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  • 1
    In: Bioengineering, MDPI AG, Vol. 10, No. 10 ( 2023-09-27), p. 1132-
    Abstract: Blood–brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging. Here, we developed an efficient method for differentiating hPSCs into BMECs that are amenable to the development and application of human BBB models. The established conditions provided an environment similar to that occurring during BBB differentiation in the presence of the co-differentiating neural cell population by the modulation of TGF-β and SHH signaling. The developed BME-like cells showed well-organized tight junctions, appropriate expression of nutrient transporters, and polarized efflux transporter activity. In addition, BME-like cells responded to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance. Moreover, the BME-like cells exhibited an immune quiescent property of BBB endothelial cells by decreasing the expression of adhesion molecules. Therefore, our novel cellular platform could be useful for drug screening and the development of brain-permeable pharmaceuticals.
    Type of Medium: Online Resource
    ISSN: 2306-5354
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2746191-9
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  • 2
    In: Healthcare, MDPI AG, Vol. 9, No. 12 ( 2021-12-04), p. 1681-
    Abstract: Background: Uric acid is one of natural antioxidants in human body. There have been several studies on the correlation between uric acid with oxidative stress and osteoporosis. However, the data are insufficient and results are controversial. In this regard, we determined the association between uric acid levels and bone mineral density (BMD) during the postmenopausal period. Methods: We analyzed data from 328 postmenopausal women (mean age, 57.3 ± 6.5 years; mean serum uric acid level, 4.6 ± 1.0 mg/dL). The participants were divided into three groups based on tertiles of the serum uric acid level. The participants receiving hormone replacement therapy (HRT), bisphosphonates, or lipid-lowering agents were included. Results: Blood urea nitrogen, serum creatinine, and serum triglyceride levels were significantly higher in the upper tertiles of uric acid levels. No significant difference was found in the mean uric acid levels between medication users and non-users. Each HRT regimen had a different mean serum uric acid level. A cross-sectional analysis showed no significant correlation between the serum uric acid levels and BMD in the spine and femoral neck (spine BMD: 1.050 ± 0.131, 1.060 ± 0.160, 1.084 ± 0.140, p = 0.22; femoral neck BMD: 0.837 ± 0.110, 0.849 ± 0.096, 0.863 ± 0.115, p = 0.28 for each tertile of uric acid). Longitudinal analysis of data from 186 women with follow-up examinations at a mean interval of 14.6 months also revealed no difference in reduction in both spine and femoral neck BMD between tertile groups of serum uric acid (the median BMD reduction for spine: −0.02, 0.01, −0.04, p = 0.95; the median BMD reduction for femoral neck: 0.008, 0.005, −0.003, p = 0.34). Conclusions: Serum uric acid level is not associated with BMD in postmenopausal women.
    Type of Medium: Online Resource
    ISSN: 2227-9032
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2721009-1
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