In a preliminary study, Cortico-Binding Globuline (CBG) has been determined in 10 depressed major inpatients (DSM3) and compared with healthy volunteers. A clear cut fall of binding activity of transcortin is reported in depressed patients associated with an increase of total and free plasmatic cortisol.
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Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.
N Engl J Med
January 2025
From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (C.T.R., S.M.P., R.P.G., D.A.M., J.F.K., E.L.G., S.A.M., S.D.W., M.S.S.); Anthos Therapeutics, Cambridge, MA (B.H., S.P., D.B.); the Heart Rhythm Center, Taipei Veterans General Hospital and Cardiovascular Center, Taipei, Taiwan (S.-A.C.); Taichung Veterans Hospital, Taichung, Taiwan (S.-A.C.); National Yang Ming Chiao Tung University, Hsinchu, Taiwan (S.-A.C.); National Chung Hsing University, Taichung, Taiwan (S.-A.C.); St. Michael's Hospital, Unity Health Toronto, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto (S.G.G.); Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.); the Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.J.); the Department of Cardiology, Central Hospital of Northern Pest-Military Hospital, Budapest, Hungary (R.G.K.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (R.G.K.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (W.W.); the Departments of Medicine and of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada (J.W.); and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.).
Background: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.
Methods: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion.
Small and Versatile Cyclotides as Anti-infective Agents.
ACS Infect Dis
January 2025
Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Mato Grosso do Sul 79117-900, Brazil.
Plants provide an abundant source of potential therapeutic agents, including a diverse array of compounds, such as cyclotides, which are peptides known for their antimicrobial activity. Cyclotides are multifaceted molecules with a wide range of biological activities. Their unique topology forms a head-to-tail cyclic structure reinforced by a cysteine knot, which confers chemical and thermal stability.
View Article and Find Full Text PDFIntranasal Administrations of AP39-Loaded Liposomes Selectively Deliver H2S to Neuronal Mitochondria to Protect Neonatal Hypoxia-Ischemia by Targeting ERK1/2 and Caspase-1.
ACS Biomater Sci Eng
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Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Mitochondrial dysfunction contributes to the pathology of hypoxia-ischemia (HI) brain damage by aberrant production of ROS. Hydrogen sulfide (HS) has been demonstrated to exert neuroprotective effects through antioxidant mechanisms. However, the diffusion of HS is not specifically targeted and may even be systemically toxic.
View Article and Find Full Text PDFDe novo design of peptide binders to conformationally diverse targets with contrastive language modeling.
Sci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFNoncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.
Sci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
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