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  • 1
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-01-25), p. 1-14
    Abstract: Cisplatin chemotherapy causes myelosuppression and often limits treatment duration and dose escalation in patients. Novel approaches to circumvent or lessen myelotoxicity may improve clinical outcome and quality of life in these patients. Chlorella sorokiniana (CS) is a freshwater unicellular green alga and exhibits encouraging efficacy in immunomodulation and anticancer in preclinical studies . However, the efficacy of CS on chemoprotection remains unclear. We report here, for the first time, that CS extract (CSE) could protect normal myeloid cells and PBMCs from cisplatin toxicity. Also, cisplatin-induced apoptosis in HL-60 cells was rescued through reservation of mitochondrial function, inhibition of cytochrome c release to cytosol, and suppression of caspase and PARP activation. Intriguingly, cotreatment of CSE attenuated cisplatin-evoked hypocellularity of bone marrow in mice. Furthermore, we observed the enhancement of CSF-GM activity in bone marrow and spleen in mice administered CSE and cisplatin, along with increased CD11b levels in spleen. In conclusion, we uncovered a novel mechanism of CSE on myeloprotection, whereby potentially supports the use of CSE as a chemoprotector against cisplatin-induced bone marrow toxicity. Further clinical investigation of CSE in combination with cisplatin is warranted.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2455981-7
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  • 2
    In: Movement Disorders, Wiley, Vol. 35, No. 9 ( 2020-09), p. 1662-1667
    Abstract: Alexander disease (AxD) is an autosomal‐dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein ( GFAP ) gene. Objectives The objective of this report is to characterize the clinical phenotype and identify the genetic mutation associated with adult‐onset AxD. Methods A man presented with progressive unsteadiness since age 16. Magnetic resonance imaging findings revealed characteristic features of AxD. The GFAP gene was screened, and a candidate variant was functionally tested to evaluate causality. Results A homozygous c.197G  〉  A (p.Arg66Gln) mutation was found in the proband, and his asymptomatic parents were heterozygous for the same mutation. This mutation affected GFAP solubility and promoted filament aggregation. The presence of the wild‐type protein rescued mutational effects, consistent with the recessive nature of this mutation. Conclusions This study is the first report of AxD caused by a homozygous mutation in GFAP . The clinical implication is while examining patients with characteristic features on suspicion of AxD, GFAP screening is recommended even without a supportive family history. © 2020 International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2041249-6
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