The heavy subunit of ferritin stimulates NLRP3 inflammasomes in hepatic stellate cells through ICAM-1 to drive hepatic inflammation.

Serum ferritin concentrations increase during hepatic inflammation and correlate with the severity of chronic liver disease. Here, we report a molecular mechanism whereby the heavy subunit of ferritin (FTH) contributes to hepatic inflammation. We found that FTH induced activation of the NLRP3 inflammasome and secretion of the proinflammatory cytokine interleukin-1β (IL-1β) in primary rat hepatic stellate cells (HSCs) through intercellular adhesion molecule-1 (ICAM-1).

Fine-tuning the standard setting of objective structured practical examinations in clinical anatomy.

The objective structured practical examination (OSPE) is a reliable assessment of practical skills in anatomy teaching. It is often administered as low-stake assessments to track progress at multiple time points in anatomy curricula. Standard-setting OSPEs to derive a pass mark and to ensure assessment quality and rigor is a complex task.

Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy.

Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ.

Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology.

Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic liver diseases (i.e., viral hepatitis, non-alcoholic fatty liver disease, metabolic liver disease, and liver cancer) requires experimental manipulation of animal models and in vitro cell cultures.

Gene Expression in Developmental Stages of Provides Further Insight into the Importance of the Schistosome Insulin-Like Peptide.

We showed previously that the insulin-like peptide (SjILP) binds the worm insulin receptors, thereby, activating the parasite's insulin pathway and emphasizing its important role in regulating uptake of glucose, a nutrient essential for parasite survival. Here we show that SjILP is differentially expressed in the schistosome life cycle and is especially highly transcribed in eggs, miracidia, and adult female worms. RNA inference was employed to knockdown SjILP in adults in vitro, with suppression confirmed by significantly reduced protein production, declined adenosine diphosphate levels, and reduction in glucose consumption.

Whole-genome sequence of the bovine blood fluke Schistosoma bovis supports interspecific hybridization with S. haematobium.

Mesenteric infection by the parasitic blood fluke Schistosoma bovis is a common veterinary problem in Africa and the Middle East and occasionally in the Mediterranean Region. The species also has the ability to form interspecific hybrids with the human parasite S. haematobium with natural hybridisation observed in West Africa, presenting possible zoonotic transmission.

Whole-genome sequence of the oriental lung fluke Paragonimus westermani.

Background: Foodborne infections caused by lung flukes of the genus Paragonimus are a significant and widespread public health problem in tropical areas. Approximately 50 Paragonimus species have been reported to infect animals and humans, but Paragonimus westermani is responsible for the bulk of human disease. Despite their medical and economic importance, no genome sequence for any Paragonimus species is available.

Calcium and Ca/Calmodulin-dependent kinase II as targets for helminth parasite control.

In eukaryotes, effective calcium homeostasis is critical for many key biological processes. There is an added level of complexity in parasites, particularly multicellular helminth worms, which modulate calcium levels while inhabiting the host microenvironment. Parasites ensure efficient calcium homeostasis through gene products, such as the calmodulin-dependent kinases (CaMK), the main focus of this review.

Live imaging of collagen deposition during experimental hepatic schistosomiasis and recovery: a view on a dynamic process.

Hepatic fibrosis is the central cause of chronic clinical pathology resulting from infection by the blood flukes Schistosoma japonicum or S. mansoni. Much has been elucidated regarding the molecular, cellular and immunological responses that correspond to the formation of the granulomatous response to trapped schistosome eggs.

Suppression of Acetylcholinesterase Affects Parasite Growth and Development.

To further investigate the importance of acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the -knockdown parasites compared with luciferase controls.

Taurocholate Induces Biliary Differentiation of Liver Progenitor Cells Causing Hepatic Stellate Cell Chemotaxis in the Ductular Reaction: Role in Pediatric Cystic Fibrosis Liver Disease.

Cystic fibrosis liver disease (CFLD) in children causes progressive fibrosis leading to biliary cirrhosis; however, its cause(s) and early pathogenesis are unclear. We hypothesized that a bile acid-induced ductular reaction (DR) drives fibrogenesis. The DR was evaluated by cytokeratin-7 immunohistochemistry in liver biopsies, staged for fibrosis, from 60 children with CFLD, and it demonstrated that the DR was significantly correlated with hepatic fibrosis stage and biliary taurocholate levels.

Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica.

For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced.

Lysosome-associated membrane glycoprotein (LAMP)--preliminary study on a hidden antigen target for vaccination against schistosomiasis.

Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis.

An ex vivo model for studying hepatic schistosomiasis and the effect of released protein from dying eggs.

Background: We report the use of an ex vivo precision cut liver slice (PCLS) mouse model for studying hepatic schistosomiasis. In this system, liver tissue is unfixed, unfrozen, and alive for maintenance in culture and subsequent molecular analysis.

Methods And Findings: Using thick naive mouse liver tissue and sterile culture conditions, the addition of soluble egg antigen (SEA) derived from Schistosoma japonicum eggs, followed 4, 24 and 48 hrs time points.

Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential.

To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S.

Transcriptional profiling of the oesophageal gland region of male worms of Schistosoma mansoni.

The intestinal tract of schistosomes opens at the mouth and leads into the foregut or oesophageal region that is lined with syncytium continuous with the apical cytoplasm of the tegument. The oesophagus is surrounded by a specialised gland, the oesophageal gland. This gland releases materials into the lumen of the oesophagus and the region is thought to initiate the lysis of erythrocytes and neutralisation of immune effectors of the host.

Gene Atlasing of digestive and reproductive tissues in Schistosoma mansoni.

Background: While considerable genomic and transcriptomic data are available for Schistosoma mansoni, many of its genes lack significant annotation. A transcriptomic study of individual tissues and organs of schistosomes could play an important role in functional annotation of the unknown genes, particularly by providing rapid localisation data and thus giving insight into the potential roles of these molecules in parasite development, reproduction and homeostasis, and in the complex host-parasite interaction.

Methodology/principal Findings: Quantification of gene expression in tissues of S.

Molecular analysis of zinc transporters in Schistosoma japonicum.

Members of the zinc-regulated transporter/iron-regulated transporter-like protein (ZIP) family of proteins transport metal ions across cell membranes. Genes encoding ZIPs are present in the genomes of schistosomes. Here, we describe molecular characterisation of six ZIPs (SjZIPA-F) from Schistosoma japonicum.

Increased iron stores correlate with worse disease outcomes in a mouse model of schistosomiasis infection.

Schistosomiasis is a significant parasitic infection creating disease burden throughout many of the world's developing nations. Iron deficiency anemia is also a significant health burden resulting from both nutritional deficit as well as parasitic infection in these countries. In this study we investigated the relationships between the disease outcomes of Schistosoma japonicum infection and iron homeostasis.

The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini.

Infection with the human liver fluke, Opisthorchis viverrini, is a serious public health problem in Thailand, Laos and nearby locations in Southeast Asia. Both experimental and epidemiological evidence strongly implicate liver fluke infection in the etiology of one of the liver cancer subtypes, cholangiocarcinoma (CCA). To identify parasite proteins critical for liver fluke survival and the etiology of CCA, OFFGEL electrophoresis and multiple reaction monitoring were employed to characterize 300 parasite proteins from the O.

Exposed proteins of the Schistosoma japonicum tegument.

The ability of the mammalian blood fluke Schistosoma japonicum to survive in the inhospitable environment of the mammalian bloodstream can be attributed, at least in part, to its host-exposed outer surface, called the tegument. The tegument is a dynamic organ and is involved in nutrition, immune evasion and modulation, excretion, osmoregulation and signal transduction. Given its importance for parasite survival, proteins exposed to the host at the surface of the tegument are ideal targets for the development of vaccines and drugs.

Tissue specific profiling of females of Schistosoma japonicum by integrated laser microdissection microscopy and microarray analysis.

Background: The functions of many schistosome gene products remain to be characterized. A major step towards elucidating function of these genes would be in defining their sites of expression. This goal is rendered difficult to achieve by the generally small size of the parasites and the lack of a body cavity, which precludes analysis of transcriptional profiles of the tissues in isolation.

Cutaneous leishmaniasis in Sri Lanka: a study of possible animal reservoirs.

Background: Cutaneous leishmaniasis (CL) has been detected with increasing frequency in Sri Lanka in recent years. Leishmania donovani has been identified as the causative agent, but no information is available on vector(s) or reservoir(s). In this paper we present data on the screening of possible reservoirs for evidence of infection.