Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ting Liu, Zhi-Shuai Hou, Hai-Shen Wen, Ya-Xiong Tao
Summary: Four mc4r genes were identified in rainbow trout, which are homologous to those of other fish and mammals. These genes have undergone different evolutionary processes. This study provides the foundation for future research on the physiological functions of mc4r paralogs and the evolution of mc4r in vertebrates.
Article
Pharmacology & Pharmacy
Veronique Pons, Cedric Garcia, Naomi Tidten-Luksch, Aengus Mac Sweeney, Eva Caroff, Celine Gales, Markus A. Riederer
Summary: This study demonstrates the inverse agonistic effect of Selatogrel on the P2Y12 receptor, which is more potent than Ticagrelor. Selatogrel stabilizes the inactive state of the receptor and prevents ADP binding, thereby inhibiting platelet activation.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Rikus Botha, Shree S. Kumar, Natasha L. Grimsey, Kathleen G. Mountjoy
Summary: This study identified a specific signaling profile in HEK293 cells transfected with obesogenic human MC4R variants, including constitutive activity for adenylyl cyclase (AC), cyclic adenosine monophosphate (cAMP) response element (CRE)-driven transcription, and calcium mobilization but not phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) activity. This abnormal signaling profile may serve as a key predictive tool for determining loss of function in obesity-associated mutations.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Biology
Agnes Ribes, Cedric Garcia, Marie-Pierre Gratacap, Evi Kostenis, Laurent O. Martinez, Bernard Payrastre, Jean-Michel Senard, Celine Gales, Veronique Pons
Summary: This study investigated the pharmacology of P2Y(1)-R signaling in various cells and platelets and found that P2Y(1)-R is constitutively active in physiological conditions. The study also identified P2Y(1)-R antagonists that can inhibit this constitutive activation. These findings suggest that targeting P2Y(1)-R constitutive activation could be a promising strategy for antiplatelet therapy.
Article
Biology
Nana Zhang, Haibo Zhu, Zijian Li, Erdan Dong
Summary: The biased ligand Higenamine acts as a novel beta-arrestin-biased ligand by inducing ERK1/2 phosphorylation via EGFR transactivation. Its action is dependent on beta-arrestin1/2 and inhibits Doxorubicin-induced cardiomyocyte apoptosis. These findings provide insight into Higenamine's potential diagnostic and therapeutic applications.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ya-Xiong Tao
Summary: Two new human MRAP2 splice variants were identified in this study, and the effects of MRAP1 and MRAP2 on MC3R and MC4R were investigated. The results suggest that MRAPs play important roles in the signaling and regulation of neural MC3R and MC4R.
Article
Biochemistry & Molecular Biology
Dayana Rodriguez-Contreras, Alec F. Condon, David C. Buck, Naeem Asad, Timothy M. Dore, Dineke S. Verbeek, Marina A. J. Tijssen, Ujwal Shinde, John T. Williams, Kim A. Neve
Summary: A novel dopamine D2 receptor mutation was found to be constitutively active and signaling-biased, with enhanced basal activation and reduced arrestin recruitment compared to the wild type receptor. The impact of this variant in a specific brain region may vary depending on the expression levels of G proteins and GRK.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wang, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: This study reports a new binding mode between a G protein and its receptor, involving a specific small-molecule agonist. The high-resolution structure of the complex is determined, providing insights for designing small-molecule agonists for class B G-protein-coupled receptors.
Review
Medicine, Research & Experimental
Lijuan Mao, Wei Wei, Jingyu Chen
Summary: Glucocorticoids (GCs) are steroid hormones that regulate various homeostatic functions in the body through the binding of glucocorticoid receptor (GR). GR signals are biased, with variations in different tissue cells, disease states, and ligands. This bias regulation of GR signaling depends on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly, and intercellular differences. Selective GR agonists and modulators (SEGRAMs) have been developed to bias therapeutic outcomes towards expected effects by influencing GR-mediated gene expression. This paper reviews the bias regulation and mechanism of GR, as well as the progress in drug research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wu, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.
Article
Neurosciences
Nathan M. Sharfman, Leslie K. Kelley, Maria E. Secci, Nicholas W. Gilpin
Summary: Chronic inflammatory pain is a significant subset of chronic pain diagnoses, affecting a large number of individuals and incurring substantial economic costs. Studies suggest that melanocortin 4 receptors (MC4Rs) may play a role in pain signaling and pain-like behaviors, particularly in the central amygdala (CeA). However, the exact role of MC4Rs in chronic inflammatory pain in males and females is not fully understood.
Article
Biochemistry & Molecular Biology
Diana Zindel, Patrick Mensat, Claire Vol, Zeinab Homayed, Fabienne Charrier-Savournin, Eric Trinquet, Jean-Louis Baneres, Jean-Philippe Pin, Julie Pannequin, Thomas Roux, Elodie Dupuis, Laurent Prezeau
Summary: The Hippo pathway is a key kinase cascade that regulates tissue homeostasis, cellular differentiation, and organ size. By studying the ghrelin receptor, a GPCR that activates Gq exclusively, researchers have shown that GPCRs can finely modulate YAP activity through the Gq pathway.
Review
Hospitality, Leisure, Sport & Tourism
Lei Li, Jinye Liang, Cong Zhang, Tiemin Liu, Chao Zhang
Summary: Melanocortin 4 receptor (MC4R) is the most important single-gene cause of human metabolic disorders and has gained significant interest in the research of energy homeostasis and public health. Previous studies primarily focused on the central roles of MC4R, leaving the local expression and behavioral regulation unclear. This article reviews recent studies on the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons, aiming to provide new directions for future research on MC4R signaling.
JOURNAL OF SPORT AND HEALTH SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Shan-Shan Jiang, Ya-Xiong Tao
Summary: The neural melanocortin receptors (MCRs) and their accessory proteins MRAP1 and MRAP2 play crucial roles in regulating energy homeostasis. This study reveals that MRAP1 and MRAP2s have species-specific effects on canine neural MCRs, providing a better understanding of their regulation.
Article
Cell Biology
Krysten E. Ferraino, Natalie Cora, Celina M. Pollard, Anastasiya Sizova, Jennifer Maning, Anastasios Lymperopoulos
Summary: Angiotensin II (AngII) utilizes AT1R and AT2R G protein-coupled receptors to exert physiological effects, particularly impacting cardiovascular homeostasis. AT1R signaling mobilizes multiple signal transducers inside cells, with Gq/11 proteins and ?-arrestins specifically activated to promote aldosterone synthesis and secretion in the adrenal cortex. "Biased" signaling refers to preferential activation of one signaling pathway over others downstream of the same receptor, with therapeutic relevance in selectively promoting beneficial effects over detrimental consequences.
CELLULAR SIGNALLING
(2021)
Article
Agriculture, Dairy & Animal Science
H. -J. Zhang, Z. -H. Cui, M. Liu, T. -Q. Min, X. Xiao, Z. -Q. Wang, Y. -X. Tao
Summary: The study investigated three naturally occurring mutations in chicken MC3R and found significant defects in receptor pharmacology for G104S and L151R, while the mechanism of action for M54L remains to be further explored.
DOMESTIC ANIMAL ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Li-Kun Yang, Zhi-Shuai Hou, Ya-Xiong Tao
Summary: GPCRs are crucial in transmitting extracellular signals and regulating physiological functions. Mutations in GPCRs can lead to diseases and studying biased agonism provides insights into disease pathogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ya-Xiong Tao
Summary: Two new human MRAP2 splice variants were identified in this study, and the effects of MRAP1 and MRAP2 on MC3R and MC4R were investigated. The results suggest that MRAPs play important roles in the signaling and regulation of neural MC3R and MC4R.
Article
Chemistry, Medicinal
Luis E. Gimenez, Terry A. Noblin, Savannah Y. Williams, Satarupa Mullick Bagchi, Ren-Lei Ji, Ya-Xiong Tao, Claus B. Jeppesen, Kilian W. Conde-Frieboes, Tomi K. Sawyer, Paolo Grieco, Roger D. Cone
Summary: Peptides containing DNal(2 ')7, reported as MC3R subtype-specific agonists, were found to lack MC3R agonist activity. The cell lines used for pharmacological characterization were mischaracterized in terms of receptor subtype expression. Furthermore, peptides containing DNal(2 ')7 primarily exhibit antagonism of MC3R and MC4R.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Huifei Sophia Zheng, Jeffrey G. Daniel, Julia M. Salamat, Laci Mackay, Chad D. Foradori, Robert J. Kemppainen, Satyanarayana R. Pondugula, Ya-Xiong Tao, Chen-Che Jeff Huang
Summary: This study investigated the early transcriptomic responses to dexamethasone (Dex) stimulation in vitro and in vivo, showing that there were distinct differences in the gene expression patterns. The adrenal glands of mice treated with Dex for 1 hour showed a strong association with the development of neuronal cells, indicating a rapid response to Dex in the adrenal medulla. However, in the Y-1 cell line, only a small proportion of genes exhibited differential expression after 1 hour of Dex treatment, and their expression returned to basal levels after 24 hours.
ENDOCRINE CONNECTIONS
(2022)
Review
Biochemistry & Molecular Biology
Li-Qin Ji, Ye Hong, Ya-Xiong Tao
Summary: MC5R is a unique melanocortin receptor with distinct tissue expression patterns, pharmacological properties, and physiological functions. It is widely distributed in both the central nervous system and peripheral tissues and is associated with lipid production, sexual behavior, immunomodulation, and energy metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Alfredo Ulloa-Aguirre, Teresa Zarinan, Ruben Gutierrez-Sagal, Ya-Xiong Tao
Summary: This article discusses the folding and trafficking of GPCRs involved in endocrine diseases, as well as experimental approaches to correct their misfolding, with a particular focus on the promising use of pharmacological chaperones.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Xiao-Chen Yuan, Ya-Xiong Tao
Summary: The discovery of melanocortins and their receptors has led to extensive research over the past 100 years, with particular focus on the neural melanocortin receptors' role in regulating energy homeostasis and potential therapeutic applications for treating metabolic conditions.
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Shan-Shan Jiang, Ya-Xiong Tao
Summary: The neural melanocortin receptors (MCRs) and their accessory proteins MRAP1 and MRAP2 play crucial roles in regulating energy homeostasis. This study reveals that MRAP1 and MRAP2s have species-specific effects on canine neural MCRs, providing a better understanding of their regulation.
Article
Endocrinology & Metabolism
Li-Qin Ji, Ying-Zhu Rao, Yong Zhang, Rong Chen, Ya-Xiong Tao
Summary: In this study, the orange-spotted grouper's Mc5r gene was cloned and its pharmacological characteristics were investigated. Four ligands were found to bind to Mc5r, increasing intracellular cAMP levels. Mrap2 was found to regulate the surface expression and activity of Mc5r. This study provides new insights into the pharmacology and regulation of fish Mc5r.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Editorial Material
Endocrinology & Metabolism
Xiao-Chen Yuan, Ya-Xiong Tao
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Yang Li, Wei-Jia Song, Shao-Kui Yi, Hui-Xia Yu, Hao-Lin Mo, Ming-Xing Yao, Ya-Xiong Tao, Li-Xin Wang
Summary: This study cloned and characterized the GPR84 gene in grass carp and found that it is responsive to medium-chain fatty acids and DIM. The expression of GPR84 in grass carp is high in the liver and spleen.
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ting Liu, Zhi-Shuai Hou, Hai-Shen Wen, Ya-Xiong Tao
Summary: Four mc4r genes were identified in rainbow trout, which are homologous to those of other fish and mammals. These genes have undergone different evolutionary processes. This study provides the foundation for future research on the physiological functions of mc4r paralogs and the evolution of mc4r in vertebrates.
Editorial Material
Multidisciplinary Sciences
Chao Zhang, Ya-Xiong Tao
Article
Chemistry, Medicinal
Kenneth A. Gruber, Ren-Lai Ji, Fabio Gallazzi, Shaokai Jiang, Steven R. Van Doren, Ya-Xiong Tao, Jessica Newton Northup
Summary: During the development of a drug for treating cachexia, we discovered the importance of peptide transport across the blood-brain barrier. Through screening the medical literature, we found that bile salt transport peptides could effectively cross the BBB. We designed a drug peptide, TCMCB07, and made modifications to its C-terminal amino acid sequence to extend its half-life, providing a platform approach for producing similar drug peptides.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
M. T. Ciubuc-Batcu, N. J. C. Stapelberg, J. P. Headrick, G. M. C. Renshaw
Summary: The nervous system relies on mitochondria, and impaired mitochondrial function is associated with major depressive disorder. Modulating mitochondrial function may be a therapeutic target for treating MDD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Correction
Biochemistry & Molecular Biology
Saowaluk Saisomboon, Ryusho Kariya, Piyanard Boonnate, Kanlayanee Sawanyawisuth, Ubon Cha'on, Vor Luvira, Yaovalux Chamgramol, Chawalit Pairojkul, Wunchana Seubwai, Atit Silsirivanit, Sopit Wongkham, Seiji Okada, Sarawut Jitrapakdee, Kulthida Vaeteewoottacharn
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Pavan Thapak, Zhe Ying, Victoria Palafox-Sanchez, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla
Summary: Traumatic brain injury (TBI) impairs cellular energy demand, compromising neuronal function and plasticity. This study demonstrates that the mitochondrial activator humanin (HN) can counteract the reduction in mitochondrial bioenergetics caused by TBI, restore memory function and synaptic protein levels, and suppress inflammation and astrocyte proliferation. HN plays an integral role in normalizing fundamental aspects of TBI pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Paul Murphy, Valeria A. Buzinova, Carrie E. Johnson
Summary: Progress has been made in the treatment of Alzheimer's disease through the development of anti-A beta therapeutics, which have shown modest efficacy in slowing the progression of the disease. However, the puzzling issue remains as to why completely removing A beta does not fully stop the disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yang Zhang, Mengqiu Hao, Xuyang Yang, Su Zhang, Junhong Han, Ziqiang Wang, Hai-Ning Chen
Summary: Colorectal cancer often requires adjuvant therapies to reduce tumor burden, and the efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). ROS-mediated colorectal cancer adjuvant therapies involve multiple mechanisms, and preliminary clinical trials have shown the potential of ROS-manipulating therapy in enhancing treatment outcomes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Mengxin Li, Xuanzhong Wang, Xuyang Chen, Jinghui Hong, Ye Du, Dong Song
Summary: Pancreatic adenocarcinoma (PAAD) is a common digestive malignant tumor with limited treatment options. This study demonstrates that TGM2 may serve as a marker for treatment and prognosis in pancreatic cancer patients. Co-treatment of low dose cisplatin (DDP) and the TGM2 inhibitor GK921 effectively inhibits PAAD cell viability and proliferation in vitro and in vivo, by inhibiting epithelial-to-mesenchymal transition (EMT) induced by TGM2 and enhancing cell cycle arrest and apoptosis caused by DDP. These findings suggest that the combination of GK921 and DDP holds promise as a treatment for PAAD patients.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Liaoran Niu, Qi Wang, Fan Feng, Wanli Yang, Zhenyu Xie, Gaozan Zheng, Wei Zhou, Lili Duan, Kunli Du, Yiding Li, Ye Tian, Junfeng Chen, Qibin Xie, Aqiang Fan, Hanjun Dan, Jinqiang Liu, Daiming Fan, Liu Hong, Jian Zhang, Jianyong Zheng
Summary: This review provides a comprehensive summary of the interaction between cancer cells and macrophages in the tumor microenvironment, and discusses the role of small extracellular vesicles (sEVs) in this process. It also explores the various effects of macrophage-secreted sEVs on tumor malignant transformation, and addresses the therapeutic advancements and challenges associated with these vesicles.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Neha Sawant, Sudhir Kshirsagar, P. Hemachandra Reddy, Arubala P. Reddy
Summary: Depression is a common neuropsychiatric comorbidity in Alzheimer's disease (AD) and other Tauopathies. Selective serotonin reuptake inhibitor (SSRI) treatment, such as Citalopram, not only has anti-depressive and anxiolytic effects, but also helps improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. In this study, Citalopram was found to reduce pathologically pTau level, increase synaptic gene expression and cytoskeletal structure, as well as improve cell survival, mitochondrial respiration, and mitochondrial morphology in cells expressing mutant APP and Tau. These findings suggest that Citalopram could be a promising therapeutic drug for treating depression and AD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Chen, Jiulin Tan, Chuan Yang, Zhiguo Ling, Jianzhong Xu, Dong Sun, Fei Luo
Summary: Bone is a self-healing organ that undergoes continuous regeneration through the cooperation of osteoclasts and osteoblasts. This study used ATAC-seq and RNA-Seq techniques to investigate the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization. The results showed that global chromatin accessibility was extensively improved during osteoblastogenesis. Additionally, several transcription factors including MEF2A, PRRX1, Shox2, and HOXB13 were found to modulate the promoter accessibility of target genes during osteoblast differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Zi-Ran Kang, Shanshan Jiang, Ji-Xuan Han, Yaqi Gao, Yile Xie, Jinxian Chen, Qiang Liu, Jun Yu, Xin Zhao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Huimin Chen, Jing-Yuan Fang
Summary: The study demonstrates that BCAA metabolism is involved in the development of colorectal cancer (CRC). BCAT2 deficiency promotes CRC progression by inhibiting BCAA metabolism and chronically activating the mTORC1 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Chao Zheng, Lingling Liu, Caiyun Liu, Fengna Chu, Yue Lang, Shan Liu, Yan Mi, Jie Zhu, Tao Jin
Summary: Inducing tolerogenic dendritic cells (tDCs) with low RelB expression could effectively alleviate symptoms and reduce immune cell infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE) mouse model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Hang Lam Li, Simei Go, Jung-Chin Chang, Arthur Verhoeven, Ronald Oude Elferink
Summary: This review highlights the distinct characteristics and crucial role of soluble adenylyl cyclase (sAC) in cellular processes, as well as recent significant advancements in the field of sAC research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Seco-Cervera, D. Ortiz-Masia, D. C. Macias-Ceja, S. Coll, L. Gisbert-Ferrandiz, J. Cosin-Roger, C. Bauset, M. Ortega, B. Heras-Moran, F. Navarro-Vicente, M. Millan, J. V. Esplugues, S. Calatayud, M. D. Barrachina
Summary: The study revealed the presence of resistance to apoptosis in complicated ileal Crohn's disease, with PDGFB inducing an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Potential targets against ileal fibrosis include PDGFRB, IL1R1, or MCL1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yunmeng Wang, Ping Cheng
Summary: Oncolytic viruses (OVs) are emerging as therapeutically relevant anticancer agents, especially when combined with genetically modified bispecific T cell engagers (BiTEs). This combination strategy can overcome the limitations of BiTEs alone and provide targeted cytotoxicity to solid tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Stephanie Tannous, Hassan Y. Naim
Summary: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene. A frameshift mutation called c.273_274delAG (p.Gly92Leufs*8) has been identified in CSID patients in Greenlandic population, which leads to loss of digestive function of SI. Surprisingly, the truncated mutant can still be located on the cell surface and interacts with wild type SI, negatively affecting its enzymatic function. Furthermore, heterozygote carriers of this mutation may also exhibit CSID symptoms.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)