Review
Pharmacology & Pharmacy
P. Boknik, J. Eskandar, B. Hofmann, N. Zimmermann, J. Neumann, U. Gergs
Summary: This review provides an overview of the localization and role of cardiac A(2A)-adenosine receptors, as well as their potential involvement in relevant cardiac pathologies. The review also discusses the cardiac utility of A(2A)-AR as therapeutic targets and identifies gaps in knowledge for future research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lisa Ernst, Zoltan Czigany, Pascal Paschenda, Mareike Schulz, Lukas Breuer, Janosch Kunczik, Michael Czaplik, Wenjia Liu, Decan Jiang, Uwe Klinge, Sonja Djudjaj, Peter Boor, Georg Lurje, Eiji Kobayashi, Rene H. Tolba
Summary: Ischemia-reperfusion injury is a significant problem in organ transplantation, and in this pilot study, a new thermal insulation bag was used to protect the transplanted organ. The bag showed good insulation capacity and usability, and the clinical outcomes suggested that its use could reduce kidney damage, although its impact on mildly damaged kidneys is still unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hanyi Liu, Jinglin Wang, Yitao Ding, Xiaolei Shi, Haozhen Ren
Summary: Our study demonstrates that prophylactic antibiotic pretreatment can attenuate liver ischemia-reperfusion injury by reshaping the gut microbiota and altering bile acid composition. This beneficial effect is mediated through the activation of the farnesoid X receptor (FXR) pathway, which suppresses inflammatory responses and cell apoptosis in the liver. These findings suggest that targeting FXR activation may be a potential therapeutic strategy for liver injury.
CELL DEATH & DISEASE
(2022)
Article
Chemistry, Medicinal
Tasia Amelia, Jacobus P. D. van Veldhoven, Matteo Falsini, Rongfang Liu, Laura H. Heitman, Gerard J. P. van Westen, Elena Segala, Gregory Verdon, Robert K. Y. Cheng, Robert M. Cooke, Daan van der Es, Adriaan P. IJzerman
Summary: In this study, the crystal structure of an engineered human adenosine A(2A) receptor bound to a partial agonist was determined and compared to structures bound to a full agonist or antagonist/inverse agonist. Interaction between the partial agonist and amino acids in the ligand binding pocket led to the development of a library of derivatives with varied activities. Some derivatives showed partial agonist properties while others acted as inverse agonists, with additional computational docking studies providing insights into this behavior.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Physiology
Antonio Hernandez, Naeem K. Patil, Maya Brewer, Rachel Delgado, Lauren Himmel, Lauren N. Lopez, Julia K. Bohannon, Allison M. Owen, Edward R. Sherwood, Mark P. de Caestecker
Summary: This study aimed to investigate whether a novel Toll-like receptor 4 agonist could attenuate acute kidney injury induced by ischemia-reperfusion injury. The results showed that pretreatment with the agonist improved kidney function, reduced renal tissue injury and apoptosis. The findings suggest that the agonist can provide protection against ischemia-reperfusion injury-induced acute kidney injury.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Immunology
Zhen Cao, Silong Mu, Maihuan Wang, Yun Zhang, Guijun Zou, Xinpu Yuan, Yun Huang, Siwang Yu, Jinming Zhang, Chaojun Zhang
Summary: Intestinal ischemia-reperfusion (I/R) injury disrupts the intestinal barrier composed of tight junction proteins, leading to the entry of bacteria and endotoxins into the bloodstream and causing distant organ damage. This study investigated the role of succinate, an intermediate product of the tricarboxylic acid cycle, in intestinal I/R injury, and found that pretreatment with succinate reduced tissue damage, necroptosis, and inflammation. The protective effect of succinate was associated with the upregulation of the inflammatory protein KLF4 and was diminished after inhibition of KLF4.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Yun Xia, Feng He, Mohamed Bassirou Moukeila Yacouba, Huimin Zhou, Jingfan Li, Ying Xiong, Jingjing Zhang, Hui Li, Yanlin Wang, Jianjuan Ke
Summary: The activation of adenosine A2a receptor plays a crucial role in protecting myocardial cells from ischemia-reperfusion injury through regulating autophagy and apoptosis processes. This finding provides a potential target for preventing and treating myocardial ischemia-reperfusion injury.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cell Biology
Kadambari Chandra Shekar, Demetris Yannopoulos, Marinos Kosmopoulos, Matthias L. Riess
Summary: In a pre-clinical porcine model of acute myocardial infarction (AMI), there were no consistent individual functional differences observed between subsarcolemmal and interfibrillar mitochondria during the initial few hours of reperfusion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Il-Gyu Ko, Jun-Jang Jin, Lakkyong Hwang, Sang-Hoon Kim, Chang-Ju Kim, Kyu Yeoun Won, Yong Gil Na, Khae Hawn Kim, Su Jin Kim
Summary: The study investigated the effect of polydeoxyribonucleotide (PDRN) on a cyclophosphamide-induced interstitial cystitis (IC) animal model in rats. Results showed that PDRN treatment alleviated voiding dysfunction, bladder edema, and histological damage caused by cyclophosphamide-induced IC. PDRN treatment also suppressed secretion of pro-inflammatory cytokines and expressions of apoptotic factors, suggesting its potential as an effective therapeutic agent for IC.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Endocrinology & Metabolism
Tito Borner, Caroline E. Geisler, Samantha M. Fortin, Richard Cosgrove, Jorge Alsina-Fernandez, Mridula Dogra, Sarah Doebley, Marcos J. Sanchez-Navarro, Rosa M. Leon, Jane Gaisinsky, Arianna White, Ankur Bamezai, Misgana Y. Ghidewon, Harvey J. Grill, Richard C. Crist, Benjamin C. Reiner, Minrong Ai, Ricardo J. Samms, Bart C. De Jonghe, Matthew R. Hayes
Summary: GIPR signaling blocks emesis and attenuates illness behaviors induced by GLP-1R activation while maintaining reduced food intake, weight loss, and improved glucose tolerance. The hindbrain AP/NTS is crucial for processing GLP-1R ligand-induced effects on food intake and weight suppression, as well as emetic stimuli.
Review
Immunology
Yanzhi Jiang, Jianxin Lin, Haiyun Zheng, Ping Zhu
Summary: This review examines the role of purinergic signaling in ischemia-reperfusion injury and rejection after heart transplantation, as well as its clinical applications and prospects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Dong, Jianyong Yin, Teng Chen, Jiejun Wen, Qunzi Zhang, Xiaomei Li, Wenjun Lin, Feng Liu, Ying Fan, Niansong Wang
Summary: The study demonstrated that Dl-3-n-butylphthalide (NBP) has a significant protective effect on preventing renal ischemia reperfusion injury by alleviating inflammation, oxidative stress, and cell apoptosis. The findings suggest that NBP could be a promising candidate for combating acute kidney injury.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Hector Godoy-Marin, Veronica Jimenez-Sabado, Carmen Tarifa, Antonino Ginel, Joana Larupa Dos Santos, Bo Hjorth Bentzen, Leif Hove-Madsen, Francisco Ciruela
Summary: Adenosine, a nucleoside, plays an important role in maintaining homeostasis under stressful conditions like energy deprivation or cellular damage. Extracellular adenosine is generated in tissues under conditions such as hypoxia, ischemia, or inflammation. In patients with atrial fibrillation (AF), adenosine levels are elevated, and the density of adenosine A(2A) receptors (A(2A)Rs) is increased. Experimental models of AF that mimic the alterations in A(2A)R density in patients with AF are needed to study the adenosinergic system in AF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela Madeira, Liliana Dias, Patricia Santos, Rodrigo A. Cunha, Paula Agostinho, Paula M. Canas
Summary: Anxiety involves abnormal glucocorticoid signaling and altered communication between glia and neurons. A blockade of the adenosine A(2A) receptor (A(2A)R) can improve mood and memory impairments by preventing synaptic dysfunction and astrogliosis. This study found that A(2A)R controls the function of astrocytes, which contribute to abnormal glucocorticoid brain signaling, suggesting that A(2A)R is a potential therapeutic target for managing mood disorders.
PURINERGIC SIGNALLING
(2022)
Article
Orthopedics
Omid Sadatpour, Mohammad Taha Ebrahimi, Maryam Akhtari, Nooshin Ahmadzadeh, Mahdi Vojdanian, Ahmadreza Jamshidi, Elham Farhadi, Mahdi Mahmoudi
Summary: The study found that A(2A)AR activation cannot reduce MMP8 expression in patients' macrophages, while it can in healthy macrophages. The effect of A(2A)AR activation on BMP2 and MMP9 expression did not reach statistical significance in either healthy macrophages or the patients' group. Additionally, a significant positive correlation was discovered between MMP8 expression and patient scores on the BASFI.
BMC MUSCULOSKELETAL DISORDERS
(2022)
Article
Cardiac & Cardiovascular Systems
Matthew R. Byler, Nathan S. Haywood, Dustin T. Money, Aimee Zhang, Jared P. Beller, Eric J. Charles, William Z. Chancellor, Huy Q. Ta, Mark H. Stoler, J. Hunter Mehaffey, Victor E. Laubach, Irving L. Kron, Mark E. Roeser
SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Nathan Haywood, Huy Q. Ta, Aimee Zhang, Eric J. Charles, Evan Rotar, Sean Noona Iv, Morgan Salmon, Zdravka Daneva, Swapnil K. Sonkusare, Victor E. Laubach
Summary: This study demonstrates that endothelial TRPV4 channels play a key role in vascular permeability and lung inflammation after ischemia-reperfusion injury (IRI). TRPV4 channels may be a promising therapeutic target to mitigate lung IRI and decrease the incidence of primary graft dysfunction after transplant.
ANNALS OF THORACIC SURGERY
(2022)
Article
Critical Care Medicine
Nathan Haywood, Matthew R. Byler, Aimee Zhang, Evan P. Rotar, Dustin Money, Sarah E. Gradecki, Huy Q. Ta, Morgan Salmon, Irving L. Kron, Victor E. Laubach, J. Hunter Mehaffey, Mark E. Roeser
Summary: The study demonstrates that A2AR agonists can mitigate burn progression by reducing local inflammatory processes, such as slowing down the rate of necrotic interspace development and decreasing dermal neutrophil infiltration. Extended dosing strategies may offer additional benefits and improve the overall cosmetic outcome for patients with severe injuries.
JOURNAL OF BURN CARE & RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Craig T. Elder, Amanda C. Filiberto, Gang Su, Zachary Ladd, Victoria Leroy, Eric Y. Pruitt, Guanyi Lu, Zhihua Jiang, Ashish K. Sharma, Gilbert R. Upchurch
Summary: MaR1 treatment attenuates abdominal aortic aneurysm (AAA) growth via LGR6 receptor signaling and macrophage-dependent efferocytosis, increasing SMC alpha-actin and TGF-beta 2 expressions.
Article
Immunology
Samira Mansouri, Himanshu Gogoi, Mauricio Pipkin, Tiago N. Machuca, Amir M. Emtiazjoo, Ashish K. Sharma, Lei Jin
Summary: This study found that exogenous IFN beta can reprogram specific lung cells involved in asthma, alleviating symptoms and potentially being used for future treatments.
SCIENCE IMMUNOLOGY
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Ashish K. Sharma
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Cardiac & Cardiovascular Systems
Huy Q. Ta, Nicholas R. Teman, Irving L. Kron, Mark E. Roeser, Victor E. Laubach
Summary: This study found that the use of Steen solution can significantly improve the pulmonary endothelial barrier function of patients with acute respiratory distress syndrome, reduce inflammation, and protect the connections of endothelial cells. These findings are of great significance for improving the treatment of severe acute respiratory distress syndrome.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Article
Multidisciplinary Sciences
Amanda C. Filiberto, Michael D. Spinosa, Craig T. Elder, Gang Su, Victoria Leroy, Zachary Ladd, Guanyi Lu, J. Hunter Mehaffey, Morgan D. Salmon, Robert B. Hawkins, Kodi S. Ravichandran, Brant E. Isakson, Gilbert R. Upchurch, Ashish K. Sharma
Summary: This study reveals that Panx1 channels on endothelial cells play a role in regulating vascular inflammation and remodeling. It acts as a conduit for ATP release, which stimulates macrophage activation and the release of inflammatory factors. Additionally, Panx1 signaling also modulates intracellular calcium release in smooth muscle cells, affecting vascular remodeling.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Amanda C. Filiberto, Zachary Ladd, Victoria Leroy, Gang Su, Craig T. Elder, Eric Y. Pruitt, Sara E. Hensley, Guanyi Lu, Joseph B. Hartman, Ali Zarrinpar, Ashish K. Sharma, Gilbert R. Upchurch
Summary: This study reveals the protective role of Resolvin D1 (RvD1) in attenuating abdominal aortic aneurysms (AAA) through formyl peptide receptor 2 (FPR2) signaling. It also demonstrates the immunomodulation of FPR2 signaling on macrophages by RvD1, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis. The study highlights the decreased expression of FPR2 in human AAA tissue compared to non-aneurysm human aortas.
Article
Cardiac & Cardiovascular Systems
Victoria Leroy, Jun Cai, Zhenxiao Tu, Alexander McQuiston, Simrun Sharma, Amir Emtiazjoo, Carl Atkinson, Gilbert R. Upchurch, Ashish K. Sharma
Summary: Combined treatment with specialized pro-resolving lipid mediators, RvD1 and MaR1, enhances inflammation-resolution of lung ischemia-reperfusion injury, providing a potential therapeutic strategy for postlung transplant complications.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Surgery
Evan P. Rotar, Nathan S. Haywood, J. Hunter Mehaffey, Dustin T. Money, Huy Q. Ta, Mark H. Stoler, Nicholas R. Teman, Victor E. Laubach, Irving L. Kron, Mark E. Roeser
Summary: This study successfully established a model of acute lung injury in pigs by superimposing gastric aspiration and ventilator-induced injury. The model may be useful for testing treatment strategies for ARDS.
JOURNAL OF SURGICAL RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Zachary Ladd, Gang Su, Joseph Hartman, Guanyi Lu, Sara Hensley, Gilbert R. Upchurch Jr, Ashish K. Sharma
Summary: This study explored the regulation role of spironolactone in endothelial cell-mediated ATP release for the mitigation of abdominal aortic aneurysm (AAA) formation. The results showed that spironolactone treatment could decrease the diameter of the abdominal aorta, reduce elastic fiber disruption, and immune cell infiltration. Furthermore, it also suppressed the expression of pro-inflammatory cytokines, inhibited MMP2 activity, and reduced ATP content in the aortic tissue. In vitro experiments demonstrated that spironolactone attenuates extracellular ATP release from endothelial cells, leading to decreased macrophage activation and smooth muscle cell-dependent vascular remodeling.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Meeting Abstract
Immunology
Ashish Kumar Sharma, Jun Cai, Victoria Leroy, Zhenxiao Tu, Alejandro Gonzalez, Joseph Hartman, Jennifer Mulligan, Carl Atkinson, Gilbert Upchurch
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hrishikesh S. Kulkarni, Janet S. Lee, Julie A. Bastarache, Wolfgang M. Kuebler, Gregory P. Downey, Guillermo M. Albaiceta, William A. Altemeier, Antonio Artigas, Jason H. T. Bates, Carolyn S. Calfee, Charles S. Dela Cruz, Robert P. Dickson, Joshua A. Englert, Jeffrey Everitt, Michael B. Fessler, Andrew E. Gelman, Kymberly M. Gowdy, Steve D. Groshong, Susanne Herold, Robert J. Homer, Jeffrey C. Horowitz, Connie C. W. Hsia, Kiyoyasu Kurahashi, Victor E. Laubach, Mark R. Looney, Rudolf Lucas, Nilam S. Mangalmurti, Anne M. Manicone, Thomas R. Martin, Sadis Matalon, Michael A. Matthay, Daniel F. McAuley, Sharon A. McGrath-Morrow, Joseph P. Mizgerd, Stephanie A. Montgomery, Bethany B. Moore, Alexandra Noel, Carrie E. Perlman, John P. Reilly, Eric P. Schmidt, Shawn J. Skerrett, Tomeka L. Suber, Charlotte Summers, Benjamin T. Suratt, Masao Takata, Rubin Tuder, Stefan Uhlig, Martin Witzenrath, Rachel L. Zemans, Gutavo Matute-Bello
Summary: Advancements in methods and technology have led to the need for an updated definition of experimental acute lung injury (ALI). Through surveys and workshops, researchers propose that ALI presents as a multidimensional entity characterized by four domains: tissue injury, alteration of the alveolar-capillary barrier, inflammatory response, and physiologic dysfunction. They suggest measurements for each domain and divide experimental ALI into a continuum of models.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Amanda Filiberto, Victoria Leroy, Zachary Ladd, Gang Su, Craig Elder, Eric Pruitt, Sara Hensley, Guanyi Lu, Ali Zarrinpar, Ashish Sharma, Gilbert R. R. Upchurch