Article
Pharmacology & Pharmacy
Nokomis Ramos-Gonzalez, Sam Groom, Katy J. Sutcliffe, Sukhvinder Bancroft, Chris P. Bailey, Richard B. Sessions, Graeme Henderson, Eamonn Kelly
Summary: The illicit use of fentanyl-like drugs and the resulting overdose deaths is a major problem. This study compared the efficacy and signaling bias of different fentanyls, and found that carfentanil is biased towards beta-arrestin.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Donghwa Kim, Alina Tokmakova, Lauren K. Lujan, Hannah R. Strzelinski, Nicholas Kim, Maliheh Najari Beidokhti, Marc A. Giulianotti, Amirhossein Mafi, Jung-A A. Woo, Steven S. An, William A. Goddard, Stephen B. Liggett
Summary: The study identified a potentially beneficial β(2)-adrenergic receptor agonist, C1-S, for treating asthma, which diverges from the influence of β-arrestin by retaining Gas signaling, resulting in biologically relevant biasing effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Endocrinology & Metabolism
Kelly L. Roszko, Tiffany Y. Hu, Lori C. Guthrie, Beth A. Brillante, Michaele Smith, Michael T. Collins, Rachel Gafni
Summary: Patients with hypoparathyroidism experience poor quality of life, including fatigue and brain fog. Treatment with PTH 1-34 had limited and non-sustained effects on improving quality of life, inconclusive changes in fatigue experience, and no change in the 6-minute walk test.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jia Duan, Heng Liu, Fenghui Zhao, Qingning Yuan, Yujie Ji, Xiaoqing Cai, Xinheng He, Xinzhu Li, Junrui Li, Kai Wu, Tianyu Gao, Shengnan Zhu, Shi Lin, Ming-Wei Wang, Xi Cheng, Wanchao Yin, Yi Jiang, Dehua Yang, H. Eric Xu
Summary: Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) regulates G-protein and arrestin signalling, which can be modulated by biased ligands. However, the molecular assembly of GRKs on GPCRs and the mechanisms of GRK-mediated biased signalling are not well understood. This study presents the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Ga-q, and the arrestin-biased ligand SBI-553. The structure provides insights into the details of GPCR-GRK interactions and the mechanisms underlying GRK2-mediated biased signalling.
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
Biology
Ignacio Portales-Castillo, Thomas Dean, Ross W. Cheloha, Brendan A. Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Juppner, Thomas J. Gardella
Summary: Three mutations in the PTH1R gene have been identified in patients with Eiken syndrome, resulting in altered cAMP signaling and impaired recruitment of beta-arrestin2. These findings highlight the critical role of PTH1R-beta-arrestin interaction in regulating bone formation.
COMMUNICATIONS BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Jean-Pierre Vilardaga, Ieva Sutkeviciute, Karina A. Pena
Summary: The study demonstrates the significant impact of localized cAMP production on cellular functions, particularly in phospho-responses, as revealed through phospho-proteomic analysis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Rita Laforgia, Giovanni Tomasicchio, Federica Cavalera, Maria Sblendorio, Annamaria Spadone, Ferdinando Massimiliano Anelli, Pierluigi Lobascio, Rinaldo Marzaioli, Annunziata Panebianco, Angela Pezzolla
Summary: This study evaluated the management and surgical treatment of parathyroid carcinoma at the Endocrine Surgery Unit of the University Hospital of Bari. The results showed that surgical approach is the best option for parathyroid carcinoma and early identification of high-risk patients is crucial for appropriate treatment.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Peripheral Vascular Disease
Zaira Palomino Jara, Terri J. Harford, Khuraijam Dhanachandra Singh, Russell Desnoyer, Avinash Kumar, Dasarathy Srinivasan, Sadashiva S. Karnik
Summary: This study found that using TRV027 can prevent the progression of aortic aneurysm by different mechanisms compared to the commonly used AT1R blocker, Olmesartan. TRV027 can increase aortic wall thickness, elastin content, and DNA and protein synthesis, while also preventing endoplasmic reticulum stress, fibrosis, and vasomotor hyperresponsiveness.
Review
Pharmacology & Pharmacy
Tianhong Chen, Yi Wang, Zhuowen Hao, Yingkun Hu, Jingfeng Li
Summary: Parathyroid hormone (PTH) regulates bone metabolism by binding to PTH1R, promoting both bone formation and bone resorption. Developing improved PTH-related peptides may address the shortcomings of teriparatide.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Critical Care Medicine
Tito Rocha, Amanda S. Cavalcanti, Ana Carolina Leal, Rhayra B. Dias, Rafaela Sartore da Costa, Gabriele de Oliveira Ribeiro, Joao Antonio Matheus Guimaraes, Maria Eugenia Leite Duarte
Summary: The study investigated the effects of teriparatide in acellular allograft treatment, indicating that it can promote new bone formation, enhance revitalization of allogeneic graft, and increase the frequency and osteogenic capacity of bone marrow stromal cells.
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
(2021)
Article
Endocrinology & Metabolism
Sofia Ish-Shalom, Yoseph Caraco, Nariman Saba Khazen, Michal Gershinsky, Auryan Szalat, Phillip Schwartz, Ehud Arbit, Hillel Galitzer, Jonathan C. Y. Tang, Gregory Burshtein, Ariel Rothner, Arthur Raskin, Miriam Blum, William D. Fraser
Summary: Oral hPTH(1-34) treatment as an adjunct to standard therapy in adult patients with hypoparathyroidism was found to be safe and effective, allowing for a reduction in exogenous calcium supplementation while maintaining normocalcemia.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Medical Laboratory Technology
Jin Cheng, Danni Mu, Danchen Wang, Ling Qiu, Xinqi Cheng
Summary: Automated immunoassays used for evaluating parathyroid function are prone to various types of interference, which can have an impact on clinical practices. This review provides a comprehensive overview of six main types of interference affecting parathyroid hormone (PTH) measurement: heterophilic antibodies, biotin, PTH fragments, oxidized PTH (oxPTH), phosphorylated PTH, and certain preanalytical factors. The prevalence of some of these conditions has been reported to be as high as 11.7%, indicating a potentially significant problem due to the importance of parathyroid function testing. Identification of potential interference typically requires additional laboratory tests, such as method comparison and polyethylene glycol precipitation.
CLINICA CHIMICA ACTA
(2023)
Article
Pharmacology & Pharmacy
Arryn T. Blaine, Yiming Miao, Jinling Yuan, Sophia Palant, Rebecca J. J. Liu, Zhong-Yin Zhang, Richard. M. van Rijn
Summary: The study found that beta-arrestin 2 is positively correlated with the intensity of delta OR agonist-induced seizures, but global beta-arrestin 1 knockout mice are not an ideal model system to investigate their mechanism of action.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Aliya A. Khan, Lars Rejnmark, Mishaela Rubin, Peter Schwarz, Tamara Vokes, Bart Clarke, Intekhab Ahmed, Lorenz Hofbauer, Claudio Marcocci, Uberto Pagotto, Andrea Palermo, Erik Eriksen, Meryl Brod, Denka Markova, Alden Smith, Susanne Pihl, Sanchita Mourya, David B. Karpf, Aimee D. Shu
Summary: This study investigated the safety, tolerability, and efficacy of TransCon PTH in adults with hypoparathyroidism. The results showed that TransCon PTH enabled most participants to achieve independence from standard of care and improved their health-related quality of life.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Cell Biology
Ke Mi, Lizhong Zeng, Yang Chen, Jingya Ning, Siyuan Zhang, Peilin Zhao, Shuanying Yang
Summary: In this study, the researchers explored the role of DHX38 in NSCLC and its underlying molecular mechanism. They found that DHX38 was overexpressed in NSCLC and patients with high DHX38 expression had poor prognosis. DHX38 promoted cell proliferation, migration, and invasion in NSCLC and activated the MAPK pathway. The researchers also identified G3BP1 as a target protein that interacted with DHX38 and showed that DHX38 regulated the expression of G3BP1. Silencing G3BP1 reversed the effects of DHX38 overexpression on tumor cell proliferation, migration, and invasion and inhibited the MAPK pathway activation.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Tiina A. Jokela, Mark A. Dane, Rebecca L. Smith, Kaylyn L. Devlin, Sundus Shalabi, Jennifer C. Lopez, Masaru Miyano, Martha R. Stampfer, James E. Korkola, Joe W. Gray, Laura M. Heiser, Mark A. Labarge
Summary: Microenvironment signals have a significant impact on cell fate and tissue homeostasis. Understanding how different microenvironment factors regulate cellular phenotype has been challenging. In this study, a high-throughput microenvironment microarray was used to identify factors that support the proliferation and maintenance of primary human mammary luminal epithelial cells. Multiple factors that modulate luminal cell number were identified and their effects were confirmed using RNA sequencing and cell-based functional studies. Hepatocyte growth factor (HGF) was found to be robust to individual variation and played a role in expanding luminal cells. Our approach demonstrates the power of high-dimensional cell-based approaches in dissecting microenvironmental signals.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chao He, Yongfeng Ding, Yan Yang, Gang Che, Fei Teng, Haohao Wang, Jing Zhang, Donghui Zhou, Yanyan Chen, Zhan Zhou, Haiyong Wang, Lisong Teng
Summary: This study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of tumor microenvironment (TME) infiltration, and varying sensitivity or resistance to treatment. A stemness risk model was constructed to predict treatment response and prognosis.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haile Zhao, Lijuan Feng, Rui Cheng, Man Wu, Xiaozhou Bai, Lifei Fan, Yaping Liu
Summary: miR-29c-3p is overexpressed in benign and malignant ovarian carcinoma and is associated with poor prognosis. Its overexpression modulates tumorigenesis in ovarian cancer cells, including epithelial-mesenchymal transition, proliferation, migration, and invasion, through the regulation of DNMT3A, TET1, and HBP1. miR-29c-3p may serve as a potential biomarker for clinical diagnosis or co-diagnosis of ovarian carcinoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haiyan Zhao, Fangfang Bi, Mengyuan Li, Yuhan Diao, Chen Zhang
Summary: This study confirmed the tumor suppressor effect of RNF180 on ovarian cancer, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in ovarian cancer, and identified a new therapeutic target for ovarian cancer.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chu Chen, Guanhua Xu, Jiajia Chen, Chunshuai Wu, Jinlong Zhang, Jiawei Jiang, Hongxiang Hong, Zhiming Cui
Summary: This study investigated the role of transcription factor FoxO1 in facet joint osteoarthritis (FJOA) and found that FoxO1 deletion led to severe osteoarthritic changes. Transcriptome sequencing and bioinformatics analysis identified differentially expressed genes (DEGs) and potential key contributors to FJOA. Additionally, over-expression of certain genes and inhibition of others were shown to counteract the impairments caused by FoxO1 deletion in chondrocyte migration and extracellular matrix synthesis. These findings help unravel the molecular mechanisms underlying FJOA and open up promising therapeutic avenues for its treatment.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Wen Deng, Ru Chen, Situ Xiong, Jianqiang Nie, Hailang Yang, Ming Jiang, Bing Hu, Xiaoqiang Liu, Bin Fu
Summary: This study demonstrates that circFSCN1 is upregulated in bladder cancer and associated with cancer-specific survival. CircFSCN1 promotes tumor progression and epithelial-mesenchymal transition in bladder cancer through enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Jun Wu, Weibin Hu, Wenhui Yang, Yihao Long, Kaizhao Chen, Fugui Li, Xiaodong Ma, Xun Li
Summary: Cholesterol biosynthesis and metabolism play critical roles in tumor development and microenvironmental conditions. Squalene Epoxidase (SQLE), the second rate-limiting enzyme in cholesterol synthesis, is found to be uniquely expressed in various cancers, and its expression level is closely associated with tumor mutation burden and microsatellite instability. SQLE expression is negatively correlated with immune cell infiltration. Inhibition of SQLE alters the immune response in the tumor microenvironment. Furthermore, protein metabolism and translation are identified as main binding factors with SQLE.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhihong Zhang, Mingyue Li, Yi Tai, Yue Xing, Hongxiang Zuo, Xuejun Jin, Juan Ma
Summary: ZNF70 plays an important role in colitis-associated colorectal cancer (CAC) by regulating macrophages IL-1 beta secretion to promote HCT116 proliferation. It may serve as a promising target for treating CAC.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zenghong Wu, Gangping Li, Weijun Wang, Kun Zhang, Mengke Fan, Yu Jin, Rong Lin
Summary: This study comprehensively explored the role of immune checkpoints and tumor microenvironment in gastric cancer patients based on genomic data. It constructed an ICIs signature and ICI score to evaluate patient prognosis and heterogeneity.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Yantong Wan, Jieshu Zhou, Panpan Zhang, Xuemei Lin, Hao Li
Summary: This study found that Rac1 plays a role in astrocyte activation and attenuates chronic inflammatory pain by blocking the phosphorylation of NLRP3 inflammasome and NF-kappa B.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhen Wang, Diankun She, Lei Liu, Xianming Hua, Hao Zhu, Lingfeng Yu, Han Wang, Yan Zhu, Gentao Fan, Yicun Wang, Meng Xu, Guangxin Zhou
Summary: Circular RNAs (circRNAs) are non-coding RNAs that play a role in the regulation of various cancers, including osteosarcoma (OS). This study identified circSATB2 as a highly expressed circRNA in OS tissues and cell lines, and demonstrated its involvement in promoting OS proliferation and migration. Mechanistically, circSATB2 was found to regulate the progression of OS by sponging miR-661 and FUS to regulate ZNFX1 mRNA. These findings suggest that circSATB2 could serve as a prognostic marker and therapeutic target for osteosarcoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Kenichi Ogata, Masafumi Moriyama, Tatsuya Kawado, Hiroki Yoshioka, Aiko Yano, Mayu Matsumura-Kawashima, Seiji Nakamura, Shintaro Kawano
Summary: This study found that extracellular vesicles released by induced pluripotent stem cells can reduce inflammatory cell infiltration, increase saliva volume, and decrease the production of antibodies associated with Sjogren's syndrome in a mouse model. The let-7 family in these vesicles may suppress the expression of TLR4 and NF-kappa B, which leads to the inhibition of pro-inflammatory cytokine production through the MAPK pathway.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Mikayla R. Erdelsky, Sarah A. Groves, Charmi Shah, Samantha B. Delios, M. Bibiana Umana, Donald H. Maurice
Summary: Recent evidence suggests that cAMP signaling within the primary cilium plays a crucial role in promoting adipogenic differentiation of 3T3-L1 preadipocytes. In this study, the researchers identified the specific cAMP phosphodiesterases expressed by these cells and found that inhibition of PDE4 promotes FFAR4-mediated adipogenesis. This work could potentially lead to the discovery of more targeted therapeutic approaches for controlling adipogenesis and differentiation of other stem cells.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chun-Hui Liu, Jun-Jie Zhang, Qian-Jin Zhang, Yang Dong, Zhen-Duo Shi, Si-Hao Hong, Hou-Guang He, Wei Wu, Cong-Hui Han, Lin Hao
Summary: Bladder cancer, the most common malignant tumor in the urinary system, is associated with significantly up-regulated expression of P3H4, which is regulated by METTL3 and plays a crucial role in the proliferation, metastasis, and EMT progression of bladder cancer. Targeting this METTL3-P3H4 pathway may serve as a potential therapeutic strategy for bladder cancer.
CELLULAR SIGNALLING
(2024)