Review
Pharmacology & Pharmacy
Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du
Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
Pedro Velica, Pedro P. Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist, Randall S. Johnson
Summary: By ectopically expressing the HIF transcription factor in CD8(+) T cells, this study demonstrated an enhanced antitumor efficacy against tumor targets. A specific mutation in HIF2 alpha showed the most effective antitumor T cell response, suggesting a potential strategy to increase therapeutic efficacy of CD8(+) T cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Medicine, Research & Experimental
Min Kyung Park, Jun Ji, Keeok Haam, Tae-Hee Han, Seona Lim, Mi-Jung Kang, Soon Sung Lim, Hyun Seung Ban
Summary: Licochalcone A, a component of Glycyrrhiza uralensis, demonstrates potential as a therapeutic agent in hypoxic cancer cells by inhibiting HIF-1 alpha accumulation and mitochondrial respiration, leading to increased oxygen content and suppression of cancer cell viability.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Savalan Babapoor- Farrokhran, Yu Qin, Miguel Flores- Bellver, Yueqi Niu, Imran A. Bhutto, Silvia Aparicio- Domingo, Chuanyu Guo, Murilo Rodrigues, Timothy Domashevich, Monika Deshpande, Haley Megarity, Rakesh Chopde, Charles G. Eberhart, Valeria Canto- Soler, Silvia Montaner, Akrit Sodhi
Summary: This study provides evidence that oxidative stress and hypoxia synergistically stimulate the accumulation of hypoxia-inducible factor in the retinal pigment epithelium, leading to the development of choroidal neovascularization in age-related macular degeneration patients. Adequate hypoxia-inducible factor expression is crucial for the protection of photoreceptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu
Summary: Cardiovascular diseases are the leading cause of death worldwide, and hypoxia-inducible factors (HIFs) play an important role in their pathogenesis. Recent studies have revealed the role of cell-specific HIFs in various cardiovascular diseases, but the potential clinical application of HIF inhibitors in the treatment of cardiovascular diseases is not well understood.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Oncology
Bich Phuong Bui, Phuong Linh Nguyen, Kyeong Lee, Jungsook Cho
Summary: This review discusses the crucial role of hypoxia-inducible factor-1 (HIF-1) in tumor biology, particularly in hypoxic environments. Despite numerous identified HIF-1 inhibitors as potential therapeutic agents for various cancers, none of them have been successfully translated into clinically available cancer treatments. The review summarizes the roles of the HIF-1 pathway in tumor proliferation, angiogenesis, metastasis, drug resistance, and cancer-related pain. Additionally, it highlights the current status of HIF-1 inhibitors in clinical trials and their future perspectives. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.
Article
Biochemistry & Molecular Biology
Cinthia C. Alves, Eduardo A. Donadi, Silvana Giuliatti
Summary: In hypoxic conditions, HIF1 interacts with the HLA-G gene, leading to higher HLA-G expression, particularly when binding with the -964G allele. The complex formed by HIF1 binding to HRE with the -964G allele is more stable due to the formation of more hydrogen bonds and van der Waals contacts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Xiaowei Zheng, Sampath Narayanan, Cheng Xu, Sofie Eliasson Angelstig, Jacob Grunler, Allan Zhao, Alessandro Di Toro, Luciano Bernardi, Massimiliano Mazzone, Peter Carmeliet, Marianna Del Sole, Giancarlo Solaini, Elisabete A. Forsberg, Ao Zhang, Kerstin Brismar, Tomas A. Schiffer, Neda Rajamand Ekberg, Ileana Ruxandra Botusan, Fredrik Palm, Sergiu-Bogdan Catrina
Summary: Excessive production of mitochondrial reactive oxygen species (ROS) in diabetes complications is mainly caused by impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Restoring HIF-1 function can attenuate ROS overproduction, protect cells against apoptosis and renal injury in diabetes. These findings suggest that targeting HIF-1 repression could be a potential therapeutic strategy for diabetic complications.
Article
Environmental Sciences
Meriam N. N. Rezk, Gerges M. Beshreda, Dalia Abdelrahman Meshref, Walaa Yehia Abdelzaher, Gaber El-Saber Batiha, Amin A. Hafiz, Duaa Althumairy, Nada H. Aljarba, Nermeen N. Welson
Summary: This study aimed to investigate the role of hypoxiainducible factor-1 alpha (HIF-1 alpha) in the diagnosis, prediction, and follow-up of Dormex-intoxicated patients. The results showed that HIF-1 alpha can effectively predict and follow up patients within 24 hours after admission. Additionally, blood-related indicators were also significantly abnormal in patients with Dormex intoxication.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Zaira Rehman, Ishrat Jabeen, Ammad Fahim, Attya Bhatti, Peter John
Summary: A ligand-based pharmacophore model was developed to identify potential HIF-1α and β dimerization inhibitors, resulting in the identification of six hits with potential anti-cancer chemotherapy activity. These compounds could serve as potential inhibitors of HIF-1 dimerization after further structure optimization.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Toxicology
Michael Aschner, Anatoly V. Skalny, Rongzhu Lu, Abel Santamaria, Ji-Chang Zhou, Tao Ke, Mikhail Yu. Karganov, Aristides Tsatsakis, Kirill S. Golokhvast, Aaron B. Bowman, Alexey A. Tinkov
Summary: This review summarizes the existing data on the effects of toxic metals on HIF-1 signaling and its underlying mechanisms, with a special focus on the prooxidant effect of metals. The effect of metals on HIF-1 pathway varies depending on the cell type, ranging from down-regulation to up-regulation. Inhibition of HIF-1 signaling may contribute to hypoxic damage in cells, while metal-induced activation may promote tumor growth and contribute to the carcinogenic effects of heavy metals.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Xin Tang, Cheng Chang, Michelle Hao, Mei Chen, David T. Woodley, Axel H. Schonthal, Wei Li
Summary: HIF-1 and Hsp90 play critical roles in spermatogenesis and tumorigenesis, with Hsp90 alpha affecting the levels of HIF-1 alpha in testis, and Hsp90 beta providing protection for signaling molecules responsible for cellular homeostasis.
CANCER GENE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Ioanna E. Stergiou, Konstantinos Kambas, Aikaterini Poulaki, Stavroula Giannouli, Theodora Katsila, Aglaia Dimitrakopoulou, Veroniki Vidali, Vasileios Mouchtouris, Ismini Kloukina, Evangelia Xingi, Stamatis N. Pagakis, Lesley Probert, George P. Patrinos, Konstantinos Ritis, Athanasios G. Tzioufas, Michael Voulgarelis
Summary: Myelodysplastic syndromes (MDS) involve a group of disorders affecting hematopoietic stem and progenitor cells, with a particular focus on the role of the transcription factor HIF-1. Aberrant HIF-1 stabilization and pseudohypoxia are prominent features in MDS pathobiology, showing potential for therapeutic manipulation in benign cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Savalan Babapoor-Farrokhran, Deanna Gill, Jafar Alzubi, Sumeet K. Mainigi
Summary: Atrial fibrillation (AF) is a common arrhythmia associated with hypoxia and the HIF pathway. Certain cytokines may serve as biomarkers for AF, aiding in diagnosis and treatment. Targeting these cytokines shows promise for the management of AF.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Je Lin Sieow, Hweixian Leong Penny, Sin Yee Gun, Ling Qiao Tan, Kaibo Duan, Joe Poh Sheng Yeong, Angela Pang, Diana Lim, Han Chong Toh, Tony Kiat Hon Lim, Edgar Engleman, Olaf Rotzschke, Lai Guan Ng, Jinmao Chen, Suet Mien Tan, Siew Cheng Wong
Summary: A large number of neutrophils infiltrate tumors and contribute to the inflammatory tumor microenvironment. The metabolic status of these neutrophils and their role in tumor progression were investigated in a mouse model of pancreatic ductal adenocarcinoma (PDAC). Tumor-infiltrating neutrophils showed enhanced glycolytic activity compared to neutrophils from the bone marrow and blood of the same mouse. Deletion of hypoxia-inducible factor 1-alpha (HIF-1 alpha) in neutrophils reduced tumor burden and improved survival in the mouse model, indicating a potential target for metabolic modulation in cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Critical Care Medicine
Roxana Wasnick, Martina Korfei, Katarzyna Piskulak, Ingrid Henneke, Jochen Wilhelm, Poornima Mahavadi, Ruth Charlotte Dartsch, Daniel von der Beck, Miriam Koch, Irina Shalashova, Astrid Weiss, Oleksiy Klymenko, Ingolf Askevold, Ludger Fink, Heiko Witt, Holger Hackstein, Elie El Agha, Saverio Bellusci, Walter Klepetko, Melanie Koenigshoff, Oliver Eickelberg, Ralph Theo Schermuly, Thomas Braun, Werner Seeger, Clemens Ruppert, Andreas Guenther
Summary: This study reveals that Notch signaling plays a crucial role in the proliferation and dedifferentiation of type II alveolar epithelial cells (AEC2s), as well as the development of lung fibrosis in idiopathic pulmonary fibrosis (IPF).
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Manuel J. Richter, Federico Fortuni, Fawaz Alenezi, Michele D'Alto, Roberto Badagliacca, Nathan W. Brunner, Arie P. van Dijk, Philipp Douschan, Henning Gall, Stefano Ghio, Francesco Lo Giudice, Ekkehard Grunig, Francois Haddad, Luke Howard, Sudarshan Rajagopal, Niels Stens, Davide Stolfo, Dick H. J. Thijssen, Carmine Dario Vizza, Roham T. Zamanian, Liang Zhong, Werner Seeger, Hossein A. Ghofrani, Khodr Tello
Summary: A meta-analysis of 35 studies found that right atrial (RA) imaging assessment is a relevant prognostic marker in patients with pulmonary hypertension (PH). RA area, RA indexed area, RA peak longitudinal strain, and RA total emptying fraction were significantly associated with combined end-points including death, clinical worsening, and/or lung transplantation. RA volume and volume index showed marginal significant associations.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Medicine, General & Internal
William G. Herrington, Natalie Staplin, Christoph Wanner, Jennifer B. Green, Sibylle J. Hauske, Jonathan R. Emberson, David Preiss, Parminder Judge, Kaitlin J. Mayne, Sarah Y. A. Ng, Emily Sammons, Doreen Zhu, Michael Hill, Will Stevens, Karl Wallendszus, Susanne Brenner, Alfred K. Cheung, Zhi-Hong Liu, Jing Li, Lai Seong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Aldo P. Maggioni, Roberto Pontremoli, Rajat Deo, Shinya Goto, Xavier Rossello, Katherine R. Tuttle, Dominik Steubl, Michaela Petrini, Dan Massey, Jens Eilbracht, Martina Brueckmann, Martin J. Landray, Colin Baigent, Richard Haynes
Summary: Empagliflozin therapy reduces the risk of disease progression or cardiovascular death in patients with chronic kidney disease.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Marija Gredic, Vinita Sharma, Stefan Hadzic, Cheng-Yu Wu, Oleg Pak, Baktybek Kojonazarov, Julia Duerr, Marcus A. A. Mall, Andreas Guenther, Ralph T. T. Schermuly, Friedrich Grimminger, Werner Seeger, Simone Kraut, Natascha Sommer, Norbert Weissmann
Summary: This study aimed to investigate the effect of iNOS gene deletion on elastase-induced emphysema in mice. The results showed that iNOS gene deletion did not produce significant therapeutic effects on elastase-induced lung emphysema and pulmonary hypertension. Therefore, this study suggests that iNOS expression in pulmonary vascular or stromal cells might play a critical role in lung regeneration in emphysema.
Article
Respiratory System
Katharina Schaefer, Khodr Tello, Oleg Pak, Manuel Richter, Mareike Gierhardt, Grazyna Kwapiszewska, Christine Veith, Ludger Fink, Henning Gall, Matthias Hecker, Baktybek Kojonazarov, Simone Kraut, Kevin Lo, Jochen Wilhelm, Friedrich Grimminger, Werner Seeger, Ralph T. Schermuly, Hossein A. Ghofrani, Daniel Zahner, Rudiger Gerstberger, Norbert Weissmann, Akylbek Sydykov, Natascha Sommer
Summary: BDNF levels are decreased in patients with pulmonary hypertension and negatively correlated with right ventricular dilatation. However, decreased BDNF levels do not worsen RV dilatation in animal models.
Article
Urology & Nephrology
Esther N. M. de Rooij, Johan W. de Fijter, Saskia Le Cessie, Ewout J. Hoorn, Kitty J. Jager, Nicholas C. Chesnaye, Marie Evans, Karin Windahl, Fergus J. Caskey, Claudia Torino, Maciej Szymczak, Christiane Drechsler, Christoph Wanner, Friedo W. Dekker, Ellen K. Hoogeveen
Summary: This study found a U-shaped relationship between serum potassium and the risk of death or initiation of kidney replacement therapy in patients with stage 4-5 chronic kidney disease, with the lowest risk observed at a potassium level of approximately 4.9 mmol/L.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Article
Critical Care Medicine
Cheng-Yu Wu, Anis Cilic, Oleg Pak, Ruth Charlotte Dartsch, Jochen Wilhelm, Magdalena Wujak, Kevin Lo, Monika Brosien, Ruoyu Zhang, Ibrahim Alkoudmani, Biruta Witte, Frauke Pedersen, Henrik Watz, Robert Voswinckel, Andreas G. Unther, Hossein A. Ghofrani, Ralf P. Brandes, Ralph T. Schermuly, Friedrich Grimminger, Werner Seeger, Natascha Sommer, Norbert Weissmann, Stefan Hadzic
Summary: CEACAM6 gene expression determines the susceptibility of some smokers to nitrosative/oxidative stress, thereby promoting the development and progression of COPD.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Neurosciences
Stephan Maxeiner, Gabriela Krasteva-Christ, Mike Althaus
Summary: Synthesis of DNA fragments based on gene sequences from public resources has replaced traditional cloning methods. However, errors in database entries can lead to false sequence information and impact protein characterization in expression systems. Five common problems in public resources: incomplete gene annotation, incorrect annotations, automated corrections in transcripts, sequence mismatches, and lack of experimental validation for splicing patterns. This review presents a strategy to bypass these issues and avoid critical mistakes in future studies.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Medicine, General & Internal
Fritz C. Roller, Armin Schuessler, Nils Kremer, Sebastian Harth, Steffen D. Kriechbaum, Christoph B. Wiedenroth, Stefan Guth, Andreas Breithecker, Manuel Richter, Khodr Tello, Werner Seeger, Eckhard Mayer, Gabriele A. Krombach
Summary: The aim of this study was to assess the RV and LV blood pool T1 and T2 values in CTEPH patients and their correlation to pulmonary hemodynamic. Results showed that compared to control subjects, CTEPH patients had significantly reduced RV T2 values, which increased significantly after balloon pulmonary angioplasty. RV T2 values were positively correlated with hemodynamic measures. Therefore, RV T2 mapping can be a novel non-invasive CMR imaging marker for assessing disease severity, prognosis, follow-up, and therapy monitoring in PH.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Athiththan Yogeswaran, Manuel J. Richter, Faeq Husain-Syed, Zvonimir Rako, Natascha Sommer, Friedrich Grimminger, Werner Seeger, Hossein Ardeschir Ghofrani, Henning Gall, Khodr Tello
Summary: In patients with idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, estimated plasma volume status is associated with central venous congestion and prognosis. Patients with high estimated plasma volume status and without edema have a poorer transplant-free survival rate, which may represent an under-recognized subgroup.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Baktybek Kojonazarov, Norbert Weissmann, Werner Seeger, Ralph Theo Schermuly
CARDIOLOGY JOURNAL
(2023)
Article
Immunology
Andres Alberro-Brage, Vitalii Kryvenko, Christina Malainou, Stefan Guenther, Rory E. Morty, Werner Seeger, Susanne Herold, Christos Samakovlis, Istvan Vadasz
Summary: Acute respiratory distress syndrome (ARDS) is a common complication of influenza virus (IV) infection, which leads to the accumulation and impairment of alveolar protein. It has been found that IV infection inhibits the clearance of alveolar protein, possibly through upregulation of a proteinase called MMP. In addition, inhibition of MMP proteinase may improve the clearance of alveolar protein and thus provide a potential therapeutic approach for ARDS.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Dirk Bandorski, Khodr Tello, Harun Erdal, Janine Sommerlad, Jochen Wilhelm, Istvan Vadasz, Matthias Hecker, Dieter Walmrath, Werner Seeger, Ekaterina Krauss, Stefan Kuhnert
Summary: This study evaluates the diagnostic value of gastric biomarkers, such as pepsin and bile acid, in detecting aspiration in the intensive care unit (ICU). The results indicate that measuring pepsin and bile acid does not reliably diagnose aspiration or significantly impact survival outcomes. Further validation studies are needed to assess the clinical usefulness and reliability of these biomarkers in diagnosing aspiration-related conditions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Dharmesh V. Hirani, Florian Thielen, Siavash Mansouri, Soula Danopoulos, Christina Vohlen, Pinar Haznedar-Karakaya, Jasmine Mohr, Rebecca Wilke, Jaco Selle, Thomas Grosch, Ivana Mizik, Margarete Odenthal, Cristina M. Alvira, Celien Kuiper-Makris, Gloria S. Pryhuber, Christian Pallasch, S. van Koningsbruggen-Rietschel, Denise Al-Alam, Werner Seeger, Rajkumar Savai, Joerg Doetsch, Miguel A. Alejandre Alcazar
Summary: Through experimental and clinical studies, it has been discovered that macrophage-derived CXCL10 plays a crucial role in the pathogenesis of BPD by causing macrophage chemotaxis through CXCR3, leading to lung fibrosis and alveolarization arrest. Targeting the CXCL10-CXCR3 axis could offer a new therapeutic approach for BPD.
INFLAMMATION AND REGENERATION
(2023)
Letter
Urology & Nephrology
Hristos Karakizlis, Vipul Agarwal, Mostafa Aly, Kevin Strecker, Benjamin Csala, Isla Esso, Jiangping Chen, Christian Nahrgang, Martin Wolter, Heiko Slanina, Christian G. Schuettler, Soenke Jessen, Claudio Ronco, Werner Seeger, Rolf Weimer, Martina Sester, Horst-Walter Birk, Faeq Husain-Syed
JOURNAL OF NEPHROLOGY
(2023)