Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis, has anti-fibrotic, anti-inflammatory, and anti-angiogenic activity. We explored the impact of nintedanib on microvascular architecture in a pulmonary fibrosis model. Lung fibrosis was induced in C57Bl/6 mice by intratracheal bleomycin (0.5 mg/kg). Nintedanib was started after the onset of lung pathology (50 mg/kg twice daily, orally). Micro-computed tomography was performed via volumetric assessment. Static lung compliance and forced vital capacity were determined by invasive measurements. Mice were subjected to bronchoalveolar lavage and histologic analyses, or perfused with a casting resin. Microvascular corrosion casts were imaged by scanning electron microscopy and synchrotron radiation tomographic microscopy, and quantified morphometrically. Bleomycin administration resulted in a significant increase in higher-density areas in the lungs detected by micro-computed tomography, which was significantly attenuated by nintedanib. Nintedanib significantly reduced lung fibrosis and vascular proliferation, normalized the distorted microvascular architecture, and was associated with a trend toward improvement in lung function and inflammation. Nintedanib resulted in a prominent improvement in pulmonary microvascular architecture, which outperformed the effect of nintedanib on lung function and inflammation. These findings uncover a potential new mode of action of nintedanib that may contribute to its efficacy in idiopathic pulmonary fibrosis.

Liver resection is an effective treatment for NCRNNE liver metastases; it gives satisfactory long-term survival especially in metachronous disease, in patients with metastases from urogenital and breast tumors and when R0 procedures can be performed.

Bioadhesives are biopolymers with potential applications in wound healing, drug delivery, and tissue engineering. Pectin, a plant-based heteropolysaccharide, has recently demonstrated potential as a mucoadhesive in the gut. Since mucoadhesion is a process likely involving the interpenetration of the pectin polymer with mucin chains, we hypothesized that pectin may also be effective at targeting the glycocalyx of the visceral mesothelium. To explore the potential role of pectin as a mesothelial bioadhesive, we studied the interaction of various pectin formulations with the mesothelium of the lung, liver, bowel, and heart. Tensile strength, peel strength, and shear resistance of the bioadhesive-mesothelial interaction were measured by load/displacement measurements. In both high-methoxyl pectins (HMP) and low-methoxyl pectins, bioadhesion was greatest with an equal weight % formulation with carboxymethylcellulose (CMC). The tensile strength of the high-methoxyl pectin was consistently greater than low-methoxyl or amidated low-methoxyl formulations (p < 0.05). Consistent with a mechanism of polymer-glycocalyx interpenetration, the HMP adhesion to tissue mesothelium was reversed with hydration and limited by enzyme treatment (hyaluronidase, pronase, and neuraminidase). Peel and shear forces applied to the lung/pectin adhesion resulted in a near-interface structural failure and the efficient isolation of intact en face pleural mesothelium. These data indicate that HMP, in an equal weight % mixture with CMC, is a promising mesothelial bioadhesive for use in experimental and therapeutic applications.