Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis

Thromboembolism is a major complication of nephrotic syndrome. Renal vein thrombosis and deep vein thrombosis are relatively common, especially in membranous nephropathy. However, the incidence of portal vein and superior mesenteric vein (SMV) thrombosis in patients with nephrotic syndrome is very rare. To date, several cases of portal vein thrombosis treated by anticoagulation therapy, not by thrombolytic therapy, have been reported as a complication of nephrotic syndrome. Here, we report a case of portal, splenic, and SMV thrombosis in a patient with a relapsed steroid dependent minimal change disease who was treated successfully with anticoagulation and thrombolytic therapy using urokinase. Radiologic findings and his clinical conditions gradually improved. Six months later, a complete remission of the nephrotic syndrome was observed and the follow-up computed tomography scan showed the disappearance of all portal vein, splenic vein, and SMV thrombi

Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1α Activation

Prolyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1α (HIF-1α) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-rasV12 signalling. Cysteine residues in the double-stranded β-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1α under oxidative stress. Oncogenic H-rasV12 signalling facilitates the accumulation of HIF-1α in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-rasV12 does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-rasV12-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1α and aerobic glycolysis in response to oxidative stress

Colloidal Suprastructures Self-Organized from Oppositely Charged All-Inorganic Nanoparticles

The self-organization of colloidal nanoparticles into programmed suprastructures is an important research area in various disciplines of nano, colloid, and polymer sciences. However, despite the recent advances in their fundamental understanding and practical applications, the self-organization of organic-free inorganic nanoparticles remains unexplored. Herein, we present the controlled organization of oppositely charged allinorganic nanoparticles through the electrostatic interaction and the colloidal behaviors of organized suprastructures. Depending on the charge states of the assembled suprastructures, three different phases, including patchy, patchy bridged, and fully coated particles, are identified, enabling the construction of the phase diagram with nanoparticle concentrations. Especially, the fully coated particles exhibit unexpected colloidal stability through the action of nanoparticles as surface stabilizers to induce the overcharged surface state; thus, we propose the concept of "nanoligands". It is demonstrated that this concept can be extended to a wide range of material combinations, including semiconducting, metallic, and oxide nanoparticles. The currently developed approach will enable the chemical designing of self-organized nanostructures