MCoTI-II is a member of a class of microproteins known as cyclotides that possess a macrolactam-cystine knot scaffold imparting exceptional physiological stability and structural rigidity. Modification of residues in the active loop and engineered truncations have resulted in MCoTI-II analogues that possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors against targets in inflammatory disease.
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http://dx.doi.org/10.1021/jm901233u | DOI Listing |
Front Oncol
December 2024
Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, Bari, Italy.
Tryptases represent the most abundant constituent of human mast cells, involved in extracellular matrix degradation, contributing to wound healing and metastasis. Moreover, most recently, it has been demonstrated that tryptase is angiogenic both and . Tryptase-positive mast cell number increases parallelly with increased microvascular density in both solid and hematological tumors.
View Article and Find Full Text PDFCurr Opin Allergy Clin Immunol
February 2025
Division of Allergic Diseases, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Purpose Of Review: Mast cell activation is defined by activation of mast cells by varying stimuli with release of chemical mediators either through degranulation or release of de novo synthesized proteins or lipid mediators. Currently, tryptase measurement increase during symptomatic episodes is the most accepted biomarker measurement for mast cell activation. However, newer diagnostic tools including clinically available urinary mast cell mediators are noninvasive and can be more readily obtained compared to serum tryptase levels.
View Article and Find Full Text PDFAllergy Asthma Proc
January 2025
From the Division of Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, California and.
Since its first description more than a decade ago, our understanding of the clinical impact of hereditary alpha-tryptasemia has continued to evolve. First considered to be a genetic disorder with a subset of patients having a syndromic presentation composed of connective tissue abnormalities, symptoms of autonomic dysfunction, and findings of mast cell activation, we now know that hereditary alpha-tryptasemia is a common genetic trait and modifier of mast cell-mediated reactions. More recent studies have shown some previously held associations with congenital hypermobility and postural orthostatic tachycardia syndrome (POTS) to be lacking, and illuminated previously unappreciated associations with clonal and nonclonal mast cell disorders.
View Article and Find Full Text PDFAllergy Asthma Proc
January 2025
Department of Pediatric Allergy and Immunology, Health Sciences University, Ankara City Hospital, Ankara, Turkey.
Cutaneous mastocytosis (CM) is the most common type of mastocytosis in children. The atopy frequency in these patients is typically similar to that in the general population, but a higher incidence of anaphylaxis is reported. This study aimed to evaluate the presence of allergic diseases in children diagnosed with CM and its impact on clinical manifestations.
View Article and Find Full Text PDFAllergy Asthma Proc
January 2025
Perioperative anaphylaxis is a serious entity with high morbidity and mortality. Perioperative anaphylaxis can be caused by any of the multitude of medications and substances used in anesthesia and surgery, and the most common causes include neuromuscular blocking agents, antibiotics, antiseptics, latex, and dyes. The differential diagnosis of perioperative anaphylaxis is wide from both an immunologic and a nonimmunologic standpoint.
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