products, fungi play a leading role in the food fermentation industry. With the shortage of global protein resources and the decrease in cultivated land, fungal protein has received much attention for its sustainability. Fungi are high in protein, rich in amino acids, low in fat, and almost cholesterol-free. These properties mean they could be used as a promising supplement for animal and plant proteins. The selection of strains and the fermentation process dominate the flavor and quality of fungal-protein-based products. In terms of function, fungal proteins exhibit better digestive properties, can regulate blood lipid and cholesterol levels, improve immunity, and promote gut health. However, consumer acceptance of fungal proteins is low due to their flavor and safety. Thus, this review puts forward prospects in terms of these issues.

Glucose fluctuations aggravated the late sodium current induced ventricular arrhythmias via the activation of ROS/CaMKII pathway.

BACKGROUND: Recent evidence revealed that glucose fluctuation might be more likely to cause arrhythmia than persistent hyperglycemia, whereas its mechanisms were elusive. We aimed to investigate the effect of glucose fluctuation on the occurrence of ventricular arrhythmia and its mechanism. METHODS: Streptozotocin (STZ) induced diabetic rats were randomized to five groups: the controlled blood glucose (C-STZ) group, uncontrolled blood glucose (U-STZ) group, fluctuated blood glucose (GF-STZ) group, and GF-STZ rats with 100 mg/kg Tempol (GF-STZ + Tempol) group or with 5 mg/kg KN93 (GF-STZ + KN93) group. Six weeks later, the susceptibility of ventricular arrhythmias and the electrophysiological dysfunctions of ventricular myocytes were evaluated using electrocardiogram and patch-clamp technique, respectively. The levels of reactive oxygen species (ROS) and oxidized CaMKII (ox-CaMKII) were determined by fluorescence assay and Western blot, respectively. Neonatal rat cardiomyocytes and H9C2 cells in vitro were used to explore the underlying mechanisms. RESULTS: The induction rate of ventricular arrhythmias was 10%, 55%, and 90% in C-STZ group, U-STZ group, and GF-STZ group, respectively (P < 0.05). The electrophysiological dysfunctions of ventricular myocytes, including action potential duration at repolarization of 90% (APD90), APD90 short-term variability (APD90-STV), late sodium current (INa-L), early after depolarization (EAD) and delayed after depolarizations (DAD), as well as the levels of ROS and ox-CaMKII, were significantly increased in GF-STZ group. In vivo and ex vivo, inhibition of ROS or ox-CaMKII reversed these effects. Inhibition of INa-L also significantly alleviated the electrophysiological dysfunctions. In vitro, inhibition of ROS increase could significantly decrease the ox-CaMKII activation induced by glucose fluctuations. CONCLUSIONS: Glucose fluctuations aggravated the INa-L induced ventricular arrhythmias though the activation of ROS/CaMKII pathway.

Characterization of the Key Aroma Compounds in Different Yeast Proteins by GC-MS/O, Sensory Evaluation, and E-Nose.

The unique odors of yeast proteins (YPs) are decisive for their application in meat substitutes. Sensory evaluation, electronic nose, and gas chromatography-mass spectrometry/olfactory (GC-MS/O) were combined to characterize the aroma profiles and aroma-active compounds of YPs. The sensory evaluation results indicate that the sweaty aroma had the strongest intensity in YP #10, followed by rice bran, sour, and plastic. The electronic nose could effectively distinguish the aroma differences among five YPs. A total of 27 aroma-active compounds in the five YPs were identified by GC-MS/O. The concentration of 2-methyl-propanoic acid (6.37 µg/kg), butanoic acid (47.46 µg/kg), 3-methyl-butanoic acid (22.50 µg/kg), and indole (943.40 µg/kg) in YP #10's aroma was higher than that of the other YPs. The partial least squares regression method results show that o-cresol, (3S)-3,7-dimethyloct-7-en-1-ol, benzyl alcohol, octanal, 2-methyl-propanoic acid, butanoic acid, 3-methyl-butanoic acid, hexanal, heptanal, and indole were predicted as the potential aroma-active compounds significantly contributing to the aroma profiles of the five YPs. Addition experiments confirmed that the overall aroma profile intensities of the five YP samples were extended with the addition of these ten compounds, verifying their significant contributions.

Yeast protein as a novel dietary protein source: Comparison with four common plant proteins in physicochemical properties.

Currently, with the preference for a healthy diet and increased awareness of reducing the carbon footprint, the demand for protein is becoming more and more diversified. In this study, the physicochemical properties of yeast protein (YP) and four common plant proteins (soy protein isolate, pea protein isolate, wheat gluten, and peanut protein) were compared. The most prevalent secondary structure in YP is the ß-sheet. Furthermore, YP is in an aggregated state, and it has a high surface hydrophobicity. The tryptophan residues are primarily exposed on the polar surface of YP. The results of in vitro digestibility indicated that YP (84.91 ± 0.52%) was a high-quality protein. Moreover, YP has a higher thermal stability and relatively stable low apparent viscosity, which provides ample possibility for its application in food processing and in foods for people with swallowing difficulties. This study provides theoretical basis in the potential of YP as an alternative protein source.

Radiofrequency ablation of premature ventricular contractions guided by robotic magnetic navigation combined with pattern matching filter.

BACKGROUND: This study's intent is to evaluate the usefulness of pattern matching filter (PMF) function combined with robotic magnetic navigation (RMN) in guiding the ablation of premature ventricular contractions (PVCs). HYPOTHESIS: Assume that PMF can improve the outcomes of PVCs ablation using RMN. METHODS: A retrospective analysis was completed consisting of 118 consecutive patients with PVCs who underwent radiofrequency ablation guided by RMN. According to the application of PMF, patients were divided into two groups: 20 patients underwent ablation without PMF (group A), and another 98 patients received ablation incorporating PMF (group B). RESULTS: Compared with group A, the procedure time (135.0 ± 28.3 min vs. 106.3 ± 37.9 min, p = 0.02) in group B was significantly decreased, while the X-ray exposure time (6.0 ± 2.6 min vs. 6.5 ± 3.6 min, p = 0.705) and dose (3.2 ± 2.4 gycm2 vs. 3.9 ± 2.7 gycm2 ，p = 0.208) had no significant difference. Group B had a more than twofold number of points acquired (66.9 ± 23.0 vs. 143.9 ± 68.3, p < 0.001) and required a shorter radiofrequency ablation time (13.2 ± 3.5 min vs. 8.1 ± 2.9 min, p < 0.001). There were no serious complications in either group. The acute success rate was similar [90.0% (18/20) vs. 87.8% (86/98), p = 1.000] in two groups, and the success rate was also similar in the long-term follow-up [83.3% (15/18) vs. 87.2% (75/86), p = 0.776]. CONCLUSIONS: The ablation of PVCs guided by RMN is safe and effective. Combined with the functional capability of PMF, both procedure time and radiofrequency ablation time were significantly decreased.

High-moisture extrusion of yeast-pea protein: Effects of different formulations on the fibrous structure formation.

The demand of meat analogues (MAs) is consistently increasing. The protein materials for MAs are primarily soy, pea, and wheat protein which can not completely meet the growing demand. Hence, this study is focused on the preparation of MAs with up to 50 % yeast protein (YP) instead of pea protein isolate (PPI). In the present study, 0 %, 10 %, 30 %, and 50 % YP powder in dry matter basis were combined with PPI; then the mixtures were used to prepare MAs with fibrous structures using high-moisture extrusion (55 % moisture). The involvement of YP significantly enhanced the hardness of MAs (P < 0.05). The optical and microstructural images illustrated that when YP ratio reached 30 %, obvious fibrous structures still were observed in MAs. Furthermore, MAs containing YP became whiter, which is conducive to reprocessing. With an increase in YP, the bound water content, sheet structures, and exposure of tryptophan residues in MAs increased, whereas the free water content, ß-turn, and random coil structures decreased. Analysis of thermal and rheological behaviors indicated that YP lowered the denaturation temperature of MAs and the viscosity of protein dispersions, which was related to the formation of protein aggregates. Overall, YP can be used to prepare MAs and regulate the fibrous structure in MAs by acting on protein conformations.

Physicochemical and structural properties of meat analogues from yeast and soy protein prepared via high-moisture extrusion.

In this study, yeast and soy protein at different ratios (0:1, 1:9, 2:8, 3:7, 4:6, and 5:5) were used to produce meat analogues (MA) via high-moisture extrusion. According to color analysis, the addition of yeast protein (YP) increased the lightness of MA from 43.12 ± 0.26 (the control) to 50.37 ± 0.46 (50 g/100 g, dry basis). Textural results indicated that when the YP content was 40 g/100 g (dry basis), the hardness, chewiness, and fibrous degree of MA reached the maximum (523.94 ± 11.91 N, 724.55 ± 22.89 N, and 2.06 ± 0.15, respectively), which were higher than the control (419.63 ± 7.52 N, 618.02 ± 14.82 N, and 1.43 ± 0.03, respectively). Furthermore, YP increased the free water ratio, SS bond, and total ß-sheets structure content, while reducing the ß-turn structure content and thermal stability of MA. Overall, YP is a promising protein source for preparing high-quality MA.

Decoding of the Saltiness Enhancement Taste Peptides from the Yeast Extract and Molecular Docking to the Taste Receptor T1R1/T1R3.

The development of saltiness or saltiness enhancement peptides is important to decrease the dietary risk factor of high sodium. Taste peptides in the yeast extract were separated by ultrafiltration and subsequently identified by UPLC-Q-TOF-MS/MS. The 377 identified peptides were placed into the umami receptor T1R1/T1R3. The results showed that eight taste peptides with higher binding energies were screened by molecular virtual docking, and the results revealed that Asp218, Ser276, and Asn150 of T1R1 play key roles in umami docking of peptides. The taste characteristic description and saltiness enhancement effect results suggested that PKLLLLPKP (sourness and umami, 0.18 mM), GGISTGNLN (sourness, 0.59 mM), LVKGGLIP (umami, 0.28 mM), and SSAVK (umami, 0.35 mM) had higher saltiness enhancement effects. The sigmoid curve analysis further confirmed that the taste detection threshold of the GGISTGNLN in the peptide and salt model (157.47 mg/L) was lower than 320.99 mg/L and exhibited a synergistic effect on saltiness perception, whereas SSAVK, PKLLLLPKP, and LVKGGLIP exhibited additive effects on the saltiness perception. This work also corroborated previous research, which indicated that the sourness and umami taste attributes could enhance the saltiness perception.

Identification of novel saltiness-enhancing peptides from yeast extract and their mechanism of action for transmembrane channel-like 4 (TMC4) protein through experimental and integrated computational modeling.

Excessive consumption of sodium salt is one of the important inducers of cardiovascular and cerebrovascular diseases. The reduction of physical labor and attention to health make research on low-sodium salt imminent. Ultrafiltration, gel filtration, preparative high-performance liquid chromatography, and liquid chromatography with tandem mass spectrometry were employed for further purification and identification of the salty enhancing peptides in yeast extracts. Moreover, human transmembrane channel-like 4 (TMC4) was constructed and evaluated by computer-based methods, and salt-enhancing peptides were identified based on its allosteric sites. PN, NSE, NE and SPE were further determined to be salty enhancing peptides through sensory evaluation, and their taste mechanism was investigated. The results presented here suggest that silicon screening focused on TMC4 allosteric sites and sensory evaluation experiments can greatly increase the discoverability and identifiability of salty enhancer peptides, and this strategy is the first to be applied to the development of salty enhancer peptides.

Reduction of sodium chloride: a review.

Sodium chloride (NaCl) is an enjoyable condiment. However, evidence is accumulating to indicate that an excessive intake of Na+ in food may lead to an increased risk of cardiovascular and cerebrovascular diseases. Previous systematic reviews have focused on replacing NaCl with other metal salts (e.g. KCl). However, new salty flavor enhancers (yeast extract, taste peptides, and odor compounds) have yet to be reviewed. This systematic review evaluates the methods for, and feasibility, of NaCl reduction. It defines NaCl reduction and considers the methods used for this purpose, especially the use of flavor enhancers (yeast extract, taste peptides, and odor compounds). © 2022 Society of Chemical Industry.

Atrial Fibrillation Ablation Using Robotic Magnetic Navigation Reduces the Incidence of Silent Cerebral Embolism.

Background: The incidence of silent cerebral embolisms (SCEs) has been documented after pulmonary vein isolation using different ablation technologies; however, it is unreported in patients undergoing with atrial fibrillation (AF) ablation using Robotic Magnetic Navigation (RMN). The purpose of this prospective study was to investigate the incidence, risk predictors and probable mechanisms of SCEs in patients with AF ablation and the potential impact of RMN on SCE rates. Methods and Results: We performed a prospective study of 166 patients with paroxysmal or persistent AF who underwent pulmonary vein isolation. Patients were divided into RMN group (n = 104) and manual control (MC) group (n = 62), and analyzed for their demographic, medical, echocardiographic, and risk predictors of SCEs. All patients underwent cerebral magnetic resonance imaging within 48 h before and after the ablation procedure to assess cerebral embolism. The incidence and potential risk factors of SCEs were compared between the two groups. There were 26 total cases of SCEs in this study, including 6 cases in the RMN group and 20 cases in the MC group. The incidences of SCEs in the RMN group and the MC group were 5.77 and 32.26%, respectively (X2 = 20.63 P < 0.05). Univariate logistic regression analysis demonstrated that ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction were significantly associated with SCEs, and multivariate logistic regression analysis showed that MC ablation was the only independent risk factor of SCEs after an AF ablation procedure. Conclusions: Ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction are associated with SCEs. However, ablation technology is the only independent risk factor of SCEs and RMN can significantly reduce the incidence of SCEs resulting from AF ablation. Clinical Trial Registration: ChiCTR2100046505.

Fractionation and identification of salty peptides from yeast extract.

ABSTRACT: Salty taste is an important sensory attribute in many foods, which stimulates the appetite. But high-salt diets bring many health risks, and salty alternatives should be explored to solve this problem. The salt-reducing agents may impart new odors in food. Therefore, the research should focus on developing a novel agent, which would replace the salt without affecting the taste of the food. Generally, some yeast extracts taste salty and can be used for replacing salts in foods without imparting any additional odor. In this study, we fractionated salty peptides from FA31 (Angel Yeast) by ultrafiltration, gel permeation chromatography, preparative liquid chromatography (pre-HPLC), with the combination of sensory evaluation, and the peptide sequence was identified by ESI-Q-TOF LC/MS as Asp-Asp, Glu-Asp, Asp-Asp-Asp, Ser-Pro-Glu, and Phe-Ile.