Cystic echinococcosis (CE) is a zoonotic parasitic disease spread worldwide caused by Echinococcus granulosus (Eg), which sometimes causes serious damage; however, in many cases, people are not aware that they are infected. A number of recombinant vaccines based on Eg are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant Eg.P29 (rEg.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4+ T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using rEg.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4+ T cells into Th1/Th2 under rEg.P29 immunization and determined the mechanisms associated with delta-like 1 homolog (DLK1) and Notch1 signaling pathway. One week after P29 immunization of mice, we found that miR-126a-5p was significantly increased and DLK1 expression was decreased, while Notch1 pathway activation was enhanced and Th1 response was significantly stronger. The identical conclusion was obtained by overexpression of mmu-miR-126a-5p in primary naive CD4+ T cells in mice. Intriguingly, mmu-miR-126a-5p was significantly raised in serum from mice infected with protoscolex in the early stages of infection and markedly declined in the late stages of infection, while has-miR-126-5p expression was dramatically reduced in serum from CE patients. Taken together, we show that miR-126a-5p functions as a positive regulator of Notch1-mediated differentiation of CD4+ T cells into Th1 through downregulating DLK1 in vivo and in vitro. Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.
Objective
Cystic echinococcosis is a kind of parasitic disease that seriously endangers human and animal health. At present, its prevention and treatment still do not achieve the desired results. The aims of this study were to explore the effect of CE on intestinal microflora in mice.
Methods
In this study, 16S rRNA metagenome sequencing and bioinformatics were used to analyze the intestinal flora of mice infected with E. granulosus s.l. Changes in intestinal microbial community abundance were investigated and the differences in microbial populations of mice infected with E. granulosus s.l. were screened.
Results
Our results show that at the phylum level, nine abundant taxa were identified, the relative abundance of Firmicutes and Proteobacteria were enriched in infected mice, whereas Bacteroidetes and Patescibacteria were enriched in control mice (P < 0.01). At the class level, 13 abundant taxa were identified, the relative abundance of Bacilli was enriched in control mice, but decreased in infected mice (P < 0.01). At the order level, 15 abundant taxa were identified, the relative abundance of Lactobacillales was enriched in control mice, but decreased in infected mice (P < 0.01). At the family level, 28 abundant taxa were identified, enriched bacteria in the infected mice was Streptococcaceae, while the enriched bacteria in the control group was Lactobacillaceae (P < 0.01). At the genus level, 79 abundant taxa were identified, enriched bacteria in the infected mice was Streptococcus, while the enriched bacteria in the control group was uncultured_bacterium_f_Eggerthellaceae (P < 0.01). At the species level, 80 abundant taxa were identified, enriched bacteria in the infected mice was uncultured_bacterium_g_Streptococcus, while the enriched bacteria in the control group was uncultured_bacterium_f_Eggerthellaceae (P < 0.01). 39 KEGG pathways were identified that were differentially enriched between the infected and control mice.
Conclusion
This study comprehensively demonstrates the differential intestinal microbiota of infected mice and analyzes the metabolic pathways related to the specific microbiota. This could provide new targets and research direction for the treatment and prevention of diseases caused by E. granulosus s.l.
Transdermal drug delivery is a promising strategy characterized by minor fluctuations in blood concentrations, few adverse effects, convenience, and excellent patient compliance, especially for biomacromolecules. Conversely, traditional delivery methods are limited by their poor penetration abilities and complex preparation and application techniques. However, some inherent properties of biomacromolecules, such as large sizes, complex structure, and poor stability, can affect their ability to overcome skin barriers and reach deeper layers. Ionic liquids (ILs) are organic salts composed of asymmetric cations and anions in liquid form below 100 °C. ILs provide excellent protection for biomacromolecules and can facilitate their passage through the stratum corneum to cells for therapeutic effects. Therefore, they represent one of the most promising approaches to promoting transdermal penetration. Here, the barriers to effective transdermal delivery, including skin properties and the stability and biocompatibility of IL‐based biomacromolecule formulations, are highlighted and the current status of IL‐based biomacromolecule formulations are focused on, the tremendous advantages of using ILs based on current challenges in transdermal drug delivery are discussed, and light is shed on several ILs frequently used in the delivery of biomacromolecules.
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