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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. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the I ntegrated Module of M ultidimensional O mics for Pe r ipheral Biomark e rs (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes., Methods and Analysis: iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants' responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase., Ethics and Dissemination: The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals., Trial Registration Number: NCT04518592., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Growth factor receptor-binding protein 14, a new member of noncatalytic adaptor proteins family, has been shown to be upregulated in breast cancer. We investigated the prognostic value of growth factor receptor-binding protein 14 expression in breast cancer patients treated with neoadjuvant chemotherapy., Methods: Primary breast cancer specimens were taken from locally advanced breast cancer patients in a Phase II clinical trial of neoadjuvant chemotherapy and the expression pattern of growth factor receptor-binding protein 14 was determined by immunohistochemistry. Kaplan-Meier analysis and Cox regression model were used to assess disease-free and overall survival, according to the expression of growth factor receptor-binding protein 14 in tumor cells., Results: Our result showed that growth factor receptor-binding protein 14 was highly expressed in 23.1% of breast cancer sections, and high expression of growth factor receptor-binding protein 14 was significantly associated with better disease-free (P = 0.016, hazard ratio 0.07, 95% confidence interval 0.06-0.08) and overall survival (P = 0.004, hazard ratio 0.02, 95% confidence interval 0.02-0.03), compared with the low-expression group. Multivariate analysis indicated that high expression of growth factor receptor-binding protein 14 was an independent good prognostic factor for both disease-free (P = 0.04, hazard ratio 0.37, 95% confidence interval 0.14-0.98) and overall survival (P = 0.03, hazard ratio 0.11, 95% confidence interval 0.10-0.82)., Conclusions: High expression of growth factor receptor-binding protein 14 in breast cancer cells may help to identify low-risk patients for additional therapies after neoadjuvant chemotherapy.