Taste Buds Research Articles

The efficacy of using metformin and/or quercetin for amelioration of gamma-irradiation induced tongue toxicity in diabetic rats

BackgroundDiabetes is a common disease that cancer patients may suffer from and may aggravate side effects of radiotherapy. This study aimed to detect whether metformin and/or quercetin will improve gamma-irradiation induced tongue toxicity in diabetic rats.Methods35 male albino rats were divided into five groups; NOR no streptozotocin, no radiation and no treatment was given, DR rats were subjected to streptozotocin then gamma-irradiation, DRM rats were subjected to streptozotocin then gamma-irradiation then metformin, DRQ rats were subjected to streptozotocin then gamma-irradiation then quercetin, DRMQ rats were subjected to streptozotocin then gamma-irradiation then metformin and quercetin. Rats were euthanized 24 h after last treatment dose. Mean blood glucose level was recorded. Tongue specimens were stained with H&E and CD68. Histomorphometric analysis of length, diameter and taste buds of lingual papillae and epithelial, keratin and lamina propria thickness and CD68 positive cells were calculated.ResultsBlood glucose level of DRMQ was significantly lower than DR, DRM and DRQ, whereas higher than NOR. Metformin or quercetin partially restored tongue structure, papillae length and diameter and tongue layers thickness. The ameliorative effect was superior when metformin and quercetin were used together. Diabetes and irradiation significantly increased number of CD68 positive macrophages in submucosa and muscles. Metformin or quercetin significantly reduced number of lingual macrophages with more noticeable effect for quercetin. Treatment with metformin and quercetin significantly decreased number of macrophages.ConclusionsCombined use of metformin and quercetin might help mitigate the harmful effects of radiotherapy and diabetes on lingual tissues.

Putative role of endothelin receptor B in the development and maintenance of taste buds within the circumvallate papillae

This study aimed to achieve a better understanding of taste receptor cell development relative to endothelin receptor B (ETB) in circumvallate papillae (CVP). ETB localization was assessed by immunohistochemistry during tongue development of the mouse. Co-localization of ETB with taste receptor type III cell marker, Synaptosomal-Associated Protein 25 kDa (SNAP25), was evident in both the developing and adult CVP. ETB was strongly localized in the stromal core region. As development progressed, ETB became localized in the CVP mesenchyme and partially in the epithelium. ETB and SNAP25 co-localization indicates that ETB may regulate innervation from the CVP mesenchyme to taste buds.

Cyclophosphamide induces the loss of taste bud innervation in mice.

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.

The duct of von Ebner's glands is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

We have recently demonstrated that Sox10-expressing (Sox10 +) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10 + cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae. In this study, we performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex and used inducible Cre mouse models to map the cell lineages of vEGs and/or connective tissue (including stromal and Schwann cells). Transcriptomic analysis indicated that Sox10 expression was enriched in the cell clusters of vEG ducts that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and vEG ductal cells. In vivo lineage mapping showed that the traced cells were distributed in circumvallate taste buds concurrently with those in the vEGs, but not in the connective tissue. Moreover, multiple genes encoding pathogen receptors were enriched in the vEG ducts hosting Sox10 + cells. Our data supports that it is the vEGs, not connective tissue core, that serve as the niche of Sox10 + taste bud progenitors. If this is also true in humans, our data indicates that vEG duct is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Give-and-take of gustation: the interplay between gustatory neurons and taste buds.

Mammalian taste buds are highly regenerative and can restore themselves after normal wear and tear of the lingual epithelium or following physical and chemical insults, including burns, chemotherapy, and nerve injury. This is due to the continual proliferation, differentiation, and maturation of taste progenitor cells, which then must reconnect with peripheral gustatory neurons to relay taste signals to the brain. The turnover and re-establishment of peripheral taste synapses are vital to maintain this complex sensory system. Over the past several decades, the signal transduction and neurotransmitter release mechanisms within taste cells have been well delineated. However, the complex dynamics between synaptic partners in the tongue (taste cell and gustatory neuron) are only partially understood. In this review, we highlight recent findings that have improved our understanding of the mechanisms governing connectivity and signaling within the taste bud and the still-unresolved questions regarding the complex interactions between taste cells and gustatory neurons.

Ultrastructural localization of calcium homeostasis modulator 1 in mouse taste buds.

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.

Differential distribution of intermediate filament proteins in the bovine and ovine tongues.

Intermediate filaments constitute the most heterogeneous class among the major classes of cytoskeletal proteins of mammalian cells. The 40 or more intermediate filament proteins have been classified into five types which show very specific rules of expression in specialized cell types. This study aimed to investigate the immunohistochemical distribution of cytokeratins (CKs) 8, 18, and 19 as well as the intermediate filaments vimentin, laminin, and desmin in bovine and ovine tongues. Immunohistochemical staining was performed for CKs 8, 18, 19, vimentin, laminin, and desmin. Our results revealed similar immunostaining intensity and distribution among various CKs, contrasting with distinct patterns for vimentin, laminin, and desmin. Immunoreactions were primarily localized in serous acini and ductal epithelium for cytokeratins, while vimentin and laminin were evident in connective tissue, endothelium, serous acini, and desmin in striated and smooth muscles. This study highlighted the absence of CKs 8, 18, 19, vimentin, and desmin in the lingual epithelium of bovine and ovine tongues. These findings enabled the classification of epithelial cells based on their specific cytokeratin patterns. Furthermore, vimentin was identified in mesodermal tissues and organs, desmin in muscle tissue, and laminin played crucial roles in basement membrane formation, nerve tissue regeneration, innervation of epithelial taste buds, and tissue separation and connection. Our findings provide essential insights into intermediate filament dynamics at the cellular and tissue levels. They serve as a foundation for future studies using systematic molecular biological techniques in this field.

Panchakarma and Satvavajaya chikitsa in the management of Pittodara caused by fast food addiction: A case report

Fast food is often consumed not as a requirement for hunger but to continuously satiate the taste buds with appealing flavors, which creates an addictive behavior. This addiction represents “Asatmendriyartha samyoga” (~improper use of sensory organs) of Rasanendriya (~sensory faculty of tongue). Toxins present in fast food can act as Dushivisha (~artificial poison) and Garavisha (~combination of non-poisonous substances) leading to Udara roga (~diseases of the abdomen). The present case followed a typical presentation of Pittodara (~Udara roga due to Pitta dosha) in a 19-year-old female, who was habituated to fast-food consumption. The patient had developed pain in the abdomen, and yellowish discoloration of eyes, urine, and stools for two weeks. Fever was the first symptom to develop followed by vomiting, causing severe weakness. The contemporary diagnosis had suspected the case to be an acute liver failure, requiring a liver transplantation. Based on Nidana (~etiology), Samprapti (~pathogenesis), and Lakshanas (~symptoms), the case was diagnosed as Pittodara. Considering the Vaya (~age), Bala (~physical endurance), Agni (~digestive/metabolic factors), and Satva (~psychic condition) of the patient, Dosha nirharana chikitsa (~evacuation of accumulated toxins), and Shothahara chikitsa (~reduction of inflammation and swelling) were planned through Nitya virechana (~therapeutic purgation on daily basis) by Gandharva hastadi eranda taila, Nasya (~medication through nasal route) with Gudanagara, Parisheka (~therapeutic streaming) with Dashamoola kwatha and Udaralepa (~application of medicated paste over abdomen). The patient was provided counseling along with specific advice on a planned diet and daily routine. A combination of Yukti vyapashraya (~logic-based treatment) and Satvavajaya chikitsa (~subjugation of mind/counsel) resulted in the reduction in yellowish discoloration of eyes, bilirubin levels, abdominal girth, pedal edema, and pain per abdomen. This case depicts the hazards of fast-food addiction among the young population, the utility of Panchakarma chikitsa in treating liver disorders, and the need for social policies to control the growth of fast-food outlets in India.

Recent Advances in the Nutrition and Metabolism of Dogs and Cats.

Domestic dogs (facultative carnivores) and cats (obligate carnivores) have been human companions for at least 12,000 and 9000 years, respectively. These animal species have a relatively short digestive tract but a large stomach volume and share many common features of physiological processes, intestinal microbes, and nutrient metabolism. The taste buds of the canine and feline tongues can distinguish sour, umami, bitter, and salty substances. Dogs, but not cats, possess sweet receptors. α-Amylase activity is either absent or very low in canine and feline saliva, and is present at low or substantial levels in the pancreatic secretions of cats or dogs, respectively. Thus, unlike cats, dogs have adapted to high-starch rations while also consuming animal-sourced foods. At metabolic levels, both dogs and cats synthesize de novo vitamin C and many amino acids (AAs, such as Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) but have a very limited ability to form vitamin D3. Compared with dogs, cats have higher requirements for AAs, some B-complex vitamins, and choline; greater rates of gluconeogenesis; a higher capacity to tolerate AA imbalances and antagonism; a more limited ability to synthesize arginine and taurine from glutamine/proline and cysteine, respectively; and a very limited ability to generate polyunsaturated fatty acids (PUFAs) from respective substrates. Unlike dogs, cats cannot convert either β-carotene into vitamin A or tryptophan into niacin. Dogs can thrive on one large meal daily and select high-fat over low-fat diets, whereas cats eat more frequently during light and dark periods and select high-protein over low-protein diets. There are increasing concerns over the health of skin, hair, bone, and joints (specialized connective tissues containing large amounts of collagen and/or keratin); sarcopenia (age-related losses of skeletal-muscle mass and function); and cognitive function in dogs and cats. Sufficient intakes of proteinogenic AAs and taurine along with vitamins, minerals, and PUFAs are crucial for the normal structures of the skin, hair, bone, and joints, while mitigating sarcopenia and cognitive dysfunction. Although pet owners may have different perceptions about the feeding and management practice of their dogs and cats, the health and well-being of the companion animals critically depend on safe, balanced, and nutritive foods. The new knowledge covered in this volume of Adv Exp Med Biol is essential to guide the formulation of pet foods to improve the growth, development, brain function, reproduction, lactation, and health of the companion animals.

Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affect glucose tolerance in humans.

The sweet taste receptor, TAS1R2-TAS1R3, is expressed in taste bud cells, where it conveys sweetness, and also in intestinal enteroendocrine cells, where it may facilitate glucose absorption and assimilation. In the present study, our objective was to determine whether TAS1R2-TAS1R3 influences glucose metabolism bidirectionally via hyperactivation with 5 mM sucralose (n = 12) and inhibition with 2 mM sodium lactisole (n = 10) in mixture with 75 g glucose loads during oral glucose tolerance tests (OGTTs) in healthy humans. Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose and their sensitivities to lactisole sweetness inhibition. The addition of sucralose to glucose elevated plasma insulin responses to the OGTT (F(1, 11) = 4.55, p = 0.056). Sucralose sweetness ratings were correlated with early increases in plasma glucose (R2 = 0.41, p<0.05), as well as increases in plasma insulin (R2 = 0.38, p<0.05) when sucralose was added to the OGTT (15 minute AUC). Sensitivity to lactisole sweetness inhibition was correlated with decreased plasma glucose (R2 = 0.84, p<0.01) when lactisole was added to the OGTT over the whole test (120 minute AUC). In summary, stimulation and inhibition of the TAS1R2-TAS1R3 receptor demonstrates that TAS1R2-TAS1R3 helps regulate glucose metabolism in humans and may have translational implications for metabolic disease risk.

Distinct expression patterns of Hedgehog signaling components in mouse gustatory system during postnatal tongue development and adult homeostasis.

The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH ligand SHH, HH receptors, and GLI transcription factors in FP, CVP and FOP in early and late postnatal and adult stages. In adults we also studied the soft palate, and the geniculate and trigeminal ganglia, which extend afferent fibers to the anterior tongue. Shh and Gas1 are the only components that were consistently expressed within taste buds of all three papillae and the soft palate. In the first postnatal week, we observed broad expression of HH signaling components in FP and adjacent, non-taste filiform (FILIF) papillae in epithelium or stroma and tongue muscles. Notably, we observed elimination of Gli1 in FILIF and Gas1 in muscles, and downregulation of Ptch1 in lingual epithelium and of Cdon, Gas1 and Hhip in stroma from late postnatal stages. Further, HH receptor expression patterns in CVP and FOP epithelium differed from anterior FP. Among all the components, only known positive regulators of HH signaling, SHH, Ptch1, Gli1 and Gli2, were expressed in the ganglia. Our studies emphasize differential regulation of HH signaling in distinct postnatal developmental periods and in anterior versus posterior taste organs, and lay the foundation for functional studies to understand the roles of numerous HH signaling components in postnatal tongue development.

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B.

Bitter taste receptors (Tas2rs) are generally considered to sense various bitter compounds to escape the intake of toxic substances. Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system invivo. To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues, multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique. A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes. Then, T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds. Perception to taste substance was also studied using two-bottle preference tests. We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique. Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice. But qRT-PCR results revealed the changed expression profile of mTas2rs gene in taste buds of these mutant mice. With two-bottle preference tests, these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105. In addition, these mutant mice showed a loss of taste perception to quinine dihydrochloride, denatonium benzoate, and cucurbitacin B (CuB). Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception. These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

STUDI KELAYAKAN BISNIS PADA PRODUK SEAFOOD SITUBONDO

Seafood Situbondo is a food restaurant that serves a variety of fresh seafood and is the first in Situbondo which is located on Jalan Merak No 1 Kel.Patokan, Situbondo, East Java. This restaurant also has Live Sea Water Lobster in the middle of Situbondo City. The restaurant's contemporary and aesthetic concept is very different from the others, not only seafood but also fried rice noodles and other menus. So this restaurant is very suitable for the taste buds of seafood lovers. This type of research is qualitative research using phenomenology as a method and technique for collecting data based on observations, interviews with Situbondo seafood owners and documentation.

Chronic social defeat stress broadly inhibits gene expression in the peripheral taste system and alters taste responses in mice

Human studies have linked stress exposure to unhealthy eating behavior. However, the mechanisms that drive stress-associated changes in eating behavior remain incompletely understood. The sense of taste plays important roles in food preference and intake. In this study, we use a chronic social defeat stress (CSDS) model in mice to address whether chronic stress impacts taste sensation and gene expression in taste buds and the gut. Our results showed that CSDS significantly elevated circulating levels of corticosterone and acylated ghrelin while lowering levels of leptin, suggesting a change in metabolic hormones that promotes food consumption. Stressed mice substantially increased their intake of food and water 3–5 days after the stress onset and gradually gained more body weight than that of controls. Moreover, CSDS significantly decreased the expression of multiple taste receptors and signaling molecules in taste buds and reduced mRNA levels of several taste progenitor/stem cell markers and regulators. Stressed mice showed significantly reduced sensitivity and response to umami and sweet taste compounds in behavioral tests. In the small intestine, the mRNA levels of Gnat3 and Tas1r2 were elevated in CSDS mice. The increased Gnat3 was mostly localized in a type of Gnat3+ and CD45+ immune cells, suggesting changes of immune cell distribution in the gut of stressed mice. Together, our study revealed broad effects of CSDS on the peripheral taste system and the gut, which may contribute to stress-associated changes in eating behavior.

Antillean manatee (Trichechus manatus manatus Linnaeus, 1758) Tongue Morphology and Adaptive Herbivorous Implications.

Morphological study of the tongue is an interesting way of understanding evolutionary processes associated with feeding habits. Therefore, the aim of the present study was to describe the tongue morphology of the Antillean manatee and to understand possible morphological relationships with its way of capturing food. Macroscopic dissections and light and scanning electron microscopy analyses of seven manatee tongues were performed. The tongue in Antillean manatees is a muscular and robust organ, divided into apex, body, and root. It is firmly adhered to the floor of the oral cavity. Lingual papillae were distributed over the entire tongue surface. They were identified as filiform papillae concentrated in the apex. Fungiform papillae were present on the apex and lateral regions. Foliate papillae were located on the dorsolateral portion of the root. Lentiform papillae were located across the dorsal tongue surface. The mucosa was lined by a keratinized stratified squamous epithelium presenting compound tubuloacinar glands and taste buds in the foliate papillae. The tongue of the Antillean manatee is similar to other Sirenia species, both of which share a completely herbivorous diet.

A REVIEW: A ROLE OF CAPSAICIN TO REGULATING T2R AND TRPV1 AND ITS ASSOCIATION IN CANCER DEVELOPMENT

Cancer is one of the leading causes of death in the world. It is estimated that this disease has caused 10 million deaths. The cause of the development of cells into cancer is still a mystery until we know that cancer is a disease that occurs due to an imbalance of molecular genes and cell receptors. Bitter taste receptors (T2R) are known to be expressed outside the taste buds and detect the perception of a bitter taste. These receptors are known to be involved in the mechanism of cancer cell development. Capsaicin is involved in a wide variety of genes that regulate the life cycle and growth of cancer cells. The activity of Capsaicin in inhibiting cell growth can be observed through various target genes, such as oncogene signaling pathways and tumor-suppressor genes. The systematics in this article is carried out using four electronic databases, namely Google Scholar, PubMed, ResearchGate, and NCBI. The keywords used are "capsaicin" combined with "T2R", "T2R8", "TAS2R", "TRPV1", "GPCRs" and also "Cancer", "Cancer cell line", "Mice", "Rat", "Man". Capsaicin affects the activity of normal cells and cancer cells through the TRPV 1 and T2r pathways. Through the TRPV1 pathway, Capsaicin increases intracellular calcium and disrupts the mitochondrial matrix. Via the T2r pathway, Capsaicin causes IP3, which increases intracellular calcium through endoplasmic reticulum stress.

Lingual Ultrastructural and Histochemical Study in the Patagonian Mara (Rodentia: Caviidae, Dolichotis patagonum) in Relation to Other Hystricomorphs.

The study describes the ultrastructure of the tongue in the Patagonian mara (Dolichotis patagonum) using light and scanning electron microscopy. Histochemical methods were used for evaluation of lingual salivary glands. The tongue is divided into a small and rounded apex, a narrow corpus, and a significantly wider radix, with a well-developed lingual prominence. The tip of the apex is free of papillae. The caudal part of the apex and the corpus are covered by filiform papillae. Round fungiform papillae are scattered among them. Papillae on the narrow stalk are conical. The radix contains caudally bent papillae forming wide flat prominences, slender, hook shaped filiform papillae, foliate papillae, and two oval vallate papillae. Taste buds were found on the lateral sides of the foliate and vallate papillae. Purely serous salivary glands are beneath the vallate and foliate papillae. Serous acini and mucous tubules are in the lingual radix. The Patagonian mara is the only hystricomorph rodent with described hyaline cartilage strengthening the lingual radix. Some typical signs of adaptation to herbivorous diet were found. The structure of the tongue is adapted to grass-feeding, as grasses form the main component of their diet.

Cellular mechanisms of taste disturbance induced by the non-steroidal anti-inflammatory drug, diclofenac, in mice.

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.

Visualization of the chemical defense molecule formoside binding to sensory structures in a model fish predator.

Sensory perception of chemical threats coming from an organism's environment relies on the coordination of numerous receptors and cell types. In many cases, the physiological processes responsible for driving behavioral responses to chemical cues are poorly understood. Here, we investigated the physiological response of fish to an unpalatable compound, formoside, which is employed as a chemical defense by marine sponges. Construction of fluorescent probe derivatives of formoside allowed visualization of this chemical defense molecule in vivo, interacting with the cells and tissues of the early larvae of a model predator, the zebrafish (Danio rerio). This revealed the precise chemosensory structures targeted by formoside to be in the taste buds and olfactory epithelium of developing zebrafish. Mechanosensory neuromasts were also targeted. This study supports the involvement of a previously identified co-receptor in detection of the chemical defense and provides a springboard for the long-term goal of identification of the cellular receptor of formoside. Extension of this approach to other predators and chemical defenses may provide insight into common mechanisms of chemoreception by predators as well as common strategies of chemical defense employed by prey.

Characterization of dysgeusia and xerostomia in patients with multiple myeloma treated with the T-cell redirecting GPRC5D bispecific antibody talquetamab.

In recent years, various immunotherapies have improved the survival of patients with multiple myeloma (MM). However, there remains an unmet need for novel agents. Talquetamab is the first-in-class GPRC5D-targeting T-cell redirecting bispecific antibody, which has substantial activity in advanced MM. Rapidly after the start of talquetamab treatment, patients reported taste changes (dysgeusia; 60% of patients), and a feeling of dry mouth (xerostomia; 30-57% of patients), which may be related to expression of the target antigen in healthy tissues, such as taste buds. Here, we aimed at better characterizing these oral toxicities. We measured salivary flow and the ability to taste (objectively and patient-reported), assessed the feeling of dry mouth, and evaluated quality of life before and 8 weeks after the start of talquetamab therapy in eight heavily pretreated MM patients. Talquetamab treatment led to the rapid and significant decrease in objectively measured taste scores (total score 8.8 ± 2.0 vs 4.9 ± 2.5). All patients reported moderate to severe taste changes. Moreover, patients experienced severe xerostomia after the initiation of talquetamab treatment, in the absence of changes in unstimulated and stimulated salivary flow. Because of these oral toxicities a significant impairment in global health status/(oral health related) quality of life was reported. Studying taste changes in patients treated with talquetamab following up on the described leads provides a new and unique opportunity to further unravel the pathophysiology of taste changes after cancer treatment.