Maraviroc Prevents HCC Development by Suppressing Macrophages and the Liver Progenitor Cell Response in a Murine Chronic Liver Disease Model.

Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms.

Human Amnion Epithelial Cells Produce Soluble Factors that Enhance Liver Repair by Reducing Fibrosis While Maintaining Regeneration in a Model of Chronic Liver Injury.

Human amnion epithelial cells (hAECs) exert potent antifibrotic and anti-inflammatory effects when transplanted into preclinical models of tissue fibrosis. These effects are mediated in part via the secretion of soluble factors by hAECs which modulate signaling pathways and affect cell types involved in inflammation and fibrosis. Based on these reports, we hypothesized that these soluble factors may also support liver regeneration during chronic liver injury.

Loss of ARF/INK4A Promotes Liver Progenitor Cell Transformation Toward Tumorigenicity Supporting Their Role in Hepatocarcinogenesis.

Liver progenitor cells (LPCs) contribute to liver regeneration during chronic damage and are implicated as cells of origin for liver cancers including hepatocellular carcinoma (HCC). The locus, which encodes the tumor suppressors alternate reading frame protein (ARF) and INK4A, was identified as one of the most frequently altered genes in HCC. This study demonstrates that inactivation of enhances tumorigenic transformation of LPCs.

Silicone Foam Dressing for Prevention of Sacral Deep Tissue Injuries Among Cardiac Surgery Patients.

Objective: To evaluate the effect of silicone foam dressings, placed preoperatively, on the incidence of postoperative sacral deep-tissue pressure injuries.

Design, Setting, And Patients: An uncontrolled before-and-after quality improvement method was used. Within a single, urban academic medical center, consecutively admitted adult cardiac surgery patients were included in the pre- and postintervention groups; only those receiving elective procedures were included.

Deep Tissue Pressure Injury: A Clinical Review.

: A deep tissue pressure injury (DTPI) is a serious type of pressure injury that begins in the muscle closest to the bone and may not be visible in its early stages. Its hallmark is rapid deterioration despite the use of appropriate preventive interventions. In 2007, the National Pressure Ulcer Advisory Panel added suspected deep tissue injuries to the traditional classification system, and by 2010 DTPIs had accounted for about 9% of all pressure injuries and were for the first time more prevalent than stage 3 or 4 pressure injuries.

Splice variant insertions in the C-terminus impairs YAP's transactivation domain.

The yes-associated protein (YAP) is a key effector of the mammalian Hippo signaling pathway. YAP has eight known alternately spliced isoforms and these are widely expressed across multiple tissues. Variable effects have been ascribed to different YAP isoforms by inducing their expression in cells, but whether these differences are due to variability in the transcriptional potency of individual YAP isoforms has not been addressed.

Risk Factors Associated With Pressure Ulcer Formation in Critically Ill Cardiac Surgery Patients: A Systematic Review.

Background: Cardiac surgery patients are among those most at risk for developing pressure ulcers (PUs), with a reported incidence as high as 29.5%. Although numerous studies documenting PU risk factors and prevention strategies exist, the availability of literature examining risk factors specific to the cardiac surgery population is limited.

A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice.

The choline-deficient, ethionine-supplemented (CDE) dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC)-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet).

TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells.

The mammalian Hippo signaling pathway regulates cell growth and survival and is frequently dysregulated in cancer. YAP and TAZ are transcriptional coactivators that function as effectors of this signaling pathway. Aberrant YAP and TAZ activity is reported in several human cancers, and normally the expression and nuclear localization of these proteins is tightly regulated.

Epigenetic Modulators Enhance Constitutive and Liver-Specific Reporter Expression in Murine Liver Progenitor Cell Lines.

Stem cells expressing reporter constructs are extremely useful for their tracking in vivo or for determining cell lineage fate in vivo and in vitro. We generated liver progenitor cell (LPC) lines from actin-EGFP and TAT-GRE-lacZ mice. LPCs from the actin-EGFP mouse facilitate cell tracing following transplant as the reporter is constitutively expressed.

Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins.

Evidence-based practice implementation strategy: the central role of the clinical nurse specialist.

The Hospital of the University of Pennsylvania Model of Excellence in Nursing Professional Practice serves to fully integrate the role of the clinical nurse specialist (CNS) in the implementation of evidence-based care and the role of organizational change agent. In this role, the CNS is responsible for the identification and remedy of system-wide challenges to optimal quality care, mentorship of clinical nurses both as clinicians and as leaders, and enhancement of interdisciplinary partnerships. Integrating the CNS role as the nursing department knowledge keepers, knowledge seekers and knowledge disseminators able to proactively develop and enhance interdisciplinary partnerships required systematic educational sessions and use of outcome measurement tools.