Article
Obstetrics & Gynecology
Yukiko Asano, Takayuki Iwaki, Kazuo Umemura, Naohiro Kanayama, Hiroaki Itoh
Summary: The study showed that fibrin had no effect on mouse blastocysts, but significantly suppressed trophoblast growth in human blastocysts. However, trophoblasts in human blastocysts then switched to growth promotion through increased fibrinolysis with urokinase-type plasminogen activator (uPA) activity.
HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Claire S. Whyte, Hadj Ahmed. Mostefai, Kim M. Baeten, Andrew J. Lucking, David E. Newby, Nuala A. Booth, Nicola J. Mutch
Summary: The resolution of arterial thrombi relies on the endogenous fibrinolytic system. tPA primarily localizes to the thrombus head in a free and active form. Thrombi formed under high shear conditions are more resistant to fibrinolysis due to less tPA and increased PAI-1 concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Esra'a Abudouleh, Fatimah Alhamlan, Arwa A. Al-Qahtani, Marie Fe Bohol, Amal Al Hazzani, Khadija Khorfan, Morad Alkaff, Tarek Owaidah, Ahmed A. Al-Qahtani
Summary: This study investigated coagulation and fibrinolysis parameters in COVID-19 patients and their association with disease severity. The results showed significantly elevated levels of thrombin activatable fibrinolysis inhibitor, fibrinogen, and tissue plasminogen activator in severe patients. Additionally, patients in the ICU had significantly higher levels of plasminogen activator inhibitor-1, tissue plasminogen activator, and thrombin activatable fibrinolysis inhibitor. These coagulation markers can serve as suitable prognostic indicators for hypofibrinolysis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Maria D. Valls, Maria Soldado, Jorge Arasa, Miguel Perez-Aso, Adrienne J. Williams, Bruce N. Cronstein, M. Antonia Noguera, M. Carmen Terencio, M. Carmen Montesinos
Summary: Activation of adenosine A(2A) receptor can promote angiogenesis by increasing the expression of annexin A2 in human dermal microvascular endothelial cells, which enhances fibrinolysis and contributes to wound healing and tissue revascularization.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kirstin Meiners, Prisca Hamm, Marcus Gutmann, Jan Niedens, Agnieszka Nowak-Krol, Salvador Pane, Tessa Luehmann
Summary: The study developed three polyethylene glycol (PEG)ylated tPA bioconjugates based on the recombinant human tPA drug Alteplase using site-specific conjugation strategies. These bioconjugates showed improved proteolytic activity, slower inhibition kinetics by PAI-1, and increased hydrodynamic size.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Obstetrics & Gynecology
Esra Demirel, Reem Sabouni, Neelima Chandra, Ov D. Slayden, David F. Archer
Summary: The study investigates the distribution and concentrations of several receptors and activators within the primate endometrium during artificial menstrual cycles, showing similarities in their expression patterns suggesting overlapping pathways. These findings indicate potential interactions between the plasminogen activator system and steroid receptors in the endometrium.
REPRODUCTIVE SCIENCES
(2022)
Article
Immunology
Florence Jeny, Jean-Francois Bernaudin, Dominique Valeyre, Marianne Kambouchner, Marina Pretolani, Hilario Nunes, Carole Planes, Valerie Besnard
Summary: Hypoxia has a significant impact on MD-macrophages from sarcoidosis patients, inducing proinflammatory and profibrotic responses while reducing antigen presentation, potentially leading to deficient T cell response.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Victor M. Schuettfort, Benjamin Pradere, David D'Andrea, Nico C. Grossmann, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Pierre I. Karakiewicz, Reza Sari Motlagh, Satoshi Katayama, Yair Lotan, Douglas Scherr, Mohammad Abufaraj, Harun Fajkovica, Eva Comperat, Dmitry Enikeev, Shahrokh F. Shariat
Summary: Elevated preoperative plasma levels of uPA, SuPAR, and PAI-one were confirmed to be associated with aggressive disease features and worse survival outcomes in patients treated with RC for UCB. These biomarkers have the potential to identify patients who may benefit from intensified/multimodal therapy and improve the discriminatory power of predictive/prognostic models.
JOURNAL OF UROLOGY
(2021)
Article
Health Care Sciences & Services
Hee Young Cho, Han Sung Park, Eun Hee Ahn, Eun Ju Ko, Hyeon Woo Park, Young Ran Kim, Ji Hyang Kim, Woo Sik Lee, Nam Keun Kim
Summary: The study revealed that PAI-1 rs1050955 and REN 10795 rs5707 alleles may decrease the risk of RPL, while the tPA rs4646972 genotype may increase the risk of RPL.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jennifer West, Sandeep Satapathy, Daniel R. Whiten, Megan Kelly, Nicholas J. Geraghty, Emma-Jayne Proctor, Pietro Sormanni, Michele Vendruscolo, Joel N. Buxbaum, Marie Ranson, Mark R. Wilson
Summary: Neuroserpin has the ability to inhibit amyloid formation by multiple proteins and protect against associated cytotoxicity. It shows unique chaperone selectivity for intermediates on the amyloid-forming pathway, but has poor ability to inhibit amorphous protein aggregation. A conserved 14-residue region containing an alpha helix is identified, which may be useful in designing anti-amyloid reagents in the future.
Review
Biochemistry & Molecular Biology
Max Liu, Khalequz Zaman, Yolanda M. Fortenberry
Summary: Aptamers are single-stranded DNA or RNA sequences that exhibit high specificity and affinity in binding target molecules. They are non-immunogenic, easier to synthesize and modify, and can bind targets with greater affinity, making them a promising therapeutic candidate for treating various conditions. Active research is ongoing in developing aptamers to target blood coagulation factors, with potential applications in treating cardiovascular diseases, blood disorders, and cancers. Although no aptamers targeting blood coagulation factors have been approved for clinical use, several have shown promise in clinical trials and preclinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kiyotaka Okada, Naoyuki Kawao, Daisho Nakai, Rei Wakabayashi, Yoshitaka Horiuchi, Katsumi Okumoto, Shinji Kurashimo, Yoshimasa Takafuji, Osamu Matsuo, Hiroshi Kaji
Summary: This study demonstrated that glucocorticoids decrease the number of macrophages at the injured site during early bone repair after femoral bone injury partly through PAI-1 and M-CSF in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Julie Brogaard Larsen, Anne-Mette Hvas
Summary: This review highlights the key changes in fibrinolysis during sepsis, points out the current lack of reliable biomarkers for assessing fibrinolysis in clinical settings, and discusses the potential value of drugs targeting the fibrinolytic system in sepsis patients.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Chemistry, Medicinal
Yang Zhou, Meiru Song, Daoqing Xie, Shufeng Yan, Song Xie, Meiqin Cai, Hanlin Li, Le Shang, Longguang Jiang, Cai Yuan, Mingdong Huang, Jinyu Li, Peng Xu
Summary: This study discovered the potential antitumor and antimetastatic effects of diltiazem and glibenclamide, commonly used hypotensive and antidiabetic drugs, on the urokinase receptor (uPAR). The study provides potent uPAR inhibitors and demonstrates the off-label antitumor and antimetastatic uses of diltiazem and glibenclamide.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Alaa Efat, Sabry Abdallah Shoeib, Ayman F. Arafa, Ashraf Abdelraof Dawod, Mohamad A. Abd ElHafez, Essam A. Abd ElMohsen, Hany F. Eladly, Reda A. Ibrahim, Aly Elkholy
Summary: SuPAR and PAI-1 were found to be significant predictors of hospital mortality among sepsis patients, and could serve as predictive markers for early death. However, the relatively small sample size may have decreased the statistical power of the study, warranting further research with larger sample sizes to validate these findings.
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jeppe Nielsen, Jakob Brandt, Thomas Boesen, Tina Hummelshoj, Rita Slaaby, Gerd Schluckebier, Poul Nissen
Summary: Insulin regulates glucose homeostasis by binding and activating the insulin receptor in an asymmetric manner. This study reveals how insulin binds at two distinct sites and disrupts the autoinhibited state, stabilizing the active state of the receptor.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Christian Staehr, Palle Duun Rohde, Nikolaj Thure Krarup, Steffen Ringgaard, Christoffer Laustsen, Jacob Johnsen, Rikke Nielsen, Hans Christian Beck, Jens Preben Morth, Karin Lykke-Hartmann, Nichlas Riise Jespersen, Denis Abramochkin, Mette Nyegaard, Hans Erik Botker, Christian Aalkjaer, Vladimir Matchkov
Summary: The study suggests that mutations in the ATP1A2 gene may lead to disturbed cardiac metabolism and reduced cardiac function, potentially mediated through Na,K-ATPase-dependent reactive oxygen species signaling.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Jonas Skogestad, Ingrid Albert, Karina Hougen, Gustav B. Lothe, Marianne Lunde, Olav Sovik Eken, Ioanni Veras, Ngoc Trang Thi Huynh, Mira Borstad, Serena Marshall, Xin Shen, William E. Louch, Emma Louise Robinson, Joseph C. Cleveland, Amrut V. Ambardekar, Jessica A. Schwisow, Eric Jonas, Ana I. Calejo, Jens Preben Morth, Kjetil Tasken, Arne Olav Melleby, Per Kristian Lunde, Ivar Sjaastad, Cathrine Rein Carlson, Jan Magnus Aronsen
Summary: The study found that PDE3A interacts with SERCA2 in cardiomyocytes and regulates its activity through direct binding. Researchers successfully disrupted the interaction between PDE3A and SERCA2 using a novel disruptor peptide and found that this disruption increases SERCA2 activity, improves cardiac contractility, and reduces the risk of cardiac events.
Article
Cardiac & Cardiovascular Systems
Harmonie Perdreau-Dahl, David B. Lipsett, Michael Frisk, Fatemeh Kermani, Cathrine R. Carlson, Andreas Brech, Xin Shen, Anna Bergan-Dahl, Yufeng Hou, Tomi Tuomainen, Pasi Tavi, Peter P. Jones, Marianne Lunde, J. Andrew Wasserstrom, Jocelyn Laporte, Nina D. Ullrich, Geir Christensen, J. Preben Morth, William E. Louch
Summary: This study reveals the collaborative roles of BIN1, MTM1, and DNM2 in controlling t-tubule growth in cardiomyocytes, which is crucial for the maturation of cardiomyocyte Ca2+ homeostasis.
CIRCULATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Bashar Shuoker, Michael J. Pichler, Chunsheng Jin, Hiroka Sakanaka, Haiyang Wu, Ana Martinez Gascuena, Jining Liu, Tine Sofie Nielsen, Jan Holgersson, Eva Nordberg Karlsson, Nathalie Juge, Sebastian Meier, Jens Preben Morth, Niclas G. Karlsson, Maher Abou Hachem
Summary: This study provides insights into the mechanism of mucin O-glycan degradation by Akkermansia muciniphila and the nutrient sharing between this symbiotic bacteria and the mucus-associated microbiota. They discovered new enzymes involved in the breakdown of protective caps on mucin, which promote the growth of A. muciniphila and the production of butyrate through cooperation with other bacteria.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Oscar Mejias-Gomez, Andreas V. Madsen, Kerstin Skovgaard, Lasse E. Pedersen, J. Preben Morth, Timothy P. Jenkins, Peter Kristensen, Steffen Goletz
Summary: This study analyzes human antibody sequences to understand the factors determining antibody diversity and specificity. The study reveals the importance of specific residue positions and their influence on antibody characteristics. These findings have significant implications for the development and optimization of antibody therapeutics.
Article
Multidisciplinary Sciences
Tanveer S. Batth, Jonas L. Simonsen, Cristina Hernandez-Rollan, Soren Brander, Jens Preben Morth, Katja S. Johansen, Morten H. H. Norholm, Jakob B. Hoof, Jesper V. Olsen
Summary: The methyltransferase NHMT responsible for N-terminal histidine methylation modification is identified and validated through mass spectrometry-based proteomics and CRISPR/Cas9. NHMT protects LPMOs from auto-oxidative inactivation by methylating the His1 site. The biotechnological potential of recombinant production of proteins and peptides with this specific post-translational modification is demonstrated.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Celeste D. Hackney, Paula Florez Salcedo, Emilie Mueller, Thomas Lund Koch, Lau R. Kjelgaard, Maren J. Watkins, Linda S. Zachariassen, Pernille Sonderby Tuelund, Jeffrey K. McArthur, David Adams, Anders Kristensen, Baldomero Olivera, Rocio Finol-Urdaneta, Helena Safavi-Hemami, Jens Preben Morth, Lars Ellgaard
Summary: Animal venom peptides, especially the conotoxins from marine cone snail venom, are valuable compounds for biomedical exploration.Through this study, an unusually large conotoxin, Mu8.1, was identified, which belongs to a new class of conotoxins and shows structural similarity with con-ikot-ikot. Functional studies revealed that Mu8.1 inhibits calcium influx in specific classes of somatosensory neurons and displays the highest potency against the R-type calcium channel. The findings suggest that Mu8.1 has potential as a molecular tool for identifying and studying neuronal subclasses, and also highlight the potential of uncovering novel structures and bioactivities within the unexplored group of macro-conotoxins.
Article
Biochemical Research Methods
Maria Dalgaard Mikkelsen, Vy Ha Nguyen Tran, Sebastian Meier, Thuan Thi Nguyen, Jesper Holck, Hang Thi Thuy Cao, Tran Thi Thanh Van, Pham Duc Thinh, Anne S. Meyer, Jens Preben Morth
Summary: This study presents the structural characterization and activity of a novel endo-alpha(1,4)-fucoidanase, Mef1, from the marine bacterium Muricauda eckloniae. Mef1 specifically catalyzes the cleavage of alpha(1,4)-linkages between fucose residues in fucoidan from Fucus evanescens. The crystal structure of Mef1 reveals a single-domain organization with an extended, positively charged groove as the active site.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Emilie Muller, Celeste Menuet Hackney, Lars Ellgaard, Jens Preben Morth
Summary: Marine cone snails produce conotoxins that bind molecular targets selectively and effectively. The Mu8.1 conotoxin from Conus mucronatus is a newly identified saposin-like conotoxin that targets the Cav2.3 voltage-gated calcium channel. A high-resolution crystal structure of Mu8.1 revealed a water-filled cavity and a lysine residue with an unusually low side-chain pK(a) value.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Biology
Lisa Merklinger, J. Preben Morth
Summary: The lipid bilayers of the cell consist of various lipids that interact with membrane proteins to regulate cell signaling. Investigating membrane protein-lipid interactions is challenging, but nanodiscs and liposomes provide a more natural environment for studying these interactions. This protocol provides clear instructions on preparing lipids and integrating them with the membrane protein MARCH5.
Article
Biochemistry & Molecular Biology
Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Soren Abel, Frank Sobott, J. Preben Morth
Summary: The study reveals the complex interaction between bacterial magnesium transporter A (MgtA) and cardiolipin 18:1 and cardiolipin 16:0, highlighting the importance of lipid environment in protein activity and stability. Further understanding of Mg2+ homeostasis in bacteria will provide insights into bacterial infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemical Research Methods
Rasmus Krogh Norrild, Kristoffer Enoe Johansson, Charlotte O'Shea, Jens Preben Morth, Kresten Lindorff-Larsen, Jakob Rahr Winther
Summary: We applied the GMMA model to analyze the effects of amino acid substitutions in a randomly mutated gene library. This method can determine mutations that increase the stability of highly stable proteins. By screening a mutant library of a computationally redesigned model protein, we identified the stability effects of 374 out of 912 possible single amino acid substitutions.
CELL REPORTS METHODS
(2022)
Article
Physiology
Natalya U. Fedosova, Michael Habeck, Poul Nissen
Summary: This article provides an overview of the well-established biochemical properties of Na,K-ATPase, focusing on its isoforms, transport mechanism and principle conformations, inhibitors, and insights gained from crystal structures.
COMPREHENSIVE PHYSIOLOGY
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
Julia Weikum, Alina Kulakova, Giulio Tesei, Shogo Yoshimoto, Line Vejby Jaegerum, Monika Schutz, Katsutoshi Hori, Marie Skepo, Pernille Harris, Jack C. Leo, J. Preben Morth
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2022)