Acyl-CoA Thioesterase 1 Contributes to Transition of Steatosis to Metabolic-Associated Steatohepatitis.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) has become the leading cause of chronic liver disease, but there has been no approved pharmacotherapy to date.

Methods: We used a network analysis approach to delineate protein-protein interactions that contribute to the transition from steatosis to MASH, in order to identify and target this transition as a potential pharmacotherapeutic strategy. Acyl-CoA thioesterase 1 (ACOT1) was identified as a critical node in the protein-protein interaction (PPI) network of the transition from steatosis to MASH in patient samples.

Harnessing Metabolites as Serum Biomarkers for Liver Graft Pathology Prediction Using Machine Learning.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic dysfunction-associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay.

Transcriptomic changes in liver transplant recipients with non-alcoholic steatohepatitis indicate dysregulation of wound healing.

Background: Non-alcoholic steatohepatitis (NASH) has become a leading indication for liver transplantation. However, it often recurs in the graft and can also arise in individuals transplanted for other indications. Post-transplant NASH (PT-NASH) is more aggressive and leads to accelerated fibrosis.

Achieving tolerance modifies cancer susceptibility profiles in liver transplant recipients.

Long-term survival of transplant recipients is significantly impacted by malignancy. We aimed to determine whether calcineurin inhibitor (CNI)-treated recipients converted to and weaned off molecular target of rapamycin inhibitor (mTOR-I) therapy have favorable changes in their molecular profiles in regard to malignancy risk. We performed gene expression profiling from liver biopsy and blood (PBMC) specimens followed by network analysis of key dysregulated genes, associated diseases and disorders, molecular and cellular functions using IPA software.

Hemojuvelin deficiency promotes liver mitochondrial dysfunction and predisposes mice to hepatocellular carcinoma.

Hemojuvelin (HJV) enhances signaling to the iron hormone hepcidin and its deficiency causes iron overload, a risk factor for hepatocellular carcinoma (HCC). We utilized Hjv mice to dissect mechanisms for hepatocarcinogenesis. We show that suboptimal treatment with diethylnitrosamine (DEN) triggers HCC only in Hjv but not wt mice.

Estrogen Receptor 1 Inhibition of Wnt/β-Catenin Signaling Contributes to Sex Differences in Hepatocarcinogenesis.

Background: Hepatocellular Carcinoma (HCC) is a sexually dimorphic cancer, with female sex being independently protective against HCC incidence and progression. The aim of our study was to understand the mechanism of estrogen receptor signaling in driving sex differences in hepatocarcinogenesis.

Methods: We integrated 1,268 HCC patient sample profiles from publicly available gene expression data to identify the most differentially expressed genes (DEGs).

Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan.

Background And Aims: Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches.

Characterization and predictive functional profiles on metagenomic 16S rRNA data of liver transplant recipients: A longitudinal study.

Long-term survival after Liver Transplantation (LT) is often compromised by infectious and metabolic complications. We aimed to delineate alterations in intestinal microbiome (IM) over time that could contribute to medical complications compromising long-term survival following LT. Fecal samples from LT recipients were collected at 3 months (3 M) and 6 months (6 M) post-LT.

Integrative analysis of layers of data in hepatocellular carcinoma reveals pathway dependencies.

Background: The broader use of high-throughput technologies has led to improved molecular characterization of hepatocellular carcinoma (HCC).

Aim: To comprehensively analyze and characterize all publicly available genomic, gene expression, methylation, miRNA and proteomic data in HCC, covering 85 studies and 3355 patient sample profiles, to identify the key dysregulated genes and pathways they affect.

Methods: We collected and curated all well-annotated and publicly available high-throughput datasets from PubMed and Gene Expression Omnibus derived from human HCC tissue.

Normothermic Ex Situ Liver Perfusion Enhances Mitochondrial Function of DCD Grafts as Evidenced by High-throughput Metabolomics.

Background: Normothermic ex situ liver perfusion (NEsLP) reduces reperfusion injury of donation after circulatory death (DCD) grafts and optimizes graft function. The goal of our study was to elucidate how NEsLP impacts global metabolism in DCD grafts using high-throughput metabolomics.

Methods: Pig livers were preserved by 2 different techniques: static cold storage and NEsLP.

Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection.

Background And Aims: Kupffer cells (KCs) are the resident intravascular phagocyte population of the liver and critical to the capture and killing of bacteria. Calcineurin/nuclear factor of activated T cells (NFAT) inhibitors (CNIs) such as tacrolimus are used to prevent rejection in solid organ transplant recipients. Although their effect on lymphocytes has been studied extensively, there are limited experimental data about if and how CNIs shape innate immunity, and whether this contributes to the higher rates of infection observed in patients taking CNIs.

Enteric dysbiosis in liver and kidney transplant recipients: a systematic review.

Several factors mediate intestinal microbiome (IM) alterations in transplant recipients, including immunosuppressive (IS) and antimicrobial drugs. Studies on the structure and function of the IM in the post-transplant scenario and its role in the development of metabolic abnormalities, infection, and cancer are limited. We conducted a systematic review to study the taxonomic changes in liver (LT) and kidney (KT) transplantation, and their potential contribution to post-transplant complications.

Lipoprotein-Like Nanoparticle Carrying Small Interfering RNA Against Spalt-Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden.

Patients with advanced hepatocellular carcinoma (HCC) are often unable to tolerate chemotherapy due to liver dysfunction in the setting of cirrhosis. We investigate high-density lipoprotein (HDL)-mimicking peptide phospholipid scaffold (HPPS), which are nanoparticles that capitalize on normal lipoprotein metabolism and transport, as a solution for directed delivery of small interfering RNA (siRNA) cargo into HCC cells. Spalt-like transcription factor 4 (SALL4), a fetal oncoprotein expressed in aggressive HCCs, is specifically targeted as a case study to evaluate the efficacy of HPPS carrying siRNA cargo.

Diabetogenic Effects of Immunosuppression: An Integrative Analysis.

Background: Posttransplant diabetes mellitus (PTDM) affects up to 50% of solid organ transplant recipients and compromises long-term outcomes. The goal of this study was to investigate how immunosuppressants affect gene expression in a manner that increases diabetes risk, by performing integrative analysis on publicly available, high-throughput gene expression data.

Methods: All high-throughput gene expression datasets of solid organ transplant recipients were retrieved from the Gene Expression Omnibus.

The basis of liver regeneration: A systems biology approach.

Introduction: Liver regeneration is a normal response to liver injury. The aim of this study was to determine the molecular basis of liver regeneration, through an integrative analysis of high-throughput gene expression datasets.

Methods: We identified and curated datasets pertaining to liver regeneration from the Gene Expression Omnibus, where regenerating liver tissue was compared to healthy liver samples.

Epigenetic basis of hepatocellular carcinoma: A network-based integrative meta-analysis.

Aim: To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network analysis.

Methods: PubMed and Gene Expression Omnibus were searched for genome-wide DNA methylation datasets. Patient clinical and demographic characteristics were obtained.

Systematic integrative analysis of gene expression identifies HNF4A as the central gene in pathogenesis of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and encompasses a spectrum from simple steatosis to steatohepatitis (NASH). There is currently no approved pharmacologic therapy against NASH, partly due to an incomplete understanding of its molecular basis. The goal of this study was to determine the key differentially expressed genes (DEGs), as well as those genes and pathways central to its pathogenesis.

Retraction: Circulating plant miRNAs can regulate human gene expression in vitro.

This corrects the article DOI: 10.1038/srep32773.

Circulating plant miRNAs can regulate human gene expression in vitro.

While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues.

Toll-Like Receptor 1/2 and 5 Ligands Enhance the Expression of Cyclin D1 and D3 and Induce Proliferation in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with a still undefined etiology. Several lines of evidence are consistent with the possible involvement of peculiar microenvironmental stimuli sustaining tumor cell growth and survival, as the activation of Toll-like receptors (TLR) 4 and 9. However, little is known about the contribution of other TLRs of pathogenic relevance in the development of MCL.

Integration, visualization and analysis of human interactome.

Data integration and visualization are crucial to obtain meaningful hypotheses from the diversity of 'omics' fields and the large volume of heterogeneous and distributed data sets. In this review we focus on network analysis as a key technique to integrate, visualize and extrapolate relevant information from diverse data. We first describe challenges in integrating different types of data and then focus on systematically exploring network properties to gain insight into network function.

High prevalence of Chlamydophila psittaci subclinical infection in Italian patients with Sjögren's syndrome and parotid gland marginal zone B-cell lymphoma of MALT-type.

Objectives: To assess Chlamydophila psittaci (Cp) subclinical infection in patients with Sjögren's syndrome (SS).

Methods: Seventy-four SS patients (55.4 ±13.

Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial.

Purpose: The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL.

Patients And Methods: Forty-seven patients were registered.