BackgroundToxoplasma gondii is an obligate intracellular protozoan parasite that can infect mammalian cells and thereby regulate host gene expression. The long non-coding RNAs (lncRNAs) have been demonstrated to be an important class of RNA molecules that regulate many biological processes, including host-pathogen interactions. However, the role of host lncRNAs in the response to T. gondii infection remains largely unknown.MethodsWe applied a microarray approach to determine the differential expression profiles of both lncRNAs and mRNAs in the human foreskin fibroblast (HFF) cells after T. gondii infection. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the potential functions of T. gondii-induced genes. Based on the co-expression networks of lncRNAs and immune-related genes, the role of NONSHAT022487 on the regulation of UNC93B1 related immune signaling was investigated by the knockdown and over-expression of lncRNA in human macrophage derived from the PMA-induced promonocytic cell line THP-1.ResultsOur data showed that 996 lncRNAs and 109 mRNAs in HFF cells were significantly and differentially expressed following T. gondii infection (fold change ≥ 5, P < 0.05). The results from the GO and KEGG pathway analyses indicated that the mRNAs with differential expression were mainly involved in the host immune response. Remarkably, we identified a novel lncRNA, NONSHAT022487, which suppresses the expression of the immune-related molecule UNC93B1. After T. gondii infection, NONSHAT022487 impaired the secretion of the cytokines IL-12, TNF-α, IL-1β and IFN-γ by downregulating UNC93B1 expression in human macrophage cells.ConclusionsOur study identified infection-induced lncRNA expression as a novel mechanism by which the Toxoplasma parasite regulates host immune signaling, which advances our understanding of the interaction of T. gondii parasites and host cells.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2697-8) contains supplementary material, which is available to authorized users.

Background and Objective: Propofol is the most commonly used sedative in gastrointestinal endoscopic procedures, but is associated with cardiorespiratory suppression, particularly in elderly patients. Remimazolam is a new short-acting GABA(A) receptor agonist with minimal impact on cardiorespiratory suppression, and may be a viable alternative in elderly patients undergoing endoscopic procedures.Methods: This multicenter, randomized controlled trial was conducted between September 2020 and September 2021. Elderly patients (65-85 years of age) scheduled to undergo upper gastrointestinal endoscopy were randomized in 1:1 ratio to receive remimazolam tosilate (300 mg/h) or propofol (3 g/h) in addition to 50-μg fentanyl, until the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) reached ≤1. MOAA/S was maintained at 0 or 1 throughout the procedure using 2.5 mg remimazolam or 0.5 mg/kg propofol boluses in the two groups, respectively. The primary outcome was the rate of hypotension (defined as systolic blood pressure at ≤90 mmHg or > 30% decline vs. the baseline). Bradycardia was defined as heart rate ≤50 per minute; respiratory depression was defined as respiratory rate <8 per minute and/or SpO 2 < 90%.Results: A total of 400 patients (161 men and 239 women; 70.4 ± 4.6 years of age) were enrolled (200 patients per group). Average body mass index was 22.2 ± 2.4 kg/m 2 . The rate of hypotension was 36.5% in the remimazolam group and 69.6% in the propofol group (p < 0.001). The remimazolam group also had a lower Kejian Lu, Shanshan Wei and Wenwen Ling contributed equally to this work.

Background Anopheles anthropophagus is one of the major vectors of malaria in Asia. MicroRNAs (miRNAs) play important roles in cell development and differentiation as well as in the cellular response to stress and infection. In a former study, we have investigated the global miRNA profiles in relation to sex in An. anthropophagus. However, the miRNAs contributing to the blood-feeding and infection with Plasmodium are still unknown.MethodsHigh-throughput sequencing was performed to identify miRNA profiles of An. anthropophagus midguts after blood-feeding and Plasmodium infection. The expression patterns of miRNA in different midgut libraries were compared based on transcripts per million reads (TPM), and further confirmed by Northern blots. Target prediction and pathway analysis were carried out to investigate the role of regulated miRNAs in blood-feeding and Plasmodium infection.ResultsWe identified 67 known and 21 novel miRNAs in all three libraries (sugar-feeding, blood-feeding and Plasmodium infection) in An. anthropophagus midguts. Comparing with the sugar-feeding, the experssion of nine (6 known and 3 novel) and ten (9 known and 1 novel) miRNAs were significantly upregulated and downregulated respectively after blood-feeding (P < 0.05, fold change ≥ 2 and TPM ≥ 10). Plasmodium infection induced the expression of thirteen (9 known and 4 novel) and eleven (9 known and 2 novel) miRNAs significantly upregulated and downregulated, respectively, compared with blood-feeding. The representative upregulated miR-92a in blood-feeding and downregulated miR-275 in Plasmodium infection were further confirmed by Northern Blot. Putative targets of these regulated miRNAs were further investigated and classified into their pathways.ConclusionsThis study suggests that miRNAs are involved in the blood-feeding and Plasmodium infection in An. anthropophagus midgut. Further studies of the function of these differential expressed miRNAs will facilitate in better understanding of mosquito biology and anti-parasite immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2027-6) contains supplementary material, which is available to authorized users.

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.

Ebola virus (EBOV) causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP) is the major protective antigen of EBOV, and can generate virus-like particles (VLPs) by co-expression with matrix protein (VP40). In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV) replicon vector DREP to express EBOV GP and matrix viral protein (VP40). EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40). Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.