The Dysregulated Galectin Network Activates NF-kappa B to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes
CALCIFIED TISSUE INTERNATIONAL
Authors: Pichler, K. M.; Weinmann, D.; Schmidt, S.; Kubista, B.; Lass, R.; Martelanz, L.; Alphonsus, J.; Windhager, R.; Gabius, H. -J.; Toegel, S.
Abstract
This work aimed to study the dysregulated network of galectins in OA chondrocyte pellets, and to assess whether their recently discovered activity as molecular switches of functional biomarkers results in degradation of extracellular matrix in vitro. Scaffold-free 3D pellet cultures were established of human OA chondrocytes. Expression and secretion of galectin(Gal)-1, -3, and -8 were monitored relative to 2D cultures or clinical tissue sections by RT-qPCR, immunohistochemistry and ELISAs. Exposure of 2D and 3D cultures to an in vivo-like galectin mixture (Gal-1 and Gal-8: 5 mu g/ml, Gal-3: 1 mu g/ml) was followed by the assessment of pellet size, immunohistochemical matrix staining, and/or quantification of MMP-1, -3, and -13. Application of inhibitors of NF-kappa B activation probed into the potential of intervening with galectin-induced matrix degradation. Galectin profiling revealed maintained dysregulation of Gal-1, -3, and -8 in pellet cultures, resembling the OA situation in situ. The presence of the galectin mixture promoted marked reduction of pellet size and loss of collagen type II-rich extracellular matrix, accompanied by the upregulation of MMP-1, -3, and -13. Inhibition of p65-phosphorylation by caffeic acid phenethyl ester effectively alleviated the detrimental effects of galectins, resulting in downregulated MMP secretion, reduced matrix breakdown and augmented pellet size. This study suggests that the dysregulated galectin network in OA cartilage leads to extracellular matrix breakdown, and provides encouraging evidence of the feasible inhibition of galectin-triggered activities. OA chondrocyte pellets have the potential to serve as in vitro disease model for further studies on galectins in OA onset and progression.
Techno-economic analysis and life-cycle assessment of jet fuels production from waste cooking oil via in situ catalytic transfer hydrogenation
RENEWABLE ENERGY
Authors: Barbera, Elena; Naurzaliyev, Rustem; Asiedu, Alexander; Bertucco, Alberto; Resurreccion, Eleazer P.; Kumar, Sandeep
Abstract
This work evaluates the feasibility of renewable jet-fuel production from waste cooking oil (WCO) via catalytic transfer hydrogenation (CTH) using isopropanol as hydrogen donor. Results were compared to a commercial hydroprocessed renewable jet (HRJ) fuel technology, employing process simulation-based techno-economic analysis (TEA) and life-cycle assessment (LCA). The two routes were compared in terms of product yield, energy consumption, economic and environmental metrics, and allocation methods. The total capital expenditure of CTH plant (7.3M$) was significantly lower than that of HRJ ($149.7M$). The annual revenues were comparable (similar to 150M$/year), due to similar fuel yields. To be profitable, the liquid fuel should be sold at $3.00/gal and $1.67/gal for CTH and HRJ, respectively. The cumulative fossil energy demand (CED) of HRJ was 1.6 times that of CTH and the total 100-year GWP of CTH was 8% less than HRJ's, with both systems not sequestering CO2 through co-product offsets. Mass-, energy-, and market-value allocations were utilized. Sensitivity analysis indicated that both systems were driven by transportation factors and not process inputs. Trend analysis on CTH's energy-return-on investment (EROI) showed that wide improvements could be made in energy efficiency (EROI = 10.30-11.30). From an investment/construction perspective, CTH (95% cheaper) appears to outperform HRJ at similar revenues. (C) 2020 Elsevier Ltd. All rights reserved.