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Taste, food, and health are terms that have since always accompanied the act of eating, but the association was simple: taste serves to classify a food as good or bad and therefore influences food choices, which determine the nutritional status and therefore health. The identification of taste receptors, particularly, the G protein-coupled receptors that mediate sweet, umami, and bitter tastes, in the gastrointestinal tract has assigned them much more relevant tasks, from nutrient sensing and hormone release to microbiota composition and immune response and finally to a rationale for the gut–brain axis. Particularly interesting are bitter taste receptors since most of the times they do not mediate macronutrients (energy). The relevant roles of bitter taste receptors in the gut indicate that they could become new drug targets and their ligands new medications or components in nutraceutical formulations. Traditional knowledge from different cultures reported that bitterness intensity was an indicator for distinguishing plants used as food from those used as medicine, and many non-cultivated plants were used to control glucose level and treat diabetes, modulate hunger, and heal gastrointestinal disorders caused by pathogens and parasites. This concept represents a means for the scientific integration of ancient wisdom with advanced medicine, constituting a possible boost for more sustainable food and functional food innovation and design.

Studies carried out in several species have demonstrated that detection of low-calorie sweeteners in the lumen of the intestine, by the sweet receptor, T1R2- T1R3, initiates a signaling pathway leading to enhanced expression and activity of intestinal Na+/glucose cotransporter 1, SGLT1. This results in an increased gut capacity to absorb glucose, sodium chloride and water, the basis for oral rehydration therapy. Horses express T1R2, T1R3 and downstream signaling elements in the intestinal tissue. As such, the potential of sweetener-stimulation of T1R2-T1R3 leading to upregulation of SGLT1 allows the provision of more glucose (energy) and hydration for horses. This is especially important when the need for glucose increases during strenuous exercise, pregnancy, and lactation. There are significant differences among species in the ability to detect sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes underlie these variations. Nothing is known about the sweetener specificity of horse T1R2-T1R3. Using heterologous expression methodology, we demonstrate that sweeteners sucralose, stevia and neohesperidin dihydrochalcone (NHDC) activate horse T1R2-T1R3, but cyclamate does not. Determination of sweetener specificity of equine sweet receptor is crucial for developing suitable dietary additives to optimize glucose absorption, hydration and avoiding the intestinal disease brought about by microbial fermentation of unabsorbed carbohydrate reaching the large intestine. [ABSTRACT FROM AUTHOR]

The tunica muscularis of mammalian esophagi is composed of striated muscle and smooth muscle. Contraction of the esophageal striated muscle portion is mainly controlled by cholinergic neurons. On the other hand, smooth muscle contraction and relaxation are controlled not only by cholinergic components but also by non-cholinergic components in the esophagus. Adenosine triphosphate (ATP) is known to regulate smooth muscle contraction and relaxation in the gastrointestinal tract via purinergic receptors. However, the precise mechanism of purinergic regulation in the esophagus is still unclear. Therefore, the aim of the present study was to clarify the effects of ATP on the mechanical responses of the esophageal muscle in mice. An isolated segment of the mouse esophagus was placed in a Magnus's tube and longitudinal mechanical responses were recorded. Exogenous application of ATP induced contractile responses in the esophageal preparations. Tetrodotoxin, a blocker of voltage-dependent sodium channels in neurons and striated muscle, did not affect the ATP-induced contraction. The ATP-evoked contraction was blocked by pretreatment with suramin, a purinergic receptor antagonist. RT-PCR revealed the expression of mRNA of purinergic receptor genes in the mouse esophageal tissue. The findings suggest that purinergic signaling might regulate the motor activity of mouse esophageal smooth muscle. [ABSTRACT FROM AUTHOR]

(1) Background: Within the framework of the European Interreg Italy–Switzerland B-ICE & Heritage project (2018–2022), this study originated from a three-year ethnobotanical survey in Valmalenco (Sondrio, Italy). Following a preliminary work published by our group, this research further explored the folk therapeutic use of Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson (Asteraceae) for dyspepsia disorders, specifically its anti-inflammatory potential at a gastrointestinal level. (2) Methods: Semi-structured interviews were performed. The bitter taste was investigated through molecular docking software (PLANTS, GOLD), while the anti-inflammatory activity of the hydroethanolic extract, infusion, and decoction was evaluated based on the release of IL-8 and IL-6 after treatment with TNFα or Helicobacter pylori. The minimum inhibitory concentration and bacterial adhesion on the gastric epithelium were evaluated. (3) Results: In total, 401 respondents were interviewed. Molecular docking highlighted di-caffeoylquinic acids as the main compounds responsible for the interaction with bitter taste receptors. The moderate inhibition of IL-6 and IL-8 release was recorded, while, in the co-culture with H. pylori, stronger anti-inflammatory potential was expressed (29–45 μg/mL). The concentration-dependent inhibition of H. pylori growth was recorded (MIC = 100 μg/mL), with a significant anti-adhesive effect. (4) Conclusions: Confirming the folk tradition, the study emphasizes the species' potentiality for dyspepsia disorders. Future studies are needed to identify the components mostly responsible for the biological effects. [ABSTRACT FROM AUTHOR]

Chemoreception – the ability to smell and taste – is an essential sensory modality of most animals. The number and type of chemical stimuli that animals can perceive depends primarily on the diversity of chemoreceptors they possess and express. In vertebrates, six families of G protein-coupled receptors form the core of their chemosensory system, the olfactory/pheromone receptor gene families OR, TAAR, V1R and V2R, and the taste receptors T1R and T2R. Here, we study the vertebrate chemoreceptor gene repertoire and its evolutionary history. Through the examination of 1,527 vertebrate genomes, we uncover substantial differences in the number and composition of chemoreceptors across vertebrates. We show that the chemoreceptor gene families are co-evolving, highly dynamic, and characterized by lineage-specific expansions (for example, OR in tetrapods; TAAR, T1R in teleosts; V1R in mammals; V2R, T2R in amphibians) and losses. Overall, amphibians, followed by mammals, are the vertebrate clades with the largest chemoreceptor repertoires. While marine tetrapods feature a convergent reduction of chemoreceptor numbers, the number of OR genes correlates with habitat in mammals and birds and with migratory behavior in birds, and the taste receptor repertoire correlates with diet in mammals and with aquatic environment in fish. Chemoreception - the ability to smell and taste - relies on diverse receptor genes. Examining 1,527 vertebrate genomes, this study explores the dynamic evolution, lineage-specific expansions and losses of chemoreceptor genes as well as ecological and morphological factors associated with these. [ABSTRACT FROM AUTHOR]

A large portion of the human GPCRome is still in the dark and understudied, consisting even of entire subfamilies of GPCRs such as odorant receptors, class A and C orphans, adhesion GPCRs, Frizzleds and taste receptors. However, it is undeniable that these GPCRs bring an untapped therapeutic potential that should be explored further. Open questions on these GPCRs span diverse topics such as deorphanisation, the development of tool compounds and tools for studying these GPCRs, as well as understanding basic signalling mechanisms. This review gives an overview of the current state of knowledge for each of the diverse subfamilies of understudied receptors regarding their physiological relevance, molecular mechanisms, endogenous ligands and pharmacological tools. Furthermore, it identifies some of the largest knowledge gaps that should be addressed in the foreseeable future and lists some general strategies that might be helpful in this process. [ABSTRACT FROM AUTHOR]

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single‐cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine the association of TAS2R16 (rs860170, rs978739, rs1357949) gene polymorphisms and TAS2R16 serum levels in patients with the occurrence of age-related macular degeneration (AMD). Subjects with early AMD, subjects with exudative AMD, and healthy controls participated in the study. DNA was isolated by salting out leukocytes from peripheral venous blood. Single nucleotide polymorphisms (SNPs) were analysed by RT-PCR. TAS2R16 levels were determined by enzyme-linked immunosorbent assay (ELISA) using the Abbexa Human Taste Receptor Type 2 Member 16 (TAS2R16) ELISA kit. Statistical data analysis was performed using "IBM SPSS Statistics 27.0" and SNPstats statistical data analysis programmes. The TAS2R16 rs860170 TT genotype is statistically significantly less frequent in the exudative AMD group than in the control group, whereas the TAS2R16 rs860170 C allele gene is statistically significantly more frequent in the exudative AMD group. Each C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased probability of occurrence of exudative AMD. The C allele of TAS2R16 rs860170 is statistically significantly more frequent in men and women with exudative AMD than in the control group. The C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased odds of occurrence of exudative AMD in women and a 2.9-fold increased odds of occurrence of exudative AMD in men. In TAS2R16 (rs860170, rs978739, and rs1357949), the T-T-A haplotype is associated with a 2.6-fold decreased likelihood of developing early AMD and the T-T-A haplotype is associated with a 3.2-fold decreased likelihood of developing early AMD in women. For TAS2R16 (rs860170, rs978739, and rs1357949), carriers of the T-T-G and T-T-A haplotypes are associated with a 2.2- and 3.2-fold decreased probability of exudative AMD, respectively. Individuals with the C-C-A haplotype are 9.2-fold more likely to develop exudative AMD. Specifically, the C-C-A haplotype is associated with a 9.3-fold increased likelihood of exudative AMD in men. In contrast, women with the T-T-A haplotype are 5.6-fold less likely to develop exudative AMD. TAS2R16 plays an important role in the development of AMD. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential. [ABSTRACT FROM AUTHOR]

Soft electromechanical sensors have led to a new paradigm of electronic devices for novel motion-based wearable applications in our daily lives. However, the vast amount of random and unidentified signals generated by complex body motions has hindered the precise recognition and practical application of this technology. Recent advancements in artificial-intelligence technology have enabled significant strides in extracting features from massive and intricate data sets, thereby presenting a breakthrough in utilizing wearable sensors for practical applications. Beyond traditional machine-learning techniques for classifying simple gestures, advanced machine-learning algorithms have been developed to handle more complex and nuanced motion-based tasks with restricted training data sets. Machine-learning techniques have improved the ability to perceive, and thus machine-learned wearable soft sensors have enabled accurate and rapid human-gesture recognition, providing real-time feedback to users. This forms a crucial component of future wearable electronics, contributing to a robust human–machine interface. In this review, we provide a comprehensive summary covering materials, structures and machine-learning algorithms for hand-gesture recognition and possible practical applications through machine-learned wearable electromechanical sensors. [ABSTRACT FROM AUTHOR]

Objective: To investigate differences in angiotensin‐converting‐enzyme‐2 (ACE2) and bitter taste receptor (TAS2R38) expression between patient age groups and comorbidities to characterize the pathophysiology of coronavirus 19(COVID‐19) pandemic. ACE2 is the receptor implicated to facilitate SARS‐CoV‐2 infections and levels of expression may correlate to the severity of COVID‐19 infection. TAS2R38 has many non‐gustatory roles in disease, with some evidence of severe COVID‐19 disease in certain receptor phenotypes. Methods: We conducted a prospective cohort study and collected nasal and lingual tissue from healthy pediatric (n = 22) and adult (n = 25) patients undergoing general anesthesia for elective procedures. RNA isolation and qPCR were performed with primers targeting ACE2 and TAS2R38. Results: A total of 25 adult (52% male; 44% obese) and 22 pediatric (50% male; 36% obese) patients were enrolled, pediatric tissue had 43% more nasal ACE2 RNA expression than adults with a median fold change of 0.69 (IQR 0.37, 0.98) in adults and 0.99 (IQR 0.74, 1.43) in children (p <.05). There were no differences between the age groups in ACE2 expression of lingual tissue (p =.14) or TAS2R38 expression collected from either nasal (p = 049) or lingual tissue (p =.49). Stratifying for obesity yielded similar differences between nasal ACE2 expression between adults and children with median fold change of 0.56 (IQR 0.32, 0.87) in adults and 1.0 (IQR 0.82, 1.52) in children (p <.05). Conclusions: ACE2 receptor expression is higher in nasal tissue collected from children compared to adults, suggesting COVID‐19 infectivity is more complicated than ACE2 and TAS2R38 mRNA expression. Level of Evidence: NA. [ABSTRACT FROM AUTHOR]

The innate immune system is crucial in fighting SARS-CoV-2 infection, which is responsible for coronavirus disease 2019 (COVID-19). Therefore, deepening our understanding of the underlying immune response mechanisms is fundamental for the development of novel therapeutic strategies. The role of extra-oral bitter (TAS2Rs) and sweet (TAS1Rs) taste receptors in immune response regulation has yet to be fully understood. However, a few studies have investigated the association between taste receptor genes and COVID-19 symptom severity, with controversial results. Therefore, this study aims to deepen the relationship between COVID-19 symptom presence/severity and TAS1R and TAS2R38 (TAS2Rs member) genetic variations in a cohort of 196 COVID-19 patients. Statistical analyses detected significant associations between rs307355 of the TAS1R3 gene and the following COVID-19-related symptoms: chest pain and shortness of breath. Specifically, homozygous C/C patients are exposed to an increased risk of manifesting severe forms of chest pain (OR 8.11, 95% CI 2.26–51.99) and shortness of breath (OR 4.83, 95% CI 1.71–17.32) in comparison with T/C carriers. Finally, no significant associations between the TAS2R38 haplotype and the presence/severity of COVID-19 symptoms were detected. This study, taking advantage of a clinically and genetically characterised cohort of COVID-19 patients, revealed TAS1R3 gene involvement in determining COVID-19 symptom severity independently of TAS2R38 activity, thus providing novel insights into the role of TAS1Rs in regulating the immune response to viral infections. [ABSTRACT FROM AUTHOR]

The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here, we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology. [ABSTRACT FROM AUTHOR]

Sweeteners are used in the food industry to provide sweetness similar to sugar and to decrease the caloric intake and risks associated with obesity. However, some sweeteners are characterized by bitter, metallic and other off-tastes. Sensory and cellular studies have demonstrated synergies between sweetener blends, which are responsible for enhancing sweetness. This study aimed to identify new sweetener blends that are able to enhance sweetness intensity without causing bitter off-taste using in vitro functional expression of taste receptors. The dose–response of the sweet taste receptor (TAS1R2/TAS1R3) was determined for sucrose and 9 sweeteners and was consistent with their sweetness potency. Stimulation of TAS1R2/TAS1R3 by 6 binary sweetener blends confirmed 3 known synergies determined by sensory analysis, including sucralose/acesulfame-K, rebaudioside A/erythritol and rebaudioside A/thaumatin, and revealed 2 new synergies, known as, neotame/D-allulose and mogroside V/thaumatin. No synergy was observed for the rebaudioside M/mogroside V blend, probably due to their common binding sites on the sweet taste receptor. The ability of the 9 selected sweeteners to activate the 25 human bitter taste receptors (TAS2Rs) was tested. The cellular-based assay demonstrated that sucralose, acesulfame-K, rebaudioside A, mogroside V and D-allulose activated at least 2 TAS2Rs. Sucralose, acesulfame-K and rebaudioside A exhibited lower EC50 values for TAS1R2/TAS1R3 than for TAS2Rs, which may explain their absence of bitter off-taste at low concentrations, unlike mogroside V and D-allulose. Our data provide a receptor-based understanding of the complex synergies among sweetener blends and an effective approach for testing new sweeteners while avoiding the activation of TAS2Rs. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre (GS) is a traditional medicinal plant known for its hypoglycemic and hypolipidemic effects. Gurmarin (hereafter Gur-1) is the only known active peptide in GS. Gur-1 has a suppressive sweet taste effect in rodents but no or only a very weak effect in humans. Here, 8 gurmarin-like peptides (Gur-2 to Gur-9) and their isoforms are reported in the GS transcriptome. The molecular mechanism of sweet taste suppression by Gur-1 is still largely unknown. Therefore, the complete architecture of human and mouse sweet taste receptors T1R2/T1R3 and their interaction with Gur-1 to Gur-9 were predicted by AlphaFold-Multimer (AF-M) and validated. Only Gur-1 and Gur-2 interact with the T1R2/T1R3 receptor. Indeed, Gur-1 and Gur-2 bind to the region of the cysteine-rich domain (CRD) and the transmembrane domain (TMD) of the mouse T1R2 subunit. In contrast, only Gur-2 binds to the TMD of the human T1R2 subunit. This result suggests that Gur-2 may have a suppressive sweet taste effect in humans. Furthermore, AF-M predicted that Gα-gustducin, a protein involved in sweet taste transduction, interacts with the intracellular domain of the T1R2 subunit. These results highlight an unexpected diversity of gurmarin-like peptides in GS and provide the complete predicted architecture of the human and mouse sweet taste receptor with the putative binding sites of Gur-1, Gur-2, and Gα-gustducin. In addition, gurmarin-like peptides may serve as promising drug scaffolds for the development of antidiabetic molecules. [ABSTRACT FROM AUTHOR]

This study examined how olfaction impacts ingestive responses of mice to sugar solutions. Experiment 1 asked whether naïve C57BL/6 (B6) mice could identify 1 M glucose, fructose, or sucrose solutions based on odor cues, during a 30-min 2-bottle acceptability test. We tested mice both before and after they were rendered anosmic with ZnSO4 treatment. We used 2 indirect measures of odor-mediated response: number of trials initiated and latency to initiate licking. Before ZnSO4 treatment, the mice learned how to identify 1 M glucose and fructose (but not sucrose) solutions based on odor cues. ZnSO4 treatment eliminated their ability to identify the glucose and fructose solutions. Experiment 2 asked whether 2 d of exposure to a 1 M glucose, fructose, or sucrose solution improved the identification of the same sugar solution. Following exposure, the B6 mice identified all 3 sugar solutions based on odor cues. Experiment 3 asked whether T1R3 knockout mice (i.e. mice lacking the T1R3 subunit of the T1R2 + R3 sweet taste receptor) could learn to discriminate 0.44 M glucose and fructose solutions based on odor cues. All mice were subjected to a 1-h preference test, both before and after exposure to the 0.44 M glucose and fructose solutions. During exposure, the experimental mice received ZnSO4 treatment, whereas the control mice received saline treatment. Before exposure, neither type of mouse preferred the glucose solution. After exposure, the control mice preferred the glucose solution, whereas the experimental mice did not. Our results reveal that mice can learn to use odor cues to identify and discriminate between sugar solutions. [ABSTRACT FROM AUTHOR]

Taste receptor cells are morphologically classified as types II and III. Type II cells form a unique type of synapses referred to as channel synapses where calcium homeostasis modulator 1 (CALHM1) together with CALHM3 forms voltage-gated channels that release the neurotransmitter, adenosine triphosphate (ATP). To validate the proposed structural model of channel synapses, the ultrastructural localization of CALHM1 in type II cells of both fungiform and circumvallate taste buds was examined. A monoclonal antibody against CALHM1 was developed and its localization was evaluated via immunofluorescence and immunoelectron microscopy using the immunogold-silver labeling technique. CALHM1 was detected as puncta using immunofluorescence and along the presynaptic membrane of channel synapses facing atypical mitochondria, which provide ATP, by immunoelectron microscopy. In addition, it was detected along the plasma membrane lined by subsurface cisternae at sites apposed to afferent nerve fibers. Our results support the validity of a previously proposed structural model for channel synapses and provide insights into the function of subsurface cisternae whose function in taste receptor cells is unknown. We also examined the localization of CALHM1 in hybrid synapses of type III cells, which are conventional chemical synapses accompanied by mitochondria similar to atypical mitochondria of channel synapses. CALHM1 was not detected in the six hybrid synapses examined using immunoelectron microscopy. We further performed double immunolabeling for CALHM1 and Bassoon, which is detected as puncta corresponding to conventional vesicular synapses in type III cells. Our observations suggest that at least some, and probably most, hybrid synapses are not accompanied by CALHM1. [ABSTRACT FROM AUTHOR]

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss. [ABSTRACT FROM AUTHOR]

Taste sensitivity in humans varies due to quantitative and qualitative differences in the structure of the sense‐perception organs. Taste perception is caused by the interaction of peripheral chemosensory organs, transmitted from the taste receptors of the taste buds on the tongue to the brain. Interestingly, taste receptors, which are classified into four types, are not only found in the oral cavity; they are also present at extraoral sites. Taste receptor type 1 (TAS1R) and type 2 (TAS2R) regulate bone remodeling. This review focuses on the effects of TAS1R1, TAS2R, TAS1R2, and TAS1R3, all of which belong to the family of G‐protein‐coupled receptors (GPCRs) related to bone remodeling. A summary of the clinical evidence that taste receptors play an essential role in bone remodeling is also provided. [ABSTRACT FROM AUTHOR]

Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (TAS2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental fluctuation. In the present study, we demonstrated that umbilical cord blood (UCB)-derived CD34+ cells express fully functional TAS2Rs along with the signal transduction cascade components and their activation by the prototypical agonist, denatonium benzoate, significantly modulated genes involved in stemness maintenance and regulation of cell trafficking. The activation of these specific pathways was confirmed in functional in vitro experiments. Denatonium exposure exerted an antiproliferative effect on UCB-derived CD34+ cells, mainly affecting the most undifferentiated progenitor frequency. It also reduced their clonogenicity and repopulating potential in vitro. In addition, the TAS2R signaling activation impaired the UCB-derived CD34+ cell trafficking, mainly reducing the migration toward the chemoattractant agent CXCL12 and modulating the expression of the adhesion molecules CD62L, CD49d, and CD29. In conclusion, our results in UCB-derived CD34+ cells expand the observation of TAS2R expression in the setting of BM-resident cells and shed light on the role of TAS2Rs in the extrinsic regulation of hematopoietic stem cell functions. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) affects 5–12% of the general population, and the most challenging patients are those with nasal polyposis (CRSwNP). Its complexity, unpredictability, and difficulties in selecting a treatment plan individually for each patient prompted scientists to look for possible genetic causes of this disease. It was proven that single nucleotide polymorphisms (SNPs) in the TAS2R38 gene may affect the mobility and the activity of the ciliated epithelium of the upper respiratory tract what can contribute to individual differences in susceptibility to CRS. There are two common haplotypes: a "protective" type (PAV), and a "non-protective" type (AVI). CRS patients who are homozygous PAV/PAV are considered as less susceptible to the severe course of the disease, whereas patients with AVI/AVI haplotype are more vulnerable. The aim of this study was to examine TAS2R38 gene polymorphisms among CRSwNP patients and control group (N = 544) with the evaluation of the association between the distribution of studied polymorphic variants and the incidence as well as severity of CRSwNP in the study group. Whole blood samples from CRSwNP patients (N = 106) and the control group (N = 438) were analyzed for alleles of the TAS2R38 gene using real-time PCR single nucleotide polymorphism genotyping assays for rs713598, rs1726866, and rs10246939. PAV (SG: 41%; CG: 49%) and AVI (SG: 59%; CG: 51%) haplotypes were the only ones detected in the study. The AVI haplotypes were 1.5 times more frequent in the study group than in the control group (p = 0.0204; OR = 1.43). AVI/AVI individuals tended to have more severe symptoms in the VAS scale, less QoL in the SNOT-22 test, and a bigger nasal obstruction upon endoscopic examination. Patients with PAV/PAV were twice more likely to have minor changes in preoperative CT scans (p = 0.0158; OR = 2.1; Fi = 0.24). Our study confirmed that the PAV/PAV diplotype might have some protective properties and carrying the AVI haplotype might predispose to the development of CRSwNP. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to develop a stable and effective form of an Orodispersible tablet containing Nicardipine Hydrochloride for the immediate treatment of high blood pressure and angina. The aim was to achieve this by using the natural sweetener stevia to improve taste. Background: Nicardipine Hydrochloride is used to treat high blood pressure and angina. However, currently available immediate release forms have limitations in terms of drug release and taste. Therefore, the goal was to develop an Orodispersible form of the drug that would enhance drug release and improve taste masking capabilities. Materials and Methods: We developed formulations of Nicardipine Hydrochloride Orodispersible tablets using the natural sweetener Stevia rebaudiana to enhance taste and reduce the caustic sensation. We confirmed the compatibility of the drug-excipient mixture using FTIR. Drug content and dissolution were determined through UV spectrophotometry. We also conducted organoleptic tests and other compendial specification tests. Precompression parameters were evaluated, and measures were taken to improve the flow behavior of the formulation blend by using excipients with excellent flow properties. Based on disintegration and dissolution time, we selected the F6 formulation as the optimized formula. We then subjected the developed trial to stability studies for three months, evaluating disintegration time, drug content, and dissolution. Results: The optimized formulation demonstrated a disintegration time of 46.25±0.85 sec and a dissolution rate of 100.50±2.50. Compendial tests remained stable without any significant fluctuations after the stability study. Also, the taste of the drug was pleasant after taste. Conclusion: Through the appropriate selection of excipients, we successfully developed a stable and effective form of Nicardipine Hydrochloride Orodispersible tablet with enhanced drug release (using the solid dispersion technique) and improved taste masking capabilities. The optimized formulation yielded favorable results in terms of disintegration and dissolution time, drug content, and stability. [ABSTRACT FROM AUTHOR]

Drug-induced taste disorders are a serious problem in an aging society. This study investigated the mechanisms underlying taste disturbances induced by diclofenac, a non-steroidal anti-inflammatory drug that reduces pain and inflammation by inhibiting the synthesis of prostaglandins by cyclooxygenase enzymes (COX-1 and COX-2). RT-PCR analyses demonstrated the expression of genes encoding arachidonic acid pathway components such as COX-1, COX-2 and prostaglandin synthases in a subset of mouse taste bud cells. Double-staining immunohistochemistry revealed that COX-1 and cytosolic prostaglandin E synthase (cPGES) were co-expressed with taste receptor type-1 member-3 (T1R3), a sweet/umami receptor component, or gustducin, a bitter/sweet/umami-related G protein, in a subset of taste bud cells. Long-term administration of diclofenac reduced the expression of genes encoding COX-1, gustducin and cPGES in mouse taste buds and suppressed both the behavioral and taste nerve responses to sweet and umami taste stimuli but not to other tastants. Furthermore, diclofenac also suppressed the responses of both mouse and human sweet taste receptors (T1R2/T1R3, expressed in HEK293 cells) to sweet taste stimuli. These results suggest that diclofenac may suppress the activation of sweet and umami taste cells acutely via a direct action on T1R2/T1R3 and chronically via inhibition of the COX/prostaglandin synthase pathway inducing down-regulated expression of sweet/umami responsive components. This dual inhibition mechanism may underlie diclofenac-induced taste alterations in humans. [ABSTRACT FROM AUTHOR]

Bitterness elicits unpleasant sensations in humans, which can hinder the acceptance of foods and medication adherence. Therefore, identifying and masking bitter tastes is crucial for developing palatable foods and promoting medication compliance in the food and pharmaceutical industries. To achieve this, employing agonism and antagonism of bitter taste receptors as effective strategies at the molecular level is essential. In this study, a bioelectronic tongue is developed to characterize the agonism and antagonism of bitter taste receptors. The human bitter taste receptors hTAS2R16 and hTAS2R31 are produced using an Escherichia coli expression system and reconstituted into nanodiscs (NDs). Subsequently, hTAS2R16‐ and hTAS2R31‐NDs are immobilized on the surface of graphene field‐effect transistors (FETs) to construct bioelectronic tongues. The developed system sensitively detected the bitter agonists, salicin and saccharin, at concentrations as low as 100 fM, with high selectivity in real‐time. The dose‐dependent curves shifted and K values decreased by the antagonists of hTAS2R16 and hTAS2R31, indicating antagonism‐based masking of bitter taste. Therefore, the developed bioelectronic tongue holds promise for identifying bitter tastes and evaluating the masking of bitterness based on the agonism and antagonism of hTAS2Rs. [ABSTRACT FROM AUTHOR]

Taste 2 receptors (T2Rs) are G-protein-coupled receptors responsible for sensing bitter tastes. Many studies have shown the expression of T2Rs in extraoral tissues and the unique role of T2Rs in each tissue. Single-nucleotide polymorphisms of T2Rs are associated with the risk of obesity and diabetes, and the organs/tissues associated with the development of these metabolic diseases, including the intestine, adipose, muscle, liver, and pancreas, are reported to express T2R genes. This result suggests that T2Rs in extraoral tissues contribute to the development of obesity and diabetes. In this narrative review, we summarize current knowledge of the associations of T2Rs with obesity and diabetes, provide an overview of extraoral tissues that are associated with the development of obesity and diabetes that express T2R genes, and summarize the current knowledge of T2Rs. [ABSTRACT FROM AUTHOR]

Baling Tieshan Reservoir is one of the important artificial inland lakes in Hunan Province, with abundant aquatic resources, including high-quality fish species such as organic bighead carp. In order to further utilize the resource advantages of Baling Tieshan Reservoir and create a high-quality brand, this experiment analysis the biological characteristics and excellent traits of Baling Tieshan organic bighead carp (BTOBC) through techniques such as gene cloning, qRT-PCR, and paraffin section, and provides experimental basis for improving the quality of BOTBC. Pond-cultured bighead carp (PCBC) was used as a control for comparison. The findings reveal that BTOBC exhibits excellent traits in terms of body color, body shape and meat quality, which better meets the market and consumers' demands. Analysis of muscle nutrient composition and observation of muscle fiber histomorphology demonstrate a higher muscle fat proportion, and umami amino acid (AA) content, higher muscle fiber density, enhanced taste in BTOBC. Blood index and liver histology observation indicate that BTOBC has relatively healthier physiological conditions. mRNA expression detection of umami taste receptor genes T1r1 and T1r3 in various tissues shows that the meat of BTOBC has a more delicious taste. This study provides a comprehensive understanding of the nutritional characteristics of BTOBC and explores its excellent traits, which can serve as a reference for subsequent processing, comprehensive utilization, and healthy breeding in the reservoir area. Moreover, it offers a scientific basis for the rational use of reservoir resources and the sustainable development of reservoir fisheries. [ABSTRACT FROM AUTHOR]

This study aimed to investigate (a) qualities Yelp reviewers (Yelpers) use to signify good taste in food, and (b) contemporary conversations about Hawaiian cuisine and Hawaii's local foods. A corpus of 1,200 online reviews of the forty-eight most popular restaurants in Hawaii was collected from the social media site Yelp to see how foods were discussed in the context of dining out in a uniquely multicultural location. The method used for analysis of the data was qualitative content analysis. The coding scheme was created by deductive category application and inductive category development. Findings revealed five main categories of food authenticity: authentic, synonym or word associated with authentic, local, four qualities (simplicity, geographic specificity, personal connection, and historicism), and other. There are two main categories of food exoticism: exotic and food containing unusualness, foreignness, or excitement. The findings build upon and expand existing literature. Categories of food authenticity and food exoticism were developed within the modern scene of dining out (before the COVID-19 pandemic). I proposed creativity as the third frame for valorizing food. Besides valorizing food, these three qualities--authenticity, exoticism, and creativity--can be used to express deliciousness. Linking authenticity with deliciousness helps explain why being "local," a dimension of authenticity, is meaningful to consumers. This might lead to food sustainability and healthy eating. Moreover, a multicultural perspective was recommended as an alternative to avoid troubles associated with imperialism. This study contributes to many fields, for example, sociology, food studies, and food communication. [ABSTRACT FROM AUTHOR]

Simple Summary: The codling moth, Cydia pomonella, is a major global agricultural pest of apple, pear, and walnut, and its behaviors are largely influenced by taste and smell. Different protein families that function as chemosensory receptors mediate detection of compounds from the environment. Manipulation of codling moth behaviors by using these compounds in orchards has been a successful approach to reduce fruit damage. This approach, however, has largely targeted male behaviors. Since it is the females that lay eggs, which propagate the species, in this report we sought to learn more about female behaviors. Specifically, we examined gene expression of the smell and taste receptors in female codling moth abdomen tip organs involved in egg-laying behaviors. We identified sets of both smell and taste receptor genes expressed in the abdomen tip that are likely candidates to influence egg-laying decisions. We also determined that expression of some of these receptors is increased or decreased after mating. These results increase our knowledge about the genes that can influence female codling moth behaviors. Future research will study the role of individual receptors with the aim of identifying taste and smell compounds that can be used to manipulate female codling moth behaviors in orchards. In insects, the chemical senses influence most vital behaviors, including mate seeking and egg laying; these sensory modalities are predominantly governed by odorant receptors (ORs), ionotropic receptors (IRs), and gustatory receptors (GRs). The codling moth, Cydia pomonella, is a global pest of apple, pear, and walnut, and semiochemically based management strategies limit the economic impacts of this species. The previous report of expression of a candidate pheromone-responsive OR in female codling moth ovipositor and pheromone glands raises further questions about the chemosensory capacity of these organs. With an RNA-sequencing approach, we examined chemoreceptors' expression in the female codling moth abdomen tip, sampling tissues from mated and unmated females and pupae. We report 37 ORs, 22 GRs, and 18 IRs expressed in our transcriptome showing overlap with receptors expressed in adult antennae as well as non-antennal candidate receptors. A quantitative PCR approach was also taken to assess the effect of mating on OR expression in adult female moths, revealing a few genes to be upregulated or downregulating after mating. These results provide a better understanding of the chemosensory role of codling moth female abdomen tip organs in female-specific behaviors. Future research will determine the function of specific receptors to augment current semiochemical-based strategies for codling moth management. [ABSTRACT FROM AUTHOR]

Simple Summary: Three bark beetle species, Tomicus yunnanensis, T. brevipilosus, and T. minor, are the most economically significant pests of the Yunnan pine in Southwestern China. Chemical and physical communication play key roles in various life activities. In this study, we described the fine structure of the adult mouthparts of these three Tomicus species using scanning and transmission electron microscopy. We identified three types of mandibular shapes, which match with their biomechanical properties, their ability to process food, and their preferred foraging locations on tree trunks. Eleven types of sensilla were discernible, including sensilla basiconica, sensilla twig basiconica, sensilla coeloconica, sensilla chaetica, sensilla trichoidea, and sensilla digitiformia. The function roles of each sensilla type were given based on its distribution and structures, especially on the internal structures such as dendrites and tubular body. Most chemoreceptors occur on the palpal tips. No significant differences among the sexes or species were identified; however, intraspecific variability in the number of sensilla twig basiconica 3 and sensilla digitiformia sensilla was evident. These findings will aid future studies of the feeding niches and reproductive behaviors of Tomicus beetles. Tomicus yunnanensis, T. brevipilosus, and T. minor are the most economically significant pests of Pinus yunnanensis in Southwestern China. Chemical and physical factors play critical roles in diverse biological activities. Here, we describe the fine structure of the adult mouthparts of these three Tomicus species using scanning and transmission electron microscopy. We identified three types of mandibular shapes, which determine their biomechanical properties, their ability to process food, and their preferred foraging locations on tree trunks. Eleven types of sensilla were discernible, including sensilla basiconica (Sb.1–2), sensilla twig basiconica (Stb.1–3), sensilla coeloconica (Sco), sensilla chaetica (Sch.1–2), sensilla trichoidea (Str.1–2), and sensilla digitiformia (Sdi). Each basiconic sensillum occurs on the palpal tips and is innervated by 2–6 dendrites. Sb.1 are gustatory receptors, Sb.2 are olfactory receptors, and the three other sensilla have dual taste and mechanical functions. Sco, Sch, and Str are mechanoreceptors. Sdi are mechanical vibration receptions, given that they are innervated by one dendrite with numerous dendritic branches into the nonporous cuticle. No significant differences among the sexes or species were identified; however, intraspecific variability in the number of Stb.3 and Sdi sensilla was evident. These results will aid future studies of Tomicus beetle behaviors. [ABSTRACT FROM AUTHOR]

Introduction: Data regarding patients presenting with severe acute respiratory syndrome (SARS-CoV-2) illness have not adequately been documented which provides distinct insights into low-resource settings like Ethiopia. Thus, the study aimed to compare epidemiological, clinical and laboratory profiles of patients presenting with acute respiratory syndrome illness in Addis Ababa Ethiopia. Methods: We used a comparative cross-sectional study design among patients with SARS-CoV-2 illness at St. Paul's Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia from October 2020 to September 2021. Using a structured questionnaire a consecutive sampling technique was applied to collect socio-demographic data. Additionally, nasal swabs were collected to confirm SARS-CoV-2 infection using a Real-Time Polymerase Chain Reaction. Blood samples were also collected from the participants for laboratory profiles (hematological tests like; white blood cell count, hematocrit, and platelet count; and biochemical and enzymatic tests like; aspartate transaminase (AST), creatinine, etc) analysis. Data were entered and analyzed using SPSS version 23.0 and p-values ≤0.05 were considered as statistically significant. Results: Of the total 413 participants presenting with SARS-CoV-2 illness, 250 (60.5%) participants tested positive for COVID-19 disease. COVID-19 patients were less likely to use an alcohol-based method of hand washing (12.5% vs 87.5%; p = 0.048). The COVID-19 patients had a higher proportion of headache (67.3% vs 32.7%, p = 0.001), sore throat (72.5% vs 27.5%, p = 0.001), and loss of sense of taste (74.4% vs 25.6%, p = 0.002). Patients with COVID-19 have significantly higher neutrophil than their counterparts (68.2% vs 31.8%; p = 0.001). Similarly, creatinine (64.9% vs 35.1%, p = 0.001) from renal function and alkaline phosphatase (66.8% vs 33.2%, p = 0.046) in the liver function tests were significantly higher in the COVID-19 patients. Conclusion: Our findings suggest the need to substantially consider headache, sore throat, and loss of taste as potential clinical diagnostic symptoms for early screening and testing. Elevation of neutrophil, creatinine, alkaline phosphatase profiles are also used for potential diagnostic biomarkers in screening and testing suspected patients. [ABSTRACT FROM AUTHOR]

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high‐fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway. [ABSTRACT FROM AUTHOR]

The present study was designed to establish the contribution of the corpus callosum (CC) to the cortical representation of unilateral taste stimuli in the human primary gustatory area (GI). Unilateral taste stimulation of the tongue was applied to eight patients with partial or total callosal resection by placing a small cotton pad soaked in a salty solution on either side of the tongue. Functional images were acquired with a 1.5 Tesla machine. Diffusion tensor imaging and tractography were also performed. Unilateral taste stimuli evoked bilateral activation of the GI area in all patients, including those with total resection of the CC, with a prevalence in the ipsilateral hemisphere to the stimulated tongue side. Bilateral activation was also observed in the primary somatic sensory cortex (SI) in most patients, which was more intense in the contralateral SI. This report confirms previous functional studies carried out in control subjects and neuropsychological findings in callosotomized patients, showing that gustatory pathways from tongue to cortex are bilaterally distributed, with an ipsilateral predominance. It has been shown that the CC does play a role, although not an exclusive one, in the bilateral symmetrical representation of gustatory sensitivity in the GI area, at least for afferents from one side of the tongue. [ABSTRACT FROM AUTHOR]

Neohesperidin dihydrochalcone (NHDC) is a sweetener, which interacts with the transmembrane domain (TMD) of the T1R3 subunit of the human sweet taste receptor. Although NHDC and a sweet taste inhibitor lactisole share similar structural motifs, they have opposite effects on the receptor. This study involved the creation of an NHDC-docked model of T1R3 TMD through mutational analyses followed by in silico simulations. When certain NHDC derivatives were docked to the model, His7345.44 was demonstrated to play a crucial role in activating T1R3 TMD. The NHDC-docked model was then compared with a lactisole-docked inactive form, several residues were characterized as important for the recognition of NHDC; however, most of them were distinct from those of lactisole. Residues such as His6413.33 and Gln7947.38 were found to be oriented differently. This study provides useful information that will facilitate the design of sweeteners and inhibitors that interact with T1R3 TMD. [ABSTRACT FROM AUTHOR]

From the nutritional perspective, the main direction of the utilization of white mulberry (Morus alba L.) parts so far has been to produce dietary supplements or functional foods for individuals with diabetes or over-weight. Its leaves are widely known as a valuable source of bioactive compounds responsible for its antioxidant and antidiabetic effects, both in animals and humans. The authors found that processed leaves can also be investigated as potential bitter and/or sweet taste modulators—an important property of new functional foods. The study aimed to validate the inhibitory effect of Morus alba L. on the TAS2R3 and TAS2R13 bitter taste and TSA1R2/TSA1R3 receptors and determine the changes that the conditioning process caused in such receptors. The effect on the receptors was evaluated in specially transfected HEK293T cells, and the inhibition ratio was measured using the calcium release test. Moreover, the stability of phenolics in the simulated intestinal in vitro digestion process was determined. Results showed that the Morus alba leaf extracts were rich in gallic, chlorogenic and caffeic acids together with rutin and quercetin 3-(6-malonyl)-glucoside, while the conditioning process positively affected their amount. Most identified phenolics were reduced during in vitro digestion. In the taste receptors test, it was found that the phytochemicals from conditioned Morus alba leaf extract enhanced sweet taste, together with a reduction of bitter taste receptor activity in some cases. To conclude, the study has found that Morus alba, especially when conditioned for 4 h, seems to be a valuable modulator of taste, which should be considered in future research as a crucial reason for its new utilization. [ABSTRACT FROM AUTHOR]

The world’s population is aging. Pneumonia is the leading cause of death among the older adults, with aspiration pneumonia being particularly common. Aspiration pneumonia is caused by a decline in swallowing function. Causes can include age-related sarcopenia of swallowing muscles, cognitive decline, cerebrovascular and other diseases or even changes in individual taste preference. Currently, the main treatment approach for dysphagia is resistance training of swallowing-related muscles. This approach has not been effective and establishment of novel methods are required. In this review, we introduce and discuss the relationship between taste, taste preference, carbonation and swallowing function. Taste and preference improve swallowing function. Recently, it has been shown that a carbonated beverage that combines the functionality of a thickening agent, the appeal of taste, and the stimulation of carbonation improves swallowing function. This may be very useful in the recovery of swallowing function. It is important to note that deliciousness is based not only on taste and preference, but also on visual information such as food form. Umami taste receptors are expressed not only in taste buds but also in skeletal muscle and small intestine. These receptors may be involved in homeostasis of the amino acid metabolic network, i.e., the process of amino acid ingestion, intestine absorption, and storage in skeletal muscle. Proper stimulation of umami receptors in organs other than taste buds may help maintain nutritional status and muscle mass. Umami receptors are therefore a potential therapeutic target for dysphagia.

Many animal and plant species synthesize toxic compounds as deterrent; thus, detection of these compounds is of vital importance to avoid their ingestion. Often, such compounds are recognized by taste 2 receptors that mediate bitter taste in humans. Until now, bitter taste receptors have only been found in bony vertebrates, where they occur as a large family already in coelacanth, a "living fossil" and the earliest-diverging extant lobe-finned fish. Here, we have revisited the evolutionary origin of taste 2 receptors (T2Rs) making use of a multitude of recently available cartilaginous fish genomes. We have identified a singular T2R in 12 cartilaginous fish species (9 sharks, 1 sawfish, and 2 skates), which represents a sister clade to all bony fish T2Rs. We have examined its ligands for two shark species, a catshark and a bamboo shark. The ligand repertoire of bamboo shark represents a subset of that of the catshark, with roughly similar thresholds. Amarogentin, one of the most bitter natural substances for humans, also elicited the highest signal amplitudes with both shark receptors. Other subsets of ligands are shared with basal bony fish T2Rs indicating an astonishing degree of functional conservation over nearly 500 mya of separate evolution. Both shark receptors respond to endogenous steroids as well as xenobiotic compounds, whereas separate receptors exist for xenobiotics both in early-and late-derived bony vertebrates (coelacanth, zebrafish, and human), consistent with the shark T2R reflecting the original ligand repertoire of the ancestral bitter taste receptor at the evolutionary origin of this family. [ABSTRACT FROM AUTHOR]

Plant-based food products have been receiving an astronomical amount of attention recently, and their demand will most likely soar in the future. However, their unpleasant, intrinsic flavor and odor are the major obstacles limiting consumer's acceptance. These off-flavors are often described as "green," "grassy," "beany," "fatty" and "bitter." This review highlights the presence and formation of common off-flavor volatiles (aldehydes, alcohols, ketones, pyrazines, furans) and nonvolatiles (phenolics, saponins, peptides, alkaloids) from a variety of plant-based foods, including legumes (e.g. lentil, soy, pea), fruits (e.g. apple, grape, watermelon) and vegetables (e.g. carrot, potato, radish). These compounds are formed through various pathways, including lipid oxidation, ethanol fermentation and Maillard reaction (and Strecker degradation). The effect of off-flavor compounds as received by the human taste receptors, along with its possible link of bioactivity (e.g. anti-inflammatory effect), are briefly discussed on a molecular level. Generation of off-flavor compounds in plants is markedly affected by the species, cultivar, geographical location, climate conditions, farming and harvest practices. The effects of genome editing (i.e. CRISPR-Cas9), various processing technologies, such as antioxidant supplementation, enzyme treatment, extrusion, fermentation, pressure application, and different storage and packaging conditions, have been increasingly studied in recent years to mitigate the formation of off-flavors in plant foods. The information presented in this review could be useful for agricultural practitioners, fruits and vegetables industry, and meat and dairy analogue manufacturers to improve the flavor properties of plant-based foods. [ABSTRACT FROM AUTHOR]

Targeting inflammation and the pathways linking inflammation with cancer is an innovative therapeutic strategy. Tastants are potential candidates for this approach, since taste receptors display various biological functions, including anti-inflammatory activity (AIA). The present study aims to explore the power different tastes have to predict a phytochemical's anti-cancer properties. It also investigates whether anti-inflammatory phytocompounds also have anti-cancer effects, and whether there are tastes that can better predict a phytochemical's bivalent biological activity. Data from the PlantMolecularTasteDB, containing a total of 1527 phytochemicals, were used. Out of these, only 624 phytocompounds met the inclusion criterion of having 40 hits in a PubMed search, using the name of the phytochemical as the keyword. Among them, 461 phytochemicals were found to possess anti-cancer activity (ACA). The AIA and ACA of phytochemicals were strongly correlated, irrespective of taste/orosensation or chemical class. Bitter taste was positively correlated with ACA, while sweet taste was negatively correlated. Among chemical classes, only flavonoids (which are most frequently bitter) had a positive association with both AIA and ACA, a finding confirming that taste has predictive primacy over chemical class. Therefore, bitter taste receptor agonists and sweet taste receptor antagonists may have a beneficial effect in slowing down the progression of inflammation to cancer. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence supports that the Western diet (WD), a diet high in saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, which are the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) has been identified in the hypothalamus, a key brain area involved in sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the influence of excessive WD intake on anxiety and mechanisms by which WD intake affects anxiety development using wild-type (WT) and Tas1r3 deficient (Tas1r3−/−) mice fed a normal diet (ND) or WD for 12 weeks. Results: WD increased anxiety in male WT mice, whereas male Tas1r3−/− mice were protected from WD-induced anxiety, as assessed by open field (OF), elevated plus maze (EPM), light–dark box (LDB), and novelty-suppressed feeding (NSF) tests. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3−/− mice, we found 1,432 genes significantly up- or down-regulated as a result of Tas1r3 deficiency. Furthermore, bioinformatic analysis revealed that the CREB/BDNF signaling-mediated maintenance of neuronal regeneration, which can prevent anxiety development, was enhanced in WD-fed Tas1r3−/− mice compared with WD-fed WT mice. Additionally, in vitro studies further confirmed that Tas1r3 knockdown prevents the suppression of Creb1 and of CREB-mediated BDNF expression caused by high levels of glucose, fructose, and palmitic acid in hypothalamic neuronal cells. Conclusions: Our results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and that inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of WD on anxiety. [ABSTRACT FROM AUTHOR]

The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain. These results suggest that the PBN-to-VTA input may relay negative emotions under threat. Consistent with this notion, optogenetic activation of PBN-to-VTA glutamatergic input results in aversion, which is sufficient to override palatable feeding. Moreover, in a palatable food-reinforced operant task, we demonstrate that transient optogenetic activation of PBN-to-VTA input during food reward retrieval disengages instrumental food-seeking behaviors but spares learned action–outcome association. By using an activity-dependent targeting approach, we show that VTA DA neurons are disengaged by the PBN afferent activation, implicating that VTA non-DA neurons may mediate PBN afferent regulation. We further show that optogenetic activation of VTA neurons functionally recruited by the PBN input results in aversion, dampens palatable feeding, and disengages palatable food self-administration behavior. Finally, we demonstrate that transient activation of VTA glutamatergic, but not GABAergic, neurons recapitulates the negative regulation of the PBN input on food self-administration behavior. Together, we reveal that the PBN-to-VTA input conveys negative affect, likely through VTA glutamatergic neurons, to disengage instrumental food-seeking behaviors. [ABSTRACT FROM AUTHOR]

CD36 is a receptor involved in physiologic, metabolic and pathologic processes. Due to its affinity for long-chain fatty acids, it has been postulated as a taste receptor of fatty taste. In this review, the emerging genetic evidence linking CD36 to oral fat perception is analyzed. A systematic literature search was conducted in PubMed, published articles from 2000 to 2022 were considered. Multiple studies have shown an association of some genetic variants in CD36 with fat foods preferences and it has been suggested that these variants can modify oral fat perception thresholds however the evidence is still heterogeneous; this can be explained by the genetic diversity of populations, the nutritional status and participant’s characteristics, as well as other methodological aspects. Other factors involved in oral fat perception were and identified and discussed including the interaction with other flavors, hormones, and epigenetic factors. The conclusion is that the evidence supporting the role of CD36 as a dietary lipid receptor, the role of its genetic variants in fat acids oral perception thresholds and food preferences is intermediate level and more research is necessary in other populations with large number of participants as well as considering the interaction between different hormones and the expression of CD36. [ABSTRACT FROM AUTHOR]

The geese's tongue filiform papillae are particularly long, and exhibit the same morphology of a tooth, evoking the lingual teeth of several fishes. In adult animals, they contain numerous mechanical Herbst's corpuscles but no taste buds. In the embryo, they appear since stage 38 and acquire their definitive shape between stages 38 and 42. They express several proteins associated with mammalian tooth development (BMP4, b-catenin, SHH, PITX2, PAX9), also known to be linked to parrot's pseudoteeth and goose's denticulations development. Neurofilaments are early present in the papillae primordia, and appear particularly numerous in adult papillae. Our results suggest that these papillae constitute a mechanical organ with a « tooth shape » derived from ancestral odontodes, whose development is controlled by numerous genes involved in classical odontogenesis. [ABSTRACT FROM AUTHOR]

Sweet and umami taste receptors recognize chemicals such as sugars and amino acids on their extracellular side and transmit signals into the cytosol of the taste cell. In contrast to ligands that act on the extracellular side of these receptors, little is known regarding the molecules that regulate receptor functions within the cytosol. In this study, we analysed the interaction between sweet and umami taste receptors and calmodulin, a representative Ca2+-dependent cytosolic regulatory protein. High prediction scores for calmodulin binding were observed on the C-terminal cytosolic side of mouse taste receptor type 1 subunit 3 (T1r3), a subunit that is common to both sweet and umami taste receptors. Pull-down assay and surface plasmon resonance analyses showed different affinities of calmodulin to the C-terminal tails of distinct T1r subtypes. Furthermore, we found that T1r3 and T1r2 showed the highest and considerable binding to calmodulin, whereas T1r1 showed weaker binding affinity. Finally, the binding of calmodulin to T1rs was consistently higher in the presence of Ca2+ than in its absence. The results suggested a possibility of the Ca2+-dependent feedback regulation process of sweet and umami taste receptor signaling by calmodulin. [ABSTRACT FROM AUTHOR]

Background: The most common symptoms of coronavirus infections are fever, cough, shortness of breath, headache, ache of joints, a loss of smell and loss of taste, and etc. Early studies suggested that smell and taste receptors were associated with pathogenic detection and immunity. Thus, we aimed to evaluate the expression profile of gene receptors that are related to taste, smell, and appetite control in COVID-19 patients and their putative correlation with SARS-CoV-19 variants. Method: Gene expression levels of TAS1R2, TAS1R3, TAS2R38, OR51E1, LEPR, GHRL were analyzed in 100 COVID-19 patients and 100 SARS-CoV-2 RT-qPCR negative group. Results: The expression levels of TAS1R2 and TAS1R3 genes were significantly decreased in COVID-19 patients who were infected with Delta variant. However, the TAS2R38 gene expression level was significantly lower when compared to the control group. The TAS1R2 gene expression was positively correlated with TAS1R3, and TAS2R38 genes (p = 0.001, p = 0.025, respectively). Conclusion: TAS1R2, TAS1R3, and TAS2R38 gene expression levels were decreased in the Delta variant compared to the Omicron BA.1 variant in the studied groups. These results provided a significant clue for the temporary taste loss, especially in patients infected with the Delta variant, which is the most disruptive and symptomatic variant causing hospitalizations, and deaths compared to other variants may be because ACE2 is expressed in the taste buds and high replication of SARS-CoV-2 in the infected gustatory cells in the taste bud generates inflammation and then could eventually destroy the cells. This gustatory cell damage may cause malfunction of the gustatory system. [ABSTRACT FROM AUTHOR]

Taste perception plays a crucial role in health and well-being but can be compromised by conditions such as diabetes mellitus (DM). This study delved into the efficacy of 4-hexylresorcinol (4-HR) in mitigating taste bud apoptosis, particularly in relation to DM-induced taste issues. Two primary rat groups were investigated: healthy rats and streptozotocin (STZ)-induced diabetic rats. Each group was further divided into control and experimental subsets, with the experimental group receiving 4-HR injections. A histological analysis of the circumvallate papillae (CVP) highlighted significant taste bud deterioration in the STZ subgroup, including loss of cellular content and a deviation from their typical morphology. Quantitatively, the control group had a mean of 39.6 ± 14.3 taste bud pores/mm2, contrasting with the 4HR, STZ, and STZ/4HR groups, which had means of 33.7 ± 14.2, 20.3 ± 6.1, and 28.0 ± 8.3, respectively. Additionally, a TUNEL assay and IHC staining for c-caspase-3 both identified increased apoptotic cells in the STZ subgroup, with the mean number of apoptotic cells per taste bud profile being notably higher in the STZ group at 3.2 ± 1.6. This study underscores the profound impact of diabetes on taste bud physiology and the potential therapeutic benefits of 4-HR. Further research is essential to delve deeper into its mechanisms and to ascertain optimal dosages, with the aim of enhancing the quality of life of diabetic patients. [ABSTRACT FROM AUTHOR]

The perceptual behavior of consumers on a product displayed in the market has a vital role in analyzing the importance given to that product. Therefore, various strategies have been developed to understand this consumer behavior in the selection of products. Immersive technologies like virtual, augmented, and mixed reality are among them. With the foremost feature of immersion in the virtual world and interaction of users with virtual objects, virtual reality, and augmented reality have unlocked their potential in research and a user‐friendly tool for analyzing consumer behavior. In addition to these technologies, mixed reality also has a significant role in investigating consumer behavior. Studies on immersive technologies in food applications are vast, hence this review focuses on the applications of virtual, augmented, and mixed reality in the food selection behavior of consumers. The behavioral studies are elicited to develop new products based on consumer needs, to understand the shopping behavior in supermarkets for real‐time usage, and to know the influence of emotions in a selection of products. The findings suggest that virtual, augmented, and mixed reality induce immersion of the users in food selection behavioral studies. Information on the technological advancements in the tools used for bringing immersion and interaction are discussed for its futuristic applications in food. Though immersive technology gives users a realistic virtual environment experience, its application in food systems is in the budding stage. More research on human response studies would contribute to its innovative and inevitable application in the future. [ABSTRACT FROM AUTHOR]

Skin, the largest organ of human body, acts as a barrier to protect body from the external environment and is exposed to a myriad of flavor compounds, especially food- and plant essential oil-derived odorant compounds. Skin cells are known to express various chemosensory receptors, such as transient potential receptors, adenosine triphosphate receptors, taste receptors, and odorant receptors (ORs). We aim to provide a review of this rapidly developing field and discuss latest discoveries related to the skin ORs activated by flavor compounds, their impacts on skin health and disease, odorant ligands interacting with ORs exerting specific biological effects, and the mechanisms involved. ORs are recently found to be expressed in skin tissue and cells, such as keratinocytes, melanocytes, and fibroblasts. To date, several ectopic skin ORs responding to flavor compounds, are involved in different skin biological processes, such as wound healing, hair growth, melanin regulation, pressure stress, skin barrier function, atopic dermatitis, and psoriasis. The recognition of physiological role of skin ORs, combined with the fact that ORs belong to a highly druggable protein family (G protein-coupled receptors), underscores the potential of skin ORs responding to flavor compounds as a novel regulating strategy for skin health and disease. [ABSTRACT FROM AUTHOR]

Despite the important role of bitter taste for the rejection of potentially harmful food sources, birds have long been suspected to exhibit inferior bitter tasting abilities. Although more recent reports on the bitter recognition spectra of several bird species have cast doubt about the validity of this assumption, the bitter taste of avian species is still an understudied field. Previously, we reported the bitter activation profiles of three zebra finch receptors Tas2r5, -r6, and -r7, which represent orthologs of a single chicken bitter taste receptor, Tas2r1. In order to get a better understanding of the bitter tasting capabilities of zebra finches, we selected another Tas2r gene of this species that is similar to another chicken Tas2r. Using functional calcium mobilization experiments, we screened zebra finch Tas2r1 with 72 bitter compounds and observed responses for 7 substances. Interestingly, all but one of the newly identified bitter agonists were different from those previously identified for Tas2r5, -r6, and -r7 suggesting that the newly investigated receptor fills important gaps in the zebra finch bitter recognition profile. The most potent bitter agonist found in our study is cucurbitacin I, a highly toxic natural bitter substance. We conclude that zebra finch exhibits an exquisitely developed bitter taste with pronounced cucurbitacin I sensitivity suggesting a prominent ecological role of this compound for zebra finch. [ABSTRACT FROM AUTHOR]