Review
Biochemistry & Molecular Biology
Jackson P. Sterling, Vincent C. Lombardi
Summary: Major burn trauma triggers inflammatory events that cause significant stress on the body, leading to detrimental responses. However, research suggests that antioxidants may help reduce the risk of complications.
Review
Biochemistry & Molecular Biology
Luisa B. B. Maia
Summary: Enzymes of the xanthine oxidase family containing molybdenum are known for catalyzing oxygen atom transfer reactions, but their ability to abstract an oxygen atom from the substrate molecule is not widely recognized. The discovery of mammalian xanthine oxidase's capability to catalyze the oxygen atom abstraction of nitrite to form nitric oxide (NO) was met with surprise and skepticism from the molybdenum community. Through extensive studies on enzymes of various families, it is now widely recognized that molybdoenzymes have the ability to form NO from nitrite.
Article
Biochemistry & Molecular Biology
Chenglong Wang, Sabine Stoeckl, Girish Pattappa, Daniela Schulz, Korbinian Hofmann, Jovana Ilic, Yvonne Reinders, Richard J. Bauer, Albert Sickmann, Susanne Graessel
Summary: In orthopedics, musculoskeletal disorders, such as non-union of bone fractures or osteoporosis, can be induced by pathological hypoxic conditions. This study found that hypoxic conditions suppressed the osteogenic differentiation of human bone marrow-derived mesenchymal cells and increased reactive oxygen species production. The extracellular vesicles derived from osteogenic differentiated cells cultured under hypoxia had distinct protein profiles compared to those cultured under normoxia. These findings suggest the importance of cellular origin and cargo of extracellular vesicles in osteogenic differentiation and highlight the potential therapeutic role of extracellular vesicles in rescuing hypoxia-induced impairment of bone formation.
Article
Ophthalmology
S. Scott Sutton, Joseph Magagnoli, Tammy H. Cummings, James W. Hardin, Jayakrishna Ambati
Summary: By inhibiting xanthine oxidase, allopurinol may reduce the risk of diabetic macular edema (DME) by limiting inflammation and blood-retina barrier breakdown. A retrospective cohort study of type 2 diabetic US veterans found that allopurinol was associated with a 24.6% reduction in the risk of DME. Further research on the effects of allopurinol on DME is warranted.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Biochemical Research Methods
Emadeldin M. Kamel, Noha A. Ahmed, Ashraf A. El-Bassuony, Omnia E. Hussein, Barakat Alrashdi, Sayed A. Ahmed, Al Mokhtar Lamsabhi, Hany H. Arab, Ayman M. Mahmoud
Summary: The study revealed the xanthine oxidase (XO) inhibitory activity of Euphorbia peplus phenolics, confirmed through in vitro, in vivo, and computational investigations. The isolated phenolics showed significant interactions with XO active site residues, forming hydrogen bonds. Molecular dynamics simulations demonstrated stability in the systems, with rigidity behavior observed at the drug binding site. The results suggest that these phenolics have potential as promising candidates for XO inhibitors.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Biochemistry & Molecular Biology
Minoru Inoue, Masahiro Enomoto, Michio Yoshimura, Takashi Mizowaki
Summary: The study shows that inhibition of Na+/Ca2+ exchange by EIPA and MIA can trigger NETotic cell death in neutrophils, indicating a new mechanism of infection-independent NET generation.
Article
Biochemistry & Molecular Biology
Tadashi Tsukamoto, Masaya Tsujii, Kazuya Odake, Takahiro Iino, Tomoki Nakamura, Akihiko Matsumine, Akihiro Sudo
Summary: The study demonstrates that febuxostat can significantly alleviate the muscle wasting caused by malignant tumors, with antioxidant and anti-inflammatory effects.
FREE RADICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tian Xie, Zehua Duan, Shilong Sun, Chengnan Chu, Weiwei Ding
Summary: The study found that beta-Lactams exert immunomodulation effects through modulating neutrophil extracellular traps (NETs) formation, depending on the PKC-Akt-mTOR signal pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Fisheries
Siwen Li, Yanling Wang, Dongke Yu, Yuan Zhang, Xiali Wang, Mei Shi, Yanxin Xiao, Xinlian Li, Hongtao Xiao, Lu Chen, Xuan Xiong
Summary: This study reveals the potential health risk of triclocarban (TCC) to fish and other aquatic organisms by inducing immunosuppression and physiological dysfunctions through the activation of NETosis. The degradation of SIRT3 serves as a potential mediator in regulating oxidative stress crosstalk between ERK1/2/p38 signals in the process of TCC-induced NET formation. These findings highlight the importance of targeting SIRT3 as a potential pharmacological intervention to alleviate TCC-induced NETosis in common carp.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Jean-Paul Cristol, Alain R. Thierry, Anne-Sophie Bargnoux, Marion Morena-Carrere, Bernard Canaud
Summary: Despite progress in dialysis modalities, intermittent renal replacement therapy remains imperfect in correcting uremic disorders and may lead to low-grade chronic inflammation and oxidative stress. Understanding dialysis bioincompatibility pathways is still a challenge, as current biomarkers cannot distinguish all components involved in these complex pathways.
FRONTIERS IN MEDICINE
(2023)
Article
Immunology
Remon Roshdy Rofaeil, Mohamed A. Ibrahim, Reham H. Mohyeldin, Nashwa F. El-Tahawy, Walaa Yehia Abdelzaher
Summary: The study aimed to investigate the protective effect of xanthine oxidase inhibitors (purine analogue; allopurinol and non-purine analogue; febuxostat) in testicular injury induced by methotrexate (MTX). The results showed that both drugs exhibited anti-inflammatory, anti-apoptotic, and antioxidant actions in countering MTX-induced testicular damage through the EGF/ERK1/2/HO-1 pathway.
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian D. Ellson, Ingred Goretti Rica, Jacob S. Kim, Yuming M. Huang, Daniel Lim, Tanya Mitra, Albert Hsu, Erin X. Wei, Christopher D. Barrett, Leo E. Otterbein, Carl J. Hauser, Martin Wahl, Heinrich Delbruck, Udo Heinemann, Hartmut Oschkinat, Chia-en A. Chang, Michael B. Yaffe
Summary: The neutrophil NADPH oxidase plays a critical role in microbial killing and inflammation by producing intracellular and extracellular reactive oxygen species (ROS). However, excessive extracellular ROS can lead to tissue damage, cancer progression, and immune dysregulation. This study identified specific signaling pathways involved in regulating the localization of ROS. The findings suggest the potential therapeutic target for modulating tissue damage and extracellular signaling during inflammation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Oncology
Ewelina Janczy-Cempa, Olga Mazuryk, Agnieszka Kania, Malgorzata Brindell
Summary: This review provides an overview of the current knowledge about the expression and activity of oxidoreductases relevant to the activation of HAPs and fluorescent imaging probes. The low efficacy of HAPs in clinical trials may be attributed to the lack of screening for tumor hypoxia and limited availability of specific oxidoreductases. Furthermore, there is insufficient understanding of the expression and activity of these enzymes in various cancer cell lines under hypoxic conditions, highlighting the need for further systematic studies. The review also discusses the use of fluorescence probes triggered by reduction with specific oxidoreductases for imaging hypoxic cancer cells.
Article
Peripheral Vascular Disease
Harri Elamaa, Mika Kaakinen, Marjut Natynki, Zoltan Szabo, Veli-Pekka Ronkainen, Ville Aijala, Joni M. Maki, Risto Kerkela, Johanna Myllyharju, Lauri Eklund
Summary: The study suggests that inducible deletion of PHD2 in endothelial cells can lead to progressive lung disease, while deletion in arterial smooth muscle cells results in elevated right ventricular pressure without alterations in vascular tone regulators. Mechanistically, PHD2 inhibition in smooth muscle cells involves actin polymerization-related tension development via activated cofilin.
Article
Medicine, Research & Experimental
Josiane Fernandes da Silva, Juliano Alves, Julio A. Silva-Neto, Rafael M. Costa, Karla B. Neves, Rheure Alves-Lopes, Livia L. Camargo, Francisco J. Rios, Augusto C. Montezano, Rhian M. Touyz, Rita C. Tostes
Summary: The study found that LPC induces oxidative stress in endothelial cells through NOX5-dependent ROS production, which is linked to increased intracellular calcium levels. Inhibition of NOX5 decreased LPC-induced ROS generation, as well as ICAM-1 expression and monocyte adhesion to endothelial cells. These results highlight the key role of NOX5 in early LPC-induced endothelial oxidative stress and inflammation, indicating its importance in atherosclerosis development.
Article
Peripheral Vascular Disease
Christopher Werlein, Maximilian Ackermann, Helge Stark, Harshit R. Shah, Alexandar Tzankov, Jasmin Dinonne Haslbauer, Saskia von Stillfried, Roman David Buelow, Ali El-Armouche, Stephan Kuenzel, Jan Lukas Robertus, Marius Reichardt, Axel Haverich, Anne Hoefer, Lavinia Neubert, Edith Plucinski, Peter Braubach, Stijn Verleden, Tim Salditt, Nikolaus Marx, Tobias Welte, Johann Bauersachs, Hans-Heinrich Kreipe, Steven J. Mentzer, Peter Boor, Stephen M. Black, Florian Laenger, Mark Kuehnel, Danny Jonigk
Summary: In this multicentre study, researchers performed a comprehensive analysis of heart samples from autopsies of COVID-19 patients and discovered that cardiac involvement in COVID-19 is a macrophage-driven inflammatory process that is distinct from the typical anti-viral inflammatory responses. The study also found the presence of intussusceptive angiogenesis in the affected hearts, which is a key characteristic of vascular remodeling in COVID-19 pneumonia.
Meeting Abstract
Biochemistry & Molecular Biology
Marissa Pokharel, Alejandro Garcia Flores, Qing Lu, Xutong Sun, Ting Wang, Kim Tieu, Stephen Black
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Peripheral Vascular Disease
Changlei Bao, Shuxin Liang, Ying Han, Zi Yang, Shiyun Liu, Yanan Sun, Shichuang Zheng, Yuzhu Li, Ting Wang, Yali Gu, Kang Wu, Stephen M. Black, Jian Wang, Steffan T. Nawrocki, Jennifer S. Carew, Jason X. -J. Yuan, Haiyang Tang
Summary: ROC-325 is a promising agent for the treatment of pulmonary hypertension (PH) that inhibits autophagy, downregulates HIF levels, and increases nitric oxide production.
Article
Critical Care Medicine
Shreya Sangam, Xutong Sun, Tae-Hwi Schwantes-An, Manivannan Yegambaram, Qing Lu, Yinan Shi, Todd Cook, Amanda Fisher, Andrea L. Frump, Anna Coleman, Yanan Sun, Shuxin Liang, Howard Crawford, Katie A. Lutz, Avinash D. Maun, Michael W. Pauciulo, Jason H. Karnes, Ketul R. Chaudhary, Duncan J. Stewart, Paul R. Langlais, Mohit Jain, Mona Alotaibi, Tim Lahm, Yan Jin, Haiwei Gu, Haiyang Tang, William C. Nichols, Stephen M. Black, Ankit A. Desai
Summary: Genetic studies suggest that deficiency of SOX17 increases the risk of pulmonary arterial hypertension (PAH). This study focuses on the pathological roles of estrogen and HIF2 alpha signaling in PAH, and suggests that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development by inhibiting HIF2 alpha. Experimental results confirm that deficiency of SOX17 increases the risk of PAH, while overexpression of SOX17 attenuates PAH development.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Kingshuk Panda, Srinivasan Chinnapaiyan, Md. Sohanur Rahman, Maria J. Santiago, Stephen M. Black, Hoshang J. Unwalla
Summary: People living with HIV are at a higher risk of developing chronic obstructive pulmonary disease (COPD) and asthma, with worse outcomes. The dysregulation of circadian rhythms and clock genes plays a significant role in lung pathology, particularly in HIV-infected patients. Understanding the mechanism of circadian clock dysregulation in HIV and its effects on COPD development and progression is important for developing potential therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Qing Lu, Xutong Sun, Manivannan Yegambaram, Wojciech Ornatowski, Xiaomin Wu, Hui Wang, Alejandro Garcia-Flores, Victoria Da Silva, Evgeny A. Zemskov, Haiyang Tang, Jeffrey R. Fineman, Kim Tieu, Ting Wang, Stephen M. Black
Summary: This study finds that mitochondrial fission and increased cellular glycolysis are involved in the pathogenesis of pulmonary hypertension. In pulmonary arterial endothelial cells, mitochondrial fission leads to increased cellular glycolysis. By reducing mitochondrial fission, the increased cellular glycolysis can be attenuated. Additionally, a nitration-mediated activation of RhoA is observed, and inhibiting RhoA nitration can reverse the increased cellular glycolysis. Therefore, targeting RhoA nitration could have therapeutic benefits for treating pulmonary hypertension.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marissa D. Pokharel, David P. Marciano, Panfeng Fu, Maria Clara Franco, Hoshang Unwalla, Kim Tieu, Jeffrey R. Fineman, Ting Wang, Stephen M. Black
Summary: Mitochondria are vital for cell metabolism, growth, and function, and play a central role in endothelial cell dysfunction associated with various lung diseases, including PAH. Multiple pathways, such as nitric oxide signaling, glucose metabolism, fatty acid oxidation, and the TCA cycle, are dysregulated in PAH, leading to alterations in mitochondrial membrane potential, proliferation, and apoptosis. Further research is urgently needed, especially in endothelial cells, to fully characterize these pathways and develop effective treatments for PAH.
Meeting Abstract
Biochemistry & Molecular Biology
David Caraballo, Marina Zemskova, Jayden Weil, Stephen Black, Evgeny Zemskov
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Marissa Pokharel, Alejandro Garcia Flores, Panfeng Fu, Qing Lu, Xutong Sun, Ting Wang, Stephen Black
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lakshmi N. R. Thota, Joaquin E. Lopez Rosales, Ivan Placencia, Evgeny A. Zemskov, Paola Tonino, Ashley N. Michael, Stephen M. Black, Andreia Z. Chignalia
Summary: The endothelial glycocalyx is an important signaling layer involved in cellular homeostasis. Its diverse composition and relative contributions of its constituents to overall function are still not well understood. The deletion of glypican 1, a glycocalyx component, results in a modified glycocalyx without affecting baseline lung endothelial function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Reem Faraj, Ying Liang, Anlin Feng, Jialin Wu, Stephen M. Black, Ting Wang
Summary: N-6-methyladenosine (m6A) is the most common methylation modification in mammalian RNA, and its deregulation has been implicated in many human diseases. Recent research suggests that targeting m6A methylation may have therapeutic potential against acute lung injury (ALI).
PULMONARY CIRCULATION
(2023)
Article
Biochemistry & Molecular Biology
Shuxin Liang, Changlei Bao, Zi Yang, Shiyun Liu, Yanan Sun, Weitao Cao, Ting Wang, Tae-Hwi Schwantes-An, John S. Choy, Samisubbu Naidu, Ang Luo, Wenguang Yin, Stephen M. Black, Jian Wang, Pixin Ran, Ankit A. Desai, Haiyang Tang
Summary: Cardiopulmonary complications caused by SARS-CoV-2 are major contributors to mortality. IL-18 has been identified as a novel mediator of cardiopulmonary pathologies, but its regulation through SARS-CoV-2 signaling is unknown. IL-18 was found to stratify mortality and hospitalization burden in COVID-19 patients. Spike protein exposure induced IL-18 expression and cardiac fibrosis in hACE2 mice. Spike protein inhibited mitophagy and increased reactive oxygen species, leading to NLRP3 inflammasome activation and IL-18 expression. Inhibition of IL-18 improved cardiac fibrosis and dysfunction. The reduced mitophagy-inflammasome link suggests IL-18 and mitophagy as potential therapeutic targets during COVID-19 pathogenesis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Jialin Wu, Ying Liang, Panfeng Fu, Anlin Feng, Qing Lu, Hoshang J. Unwalla, David P. Marciano, Stephen M. Black, Ting Wang
Summary: Mechanical ventilation (MV) is a life-supporting strategy used in the Intensive Care Unit (ICU). However, MV-associated mechanical stress worsens lung inflammation and leads to Ventilator-Induced Lung Injury (VILI). This study reveals that mechanical stress increases levels of S1PR3, which in turn alters the pulmonary endothelial response and impairs barrier recovery. Inhibiting S1PR3 is validated as an effective therapeutic strategy for VILI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Respiratory System
Anlin Feng, Yesenia Moreno Caro, Colin Gardner, Garrett Grischo, Ying Liang, Praveen D. Wickremasinghe, Michaela Polmann, Mrinalini Kala, Timothy Marlowe, Stephen M. Black, Kenneth S. Knox, Ting Wang
Summary: This study aimed to create a gene signature based on PTK2-associated genes and microarray data from blood cells to predict disease prognosis in patients with IPF. The findings suggested that PTK2 is a molecular target of IPF and the PTK2 molecular signature is an effective IPF prognostic biomarker.
RESPIRATORY RESEARCH
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Christopher Werlein, Maximilian Ackermann, Harshit R. Shah, Helge Stark, Florian Laenger, Tim Salditt, Tobias Welte, Johann Bauersachs, Axel Haverich, Saskia von Stillfried, Mark Kuehnel, Roman Buelow, Peter Boor, Stephen M. Black, Steven J. Mentzer, Danny Jonigk
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)