More Dangers Of Alcohol

The dangers of alcohol consumption is underscored by changes in gene expression observed in alcoholic steatohepatitis.  Lifestyle factors do in fact alter us at the cellular and molecular level, sometimes to our benefit and sometimes to our detriment.  Abstract:

Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods. Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via four different isolation methods: side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection. Gene expression profiles of fluorescent-activated cell-sorted HPCs, whole liver extracts and laser microdissected HPC niches were determined by RNA-sequencing. Immunohistochemical evaluation of the isolated populations indicated the enrichment of HPCs in the SP, EpCAM+ and TROP-2+ cell populations. Pathway analysis of the transcription profiles of human HPCs showed an enrichment and activation of known HPC pathways like Wnt/β-catenin, TWEAK and HGF. Integration of the HPC niche profile suggests autocrine signalling by HPCs (TNFα, PDGFB and VEGFA) as well as paracrine signalling from the surrounding niche cells including MIF and IGF-1. In addition, we identified IL-17 A signalling as a potentially novel pathway in HPC biology. In conclusion, we provide the first RNA-seq-based, comparative transcriptome analysis of isolated human HPCs from ASH patients and revealed active signalling between HPCs and their surrounding niche cells in ASH livers and suggest that HPCs can actively contribute to liver inflammation.

Inflammation, Immune Cells, And Liver Cancer

Chronic inflammation due to non-alcoholic fatty liver disease alters immune cells, resulting in more cells that produce factors that suppress anti-cancer immunity, therefore increasing the risk for liver cancer.  Note that non-alcoholic fatty liver disease is associated with metabolic syndrome, which is itself associated with being overweight/obese.  An association between poor weight control and liver cancer>  You do the math. Abstract:

The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8+ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA+ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism.

Another documentary about sugar

There are several great documentaries about the dangers of sugar consumption.  I may have watched them all, several times. However, I just found yet another one, Sugar Crash - Documentary about Sugar and Disease (2016). 

It is an Irish production, but the background really does not matter - the deadly story of sugar unravels the same way everywhere in the world. Watch it, learn and protect yourself and your family.

The images of the decaying teeth, the necrotizing tissues of the diabetics and the fatty liver should be a sufficient impulse to stop you from eating sugar. Print these images from the Internet, paste them in your kitchen, carry some of them as a reminder in your purse or wallet. May be it will help?