The bitter side of toxicity: A big data analysis spotted the interaction between trichothecenes and bitter receptors.

The bitter taste perception evolved in human and animals to rapidly perceive and avoid potential toxic compounds. This is mediated by taste receptors type 2 (TAS2R), expressed in various tissues, which recently proved to be involved in roles beyond the bitter perception itself. With this study, the interaction between food-related toxic compounds and TAS2R46 has been investigated via computational approaches, starting with a virtual screening and moving to molecular docking and dynamics simulations. The virtual screening analysis identified trichothecolone and the trichothecenes class it belongs to, which includes mycotoxins widespread in several commodities raising food safety concerns, as possible TAS2R46 binders. Molecular docking and dynamics simulations were performed to further explore the trichotecenes-TAS2R46 interaction. The results indicated that deoxynivalenol and its 15-acetylated derivative could activate TAS2R46. Eventually, this study provided initial evidence supporting the involvement of TAS2R46 in the underpinning mechanisms of deoxynivalenol action highlighting the need of digging into the involvement of TAS2R46 and TAS2Rs in the adverse effects of deoxynivalenol and congeners.

Bitter Peptides in Fermented Soybean Foods - A Review.

Fermented soybean foods with a long history are popular worldwide because of rich nutrition. However, many traditional fermented soybean foods have unacceptable bitterness, which mostly comes from the bitter peptides produced from the hydrolysis of soybean proteins. In this review, the bitter peptides in fermented soybean foods is briefly reviewed. The structural properties of bitter receptors and bitter peptides were reviewed. Bitterness is perceived through the binding between bitter compounds and specific sites of bitter receptors (25 hTAS2Rs), which further activate the downstream signal pathway mediated by G-protein. And it converts chemical signals into electrical signals, and transmit them to the brain. In addition, the influencing factors of bitter peptides in fermented soybean foods were summarized. The bitterness of fermented soybean foods primarily results from the raw materials, microbial metabolism during fermentation, unique techniques, and interactions of various flavor compounds. Moreover, the structure-bitterness relationship of bitter peptides was also discussed in this review. The bitterness degree of the bitter peptide is related to the polypeptide hydrophobicity, amino acids in the peptide, peptide molecular weight and polypeptide spatial structure. Studying the bitter peptides and their bitter characteristics in fermented soybean foods is beneficial for improving the sensory quality of fermented soybean foods and prompting more consumers accept them.

Chromosome-Scale Genome Assembly of the Solitary Parasitoid Wasp Microplitis manilae Ashmead, 1904 (Braconidae: Microgastrinae).

Parasitoid wasps are invaluable natural enemies extensively used to control coleopteran, dipteran, and lepidopteran pests in agriculture and forestry owing to their killing and reproductive actions on hosts. The important larval endoparasitoid wasp Microplitis manilae, which belongs to the Microgastrinae subfamily, parasitizes the larval stages of Spodoptera spp., such as Spodoptera litura and Spodoptera frugiperda. The absence of a genomic resource for M. manilae has impeded studies on chemosensory- and detoxification-related genes. This study presents a chromosome-level genome assembly of M. manilae with a genome size of 293.18 Mb, which includes 222 contigs (N50 size, 7.58 Mb) and 134 scaffolds (N50 size, 27.33 Mb). A major proportion of the genome (284.76 Mb; 97.13%) was anchored to 11 pseudochromosomes with a single-copy BUSCO score of 98.4%. Furthermore, 14,316 protein-coding genes, 165.14 Mb (57.99%) repetitive elements, and 871 noncoding RNAs were annotated and identified. Additionally, a manual annotation of 399 genes associated with chemosensation and 168 genes involved in detoxification was conducted. This study provides a valuable and high-quality genomic resource to facilitate further functional genomics research on parasitoid wasps.

Optimization, identification, and comparison of peptides from germinated chickpea (Cicer arietinum) protein hydrolysates using either papain or ficin and their relationship with markers of type 2 diabetes.

The objective was to optimize and compare the production of antidiabetic peptides from germinated chickpea isolated protein using either papain or ficin. Kabuli chickpeas were germinated for 2, 4 and 6 days. Proteins were isolated, and peptides were produced based on a central composite design selecting human dipeptidyl peptidase (DPP-IV) inhibition as a response. Peptide sequencing was performed to identify and evaluate the physiochemical, biochemical and bitterness properties. DPP-IV inhibition using papain was 84.66 ± 8.72%, with ficin being 72.05 ± 1.20%. The optimum hydrolysate conditions were 6 days germination, 1:10 E/S, and 30 min ficin hydrolysis; SPGAGKG, GLAR, and STSA were identified. Pure SPGAGKG had relatively high affinity for DPP-IV (-7.2 kcal/mol) and α-glucosidase inhibition (-5.9 kcal/mol), with an IC50 of 0.27 mg/mL for DPP-IV inhibition. Peptides in the chickpea hydrolysate inhibited markers of T2D, indicating that the optimal conditions could be used to prepare a functional food ingredient.

Taste receptors in aquatic mammals: Potential role of solitary chemosensory cells in immune responses.

The sense of taste is associated with the evaluation of food and other environmental parameters such as salinity. In aquatic mammals, anatomic and behavioral evidence of the use of taste varies by species and genomic analysis of taste receptors indicates an overall reduction and, in some cases, complete loss of intact bitter and sweet taste receptors. However, the receptors used by taste buds in the oral cavity are found on cells in other areas of the body and play an important role in immune responses. In the respiratory tract, an example of such cells is solitary chemosensory cells (SCCs) which have bitter and sweet taste receptors. The bitter receptors detect chemicals given off by pathogens and initiate an innate immune response. Although many aquatic mammals may not have a role for taste in the assessment of food, they likely would benefit from the added protection that SCCs provide, especially considering respiratory diseases are a problem for many aquatic mammals. While evidence indicates that some species do not possess functional bitter receptors for taste, many do have intact bitter receptor genes and it is important for researchers to be aware of all roles for these receptors in homeostasis. Through a better understanding of the anatomy and physiology of aquatic mammal's respiratory systems, better treatment and management is possible.

Biomimetic in vitro respiratory system using smooth muscle cells on ECIS chips for anti-asthma TCMs screening.

Airway smooth muscle (ASM) contraction is a major pathophysiological characteristic of asthma. Although ß2-adrenoceptor (ß2-AR) agonists are currently used as bronchodilators, they cause rapid effect and long-term agonist-induced desensitization. Thus, it is necessary to search for more effective and safer relaxant agents for ASM cells. In this work, bitter taste receptors (TAS2Rs) were demonstrated to be expressed in primary mouse ASM cells endogenously, and they were considered as new drug targets for asthma treatment. Traditional Chinese medicines (TCMs) contained a wide range of TAS2R agonists and some of them had the efficacy of relieving cough and asthma with less toxic side effects. Then the electronic cell-substrate impedance sensor (ECIS) was used for the first time to establish a method to detect the contraction/relaxation effects of ASM cells. Therefore, we introduced a biomimetic in vitro respiratory system using ASM cells on ECIS chips to screen for potential TCMs against asthma. Quinine, nobiletin, and picfeltarraenin IA screened in this study could effectively inhibit the ASM contraction in a concentration-dependent manner, showing potential value as novel anti-asthma drugs. Furthermore, the effective screening of anti-asthma drugs was realized based on 3D ASM cell arrays and gel imaging system. Consistent results were found and the reliability of the biomimetic in vitro respiratory system for the screening of TCMs against asthma was further verified. The biomimetic system designed in this study has the advantages of operation simplicity, high throughput, non-invasive, real-time, and high sensitivity, and therefore provides a promising drug screening platform for asthma disease.

Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides.

Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.

Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions.

It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.

Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10.

Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines. Caffeine, a known ligand for T2R10, rendered the tumor cells more susceptible to two standard chemotherapeutics, Gemcitabine and 5-Fluoruracil. Knocking down T2R10 in the cell line BxPC-3 reduced the caffeine-induced effect. As possible underlying mechanism, we found that caffeine via triggering T2R10 inhibited Akt phosphorylation and subsequently downregulated expression of ABCG2, the so-called multi-drug resistance protein that participates in rendering cells resistant to a variety of chemotherapeutics. In conclusion, T2R10 is expressed in pancreatic cancer and it downmodulates the chemoresistance of the tumor cells.

The génépi Artemisia species. Ethnopharmacology, cultivation, phytochemistry, and bioactivity.

Wormwoods (Artemisia species) from the génépi group are, along with Edelweiss, iconic plants of the Alpine region and true symbols of inaccessibility because of their rarity and their habitat, largely limited to moraines of glaciers and rock crevices. Infusions and liqueurs prepared from génépis have always enjoyed a panacea status in folk medicine, especially as thermogenic agents and remedies for fatigue, dyspepsia, and airway infections. In the wake of the successful cultivation of white génépi (Artemisia umbelliformis Lam.) and the expansion of its supply chain, modern studies have evidenced the occurrence of unique constituents, whose chemistry, biological profile, and sensory properties are reviewed along with the ethnopharmacology, botany, cultivation and conservation strategies of their plant sources.

Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31.

Multiple psychophysical gene-association studies suggest a single nucleotide polymorphism (SNP) within the bitter receptor gene TAS2R19 on chromosome 12 may be functional. Previously, the Arg299Cys SNP (rs10772420) has been associated with differential bitterness of quinine and differential liking for grapefruit juice. However, quinine does not activate TAS2R19 in vitro; likewise, limonin and naringin, bitter compounds in grapefruit, do not activate TAS2R19 in vitro. Here, we examined quinine bitterness (whole-mouth swish-and-spit stimuli and regionally delivered quinine across 4 loci) and remembered liking for grapefruit juice to test whether they associate with SNPs in another nearby gene, TASR2R31. We observed SNP-phenotype associations between whole-mouth quinine bitterness and self-reported liking for grapefruit juice with SNPs in TAS2R31, and regional quinine bitterness followed a similar trend, but did not reach significance. Present data provide independent replication of prior associations reported for TAS2R19. However, we also observed strong linkage disequilibrium (LD) between TAS2R19 and TAS2R31 SNPs. When present data are considered in light of existing functional expression data, this suggests phenotypic associations reported previously for rs10772420 may potentially be due to LD between this SNP and polymorphism(s) in, or closer to, TAS2R31. If confirmed, this would reduce the number of TAS2Rs with putatively functional polymorphisms to 5.