Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD

ADAR enzyme and miRNA story: A nucleotide that can make the difference

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine (A) to inosine (I) in double-stranded (ds) RNAs. Since Inosine is read as Guanosine, the biological consequence of ADAR enzyme activity is an A/G conversion within RNA molecules. A-to-I editing events can occur on both coding and non-coding RNAs, including microRNAs (miRNAs), which are small regulatory RNAs of ~20-23 nucleotides that regulate several cell processes by annealing to target mRNAs and inhibiting their translation. Both miRNA precursors and mature miRNAs undergo A-to-I RNA editing, affecting the miRNA maturation process and activity. ADARs can also edit 3' UTR of mRNAs, further increasing the interplay between mRNA targets and miRNAs. In this review, we provide a general overview of the ADAR enzymes and their mechanisms of action as well as miRNA processing and function. We then review the more recent findings about the impact of ADAR-mediated activity on the miRNA pathway in terms of biogenesis, target recognition, and gene expression regulation

Jenis Kupu-kupu Pengunjung Bunga Mussaenda dan Asoka di Kawasan Cagar Alam Gunung Sibela Pulau Bacan

Musaenda dan Asoka merupakan salah satu tanaman hostplant dan sekaligus foodplant bagi kupu-kupu di Gunung Sibela. Hostplant adalah tumbuhan inang yang menjadi makanan larva dan foodplant adalah tumbuhan yang menjadi makanan kupu-kupu dewasa. Penelitian ini bertujuan untuk mengetahui jenis kupu-kupu yang mengunjungi tanaman mussaenda dan asoka di kawasan cagar alam gunung Sibela pulau Bacan. Metode yang digunakan dalam penelitian ini adalah direct sampling. Hasil penelitian menunjukkan bahwa lokasi dataran rendah (20 mdpl) ditemukan 10 spesies kupu-kupu pengunjung tanaman mussaenda dan asoka, 5 genus, 2 famili. Kupu-kupu pengunjung tanaman mussaenda di dataran rendah yaitu: Ornithopthera croesus, Papilio ulysses, Papilio deiphobus, Papilio lorquinianus gelia, Troides hypolitus, Troides criton, Graphium milon, Graphium codrus dan Hebomoia glaucippe sulphure. Kupu-kupu pengunjung tanaman asoka di dataran rendah yaitu: Ornithopthera croesus, Papilio ulysses, Papilio fuscus lapathus dan Troides hypolitus. Pada lokasi dataran tinggi (400 mdpl) ditemukan 9 spesies kupu-kupu pengunjung tanaman mussaenda dan asoka, 5 genus, 2 famili. Kupu-kupu pengunjung tanaman mussaenda di dataran tinggi yaitu: Ornithopthera croesus, Papilio ulysses, Papilio deiphobus, Papilio lorquinianus gelia, Troides hypolitus, Troides criton, Graphium milon, dan Hebomoia glaucippe sulphurea, sedangkan kupu-kupu pengunjung tanaman asoka di dataran tinggi yaitu: Papilio ulysses, Papilio fuscus lapathus dan Troides hypolitus

Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-Alcoholic fatty liver disease

The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-Alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) -59% to -42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (-12%, 95% CI -21% to -3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD. \ua9 Copyright 2013, Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2013

Epigenetic remodelling in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, being the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death. As other heterogeneous solid tumours, HCC results from a unique synergistic combination of genetic alterations mixed with epigenetic modifications. In HCC the patterns and frequencies of somatic variations change depending on the nearby chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutations. Epigenetics refers to heritable states of gene expression without alteration to the DNA sequence itself and, unlike genetic changes, the epigenetic modifications are reversible and affect gene expression more extensively than genetic changes. Thus, studies of epigenetic regulation and the involved molecular machinery are greatly contributing to the understanding of the mechanisms that underline HCC onset and heterogeneity. Moreover, this knowledge may help to identify biomarkers for HCC diagnosis and prognosis, as well as future new targets for more efficacious therapeutic approaches. In this comprehensive review we will discuss the state-of-the-art knowledge about the epigenetic landscape in hepatocarcinogenesis, including evidence on the diagnostic and prognostic role of non-coding RNAs, modifications occurring at the chromatin level, and their role in the era of precision medicine. Apart from other better-known risk factors that predispose to the development of HCC, characterization of the epigenetic remodelling that occurs during hepatocarcinogenesis could open the way to the identification of personalized biomarkers. It may also enable a more accurate diagnosis and stratification of patients, and the discovery of new targets for more efficient therapeutic approaches