Implications of MicroRNAs in the Vascular Homeostasis and Remodeling

Vascular remodeling or arterial remodeling is a process of adaptive alteration of vascular wall architecture and leads to the endothelial cell (EC) dysfunction and synthetic or contractile phenotypic change of VSMCs, and the infiltration of monocytes and Macrophages that promotes vascular diseases including atherosclerosis. Recent findings have demonstrated that microRNAs (miRNAs) are involved in regulating gene expression at posttranscriptional level and disease pathogenesis. A change of miRNA expression profiles plays key roles in the gene expressions and the regulation of cellular functions. In this chapter, we summarize the vascular remodeling-related miRNAs and their functions in vascular biology

The Origin of Star Formation in Early-type Galaxies Inferred from Spatially Resolved Spectroscopy

We investigate the origin of star formation activity in early-type galaxies with current star formation using spatially resolved spectroscopic data from the Mapping Nearby Galaxies at APO (MaNGA) in the Sloan Digital Sky Survey (SDSS). We first identify star-forming early-type galaxies from the SDSS sample, which are morphologically early-type but show current star formation activity in their optical spectra. We then construct comparison samples with different combinations of star formation activity and morphology, which include star-forming late-type galaxies, quiescent early-type galaxies and quiescent late-type galaxies. Our analysis of the optical spectra reveals that the star-forming early-type galaxies have two distinctive episodes of star formation, which is similar to late-type galaxies but different from quiescent early-type galaxies with a single star formation episode. Star-forming early-type galaxies have properties in common with star-forming late-type galaxies, which include stellar population, gas and dust content, mass and environment. However, the physical properties of star-forming early-type galaxies derived from spatially resolved spectroscopy differ from those of star-forming late-type galaxies in the sense that the gas in star-forming early-type galaxies is more concentrated than their stars, and is often kinematically misaligned with stars. The age gradient of star-forming early-type galaxies also differs from those of star-forming late-type galaxies. Our findings suggest that the current star formation in star-forming early-type galaxies has an external origin including galaxy mergers or accretion gas from the cosmic web.Comment: 19 pages, 12 figures, Accepted for publication in Ap

Fetal gender determination and BclI polymorphism using nucleated erythrocytes in maternal blood

This study demonstrated determination of fetal gender from nucleated red blood cells (NRBCs) in maternal blood and attempted to apply prenatal diagnosis of hemophilia A using BclI DNA polymorphism. Venous blood was drawn from 20 pregnant women, and NRBCs were recovered by magnetic activated cell sorting and anti-GPA (glycophorin A) immunostaining. After microdissector isolation of the NRBCs, primer extension preamplification (PEP) and nested PCR of the amelogenin gene were performed to determine fetal gender. We also performed PEP and nested PCR of BclI polymorphism to verify the validity of prenatal diagnosis of hemophilia A. DNA amplification was achieved in 107 cells (51.9%) and fetal gender determined with 65.0% accuracy. Unfortunately, we could not verify the validity within the scope of this study. However, in a larger number of cases that are informative in BclI polymorphism, we will be able to identify patients affected by hemophilia A using fetal NRBCs in maternal blood

MicroRNA-143 and-145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis

Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets. © 2017 KSBMB4

Complete Binocular Blindness as the First Manifestation of HIV-Related Cryptococcal Meningitis

Ocular complications of HIV-related cryptococcal meningitis are reasonably common, but complete binocular blindness as the first manifestation of HIV is extremely rare. A 58-year-old man presented with binocular blindness. He experienced blurred vision for 3 days before the blindness. Mild pleocytosis was present in the cerebrospinal fluid, from which Cryptococcus neoformans was cultured. Serology revealed positivity for HIV antibody. He was treated with antifungal and antiretroviral therapy. This case indicates that HIV-related cryptococcal meningitis should be taken into consideration when determining the cause of unexpected sudden binocular blindness

Reappraisal of Plasmapheresis as a Supportive Measure in a Patient with Hepatic Failure after Major Hepatectomy

Major resection of cirrhotic livers can result in hepatic failure, but no supportive treatment has been found to be generally effective. We successfully treated a 63-year-old woman with post-hepatectomy liver failure with plasmapheresis. Following right hepatectomy, the initial postoperative recovery of liver function was favorable, except for ascites. One month later, however, the amount of drained ascites increased up to 2 l/day. In addition, serum cholesterol concentration gradually decreased to around 30 mg/dl, and serum total bilirubin rose to 11.1 mg/dl. Plasmapheresis was performed, and after just 2 sessions, serum cholesterol level was rapidly corrected and prothrombin time was restored. After 3 sessions of plasmapheresis, the usual rebound rise of serum bilirubin disappeared, and the amount of ascites drained also decreased slowly. The patient underwent a total of 5 sessions of plasmapheresis over 2 weeks, after which liver function improved slowly, and she was finally discharged 72 days after liver resection. Mild ascites requiring diuretic therapy persisted over 3 months. She is doing well to date 10 months after liver resection without tumor recurrence or hepatic decompensation. This limited experience suggests that plasmapheresis can be a useful liver support for post-hepatectomy liver failure