Review
Biochemistry & Molecular Biology
Mengchao Yu, Jie Lun, Hongwei Zhang, Lei Zhu, Gang Zhang, Jing Fang
Summary: The hypoxia-inducible factor prolyl hydroxylases (PHDs) are enzymes that regulate the response to oxygen levels by hydroxylating prolyl residues of HIF alpha. Studies show they also have additional functions in protein stability, enzyme activity, and protein-protein interactions.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Franziska Dengler, Sofia Sova, Antti M. Salo, Joni M. Maki, Peppi Koivunen, Johanna Myllyharju
Summary: HIF prolyl 4-hydroxylases (HIF-P4H) control the powerful mechanism regulating cellular adaptation to decreased oxygenation and the gastrointestinal epithelium has a well-designed control over this adaptation. The gene expression levels of HIF pathway components were found to be higher towards the distal end of the gastrointestinal tract, with HIF-P4H-2 playing a predominant role in the gut epithelium. These findings suggest the development of selective inhibitors targeting specific HIF-P4H isoforms may be useful for diverging therapeutic needs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Hanjin Cui, Ali Yang, Huajun Zhou, Yang Wang, Jiekun Luo, Jun Zhou, Tao Liu, Pengfei Li, Jing Zhou, En Hu, Zehui He, Wang Hu, Tao Tang
Summary: Thrombin induces angiogenesis after intracerebral hemorrhage by increasing miR-24, which targets PHD1 to reduce HIF-1 alpha degradation. This study suggests a potential mechanism for thrombin-induced angiogenesis post-ICH.
JOURNAL OF NEUROSURGERY
(2021)
Article
Medicine, Research & Experimental
Xuejie Zhang, Ruoyu Jia, Zhifang Zheng, Luhua Jiang, Yizhou Xu, Ashok Raj, Dong Sun
Summary: Compared with ESAs, roxadustat significantly decreased hepcidin level, attenuated the increase in serum soluble transferrin receptor level, and reduced the proportion of patients with functional iron deficiency in PD patients.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Urology & Nephrology
David A. Goodkin, Junhui Zhao, Aleix Cases, Masaomi Nangaku, Angelo Karaboyas
Summary: This study investigated factors associated with erythropoiesis-stimulating agent (ESA) hyporesponsiveness, including its duration, frequency, and variation across countries. The findings showed that most patients changed their ESA Resistance Index (ERI) quintile within 4 months, with only a small percentage remaining in the top quintile throughout the 12-month follow-up. A significant proportion of patients experienced an upper-quintile ERI at some point, and the median duration of a new episode of ESA resistance was 2 months. Factors associated with high ERI included catheter hemoaccess, elevated C-reactive protein, lower transferrin saturation, lower serum albumin concentration, and recent hospitalization. ERI values were highest in the USA, Italy, and Mideastern nations, and lowest in Russia and Japan.
AMERICAN JOURNAL OF NEPHROLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Tatsuyuki Sato, Norihiko Takeda
Summary: Oxygen is vital for living organisms as it binds to hemoglobin and is transported throughout the body. In conditions of cardiovascular diseases or anemia, the local oxygen levels decrease and tissue hypoxia occurs, leading to the upregulation of hypoxia-responsive genes. These genes include erythropoietin (EPO), vascular endothelial growth factor-A, and glycolytic enzymes. Hypoxia-inducible factors (HIF) such as HIF-1 alpha and HIF-2 alpha play crucial roles in regulating these genes, and their degradation is halted during hypoxia. HIF-alpha signaling pathway has therapeutic potential in renal anemia, and small molecule HIF-PH inhibitors are employed to restore EPO production.
JOURNAL OF CARDIOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Tatsuyuki Sato, Norihiko Takeda
Summary: Oxygen is vital for living organisms. It binds to hemoglobin and is distributed to all organs in the body. In cardiovascular diseases and anemia, the drop in local oxygen levels causes tissue hypoxia and triggers the expression of hypoxia-responsive genes. Hypoxia-inducible factors (HIFs) regulate these genes, and their degradation is inhibited under hypoxic conditions. HIF-alpha proteins form complexes with HIF-1 beta, leading to the activation of hypoxia-responsive genes. HIF-alpha signaling is a potential target for treating renal anemia, and HIF-PH inhibitors are used to restore EPO production. This review focuses on the role of HIF-alpha signaling in cardiovascular diseases, including its impact on cardiomyocytes and stromal cells such as macrophages.
JOURNAL OF CARDIOLOGY
(2023)
Article
Clinical Neurology
Fatih Seker, Johannes Alex Rolf Pfaff, Yahia Mokli, Anne Berberich, Rafael Namias, Steven Gerry, Simon Nagel, Martin Bendszus, Christian Herweh
Summary: The study evaluated the diagnostic accuracy of e-CTA in automatically detecting large vessel occlusions in anterior circulation stroke. The results showed that e-CTA performs similarly to less experienced physicians in detecting any large vessel occlusions, but is comparable to experienced physicians in detecting proximal large vessel occlusions.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Article
Clinical Neurology
Leon D. Kaulen, Sofia Doubrovinskaia, Christoph Mooshage, Berit Jordan, Jan Purrucker, Carmen Haubner, Corinna Seliger, Hanns-Martin Lorenz, Simon Nagel, Brigitte Wildemann, Martin Bendszus, Wolfgang Wick, Silvia Schoenenberger
Summary: Various neurological autoimmune disorders were observed following SARS-CoV-2 vaccinations, with most patients achieving favorable outcomes. The benefits of vaccinations outweigh the relatively small risks associated with autoimmune responses.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
N. Schmitt, Y. Mokli, C. S. Weyland, S. Gerry, C. Herweh, P. A. Ringleb, S. Nagel
Summary: The study demonstrated that an AI-based algorithm showed high sensitivity and specificity in detecting acute intracranial hemorrhages (ICH) and intraparenchymal hemorrhages (IPH) in non-contrast-enhanced head CT scans of suspected acute stroke patients. The algorithm also exhibited strong agreements with neuroradiology residents in detecting ICH and IPH. Additionally, excellent agreement was found between the algorithm and the reference standard in quantifying IPH volumes.
EUROPEAN RADIOLOGY
(2022)
Article
Health Care Sciences & Services
Loraine Busetto, Johanna Hoffmann, Christina Stang, Hemasse Amiri, Fatih Seker, Jan Purrucker, Peter Arthur Ringleb, Simon Nagel, Martin Bendszus, Wolfgang Wick, Christoph Gumbinger
Summary: This study provides an overview of the pathways followed by patients with acute ischemic stroke during in-hospital treatment, revealing that most direct interactions between staff members and patients are focused within one phase, with a smaller number of interactions extending to other phases.
INTERNATIONAL JOURNAL OF INTEGRATED CARE
(2022)
Article
Biology
Jeffrey Y. Lee, Peter A. C. Wing, Dalia S. Gala, Marko Noerenberg, Aino Jarvelin, Joshua Titlow, Xiaodong Zhuang, Natasha Palmalux, Louisa Iselin, Mary Kay Thompson, Richard M. Parton, Maria Prange-Barczynska, Alan Wainman, Francisco J. Salguero, Tammie Bishop, Daniel Agranoff, William James, Alfredo Castello, Jane A. McKeating, Ilan Davis
Summary: Despite extensive research, early replication events of SARS-CoV-2 are still poorly understood. This study used smFISH to quantify viral RNA and found that SARS-CoV-2 genomic RNA has a long lifespan in cells and replication varies significantly between cells. Additionally, the B.1.1.7 variant exhibits slower replication kinetics than the Victoria strain, suggesting a novel mechanism contributing to its higher transmissibility.
Article
Clinical Neurology
A. Potreck, E. Scheidecker, C. S. Weyland, U. Neuberger, C. Herweh, M. A. Mohlenbruch, M. Chen, S. Nagel, M. Bendszus, F. Seker
Summary: This study found that automated CT perfusion analysis allows accurate identification of collateral status in acute ischemic stroke. A relative CBF < 38% may be a better perfusion-based indicator of good collateral supply compared with other parameters like time-to-maximum, the hypoperfusion intensity ratio, and the CBV-index.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
E. Gamen, E. L. Price, D. Pezzolla, C. De Villiers, M. Gunadasa-Rohling, R. Salama, D. R. Mole, T. Bishop, C. W. Pugh, R. P. Choudhury, C. A. Carr, J. M. Vieira, P. R. Riley
CARDIOVASCULAR RESEARCH
(2022)
Article
Clinical Neurology
Pierre Seners, Caroline Arquizan, Louis Fontaine, Wagih Ben Hassen, Mirjam R. Heldner, Davide Strambo, Simon Nagel, Emmanuel Carrera, Laura Mechtouff, Margy McCullough-Hicks, Mahmoud H. Mohammaden, Jean-Philippe Cottier, Hilde Henon, Andreea Aignatoaie, Nadia Laksiri, Jeremie Papassin, Ludovic Lucas, Pierre Garnier, Aude Triquenot, Gioia Mione, Steven Hajdu, Vincent Costalat, Arne Potreck, Olivier Detante, Fabrice Bonneville, Yves Berthezene, Serge Bracard, Igor Sibon, Nicolas Bricout, Claire Boutet, Pasquale Mordasini, Patrik Michel, Catherine Oppenheim, Jean-Marc Olivot, Raul G. Nogueira, Gregory W. Albers, Jean-Claude Baron, Guillaume Turc
Summary: This study found that bridging therapy (intravenous thrombolysis followed by mechanical thrombectomy) was associated with lower rates of good outcome compared to intravenous thrombolysis alone in minor stroke patients with large vessel occlusion. However, mismatch volume was a strong modifier of the effect of bridging therapy, with worse outcome observed in patients with mismatch volume <= 40 mL. Randomized trials should consider adding perfusion imaging for patient selection.
Article
Clinical Neurology
Sofia Doubrovinskaia, Christoph M. Mooshage, Corinna Seliger, Hanns-Martin Lorenz, Simon Nagel, Pascal Lehnert, Jan Purrucker, Brigitte Wildemann, Martin Bendszus, Wolfgang Wick, Silvia Schoenenberger, Leon D. Kaulen
Summary: This study reports the long-term clinical, laboratory, and imaging characteristics of patients with neurological autoimmunity diagnosed in temporal association (<= 6 weeks) with SARS-CoV-2 vaccinations. The condition of most patients improved following therapy, and re-vaccinations were well tolerated. The results suggest that re-vaccinations should be considered based on individual risk-benefit analysis.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Jakob Walther, Elena Marie Kirsch, Lina Hellwig, Sarah S. Schmerbeck, Paul M. Holloway, Alastair M. Buchan, Philipp Mergenthaler
Summary: The concept of the ischemic penumbra refers to hypoperfused brain tissue with decreased oxygen and glucose availability, which is considered salvageable and a potential target for neuroprotection in focal stroke. However, achieving improved neurological outcome based on the pathophysiological mechanisms in the penumbra has not been fully accomplished. Recent findings highlight the importance of glucose availability and bioenergetic failure in understanding the dynamic ischemic penumbra.
TRANSLATIONAL STROKE RESEARCH
(2023)
Review
Clinical Neurology
Anna M. Schneider, Robert W. Regenhardt, Adam A. Dmytriw, Aman B. Patel, Joshua Adam Hirsch, Alastair M. Buchan
Summary: Despite advances in clinical diagnosis and increasing numbers of eligible patients for revascularisation, ischaemic stroke remains a significant public health concern. Recanalisation therapy alone is not sufficient, and successful translational attempts for cerebroprotection are lacking. Therefore, understanding the diverse cellular effects and complex pathophysiological cascade of ischaemic stroke, as well as developing new multimodal and multicellular cerebroprotective agents, is crucial for improving patient outcomes.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Matthias A. A. Mutke, Arne Potreck, Niclas Schmitt, Fatih Seker, Peter A. A. Ringleb, Simon Nagel, Markus A. A. Moehlenbruch, Martin Bendszus, Charlotte S. S. Weyland, Jessica Jesser
Summary: This study aimed to determine the impact of the exact location of basilar artery occlusion (BAO) on stroke etiology, recanalization success, and favorable clinical outcomes in patients receiving endovascular stroke treatment (EST). The results showed that the occlusion site correlated with stroke etiology and recanalization success, but did not predict favorable clinical outcomes.
CLINICAL NEURORADIOLOGY
(2023)
Article
Biology
Veronique N. Lafleur, Silvia Halim, Hani Choudhry, Peter J. Ratcliffe, David R. Mole
Summary: Hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR) are transcription factors that play central roles in the pathogenesis of renal cancer. They have both antagonistic and cooperative interactions, including competition for a common subunit, synergy in chromatin binding, and overlapping transcriptional targets. Inhibition of one pathway may promote the oncogenic effects of the other, suggesting that combination therapy targeting both pathways might be more effective.
LIFE SCIENCE ALLIANCE
(2023)
Article
Clinical Neurology
Jeffrey B. Saver, Elizabeth M. Klerman, Alastair Buchan, Patricia Calleja, Ignacio Lizasoain, Mersedeh Bahr-Hosseini, Sarah S. Lee, David Liebeskind, Philipp T. Mergenthaler, Katherine Mun, MingMing Ning, David Pelz, David M. Ray, Peter Rothwell, Pierre Seners, Anirudh Sreekrishnan, Eleanor Mina Sung, Steffen Tiedt, Alastair J. S. Webb, Teresa W. Woelfer, Gregory Albers
Summary: There is increasing evidence that circadian and diurnal rhythms have a strong influence on stroke onset, mechanism, progression, recovery, and response to therapy. To enhance our understanding, standardized definitions and coding guides for data collection are needed, as well as advanced imaging techniques and large data registries. The development of standardized data structures will aid researchers in studying the impact of circadian/diurnal biology on stroke.
Meeting Abstract
Cardiac & Cardiovascular Systems
E. Elisabetta Gamen, E. L. Price, D. Pezzolla, C. De Villiers, M. Gunadasa-Rohling, R. Salama, D. R. Mole, T. Bishop, C. W. Pugh, R. P. Choudhury, C. A. Carr, J. M. Vieira, P. R. Riley
EUROPEAN JOURNAL OF HEART FAILURE
(2022)