Publications

BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α-based therapies to IFN-α-free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia. METHODS.

Using laser microdissection and mass spectrometry (MS)-based proteomics, we subtyped amyloid deposits from 130 cases of hepatic amyloidosis. Although we confirmed that immunoglobulin light chain amyloidosis was the most frequent cause of hepatic amyloidosis, leukocyte cell-derived chemotaxin 2 (LECT2) amyloidosis (ALect2) accounted for 25% of cases. This novel finding was associated with Hispanic ancestry, incidental discovery of amyloid in liver specimens sampled for other unrelated conditions, and a characteristic pattern of hepatic amyloid deposition.

Background:Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs.

The Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and organoid culture approaches, we demonstrate that Hippo pathway activity is essential for the maintenance of the differentiated hepatocyte state. Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient to dedifferentiate, at very high efficiencies, adult hepatocytes into cells bearing progenitor characteristics.

Many protein-coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein, we examined the expression profiles of long non-coding RNAs (lncRNAs) found in fetal and adult liver in mice.

Phosphaturic mesenchymal tumors of the mixed connective tissue type (PMT) are very rare tumors of bone and soft tissues. Most patients with PMT have long-standing osteomalacia secondary to production of fibroblast growth factor 23 (FGF23), a hormone that inhibits phosphate reuptake within the renal proximal tubule. Previously, we have reported the detection of FGF23 mRNA in PMT by reverse transcription polymerase chain reaction (PCR); however, the low specificity and risk for nontumoral tissue contamination inherent in PCR-based methodology limit its clinical utility.

This study aimed to examine the contributions of brain-derived neurotrophic factor (BDNF) at the injury site toward neuroma formation and nerve regeneration after inferior alveolar nerve transection. Histological analysis confirmed neuroma formation at 2 weeks after complete transection of the inferior alveolar nerve. A local administration of an antibody to BDNF inhibited connective tissue proliferation at the injury site and promoted nerve fiber integrity.

The application of fluorescently-labeled antibodies for flow cytometric identification and characterization of specific cell types within heterogeneous populations by their protein expression profile is well established. While detection of proteins is informative, concomitant transcript analysis in the same cells would provide a more complete and comprehensive view of intracellular signaling events. We recently reported on the efficient detection of RNA in suspension cells for flow cytometric analysis.

Abstract

In Alzheimer’s disease (AD) brain, exposure of axons to Aβ causes pathogenic changes that spread retrogradely by unknown mechanisms, affecting the entire neuron. We found that locally applied Aβ1-42 initiates axonal synthesis of a defined set of proteins including the transcription factor ATF4. Inhibition of local translation and retrograde transport or knockdown of axonal Atf4 mRNA abolished Aβ-induced ATF4 transcriptional activity and cell loss. Aβ1-42 injection into the dentate gyrus (DG) of mice caused loss of forebrain neurons whose axons project to the DG.