Collagenase Clostridium histolyticum (CCH) contains a fixed ratio of class I (AUX-I) and class II (AUX-II) collagenases and is used as treatment for Dupuytren's contracture. These two Zn-dependent enzymes, produced by the Gram-positive bacterium Clostridium histolyticum, are related functionally to matrix metalloproteinases (MMPs) which, among other functions, degrade the extracellular matrix. Since AUX-I and AUX-II exhibit sequence similarities to human MMPs, we assessed MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-8 (collagenase 2), and MMP-13 (collagenase 3) for cross-reactivity with anti-AUX-I and anti-AUX-II antibodies in patient serum. Serum samples from 71 subjects enrolled in a long-term clinical study (58 males and 13 females; 63 ± 10 years old [mean ± standard error]) were evaluated for cross-reactivity with the five MMPs using the two validated enzyme-linked immunosorbent assays (ELISAs). Inhibition cutoff points for anti-AUX-I and anti-AUX-II antibodies were based on assay inhibition obtained with a nonspecific protein, bovine gamma globulin, which was tested for each clinical sample. No MMP cross-reactivity was found for any of the 71 clinical antibody-positive sera evaluated. Sequence identity assessments indicated minimal, nonmeaningful alignments of the MMPs and AUX-I/AUX-II. Furthermore, clinical adverse event assessments indicated no safety signals related to MMP inhibition. The bioanalytical results, sequence identity, and clinical assessments consistently did not demonstrate cross-reactivity between CCH antidrug antibodies and endogenous human matrix metalloproteinases. The results presented here suggest that treatment of Dupuytren's contracture patients with CCH does not lead to any clinical adverse events associated with MMP inhibition.
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http://dx.doi.org/10.1128/CVI.00018-12 | DOI Listing |
Cell Death Dis
January 2025
Department of Pathology, Qilu Hospital and School of Basic Medical Sciences Shandong University, Jinan, Shandong, PR China.
Long noncoding RNAs (lncRNAs) are key regulators during gastric cancer (GC) development and may be viable treatment targets. In the present study, we showed that the expression of the long intergenic noncoding RNA 01016 (LINC01016) is significantly higher in GC tissues with lymph node metastasis (LNM) than those without LNM. LINC01016 overexpression predicts a poorer relapse-free survival (RFS) and overall survival (OS).
View Article and Find Full Text PDFBiochem Genet
January 2025
Department of Physiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Although DNA methyltransferase 1 (DNMT1) and RNA editor ADAR triplications exist in Down syndrome (DS), their specific roles remain unclear. DNMT methylates DNA, yielding S-adenosine homocysteine (SAH), subsequently converted to homocysteine (Hcy) and adenosine by S-adenosine homocysteine (Hcy) hydrolase (SAHH). ADAR converts adenosine to inosine and uric acid.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
The glomerular filtration barrier (GFB) has a unique spatial structure, including porous capillary endothelial cells, glomerular basal membrane (GBM) and highly specialized podocytes. This special structure is essential for the hemofiltration process of nephrons. GBM is the central meshwork structure of GFB formed by the assembly and fusion of various extracellular matrix (ECM) macromolecules, such as laminins and collagens, which undergo isoform transformation and maturation that may require precise regulation by metalloproteinases.
View Article and Find Full Text PDFAn Acad Bras Cienc
January 2025
Universidade Federal de Pernambuco, Departamento de Histologia e Embriologia, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50760-420 Recife, PE, Brazil.
Matrix metalloproteinases (MMP) have been identified as biomarkers for several diseases, including cancer. The increase in the expression of these enzymes has been related to greater tumor aggressiveness. MMP-26 is expressed constitutively in the endometrium and some cancer cells of epithelial origin.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China.
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