Article
Hematology
Danying Liao, Jesse Sundlov, Jieqing Zhu, Heng Mei, Yu Hu, Debra K. Newman, Peter J. Newman
Summary: This study investigated the impact of amino acid substitutions at interfaces between PECAM-1 molecules on homophilic binding and endothelial cell function. It was found that substitutions at key residues within the IgD1-IgD1 and IgD1-IgD2 interfaces disrupted PECAM-1 homophilic binding and downstream effector functions.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Natalia Marcinczyk, Tomasz Misztal, Anna Gromotowicz-Poplawska, Agnieszka Zebrowska, Tomasz Rusak, Piotr Radziwon, Ewa Chabielska
Summary: The study introduced the PECAM-1/thrombus ratio as a parameter indicating platelet activation status, verified its usefulness in animal and human studies using a flow chamber model, and found that acetylsalicylic acid (ASA) could decrease thrombus area while increasing PECAM-1/thrombus ratio in a dose-dependent manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Dennis E. M. de Bakker, Mara Bouwman, Esther Dronkers, Filipa C. Simoes, Paul R. Riley, Marie-Jose Goumans, Anke M. Smits, Jeroen Bakkers
Summary: The homeobox-containing transcription factor Prrx1b is essential for scar-free regeneration of the zebrafish heart by regulating fibrosis and cardiomyocyte proliferation. Prrx1b is activated in epicardial-derived cells where it inhibits TGF beta ligand expression and collagen production while promoting Nrg1 expression to stimulate cardiomyocyte proliferation, maintaining a balance between fibrosis and regeneration in the injured zebrafish heart.
Article
Pharmacology & Pharmacy
Yoshinori Mikami, Fumiki Iwase, Daisuke Ohshima, Taichiro Tomida, Satomi Adachi-Akahane
Summary: This study found that diastolic dysfunction precedes systolic dysfunction in the early stage of diabetic cardiomyopathy. The downregulation of cardioprotective factors in diabetic patients is believed to contribute to this pathophysiological process.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Alexander M. M. Loiben, Wei-Ming Chien, Clayton E. E. Friedman, Leslie S. -L. Chao, Gerhard Weber, Alex Goldstein, Nathan J. J. Sniadecki, Charles E. E. Murry, Kai-Chun Yang
Summary: This study generated cardiomyocytes from induced pluripotent stem cells to model a pathogenic MYH7 missense variant associated with hypertrophic cardiomyopathy (HCM). The findings showed that this variant led to enlarged cardiomyocytes and reduced contractile function, as well as increased apoptosis. Interestingly, the apoptosis and contractile dysfunction were independent of p53 activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Reproductive Biology
Saswati Banerjee, Sameer Mishra, Wei Xu, Winston E. Thompson, Indrajit Chowdhury
Summary: This study reveals that decreased NRG1 levels in granulosa cells (GCs) leads to increased expression and secretion of cytokines and chemokines, as well as decreased phosphorylation of PI3K/Akt/ERK1/2. Exogenous co-treatment with NRG1 delays TNFα-induced apoptosis and inhibits caspase-3/7 activation. Furthermore, gonadotropins may support follicular maturation and ovulation by regulating the expression of NRG1 and ErbB3 receptors in GCs.
JOURNAL OF OVARIAN RESEARCH
(2022)
Article
Cell Biology
Maria Shoykhet, Jens Waschke, Sunil Yeruva
Summary: ADAM family proteins, especially ADAM17, play a role in cardiac diseases, and inhibiting ADAM17 can enhance cardiomyocyte cohesion by stabilizing desmosomal adhesion. In a murine AC model, elevated levels of p38MAPK were found, suggesting an activation of ADAM17. However, ADAM17 levels were unaffected. Acute inhibition of ADAM17 enhanced the localization of DSG2 and DP at the cell membrane, leading to increased cardiomyocyte cohesion. This study suggests the potential therapeutic use of ADAM17 inhibition in AC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Hongchao Wang, Lijie Wang, Fuli Hu, Pengfei Wang, Yanan Xie, Fang Li, Bingyan Guo
Summary: The study found that Nrg4 can improve diabetic-induced myocardial injury by activating autophagy. Nrg4 intervention promotes autophagy and achieves this effect through the AMPK/mTOR signaling pathway.
CARDIOVASCULAR DIABETOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bei Wang, Yuxuan Jin, Jiao Liu, Qian Liu, Yujun Shen, Shengkai Zuo, Ying Yu
Summary: Chemotherapeutic agent doxorubicin (DOX) can cause cardiomyopathy and potentially life-threatening arrhythmias in cancer patients. This study reveals that the prostaglandin E2 (PGE2)/EP1 axis plays a critical role in protecting cardiomyocytes from DOX-induced ferroptosis. EP1 activation promotes nuclear factor erythroid 2-related factor 2 (Nrf2)-driven anti-oxidative gene expression and prevents ferroptotic cell death. The findings suggest that activating EP1 may be a promising strategy for preventing and treating DOX-induced cardiomyopathy.
Article
Multidisciplinary Sciences
Yuxuan Guo, Yangpo Cao, Blake D. Jardin, Isha Sethi, Qing Ma, Behzad Moghadaszadeh, Emily C. Troiano, Neil Mazumdar, Michael A. Trembley, Eric M. Small, Guo-Cheng Yuan, Alan H. Beggs, William T. Pu
Summary: The lack of knowledge about cardiomyocyte maturation is a major obstacle in cardiac regenerative medicine. Actn2 mutation in mice resulted in defective structural maturation of transverse-tubules and mitochondria, triggering transcriptional dysregulation and impairing the normal progression of maturational gene expression. Actn2-based sarcomere organization regulates cardiomyocyte structural and transcriptional maturation through MRTF-SRF signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Food Science & Technology
Basma Tarek, Julia Bruggisser, Filippo Cattalani, Horst Posthaus
Summary: Beta toxin (CPB) is a toxin produced by Clostridium perfringens type C that targets intestinal endothelial cells by interacting with the membrane protein CD31. This study confirms CD31 as the receptor of CPB on human endothelial and monocytic cells, explaining the cell type specificity of CPB observed in vitro and in vivo.
Article
Multidisciplinary Sciences
Kiyoshi Masuyama, Tomoaki Higo, Jong-Kook Lee, Ryohei Matsuura, Ian Jones, Chris Bakal, Shuichiro Higo, Sachio Morimoto, Shigeru Miyagawa, Yoshiki Sawa, Yasushi Sakata
Summary: A novel method was established to evaluate cardiomyocyte alignment in 3D, showing homogeneous alignment in dilated cardiomyopathy (DCM) mice. This homogeneous alignment may serve as a compensatory mechanism for cardiac dysfunction in DCM.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Jonathan D. Moreno, Druv Bhagavan, Allie Li, Nels C. Gerstner, Evan W. Miller, Nathaniel Huebsch, Sharon Cresci, Jonathan R. Silva
Summary: Supplemental Digital Content is accessible in the text.
CIRCULATION-HEART FAILURE
(2022)
Article
Biochemistry & Molecular Biology
Andrea Ramirez-Sagredo, Clara Quiroga, Valeria Garrido-Moreno, Camila Lopez-Crisosto, Sebastian Leiva-Navarrete, Ignacio Norambuena-Soto, Jafet Ortiz-Quintero, Magda C. Diaz-Vesga, William Perez, Troy Hendrickson, Valentina Parra, Zully Pedrozo, Francisco Altamirano, Mario Chiong, Sergio Lavandero
Summary: The study reveals that PC1 plays a regulatory role in mitochondrial morphology and function in cardiomyocytes, with downregulation leading to dysfunction and excessive fission, activating mitophagy. Additionally, PC1 silencing also affects the AKT-FoxO1 signaling pathway related to mitochondrial morphology and function.
Article
Plant Sciences
Jing Ni, Yuanmin Li, Yawei Xu, Rong Guo
Summary: Salidroside has been found to significantly improve diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis by up-regulating HO-1 expression through activation of the AKT signaling pathway. This demonstrates the cardio-protective effect of salidroside in diabetic mice, which is dependent on AKT signaling activation.
Article
Oncology
Dimitri G. Trembath, Eric S. Davis, Shanti Rao, Evan Bradler, Angelica F. Saada, Bentley R. Midkiff, Anna C. Snavely, Matthew G. Ewend, Frances A. Collichio, Carrie B. Lee, Georgia-Sofia Karachaliou, Fatih Ayvali, David W. Ollila, Michal T. Krauze, John M. Kirkwood, Benjamin G. Vincent, Nana Nikolaishvilli-Feinberg, Stergios J. Moschos
Summary: The presence of high tumor-infiltrating lymphocytes (TILs) in patients undergoing craniotomy for melanoma brain metastases (MBM) before 2011 may have prognostic significance. Intratumoral hemorrhage is associated with tumor volume, high expression of basic fibroblast growth factor (bFGF), and high density of CD31+alpha SMA- blood vessels.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Kathryn M. Meurs, Brian G. Williams, Dylan DeProspero, Steven G. Friedenberg, David E. Malarkey, J. Ashley Ezzell, Bruce W. Keene, Darcy B. Adin, Teresa C. DeFrancesco, Sandra Tou
Summary: This study identifies a novel form of cardiomyopathy associated with ALMS1 in Sphynx cats. The presence of a specific mutation in the ALMS1 gene was positively associated with hypertrophic cardiomyopathy in affected cats. These findings suggest that genes involved in cardiac development and cell regulation, such as ALMS1, may play a role in familial hypertrophic cardiomyopathy.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Hong Ma, Ziqing Liu, Yuchen Yang, Dong Feng, Yanhan Dong, Tiffany A. Garbutt, Zhiyuan Hu, Li Wang, Changfei Luan, Cynthia D. Cooper, Yun Li, Joshua D. Welch, Li Qian, Jiandong Liu
Summary: Single-cell transcriptomic analysis reveals the diversity and subpopulation distribution of non-cardiomyocytes during cardiac regeneration, with macrophages playing a key role in activating fibroblast and endothelial cell subpopulations. The study also identifies dynamic transitions between macrophage functional states and factors associated with mRNA processing and transcriptional regulation. A blueprint for interrogating the molecular and cellular basis of cardiac regeneration is provided.
Article
Oncology
Georgia Sofia Karachaliou, Rached Alkallas, Sarah B. Carroll, Chongshan Caressi, Danny Zakria, Nirali M. Patel, Dimitri G. Trembath, Jennifer A. Ezzell, Guillaume J. Pegna, Paul B. Googe, Jonathan P. Galeotti, Fatih Ayvali, Frances A. Collichio, Carrie B. Lee, David W. Ollila, Margaret L. Gulley, Douglas B. Johnson, Kevin B. Kim, Ian R. Watson, Stergios J. Moschos
Summary: This study found that APC/CTNNB1 gene mutations are associated with worse prognosis and early brain metastases in stage IV melanoma. However, PD-1 inhibitor-based treatments provide comparable benefits to both mutated and wild-type patients with stage IV melanoma.
Article
Biotechnology & Applied Microbiology
Zheng Chai, Xintao Zhang, Amanda Lee Dobbins, Richard Jude Samulski, Elizabeth P. Merricks, Timothy C. Nichols, Chengwen Li
Summary: Glucocorticoids, such as dexamethasone, have different effects on transgene expression in AAV-transduced livers in different species. In mouse experiments, dexamethasone significantly increased transgene expression, while no similar effect was observed in hemophilia B dogs. This study provides valuable information for the rational application of dexamethasone in future clinical studies.
HUMAN GENE THERAPY
(2022)
Article
Multidisciplinary Sciences
Catherine A. Makarewich, Amir Z. Munir, Svetlana Bezprozvannaya, Aaron M. Gibson, Soo Young Kim, Misty S. Martin-Sandoval, Thomas P. Mathews, Luke I. Szweda, Rhonda Bassel-Duby, Eric N. Olson
Summary: New evidence suggests that certain noncoding RNA molecules actually code for microproteins. By using comparative genomics, researchers identified a microprotein called Mtlbn that is abundantly expressed in the heart. Mtlbn localizes to the inner mitochondrial membrane and interacts with subunits of the electron transport chain and respiratory supercomplexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Gastroenterology & Hepatology
Joseph Burclaff, R. Jarrett Bliton, Keith A. Breau, Meryem T. Ok, Ismael Gomez-Martinez, Jolene S. Ranek, Aadra P. Bhatt, Jeremy E. Purvis, John T. Woosley, Scott T. Magness
Summary: This study utilizes single-cell transcriptomics to analyze the cellular function of the healthy adult human small intestine and colon. The findings reveal novel lineage marker genes, regional differences, and the response of cells to the environment and drugs. It advances our understanding of human intestinal physiology.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Catherine A. Makarewich, Thomas Thum
Article
Medicine, Research & Experimental
Robert H. Lee, Dorsaf Ghalloussi, Gabriel L. Harousseau, Joseph P. Kenny, Patrick A. Kramer, Fabienne Proamer, Bernhard Nieswandt, Matthew J. Flick, Christian Gachet, Caterina Casari, Anita Eckly, Wolfgang Bergmeier
Summary: Platelet homeostasis relies on tight regulation of production and clearance, with Rap1 signaling crucial for both processes. Deficiency in Rasa3 causes macrothrombocytopenia in mice due to platelet clearance in the spleen and liver, rather than impaired thrombopoiesis. Inhibiting the Rap1/talin1/alpha(IIb)beta(3) integrin axis can restore platelet count and lifespan in Rasa3-mutant mice, suggesting a potential new mechanism of platelet clearance.
Article
Multidisciplinary Sciences
Omar Brito-Estrada, Keira R. Hassel, Catherine A. Makarewich
Summary: This article presents a detailed protocol for using bioinformatic tools to query genomic regions for microprotein-coding potential and provides methods for multiple species alignments and microprotein characteristic analysis. These tools can help identify microprotein-coding sequences in noncanonical genomic regions or rule out the presence of a conserved coding sequence in noncoding transcripts of interest.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Cardiac & Cardiovascular Systems
Emily D. D. Morales, Yongping Yue, Thais B. B. Watkins, Jin Han, Xiufang Pan, Aaron M. M. Gibson, Bryan Hu, Omar Brito-Estrada, Gang Yao, Catherine A. A. Makarewich, Gopal J. J. Babu, Dongsheng Duan
Summary: This study identified DWORF as a potential therapeutic target for Duchenne muscular dystrophy (DMD) cardiomyopathy. Gene therapy using adeno-associated virus serotype 9-DWORF vector significantly enhanced SERCA activity, reduced myocardial fibrosis, and improved exercise capacity, cardiac function, and hemodynamics in mdx mice. These findings suggest that DWORF gene therapy holds promise for treating DMD cardiomyopathy.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Multidisciplinary Sciences
Keira R. Hassel, Omar Brito-Estrada, Catherine A. Makarewich
Summary: Ongoing efforts to annotate the genome have revealed a blind spot for small proteins originating from short open reading frames. The discovery of microproteins, which play diverse roles in cellular processes, has ignited the field of microprotein biology. Large-scale efforts are currently underway to identify and characterize sORF-encoded microproteins.
Review
Cell Biology
Michael L. Kamradt, Catherine A. Makarewich
Summary: Mitochondrial microproteins play important roles in maintaining mitochondrial function and regulating cellular stress responses. Despite being a relatively new field, recent studies suggest that there are still many unknown functions of microproteins in the mitochondrial microproteome that require further investigation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Joseph Burclaff, Jarrett Bliton, Keith A. Breau, Meryem T. Ok, Ismael Gomez Martinez, Jolene S. Ranek, Aadra Bhatt, Jeremy E. Purvis, John T. Woosley, Scott Magness
Article
Physiology
Evan M. Zeitler, J. Charles Jennette, Jennifer E. Flythe, Ronald J. Falk, John S. Poulton
Summary: This study on zebrafish shows that a high-calorie diet, regardless of fat content, can lead to kidney pathology, but these changes can be reversed after 4 weeks of calorie restriction.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)