Nanofluid to Nanocomposite Film: Chitosan and Cellulose-Based Edible Packaging

Chitosan (CH)-based materials are compatible to form biocomposite film for food packaging applications. In order to enhance water resistance and mechanical properties, cellulose can be introduced to the chitosan-based film. In this work, we evaluate the morphology and water resistance of films prepared from chitosan and cellulose in their nanoscale form and study the phenomena underlying the film formation. Nanofluid properties are shown to be dependent on the particle form and drive the morphology of the prepared film. Film thickness and water resistance (in vapor or liquid phase) are clearly enhanced by the adjunction of nanocrystalline cellulose

Disruption of GCN2 Pathway Aggravates Vascular and Parenchymal Remodeling During Pulmonary Fibrosis.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 gene (EIF2AK4) were recently associated with pulmonary veno-occlusive disease. This study aims to explore the involvement of the GCN2/eIF2α pathway in the development of PH during PF, in both human disease and in an experimental animal model. Lung tissue from PF patients with or without PH were collected at the time of lung transplantation, and controls were obtained from tumor resection surgery. Experimental lung disease was induced in either male wild-type or EIF2AK4-mutated Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin or saline. Hemodynamic studies, as well as organ collection were performed 3 weeks post-instillation. Only significant results (p<0.05) are given. In PF lung tissue, GCN2 protein expression was decreased, when compared with controls. GCN2 expression was reduced in CD31+ endothelial cells. In line with human data, GCN2 protein expression was decreased in the lung of bleomycin rats when compared with saline. EIF2AK4-mutated rats treated with bleomycin showed increased parenchymal fibrosis (hydroxyproline levels) and vascular remodeling (media wall thickness) as well as increased right ventricular systolic pressure when compared to wild-type animals. Our data shows that GCN2 is dysregulated in both human and in an animal model of combined PF+PH. The possibility of a causative implication of GCN2 dysregulation in PF and/or PH development should be further studied

Comparison of Human and Experimental Pulmonary Veno-Occlusive Disease

Pulmonary veno-occlusive disease (PVOD) occurs in humans either as a heritable form (hPVOD) due to biallelic inactivating mutations of EIF2AK4 (encoding GCN2) or as a sporadic form in older age (sPVOD). The chemotherapeutic agent mitomycin C (MMC) is a potent inducer of PVOD in humans and in rats (MMC-PVOD). Here, we compared human hPVOD and sPVOD, and MMC-PVOD pathophysiology at the histological, cellular, and molecular levels to unravel common altered pathomechanisms. MMC exposure in rats was associated primarily with arterial and microvessel remodeling, and secondarily by venous remodeling, when PVOD became symptomatic. In all forms of PVOD tested, there was convergent GCN2-dependent but eIF2α-independent pulmonary protein overexpression of HO-1 (heme oxygenase 1) and CHOP (CCAAT-enhancer-binding protein [C/EBP] homologous protein), two downstream effectors of GCN2 signaling and endoplasmic reticulum stress. In human PVOD samples, CHOP immunohistochemical staining mainly labeled endothelial cells in remodeled veins and arteries. Strong HO-1 staining was observed only within capillary hemangiomatosis foci, where intense microvascular proliferation occurs. HO-1 and CHOP stainings were not observed in control and pulmonary arterial hypertension lung tissues, supporting the specificity for CHOP and HO-1 involvement in PVOD pathobiology. In vivo loss of GCN2 (EIF2AK4 mutations carriers and Eif2ak4 -/- rats) or in vitro GCN2 inhibition in cultured pulmonary artery endothelial cells using pharmacological and siRNA approaches demonstrated that GCN2 loss of function negatively regulates BMP (bone morphogenetic protein)-dependent SMAD1/5/9 signaling. Exogenous BMP9 was still able to reverse GCN2 inhibition-induced proliferation of pulmonary artery endothelial cells. In conclusion, we identified CHOP and HO-1 inhibition, and BMP9, as potential therapeutic options for PVOD.status: publishe