Bindarit encapsulated nanoparticles prevent venous neointimal hyperplasia and restenosis in a murine angioplasty model.

Monocyte and macrophage recruitment occur to the injured vessel wall after percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVF) through increased expression of MCP-1 leading to venous neointimal hyperplasia (VNH) and venous stenosis (VS). We hypothesized that adventitial delivery of Bindarit, an oral selective inhibitor of MCP-1, -2, and -3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (BN NP) could prevent VNH/VS formation in a murine model of PTA with AVF. Scanning electron microscope and dynamic light scattering were used to characterize the BN NP and control nanoparticles (NP C).

Adventitial delivery of nanoparticles encapsulated with 1α, 25-dihydroxyvitamin D attenuates restenosis in a murine angioplasty model.

Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF.

1α,25-Dihydroxyvitamin D Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas.

Background: Few therapies prevent venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation in arteriovenous fistulas (AVF). Expression of the immediate early response gene X-1 (), also known as is associated with VNH and stenosis in murine AVFs. The study aimed to determine if local release of long-acting inhibitor 1α,25(OH)D from poly(lactic-co-glycolic acid) (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (1,25 NP) could affect VNH/VS formation in a large animal model.

Identification of miRNAs associated with dendritic cell dysfunction during acute and chronic hepatitis B virus infection.

The uptake or expression of hepatitis B virus (HBV) proteins by dendritic cells (DCs) is considered important for disease outcome. Differential expression of microRNA (miRNA) may have a role in viral persistence and hepatocellular injury. The miRNA expression was investigated by microarray in DCs from different stages of HBV infection and liver disease namely, immune active (IA; n = 20); low replicative (LR; n = 20); HBeAg negative (n = 20); acute viral hepatitis (AVH, n = 20) and healthy controls (n = 20).

Experimental murine arteriovenous fistula model to study restenosis after transluminal angioplasty.

Percutaneous transluminal angioplasty (PTA) is a very common interventional treatment for treating stenosis in arteriovenous fistula (AVF) used for hemodialysis vascular access. Restenosis occurs after PTA, resulting in vascular lumen loss and a decrease in blood flow. Experimental animal models have been developed to study the pathogenesis of stenosis, but there is no restenosis model after PTA of stenotic AVF in mice.

Differences in Transforming Growth Factor-β1/BMP7 Signaling and Venous Fibrosis Contribute to Female Sex Differences in Arteriovenous Fistulas.

Background Women have decreased hemodialysis arteriovenous fistula (AVF) maturation and patency rates. We determined the mechanisms responsible for the sex-specific differences in AVF maturation and stenosis formation by performing whole transcriptome RNA sequencing with differential gene expression and pathway analysis, histopathological changes, and in vitro cell culture experiments from male and female smooth muscle cells. Methods and Results Mice with chronic kidney disease and AVF were used.

Effect of sex differences in treatment response to angioplasty in a murine arteriovenous fistula model.

Failure to mature and venous neointimal hyperplasia formation are the two major causes of hemodialysis arteriovenous fistula (AVF) vascular access failure. Percutaneous transluminal angioplasty (PTA) is the firstline treatment for both of these conditions, but, clinically, women have decreased patency rates compared with men. The hypothesis to be tested in the present study was that female mice after PTA of venous areas of higher intimal thickening have increased gene expression of transforming growth factor-β1 (TGF-β1) and TGF-β receptor 1 (TGFβ-R1) accompanied with histological changes of fibrosis compared with male mice.

Global microRNA expression profiling in the liver biopsies of hepatitis B virus-infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury.

Unlabelled: Hepatitis B virus (HBV) can manipulate the microRNA (miRNA) regulatory networks in infected cells to create a permissive environment for viral replication, cellular injury, disease onset, and its progression. The aim of the present study was to understand the miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury, and liver fibrosis. We investigated differentially expressed miRNAs by microarray in liver biopsy samples from different stages of HBV infection and liver disease (immune-tolerant [n = 8], acute viral hepatitis [n = 8], no fibrosis [n = 16], early [F1+F2, n = 19] or late [F3+F4, n = 14] fibrosis, and healthy controls [n = 7]).

Targeted delivery of microRNA-199a-3p using self-assembled dipeptide nanoparticles efficiently reduces hepatocellular carcinoma in mice.

Unlabelled: Hepatocellular carcinoma (HCC) is an aggressive tumor with limited systemic and locoregional modalities of treatment. Although microRNA (miRNA) based therapies have significant potential, their targeted delivery remains a major challenge. miR-199a-3p functions as an important tumor suppressor in HCC, which regulates various cellular processes.

An RNAi-based high-throughput screening assay to identify small molecule inhibitors of hepatitis B virus replication.

Persistent or chronic infection with the hepatitis B virus (HBV) represents one of the most common viral diseases in humans. The hepatitis B virus deploys the hepatitis B virus X protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes. Because of its critical role in countering host defenses, HBx represents an attractive target for antiviral drugs.

Analysis of hepatitis B virus genotype changes in patients with chronic hepatitis B infection on tenofovir therapy.

Antiviral therapy for chronic hepatitis B (CHB) is often required for prolonged periods. We investigated the instance of one HBV genotype switching to another during tenofovir therapy. Of the 67 patients, genotype A was present in 6 (8.

Key elements of the RNAi pathway are regulated by hepatitis B virus replication and HBx acts as a viral suppressor of RNA silencing.

The host-mediated RNAi pathways restrict replication of viruses in plant, invertebrate and vertebrate systems. However, comparatively little is known about the interplay between RNAi and various viral infections in mammalian hosts. We show in the present study that the siRNA-mediated silencing of Drosha, Dicer and Ago2 [argonaute RISC (RNA-induced silencing complex) catalytic component 2] transcripts in Huh7 cells resulted in elevated levels of HBV (hepatitis B virus)-specific RNAs and, conversely, we observed a decrease in mRNA and protein levels of same RNAi components in HepG2 cells infected with HBV.