VP1 and VP2. B19 NS1 protein is known to 
function as a transactivator of the B19 viral p6 and various cellular promoters, including those for the expression of tumor necrosis factor-a and IL-6, which play crucial roles in pathogenesis of SLE. Accordingly, our very recent study also revealed the aggravated effects of B19 NS1 protein on hepatic injury in NZB/W F1 mice by significantly enhancing the expression of inflammatory proteins including IL-6 and MMP-9 through TNF-a/NF-kB signaling. Since elevated TNF-a and IL-6 are also acknowledged to play crucial roles on hepatic fibrosis, these findings did provide a rational connection between B19 NS1 and liver fibrosis in SLE. As illustrated in figure seven, B19 NS1 protein aggravates the hepatic fibrosis by enhancing the expression of TGF-b isoforms and activation of Smad2/3, which urge phosphorylated Smad2/3 to cooperate with Smad4 and Sp1 and induce the consequent fiboriss-related proteins, including PAI-1 and a-SMA. Taken together, this study firstly demonstrated an aggravated effects of B19 NS1 protein on hepatic fibrosis in NZB/W F1 mice through enhancing the TGF-b/Smad fibrotic signaling and could provide a possible AbMole BI-9564 explanation in exacerbating the hepatic fibrosis in SLE patients with B19 infection. Hyperglycemia and diabetes play an important role in the pathogenesis of vascular complications including macroangiopathy and microangiopathy, which lead to retinopathy, nephropathy, arteriosclerosis and increased ischemic stroke risk by 2-4 fold relative to those without diabetes. Diabetes mellitus induces vascular endothelial damage and dysfunction, decreases cerebral tight junction protein expression, and promotes artery intima-media thickness and atherosclerotic vascular disease. Endothelial damage and reduction of tight junction protein expression are also related with cerebral aneurysm formation. However, DM has been related to a decreased risk of aneurysm rupture in patients 60 years or older and in women and does not predispose to the development or rupture of saccular cerebral aneurysms. Patients with aneurysmal subarachnoid hemorrhages have a lower or equivalent prevalence of DM than the general population. The mechanisms responsible for this negative association remain unknown. Atherosclerotic blood vessels in diabetes are associated with inflammation and remodeling of the extracellular matrix. Advanced glycation end-products are a complex group of compounds formed via a nonenzymatic reaction between reducing sugars and amine residues on proteins, lipids, or nucleic acids. Receptor of advanced glycation end-products is the receptor of AGEs. The AGE/RAGE signaling pathway plays a critical role in arterial diseases that are characterized by endothelial dysfunction, accumulation of extracellular matrix proteins, intima-media thickening, and decreased elasticity, which accelerate the development of atherosclerosis in the diabetic patients and animals.