Search results for "FAS"

On the presence and immunoregulatory functions of extracellular microRNAs in the trematode Fasciola hepatica.

2017

Summary Liver flukes represent a paraphyletic group of endoparasitic flatworms that significantly affect man either indirectly due to economic damage on livestock or directly as pathogens. A range of studies have focussed on how these macroscopic organisms can evade the immune-system and live inside a hostile environment such as the mammalian liver and bile-ducts. Recently, microRNAs, a class of short non-coding gene-regulators, have been proposed as likely candidates to play roles in this scenario. MicroRNAs (miRNAs) are key players in development and pathogenicity and are highly conserved between metazoans: identical miRNAs can be found in flatworms and mammalians. Interestingly, miRNAs a…

Potential Influence of Helminth Molecules on COVID-19 Pathology

2020

In recent months, the parasitology research community has been tasked with investigation of the influence of parasite coinfection on coronavirus disease 2019 (COVID-19) outcomes. Herein, we share our approach to analyze the effect of the trematode Fasciola hepatica as a modulator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of COVID-19 pathology.

Sub-analysis of long-term elosulfase alfa treatment outcomes in adults with Morquio syndrome type A

2017

The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis

2020

Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…

Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells

2017

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. METHODS: 24 hour fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cyto…

ParDRe: faster parallel duplicated reads removal tool for sequencing studies

2016

This is a pre-copyedited, author-produced version of an article accepted for publication in Bioinformatics following peer review. The version of record [insert complete citation information here] is available online at: https://doi.org/10.1093/bioinformatics/btw038 [Abstract] Summary: Current next generation sequencing technologies often generate duplicated or near-duplicated reads that (depending on the application scenario) do not provide any interesting biological information but can increase memory requirements and computational time of downstream analysis. In this work we present ParDRe , a de novo parallel tool to remove duplicated and near-duplicated reads through the clustering of S…

Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy

2017

Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (P…

The influence of meal frequency and timing on health in humans: The role of fasting

2019

The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective research has demonstrated a significant increase in disease risk with a high meal frequency (≥6 meals/day) as compared to a low meal frequency (1–2 meals/day). Apart from meal frequency and timing we also have to consider breakfast consumption and the distribution of daily energy intake, caloric restriction, and night-time eating. A central role in this complex scenario is playe…

VISMapper: ultra-fast exhaustive cartography of viral insertion sites for gene therapy

2017

The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org . Because it uses novel mapping algorithms VISMapper is remarkably faster t…

Isolation and Analysis of Fasciola hepatica Extracellular Vesicles

2020

The finding of extracellular vesicles (EVs) as important players in parasite-parasite and host-parasite communications has led to an increasing number of reports in the literature. Different protocols have been developed for isolation and further characterization of EVs from parasitic helminths. In this chapter, we describe step by step procedures to isolate EVs secreted by Fasciola hepatica adults in culture, which could be also applied for other developmental stages of the parasite, as well as EVs present in plasma and urine. Along with classical isolation methods like differential ultracentrifugation, and more recent techniques like size exclusion chromatography (SEC), here we also refer…