To better understand the bitterness effect and molecule mechanism of myosin-derived peptides activating bitter receptors,the interaction between myosin-derived peptides of dry-cured ham and bitter receptors was invest...To better understand the bitterness effect and molecule mechanism of myosin-derived peptides activating bitter receptors,the interaction between myosin-derived peptides of dry-cured ham and bitter receptors was investigated by molecular docking and molecular dynamics simulation;the signal transduction mechanism of myosinderived peptides was explored by HEK-293T cells using calcium imaging and transcriptomics analysis.Lower CDOCKER energy was observed during the interaction between myosin-derived peptides and hT2R1 by molecular docking compared with hT2R4,hT2R5,hT2R8,hT2R14 and hT2R16.Hydrogen bonds and hydrophobic interaction were the most important interaction forces which stabilized the interaction of hT2R1 and myosinderived peptides.Compared with LEKEKSELK and TEELEEAKK,the RMSF values and EC50 values of HVLATLGEK were lower,indicating that hT2R1 was more sensitive to HVLATLGEK stimulation.Transcriptomics and KEGG analyses showed that 767 differentially expressed genes were found and mainly involved in cAMP signaling pathway,neuroactive ligand-receptor interaction,calcium signaling pathway and MAPK signaling pathway after stimulating of HVLATLGEK.Protein-protein interaction network further demonstrated that DDIT3,FOS,FOSB,MYC,EGR1 and CCN2 were the key genes to connect the six functional clusters including ligandreceptor interaction and signal transduction.展开更多
Bitter receptors were initially identified within the gustatory system.In recent years,bitter receptors have been found in various non-gustatory tissues,including the cardiovascular system,where they participate in di...Bitter receptors were initially identified within the gustatory system.In recent years,bitter receptors have been found in various non-gustatory tissues,including the cardiovascular system,where they participate in diverse physiological processes.To investigate the electrophysiological and potential therapeutic implications of bitter receptors,we have developed a highly sensitive,multifunctional planar-electroporated cell biosensor(PECB)for high-throughput evaluation of the effects of bitter substances on cardiomyocytes.The PECB demonstrated the capability for highthroughput,stable,and reproducible detection of intracellular action potentials(IAPs).In comparison to conventional biosensors that utilize extracellular action potentials(EAPs)for data analysis,the IAPs recorded by the PECB provided high-resolution insights into action potentials,characterized by increased amplitudes and an enhanced signal-to-noise ratio(SNR).The PECB successfully monitored IAPs induced by the activation of bitter receptors by using three bitter substances:diphenidol,denatonium benzoate,and arbutin in cardiomyocytes.To further assess the drug development ability of our PECB,we established an in vitro long QT syndrome(LQTS)model to investigate the potential therapeutic effects of arbutin.The results indicated that arbutin altered the electrophysiological properties of cardiomyocytes and significantly shortened the repolarization time in the LQTS model.Moreover,it demonstrated its potential mechanistic pathway by activating bitter receptors to modulate cardiac ion channel activities.The developed PECB provides an effective platform for high-throughput screening of substrates of bitter receptors for the treatment of heart disease,presenting new opportunities for the development of antiarrhythmic therapies.展开更多
Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review...Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.展开更多
Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications,including infertility,ectopic pregnancy,preterm delive...Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications,including infertility,ectopic pregnancy,preterm delivery,and neonatal death.Despite improved understanding of the mechanisms of pathogenic invasion,the etiopathogenesis of reproductive tract infections is yet to be completely understood.Recent data has suggested a critical role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Here,we review the literature on current etiopathogenesis of reproductive tract infections and the role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Emerging evidence suggests a critical role of microbiota disorder of the reproductive tract in reproductive tract infections.Several bacterial,protozoan parasitic,helminthic parasitic and viral pathogens have been identified as causative agents of reproductive tract infections.These pathogens subvert host defenses and activate specific architectural units of the uroepithelium such as Toll-like receptors,which recognize conserved motifs on the pathogens.The activated Toll-like receptors mediate downstream signaling,stimulating nuclear factor-κB,which in turn activates the production of proinflammatory cytokines.This pathway is also associated with recruitment of immunocytes to the site of aggression and release of proteinases,which drive tissue damage in the reproductive tract.Defects in detection of pathogenic components by the bitter taste receptors of the reproductive tract may play a critical role in the etiopathogenesis of reproductive tract infections.This review provides important information for identification of novel frontiers for the treatment of reproductive tract infections.展开更多
Intestinal obstruction is a blockage that keeps digesta from passing through upper or lower intestine.Traditional Mongolian medicine(TMM)has been proven to be efficacious in the clinical treatment of intestinal obstru...Intestinal obstruction is a blockage that keeps digesta from passing through upper or lower intestine.Traditional Mongolian medicine(TMM)has been proven to be efficacious in the clinical treatment of intestinal obstruction.However,the mechanism of its treatment has not been studied.The bitter taste receptors(T2Rs)are highly expressed in the extra-oral digestive system,such as gastrointestinal tract,which can regulate gastrointestinal peristalsis and contraction of gastrointestinal smooth muscle.In the respiratory system,T2Rs can relax the airway smooth muscle and effectively alleviate asthma symptoms.In this review,the theory and clinical applications of bitter herbs in TMM were discussed and the functional expression of T2Rs and bitter taste signal transduction pathway were analyzed to investigate whether bitter Mongolian medicine may play an effective role in promoting gastrointestinal peristalsis.Therefore,the scientific connotation of the theory of bitter medicinal property of TMM was interpreted by combining T2Rs research and application of modern technology.This new research approach may enrich and improve the basic theory and accelerate the modernization of TMM.展开更多
The interaction mechanism between soyasaponin(Ssa)and bitter receptors/mucin,as well as the saliva interface behavior of Ssa,were investigated to explore the presentation mechanism of Ssa bitterness and astringency(BA...The interaction mechanism between soyasaponin(Ssa)and bitter receptors/mucin,as well as the saliva interface behavior of Ssa,were investigated to explore the presentation mechanism of Ssa bitterness and astringency(BA).Strong bitterness arising from high Ssa concentrations(0.5–1.5 mg/mL)had a masking effect on astringency.At Ssa concentrations of 1.0–1.5 mg/mL,Ssa micelles altered the structure of mucin,exposing its internal tryptophan to a more polar environment.At Ssa concentrations of 0.05–1.50 mg/mL,its reaction with mucin increased the aggregation of particles in artificial saliva,which reduced the frictional lubricating properties of oral saliva.Ssa-mucin interactions affected the salivary interfacial adsorption layer,and their complexes synergistically reduced the interfacial tension.Ssa monomers and soyasapogenols bind to bitter receptors/mucin via hydrogen bonding and hydrophobic interactions.Class A Ssa binds more strongly than class B Ssa,and thus likely presents a higher BA.In conclusion,Ssa interacts with bitter receptors/mucin causing conformational changes and aggregation of salivary mucin,resulting in diminished frictional lubricating properties of oral saliva.This,in turn,affects taste perception and gustatory transmission.展开更多
目的采用可视化方法分析苦味受体领域的研究现状,为该方向的深入探索及临床转化提供参考。方法基于Web of Science核心数据库,检索2000年1月1日至2024年7月1日发表的苦味受体相关英文论文及综述,共获取2884篇文献。运用CiteSpace 6.3.R...目的采用可视化方法分析苦味受体领域的研究现状,为该方向的深入探索及临床转化提供参考。方法基于Web of Science核心数据库,检索2000年1月1日至2024年7月1日发表的苦味受体相关英文论文及综述,共获取2884篇文献。运用CiteSpace 6.3.R1软件对文献进行去重处理,并进行可视化分析。结果结果显示,苦味受体相关研究的年度发文量呈持续增长趋势。美国及莫奈尔化学感官中心在该领域的发文量居首。关键词共现与聚类分析表明,当前研究热点主要集中在苦味受体在不同系统疾病中的炎症机制以及苦味受体激动剂的开发方面。结论靶向调控苦味受体在临床治疗中具有广阔的应用前景.展开更多
目的旨在建立一种基于生物传感器联合超高效液相色谱/串联质谱(ultra-performance liquid chromatography with electrospray tandem mass spectrometry,UPLC-MS/MS)的中药苦味关键质量属性辨识方法。以白术内酯类成分为研究对象,通过...目的旨在建立一种基于生物传感器联合超高效液相色谱/串联质谱(ultra-performance liquid chromatography with electrospray tandem mass spectrometry,UPLC-MS/MS)的中药苦味关键质量属性辨识方法。以白术内酯类成分为研究对象,通过分子对接与生物传感技术揭示其与苦味受体的相互作用机制,实现苦味属性从传统经验判定到分子水平表征的跨越,为完善白术质量控制体系提供支撑。方法采用D101大孔吸附树脂结合紫外分光光度法,制备并筛选富含内酯类成分的白术组分;通过UPLC-MS/MS与分子对接技术,在分子水平解析白术组分与味觉受体的相互作用特征;采用生物传感器与UPLCMS/MS联用技术,实现白术组分苦味关键质量属性的精准辨识。结果成功制得白术不同极性组分11个,其中白术醇提物70%组分的总内酯含量最高,为后续性味研究的理想载体;分子对接实验显示白术组分与Ⅱ型味觉受体家族14号成员(taste receptor type 2 member 14,TAS2R14)的结合展现出明显优势,在分子层面揭示了白术组分具有强烈趋于苦味属性的作用特质;进一步构建苦味生物传感器,对白术组分的苦味属性进行表征,结果显示白术组分与TAS2R14的相互结合强度为49.0ng/L,属于强相互作用,表明以内酯类成分为主的白术组分具有显著的苦味属性,该结果与分子对接结果相互印证,增强了实验结论的可靠性;最后,联合UPLC-MS/MS技术,共辨识得到包括白术内酯Ⅱ在内的苦味关键质量属性13个,在物质基础层面表明白术组分与苦味受体TAS2R14的结合受关键质量属性驱动,为理解白术内酯类成分苦味特性提供直接证据。结论通过多技术融合的系统性研究,从分子相互作用到物质基础层面揭示了白术内酯类成分苦味属性的本质,所发现的苦味关键质量属性为建立基于苦味特征的白术质量控制方法奠定了理论基础,此外,提出的技术路线为中药苦味物质基础研究提供了新的方法学参考。展开更多
基金supported by National Natural Science Foundation of China(32101975)National Key Research and Development Program of China(2021YFD2100104)+4 种基金Modern Agricultural Technical Foundation of China(CARS-42-25)Zhejiang Province Natural Science Foundation(LQ22C200017)Open Project of China Food Flavor and Nutrition Health Innovation Center(CFC2023A-001)Young leading Talents program of Ningbo(2023QL034)Natural Science Foundation of Ningbo(2022J086).
文摘To better understand the bitterness effect and molecule mechanism of myosin-derived peptides activating bitter receptors,the interaction between myosin-derived peptides of dry-cured ham and bitter receptors was investigated by molecular docking and molecular dynamics simulation;the signal transduction mechanism of myosinderived peptides was explored by HEK-293T cells using calcium imaging and transcriptomics analysis.Lower CDOCKER energy was observed during the interaction between myosin-derived peptides and hT2R1 by molecular docking compared with hT2R4,hT2R5,hT2R8,hT2R14 and hT2R16.Hydrogen bonds and hydrophobic interaction were the most important interaction forces which stabilized the interaction of hT2R1 and myosinderived peptides.Compared with LEKEKSELK and TEELEEAKK,the RMSF values and EC50 values of HVLATLGEK were lower,indicating that hT2R1 was more sensitive to HVLATLGEK stimulation.Transcriptomics and KEGG analyses showed that 767 differentially expressed genes were found and mainly involved in cAMP signaling pathway,neuroactive ligand-receptor interaction,calcium signaling pathway and MAPK signaling pathway after stimulating of HVLATLGEK.Protein-protein interaction network further demonstrated that DDIT3,FOS,FOSB,MYC,EGR1 and CCN2 were the key genes to connect the six functional clusters including ligandreceptor interaction and signal transduction.
基金supported by the National Key Research and Development Program of China(2024YFB3212300)Key Project of Zhejiang Province(2023C03104,2024C03146)+4 种基金National Natural Science Foundation of China(32201082,62301481,62401505)Scientific Research Fund of Zhejiang Provincial Education Department(Y202353232)the Postdoctoral Fellowship Program of CPSF(GZC20232333)Postdoctoral Science Foundation Funded Project(BX2021265,2021M702859)the Fundamental Research Funds for the Central Universities(226-2024-00059).
文摘Bitter receptors were initially identified within the gustatory system.In recent years,bitter receptors have been found in various non-gustatory tissues,including the cardiovascular system,where they participate in diverse physiological processes.To investigate the electrophysiological and potential therapeutic implications of bitter receptors,we have developed a highly sensitive,multifunctional planar-electroporated cell biosensor(PECB)for high-throughput evaluation of the effects of bitter substances on cardiomyocytes.The PECB demonstrated the capability for highthroughput,stable,and reproducible detection of intracellular action potentials(IAPs).In comparison to conventional biosensors that utilize extracellular action potentials(EAPs)for data analysis,the IAPs recorded by the PECB provided high-resolution insights into action potentials,characterized by increased amplitudes and an enhanced signal-to-noise ratio(SNR).The PECB successfully monitored IAPs induced by the activation of bitter receptors by using three bitter substances:diphenidol,denatonium benzoate,and arbutin in cardiomyocytes.To further assess the drug development ability of our PECB,we established an in vitro long QT syndrome(LQTS)model to investigate the potential therapeutic effects of arbutin.The results indicated that arbutin altered the electrophysiological properties of cardiomyocytes and significantly shortened the repolarization time in the LQTS model.Moreover,it demonstrated its potential mechanistic pathway by activating bitter receptors to modulate cardiac ion channel activities.The developed PECB provides an effective platform for high-throughput screening of substrates of bitter receptors for the treatment of heart disease,presenting new opportunities for the development of antiarrhythmic therapies.
基金the financial support provided by“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2022C020122022C02078)。
文摘Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.
文摘Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications,including infertility,ectopic pregnancy,preterm delivery,and neonatal death.Despite improved understanding of the mechanisms of pathogenic invasion,the etiopathogenesis of reproductive tract infections is yet to be completely understood.Recent data has suggested a critical role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Here,we review the literature on current etiopathogenesis of reproductive tract infections and the role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Emerging evidence suggests a critical role of microbiota disorder of the reproductive tract in reproductive tract infections.Several bacterial,protozoan parasitic,helminthic parasitic and viral pathogens have been identified as causative agents of reproductive tract infections.These pathogens subvert host defenses and activate specific architectural units of the uroepithelium such as Toll-like receptors,which recognize conserved motifs on the pathogens.The activated Toll-like receptors mediate downstream signaling,stimulating nuclear factor-κB,which in turn activates the production of proinflammatory cytokines.This pathway is also associated with recruitment of immunocytes to the site of aggression and release of proteinases,which drive tissue damage in the reproductive tract.Defects in detection of pathogenic components by the bitter taste receptors of the reproductive tract may play a critical role in the etiopathogenesis of reproductive tract infections.This review provides important information for identification of novel frontiers for the treatment of reproductive tract infections.
文摘Intestinal obstruction is a blockage that keeps digesta from passing through upper or lower intestine.Traditional Mongolian medicine(TMM)has been proven to be efficacious in the clinical treatment of intestinal obstruction.However,the mechanism of its treatment has not been studied.The bitter taste receptors(T2Rs)are highly expressed in the extra-oral digestive system,such as gastrointestinal tract,which can regulate gastrointestinal peristalsis and contraction of gastrointestinal smooth muscle.In the respiratory system,T2Rs can relax the airway smooth muscle and effectively alleviate asthma symptoms.In this review,the theory and clinical applications of bitter herbs in TMM were discussed and the functional expression of T2Rs and bitter taste signal transduction pathway were analyzed to investigate whether bitter Mongolian medicine may play an effective role in promoting gastrointestinal peristalsis.Therefore,the scientific connotation of the theory of bitter medicinal property of TMM was interpreted by combining T2Rs research and application of modern technology.This new research approach may enrich and improve the basic theory and accelerate the modernization of TMM.
基金supported by the Natural Science Foundation of Liaoning Province(2021-MS-311)National Natural Science Foundation of China(31601510).
文摘The interaction mechanism between soyasaponin(Ssa)and bitter receptors/mucin,as well as the saliva interface behavior of Ssa,were investigated to explore the presentation mechanism of Ssa bitterness and astringency(BA).Strong bitterness arising from high Ssa concentrations(0.5–1.5 mg/mL)had a masking effect on astringency.At Ssa concentrations of 1.0–1.5 mg/mL,Ssa micelles altered the structure of mucin,exposing its internal tryptophan to a more polar environment.At Ssa concentrations of 0.05–1.50 mg/mL,its reaction with mucin increased the aggregation of particles in artificial saliva,which reduced the frictional lubricating properties of oral saliva.Ssa-mucin interactions affected the salivary interfacial adsorption layer,and their complexes synergistically reduced the interfacial tension.Ssa monomers and soyasapogenols bind to bitter receptors/mucin via hydrogen bonding and hydrophobic interactions.Class A Ssa binds more strongly than class B Ssa,and thus likely presents a higher BA.In conclusion,Ssa interacts with bitter receptors/mucin causing conformational changes and aggregation of salivary mucin,resulting in diminished frictional lubricating properties of oral saliva.This,in turn,affects taste perception and gustatory transmission.
文摘目的采用可视化方法分析苦味受体领域的研究现状,为该方向的深入探索及临床转化提供参考。方法基于Web of Science核心数据库,检索2000年1月1日至2024年7月1日发表的苦味受体相关英文论文及综述,共获取2884篇文献。运用CiteSpace 6.3.R1软件对文献进行去重处理,并进行可视化分析。结果结果显示,苦味受体相关研究的年度发文量呈持续增长趋势。美国及莫奈尔化学感官中心在该领域的发文量居首。关键词共现与聚类分析表明,当前研究热点主要集中在苦味受体在不同系统疾病中的炎症机制以及苦味受体激动剂的开发方面。结论靶向调控苦味受体在临床治疗中具有广阔的应用前景.
文摘目的旨在建立一种基于生物传感器联合超高效液相色谱/串联质谱(ultra-performance liquid chromatography with electrospray tandem mass spectrometry,UPLC-MS/MS)的中药苦味关键质量属性辨识方法。以白术内酯类成分为研究对象,通过分子对接与生物传感技术揭示其与苦味受体的相互作用机制,实现苦味属性从传统经验判定到分子水平表征的跨越,为完善白术质量控制体系提供支撑。方法采用D101大孔吸附树脂结合紫外分光光度法,制备并筛选富含内酯类成分的白术组分;通过UPLC-MS/MS与分子对接技术,在分子水平解析白术组分与味觉受体的相互作用特征;采用生物传感器与UPLCMS/MS联用技术,实现白术组分苦味关键质量属性的精准辨识。结果成功制得白术不同极性组分11个,其中白术醇提物70%组分的总内酯含量最高,为后续性味研究的理想载体;分子对接实验显示白术组分与Ⅱ型味觉受体家族14号成员(taste receptor type 2 member 14,TAS2R14)的结合展现出明显优势,在分子层面揭示了白术组分具有强烈趋于苦味属性的作用特质;进一步构建苦味生物传感器,对白术组分的苦味属性进行表征,结果显示白术组分与TAS2R14的相互结合强度为49.0ng/L,属于强相互作用,表明以内酯类成分为主的白术组分具有显著的苦味属性,该结果与分子对接结果相互印证,增强了实验结论的可靠性;最后,联合UPLC-MS/MS技术,共辨识得到包括白术内酯Ⅱ在内的苦味关键质量属性13个,在物质基础层面表明白术组分与苦味受体TAS2R14的结合受关键质量属性驱动,为理解白术内酯类成分苦味特性提供直接证据。结论通过多技术融合的系统性研究,从分子相互作用到物质基础层面揭示了白术内酯类成分苦味属性的本质,所发现的苦味关键质量属性为建立基于苦味特征的白术质量控制方法奠定了理论基础,此外,提出的技术路线为中药苦味物质基础研究提供了新的方法学参考。
