Reproducible lung protective effects of a TGFβR1/ALK5 inhibitor in a bleomycin-induced and spirometry-confirmed model of IPF in male mice.

This study comprehensively validated the bleomycin (BLEO) induced mouse model of IPF for utility in preclinical drug discovery. To this end, the model was rigorously evaluated for reproducible phenotype and TGFβ-directed treatment outcomes. Lung disease was profiled longitudinally in male C57BL6/JRJ mice receiving a single intratracheal instillation of BLEO (n = 10-12 per group).

Histological and immunohistochemical guide to tendon tissue.

Tendons are unique dense connective tissues with discrete zones having specific structure and function. They are juxtaposed with other tissues (e.g.

Development of three-layer collagen scaffolds to spatially direct tissue-specific cell differentiation for enthesis repair.

Enthesis repair remains a challenging clinical indication. Herein, a three-layer scaffold composed of a tendon-like layer of collagen type I, a fibrocartilage-like layer of collagen type II and a bone-like layer of collagen type I and hydroxyapatite, was designed to recapitulate the matrix composition of the enthesis. To aid tenogenic and fibrochondrogenic differentiation, bioactive molecules were loaded in the tendon-like layer or the fibrocartilage-like layer and their effect was assessed in setting using human bone marrow derived mesenchymal stromal cells and in an model.

Macromolecular crowding in animal component-free, xeno-free and foetal bovine serum media for human bone marrow mesenchymal stromal cell expansion and differentiation.

Cell culture media containing undefined animal-derived components and prolonged culture periods in the absence of native extracellular matrix result in phenotypic drift of human bone marrow stromal cells (hBMSCs). Herein, we assessed whether animal component-free (ACF) or xeno-free (XF) media formulations maintain hBMSC phenotypic characteristics more effectively than foetal bovine serum (FBS)-based media. In addition, we assessed whether tissue-specific extracellular matrix, induced macromolecular crowding (MMC) during expansion and/or differentiation, can more tightly control hBMSC fate.

Destabilization of the SHP2 and SHP1 protein tyrosine phosphatase domains by a non-conserved "backdoor" cysteine.

Protein tyrosine phosphatases (PTPs) are critical regulators of cellular signal transduction that catalyze the hydrolytic dephosphorylation of phosphotyrosine in substrate proteins. Among several conserved features in classical PTP domains are an active-site cysteine residue that is necessary for catalysis and a "backdoor" cysteine residue that can serve to protect the active-site cysteine from irreversible oxidation. Curiously, two biologically important phosphatases, Src homology domain-containing PTPs 2 and 1 (SHP2 and SHP1), each contain an additional backdoor cysteine residue at a position of the PTP domain that is occupied by proline in almost all other classical PTPs (position 333 in human SHP2 numbering).