Nuclear factor erythroid 2-related factor 2 nuclear translocation induces myofibroblastic dedifferentiation in idiopathic pulmonary fibrosis

AIMS: Oxidants have been implicated in the pathophysiology of idiopathic pulmonary fibrosis (IPF), especially in myofibroblastic differentiation. We aimed at testing the hypothesis that nuclear factor erythroid 2-related factor 2 (Nrf2), the main regulator of endogenous antioxidant enzymes, is involved in fibrogenesis via myofibroblastic differentiation. Fibroblasts were cultured from the lungs of eight controls and eight IPF patients. Oxidants-antioxidants balance, nuclear Nrf2 expression, and fibroblast phenotype (α-smooth muscle actin and collagen I expression, proliferation, migration, and contraction) were studied under basal conditions and after Nrf2 knockdown or activation by Nrf2 or Keap1 siRNA transfection. The effects of sulforaphane (SFN), an Nrf2 activator, on the fibroblast phenotype were tested under basal and pro-fibrosis conditions (transforming growth factor β [TGF-β]). RESULTS: Decreased Nrf2 expression was associated with a myofibroblast phenotype in IPF compared with control fibroblasts. Nrf2 knockdown induced oxidative stress and myofibroblastic differentiation in control fibroblasts. Conversely, Nrf2 activation increased antioxidant defences and myofibroblastic dedifferentation in IPF fibroblasts. SFN treatment decreased oxidants, and induced Nrf2 expression, antioxidants, and myofibroblastic dedifferentiation in IPF fibroblasts. SFN inhibited TGF-β profibrotic deleterious effects in IPF and control fibroblasts and restored antioxidant defences. Nrf2 knockdown abolished SFN antifibrosis effects, suggesting that they were Nrf2 mediated. INNOVATION AND CONCLUSION: Our findings confirm that decreased nuclear Nrf2 plays a role in myofibroblastic differentiation and that SFN induces human pulmonary fibroblast dedifferentiation in vitro via Nrf2 activation. Thus, Nrf2 could be a novel therapeutic target in IPF

Large-scale geological structures of the Egyptian Nubian Shield

Abstract Integration of potential field- and structural data make it possible to trace surface and subsurface large-scale geological structures of the Egyptian Nubian Shield (ENS). Obtained results indicate that the Northern Eastern Desert (NED) of the ENS is dominated by relatively younger (c. 580 Ma) E–W and NE–SW trending extensional structures that were controlled by the evolution and retreat of the Cadomian Arc. Density of such extensional structures increases with depth as displayed by the potential data. The prevailing structural trends in the Central Eastern Desert (CED) are NW–SE and WNW–ESE. Both trends are highly prompted by the timing of deformation upon the Najd Fault System, and are themselves dissected by a relatively younger NE–SW shearing trend. Lineament density in the CED is subordinate for both subsurface and near surface structures. The South Eastern Desert exhibits compressional and extrusion-related structures of two main prominent trends; WNW-to-NW (to the western part) and the N-, NNE- to NE (to the eastern part). The previously mentioned Neoproterozoic trends are remarkably influenced by the Oligocene–Miocene Red Sea-Gulf of Suez rift related fractures in the vicinity of the rift shoulder. The remarkable change in trends and densities of structural trends, especially in the NED, is interpreted in terms of concealing of the older structures by the younger extensional structures which in turns reflect an N-ward progressive deformation in the entire ENS. Gravity data are more appropriate in delineating the structural trends compared to the magnetic data which are largely affected by lithological variations and/or alteration zones and magnetic mineralogy

Effect of drying methods on nutrient composition and physicochemical properties of Malaysian seaweeds

Sample drying is an important step in the sample preparation of materials. In this study, the effects of two drying methods which are oven-drying and freeze-drying on the proximate composition, mineral content and physicochemical properties of seaweeds Kappaphycus alvarezii and Sargassum polycystum were investigated. There were significant differences (p< 0.05) in the moisture, fat, crude protein, crude fiber and ash contents of both seaweeds treated by different drying methods. The highest values of nutrient composition were detected in the moisture, protein, crude fiber and fat content of samples treated with the oven-dried method. In contrast, the amount of ash and mineral in both seaweeds were found higher in freeze-dried compared to oven-dried. As for the physicochemical properties of both seaweeds, swelling capacity and water retention capacity of freeze-dried K. alvarezii were significantly higher than those of the oven-dried seaweed samples (p< 0.05). Thus, the results show that the nutritional composition of seaweeds S. polycystum and K. alvarezii are greatly affected by different drying methods