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Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68(+) macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer.
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http://dx.doi.org/10.1152/ajpgi.00047.2016 | DOI Listing |
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December 2024
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Raman spectroscopy (RS) has emerged as a novel optical imaging modality by identifying molecular species through their bond vibrations, offering high specificity and sensitivity in molecule detection. However, its application in intracellular molecular probing has been limited due to challenges in combining vibrational tags with functional probes. DNA nanostructures, known for their high programmability, have been instrumental in fields like biomedicine and nanofabrication.
View Article and Find Full Text PDFAn Acad Bras Cienc
December 2024
Universidade Federal do Rio Grande do Sul - UFRGS, Programa de Pós-Graduação em Biologia Celular e Molecular - PPGBCM, Centro de Biotecnologia, Av. Bento Gonçalves, 9500, Agronomia, 90650-001 Porto Alegre, RS, Brazil.
The cystatin superfamily includes proteins crucial for inhibiting cysteine proteases, enzymes involved in many biological processes. In plants, cystatins regulate seed germination, development, and pathogen defense. In humans, inhibiting legumain-type cysteine proteases offers a promising cancer treatment strategy, as this enzyme's expression often rises during tumor progression.
View Article and Find Full Text PDFParasit Vectors
December 2024
College of Animal Science and Technology, Guangxi University, Nanning, 530004, Guangxi Zhuang Autonomous Region, People's Republic of China.
Background: Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica, which poses a serious threat to global public health and livestock farming. Fasciola gigantica secretes and excretes various components to manipulate the immune response, thereby enhancing its invasion, migration, and survival in vivo. However, the roles of specific components in immune modulation, such as asparagine endopeptidase, remain unknown.
View Article and Find Full Text PDFMicrobiol Res
February 2025
Institute for Sustainable Plant Protection, National Research Council (IPSP-CNR), Turin, Italy.
Phytoplasmas are phloem-limited plant pathogenic bacteria causing diseases in many plant species. They are transmitted by Hemipteran insect species in a persistent-propagative manner. Phytoplasmas are wall-less, and their membrane proteins are involved in pathogen internalization into host cells.
View Article and Find Full Text PDFMicrob Cell Fact
November 2024
Department of Chemical Biology, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, Wrocław, 50-383, Poland.
The expanding field of site-specific ligation of proteins and peptides has catalyzed the development of novel methods that enhance molecular modification. Among these methods, enzymatic strategies have emerged as dominant due to their specificity and efficiency in modifying proteins under mild conditions. Asparaginyl endopeptidase is a group of cyclotide-producing cysteine proteases from plants.
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