Review
Nutrition & Dietetics
Maria Descamps-Sola, Adria Vilalta, Florijan Jalsevac, M. Teresa Blay, Esther Rodriguez-Gallego, Montserrat Pinent, Raul Beltran-Debon, Ximena Terra, Anna Ardevol
Summary: For decades, bitter taste receptors (TAS2R) were believed to be located only in the mouth and serve as sensors for nutrients and harmful substances. However, recent studies have shown their presence in extraoral tissues such as the skin, lungs, and intestine, with unclear functions. This paper focuses on the intestine to understand their physiological role, comparing the presence of these receptors in mice, rats, and humans using sequence homology. Results indicate that expression profiles do not always coincide between species, possibly due to evolutionary divergence and adaptations to different diets. More studies are needed to fully understand these receptors and their functionality along the gastrointestinal tract.
FRONTIERS IN NUTRITION
(2023)
Article
Chemistry, Applied
Mehmet Hakan Ozdener, Andrew Spielman, Paul M. Wise
Summary: Research suggests that sophorolipids may reduce perceived bitterness, as demonstrated by experiments showing reduced responses to bitter compounds in both cultured human taste cells and human participants. This indicates that sophorolipids have potential as candidate ingredients to reduce bitterness.
JOURNAL OF SURFACTANTS AND DETERGENTS
(2021)
Article
Multidisciplinary Sciences
Xiangyu Hao, Hengwu Jiao, Dahu Zou, Qiyang Li, Xiangqun Yuan, Wenbo Liao, Peihua Jiang, Huabin Zhao
Summary: Previous studies have found substantial variation in the number of Tas2r taste receptor genes in vertebrates, with some frog species carrying the largest number. A possible explanation for this is the dietary shift between tadpoles and adults during frog metamorphosis, which may require distinct sets of Tas2r genes. Our study found that amphibians in general possess more Tas2r genes and that around one fifth of the Tas2r genes in the American bullfrog are differentially expressed between tadpoles and adults, suggesting a role of these genes in the ontogenetic dietary shift of frogs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Oncology
Sofie Zehentner, Agnes T. Reiner, Christoph Grimm, Veronika Somoza
Summary: Bitter taste receptors (TAS2Rs) are functionally expressed in various extra-oral cells and their role in cancer is not yet clear, but studies suggest downregulated gene expression in cancerous cells and potential anti-cancer effects through their activation.
Article
Nutrition & Dietetics
Alexandria Turner, Martin Veysey, Simon Keely, Christopher J. Scarlett, Mark Lucock, Emma L. Beckett
Summary: Genetic polymorphisms in taste receptors TAS2R4 and TAS2R5 are associated with lower BMI in males, suggesting a potential role for taste receptors in obesity risk. However, this association seems to be through altered extra-oral responses rather than directly affecting epicatechin intake.
Article
Chemistry, Multidisciplinary
Jun Young Hwang, Kyung Ho Kim, Sung Eun Seo, Youngju Nam, Sanghee Jwa, Inwoo Yang, Tai Hyun Park, Oh Seok Kwon, Seung Hwan Lee
Summary: A bioelectronic tongue system is developed to characterize the agonism and antagonism of bitter taste receptors through the combination of human bitter taste receptors with nanodiscs and graphene field-effect transistors. The system can sensitively detect bitter agonists and evaluate antagonism-based bitterness masking. This is of great importance in the food and pharmaceutical industries.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Review
Medicine, Research & Experimental
Ana R. Costa, Ana C. Duarte, Ana R. Costa-Brito, Isabel Goncalves, Cecilia R. A. Santos
Summary: Pharmacoresistance of cancer cells to chemotherapy drugs is a major challenge. ABC transporters are a leading cause of drug resistance as they transport drugs out of the cells. TAS2Rs, regulated by bitter taste receptors, have been found in various cancer types and organs, and their activation has been linked to multiple biological actions. Bitter compounds, such as flavonoids and alkaloids, have shown potential as adjuvants in cancer therapy. This review discusses the therapeutic role of TAS2Rs and bitter compounds in overcoming chemoresistance in different types of cancer.
Article
Chemistry, Applied
Mathieu Schwartz, Helene Brignot, Gilles Feron, Thomas Hummel, Yunmeng Zhu, Dorothee von Koskull, Jean-Marie Heydel, Federic Lirussi, Francis Canon, Fabrice Neiers
Summary: The molecules that cause taste sensation interact with taste receptors in the taste buds. Enzymes involved in detoxification processes exist in saliva as well as in type II cells where taste receptors, including bitter taste receptors, are located. These enzymes are known to have interactions with various molecules. The study shows that salivary glutathione transferases (GSTA1 and GSTP1) can metabolize bitter molecules, and their levels in the saliva of people with taste disorders are significantly lower than those in the control group.
Article
Biochemistry & Molecular Biology
Hengwu Jiao, Qian Wang, Bing-Jun Wang, Kexin Li, Matej Lovy, Eviatar Nevo, Qiyang Li, Wenchuan Su, Peihua Jiang, Huabin Zhao
Summary: The study demonstrates that bitter taste receptor genes in a wild mammal have undergone local adaptation in different soil environments, affecting food selection and ecological speciation.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Food Science & Technology
Molly J. Higgins, Jacob T. Gipple, John E. Hayes
Summary: Analysis of time-intensity relationships for ten bitterants revealed two distinct groups, characterized by differences in onset and decay rates. Group 1 (including caffeine, quinine, L-phenylalanine, L-tryptophan, urea) showed faster onset and decay, while Group 2 (naringin, SOA, hop extracts) exhibited slower onset, increased intensity post-swallowing, and slower decay. Further research is needed to understand the causes of these temporal differences and their potential impact on liking and consumption of bitter food products.
FOOD QUALITY AND PREFERENCE
(2021)
Article
Plant Sciences
Dorin Dragos, Madalina Petran, Teodora-Cristiana Gradinaru, Marilena Gilca
Summary: This study investigated the potential correlations between the taste of herbal compounds and their anti-inflammatory activity, and found that phytochemical taste may be a better predictor of anti-inflammatory activity than the chemical class.
Article
Multidisciplinary Sciences
Weixiu Xu, Lijie Wu, Shenhui Liu, Xiao Liu, Xiaoling Cao, Cui Zhou, Jinyi Zhang, You Fu, Yu Guo, Yiran Wu, Qiwen Tan, Ling Wang, Junlin Liu, Longquan Jiang, Zhongbo Fan, Yuan Pei, Jingyi Yu, Jianjun Cheng, Suwen Zhao, Xiaojiang Hao, Zhi-Jie Liu, Tian Hua
Summary: This study reports the cryo-electron microscopy structures of human TAS2R46 complexed with chimeric mini-G protein gustducin, providing insights into the features and potential ligand recognition and activation processes of the receptor. These findings lay the foundation for further exploration of bitter taste receptors and their therapeutic applications.
Article
Chemistry, Multidisciplinary
Eitan Margulis, Yuli Slavutsky, Tatjana Lang, Maik Behrens, Yuval Benjamini, Masha Y. Niv
Summary: This study developed the BitterMatch algorithm to predict associations between bitter substances and receptors, achieving encouraging results in experiments. The algorithm combines receptor properties and experimental data, making it useful for predicting off-target effects, identifying new ligands, and guiding flavor design.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Behavioral Sciences
Qiufang Liang, Fanglan Shu, Xiaoyan Dong, Ping Feng
Summary: The study aimed to characterize the evolution of the T2R4 gene and found different regions were subjected to varying selective pressures, with extracellular regions and T2R4 undergoing neutral evolution and purifying selection, while transmembrane and intracellular regions showed purifying selection. Different species with specialized diets affected the evolution of T2R4.
Review
Pharmacology & Pharmacy
Danielle Andrews, Smita Salunke, Anne Cram, Joanne Bennett, Robert S. Ives, Abdul W. Basit, Catherine Tuleu
Summary: The palatability of an oral dosage form is crucial for patient compliance, and excipients can be used to mask the bitterness of a drug. Bitter-blockers are compounds that interact with the molecular pathway of bitterness at a taste-cell level. Some compounds, such as sodium acetate and adenosine 5 ' monophophate, have shown evidence of bitter-blocking and could provide an option for taste-masking aversive medicines.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Cheng-xiang Wang, Ting-ting Wang, Kun-dong Zhang, Ming-yu Li, Qian-cheng Shen, Shao-yong Lu, Jian Zhang
Summary: This study investigated the antitumor potency of two pan-KRAS inhibitors, BI-2852 and BAY-293, in pancreatic ductal adenocarcinoma (PDAC). The inhibitory effects on KRAS activation were validated in vitro and their antiproliferative potency in PDAC cell lines were profiled. However, feedback regulation in the KRAS pathway weakened the inhibitor activity and variations were observed in cell proliferation inhibition in 3D organoids cultured from PDAC patient samples. These results provide a theoretical foundation for KRAS as a clinical therapeutic target and the application of pan-KRAS inhibitors in PDAC treatment, with important scientific significance in translational medicine.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Pharmacology & Pharmacy
Duan Ni, Yaqin Liu, Ren Kong, Zhengtian Yu, Shaoyong Lu, Jian Zhang
Summary: This review comprehensively reviews bioinformatic methods for elucidating allosteric communication and discusses their successful applications in allosteric drug design. Current challenges and future perspectives are also discussed.
DRUG DISCOVERY TODAY
(2022)
Article
Cell Biology
Yiting Jia, Lu Zhang, Ziyi Liu, Chenfeng Mao, Zihan Ma, Wenqiang Li, Fang Yu, Yingbao Wang, Yaqian Huang, Weizhen Zhang, Jingang Zheng, Xian Wang, Qingbo Xu, Jian Zhang, Wei Feng, Caihong Yun, Chuanju Liu, Jinpeng Sun, Yi Fu, Qinghua Cui, Wei Kong
Summary: The study finds that naringenin, a naturally occurring citrus flavonoid, can effectively inhibit the formation and progression of abdominal aortic aneurysm (AAA). This is achieved by activating TFEB, which promotes lysosome-dependent inflammation inhibition and reparative macrophage polarization. Overall, naringenin or TFEB activation shows promising efficacy for AAA treatment.
Article
Obstetrics & Gynecology
Yongxiu Hao, Rui Yang, Jia Li, Zehong Zhou, Weiping Qian, Jian Zhang, Ze Wu, Lei Jin, Xueqing Wu, Cuilian Zhang, Beihong Zheng, Jichun Tan, Guimin Hao, Shangwei Li, Qin Li, Danni Zheng, Yuanyuan Wang, Rong Li, Ping Liu, Jie Qiao
Summary: This study aimed to establish age-specific antimullerian hormone percentile reference values for women of reproductive age and describe the changes of antimullerian hormone.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Article
Chemistry, Organic
Meimei Cheng, Xuechao Cui, Yu Tang, Zongze Shao, Xiupian Liu, Juncheng Su, Jian Zhang, Qi Wang, Guoqiang Li
Summary: Leptochartamides A and B, two pairs of enantiomeric hybrids with a unique core structure, were isolated from the deep-sea-derived fungus Leptosphaerulina chartarum. They exhibited selective cytotoxicity against Ewings sarcoma cells A673.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hao Zhang, Duan Ni, Jigang Fan, Minyu Li, Jian Zhang, Chen Hua, Ruth Nussinov, Shaoyong Lu
Summary: This study reveals the transition pathway of the C-terminal hypervariable region (HVR) of K-Ras4B, identifies key conformational substates, and uncovers important interactions between the HVR and the catalytic domain. These findings are essential for a deeper understanding of the HVR transition mechanism and the regulation of K-Ras4B activity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemical Research Methods
Xiaokun Hong, Ningshan Li, Jiyang Lv, Yan Zhang, Jing Li, Jian Zhang, Hai-Feng Chen
Summary: In this study, a publicly accessible PTMint database was constructed, which contains complete experimental evidence of PTM regulation on PPIs in multiple organisms, covering various diseases. The establishment of this database helps in gaining insight into disease mechanisms, disease diagnosis, and drug discovery associated with PTM and PPI.
Article
Chemistry, Medicinal
Xiaoyue Ji, Xiaochen Cui, Zhengxin Li, Taeyoung Choi, Ying Wang, Wen Xiao, Yunshuo Zhao, Jinyin Zha, Jian Zhang, Hai-Feng Chen, Zhengtian Yu
Summary: Allosteric modulators are regulatory elements that bind to allosteric sites and can impact the properties of proteins. Molecular dynamics simulation has become an important complement to experimental methods in identifying allosteric sites. In this study, a precise force field called APSF was developed using deep learning and reweighting methods, and its performance was evaluated on multiple allosteric proteins. The results showed that APSF could effectively capture different types of allosteric pockets and sample multiple energy-minimum reference conformations. The efficiency of conformation sampling for APSF was also higher than the current force field ff14SB. These findings highlight the potential of APSF in identifying allosteric sites and screening allosteric drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Jixiao He, Xinyi Liu, Chunhao Zhu, Jinyin Zha, Qian Li, Mingzhu Zhao, Jiacheng Wei, Mingyu Li, Chengwei Wu, Junyuan Wang, Yonglai Jiao, Shaobo Ning, Jiamin Zhou, Yue Hong, Yonghui Liu, Hongxi He, Mingyang Zhang, Feiying Chen, Yanxiu Li, Xinheng He, Jing Wu, Shaoyong Lu, Kun Song, Xuefeng Lu, Jian Zhang
Summary: This article introduces the role and importance of allosteric regulation in fine-tuning macromolecular function. It also highlights the recent updates in the Allosteric Database (ASD), including potential allosteric sites, allosteric protein-protein interaction modulators, and allosteric hit-to-lead compounds. These novel features make ASD a comprehensive database, facilitating allosteric target identification, mechanistic exploration, and drug discovery.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Organic
Fengkai Sun, Man Miao, Wenxue Li, Xiao-Bing Lan, Jian-Qiang Yu, Jian Zhang, Zhenyu An
Summary: An array of pyrrolo[1,2-a]quinoxaline derivatives were synthesized with moderate to good yields via the electrochemical redox reaction, involving the functionalization of C(sp(3))-H bonds and construction of C-C and C-N bonds. This atom economical reaction utilized THF as both a reactant and a solvent, with H-2 as the sole by-product.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Jinyin Zha, Jixiao He, Chengwei Wu, Mingyang Zhang, Xinyi Liu, Jian Zhang
Summary: Traditionally, drugs have targeted only one site on the protein surface, which limits their potency and selectivity. Dualsteric modulators, with their bivalent nature, offer a solution by targeting both orthosteric and allosteric sites, allowing for a balance of potency and selectivity, and overcoming drug resistance. They can also be used for designing fluorescent tracers and studying protein conformations.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Jie Zhong, Yuegui Guo, Shaoyong Lu, Kun Song, Ying Wang, Li Feng, Zhen Zheng, Qiufen Zhang, Jiacheng Wei, Peng Sang, Yan Shi, Jianfeng Cai, Guoqiang Chen, Chen-Ying Liu, Xiuyan Yang, Jian Zhang
Summary: This study identifies a best-in-class inhibitor for the protein-protein interaction crucial to colorectal cancer metastasis and develops a sensitivity-enhanced tracer for fluorescence polarization assays to accurately detect high-activity inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Health Care Sciences & Services
Rui Yang, Qin Li, Zehong Zhou, Weiping Qian, Jian Zhang, Ze Wu, Lei Jin, Xueqing Wu, Cuilian Zhang, Beihong Zheng, Jichun Tan, Guimin Hao, Shangwei Li, Tian Tian, Yongxiu Hao, Danni Zheng, Yuanyuan Wang, Robert J. Norman, Rong Li, Ping Liu, Jie Qiao
Summary: The prevalence of polycystic ovary syndrome (PCOS) has significantly increased in Chinese women over the past 10 years, with the current patients exhibiting more severe symptoms possibly related to the higher prevalence of obesity, hyperandrogenism, and infertility. This study highlights PCOS as a significant public health problem in reproductive-aged women in China.
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2022)
Article
Oncology
Chaping Cheng, Jinming Wang, Penghui Xu, Kai Zhang, Zhixiang Xin, Huifang Zhao, Zhongzhong Ji, Man Zhang, Deng Wang, Yuman He, Na Jing, Liancheng Fan, Kaiyuan Liu, Fei Li, Chengcheng Liu, Yiming Gong, Suli Cui, Zhe Sun, Di Sun, Xinlai Yao, Hongjun Li, Jian Zhang, Pengcheng Zhang, Baijun Dong, Wei Xue, Xueming Qian, Wei-Qiang Gao, Helen He Zhu
Summary: Zhu and colleagues identify GREMLIN1 as an FGFR1 ligand that promotes plasticity and castration resistance in prostate cancer through regulation of MAPK signaling. They have generated a specific anti-Gremlin1 therapeutic antibody and demonstrated its synergistic effect with androgen deprivation therapy (ADT) in CRPC, providing a promising candidate therapeutic target for the disease.
Meeting Abstract
Biophysics
Jun Chen, Xiaoyue Ji, Wen Xiao, Zhiyi Wu, Cheng Jiang, Jian Zhang, Zhengtian Yu, Hai-Feng Chen
BIOPHYSICAL JOURNAL
(2022)
