Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Cholangiocarcinoma is an adenocarcinoma of the liver which has increased in incidence over the last thirty years to reach similar levels to other liver cancers. Diagnosis of this disease is usually late and prognosis is poor, therefore it is of great importance to identify novel candidate markers and potential early indicators of this disease as well as molecules that may be potential therapeutic targets. We have used a proteomic approach to identify differentially expressed proteins in peripheral cholangiocarcinoma cases and compared expression with paired non-tumoral liver tissue from the same patients. Two-dimensional fluorescence difference gel electrophoresis after labeling of the proteins with cyanines 3 and 5 was used to identify differentially expressed proteins. Overall, of the approximately 2,400 protein spots visualised in each gel, 172 protein spots showed significant differences in expression level between tumoral and non-tumoral tissue with p < 0.01. Of these, 100 spots corresponding to 138 different proteins were identified by mass spectrometry: 70 proteins were over-expressed whereas 68 proteins were under-expressed in tumoral samples compared to non-tumoral samples. Among the over-expressed proteins, immunohistochemistry studies confirmed an increased expression of 14-3-3 protein in tumoral cells while α-smooth muscle actin and periostin were shown to be overexpressed in the stromal myofibroblasts surrounding tumoral cells. α-Smooth muscle actin is a marker of myofibroblast differentiation and has been found to be a prognostic indicator in colon cancer while periostin may also have a role in cell adhesion, proliferation and migration and has been identified in other cancers. This underlines the role of stromal components in cancer progression and their interest for developing new diagnostic or therapeutic tools

Food-borne trematodiases in East Asia: epidemiology and burden

Food-borne trematodiases are a cluster of parasitic helminth infections in humans and animals and belong to the cluster of neglected tropical diseases. The causative helminths dispose of a complex life cycle. As with many helminth infections, most infected people may only experience mild and non-specific clinical signs and symptoms. However, repeated, heavy and long-term infections may lead to severe clinical manifestations and also potentially fatal complications such as cholangiocarcinoma. Diagnosis remains a challenge as reliable, affordable, rapid, and simple-to-use diagnostic techniques are not available. If correctly and early diagnosed, safe, cheap, efficacious, orally administered drugs are available. Globally, the disease burden of food-borne trematodiases is estimated to be well within the range of other and better known neglected tropical diseases (e.g. dengue, leishmaniasis, lymphatic filariasis, onchocerciasis, and schistosomiasis) with a concentration in East and Southeast Asia. Food-borne trematodiases are zoonoses and may also have a negative impact on agri- and aquacultural production in affected regions. Mathematical modelling and analysis of food-borne trematodiases transmission dynamics to inform control and prevention is still in a very early stage, also due to the very limited availability of essential data. The current mainstay of human food-borne trematodiases control is drug-based morbidity control. For improved control, prevention or even elimination, more integrated efforts adopting also an ecosystem and “One Health” perspective are needed