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Rat Thiostatin: Structure and Possible Function in the Acute Phase Response
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Gerhard Schreiber, Timothy J. Cole
The second alternative for the physiological function of thiostatin is that of an inhibitor of cysteine proteinases. Such proteinases are released from lysosomes during inflammation.14 Inhibition of these proteinases becomes important during the acute phase response. Not only cysteine proteinases released from lysosomes, such as cathepsins, but also papain, whose amino acid sequence is partially homologous49 to that of cathepsin H and B, are inhibited by thiostatin. In summary, the function of thiostatin seems more likely to be that of a proteinase inhibitor rather than that of a kinin precursor, suggesting that the name “thiostatin” is more appropriate for the protein than the name “T-kininogen”.
Optical Techniques for Imaging of Cell Trafficking
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
A number of studies with NIRF probes, both in culture and in vivo, have shown that the nonactivated probes have a very-low background fluorescence and that protease activation of probes can increase the fluorescence over several hundredfold (19) with probes detectable in the nanomolar range and with no apparent toxicity (20). Autoquenched NIRF probes that become active after protease activation have been used in imaging tumors that have upregulated levels of certain PR, like cathepsins (14). Cathepsin B and cathepsin H protease activities have also been used to detect submillimeter-sized tumors using NIR fluorescent probes (14) and cathepsin D-positive tumors (21) have been imaged in mouse models (Fig. 2). In another study, cathepsin B activity has been used as a biomarker to readily identify dysplastic adenomatous polyps, which contrasts particularly well against normal adjacent mucosa (22). This detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and allows the potential for molecular profiling of protease activity in vivo. A number of different matrix metalloproteinase (MMP) inhibitors, which act as cytostatic and antiangiogenic agents are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to detect or image antiproteinase activity directly and noninvasively in vivo. Recent developments allow NIRF-MMP substrates to be used as activatable NIRF reporter probes to monitor MMP activity in intact tumors (12). These probes have the advantage of directly imaging MMP activity within hours after treatment with potent MMP inhibitors.
Patented therapeutic drug delivery strategies for targeting pulmonary diseases
Published in Expert Opinion on Therapeutic Patents, 2020
Ajay Kumar Thakur, Dinesh Kumar Chellappan, Kamal Dua, Meenu Mehta, Saurabh Satija, Inderbir Singh
Proteolytic enzymes, surfactants, and alveolar macrophages constitute the chemical and immunological barriers in pulmonary drug delivery. Proteolytic enzymes such as cathepsin H and endopeptidase are responsible for the hydrolysis of protein and peptides in lungs [11]. Alveolar macrophages are the phagocytic cells that engulf harmful particles and remove them from the lungs. Surfactants prevent the adherence of the inhaled particles to the epithelial surface of the lungs and also make the particles accessible to be engulfed and removed by macrophages [12].