We present a concept for reducing formation of fibrotic deposits by inhibiting self-assembly collagen molecules into fibrils, main component lesions. Employing monoclonal antibodies that bind to the telopeptide region molecule, we found blocking telopeptide-mediated collagen/collagen interactions reduces amount fibrils accumulated in vitro and keloid-like organotypic constructs. conclude extracellular steps process provides novel approach limit fibrosis number tissues organs. Collagen I is...

The most common mutations in type I collagen causing types II–IV osteogenesis imperfecta (OI) result substitution for glycine a Gly-Xaa-Yaa triplet by another amino acid. We delineated Y-position small pedigree with combined OI/Ehlers-Danlos Syndrome (EDS) phenotype, characterized moderately decreased DEXA z-score (–1.3 to −2.6), long bone fractures, and large-joint hyperextensibility. Affected individuals have an α1(I)R888C (p.R1066C) one COL1A1 allele. Polyacrylamide gel electrophoresis...

Abstract Asthma is a chronic lung disease exhibiting airway obstruction, hyperresponsiveness, and inflammation, characterized by the infiltration of eosinophils into airways underlying tissue. Prolonged eosinophilic inflammation depends on balance between cell’s inherent tendency to undergo apoptosis local eosinophil-viability enhancing activity. TRAIL, member TNF family, induces in most transformed cells; however, its role health remains unknown. To test hypothesis that Ag-induced...

The myelin basic protein (MBP) gene is expressed only in oligodendrocytes and Schwann cells, expression follows a tightly regulated developmental time course. Cell type- stage-specific of the MBP appears to be by series cis-acting elements located upstream transcription start site. proximal element regulatory region (MB1), between nucleotides −14 −50, one several participating programmed MBP. In this report, we describe molecular cloning characterization factor-2 (Myef-2), isolated from...

Post-traumatic joint contracture is a frequent orthopaedic complication that limits the movement of injured joints, thereby severely impairing affected patients. Non-surgical and surgical treatments for often fail to improve range motion. In this study, we tested hypothesis limiting formation collagen-rich tissue in capsules joints would reduce consequences fibrotic response mobility. We targeted collagen fibrils, main component deposits formed within tissues by employing relevant rabbit...

Abstract Collagens are attractive proteins as materials for tissue engineering. Over the last decade, significant progress has been made in developing technologies large‐scale production of native‐like human recombinant collagens. Yet, rational design customized collagen‐like smart biomaterials to enhance quality engineered tissues not explored. We mapped D4 domain collagen II most critical supporting migration chondrocytes and used this information genetically engineer a protein consisting...

Increased tendon pain and damage is a significant complication related to hyperlipidemia. Unlike the well-established pathogenesis associated with increased serum concentrations of total cholesterol, triglycerides, low-density lipoprotein in atherosclerotic cardiovascular disease, role hyperlipidemia promoting remains controversial requires mechanistic clarity. In this study, we analyzed consequences hypercholesterolemia on integrity collagen-based architecture Achilles tendon. The tendons...

We investigated the effects of presence R75C (p.R275C), R519C (p.719C), R789C (p.R989C), and G853E (p.G1053E) type II collagen (COL2A1) mutants, associated with distinct forms spondyloepiphyseal dysplasia (SED), on biological processes occurring in chondrocytic cells harboring those mutants. Mutant-specific responses were initiated by activating tetracycline (Tet)-dependent expression Employing microscopic biochemical assays, we determined that expressing thermolabile (p.R989C) mutant...

ABSTRACT Post‐traumatic joint contracture is a debilitating consequence of trauma or surgical procedures. It associated with fibrosis that develops regardless the nature initial and results from complex biological processes inflammation cell activation. These accelerate production structural elements extracellular matrix, particularly collagen fibrils. Although increased collagenous proteins has been demonstrated in tissues contracted joints, researchers have not yet determined protein...

Age-related tendon degeneration (tendinosis) is characterized by a phenotypic change in which tenocytes display characteristics of fibrochondrocytes and mineralized fibrochondrocytes. As has been noted vivo areas decreased vascularity, we hypothesized that hypoxia responsible for the development tendinosis phenotype, these effects are more pronounced aged tenocytes. Hypoxic (1% O2 ) culture aged, tendinotic, young human resulted fibrochondrocyte phenotype tenocytes, tendinotic Investigation...

Abstract Introduction Posttraumatic scarring of peripheral nerves produces unwanted adhesions that block axonal growth. In the context surgical nerve repair, organization scar tissue adjacent to conduits used span gap between stumps transected is poorly understood. The goal this study was elucidate patterns distribution collagen‐rich and analyze spatial cells produce fibrotic deposits around within conduit's lumen. Methods Employing a rabbit model sciatic transection injury, we studied...

The glucocorticoid and mineralocorticoid receptors (GR MR) share considerable structural functional homology bind as homodimers to hormone-response elements. We have shown previously that MR GR can form heterodimers inhibit transcription from a (GC)-responsive gene this inhibition was mediated by the N-terminal domain (NTD) of MR. In report, we examined effect NTD-MR on GC-induced apoptosis in GC-sensitive pre-B lymphoma cell line, 697. GC-treated 697 cells, demonstrated stable expression...

The overall aim of presented study is to test the inhibition formation collagen fibrils as novel approach reduce accumulation pathological fibrotic deposits. main hypothesis that by interfering with initial steps extracellular process fibril formation, it possible tissue.The experimental model includes antibody-based inhibitors specifically bind sites participate in collagen/collagen interaction.Employed effectively limit amount formed vitro and engineered tissue models localized...

Procollagen VII is a homotrimer of 350-kDa pro-α1(VII) chains, each consisting central collagenous domain flanked by the noncollagenous N-terminal NC1 and C-terminal NC2 domain. After secretion from cells, procollagen molecules form anti-parallel dimers with 60-nm overlap. Characteristic alignment monomers forming dimer depends on site-specific binding between triple-helical region adjacent to Cys-2634 interacting molecules. Formation intermolecular disulfide bonds either Cys-2802 or...

Inhibition of the extracellular process collagen fibril formation represents a new approach to limiting posttraumatic or postsurgical localized fibrosis. It has been demonstrated that employing monoclonal antibody targets C-terminal telopeptide α2 chain I blocks critical I–collagen interaction, thereby reducing amount deposits in vitro and animal models. Here, we developed chimeric variant prototypic inhibitory mouse origin. The structure this novel was analyzed by biochemical biophysical...

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As result, their use not fully effective may cause unwanted side effects. Our group previously demonstrated extracellular collagen fibrillogenesis valid specific target collagen-rich scar buildup. previous studies showed rationally...

This study focuses on the single-chain fragment variable (scFv) variant of original IgA-type antibody, recognizing α2 C-terminal telopeptide (α2Ct) human collagen I, designed to inhibit post-traumatic localized fibrosis via blocking formation collagen-rich deposits. We have demonstrated that scFv construct expressed in yeast cells was able fold into an immunoglobulin-like conformation, but it prone forming soluble aggregates. Functional assays, however, indicate specifically binds α2Ct...

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology (PD53)1 May 2024PD53-01 ARE MICROPLASTICS PRESENT IN HUMAN TESTICLE TISSUE? ANALYSIS USING INFRARED SPECTROSCOPY John M. Masterson, Azita HassanMazandarani, William Querido, Andrzej Steplewski, Yi Zhang, Carissa Huynh, Fertala, Nancy Pleshko, and Maurice Garcia MastersonJohn Masterson , HassanMazandaraniAzita HassanMazandarani QueridoWilliam Querido SteplewskiAndrzej Steplewski ZhangYi Zhang HuynhCarissa Huynh...