Cystatins comprise a vast superfamily of evolutionary conserved proteins, predominantly recognized for their roles as endogenous inhibitors by regulating the activity of cysteine proteases. Emerging lines of research evidence also provides insight into their alternative roles in a spectrum of biological and pathological processes, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. Nowadays, various type-1 cystatins (stefins) have been demonstrated among a variety of discovered vertebrate groups, while little is known about the related homologue in cephalochordate amphioxus, which are repositioned at the base of the chordate phylum. In the present study, a single type-1 cystatin homologue in Branchiostoma japonicum was first successfully cloned and designated as Bjcystatin-1. The deduced Bjcystatin-1 protein is structurally characterized by the presence of typical wedge-shaped cystatin features, including the 'QxVxG' and 'Px' motif, as well as the conserved N-terminal glycine residue. Phylogenomic analyses utilizing different cystatin counterparts affirmed the close evolutionary relationship of Bjcystatin-1 and type-1 cystatin homologue. Bjcystatin-1 was predominantly expressed in the gills and hind-gut in a tissue-specific pattern, and its expression was remarkably up-regulated in response to challenge with bacteria or their signature molecules LPS and LTA, suggesting the involvement in immune response. Additionally, the recombinant Bjcystatin-1 (rBjcystatin-1) protein showed significant inhibitory activity towards papain and binding ability to LPS and LTA, indicating its hypothesized role as a pattern recognition receptor in immune response. Subcellular localization results also showed that Bjcystatin-1 was located in the cytoplasm and nucleus, and its overexpression could attenuate the activation of LPS-induced nuclear transcription factors NF-κB. Taken together, our study suggests that amphioxus Bjcystatin-1 acts as a dual role in protease inhibitor and an immunocompetent factor, providing new insights into the immune defense effect of type-1 cystatin in amphioxus.
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http://dx.doi.org/10.1016/j.fsi.2024.109423 | DOI Listing |
Mol Oncol
January 2025
System Biology, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Japan.
Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis due to diagnostic and therapeutic limitations. We previously identified cystatin A (CSTA) as a PDAC biomarker and have conducted the present study to investigate the antitumor effects of CSTA. PDAC murine models were established with genetically modified PAN02 tumor cell lines to evaluate the antitumor immune response.
View Article and Find Full Text PDFJ Nephrol
January 2025
Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.
Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.
Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.
Curr Protein Pept Sci
December 2024
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Campus do Pici, Fortaleza-Ceará, Brazil. CEP 60451-970.
Introduction: Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Pediatric Cardiology, University Children's Hospital, University of Tübingen, Tübingen, Germany.
Recent research in patients with functionally univentricular hearts (UVH) is focusing on pathologies of the lymphatic vessels. Morphology of the abdominal lymphatic vessels was analyzed by MRI in patients with UVH following total cavopulmonary connection (TCPC) and it was examined, if clinical and laboratory parameters correlate with changes after TCPC. We prospectively examined 33 patients at the age of 19.
View Article and Find Full Text PDFJ Physiol Investig
November 2024
Department of Geriatrics, Minhang Hospital, Fudan University, Shanghai, China.
Type 2 diabetes mellitus (T2DM) patients always develop osteoporosis (OP). We examined correlations of N-terminal mid-fragment of osteocalcin (N-MID) and cystatin C (Cys C) levels with glycolipid metabolism, bone metabolism markers, and bone mineral density (BMD) in elderly T2DM-OP patients. Grouping was performed as per whether T2DM patients developed OP (OP group) or not (N-OP group).
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