Search Results (132)

Bitterness of oral active pharmaceutical ingredients (APIs) remains a major barrier to patient adherence, particularly in pediatric and geriatric populations. Conventional taste-masking strategies primarily rely on formulation-based approaches, but do not always sufficiently suppress activation of bitter taste pathways. Increasing attention has focused on taste-modulating compounds, including umami substances, which reduce bitterness through multiple stages of taste processing, including peripheral receptor responses, perceptual taste interactions, and central sensory integration. This review provides an integrated overview of umami-mediated bitterness suppression from molecular, sensory, neural, and analytical perspectives. Interactions between TAS2R bitter receptors and T1R1/T1R3 umami receptors, including possible downstream signaling convergence and sensory integration mechanisms, are discussed in relation to bitterness suppression. Representative umami compounds, including monosodium glutamate (MSG) and umami peptides, have been reported to suppress the bitterness of several bitter APIs, suggesting potential applicability beyond compound-specific taste-masking strategies. Recent advances in electronic taste-sensing technologies, particularly lipid/polymer membrane-based systems, enable quantitative evaluation of bitterness modulation. Because taste sensors primarily reflect peripheral physicochemical interactions rather than central sensory processing, this review further discusses the potential utility of the bitterness sensor BT0 for evaluating the peripheral component of bitterness suppression, drawing primarily on studies using MSG and representative umami peptides. Collectively, current evidence suggests that umami-mediated taste modulation may provide a rational framework for improving oral pharmaceutical palatability. Full article

Background/Objectives: Taste perception has emerged as a key determinant of eating behavior and metabolic regulation, but its relationship with body mass index (BMI) remains incompletely understood. We investigated the relationships among global, sweet, and lipid taste sensitivity; sweet- and lipid-taste-related polymorphisms; caloric intake; and BMI. Methods: Taste sensitivity was assessed using taste strips (overall and sweet) and detection thresholds for fatty acids (oleic, linoleic, and palmitic acids). Genotyping of polymorphism genes was conducted. Pearson correlation analyses examined bivariate associations between taste variables and BMI. Multiple regression models were performed to identify independent predictors of BMI and to evaluate the mediating role of caloric intake. Results: A strong inverse correlation was found between total and sweet taste sensitivity and BMI, particularly in super-tasters (STs) and participants with the sensitive genotype of sweet-taste-related polymorphisms. Similarly, greater sensitivity to fatty acids was associated with lower BMI, specifically in non-tasters (NTs) and participants with the insensitive genotype of CD36 polymorphisms. In multiple regression models, overall and lipid sensitivity were the most significant predictors of BMI, which were inversely associated with it. TAS1R2 and TAS1R3 also showed independent effects. Importantly, caloric intake was not retained in the final model. Conclusions: Taste sensitivity is inversely associated with BMI independently of caloric intake. These findings suggest that the gustatory system could influence body weight through mechanisms beyond energy consumption, probably involving food choice and extra-oral receptor-mediated metabolic regulation. Taste perception and related genetic factors may represent important targets for personalized nutrition and obesity prevention strategies. Full article

Excessive fructose consumption is associated with metabolic syndrome (MS). This study evaluated the effect of two coffee by-products, coffee pulp (CP) and coffee silverskin (SK), on fructose-induced intestinal changes. Sprague–Dawley rats were assigned to six groups (n = 6/group) for 10 weeks: Control, Fructose (FRU; 20% fructose in drinking water), CP, CP + FRU, SK, and SK + FRU. CP and SK were administered by oral gavage (250 mg/kg/day) using corn oil as vehicle. Intestinal morphology, gene expression (RT-qPCR), and gut microbiota composition (16S rRNA sequencing) were assessed. Fructose significantly increased jejunal expression of the glucose transporters SGLT1 and GLUT2. CP and SK reversed SGLT1 and GLUT2 overexpression and reduced GLUT5 expression relative to the FRU group. Fructose also markedly increased expression of sweet taste receptors TAS1R2 and TAS1R3 and the transcription factors SREBP-1c and ChREBP. Both CP and SK normalized TAS1R2 and TAS1R3 expression, whereas SK additionally prevented SREBP-1c and ChREBP overexpression. Both by-products restored fructose-induced reductions in microbial richness and alpha diversity. CP also modified beta diversity and increased the abundance of the genus Blautia compared with FRU. In conclusion, CP and SK reversed several fructose-induced intestinal alterations, namely in the jejunal expression of sugar-sensing and absorption-related genes. Additionally, CP showed microbiota-modulating effects, whereas SK modulated the jejunal expression of key transcription factors (SREBP-1c and ChREBP) involved in carbohydrate and lipid metabolism. Overall, these findings suggest that CP and SK may represent promising candidates for mitigating fructose-induced intestinal alterations. Full article

Tuta absoluta is a globally significant invasive pest that has rapidly developed resistance to multiple classes of insecticides, highlighting the critical need for RNA interference (RNAi) targets for sustainable pest management. The insulin signaling pathway is a key regulator of insect reproduction; however, the role of PIK3AP, an adaptor protein that links receptor tyrosine kinases to the PI3K-Akt signaling pathway, remains poorly understood in Lepidopteran pests. In this study, TaPIK3AP was identified in T. absoluta, exhibiting elevated expression levels in the heads of female adults and during the early reproductive period. RNAi-mediated knockdown of TaPIK3AP reduced fecundity by 76%, decreased egg hatching rate by 43%, shortened the oviposition period by two days, and caused pronounced ovarian atrophy accompanied by impaired yolk deposition. Mechanistically, knockdown of TaPIK3AP led to the suppression of Vg and VgR expression, a reduction in juvenile hormone (JH) titer, downregulation of JH signaling genes, and a significant decrease in the transcript levels of key components of the target of rapamycin (TOR) pathway, including mTOR, Rheb, and S6K. These findings demonstrate that TaPIK3AP integrates Vg, JH, and TOR signaling pathways to regulate female reproduction in T. absoluta, thereby identifying it as a potential molecular target for RNAi-based sustainable pest management strategies. Full article

Bioactive peptides have health benefits, but the intense bitterness associated with their hydrolysis severely restricts their industrial applications. This paper systematically constructs a collaborative theoretical framework that integrates intelligent prediction, targeted debittering, and multi-dimensional evaluation. Firstly, it reviews the core applications of deep learning (such as quantitative structure–activity relationship (QSAR) and graph convolutional network (GCN)) combined with molecular docking technology in the high-throughput identification of bitter peptides and the analysis of target receptor interaction mechanisms. Secondly, it discusses how artificial intelligence and computational simulation can improve the efficiency of traditional debittering processes, emphasizing the advantages of multifunctional composite wall materials in the targeted encapsulation and delivery of bitter peptides, as well as the metabolic regulatory mechanisms behind controlling microbial fermentation for the debittering of specific peptide substrates. Finally, to provide a high-fidelity data closed loop for artificial intelligence (AI) models, a three-dimensional cross-validation system integrating standardized quantitative sensory evaluation and biomimetic electronic tongues was established. Future research should focus on developing large models for flavor generation to drive the green and targeted creation of low-bitterness and highly active peptides. Full article

Bitter phytochemicals, including alkaloids, terpenoids, and bitter glycosides, are abundant in medicinal food plants and exhibit well-documented anti-inflammatory, hypoglycemic, and other bioactivities relevant to human health. However, the inherent bitterness of these compounds presents a significant sensory barrier to patient compliance and limits their application as functional food ingredients. This review provides a comprehensive and interdisciplinary synthesis of current knowledge on bitter compounds in medicinal food plants, integrating perspectives from phytochemistry, molecular pharmacology, and sensory science. We summarize the major chemical classes of bitter phytochemicals, critically evaluate methods for their isolation and identification—from classical sensory-guided fractionation to modern computational approaches such as molecular docking and metabolomics—and analyze three principal strategies for bitterness regulation: physical removal, biological transformation, and sensory modulation (including molecular inclusion and TAS2R receptor blocking). We also briefly touch upon the extraoral expression of TAS2Rs and there suggested links to local immune responses and metabolic regulation, noting that this may be relevant to the concept of “taste–bioactivity homology.” The review further highlights ongoing challenges, such as the identification of unknown bitter compounds and the lack of standardized sensory evaluation systems, and outlines possible directions for improving bitterness analysis and regulation in medicinal food plants. Full article

Background/Objectives: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although TAS2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. We aim to establish a proof-of-concept methodology for investigating TAS2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective pilot case–control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. TAS2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: Among fully classifiable canonical TAS2R38 phenotypes (32 ORS patients, 28 controls), distributions were: tasters 12.5% vs. 25.0%, non-tasters 31.3% vs. 25.0%, and intermediate 56.3% vs. 50.0%. AVI/AVI non-taster status was not significantly associated with ORS susceptibility (OR = 1.36, 95% CI: 0.44–4.25; Fisher’s exact p = 0.775). Conclusions: This proof-of-concept study demonstrates that genotyping-grade genomic DNA can be recovered from acutely inflamed maxillary sinus mucosa, validating this substrate for future tissue-based expression, functional, and microbiome analyses not obtainable from peripheral samples; germline genotyping itself does not require sinus tissue. The observed difference in non-taster prevalence (31.3% vs. 25.0%) did not reach statistical significance and is reported descriptively. This directional trend is hypothesis-generating only and, given the limited statistical power, does not constitute evidence for an association. The demonstrated feasibility, together with the established biological rationale, supports an adequately powered confirmatory study and lays the foundation for future investigation of taste receptor genetics in ORS pathogenesis, and potentially personalized therapeutic strategies. Full article

Background: Instant Cascara (IC) beverages, derived from dried coffee cherry pulp, represent an upcycled plant-based ingredient rich in phenolic compounds and methylxanthines. Although spray-drying enables the production of soluble cascara powders without carriers, previous sensory evaluation highlighted limitations in palatability, supporting the need for formulation strategies. Objective: To evaluate how the incorporation of inulin-type carriers with different degrees of polymerization modulates production yield, the apparent recovery of bioactive compounds, and formulation-dependent in vitro biological and receptor-level responses of Instant Cascara beverages. Methods: Formulations without carrier (IC 0.0) and with long-chain inulin (IC 1.0) or oligofructose-enriched inulin (IC 2.0) were prepared and characterized. Production yield, phytochemical composition, and in vitro antioxidant, anti-inflammatory, antiproliferative, and receptor-mediated responses were assessed using analytical tools, cell-based assays, and receptor-based platforms. Results: Carrier incorporation improved production yield, particularly for IC 1.0. Although differences in apparent recovery of bioactive compounds were observed, all formulations preserved relevant in vitro biological activities. IC 2.0 showed stronger nitric oxide inhibition and apoptosis induction in colorectal cancer cell models. Receptor-based assays revealed formulation-dependent differences, including reduced activation of bitter taste receptors (TAS2Rs), absence of sweet receptor (TAS1R2/TAS1R3) activation, and modulation of muscarinic (M3) and dopaminergic (D3/D4) receptor responses. These effects are consistent with variations in the composition and effective concentration of bioactive compounds between formulations, particularly caffeine. Conclusions: The incorporation of inulin-type carriers influences production yield and modulates in vitro biological responses and receptor-level responses of Instant Cascara beverages. IC 2.0 represents a formulation with a favorable balance between technological performance and functional responses, associated with a distinct receptor-level profile. This balance may be related to a reduced contribution of bitterness-associated compounds, such as caffeine, together with the preservation of other bioactive components contributing to the observed biological responses. These findings provide a mechanistic in vitro basis for future sensory and in vivo studies evaluating how formulation-dependent differences in bioactive composition may influence physiological responses and consumer perception. Full article

Background/Objectives: Genetic generalized epilepsies (GGE) often remit in childhood, yet a subset of adults remain pharmacoresistant with substantial morbidity. The genetic basis of adult pharmacoresistant GGE is poorly defined. This descriptive study used whole-genome sequencing (WGS) to identify recurrent coding variants and pathways associated with pharmacoresistant adult GGE. Methods: WGS was performed in ten racially diverse adults (mean age 37.2 years; range 20–52) with electroencephalographically confirmed, pharmacoresistant GGE (mean onset 13.7 years). Analysis prioritized variants present in at least 80% of participants and which were either (i) missense variants predicted deleterious with ANNOVAR or (ii) loss-of-function variants predicted high-impact from snpEff. Pathway enrichment and overlap with a commercial clinical epilepsy gene panel were assessed. Results: Filtering identified 133 unique, deleterious coding variants across 69 genes shared by at least eight participants. Four genes (APOL4, KMT2C, SON, VDR) overlapped a clinical epilepsy panel, supporting the capacity of WGS to recover clinically relevant loci. Prioritized loci implicated gastrointestinal and metabolic regulators (e.g., MUC6, PNLIPRP2), chemosensory receptors (OR10D3, OR8U1, TAS2R19), neuroimmune mediators (LILRA2, SIGLEC12, OAS2), and ion transporters (KCNJ12, P2RX5, RHBG), consistent with multifactorial mechanisms of pharmacoresistance. Conclusions: This exploratory WGS study focused exclusively on adults with pharmacoresistant GGE, revealing shared high-impact variants and convergent pathways spanning absorption/metabolism, vitamin D signaling, immunity, and ion transport. Findings broaden the genetic landscape of pharmacoresistant GGE while motivating validation in larger, multiethnic cohorts. Full article

Background: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP₃-dependent intracellular Ca²⁺ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4⁺CD25⁺Foxp3⁺ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy. Full article

The distinctive bitter profile of Castanopsis fissa honey (LSZH) has not yet been clearly characterized at the chemical and molecular levels. Based on the LSZH samples (n = 6), this study investigated bitterness-associated compounds and their potential receptor interactions by integrating sensory evaluation, machine learning, untargeted metabolomics, electronic tongue analysis, targeted UPLC-QQQ-MS/MS quantification, and molecular docking. A Random Forest model combined with untargeted metabolomics screened 71 candidate bitter compounds, among which alkaloid-related metabolites were prominently represented. Electronic tongue analysis showed that several compounds exhibited higher bitterness-related sensor responses than quinine under the tested conditions. Targeted UPLC-QQQ-MS/MS analysis identified and quantified five key compounds, among which kynurenic acid was the most abundant, reaching approximately 4500 ppm (mg/kg). Molecular docking suggested that these compounds could favorably interact with the human bitter taste receptor TAS2R46, with binding affinities ranging from −5.4 to −6.5 kcal/mol, mainly through hydrogen bonding, hydrophobic interactions, and π-related interactions. Overall, this study provides chemical evidence and mechanistic clues for understanding the bitterness of LSZH and offers an integrated analytical framework for screening bitterness-associated compounds in complex food systems. Full article

Inflammatory joint diseases, including osteoarthritis, are multifactorial disorders in which dysregulated innate immune signaling and non-coding RNA (ncRNA)-mediated regulation of gene expression play essential roles. MicroRNA-155 (miR-155), its host gene MIR155HG, and Toll-like receptor 4 (TLR4) form a tightly linked inflammatory signaling axis, yet their combined genetic variability in chronic joint inflammation remains insufficiently characterized. The aim of this study was to investigate genetic variants in MIR155HG exon 3, mature miR-155, and TLR4 exon 3 and assess their potential synergistic role in chronic inflammatory joint disease. A case–control study was conducted with 100 cases (50 osteoarthritis patients and 50 matched healthy controls). Genomic DNA was analysed using polymerase chain reaction (PCR) and Sanger sequencing. Variant alleles and genotypes were identified, and their allele frequencies and genotypes were calculated using Mutation Surveyor. Detected variants were compared with public databases, and in silico tools were used to estimate the structural impact of TLR4 missense mutations. Sixteen heterozygous variants were identified in MIR155HG exon 3, most of them novel and population-specific. Interestingly, the highest variant frequencies for MIR155HG exon 3 were observed at positions 12448G>GC and 12481T>TA (both 64.3%), followed by 12442T>TC (57.1%). Additionally, two novel variants were detected in the miR-155 gene (chr21:29,694,314 G>A and chr21:29,646,351 T>C), each present at an allele frequency of 7.1% and absent from current external variant databases. Moreover, two rare TLR4 exon-3 variants were identified; a synonymous variant, c.147C>A (Pro49Pro; rs375037549), and a missense mutation, c.148G>A (Asp50Asn; rs776561489). Notably, in silico analyses and molecular dynamic simulations indicated that the Asp50Asn (D50N) substitution destabilizes the TLR4 protein. Conclusion: Concurrent variants in MIR155HG, miR-155, and TLR4 suggest a convergent regulatory molecular axis that may contribute to disease susceptibility and inflammatory progression. Full article

Background/Objectives: Individual differences in sweet taste sensitivity, influenced by genetic factors such as variants of the taste receptor type 1 member 2 (TAS1R2), are associated with food preferences and nutrient intake. However, the relationship between TAS1R2 polymorphisms and diet quality in Koreans remains unexplored. This study investigated the association between the TAS1R2 rs35874116 (T>C, Ile191Val) variant and diet quality, assessed using the Korean Healthy Eating Index (KHEI). Methods: Analyzing data from the Korean Genome and Epidemiology Study, we evaluated the dietary quality of 41,669 Koreans based on KHEI scores and TAS1R2 rs35874116 genotypes (TT versus CT+CC). Results: The findings indicate that genetic variation in the sweet taste receptor is linked to specific components of dietary quality. Although total KHEI scores did not differ between genotypes, TT genotype carriers had significantly higher vegetable intake scores compared to C allele carriers (3.42 ± 1.35 vs. 3.37 ± 1.36, p_adjusted = 0.002). Additionally, TT carriers exhibited higher sodium intake (6.85 ± 3.53 vs. 6.95 ± 3.51, p_adjusted = 0.002) and lower scores in the moderation domain (18.82 ± 5.15 vs. 18.98 ± 5.07, p_adjusted = 0.002). Conclusions: The TAS1R2 rs35874116 variant is associated with specific aspects of diet quality in Koreans, particularly vegetable and sodium intake. These findings suggest that genetic variations in sweet taste perception influence dietary behaviors among Koreans. Full article

Bitter taste receptors (TAS2Rs) are increasingly recognised as extraoral chemosensors that modulate diverse biological processes, including cancer cell behaviour and drug responsiveness. Many TAS2R ligands correspond to therapeutic compounds; however, their contribution to the response of brain tumours to chemotherapy remains unexplored. Here, we investigated whether the bitter taste signalling pathway is modulated by temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma, with an impact on treatment efficacy in glioblastoma cells. We show that TMZ elicits intracellular Ca²⁺ responses compatible with activation of G-protein-coupled receptor signalling and induces anti-proliferative and pro-apoptotic effects in multiple human glioblastoma cell lines. Pharmacological inhibition of bitter taste receptors, as well as genetic silencing of the taste transduction G protein GNAT3, significantly attenuated TMZ-induced cytotoxicity, suggesting that bitter taste signalling is involved in this process. In silico ligand prediction combined with receptor expression profiling identified TAS2R43 as a candidate modulator of these effects, and TAS2R43 knockdown markedly reduced TMZ-induced loss of cell viability and apoptosis. Moreover, TMZ enhanced intracellular accumulation of the ABC transporter substrate doxorubicin, suggesting modulation of multidrug efflux mechanisms. Collectively, our findings identify TAS2R43 as a potential biomarker that warrants further validation to improve responses to TMZ and other ABC transporter-limited anticancer drugs. Full article

Bitter taste receptors (TAS2Rs) are G protein-coupled receptors best known for detecting bitter compounds in the oral cavity. However, their expression patterns and physiological roles in the liver remain largely unexplored. Here, we employed molecular and immunohistochemical approaches to demonstrate that multiple TAS2Rs are expressed in human Hep3B cells and mouse primary hepatocytes (MPHs) and co-localized with β-adrenergic receptors (βARs) at the bile canaliculi. Bioluminescence resonance energy transfer (BRET), cAMP assays, and Western blot analyses revealed that certain TAS2Rs exhibit ligand-dependent coupling preferences for the G protein subunits Gαi1, Gαi2, and Gαi3. This coupling leads to inhibition of cAMP production and a reduction in protein kinase A (PKA) substrate phosphorylation. Biochemical assays further showed that TAS2R activation significantly attenuates βAR-mediated lipolysis, as well as the production of glycerol and free fatty acid in both Hep3B cells and MPHs. These effects were partially reversed by small interfering RNA (siRNA)-mediated knockdown of TAS2Rs. Moreover, studies using a steatotic mouse model demonstrated that bitter compounds inhibit lipid droplet degradation, resulting in hepatic triacylglycerol accumulation. Collectively, these findings reveal a role for TAS2Rs in modulating hepatic lipid metabolism and highlight their potential as therapeutic targets for the prevention and treatment of liver diseases. Full article