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Taste peptides are oligopeptides that enhance both aroma and taste of food, and they are classified into five categories based on their taste characteristics: salty, sour, umami, sweet, bitter, and kokumi peptide. Recently, taste peptides have attracted the attention of several fields of research in food science and commercial applications. However, research on taste receptors of taste peptides and their taste transduction mechanisms are not clearly understood and we present a comprehensive review about these topics here. This review covers the aspects of taste peptides perceived by their receptors in taste cells, the proposed transduction pathway, as well as structural features of taste peptides. Apart from traditional methods, molecular docking, peptidomic analysis, cell and animal models and taste bud biosensors can be used to explore the taste mechanism of taste peptides. Furthermore, synergistic effect, Maillard reaction, structural modifications and changing external environment are employed to improve the taste of taste peptides. Consequently, we discussed the current challenges and future trends in taste peptide research. Based on the summarized developments, taste peptides derived from food proteins potentially appear to be important taste substances. Their applications meet the principles of "safe, nutritious and sustainable" in food development. [ABSTRACT FROM AUTHOR]

Background: Stevia glycosides (SGs) have been widely used as an ideal sugar alternative in the food industry. However, the potential application of SGs mixture in the diets of weaned piglets remains unexplored. This study aimed to investigate the effect of dietary SGs mixture supplementation on growth performance, gene expression of gut chemoreceptors, and antioxidant capacity in weaned piglets. Methods: A total of 216 weaned piglets (Duroc × Landrace × Yorkshire, 7.36 ± 0.04 kg body weight) were randomly assigned to 6 groups (6 pens/group with 6 piglets/pen), and were fed with the basal diet supplemented with 0, 100, 150, 200, 250, or 300 mg/kg SGs mixture for 42 days. The serum, liver, longissimus thoracis, and jejunal samples were collected on day 43. Results: The results showed that inclusion the SGs mixture in the diet did not have a significant impact on growth performance from days 1 to 28 (P > 0.05). But increasing the concentration of SGs mixture tended to linearly decrease the average daily gain from days 1 to 42 (P = 0.052). However, 150 mg/kg SGs mixture supplementation significantly increased the mRNA expression of taste receptor family 1 member 2 (T1R2) and glucose transporters 2 (GLUT2) in the jejunum (P < 0.05), while 150 and 200 mg/kg SGs mixture supplementation significantly increased T1R3 mRNA expression (P < 0.05). Moreover, 150 mg/kg SGs mixture supplementation significantly reduced serum malondialdehyde content (P < 0.05). Increasing the concentration of SGs mixture linearly and quadratically increased serum total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity, as well as hepatic T-SOD, GSH-Px activity, and muscle total antioxidant capacity contents (P < 0.05). Furthermore, piglets fed a diet supplemented with 100 mg/kg SGs mixture had higher serum T-SOD, CAT, and GSH-Px activities compared with the other treatments (P < 0.05). Conclusions: Therefore, our results suggest that dietary 100 ~ 150 mg/kg SGs mixture supplementation modulates gene expression of sweet taste recognition receptors and glucose transporters, while also enhancing the antioxidant capacity of weaned piglets. [ABSTRACT FROM AUTHOR]

The sense of taste is mediated primarily by taste buds on the tongue. These multicellular sensory organs are induced, patterned and become innervated during embryogenesis such that a functional taste system is present at birth when animals begin to feed. While taste buds have been considered ectodermal appendages, this is only partly accurate as only fungiform taste buds in the anterior tongue arise from the ectoderm. Taste buds found in the posterior tongue actually derive from endoderm. Nonetheless, both anterior and posterior buds are functionally similar, despite their disparate embryonic origins. In this review, I compare the development of ectodermal vs endodermal taste buds, highlighting the many differences in the cellular and molecular genetic mechanisms governing their formation. • In vertebrates taste buds reside on the tongue, and the head and trunk of some fish. • Anterior taste buds derive from embryonic ectoderm; posterior buds are endodermal. • Embryonic origins underlie differences in taste specification and patterning. • Taste buds house 5 functional cell types that detect sweet, sour, bitter, etc. • Tight regulation of taste receptor cell fate is required for taste function. [ABSTRACT FROM AUTHOR]

TAS2Rs are a family of G protein-coupled receptors that function as bitter taste receptors in vertebrates. Mammalian TAS2Rs have historically garnered the most attention, leading to our understanding of their roles in taste perception relevant to human physiology and behaviors. However, the evolution and functional implications of TAS2Rs in other vertebrate lineages remain less explored. Here, we identify 9,291 TAS2Rs from 661 vertebrate genomes. Large-scale phylogenomic analyses reveal that frogs and salamanders contain unusually high TAS2R gene content, in stark contrast to other vertebrate lineages. In most species, TAS2R genes are found in clusters; compared to other vertebrates, amphibians have additional clusters and more genes per cluster. We find that vertebrate TAS2Rs have few one-to-one orthologs between closely related species, although total TAS2R count is stable in most lineages. Interestingly, TAS2R count is proportional to the receptors expressed solely in extra-oral tissues. In vitro receptor activity assays uncover that many amphibian TAS2Rs function as tissue-specific chemosensors to detect ecologically important xenobiotics. Author summary: Most vertebrates are able to taste five cardinal tastes: sweet, sour, salty, umami, and bitter, using a specialized suite of receptor proteins. Amphibians have a much larger repertoire of bitter taste receptors, called TAS2Rs, than other vertebrates. We investigated the evolutionary history of TAS2Rs across vertebrates, and found that frogs and salamanders experienced a ~10-fold increase in the number of receptors, possibly associated with shifts in the selective pressures for the perception of bitter chemicals. Furthermore, this increase may have been facilitated by the TAS2Rs' location in the genome. We explored TAS2R expression in five amphibian species, and found expression in multiple tissues beyond the tongue. Interestingly, species with larger TAS2R repertoires exhibited more expression outside the mouth, which could mean that amphibian TAS2R expansion may have been related to the acquisition of new sensing roles for some genes. Finally, we evaluated whether some TAS2Rs were able to perceive known or suspected bitterants. Most receptors reacted to at least one of the tested substances, and some showed interesting patterns. For instance, a receptor expressed in the skin of toads was able to sense toad toxins, suggesting TAS2R receptors may play roles beyond tasting food in the chemical ecology of amphibians. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cyclocarya paliurus, as a new food resource, is utilized extensively in human and animal diets due to its bioactive compounds, health benefits, and its highly prized sweet flavor. This study aimed to investigate the sweet‐taste ingredient of C. paliurus leaves. RESULTS: Five new dammarane triterpenoid glycosides were isolated and identified as qingqianliutianosides A–E (1–5) by comprehensive spectroscopic data analysis and a single crystal X‐ray diffraction experiment. Qingqianliutianoside A (1) and qingqianliutianoside C (3), present in relatively high quantities in the plant, were shown to exhibit sweetness by sensory evaluation and electronic tongue analysis. Further monitoring was conducted on the content changes in 3 in leaves at different growth stages, indicating that 3 reached its peak content in April and then showed a decreasing trend. Molecular docking studies revealed that T1R2/T1R3 receptors Ser212, Ser105, Thr239, Asn380, Thr305, and Val381 may play critical roles, demonstrating that hydrogen bonding and hydrophobic interactions were the dominant interaction forces between all of the identified compounds and the active sites in the Venus flytrap module of the T1R2/T1R3 receptors. CONCLUSION: Qingqianliutianosides A–E are promising natural source sugar substitutes for use in functional foods and beverages. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The ENaC receptor acts as a taste receptor to recognize and perceive salty substances. This study explored the mechanisms by which the ENaC taste receptor recognizes and binds mushroom-derived salty peptides using molecular interaction and molecular simulation. The three subunits α, β, and γ of the ENaC taste receptor (SCNN1α, SCNN1β, and SCNN1γ) showed different recognition characteristics for the salty peptide. The salty peptide binding to the SCNN1α receptor was an entropy-driven reaction, while to SCNN1β and SCNN1γ was an enthalpy-driven reaction. With the salty peptide spatial resistance increasing, salty peptides bind to the ENaC taste receptor shifted from receptor pockets binding to receptor surface binding, with salty octapeptide ESPERPFL preferentially binding to amino acid residues in the receptor pockets 2, 3, and 4, salty nonapeptide KSWDDFFTR and decapeptide RIEDNLVIIR binding to amino acid residues in the pockets 2, 4 and on the surface of the receptor, and salty undecapeptide GQEDYDRLRPL preferentially binding to the atoms on the surface of the receptor. Receptor extracellular arginine, glutamate, aspartate, and lysine residues were the critical amino acid residues recognized to bind salty peptides. The salty peptide-ENaC receptor binding complex was stable around 0.3 nm, and the tight and multisite binding was the main reason the ENaC receptor sensed the salty peptide, enabling it to exert its taste effect. This research can provide a theoretical basis for understanding the taste properties of salty peptides recognized and perceived by the ENaC taste receptor. [ABSTRACT FROM AUTHOR]

Protein-Protein Interactions (PPIs) are a key interface between virus and host, and these interactions are important to both viral reprogramming of the host and to host restriction of viral infection. In particular, viral-host PPI networks can be used to further our understanding of the molecular mechanisms of tissue specificity, host range, and virulence. At higher scales, viral-host PPI screening could also be used to screen for small-molecule antivirals that interfere with essential viral-host interactions, or to explore how the PPI networks between interacting viral and host genomes co-evolve. Current high-throughput PPI assays have screened entire viral-host PPI networks. However, these studies are time consuming, often require specialized equipment, and are difficult to further scale. Here, we develop methods that make larger-scale viral-host PPI screening more accessible. This approach combines the mDHFR split-tag reporter with the iSeq2 interaction-barcoding system to permit massively-multiplexed PPI quantification by simple pooled engineering of barcoded constructs, integration of these constructs into budding yeast, and fitness measurements by pooled cell competitions and barcode-sequencing. We applied this method to screen for PPIs between SARS-CoV-2 proteins and human proteins, screening in triplicate >180,000 ORF-ORF combinations represented by >1,000,000 barcoded lineages. Our results complement previous screens by identifying 74 putative PPIs, including interactions between ORF7A with the taste receptors TAS2R41 and TAS2R7, and between NSP4 with the transmembrane KDELR2 and KDELR3. We show that this PPI screening method is highly scalable, enabling larger studies aimed at generating a broad understanding of how viral effector proteins converge on cellular targets to effect replication. [ABSTRACT FROM AUTHOR]

Genetic variations in taste receptors are associated with gustatory perception and obesity, which in turn affects dietary preferences. Given the increasing tendency of people with obesity choosing sweet, high-fat meals, the current study assessed the cross-regulation of two polymorphisms of the sweet taste receptor (T1R2/T1R3), rs35874116 and rs307355, on fat sensitivity in Indian adults. We investigated the association between taste sensitivity and BMI in the T1R2, T1R3, and CD36 polymorphic and non-polymorphic groups. The general labelled magnitude scale (gLMS) was used to assess the taste sensitivity of 249 participants in addition to anthropometric data. TaqMan Probe-based RT-PCR was employed to determine the polymorphisms. Additionally, the colorimetric method utilizing 3, 5-dinitro salicylic acid was used to evaluate the participants' salivary amylase activity. The mean detection thresholds for linoleic acid (LA) and sucrose were greater in individuals with obesity (i.e., 0.97 ± 0.08 mM and 0.22 ± 0.02 M, respectively) than in healthy adults (p < 0.0001), indicating lower sensitivity. Moreover, it was found that a greater proportion of persons with obesity fall into the polymorphic groups (i.e., 52% with genotype CD36 AA, 44% with genotype T1R2 CC, and 40% with genotype T1R3 TT). All three single nucleotide polymorphisms support the Hardy–Weinberg equilibrium (p = 0.78). The Pearson correlation analysis between LA and the sucrose detection threshold revealed a significant (p < 0.0001) positive relationship with an r value of 0.5299. Moreover, salivary amylase activity was significantly (p < 0.05) higher in the polymorphic sub-groups. The results of our study imply that genetic variations in T1R2/T1R3 receptors affect perception of both sweetness and fat, which may have an effect on obesity. [ABSTRACT FROM AUTHOR]

Taste receptor type 1 subunit 3 (T1R3) is a G protein-coupled receptor encoded by the TAS1R3 gene that can be specifically activated by certain sweeteners or umami agents for sweet/umami recognition. T1R3 is a potential target for regulating male reproduction. However, studies on the impact of non-nutritive sweeteners on reproduction are limited. In the present study, we evaluated the impact of the non-nutritive sweeteners (saccharin sodium, sucralose and acesulfame-K) on testosterone synthesis in testicular Leydig cells of Xiang pigs by comparing the relative abundance of mRNA transcripts and protein expression of T1R3, steroidogenic related factors, and intracellular cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), as well as testosterone levels using Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). To clarify the specific mechanism, a dual luciferase assay was used to uncover the relationship between the transcription factors and steroidogenic enzyme. The acute intratesticular injection of a typical non-nutritive sweeteners was conducted to verify this impact in mouse. The results showed that saccharin sodium not only enhanced T1R3 expression in Leydig cells of Xiang pigs, but also caused significant increases in testosterone, cAMP, PKA, phosphorylation of specificity protein 1 (p-SP1), total protein of specificity protein 1 (SP1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) (P < 0.05). Similarly, treatment of Leydig cells with sucralose and acesulfame-K also increased testosterone level, protein expression of T1R3, 17-α-hydroxylase/17, 20-lyase (CYP17A1), and 3β-HSD1 (P < 0.05). Treatment with SQ22536 (an adenylate cyclas inhibitor) or H89 (a PKA inhibitor) significantly reduced saccharin sodium-induced protein levels of p-SP1, StAR, CYP17A1, and 3β-HSD1 (P < 0.05). In addition, a dual luciferase assay further demonstrated that SP1 significantly increased the promoter activity of CYP17A1 (P < 0.05). When mouse testes were injected with saccharin sodium, T1R3, p-SP1, CYP17A1, and 3β-HSD1 were upregulated, leading to a significant testicular increase in testosterone and cAMP levels (P < 0.05). These results suggest a mechanism by which the taste receptor T1R3 regulates testosterone production, and this mechanism may be linked to the cAMP-PKA pathway. Understanding the interrelationship between T1R3 and the cAMP-PKA-SP1 pathway contributes to clarify the regulatory mechanisms of male reproduction. [ABSTRACT FROM AUTHOR]

Analysis of genome-scale evolution has been difficult in large, endangered animals because opportunities to collect high-quality genetic samples are limited. There is a need for novel field-friendly, cost-effective genetic techniques. This study conducted an exome-wide analysis of a total of 42 chimpanzees (Pan troglodytes) across six African regions, providing insights into population discrimination techniques. Wild chimpanzee DNA was extracted noninvasively from collected fecal samples using the lysis-buffer storage method. To target genome-scale regions of host DNA, exome-capture sequencing was performed using cost-effective baits originally designed for humans (closely related to chimpanzees). Multivariate analysis effectively discriminated differences in local populations, aiding in the identification of samples' geographical origins. Exome-wide heterozygosity was negatively correlated significantly with genome-wide nonsynonymous–synonymous substitution ratios, suggesting that mutation loads exist at the local population level. Exome sequences revealed functional diversity and protein-coding gene divergence. Segregating pseudogenes were comprehensively annotated, with many being population-specific and others shared among populations. Focusing on multicopy chemosensory receptor genes, the segregating pseudogenes OR7D4 (an olfactory receptor) and TAS2R42 (a bitter taste receptor) were shared among western and eastern chimpanzees. Overall, our analytical framework offers ecological insights into chimpanzees and may be applicable to other organisms. [ABSTRACT FROM AUTHOR]

Glucose and energy metabolism disorders are the main reasons induced type 2 diabetes (T2D) and obesity. Besides providing energy, dietary nutrients could regulate glucose homeostasis and food intake via intestinal nutrient sensing induced gut hormone secretion. However, reviews regarding intestinal protein sensing are very limited, and no accurate information is available on their underlying mechanisms. Through intestinal protein sensing, dietary proteins regulate glucose homeostasis and food intake by secreting gut hormones, such as glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP). After activating the sensory receptors, such as calcium-sensing receptor (CaSR), peptide transporter-1 (PepT1), and taste 1 receptors (T1Rs), protein digests induced Ca2+ influx and thus triggered gut hormone release. Additionally, research models used to study intestinal protein sensing have been emphasized, especially several innovative models with excellent physiological relevance, such as co-culture cell models, intestinal organoids, and gut-on-a-chips. Lastly, protein-based dietary strategies that stimulate gut hormone secretion and inhibit gut hormone degradation are proposed for regulating glucose homeostasis and food intake. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Inflammatory bowel disease (IBD), a persistent gastrointestinal disease, is featured with impaired gut immunity. Previous studies have demonstrated that tuft cells can regulate the intestinal type 2 immune response by activating downstream ILC2 and Th2 cells and repair gut barrier upon invasion of parasitic helminths, bacteria, protozoans, and enteritis through different chemo-sensing receptors, such as bitter taste receptors. Berberine is a widely used in the treatment of diarrhea in clinic, however the mechanism underlying this effect is not clear. In this study, we aim to explore the relationship between berberine and tuft cells in dextran sulfate sodium (DSS) -induced colitis. Results: Our data showed that berberine significantly ameliorated DSS-induced colitis and regulating type 2 innate immune lymphocytes (ILC2) and Th2 immune cells via tuft cells in the gut. Furthermore, the effect of berberine on colitis was partially abolished by U73122, a bitter taste receptor inhibitor, suggesting that bitter taste signalling pathway played an important role in the effect of berberine on relieving colitis. Conclusions: Berberine ameliorates dextran sulfate sodium -induced colitis through tuft cells and bitter taste signalling. Our study reveals the unique pharmacological mechanisms of berberine in the context of colitis, laying the foundation for further clinical applications of this compound. [ABSTRACT FROM AUTHOR]

Taste receptors, first described for their gustatory functions within the oral cavity and oropharynx, are now known to be expressed in many organ systems. Even intraoral taste receptors regulate non-sensory pathways, and recent literature has connected bitter taste receptors to various states of health and disease. These extragustatory pathways involve previously unexplored, clinically relevant roles for taste signaling in areas including susceptibility to infection, antibiotic efficacy, and cancer outcomes. Among other physicians, otolaryngologists who manage head and neck diseases should be aware of this growing body of evidence and its relevance to their fields. In this review, we describe the role of extragustatory taste receptors in head and neck health and disease, highlighting recent advances, clinical implications, and directions for future investigation. Additionally, this review will discuss known TAS2R polymorphisms and the associated implications for clinical prognosis. [ABSTRACT FROM AUTHOR]

Three new triterpene glycosides were isolated from Deutzia x hybrida "Strawberry Fields" cultivar via aqueous–ethanolic extraction of the roots, including one derivative of sumaresinolic acid and two of echinocystic acid: 3-O-β-D-glucuronopyranosylsumaresinolic acid 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester, 3-O-β-D-glucuronopyranosylechinocystic acid 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester, and 3-O-α-L-arabinopyranosyl-(1→3)-β-D-glucuronopyranosylechinocystic acid 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester. As none of the isolated saponins were previously documented in the literature, their structural elucidation required extensive 1D and homo- and heteronuclear 2D NMR spectroscopy, as well as mass spectrometry analysis. All three glycosides were tested for their stimulatory activity of the sweet taste receptor TAS1R2/TAS1R3. It is the first chemical and biological investigation of Deutzia x hybrida "Strawberry Fields" as well as the first report of sumaresinolic acid glycosides in Deutzia genus. [ABSTRACT FROM AUTHOR]

Bitter taste perception is crucial for animal survival. By detecting potentially harmful substances, such as plant secondary metabolites, as bitter, animals can avoid ingesting toxic compounds. In vertebrates, this function is mediated by taste receptors type 2 (T2Rs), a family of G protein-coupled receptors (GPCRs) expressed on taste buds. Given their vital roles, T2Rs have undergone significant selective pressures throughout vertebrate evolution, leading to frequent gene duplications and deletions, functional changes, and intrapopulation differentiation across various lineages. Recent advancements in genomic and functional research have uncovered the repertoires and functions of bitter taste receptors in a wide range of vertebrate species, shedding light on their evolution in relation to dietary habits and other ecological factors. This review summarizes recent research on bitter taste receptors and explores the mechanisms driving the diversity of these receptors from the perspective of vertebrate ecology and evolution. [ABSTRACT FROM AUTHOR]

Aspartame is a high potency artificial sweetener which is popularly used in foods and beverages. The species-dependent sweet taste toward aspartame has not been completely understood. In a recent publication, we reported that the prosimians Lemuriformes species, which are proposed as aspartame nontasters, could taste aspartame based on the sequence and structure analysis. In this study, by mutagenesis, cell-based functional analysis and molecular simulations, we reveal that Lemuriformes species can respond to aspartame at the cell-based receptor activity level. Furthermore, it is proved that the conserved critical residues D142 and S40 mediate the species-dependent sweet taste toward aspartame. This research provides a deeper insight on the species taste, structure-activity relationship and evolution for eliciting the sweetness of this important synthetic sweetener. • The Tas1R2/Tas1R3 of Lemuriformes species Coquerel's sifaka can respond to aspartame. • Lemuriformes species gray mouse and ring-tailed lemurs are also aspartame tasters. • Two critical residues D142 and S40 mediate the species-dependent taste to aspartame. • Sequence alignment indicates conserved residues involved in aspartame recognition. • Molecular simulations show essential residues of receptor interacting with aspartame. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) regulate multiple cellular responses and represent highly successful therapeutic targets. The mechanisms by which agonists activate the G protein are unclear for many GPCR families, including the bitter taste receptors (TAS2Rs). We ascertained TAS2R5 properties by live cell-based functional assays, direct binding affinity measurements using optical resonators, and atomistic molecular dynamics simulations. We focus on three agonists that exhibit a wide range of signal transduction in cells despite comparable ligand–receptor binding energies derived from direct experiment and computation. Metadynamics simulations revealed that the critical barrier to activation is ligand-induced opening of the G protein between the α-helical (AH) and Ras-like domains of Gα subunit from a precoupled TAS2R5-G protein state to the fully activated state. A moderate agonist opens the AH-Ras cleft from 22 Å to 31 Å with an energy gain of −4.8 kcal mol−1, making GDP water-exposed for signaling. A high-potency agonist had an energy gain of −11.1 kcal mol−1. The low-potency agonist is also exothermic for Gα opening, but with an energy gain of only −1.4 kcal mol−1. This demonstrates that TAS2R5 agonist-bound functional potencies are derived from energy gains in the transition from a precoupled complex at the level of Gα opening. Our experimental and computational study provides insights into the activation mechanism of signal transduction that provide a basis for rational design of new drugs. [ABSTRACT FROM AUTHOR]

The sweet taste of saccharides, such as sucrose and glucose, and other sweeteners is known to result from activation of the TAS1R2/R3 receptor expressed in taste receptor cells (TRCs) of the taste bud. Recent reports have suggested the existence of an additional sweet taste signaling pathway for metabolizable saccharides that is dependent on the activity of glucose transporters, especially SGLT1, also expressed in TRCs. We have investigated the potential contribution of SGLT1 to glucose taste signaling in humans. Concentration-response analysis of glucose mediated changes in membrane potential measured in Chinese hamster ovary (CHO) cells transiently expressing the human SGLT1 (hSGLT1) yielded an EC50 value of 452 μM. The SGLT inhibitor phlorizin inhibited the membrane potential response to 10 mM glucose with an IC50 of 3.5 μM. In contrast, EC50 values of 127 and 132 mM were obtained from concentration-response analysis of glucose taste in vehicles of water or 20 mM NaCl, respectively, by rapid throughput taste discrimination with human subjects. Lactisole, an antagonist of TAS1R2/R3, at a concentration of 1 mM completely inhibited taste responses to glucose concentrations of 250 mM and below. Phlorizin (0.2 mM) and the high potency SGLT1-selective inhibitor mizagliflozin (10 μM) failed to inhibit glucose taste detection measured at peri-threshold concentrations in the rapid throughput taste discrimination assay. A Yes/No experiment using the taste discrimination assay revealed that 0.2 mM phlorizin was discriminable from water for some subjects. Taken together the results indicate that agonist activation of TAS1R2/R3 is sufficient to account for all glucose taste without contribution by an alternative SGLT-mediated signaling pathway. Furthermore, the taste of phlorizin could be a confounding variable for studies evaluating a role for SGLTs in taste. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs) expressed orally and extraorally, elicit signaling in response to a large set of tastants. Among 25 functional TAS2Rs encoded in the human genome, TAS2R14 is the most promiscuous, and responds to hundreds of chemically diverse ligands. Here we present the cryo–electron microscopy (cryo-EM) structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to flufenamic acid (FFA), a clinically approved nonsteroidal anti-inflammatory drug. The structure reveals an unusual binding mode, where two copies of FFA are bound at distinct pockets: one at the canonical receptor site within the trans-membrane bundle, and the other in the intracellular facet, bridging the receptor with gustducin. Together with a pocket-specific BRET-based ligand binding assay, these results illuminate bitter taste signaling and provide tools for a site-targeted compound design. Bitter taste receptors (TAS2Rs) are a subfamily of G-protein coupled receptors (GPCRs). Here, the authors report a cryo-EM structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to an anti-inflammatory drug flufenamic acid (FFA). [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Protein hydrolysates possess various bioactive functions (e.g. antioxidant), but their bitter taste is unacceptable to most consumers. In the present study, a novel approach for debittering was introduced, which involved the utilization of a hydrophobic compound, curcumin (Cur). Soy protein hydrolysates (SPH), prepared through alcalase hydrolysis, served as the research model for this investigation.It was found that bitter intensity of SPH was dominated by the hydrophobic amino acid residues, and the addition of Cur could remarkably reduce bitterness. The debittering mechanism is attributed to the direct binding of Cur to the exposed hydrophobic amino acid residues of SPH via hydrophobic interaction, thereby shielding the hydrophobic bitter groups and hindering their interaction with the bitter taste receptors. Moreover, this debittering strategy leads to the generation of stable nanoparticles with a Cur‐core/SPH‐shell architecture, which can significantly improve the antioxidant capacity of SPH compared to those using biomacromolecules for encapsulation.Using curcumin as a hydrophobic core is a facile and feasible strategy with bifunction of debittering as well as improving bioactive effect of SPH, which may extend its application in foods. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Extraoral bitter taste receptors offer intriguing potential for modulating metabolism and the gut-brain axis through dietary interventions. Our understanding of these receptors is limited, and data on their effects on ageing are scarce. The complexity conveyed by their high diversity, low expression levels and species-dependent variability challenges our comprehension. We used real-time PCR to examine the relative abundance of multiple TAS2R across different segments of gastrointestinal mucosa in four human cohorts and related them to enteroendocrine secretions at the colon site. TAS2R14 exhibited the highest expression levels in all analyzed tissues. In contrast, TAS2R39, -38 and -42 consistently exhibited lower expression levels. Ageing was found to upregulate TAS2R4, -5, -13, -20 and GLP-1 mRNA in the descending colon. Stimulating TAS2R14 in Hutu-80 cells induced GLP-1 secretion, while stimulating TAS2R5 modulated GLP-1 and PYY secretion. Given the modifications TAS2R agonists may undergo along the GIT, as well as the distinctive expression patterns and possible functional roles of TAS2R receptors along the intestinal tract, our findings suggest the viability of a targeted strategy aimed at enhancing specific functions to improve health outcomes. This study offers valuable insights into the intricate interplay between bitter taste receptors, gut physiology and potential dietary interventions. [ABSTRACT FROM AUTHOR]

Summary: The emergence of kokumi sensation as a flavour enhancer prompted the search for cost effective and the sustainable production of kokumi flavour substances (KS), including small γ‐glutamyl peptides (GGP) and aromatic free amino acids (FAA). We sought to investigate the potential of mechanically deboned meat (MDM) from beef, mutton, lamb and venison for KS production through enzymatic γ‐glutamylation. Liquid chromatography‐mass spectrometry (LC–MS) and in vitro calcium‐sensing receptor (CaSR) activity assays were utilised to identify GGPs and their kokumi intensity, respectively. The enzymatic method significantly increased GGP and FAA in all MDM samples with differences in individual peptides across the species. Notably, all four sources of MDM activated CaSR in a dose‐dependent manner, displaying varying potency and efficacy levels. Beef, lamb and mutton showed a similar range of higher potency, while venison exhibited lower potency but higher efficacy. The thermal stability of γ‐glutamylated beef samples, used as an exemplar, was confirmed at temperatures of 80 °C, 120 °C and 150 °C. Given these findings, MDM represents a promising substrate for KS production and warrants further investigation to assess its practical applicability for enhancing kokumi flavour in the food industry. [ABSTRACT FROM AUTHOR]

Mammals induce an innate aversive response by sensing H+ dissociated from sour substances to prevent the ingestion of harmful substances. Several sour taste candidate receptors have been ruled out over the past decades, only in recent years Otopetrinl (Otop1) has been identified as a sour taste receptor, and sour taste neurotransmitters and sensing pathways have been discovered. This paper reviewed three sour taste perception pathways, detailing the structure of the Otop1 sour taste receptor and its function. The Otop1 signaling pathway was explained with emphasis on the H+ inward flow blocking the inwardly-rectifying potassium channel 2.1 (Kir2.1) to enhance cell depolarization, the release of the activating sour taste neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), and the pathway of sour taste information from the periphery to the centre via. The effects of specific diet, individual differences, transmembrane state perception, and disease on sour taste perception were discussed. The aim was to understand the causes of changes in personal sour taste perception, to provide a theoretical reference for the development of sour foods for different populations and looked forward to future research on unknown signaling pathways in sour taste transmission. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Condiments (such as sodium chloride and glutamate sodium) cause consumers to ingest too much sodium and may lead to a variety of diseases, thus decreasing their quality of life. Recently, a salt reduction strategy using flavor peptides has been established. However, the development of this strategy has not been well adopted by the food industry. There is an acute need to screen for peptides with salty and umami taste, and to understand their taste characteristic and taste mechanism. This review provides a thorough analysis of the literature on flavor peptides with sodium-reducing ability, involving their preparation, taste characteristic, taste mechanism and applications in the food industry. Flavor peptides come from a wide range of sources and can be sourced abundantly from natural foods. Flavor peptides with salty and umami tastes are mainly composed of umami amino acids. Differences in amino acid sequences, spatial structures and food matrices will cause different tastes in flavor peptides, mostly attributed to the interaction between peptides and taste receptors. In addition to being used in condiments, flavor peptides have also anti-hypertensive, anti-inflammatory and anti-oxidant abilities, offering the potential to be used as functional ingredients, thus making their future in the food industry extremely promising. [ABSTRACT FROM AUTHOR]

Sucrose provides both sweetness and energy by binding to both Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose and aspartame only bind to one specific domain (VFD2) of T1R2, resulting in high-intensity sweetness. In this study, we investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites: VFD2, VFD3, transmembrane domain 2 (TMD2), and TMD3 through binding experiments and computational docking studies. Our docking results reveal multiple binding sites for the tested ligands, including the radiolabeled ligands. Our experimental evidence demonstrates that the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to the high-affinity state for steviol glycosides. These findings provide a mechanistic understanding of the structure and function of this heterodimeric sweet taste receptor. Sucrose and other non-caloric sweeteners can bind to different domains of the heterodimeric sweet taste receptor (T1R2/T1R3), resulting in different levels of sweetness. Here, the authors investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites of T1R2/T1R3 through binding experiments and computational docking studies, revealing multiple binding sites for the tested ligands and structural– function correlations of ligand–receptor interactions. [ABSTRACT FROM AUTHOR]

Sea robins, fish with legs, walk on the ocean bottom. They have evolved taste receptors on their legs that direct digging to access prey. Examining these structures and behaviors advances our understanding of the origin of novel phenotypes. [ABSTRACT FROM AUTHOR]

How do animals evolve new traits? Sea robins are fish that possess specialized leg-like appendages used to "walk" along the sea floor. Here, we show that legs are bona fide sense organs that localize buried prey. Legs are covered in sensory papillae that receive dense innervation from touch-sensitive neurons, express non-canonical epithelial taste receptors, and mediate chemical sensitivity that drives predatory digging behavior. A combination of developmental analyses, crosses between species with and without papillae, and interspecies comparisons of sea robins from around the world demonstrate that papillae represent a key evolutionary innovation associated with behavioral niche expansion on the sea floor. These discoveries provide unique insight into how molecular-, cellular-, and tissue-scale adaptations integrate to produce novel organismic traits and behavior. [Display omitted] • Sea robins are walking fish that use novel leg-like appendages as sensory organs • A small clade of specialists elaborated sensory legs for locating buried prey • Sensation is mediated by mechanosensitive neurons and epithelial taste receptors • Leg papillae mediate sensory specialization across species and development Allard et al. exploit an unusual fish called the sea robin, which possesses six leg-like sensory appendages, to understand how novel traits arise and diversify to drive new behaviors. [ABSTRACT FROM AUTHOR]

The molecular basis of sweet taste toward various amino acids has not been fully elucidated. In this study, by correlation of their sweetness intensities with molecular properties, it is revealed that hydrophobic or dispersion force between side chains and sweet taste receptor (Tas1R2/Tas1R3) plays a prominent role for eliciting sweetness. Furthermore, the interaction modes of 13 amino acids with receptor indicate that amino (AH) and carboxyl (B) glucophores of different amino acids interact with identical residues of receptor, while the hydrophobic side chains (X glucophores) conduct distinct topological orientations with receptor, determining their chirality selection and sweetness intensities. Molecular dynamics analysis shows that sweet d‐amino acids move toward the hydrophobic transmembrane domain during activation with more contact numbers with receptor than nonsweet l‐amino acids, providing a mechanistic elucidation of previous inconsistent sensory evaluation results of specific amino acids. Moreover, by comparison with the interactions of a dipeptide sweetener, aspartame with Tas1R2/Tas1R3 and nonsweet l‐glutamate with class C G protein‐coupled receptors, we conclude that a complementary interaction mode with both hydrophilic and hydrophobic contacts accounts for the molecular origin of their sweet taste, presenting in‐depth insights and valuable guidelines for further molecular designs or modifications of amino acids‐derived sweeteners. [ABSTRACT FROM AUTHOR]

In 2004, we started the initial attempt to evaluate the efficacy of SLIT for Japanese cedar pollinosis (JCP) using Japanese cedar (JC) pollen extract solution through a multicenter, placebo-controlled, double-blind comparative study. Based on its success in demonstrating the substantial efficacy of SLIT, we next conducted a larger-scale study by administering JC pollen to all JCP patients recruited. It was because of aiming to ascertain the effectiveness and safety of SLIT and its underlying mechanisms by comparing high- and non-responder patients. Despite limitations posed by liquid medication, significant effectiveness and safety demonstrated by the 2-year treatment served as the foundation for launching the first SLIT medicine for JCP, in 2014. Furthermore, in addition to the clearer Th1/Th2-imbalanced property in the high-responders, the possible involvement of bitter taste receptors in CD4+ T cells, apoptosis pathways in CD4+ T cells and basophils, and inducing a mast cell degranulation inhibitory molecule in the effect of SLIT was demonstrated. To solve the limitations posed by liquid medication, clinical trials evaluating JC pollen sublingual tablets started in 2014. Due to the minimal side effects, ease of administration, and convenient storage, the sublingual tablet medicine was launched in 2018. Giving the ongoing rise in demand for SLIT and considering that more than 1% of JCP patients are currently undergoing SLIT, the practical use of this treatment for multiple allergens is becoming increasingly important. [ABSTRACT FROM AUTHOR]

The gustatory system is responsible for detecting and evaluating the palatability of the various chemicals present in food and beverages. Taste bud cells, located primarily on the tongue, communicate with the gustatory sensory neurons by means of neurochemical signals, transmitting taste information to the brain. It has also been found that the endocannabinoid system (ECS) may modulate food intake and palatability, and that taste bud cells express cannabinoid receptors. The purpose of this study was to investigate the expression of cannabinoid and cannabinoid-related receptors in the gustatory cells of the papillae vallatae and foliatae of ten piglets. Specific antibodies against the cannabinoid receptors (CB1R and CB2R), G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) were applied on cryosections of lingual tissue; the lingual tissue was also processed using Western blot analysis. Cannabinoid and cannabinoid-related receptors were found to be expressed in the taste bud cells and the surrounding epithelial cells. The extra-papillary epithelium also showed strong immunolabeling for these receptors. The results showed that these receptors were present in both the taste bud cells and the extra-gustatory epithelial cells, indicating their potential role in taste perception and chemesthesis. These findings contributed to understanding the complex interactions between cannabinoids and the gustatory system, highlighting the role of the ECS within taste perception and its potential use in animal production in order to enhance food intake. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (TAS2Rs) are not only expressed in the oral cavity but also in skin. Extraoral TAS2Rs are thought to be involved in non‐taste perception and tissue‐specific functions. Keratinocytes that express TAS2Rs in the skin provide a first‐line defense against external threats. However, the functional roles of these receptors in host defense remain unclear. Here, we demonstrated the sensory role of intracellularly located TAS2Rs against toxic substances in keratinocytes. Although many G protein‐coupled receptors elicit signals from the surface, TAS2Rs were found to localize intracellularly, possibly to the ER, in human keratinocytes and HaCaT cells. TAS2R38, one of the TAS2R members, activated the Gα12/13/RhoA/ROCK/p38 MAP kinase/NF‐κB pathway upon stimulation by phenylthiocarbamide (PTC), an agonist for this receptor, leading to the production of ABC transporters, such as ABCB1, in these cells. Notably, treatment with bitter compounds, such as PTC and saccharin, induced the upregulation of ABCB1 in HaCaT cells. Mechanistically, intracellular TAS2R38 and its downstream signaling Gα12/13/RhoA/ROCK/p38 MAP kinase/NF‐κB pathway were identified to be responsible for the above effect. Pretreatment with PTC prevented the accumulation of rhodamine 123 because of its excretion via ABCB1. Furthermore, pretreatment with PTC or saccharin counteracted the effect of the toxic compound, diphenhydramine, and pretreated HaCaT cells were found to proliferate faster than untreated cells. This anti‐toxic effect was suppressed by treatment with verapamil, an ABCB1 inhibitor, indicating that enhanced ABCB1 helps clear toxic substances. Altogether, harmless activators of TAS2Rs may be promising drugs that enhance the excretion of toxic substances from the human skin. [ABSTRACT FROM AUTHOR]

Rationale: Muscarinic receptor activity in the basolateral amygdala (BLA) is known to be involved in plasticity mechanisms that underlie emotional learning. The BLA is involved in the Attenuation of Neophobia, an incidental taste learning task in which a novel taste becomes familiar and recognized as safe. Objective: Here we assessed the role of muscarinic receptor activity in the BLA in incidental taste learning. Methods: Young adult male Wistar rats were bilaterally implanted with cannulas aimed at BLA. After recovery, rats were randomly assigned to either vehicle or muscarinic antagonist group, for each experiment. We tested the effect of specific and non-specific muscarinic antagonists administered either 1) 20 min before novel taste presentation; 2) immediately after novel taste presentation; 3) immediately after retrieval (the second taste presentation on Day 5 -S2-) or immediately after the fifth taste presentation on Day 8 (S5). Results: Non-specific muscarinic receptor antagonist scopolamine infused prior to novel taste, while not affecting novel taste preference, abolished AN, i.e., the increased preference observed in control animals on the second presentation. When administered after taste consumption, intra-BLA scopolamine not only prevented AN but caused a steep decrease in the taste preference on the second presentation. This scopolamine-induced taste avoidance was not dependent on taste novelty, nor did it generalize to another novel taste. Targeting putative postsynaptic muscarinic receptors with specific M1 or M3 antagonists appeared to produce a partial taste avoidance, while M2 antagonism had no effect. Conclusion: These data suggest that if a salient gustatory experience is followed by muscarinic receptors antagonism in the BLA, it will be strongly and persistently avoided in the future. The study also shows that scopolamine is not just an amnesic drug, and its cognitive effects may be highly dependent on the task and the structure involved. [ABSTRACT FROM AUTHOR]

The human palate can discern multiple tastes; however, it predominantly perceives five fundamental flavors: sweetness, saltiness, sourness, bitterness, and umami. Sweetness is primarily mediated through the sweet taste receptor, a membrane-bound heterodimeric structure comprising T1R2-T1R3. However, unraveling the structural and mechanistic intricacies of the sweet taste receptor has proven challenging. This study aimed to address this knowledge gap by expressing an extracellular N-terminal domain encompassing the cysteine-rich domain of human hT1R3 (hT1R3-TMD) in Escherichia coli. The expressed protein was obtained as inclusion bodies, purified by metal affinity chromatography, and refolded using the dilution-refolding method. Through rigorous analysis, we confirmed the successful refolding of hT1R3-TMD and elucidated its structural characteristics using circular dichroism spectroscopy. Notably, the refolded protein was found to exist as either a monomer or a dimer, depending on its concentration. A tryptophan fluorescence quenching assay revealed that the dissociation constants for sucrose, sucralose, and brazzein were >9500 μM, 2380 μM and 14.3 μM, respectively. Our findings highlight the utility of this E. coli expression system for producing functional hT1R3-TMD for investigations and demonstrate the efficacy of the tryptophan fluorescence quenching assay in revealing complex interactions between sweet taste receptors and various sweeteners. [ABSTRACT FROM AUTHOR]

While previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimer's disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimer's disease. This study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimer's Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel. The eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimer's disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation of TAS2R41, and two of them were additionally associated with the down-regulation of TAS2R60. In the subsequent pQTL analysis, two of the SNPs linked to TAS2R41 and TAS2R60 genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3. Our investigation introduces a new perspective to the understanding of Alzheimer's disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the disease's progression across diverse populations. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to identify the regulatory role of intestinal sweet taste receptors (STRs) and glucose transporters (SGLT1, GLUT2) and gut peptide secretion in duodenal–jejunal bypass (DJB)–ameliorated glycemic control in Type 2 diabetes. Materials and Methods: DJB and sham surgeries were performed in streptozotocin‐induced diabetic male rats. The blood GLP‐1 and GLP‐2 levels were evaluated under feeding and fasting conditions. The expression of STRs (T1R2, T1R3), sweet taste signaling effector (Gα‐gustducin), SGLT1, and GLUT2 was detected in the intestinal alimentary limb (A limb), biliopancreatic limb (BP limb), and common limb (C limb). The effects of STR inhibition on glucose control were measured with lactisole. Results: Glucose tolerance was improved in DJB‐operated rats compared with the sham group, similar to that of normal control rats, without significant differences in food intake and body weight. The plasma GLP‐1 levels of DJB rats were increased under diet‐fed condition, and GLP‐2 levels were increased after fasting. The villus height and crypt depth were significantly increased in the A limb of DJB‐operated rats. In addition, GLP‐1 expression was restored in enterocytes. The expression of T1R2, Gα‐gustducin, and SGLT1 was elevated in the A limb after DJB, while GLUT2 was downregulated in the A, BP, and C limbs. The localization of GLUT2 was normalized in the three intestinal limbs after DJB. However, the beneficial effects of DJB on glucose control were abolished in the presence of lactisole in vivo. Conclusion: DJB ameliorates glycemic control probably by restoring STR‐mediated glucose sensing and absorption with the responses of GLP‐1 and GLP‐2 to carbohydrate. [ABSTRACT FROM AUTHOR]

A proton (H+) channel, Otopetrin 1 (OTOP1) is an acid sensor in the sour taste receptor cells. Although OTOP1 is known to be activated by extracellular acid, no posttranslational modification of OTOP1 has been reported. As one of the posttranslational modifications, glycosylation is known to modulate many ion channels. In this study, we investigated whether OTOP1 is glycosylated and how the glycosylation affects OTOP1 function. Pharmacological and enzymatic examinations (using an N‐glycosylation inhibitor, tunicamycin and peptide: N‐glycanase F [PNGase F]) revealed that overexpressed mouse OTOP1 was N‐glycosylated. As the N‐glycans were Endoglycosidase H (Endo H)‐sensitive, they were most likely high‐mannose type. A site‐directed mutagenesis approach revealed that both two asparagine residues (N238 and N251) in the third extracellular loop between the fifth transmembrane region and the sixth transmembrane region (L5‐6) were the glycosylation sites. Prevention of the glycosylations by the mutations of the asparagine residues or by tunicamycin treatment diminished the whole‐cell OTOP1 current densities. The results of cell surface biotinylation assay showed that the prevention of the glycosylations reduced the surface expression of OTOP1 at the plasma membrane. These results indicate that mouse OTOP1 is N‐glycosylated at N238 and N251, and that the glycosylations are necessary for OTOP1 to show the maximum degree of H+ current densities at the plasma membrane through promoting its targeting to the plasma membrane. These findings on glycosylations of OTOP1 will be a part of a comprehensive understanding on the regulations of OTOP1 function. [ABSTRACT FROM AUTHOR]

The freshness of Atlantic salmon is influenced mainly by tissue metabolism, which in turn is affected by storage time and conditions. The alterations in taste profiles and nutritional values of salmon when packaged using vacuum methods have not been fully understood, and the factors contributing to these changes require further research. In this work, the extraction method for flavor nutrients from salmon was optimized via the Plackett–Burman (PB) test. A sensitive and rapid targeted metabolomics method for the simultaneous determination of 34 nutrients was successfully established via ultra-performance liquid chromatography–triple quadrupole/linear ion trap composite mass spectrometry (UHPLC-QTRAP/MS), and various nutritional compositions during storage at 0 °C under different vacuum conditions (0 kPa or −90 kPa) for 4 and 8 days were analyzed. Results showed that storage time had a significant effect on salmon metabolism. The total amino acids decreased by 62.95% and 65.89% at 0 kPa and −90 kPa, respectively. Notably, a marked reduction in histidine after 8 days at −90 kPa may have diminished bitterness, while decreased levels of umami-tasting amino acids like glutamine and aspartic acid affected the overall flavor profile. Overall, the packaging conditions at 0 °C and 0 kPa were more suitable for the preservation of most nutrients in salmon. Pathway enrichment analysis revealed that the reduction in substances was mainly related to the alanine, aspartate, and glutamate metabolism pathways. Alanine, inosine, and histidine, whose levels changed significantly, can bind to the typical umami taste receptor TIR1/TIR3 and can be biomarkers to monitor and determine the freshness or spoilage of salmon after 4–8 days of storage. This study revealed the changes in small-molecule nutrients in salmon during storage under different packaging conditions, which provides a reference for the packaging preservation technology of fresh salmon and new ideas for the evaluation of salmon quality and determination of freshness. [ABSTRACT FROM AUTHOR]

The simulation of human sensory functions is a key trend in the field of sensor development. In taste sensing, taste biosensors emulate taste perception using biorecognition elements that participate in taste transduction, such as taste receptors, cells, tissues, etc. This approach obtains high selectivity and a wide detection range of human taste perception, making taste biosensors widely used in food analysis and taste perception studies. By combining biorecognition elements with suitable data processing and analysis techniques, the taste information generated during the process of taste transduction, obtained by the sensing elements of the sensor, can be accurately captured. In this paper, we explore current available solutions to stability and sensitivity, and other challenges in taste biosensors using taste receptors, cells, and tissues as sensing elements. We also outline the applied signal processing techniques based on the signal characteristics from different types of taste biosensors. Finally, it is proposed that the development of taste biosensing sensors will further promote the application of intelligent sensory evaluation and human perception analysis systems in food, medicine, and other fields. [ABSTRACT FROM AUTHOR]

Multifunctional wearable sensors have gained significant popularity in recent years for point of care diagnosis, tackling the myriad of obstacles faced in coping with health-related issues. However, complex fabrication, lack of biocompatibility, non-reusability, and accuracy limit their widespread use. In this work, we report a clean-room-free fabrication of molybdenum diselenide (MoSe2) interspersed with polyvinyl alcohol (PVA) based multifunctional device for in situ and non-invasive high-fidelity human gesture recognition, pulse rate monitoring, and skin hydration sensing. Detailed morphological characterization studies reveal the formation of a rhombohedral structure for MoSe2 nanoflakes stacked vertically to form a micro flower structure. Group synaptic activity of neurons results in a subtle electrical impulse, which, in turn, generates an electric field that is detected by the as-fabricated MoSe2/PVA device when attached to the forehead and interfaced to Open Brain-Computer Interface platform-based Cyton biosensing board. The device is also used as an ultrasensitive pressure sensor for arterial pulse pressure monitoring. This detection mechanism of the multifunctional sensor can be attributed to the piezoresistive effect of MoSe2 nanoparticles, wherein the dipoles reorient to form an internal polarization upon detection of physiological information. The strategy employed here paves the way toward replacing wet electrodes in conventional electroencephalogram (EEG)/electrocardiogram (ECG) measurements that result in skin abrasion and signal quality degradation with low-cost, reliable, skin-friendly, wearable MoSe2/PVA dry electrodes for rapid assessment. [ABSTRACT FROM AUTHOR]

Several chronic respiratory diseases could be risk factors for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunction of the respiratory cilia. In this study, we aimed to investigate whether PCD subjects are more susceptible to infection by SARS-CoV-2 and whether some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms. Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms, and vaccinations; in the case of infection, they also filled out a SNOT-22 questionnaire and ARTIQ. Forty PCD adult patients (mean age, 36.6 ± 16.7 years; 23 females, 17 males) participated in this study, out of which 30% had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistically significant difference (p = 0.03) was observed in body mass index (BMI), which was higher in the COVID-acquired group (23.2 ± 3.3 vs. 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI, and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of the PAV allele towards SARS-CoV-2 infection. Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype does not affect SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors. [ABSTRACT FROM AUTHOR]

Bitter taste receptors, also known as type 2 taste receptors (T2Rs), are found not only in the mouth's taste bud cells but also in various tissues and cells, including macrophages. Macrophages, known for their remarkable plasticity, play a crucial role in regulating innate immunity, managing inflammation, and orchestrating immune responses to antigens, pathogens, and environmental factors. Recently, the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest. This review summarizes the expression levels and distribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization, phagocytosis, and chemotaxis, as well as their potential molecular mechanisms. The purpose of this review is to provide insight and perspectives for research on the regulatory role of T2Rs in macrophage functions. [ABSTRACT FROM AUTHOR]

Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection. [ABSTRACT FROM AUTHOR]

Odorant receptors (ORs) and taste receptors (TRs) are expressed primarily in the nose and tongue in which they transduce electrical signals to the brain. Advances in deciphering the dietary component-sensing mechanisms in the nose and tongue prompted research on the role of gut chemosensory cells. Acting as the pivotal interface between the body and dietary cues, gut cells "smell" and "taste" dietary components and metabolites by taking advantage of chemoreceptors—ORs and TRs, to maintain physiological homeostasis. Here, we reviewed this novel field, highlighting the latest discoveries pertinent to gut ORs and TRs responding to dietary components, their impacts on gut hormone secretion, and the mechanisms involved. Recent studies indicate that gut cells sense dietary components including fatty acid, carbohydrate, and phytochemical by activating relevant ORs, thereby modulating GLP-1, PYY, CCK, and 5-HT secretion. Similarly, gut sweet, umami, and bitter receptors can regulate the gut hormone secretion and maintain homeostasis in response to dietary components. A deeper understanding of the favorable influence of dietary components on gut hormone secretion via gut ORs and TRs, coupled with the facts that gut hormones are involved in diverse physiological or pathophysiological phenomena, may ultimately lead to a promising treatment for various human diseases. [ABSTRACT FROM AUTHOR]