NMR study of lipid changes in organs of jirds infected with Echinococcus multilocularis

Kepron, Charis; Schoen, Jodi M.; Novak, Marie; Blackburn, B. J.

doi:10.1016/s0305-0491(99)00126-1

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…The gerbil Meriones unguiculatus which has similar habitat preferences to jerboas has been reported in the area [40] . Gerbils [66] , [67] and hamsters [26] provide excellent laboratory models for E. multilocularis and natural infections have been found in M. unguiculatus in NHAR [17] and in C. kamensis in Sichuan [unpub data]. Ochotona daurica has been found infected in Tuva, southern central Russia [17] and O. curzoniae is frequently present in fox faeces from NW Sichuan where it is predated preferentially, even when hamsters are visibly abundant [unpub data].…”

Section: Discussionmentioning

confidence: 99%

Landscape Composition and Spatial Prediction of Alveolar Echinococcosis in Southern Ningxia, China

et al. 2008

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BackgroundAlveolar echinococcosis (AE) presents a serious public health challenge within China. Mass screening ultrasound surveys can detect pre-symptomatic AE, but targeting areas identified from hospital records is inefficient regarding AE. Prediction of undetected or emerging hotspots would increase detection rates. Voles and lemmings of the subfamily Arvicolinae are important intermediate hosts in sylvatic transmission systems. Their populations reach high densities in productive grasslands where food and cover are abundant. Habitat availability is thought to affect arvicoline population dynamic patterns and definitive host–intermediate host interactions. Arvicoline habitat correlates with AE prevalence in Western Europe and southern Gansu Province, China.Methods and FindingsXiji County, Ningxia Hui Autonomous Region, borders southern Gansu. The aims of this study were to map AE prevalence across Xiji and test arvicoline habitat as a predictor. Land cover was mapped using remotely sensed (Landsat) imagery. Infection status of 3,205 individuals screened in 2002–2003 was related, using generalised additive mixed models, to covariates: gender; farming; ethnicity; dog ownership; water source; and areal cover of mountain pasture and lowland pasture. A Markov random field modelled additional spatial variation and uncertainty. Mountain pasture and lowland pasture were associated with below and above average AE prevalence, respectively.ConclusionsLow values of the normalised difference vegetation index indicated sub-optimality of lowland pasture for grassland arvicolines. Unlike other known endemic areas, grassland arvicolines probably did not provide the principal reservoir for Echinococcus multilocularis in Xiji. This result is consistent with recent small mammal surveys reporting low arvicoline densities and high densities of hamsters, pikas and jerboas, all suitable intermediate hosts for E. multilocularis, in reforested lowland pasture. The risk of re-emergence is discussed. We recommend extending monitoring to: southern Haiyuan County, where predicted prevalence was high; southern Xiji County, where prediction uncertainty was high; and monitoring small mammal community dynamics and the infection status of dogs.

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Section: Discussionmentioning

confidence: 99%

Landscape Composition and Spatial Prediction of Alveolar Echinococcosis in Southern Ningxia, China

et al. 2008

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“…Since E. multilocularis is unable to synthesize FAs, cholesterol and other sterols de novo, [94] it is not surprising that AE might promote lipid synthesis in the liver. It was suggested that experimental AE in jirds could stimulate fatty acid biosynthesis [95], nevertheless further investigations are required to determine quantitative and qualitative effects of AE on host lipid metabolism and to define the exact role of miRNAs in this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg infection in C57BL/6 mice

et al. 2020

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We present a comprehensive analysis of the hepatic miRNA transcriptome at one month post-infection of experimental primary alveolar echinococcosis (AE), a parasitic infection caused upon ingestion of E. multilocularis eggs. Liver tissues were collected from infected and non-infected C57BL/6 mice, then small RNA libraries were prepared for next-generation sequencing (NGS). We conducted a Stem-loop RT-qPCR for validation of most dysregulated miRNAs. In infected mice, the expression levels of 28 miRNAs were significantly altered. Of these, 9 were up-regulated (fold change (FC) � 1.5) and 19 were down-regulated (FC � 0.66) as compared to the non-infected controls. In infected livers, mmu-miR-148a-3p and mmu-miR-101b-3p were 8-and 6-fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 1.8). In addition, the relative mRNA expression levels of five genes (vegfa, mtor, hif1-α, fasn and acsl1) that were identified as targets of down-regulated miRNAs were significantly enhanced. All the five genes exhibited a higher expression level in livers of E. multilocularis infected mice compared to non-infected mice. Finally, we studied the issue related to functionally mature arm selection preference (5p and/or 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. In conclusion, this study provides first evidence that miRNAs are regulated early in primary murine AE. Our findings raise intriguing questions such as (i) how E. multilocularis affects hepatic miRNA expression;(ii) what are the alterations in miRNA expression patterns in more advanced AE-stages; and (iii) which hepatic cellular, metabolic and/or immunologic processes are modulated through altered miRNAs in AE. Thus, further research on the regulation of miRNAs during AE is needed, since miRNAs constitute an attractive potential option for development of novel therapeutic approaches against AE.

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“…This difference can be explained by the fact that FAs have different implications in various infectious and non-infectious liver diseases. In fact, in contrast to tumor cells, E. multilocularis larvae are unable to synthesize FAs, cholesterol and other sterols de novo , thus they must scavenge these components from their host [95], and mobilization of host lipid resources to the parasite may imply stimulation of fatty acid biosynthesis [96].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hepatic MicroRNAs in Response to Early Stage Echinococcus multilocularis Egg Infection in C57BL/6 mice

Boubaker

Strempel

Hemphill

et al. 2019

Preprint

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22In this study, we present a comprehensive analysis of the hepatic miRNA transcriptome in 23 mice suffering from experimental primary alveolar echinococcosis (AE), a parasitic infection 24 caused upon ingestion of Echinococcus multilocularis (E. multilocularis) eggs. At one month 25 post-infection, infected C57BL/6 mice, along with non-infected control mice, were 26 euthanized. Subsequently livers were collected and used for small RNA library preparation 27 and next-generation sequencing (NGS). The most significantly dysregulated hepatic miRNAs 28 were validated by Stem-loop RT-qPCR. We identified 28 miRNAs with significantly altered 29 expression levels upon infection with E. multilocularis. Of these, 9 were up-regulated (fold 30 change (FC) ≥ 1.5) and 19 were down-regulated (FC ≤ 0.66) as compared to the non-infected 31 controls. In infected liver tissues, mmu-miR-148a-3p and mmu-miR-101b-3p were 8-and 6-32 fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 33 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels 34 were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 35 1.8). Down-regulated miRNAs were highly enriched in Reactome and KEGG pathways of 36 angiogenesis and fatty acids biosynthesis. Moreover, relative mRNA expression levels of 37 three pro-angiogenic (VEGFA, MTOR and HIF1-α) and two lipogenic (FASN and ACSL1) 38 genes were significantly higher in livers of E. multilocularis infected mice. 39Lastly, we studied the issue related to functionally mature arm selection preference (5p and/or 40 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm 41 selection preferences in normal versus infected liver tissues. Our study provides first evidence 42 of miRNA involvement in liver pathogenesis during AE. Our future research will focus on the 43 characterization of miRNA transcriptome patterns in more advanced AE-stages towards the 44 assessment of microRNA therapy for AE, and experimentally address functional 45 characteristics of selected features presently found. 48of microRNAs (miRNAs), a class of small non-coding RNAs involved in negative regulation 49 of gene expression. Herein, we revealed that significant alterations of miRNA expression 50 occurred in murine liver subsequently to experimental infection with Echinococcus 51 multilocularis (E. multilocularis) eggs when compared to non-infected controls. 52At the early stage of murine AE, hepatic miRNAs were mainly downregulated. Respective 53 target genes of the most extensively downregulated miRNAs were involved in angiogenesis 54 and fatty acid synthesis. Indeed, angiogenic and lipogenic genes were found to be 55 significantly higher expressed in E. multilocularis infected livers relative to non-infected 56 controls. These boosted cellular pathways are advantageous for development of the E. 57 multilocularis metacestodes, since this larval stage is not able to undertake de novo fatty acid 58 synthesis, and angiogenesis ...

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NMR study of lipid changes in organs of jirds infected with Echinococcus multilocularis

Cited by 6 publications

References 28 publications

Landscape Composition and Spatial Prediction of Alveolar Echinococcosis in Southern Ningxia, China

Landscape Composition and Spatial Prediction of Alveolar Echinococcosis in Southern Ningxia, China

Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg infection in C57BL/6 mice

Regulation of Hepatic MicroRNAs in Response to Early Stage Echinococcus multilocularis Egg Infection in C57BL/6 mice

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