Neuropeptide signalling systems comprising peptide ligands and cognate receptors are evolutionarily ancient regulators of physiology and behaviour. However, there are challenges associated with determination of orthology between neuropeptides in different taxa. Orthologs of vertebrate neuropeptide-Y (NPY) known as neuropeptide-F (NPF) have been identified in protostome invertebrates, whilst prolactin-releasing peptide (PrRP) and short neuropeptide-F (sNPF) have been identified as paralogs of NPY/NPF in vertebrates and protostomes, respectively. Here we investigated the occurrence of NPY/NPF/PrRP/sNPF-related signalling systems in a deuterostome invertebrate phylum – the Echinodermata. Analysis of transcriptome/genome sequence data revealed loss of NPY/NPF-type signalling, but orthologs of PrRP-type neuropeptides and sNPF/PrRP-type receptors were identified in echinoderms. Furthermore, experimental studies revealed that the PrRP-type neuropeptide pQDRSKAMQAERTGQLRRLNPRF-NH2 is a potent ligand for a sNPF/PrRP-type receptor in the starfish Asterias rubens. Our findings indicate that PrRP-type and sNPF-type signalling systems are orthologous and originated as a paralog of NPY/NPF-type signalling in Urbilateria.
Heart disease is still the leading killer all around the world, and its incidence is expected to increase over the next decade. Previous reports have already shown the role of fibroblast growth factor10 (FGF10) in alleviating heart diseases. However, FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity. Here, an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction (MI) model. As shown in our echocardiographic results, a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI. It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment. Furthermore, FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells. However, with the same dosage, no statistically significant difference was shown between free FGF10, heparin+FGF10 and saline treatment, especially in long term. On another hand, FGF10 coacervate also increased the expression of cardiac-associated the mRNA (cTnT, Cx43 and α-SMA), angiogenic factors (Ang-1 and VEGFA) and decreased the level of inflammatory factor (tumor necrosis factor-α). The downstream signaling of the FGF10 was also investigated, with the western blot results showing that FGF10 coacervate activated the p -FGFR, PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10. In general, it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.
Background The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS). Case presentation Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22–52 years). The median symptoms onset to clinic time was 3.5 days (range 3–6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3–7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165–400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147–478 × 10^6/L; median 1.41 g/L, range 0.57–1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10–14 days. All patients recovered completely. Conclusions VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.
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