The overexpression of growth factors and receptors on neovascular endothelial cells (ECs) and their binding may promote the abnormal growth of new blood vessels, leading to corneal neovascularization (CNV). Normally, monoclonal antibodies may bind and block only one growth factor or receptor, such as bevacizumab binding and blocking vascular endothelial growth factor (VEGF). Herein, we develop a monotargeting peptidic network antibody (pepnetibody) that blocks multiple receptors on the membrane of ECs through forming a fibrous network and ultimately achieves high-efficient treatment of CNV. The pepnetibody could bind to integrin αβ in particulate formulation and fibrillogenesis on ECs, mimicking the process of fibronectin fibrillogenesis on the cell membrane. The formed peptidic network could firmly block integrin and cover other angiogenesis-related receptors, such as VEGF receptor-2 and neuropilin-1, exhibiting competitive efficacy of antiangiogenesis compared with traditional monoclonal antibody bevacizumab with 97.7 times lower dose.
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http://dx.doi.org/10.1021/acsnano.1c02194 | DOI Listing |
Chin Med
January 2025
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Background: Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu 610041, China.
Radiolabeled peptides are vital for positron emission tomography (PET) imaging, yet the F-labeling peptides remain challenging due to harsh conditions and time-consuming premodification requirements. Herein, we developed a novel vinyltetrazine-mediated bioorthogonal approach for highly efficient F-radiolabeling of a native peptide under mild conditions. This approach enabled radiosynthesis of various tumor-targeting PET tracers, including targeting the neurofibromin receptor (), the integrin αβ (), and the platelet-derived growth factor receptor β (), with a radiochemical yield exceeding 90%.
View Article and Find Full Text PDFMicrob Biotechnol
January 2025
Machine Biology Group, Department of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Antimicrobial peptides (AMPs) are promising candidates to combat multidrug-resistant pathogens. However, the high cost of extensive wet-lab screening has made AI methods for identifying and designing AMPs increasingly important, with machine learning (ML) techniques playing a crucial role. AI approaches have recently revolutionised this field by accelerating the discovery of new peptides with anti-infective activity, particularly in preclinical mouse models.
View Article and Find Full Text PDFJ Transl Med
January 2025
Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Background: Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, the Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Alas, ageing-associated decline in the efficiency of this network enables protein aggregation and consequently the development of late-onset neurodegenerative disorders, such as Alzheimer's disease. Accordingly, the maintenance of proteostasis through late stages of life bears the promise to delay the emergence of these devastating diseases.
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