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

Focal adhesion kinase: Insight into molecular roles and functions in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Due to the high incidence of post-operative recurrence after current treatments, the identification of new and more effective drugs is required. In previous years, new targetable genes/pathways involved in HCC pathogenesis have been discovered through the help of high-throughput sequencing technologies. Mutations in TP53 and β-catenin genes are the most frequent aberrations in HCC. However, approaches able to reverse the effect of these mutations might be unpredictable. In fact, if the reactivation of proteins, such as p53 in tumours, holds great promise as anticancer therapy, there are studies arguing that chronic activation of these types of molecules may be deleterious. Thus, recently the efforts on potential targets have focused on actionable mutations, such as those occurring in the gene encoding for focal adhesion kinase (FAK). This tyrosine kinase, localized to cellular focal contacts, is over-expressed in a variety of human tumours, including HCC. Moreover, several lines of evidence demonstrated that FAK depletion or inhibition impair in vitro and in vivo HCC growth and metastasis. Here, we provide an overview of FAK expression and activity in the context of tumour biology, discussing the current evidence of its connection with HCC development and progression

The use of ultrasound in clinical setting for children affected by NAFLD. is it safe and accurate?

Non-alcoholic fatty liver disease (NAFLD) has become over the last decade the most common form of chronic liver disease in children and adults. Thus, establishing the diagnosis of NAFLD is of utmost importance and represents a major challenge as the disease is generally silent and the current gold standard for diagnosis is an invasive liver biopsy, a procedure that is not suitable for screening purposes. Many non-invasive diagnostic tools have been evaluated so far. Recently the utility of ultrasonography for non-invasive diagnosis and estimation of hepatic steatosis has been demonstrated in a large prospective pediatric study

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

Pediatric liver diseases: current challenges and future perspectives

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases

Emodin Prevents Intrahepatic Fat Accumulation, Inflammation and Redox Status Imbalance During Diet-Induced Hepatosteatosis in Rats

High-fat and/or high-carbohydrate diets may predispose to several metabolic disturbances including liver fatty infiltration (hepatosteatosis) or be associated with necro-inflammation and fibrosis (steatohepatitis). Several studies have emphasized the hepatoprotective effect of some natural agents. In this study, we investigated the potential therapeutic effects of the treatment with emodin, an anthraquinone derivative with anti-oxidant and anti-cancer abilities, in rats developing diet-induced hepatosteatosis and steatohepatitis. Sprague-Dawley rats were fed a standard diet (SD) for 15 weeks, or a high-fat/high-fructose diet (HFD/HF). After 5 weeks, emodin was added to the drinking water of some of the SD and HFD/HF rats. The experiment ended after an additional 10 weeks. Emodin-treated HFD/HF rats were protected from hepatosteatosis and metabolic derangements usually observed in HFD/HF animals. Furthermore, emodin exerted anti-inflammatory activity by inhibiting the HFD/HF-induced increase of tumor necrosis factor (TNF)-α. Emodin also affected the hepatocytes glutathione homeostasis and levels of the HFD/HF-induced increase of glutathionylated/phosphorylated phosphatase and tensin homolog (PTEN). In conclusion, we demonstrated that a natural agent such as emodin can prevent hepatosteatosis, preserving liver from pro-inflammatory and pro-oxidant damage caused by HFD/HF diet. These findings are promising, proposing emodin as a possible hindrance to progression of hepatosteatosis into steatohepatitis

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

Elemental analysis of Itakpe iron ore by energy dispersive x-ray fluorescence spectrometry

Elemental analysis of Itakpe Hematite by Energy Dispersive X-Ray Fluorescence spectrometry was carried out. The iron ore contained the following: Fe (29.55%) Si (24.68%), Zr(0.33%), Ti (0.19%),  Zn(0.02%),  Ca(0.04%),  Cr(0.05%),  Mn(0.05%),  Nb(0.05%)  and  V(0.003%) respectively. The study opines that the hazards to human health caused by exposure to heavy metals are associated with a range of neurological deficits in both children and adults. The EDXRF technique can also provide a rapid evaluation of the economic potential of a geological deposits thereby providing its value both to the mining industry and to the health of the community impacted by the geological exploitation process.Keywords: Iron ore, Itakpe, Energy Dispersive X-ray Fluorescence spectrometry, pelle

Ambient air ammonia (NH3) concentration in two solid waste dump sites in Abakaliki, Ebonyi State, Nigeria

This work monitored the level of ammonia in the ambient air of two major solid waste dump sites in Abakaliki urban, Ebonyi State, in the morning for a period of a month on the onset of wet season, using portable monitor based on electrochemical sensor. The result showed that site 1 had a relatively higher mean ammonia level of 0.152 ±0.003ppm as against 0.09 ± 0.002ppm for site 2 while the corresponding minimum levels were 0.027 ±0.001ppm and 0.03 ± 0.001ppm for site 1 and 2 respectively. The ammonia levels peak on weekends (Friday to Sunday) and the beginning of the week day (Monday). The one-way Analysis of variance of mean difference in NH3 concentration in the two sites monitored revealed a no statistical significant difference in the mean (p<0.05). There is no national/ international threshold limit for ammonia but the concentrations of ammonia obtained in this study is within the values obtained in some studies in Asian and European cities reported in literature.Keywords: Abakaliki, Ambient Air, Ammonia, Dump Sites, Portable Monito