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
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
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
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
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
Medicine, Research & Experimental
Florence Boissiere-Michot, Caroline Mollevi, Volker Baecker, Evelyne Crapez, William Jacot
Summary: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) have been identified as prognostic and predictive biomarkers in breast cancer, but their clinical use is limited due to the need for fresh-frozen or fresh tumor samples for quantification. This study compared the expression levels of PLAU and SERPINE1 mRNA (corresponding to uPA and PAI-1 proteins) using in situ hybridization with immunometric assay in breast tumor samples. The results showed that in situ hybridization cannot replace the immunometric assay for quantification of uPA and PAI-1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
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
Oncology
Bofang Wang, Baohong Gu, Tao Zhang, Xuemei Li, Na Wang, Chenhui Ma, Lin Xiang, Yunpeng Wang, Lei Gao, Yang Yu, Kewei Song, Puyi He, Yueyan Wang, Jingyu Zhu, Hao Chen
Summary: The fibrinolytic system is involved in various physiological functions and plays a significant role in the pathogenesis of many diseases. Plasminogen activator inhibitor 1 (PAI-1) is a crucial element of this system and acts as an anti-fibrinolytic agent in the normal blood clotting process. PAI-1 is involved in blood diseases, inflammation, obesity, metabolic syndrome, and tumor pathology, exhibiting a paradoxical role in different digestive system tumors.
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
Multidisciplinary Sciences
Hideki Furuya, Yuka Sasaki, Runpu Chen, Rafael Peres, Kanani Hokutan, Kaoru Murakami, Nari Kim, Owen T. M. Chan, Ian Pagano, Lars Dyrskjot, Jorgen B. Jensen, Per-Uno Malmstrom, Ulrika Segersten, Yijun Sun, Abolfazl Arab, Hani Goodarzi, Steve Goodison, Charles J. Rosser
Summary: The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, but recent studies have revealed its role in promoting human cancers by regulating angiogenesis and tumor cell survival. This study found that PAI-1 expression levels correlated with tumor grade, stage, and overall survival in bladder cancer. Further investigation showed that nuclear PAI-1 can influence gene expression programs and support malignancy.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Kaito Harada, Takashi Yahata, Makoto Onizuka, Abd Aziz Ibrahim, Eri Kikkawa, Toshio Miyata, Kiyoshi Ando
Summary: The study highlights the inhibitory role of plasminogen activator inhibitor type-1 (PAI-1) in hematopoietic regeneration in bone marrow microenvironments with abundant bone marrow adipocytes (BMAs), suggesting that blocking PAI-1 activity could be a novel therapeutic approach. PAI-1 inhibitor treatment significantly increases stem cell factor concentration in obese patients, contributing to improved hematopoietic regeneration.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Dermatology
Yu-Ju Tseng, Chih-Hung Lee, Wei-Yu Chen, Jenq-Lin Yang, Hong-Tai Tzeng
Summary: The study demonstrates that PAI-1 activity regulates immune checkpoints by promoting lysosomal degradation of PD-L1. Inhibition of PAI-1 combined with anti-PD-L1 immunotherapy shows promise as a therapeutic regimen for melanoma treatment.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Hematology
Tae Ito, Yuko Suzuki, Hideto Sano, Naoki Honkura, Francis J. Castellino, Tetsumei Urano
Summary: The study demonstrates the existence of three distinct forms of high-molecular-weight complexes between tPA and PAI-1. Peptide sequence analysis revealed that these complexes consist of nonacylated-enzyme inhibitor complexes, with only a fraction of the population releasing free tPA under physiological conditions.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Mette Dahl, Simon Husby, Christian W. Eskelund, Soren Besenbacher, Soren Fjelstrup, Christophe Come, Sara Ek, Arne Kolstad, Riikka Raty, Mats Jerkeman, Christian H. Geisler, Jorgen Kjems, Lasse S. Kristensen, Kirsten Gronbaek
Summary: Circular RNAs (circRNAs) show promise as prognostic biomarkers in mantle cell lymphoma (MCL); the circSCORE signature improves the identification of high-risk disease in younger patients receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.
Article
Biochemical Research Methods
Anne F. Nielsen, Albrecht Bindereif, Irene Bozzoni, Mor Hanan, Thomas B. Hansen, Manuel Irimia, Sebastian Kadener, Lasse S. Kristensen, Ivano Legnini, Mariangela Morlando, Morten T. Jarlstad Olesen, R. Jeroen Pasterkamp, Stephan Preibisch, Nikolaus Rajewsky, Christin Suenkel, Jorgen Kjems
Summary: There is a growing number of circular RNA (circRNA) papers in recent years, highlighting the urgent need for common experimental standards and best practice principles to advance the field and enhance understanding of this group of RNA molecules.
Article
Oncology
Doron Tolomeo, Debora Traversa, Santina Venuto, Karoline K. Ebbesen, Juan L. Garcia Rodriguez, Grazia Tamma, Marianna Ranieri, Giorgia Simonetti, Martina Ghetti, Matteo Paganelli, Grazia Visci, Arcangelo Liso, Klaas Kok, Lucia Anna Muscarella, Federico Pio Fabrizio, Maria Antonia Frassanito, Aurelia Lamanuzzi, Ilaria Saltarella, Antonio Giovanni Solimando, Alessandro Fatica, Zaira Ianniello, Rene Massimiliano Marsano, Antonio Palazzo, Amalia Azzariti, Vito Longo, Stefania Tommasi, Domenico Galetta, Annamaria Catino, Alfredo Zito, Tommaso Mazza, Alessandro Napoli, Giovanni Martinelli, Jorgen Kjems, Lasse Sommer Kristensen, Angelo Vacca, Clelia Tiziana Storlazzi
Summary: Small cell lung cancer (SCLC) is a heterogeneous disease characterized by distinct molecular subtypes. The amplification of MYC oncogene in SCLC is associated with different histological classes. Circular (circRNA) and chimeric RNAs derived from the co-amplified PVT1 gene were found to have a functional role in SCLC, promoting cell growth and preventing apoptosis. These PVT1 transcripts also showed a connection between MYC and YAP1/POU2F3, contributing to the transcriptional landscape of MYC-amplified tumors. These findings suggest that circular and chimeric PVT1 transcripts could serve as novel biomarkers for MYC-amplified SCLC.
GENES CHROMOSOMES & CANCER
(2023)
Editorial Material
Cell Biology
Ling-Ling Chen, Albrecht Bindereif, Irene Bozzoni, Howard Y. Y. Chang, A. Gregory Matera, Myriam Gorospe, Thomas B. B. Hansen, Jorgen Kjems, Xu-Kai Ma, Jun Wei Pek, Nikolaus Rajewsky, Julia Salzman, Jeremy E. E. Wilusz, Li Yang, Fangqing Zhao
Summary: This Comment calls for a common nomenclature for naming circRNAs to ensure clarity and reproducibility in studies.
NATURE CELL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xialin Zhang, Nicole Stephanie Galenkamp, Nieck Jordy van der Heide, Giovanni Maglia, Jorgen Kjems, Julian Moreno
Summary: Nanopores functionalized with different nanobodies show great potential for stochastic sensing of proteins. They can detect Spike protein, HER2 receptor, and muPA protein through reversible blockade events or larger blockage signals, enabling the clinical detection of protein biomarkers.
Article
Biochemistry & Molecular Biology
Claudia Catapano, Johanna V. Rahm, Marjan Omer, Laura Teodori, Jorgen Kjems, Marina S. Dietz, Mike Heilemann
Summary: HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and is activated through heterodimerization with other ErbB receptors. This study found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFa, with a distinguishable temporal fingerprint. HER4-targeting ligands EREG and NRG beta 1 showed weaker activation of HER2, with a preference for EREG and a delayed response to NRG beta 1.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Immunology
Dirk Reinhold, Vadim Farztdinov, Yan Yan, Christian Meisel, Henrik Sadlowski, Joachim Kuehn, Frank H. Perschel, Matthias Endres, Emrah Duezel, Stefan Vielhaber, Karina Guttek, Alexander Goihl, Morten Veno, Bianca Teegen, Winfried Stoecker, Paula Stubbemann, Florian Kurth, Leif E. Sander, Markus Ralser, Carolin Otto, Simon Streit, Sven Jarius, Klemens Ruprecht, Helena Radbruch, Jorgen Kjems, Michael Muelleder, Frank Heppner, Peter Koertvelyessy
Summary: Patients with COVID-19 may experience various neurological symptoms, but the role of the central nervous system (CNS) in COVID-19 is still unclear. The inflammatory response in the cerebrospinal fluid (CSF) of COVID-19 patients was studied, and it was found that there were attenuated inflammatory changes compared to patients with herpes simplex virus encephalitis (HSVE). The inflammatory mediators in the CSF of COVID-19 patients were likely derived from the systemic circulation rather than produced within the CNS. Further investigation is needed to understand the relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Oncology
Eileen Wedge, Ulvi Ahmadov, Thomas B. Hansen, Zongliang Gao, Morten Tulstrup, Christophe Come, Sridhar Nonavinkere Srivatsan, Tanzir Ahmed, Jakob S. Jespersen, Balthasar C. Schlotmann, Claudia Schollkopf, Klas Raaschou-Jensen, Niels Odum, Jorgen Kjems, Rasmus O. Bak, Matthew J. Walter, Kirsten Gronbaek, Lasse S. Kristensen
Summary: Mutations in the U2AF1 gene are associated with a higher occurrence of myelodysplastic neoplasms (MDS) and a worse prognosis, but the exact molecular mechanisms are not fully understood. This study found that U2AF1 mutations may impact circRNA production, leading to increased cancer development. Increased circRNA expression levels were observed in cells and patient samples with U2AF1 mutations, suggesting a potential role of circRNA as a biomarker and therapeutic target in MDS.
Article
Neurosciences
Sabine Seeler, Maria Schertz Andersen, Tamas Sztanka-Toth, Mateja Rybiczka-Tesulov, Marleen H. van den Munkhof, Chi-Chih Chang, Muyesier Maimaitili, Morten Trillingsgaard Veno, Thomas Birkballe Hansen, R. Jeroen Pasterkamp, Agnieszka Rybak-Wolf, Mark Denham, Nikolaus Rajewsky, Lasse Sommer Kristensen, Jorgen Kjems
Summary: Using RNA-sequencing, this study reveals that circRNA levels significantly increase during the differentiation of human embryonic stem cells into neural progenitor cells. Knockdown of circFAT3 leads to transcriptional alterations and loss of specific cell types in cerebral organoids. Depletion of circFAT3 in mouse prefrontal cortex affects the positioning of electroporated cells. These findings highlight the important role of circFAT3 in neural development.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Alexey Ferapontov, Marjan Omer, Isabelle Baudrexel, Jesper Sejrup Nielsen, Daniel Miotto Dupont, Kristian Juul-Madsen, Philipp Steen, Alexandra S. Eklund, Steffen Thiel, Thomas Vorup-Jensen, Ralf Jungmann, Jorgen Kjems, Soren Egedal Degn
Summary: The binding between B cell receptors (BCRs) and antigens triggers a response in B cells and eventually leads to antibody production. However, it is still unclear how BCRs are distributed on naive B cells and how antigen binding initiates the first step of BCR signaling. Using DNA-PAINT super-resolution microscopy, it has been discovered that most BCRs exist as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30nm. By engineering monoclonal model antigens with precise control over affinity and valency, researchers found that the antigen can activate the BCR in an agonistic manner as affinity and avidity increase.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Sadegh Ghorbani, Annette Christine Fuchtbauer, Andreas Mollebjerg, Pia Moller Martensen, Sara Hvidbjerg Laursen, David Christian Evar Kraft, Jorgen Kjems, Rikke Louise Meyer, Karim Rahimi, Morten Foss, Ernst-Martin Fuchtbauer, Duncan S. Sutherland
Summary: Biochemical and biomechanical signals in the niche environments regulate stem cell function. A study compared in vitro signals from LN-511 and/or topographic cues to maintain stemness in mESCs. The integration of LN-511 with nanotopography decreased colony growth but maintained stemness markers, suggesting the antagonistic effect of combining biochemical and topographic signals. Faster colony growth was observed at nanotopographies without LN-511, indicating improved ESC expansion.
Article
Oncology
Juan L. Garcia-Rodriguez, Ulrik Korsgaard, Ulvi Ahmadov, Morten T. Jarlstad Olesen, Kim-Gwendolyn Dietrich, Emma B. Hansen, Stine M. Vissing, Benedichte P. Ulhoi, Lars Dyrskjot, Karina D. Sorensen, Jorgen Kjems, Henrik Hager, Lasse S. Kristensen
Summary: The abundance of circRNAs varies systematically between subcompartments of solid tumors and adjacent tissues, suggesting that differentially expressed circRNAs may reflect differences in cell type composition. These findings highlight the limitations of bulk tissue analyses and emphasize the need for spatial analysis in cancer research.
Article
Multidisciplinary Sciences
Mona Heiland, Niamh M. C. Connolly, Omar Mamad, Ngoc T. Nguyen, Jaideep C. Kesavan, Elena Langa, Kevin Fanning, Albert Sanfeliu, Yan Yan, Junyi Su, Morten T. Veno, Lara S. Costard, Valentin Neubert, Tobias Engel, Thomas D. M. Hill, Thomas M. Freiman, Arun Mahesh, Vijay K. Tiwari, Felix Rosenow, Sebastian Bauer, Jorgen Kjems, Gareth Morris, David C. Henshall
Summary: This study suggests that modulation of miR-335-5p may be a potential strategy to regulate voltage-gated sodium channels (VGSCs) and affect neuronal excitability and seizures. Changes in miR-335-5p may reflect compensatory mechanisms to control excitability and could provide biomarker or therapeutic strategies for different types of treatment-resistant epilepsy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Soren Fjelstrup, Daniel M. Dupont, Claus Bus, Jan J. Enghild, Jorgen B. Jensen, Karin Birkenkamp-Demtroder, Lars Dyrskjot, Jorgen Kjems
Summary: The APTASHAPE method allows for the rapid and accurate discovery of potential disease biomarkers by using aptamers to recognize proteins in complex biofluids.