Preliminary expression profile of cytokines in brain tissue of BALB/c mice with Angiostrongylus cantonensis infection

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can result in increased risk of eosinophilic meningitis. Accumulation of eosinophils and inflammation can result in the A. cantonensis infection playing an important role in brain tissue injury during this pathological process. However, underlying mechanisms regarding the transcriptomic responses during brain tissue injury caused by A. cantonensis infection are yet to be elucidated. This study is aimed at identifying some genomic and transcriptomic factors influencing the accumulation of eosinophils and inflammation in the mouse brain infected with A. cantonensis. METHODS: An infected mouse model was prepared based on our laboratory experimental process, and then the mouse brain RNA Libraries were constructed for deep Sequencing with Illumina Genome Analyzer. The raw data was processed with a bioinformatics’ pipeline including Refseq genes expression analysis using cufflinks, annotation and classification of RNAs, lncRNA prediction as well as analysis of co-expression network. The analysis of Refseq data provides the measure of the presence and prevalence of transcripts from known and previously unknown genes. RESULTS: This study showed that Cys-Cys (CC) type chemokines such as CCL2, CCL8, CCL1, CCL24, CCL11, CCL7, CCL12 and CCL5 were elevated significantly at the late phase of infection. The up-regulation of CCL2 indicated that the worm of A. cantonensis had migrated into the mouse brain at an early infection phase. CCL2 could be induced in the brain injury during migration and CCL2 might play a major role in the neuropathic pain caused by A. cantonensis infection. The up-regulated expression of IL-4, IL-5, IL-10, and IL-13 showed Th2 cell predominance in immunopathological reactions at late infection phase in response to infection by A. cantonensis. These different cytokines can modulate and inhibit each other and function as a network with the specific potential to drive brain eosinophilic inflammation. The increase of ATF-3 expression at 21 dpi suggested the injury of neuronal cells at late phase of infection. 1217 new potential lncRNA were candidates of interest for further research. CONCLUSIONS: These cytokine networks play an important role in the development of central nervous system inflammation caused by A. cantonensis infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0939-6) contains supplementary material, which is available to authorized users

Identifying Schistosoma japonicum Excretory/Secretory Proteins and Their Interactions with Host Immune System

Schistosoma japonicum is a major infectious agent of schistosomiasis. It has been reported that large number of proteins excreted and secreted by S. japonicum during its life cycle are important for its infection and survival in definitive hosts. These proteins can be used as ideal candidates for vaccines or drug targets. In this work, we analyzed the protein sequences of S. japonicum and found that compared with other proteins in S. japonicum, excretory/secretory (ES) proteins are generally longer, more likely to be stable and enzyme, more likely to contain immune-related binding peptides and more likely to be involved in regulation and metabolism processes. Based on the sequence difference between ES and non-ES proteins, we trained a support vector machine (SVM) with much higher accuracy than existing approaches. Using this SVM, we identified 191 new ES proteins in S. japonicum, and further predicted 7 potential interactions between these ES proteins and human immune proteins. Our results are useful to understand the pathogenesis of schistosomiasis and can serve as a new resource for vaccine or drug targets discovery for anti-schistosome

Clonorchiasis sinensis detected by laparoscopic exploration of biliary tracts in two patients with obstructive jaundice

Abstract Background Hepatic clonorchiasis is one of the most prevalent food-borne parasitic diseases worldwide. Clonorchis sinensis, the pathogen, is the major parasitic trigger contributing to cholangitis, cholelithiasis, and even cholangiocarcinoma. Unfortunately, unspecific clinical manifestations of patients with hepatic clonorchiasis tend to mislead clinicians to neglect or misdiagnose them, following ignorance of appropriate therapy. Our case report may shed light on definite diagnosis of clonorchiasis with concomitant cholelithiasis, methodology for surgical drainage of the parasites, and postoperative anthelmintic therapy. Case presentation Two patients with habit of eating infected raw or undercooked freshwater fish were hospitalized due to right upper quadrant pain and jaundice. Magnetic resonance cholangiopancreatography (MRCP)/computed tomography (CT) detection indicated cholangiolithiasis and cholangiolithiasis with concurrent cholecystolithiasis, respectively. Fecal examinations were both negative for adult worms or eggs of parasites. However, adults of Clonrochis sinensis were detected within hepatobiliary tracts during laparoscopic cholecystectomy. Postoperative drainage and anthelmintic therapy contributed to complete recovery with good prognosis. Conclusions Clonorchiasis provokes cholangiolithiasis and cholecystolithiasis. Standardized treatments for these gallstone patients with concomitant clonorchiasis include surgical removal of the calculus, postoperative T tubule drainage and anthelmintic therapy. Serological test or polymerase chain reaction (PCR)-based approaches might be helpful for diagnosis of clonorchiasis when no eggs are found by stool microscopy. Public health promotion on ceasing to eat raw freshwater fish is essential for prevention and control of clonorchiasis

Reinforcement of Bonding Strength between Dental Y‐TZP and Resin via Nano‐Thin and Conformal SiO2 Films by Atomic Layer Deposition

Abstract The retentive strength of zirconia crowns is derived from resin cement, and the weak interface between the two is the main reason for their failure. In this work, nano‐thin silica (SiO2) films of precisely controlled thickness are deposited over yttrium‐stabilized tetragonal zirconia polycrystal (Y‐TZP) ceramics via atomic layer deposition (ALD). The deposited films are modified using a silane coupling agent, which significantly improves the bonding strength between Y‐TZP and resin. Scanning electron microscopy shows that the SiO2 films deposited by ALD are uniform and can accurately maintain the morphology of grit‐blasted Y‐TZP. Spectroscopic ellipsometry demonstrates that the films are nano‐thin, with thicknesses in the range of 5.58–26.58 nm. The increase in the shear bond strength is attributed to the chemical bonding between the conformal nano‐SiO2 films and Y‐TZP. However, the stability of the bond decreases when the SiO2 films are too thick. Overall, the results indicate that SiO2 films deposited in 400 ALD cycles have both good bonding strength and stability after aging, much higher than those of Z‐Prime Plus films

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice

Abstract Background Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. Methods To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensisand the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). Results Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. Conclusions The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic

Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis.

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC