Project description:Altered levels of microRNAs (miRNAs) in blood may contribute to identification of individuals with lung cancer (LC) but may also be early systemic signals of increased LC risk. We compared expression of 1663 miRNAs in blood collected during diagnostic workup for confirmed LC cases (n=128) to that in individuals with suspected but confirmed negative LC (n=62) and identified nine candidate miRNAs upregulated in LC cases. Higher expression of three candidates, miR-320b, 320c, and 320d, was associated with poor survival, independent of LC stage and subtype. To investigate pre-diagnostic profiles of the candidate miRNAs, we assessed their blood expression up to eight years prior to LC diagnosis in population-based cohorts compared to matched controls (n=360 cases, 375 controls). Expression of miR-320c and miR-320d was higher especially in cases sampled within two years prior to LC diagnosis. Thus, elevated levels of miR-320c and miR-320d may be early indications of severe LC.
Project description:Hepatitis B virus-related liver cirrhosis (HBV-LC) is susceptible to bacterial infections, which could lead to adverse prognosis in patients. MicroRNA (miRNA) is easily detected in peripheral blood and is involved in multiple liver diseases. This pilot study aimed to investigate the differentially expressed (DE) miRNAs in the serum of patients with HBV-LC and bacterial infection, and to identify the potential biomarker. The clinical samples was collected, including four patients with HBV-LC and infection, four patients with HBV-LC without infection, four patients with chronic hepatitis B (CHB) and four healthy controls. miRNA expression was analyzed by Affymetrix GeneChip miRNA 4.0 Array. A total of 385 DE miRNAs (upregulated, 160; downregulated, 225) were detected in patients with HBV-LC and infection compared with patients with HBV-LC without infection.
Project description:As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates both arousal and stress responses, but how neuromodulatory inputs contribute to LC modulation remains incompletely understood. In this study, we isolated a network of transcriptionally diverse inhibitory pericoerulear (peri-LC) GABAergic neurons that integrate distant stimuli and modulate modes of LC firing. To define the peri-LC anatomy, we used viral tracing, single-nuclei and high-resolution spatial RNA transcriptomics to molecularly characterize both LC and peri-LC cell types. We complemented this approach with techniques in electrophysiology, photometry, optogenetics, and chemogenetics to probe the function of peri-LC neurons in behaving mice. These findings indicate that LC and peri-LC neurons comprise transcriptionally heterogenous neuronal groups which integrate diverse inputs to influence behavioral arousal states and avoidance. We used snRNAseq to characterize the peri-LC and LC brain regions. Our dataset contains 30,838 cells, of which 12,278 are neurons.
Project description:As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates both arousal and stress responses1,2. However, how local neuromodulatory inputs contribute to LC function remains unresolved. Here we identify a network of transcriptionally and functionally diverse GABAergic neurons in the LC dendritic field that integrate distant inputs and modulate modes of LC firing to control arousal. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing and spatial transcriptomics to molecularly define both LC and peri-LC cell types. We identify several cell types which underlie peri-LC functional diversity using a series of complementary approaches in behaving mice. Our findings indicate that LC and peri-LC neurons comprise transcriptionally and functionally heterogenous neuronal populations, alongside anatomically segregated features which coordinate specific influences on behavioral arousal and avoidance states. Defining the molecular, cellular and functional diversity in the LC provides a road map for understanding the neurobiological basis of arousal alongside hyperarousal-related neuropsychiatric phenotypes.