Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.

Reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX) play a key role in liver injury and fibrosis. Previous studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs) as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared. HSCs are the primary myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation. Mice were treated with carbon tetrachloride (CCl4) to induce liver fibrosis. Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4 deficiency are approximately equally effective in preventing liver injury in the mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as inflammatory and proliferative genes induced by lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), or sonic hedgehog (Shh) in primary mouse HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for 5 days). Finally, NOX1 and NOX4 protein levels were increased in human livers with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling mediates the pathogenesis of liver fibrosis, including the direct activation of HSC

Burma (Myanmar): exploring the frontiers of Southeast Asia’s last frontier economy

David Brenner contextualises Indian and Chinese investments in Burma and argues that economic development alone cannot address political grievances in the country’s restive border areas

Ashes of co-optation: from armed group fragmentation to the rebuilding of popular insurgency in Myanmar

This article argues that attempts to buy insurgency out of violence can achieve temporary stability but risk producing new conflict. While co-optation with economic incentives might work in parts of a movement, it can spark ripple effects in others. These unanticipated developments result from the interactions of differently situated elite and non-elite actors, which can create a momentum of their own in driving collective behaviour. This article develops this argument by analysing the re-escalation of armed conflict between the Kachin Independence Organisation (KIO) and Myanmar's armed forces after a 17-year-long ceasefire broke down in 2011. After years of mutual enrichment and collaboration between rebel and state elites and near organisational collapse, the insurgency's new-found resolve and capacity is particularly puzzling. Based on extensive field research, this article explains why and how the state's attempt to co-opt rebel leaders with economic incentives resulted in group fragmentation, loss of leadership legitimacy, increased factional contestation, growing resentment among local communities and the movement's rank and file and ultimately the rebuilding of popular resistance from within