Search results for "HEP"
showing 10 items of 12243 documents
In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by alpha-Mannosyl-Functionalized Cationic Nanohydrogel Particles
2020
Macrophages are the front soldiers of the innate immune system and are vital for immune defense, tumor surveillance, and tissue homeostasis. In chronic diseases, including cancer and liver fibrosis, macrophages can be forced into an immunosuppressive and profibrotic M2 phenotype. M2-type macrophages overexpress the mannose receptor CD206. Targeting these cells via CD206 and macrophage repolarization towards an immune stimulating and antifibrotic M1 phenotype through RNA interference represents an appealing therapeutic approach. We designed nanohydrogel particles equipped with mannose residues on the surface (ManNP) that delivered siRNA more efficiently to M2 polarized macrophages compared t…
Understanding the implication of autophagy in the activation of hepatic stellate cells in liver fibrosis: are we there yet?
2021
Liver fibrosis (LF) occurs as a result of persistent liver injury and can be defined as a pathologic, chronic, wound-healing process in which functional parenchyma is progressively replaced by fibrotic tissue. As a phenomenon involved in the majority of chronic liver diseases, and therefore prevalent, it exerts a significant impact on public health. This impact becomes even more patent given the lack of a specific pharmacological therapy, with LF only being ameliorated or prevented through the use of agents that alleviate the underlying causes. Hepatic stellate cells (HSCs) are fundamental mediators of LF, which, activated in response to pro-fibrotic stimuli, transdifferentiate from a quies…
RAS/RAF/MEK/ERK, PI3K/PTEN/AKT/mTORC1 and TP53 pathways and regulatory miRs as therapeutic targets in hepatocellular carcinoma
2019
Introduction: Hepatocellular carcinoma (HCC) is a significant problem globally because of viral infections and the increasing incidence of obesity and fatty liver disease. However, it is difficult to treat because its inherent genetic heterogeneity results in activation of numerous signaling pathways. Kinases have been targeted for decades with varying results, but the development of therapeutic resistance is a major challenge. Areas covered: The key roles of the RAS/RAF/MEK/ERK, PI3K/PTEN/AKT/mTORC1, TP53 microRNAs (miRs) as therapeutic targets are discussed and we suggests novel approaches for targeting miRs or their downstream targets to combat HCC. We performed literature searches using…
A PTEN inhibitor displays preclinical activity against hepatocarcinoma cells
2016
Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32–44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability…
Ellagitannin-rich cloudberry inhibits hepatocyte growth factorinduced cell migration and phosphatidylinositol 3-kinase/AKT activation in colon carcin…
2016
// Anne-Maria Pajari 1, 2 , Essi Paivarinta 1 , Lassi Paavolainen 3 , Elina Vaara 1 , Tuuli Koivumaki 4 , Ritu Garg 5 , Anu Heiman-Lindh 1 , Marja Mutanen 1 , Varpu Marjomaki 3 , Anne J. Ridley 2, 5 1 Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, Helsinki, Finland 2 University College London, Ludwig Institute for Cancer Research, London, UK 3 Department of Biological and Environmental Science / Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland 4 Department of Food and Environmental Sciences, Division of Food Chemistry, University of Helsinki, Helsinki, Finland 5 Randall Division of Cell & Molecular Biophysics, King’s College Lond…
Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma
2019
Background Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. Objective This study aims to analyze the presence of a regulation loop like that between MDA-9/Syntenin - NF-κB - RKIP in human liver carcinoma. Methods Transient transfection was performed with siRNA anti-MDA-9/Syntenin. Expression of different factors was evaluated by Real time-PCR and Western blotting, while NF-κB activation by TransAM assay. Invasion capacity was analyzed by Matrigel Invasion Assay and the effects…
AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome
2016
et al.
Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis.
2016
Background The metabolic regulator Fibroblast Growth Factor 21 (FGF21) is highly expressed in the acinar pancreas, but its role in pancreatic function is obscure. It appears to play a protective role in acute experimental pancreatitis in mice. The aim of this study was to define an association between FGF21 and the course and resolution of acute pancreatitis in humans. Methods and Principal Findings Twenty five subjects with acute pancreatitis admitted from May to September 2012 to the Beth Israel Deaconess Medical Center (BIDMC) were analyzed. Serial serum samples were collected throughout hospitalization and analyzed for FGF21 levels by ELISA. Twenty healthy subjects sampled three times o…
Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic a…
2017
Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was r…
Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin.
2021
Abstract Background Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced…