Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease (AD) involving imbalanced beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). MicroRNAs (miRNAs) are associated with AD. Objective: This study aimed to investigated whether plasma miRNAs can predict prodromal AD or are associated with AD pathology. Methods: Participants in the discovery set (n = 10), analysis set (n = 30), and validation set (n = 80) were screened from the China Longitudinal Aging Study. RNA was extracted from the participants’ plasma. Microarray sequencing provided miRNA profiles and differentially expressed miRNAs (DEmiRNAs) in the discovery set included patients with 18F-Flutemetamol positron emission tomography scan-confirmed aMCI. Potential biomarkers were screened in the analysis set. The predict capability of candidate miRNAs was assessed in the validation set. Candidate miRNAs modulation of BACE1 expression was explored in rat and human hippocampal neurons in vitro. Results: We verified 46 significant DEmiRNAs between the aMCI and NC groups (p <  0.05), among which 33 were downregulated. In the analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p levels decreased significantly in the aMCI group. These miRNAs and previously identified miR-107 were selected as potential biomarkers. A prediction model comprising these five miRNAs showed outstanding accuracy (81.25%) to discriminate aMCI at cut-off value of 0.174. Except for miR-134-3p, the other four miRNAs significantly suppressed Bace1 expression in rat hippocampal neurons in vitro. BACE1 modulation of miR-1185-2-3p, miR-1909-3p, and miR-134-3p was confirmed in human hippocampal neurons in vitro. Conclusion: A predictive model consisting of five BACE1-related plasma miRNAs could be a novel biomarker for aMCI.

C-type allatostatins are a family of peptides that characterized by a conserved unblocked-PISCF in C-terminal. In insects, it is well known that C-type allatostatin has a potent inhibitory effect on juvenile hormone biosynthesis by the corpora allata. Recently, C-type allatostatin has been widely identified from crustacean species but little is known about its roles. Therefore, this study described the tissue distribution patterns of C-type allatostatin and its putative receptor in the mud crab Scylla paramamosain, and further explored its potential effect on vitellogenesis. Firstly, the cDNAs encoding C-type allatostatin (Sp-AST-C) precursor and its putative receptor (Sp-AST-CR) were isolated, respectively. Subsequently, RT-PCR results suggested that, Sp-AST-C was mainly expressed in the nervous tissue, middle gut and the heart while Sp-AST-CR had an extensive expression in the detected tissues except the eyestalk ganglion and hepatopancreas. Furthermore, the Sp-AST-C expressing cells in the cerebral ganglion were detected through in situ hybridization, it showed that Sp-AST-C was localized in cluster 6, 8 of protocerebrum, cluster 9, 10, 11 of deutocerebrum, and cluster 14, 15 of tritocerebrum. The whole-mount immunofluorescence gave a similar distribution pattern. An in vitro experiment showed that, the synthetic Sp-AST-C had no effect on the abundance of Sp-Vg in the hepatopancreas and ovary but significantly reduced the expression of Sp-VgR in the ovary in a dose-dependent manner. Furthermore, it was demonstrated that the Sp-VgR expression, Vn content, and oocyte diameter in ovary were reduced after 16-days injection of Sp-AST-C. Finally, the transcripts of Sp-AST-CR were specifically localized in the oocytes of ovary by in situ hybridization, which further revealed that the oocytes were target cells for Sp-AST-C. In conclusion, our results suggested that Sp-AST-C signaling system was involved in the regulation of ovarian development, in which Sp-AST-C might inhibit the uptake of yolk by oocytes directly and obstruct oocyte growth.

Alzheimer’s disease (AD) is the most common dementia in the world. Increasing evidence has shown that exosomes from hypoxic pretreated adipose-derived stem cells (ADSCs) could be an effective cognitive function therapeutic in AD-associated pathophysiology. However, their role and regulatory mechanism remain largely unknown. High-throughput sequencing was used to identify differentially expressed circRNAs from ADSCs or hypoxia pretreated ADSC exosomes. Luciferase reporter assays and RT-qPCR were used to investigate the relationships between circ-Epc1, miR-770-3p, and TREM2. APP/PS1 double transgenic AD model mice were then used to study therapeutic effects regarding circ-Epc1 in ADSC exosomes. BV2 cells were used to show the regulatory relationships between circ-Epc1, miR-770-3p, and TREM2 and to show how these interactions modulated phenotypic transformations and inflammatory cytokine expressions in microglia. The results showed that exosomes from hypoxia pretreated ADSCs had a good therapeutic effect on improving cognitive functions by decreasing neuronal damage in the hippocampus. High-throughput sequencing showed that circ-Epc1 played an important role in hypoxia-pretreated ADSC exosomes regarding their ability to improve cognitive functions. Luciferase reporter assays showed that TREM2 and miR-770-3p were downstream targets of circ-Epc1. Overexpressing miR-770-3p or downregulating TREM2 reversed the effects of circ-Epc1 on M2 microglia during lipopolysaccharide treatment. In vivo experiments showed that circ-Epc1-containing ADSC exosomes increased the therapeutic effect of exosomes by improving cognitive function, decreasing neuronal damage, and shifting hippocampal microglia from the M1 polarization to the M2 polarization stages. Taken together, the data show that hypoxic pretreatment of ADSC exosomes improved cognition by delivery of circ-Epc1 and by shifting microglial M1/M2 polarization in an AD mouse model.