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胸腺醌对牙龈间充质干细胞/祖细胞中 Toll 样受体和多能性因子的调节作用。

Thymoquinone-Mediated Modulation of Toll-like Receptors and Pluripotency Factors in Gingival Mesenchymal Stem/Progenitor Cells.

机构信息

Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrecht's University, 24105 Kiel, Germany.

Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo 12613, Egypt.

出版信息

Cells. 2022 Apr 25;11(9):1452. doi: 10.3390/cells11091452.

DOI:10.3390/cells11091452
PMID:35563755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9101758/
Abstract

Thymoquinone (TQ), the key active component of Nigella sativa (NS), demonstrates very promising biomedical anti-inflammatory, antioxidant, antimicrobial and anticancer properties. Several investigations have inspected the modulative activities of TQ on different stem/progenitor cell types, but its possible role in the regulation of gingival mesenchymal stem/progenitor cells (G-MSCs) has not yet been characterized. For the first time, this study investigates the effects of TQ on G-MSCs’ stemness and Toll-like receptor expression profiles. G-MSCs (n = 5) were isolated, sorted via anti-STRO-1 antibodies and then disseminated on cell culture dishes to create colony-forming units (CFUs), and their stem/progenitor cell attributes were characterized. TQ stimulation of the G-MSCs was performed, followed by an examination of the expression of pluripotency-related factors using RT-PCR and the expression profiles of TLRs 1−10 using flowcytometry, and they were compared to a non-stimulated control group. The G-MSCs presented all the predefined stem/progenitor cells’ features. The TQ-activated G-MSCs displayed significantly higher expressions of TLR3 and NANOG with a significantly reduced expression of TLR1 (p < 0.05, Wilcoxon signed-rank test). TQ-mediated stimulation preserves G-MSCs’ pluripotency and facilitates a cellular shift into an immunocompetent-differentiating phenotype through increased TLR3 expression. This characteristic modulation might impact the potential therapeutic applications of G-MSCs.

摘要

姜酮(TQ)是黑种草(NS)的关键活性成分,具有非常有前景的生物医学抗炎、抗氧化、抗菌和抗癌特性。一些研究已经研究了 TQ 对不同干细胞/祖细胞类型的调节活性,但它在调节牙龈间充质干细胞/祖细胞(G-MSCs)中的作用尚未得到表征。本研究首次探讨了 TQ 对 G-MSCs 干性和 Toll 样受体表达谱的影响。分离 G-MSCs(n = 5),通过抗 STRO-1 抗体进行分选,然后铺板培养以形成集落形成单位(CFUs),并对其干细胞/祖细胞特性进行了鉴定。用 TQ 刺激 G-MSCs,然后使用 RT-PCR 检测多能性相关因子的表达,使用流式细胞术检测 TLRs 1-10 的表达谱,并与未经刺激的对照组进行比较。G-MSCs 表现出所有预先定义的干细胞/祖细胞特征。TQ 激活的 G-MSCs 显示 TLR3 和 NANOG 的表达显著升高,而 TLR1 的表达显著降低(p < 0.05,Wilcoxon 符号秩检验)。TQ 介导的刺激通过增加 TLR3 的表达,保留 G-MSCs 的多能性,并促进细胞向具有免疫功能的分化表型转变。这种特征性的调节可能会影响 G-MSCs 的潜在治疗应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/55153205fdab/cells-11-01452-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/c545cf487530/cells-11-01452-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/188ee2551839/cells-11-01452-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/e29715f4f926/cells-11-01452-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/b6ab1db929ca/cells-11-01452-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/55153205fdab/cells-11-01452-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/c545cf487530/cells-11-01452-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/188ee2551839/cells-11-01452-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/e29715f4f926/cells-11-01452-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/b6ab1db929ca/cells-11-01452-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05c/9101758/55153205fdab/cells-11-01452-g005.jpg

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本文引用的文献

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Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells.黑种草醌在癌症及癌症干细胞联合治疗中的治疗潜力
World J Clin Oncol. 2021 Jul 24;12(7):522-543. doi: 10.5306/wjco.v12.i7.522.
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PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus.
高压氧和炎症对人牙龈间充质干细胞/祖细胞的影响。
Cells. 2023 Oct 18;12(20):2479. doi: 10.3390/cells12202479.
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: Nature's Gift for Periodontal Health.大自然赋予的牙周健康礼物。
Antioxidants (Basel). 2021 Apr 30;10(5):712. doi: 10.3390/antiox10050712.
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Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies.样本量、功效和效应量再探:临床前、临床和实验室研究中简化而实用的方法。
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