H19/Mir-130b-3p/Cyp4a14 potentiate the effect of praziquantel on liver in the treatment of Schistosoma japonicum infection.

BACKGROUND: Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated. RESULTS: In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR. CONCLUSIONS: Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.

Gut Microbiota Taxon-Dependent Transformation of Microglial M1/M2 Phenotypes Underlying Mechanisms of Spatial Learning and Memory Impairment after Chronic Methamphetamine Exposure.

Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75NTR-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that Clostridia, Bacteroides, Lactobacillus, and Muribaculaceae might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75NTR/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. IMPORTANCE Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.