Article
Multidisciplinary Sciences
Anbukkarasi Muniyandi, Matthew Martin, Kamakshi Sishtla, Aishat Motolani, Mengyao Sun, Nathan R. Jensen, Xiaoping Qi, Michael E. Boulton, Lakshmi Prabhu, Tao Lu, Timothy W. Corson
Summary: PRMT5 has been identified as a novel therapeutic target for nvAMD, and its inhibitor PR5-LL-CM01 can reduce angiogenesis and activation of NF-kappa B.
SCIENTIFIC REPORTS
(2023)
Article
Behavioral Sciences
Chih-Hsiang Lin, Sung-Chou Li, Ming-Hong Lin, Chen-Jui Ho, Yan-Ting Lu, Yuyu Lin, Pei-Hsien Lin, Kuo-Wang Tsai, Meng-Han Tsai
Summary: This study found that the methylation level of S100A6 gene was decreased in patients with autoimmune encephalitis (AE), and S100A6 promoted the infiltration of B lymphocytes across the blood-brain barrier. S100A6 antibodies could counteract the effect of S100A6, which may be a potential treatment target for AE.
BRAIN AND BEHAVIOR
(2023)
Article
Neurosciences
Young-Geun Choe, Jin-Hui Yoon, Jongyoon Joo, Bokyung Kim, Seon Pyo Hong, Gou Young Koh, Dong-Seok Lee, Wang-Yuhl Oh, Yong Jeong
Summary: The neurovascular unit, consisting of neurons, glial cells, pericytes, and endothelial cells, plays a crucial role in sustaining brain activity. However, the specific function of pericytes in regulating cerebral blood flow remains unclear. This study investigates the impact of pericyte loss on capillary stalling and the potential causes, such as changes in cerebral endothelial glycocalyx and leukocyte adhesion molecules. The results reveal that pericyte loss leads to increased capillary stalling and enhanced interaction between leukocytes and endothelial cells, ultimately resulting in cerebral hypoxia and gliosis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Xu Yang, Dongbin Chen, Shirui Zheng, Meiyan Yi, Shanshan Wang, Yongjian Liu, Lianyan Jing, Zulian Liu, Dehong Yang, Yujia Liu, Linmeng Tang, James R. Walters, Yongping Huang
Summary: In lepidopteran insects, both nucleated and anucleated sperm are essential for fertilization. Prmt5 and Vasa genes play critical roles in regulating spermatogenesis in these insects.
Article
Cell Biology
He Liu, Kunpeng Jia, Zhengnan Ren, Jia Sun, Li-Long Pan
Summary: A high plasma level of trimethylamine N-oxide (TMAO) is closely associated with the development of cardiovascular disease. This study demonstrates that protein arginine methyltransferase 5 (PRMT5) expression is positively correlated with TMAO-induced vascular inflammation, leading to increased vascular cell adhesion molecule-1 (VCAM-1) expression. Knockdown of PRMT5 inhibits VCAM-1 expression and macrophage adhesion to TMAO-stimulated vascular smooth muscle cells (VSMC). The study also reveals that TMAO induces nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) expression and reactive oxygen species production, which contributes to PRMT5 expression and subsequent VCAM-1 expression.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Shelby L. Sloan, Fiona Brown, Mackenzie Long, Christoph Weigel, Shirsha Koirala, Ji-Hyun Chung, Betsy Pray, Lynda Villagomez, Claire Hinterschied, Anuvrat Sircar, Jobeth Helmig-Mason, Alexander Prouty, Eric Brooks, Youssef Youssef, Walter Hanel, Samir Parekh, Wing Keung Chan, Zhengming Chen, Rosa Lapalombella, Lalit Sehgal, Kris Vaddi, Peggy Scherle, Selina Chen-Kiang, Maurizio Di Liberto, Olivier Elemento, Cem Meydan, Jonathan Foox, Daniel Butler, Christopher E. Mason, Robert A. Baiocchi, Lapo Alinari
Summary: Inhibition of PRMT5 in mantle cell lymphoma demonstrated antitumor activity and restored regulatory activity of the cell cycle, apoptotic cell death, and negative regulators of the B-cell receptor-PI3K/AKT signaling pathway. The selective targeting of PRMT5 shows promise as a potential therapy for patients with relapsed/refractory MCL.
Article
Oncology
Shuangjie Liu, Zhuonan Liu, Chiyuan Piao, Zhe Zhang, Chuize Kong, Lei Yin, Xi Liu
Summary: The study reveals PRMT5 as a therapeutic target for bladder cancer and identifies FKA, extracted from the kava plant, as an inhibitor of PRMT5 for the treatment of bladder cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Summary: Cancer cells regulate their response to the chemotherapeutic drug doxorubicin through RNA m6A modification. They do this by inhibiting RNA m6A modification through PRMT5 and enhancing the nuclear translocation of the demethylase ALKBH5. This leads to increased DNA repair ability and decreased efficacy of doxorubicin. The approved drug tadalafil was identified as a PRMT5 inhibitor that could enhance doxorubicin sensitivity in breast cancer cells by decreasing RNA m6A methylation.
Article
Biochemistry & Molecular Biology
Taiki Tojo, Minako Yamaoka-Tojo
Summary: This study investigated the molecular and cellular mechanisms underlying stenotic calcification of the aortic valve. Gene expression analysis of human aortic stenosis and normal aortic valve tissue identified differentially expressed genes (DEGs) associated with valve calcification and disease progression. Protein-protein interaction analysis revealed hub genes that could serve as potential biomarkers and therapeutic targets for aortic stenosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Salik Miskat Borbora, Raju S. Rajmani, Kithiganahalli Narayanaswamy Balaji
Summary: Mycobacterium tuberculosis infection can lead to the formation of lipid-rich foamy macrophages (FMs) that provide a favorable environment for pathogen persistence. During infection, the expression of the E3 ubiquitin ligase ITCH is significantly reduced, allowing key lipid accumulation molecules (ADRP and CD36) to be spared from proteasomal degradation. Furthermore, this repression of ITCH depends on the coordinated action of the bifunctional transcription factor YY1 and the arginine methyl transferase PRMT5. The NOTCH signaling pathway is identified as a master regulator of YY1 expression. In vitro and in vivo analyses demonstrate the importance of PRMT5 in regulating FM formation and mycobacterial burden.
Review
Cardiac & Cardiovascular Systems
Carina Mauersberger, Julia Hinterdobler, Heribert Schunkert, Thorsten Kessler, Hendrik B. Sager
Summary: This article comprehensively reviews the process of leukocyte recruitment relevant to atherosclerosis, with a focus on endothelial cells, monocytes and macrophages, neutrophils, T lymphocytes and platelets. Therapeutic options targeting leukocyte recruitment into atherosclerotic lesions, as well as potential insights into its precise mechanisms, are also highlighted.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Sreelakshmi N. Menon, Farzana Zerin, Emmanuella Ezewudo, Nimi P. Simon, Sreeranjini N. Menon, Morgan L. Daniel, Andrea J. Green, Ajay Pandey, Charles E. Mackay, Sherif Hafez, Nader H. Moniri, Raquibul Hasan
Summary: Neflamapimod effectively inhibits endothelial cell activation, adhesion molecule expression, and leukocyte attachment, thereby reducing vascular inflammation.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Noureddine Ben Khalaf, Dalal Al-Mehatab, Dahmani M. Fathallah
Summary: In this study, it was shown that ERp72 is overexpressed on vascular endothelial cells in the early phase of the inflammatory response following skeletal muscle injury. This upregulation of ERp72 may potentially play a role in skeletal muscle inflammation and modulate leukocyte-endothelial cell interactions.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Chemistry, Medicinal
Andrew M. Asberry, Xinpei Cai, Xuehong Deng, Ulises Santiago, Sheng Liu, Hunter S. Sims, Weida Liang, Xueyong Xu, Jun Wan, Wen Jiang, Carlos J. Camacho, Mingji Dai, Chang-Deng Hu
Summary: Protein arginine methyltransferase 5 (PRMT5) is a crucial epigenetic regulator and a validated therapeutic target in multiple cancers. Researchers have developed a novel small-molecule inhibitor, compound 17, which can target the protein-protein interaction between PRMT5 and MEP50. In vitro experiments demonstrated that compound 17 inhibits PRMT5 and MEP50 substrate methylation selectively, with an IC50 < 500 nM in prostate and lung cancer cells. It also dysregulates the TGF-beta signaling pathway according to RNA-seq analysis. This study provides proof of concept for targeting PRMT5:MEP50 protein-protein interaction and supports further preclinical development of inhibitors in this class.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Yunfeng Yang, Daniel P. Harris, Feng Luo, Liyou Wu, Andrea B. Parsons, Anthony V. Palumbo, Jizhong Zhou
Article
Biotechnology & Applied Microbiology
Yunfeng Yang, Daniel P. Harris, Feng Luo, Wenlu Xiong, Marcin Joachimiak, Liyou Wu, Paramvir Dehal, Janet Jacobsen, Zamin Yang, Anthony V. Palumbo, Adam P. Arkin, Jizhong Zhou
Article
Biochemistry & Molecular Biology
Daniel P. Harris, Smarajit Bandyopadhyay, Tyler J. Maxwell, Belinda Willard, Paul E. DiCorleto
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Rheumatology
Pamela F. Weiss, Timothy G. Brandon, John Bohnsack, Merav Heshin-Bekenstein, Michael L. Francavilla, Jacob L. Jaremko, Lester Liao, Anne McHugh, Edward J. Oberle, Dax Rumsey, Hemalatha Srinivasalu, Matthew L. Stoll, Nancy A. Chauvin
Summary: The study evaluated the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac joints in children. Local reports showed high sensitivity but low positive predictive value for inflammation, while low sensitivity but high specificity for structural damage. Additional training in MRI appearance of the maturing SI joint is needed for reliable pathology identification.
ARTHRITIS CARE & RESEARCH
(2021)
Article
Pediatrics
Sara Pavitt, Anne McHugh, Kevin Chi, Kim Hoang, Elizabeth Lippner, Jennifer Tsai, Rachel Goldstein, Hannah Bassett, Nivedita S. Srinivas
Summary: The implementation of a standardized consult communication tool successfully increased the inclusion of ECEs, improved the clarity of consult questions, decreased perceived miscommunication, and enhanced overall consult satisfaction.
Article
Rheumatology
Anne McHugh, Avis Chan, Carolyn Herrera, Jennifer M. Park, Imelda Balboni, Dana Gerstbacher, Joyce J. Hsu, Tzielan Lee, Margo Thienemann, Jennifer Frankovich
Summary: This study aimed to evaluate emotional and behavioral symptoms in children with juvenile spondyloarthritis (SpA) and polyarticular arthritis (PolyA) and investigate the relationship between these symptoms and disease activity. The results showed that more active disease was associated with worse psychological functioning and more internalized emotional disturbances.
JOURNAL OF RHEUMATOLOGY
(2022)
Article
Physiology
Daniel P. Harris, Arvind Balasubramaniam, M. Safwan Badr, Jason H. Mateika
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2006)