Structural analysis of an Asterias rubens peptide indicates the presence of a disulfide-directed β-hairpin fold.

Sea stars are an abundant group of marine invertebrates that display remarkably robust regenerative capabilities throughout all life stages. Numerous proteins and peptides have been identified in a proteome study on the coelomic fluid (biofluid) of the common sea star Asterias rubens, which appear to be involved with the wound-healing response in the organism. However, the three-dimensional structure and function of several of these injury-responsive peptides, including the peptide KASH2, are yet to be investigated.

Mechanistic insights into liver-fluke-induced bile-duct cancer.

Liver fluke infection is a major risk for cholangiocarcinoma (CCA). It has been established that the Asian liver flukes, Clonorchis sinensis and Opisthorchis viverrini secrete growth factors, digestive enzymes, and extracellular vesicles (EVs) which contribute to abnormal cell development in the bile ducts where the worms reside. These secretions - combined with aberrant inflammation and repeated cycles of chronic wounding at the site of parasite attachment and grazing on the epithelium - promote biliary hyperplasia and fibrosis and ultimately malignant transformation.

Tetraspanins from the liver fluke Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production.

The liver fluke Opisthorchis viverrini (Poirier, 1886) (Digenea) secretes extracellular vesicles (EVs) bearing CD63-like tetraspanins on their surface. Fluke EVs are actively internalised by host cholangiocytes in the bile ducts, where they drive pathology and promote neoplasia through induction of cellular proliferation and secretion of inflammatory cytokines. We investigated the effects of tetraspanins of the CD63 superfamily by co-culturing recombinant forms of the large extracellular loop (LEL) of O.

Tetraspanins from stimulate cholangiocyte migration and inflammatory cytokine production.

The liver fluke secretes extracellular vesicles (EVs) bearing CD63-like tetraspanins on their surface. Fluke EVs are actively internalized by host cholangiocytes in the bile ducts, where they drive pathology and promote neoplasia through induction of cellular proliferation and secretion of inflammatory cytokines. We investigated the effects of tetraspanins of the CD63 superfamily by co-culturing recombinant forms of the large extracellular loop (LEL) of tetraspanin-2 (rLEL- -TSP-2) and tetraspanin-3 (rLEL- -TSP-3) with non-cancerous human bile duct (H69) and cholangiocarcinoma (CCA, M213) cell lines.

Peptide derived from progranulin of the carcinogenic liver fluke, Opisthorchis viverrini stimulates cell hyperproliferation and proinflammatory cytokine production.

Purpose: Progranulin (PGRN) is a secreted glycoprotein growth factor with roles in wound healing, inflammation, angiogenesis and malignancy. An orthologue of the gene encoding human PGRN was identified in the carcinogenic liver fluke .

Methods: Sequence structure, general characteristics and possible function of PGRN was analyzed using bioinformatics.

Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini.

Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor for cholangiocarcinoma (CCA) in the Mekong Basin countries of Thailand, Lao PDR, Vietnam, Myanmar and Cambodia. Using a novel model of CCA, involving infection with gene-edited liver flukes in the hamster during concurrent exposure to dietary nitrosamine, we explored the role of the fluke granulin-like growth factor Ov-GRN-1 in malignancy. We derived RNA-guided gene knockout flukes (ΔOv-grn-1) using CRISPR/Cas9/gRNA materials delivered by electroporation.

Newly Discovered Peptides from the Coral Show Structural and Functional Diversity.

Scleractinian corals are crucially important to the health of some of the world's most biodiverse, productive, and economically important marine habitats. Despite this importance, analysis of coral peptidomes is still in its infancy. Here we show that the tentacle extract from the stony coral is rich in peptides with diverse and novel structures.

IPSE, an abundant egg-secreted protein of the carcinogenic helminth , promotes proliferation of bladder cancer cells and angiogenesis.

Background: the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between and bladder cancer, the underlying mechanisms are poorly understood. oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia.

Orally Administered Bacillus Spores Expressing an Extracellular Vesicle-Derived Tetraspanin Protect Hamsters Against Challenge Infection With Carcinogenic Human Liver Fluke.

Background: The human liver fluke Opisthorchis viverrini is a food-borne trematode that causes hepatobiliary disease in humans throughout Southeast Asia. People become infected by consuming raw or undercooked fish containing metacercariae. Development of a vaccine to prevent or minimize pathology would decrease the risk of severe morbidity, including the development of bile duct cancer.

Folding of Truncated Granulin Peptides.

Granulins are a family of unique protein growth factors which are found in a range of species and have several bioactivities that include cell proliferation and wound healing. They typically contain six disulfide bonds, but the sequences, structures and bioactivities vary significantly. We have previously shown that an N-terminally truncated version of a granulin from the human liver fluke, , can fold independently into a "mini-granulin" structure and has potent wound healing properties in vivo.

Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.

Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity.

Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity.

Infection with the food-borne liver fluke is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the GRN-1 gene from the liver fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within GRN-1.

Defined Small Molecules Produced by Himalayan Medicinal Plants Display Immunomodulatory Properties.

Plant-derived compounds that modulate the immune responses are emerging as frontline treatment agents for cancer, infectious diseases and autoimmunity. Herein we have isolated 40 phytochemicals from five Bhutanese medicinal plants-, , , and -and tested 14 purified compounds for their immunomodulatory properties using a murine dendritic cell (DC) line, and cytotoxicity against a human cholangiocyte cell line using xCELLigence real time cell monitoring. These compounds were: pseudaconitine, 14-veratryolpseudaconitine, 14--acetylneoline, linalool oxide acetate, ()-spiroether, luteolin, luteolin-7--β-d-glucopyranoside, protopine, ochrobirine, scoulerine, capnoidine, isomyristicin, bergapten, and isoimperatorin.

Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate Wound Healing.

Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead.

Structural Characterisation of Predicted Helical Regions in the CfTX-1 Toxin.

The Australian jellyfish , belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins is integral to the understanding of the mechanism of these toxins and the development of an effective treatment.

Developmental Sensitivity in Schistosoma mansoni to Puromycin To Establish Drug Selection of Transgenic Schistosomes.

Schistosomiasis is considered the most important disease caused by helminth parasites, in terms of morbidity and mortality. Tools to facilitate gain- and loss-of-function approaches can be expected to precipitate the discovery of novel interventions, and drug selection of transgenic schistosomes would facilitate the establishment of stable lines of engineered parasites. Sensitivity of developmental stages of schistosomes to the aminonucleoside antibiotic puromycin was investigated.

Granulin Secreted by the Food-Borne Liver Fluke Promotes Angiogenesis in Human Endothelial Cells.

The liver fluke is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades.

Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control.

Historically, sustained control of Aedes aegypti, the vector of dengue, chikungunya, yellow fever, and Zika viruses, has been largely ineffective. Subsequently, two novel 'rear and release' control strategies utilizing mosquitoes infected with Wolbachia are currently being developed and deployed widely. In the incompatible insect technique, male Aedes mosquitoes, infected with Wolbachia, suppress populations through unproductive mating.

Spine-bellied sea snake (Hydrophis curtus) venom shows greater skeletal myotoxicity compared with cardiac myotoxicity.

For the first time the impedance-based xCELLigence real-time cell analysis system was used to measure the myotoxicity of sea snake venom. With a focus on the spine-bellied sea snake (Hydrophis curtus), the venom of four sea snake species and three terrestrial snake species were compared for myotoxicity against a human skeletal muscle cell line (HSkMC). Hydrophis curtus venom was also tested on a human cardiac muscle cell line (HCM).

Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases.

Background: Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ)-the only licenced anti-schistosome compound) is sustainable, necessitating the development of new drugs.

Methodology/principal Findings: We investigated the anti-schistosome efficacy of polypyridylruthenium(II) complexes and showed they were active against all intra-mammalian stages of S. mansoni.

Conotoxin Φ-MiXXVIIA from the Superfamily G2 Employs a Novel Cysteine Framework that Mimics Granulin and Displays Anti-Apoptotic Activity.

Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Φ-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Φ-MiXXVIIA was determined by NMR spectroscopy.

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold.

Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle for clinical development.

Identification of lead chemotherapeutic agents from medicinal plants against blood flukes and whipworms.

Schistosomiasis and trichuriasis are two of the most common neglected tropical diseases (NTD) that affect almost a billion people worldwide. There is only a limited number of effective drugs to combat these NTD. Medicinal plants are a viable source of parasiticides.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.

Background: Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides.