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Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL. 相似文献
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Lei Yang You-Ling Shi Yan Ma Wei-Wei Ren Guang-Ming Pang Jiao Liu 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2022,130(1):43-52
Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis. 相似文献
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文题释义:
细胞膜片技术:是在体外接种培养高密度的细胞,使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞,因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点,已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。
成骨细胞:主要由内外骨膜和间充质始祖细胞分化而来,在复杂的骨形成过程中发挥着主要的功能,承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能,能定向分化为成骨细胞,其成骨分化过程可受多种因素的影响,如细胞因子的调控、遗传因素和激素水平等。背景:现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知,如何将生长因子与组织工程细胞膜片技术相整合,最终将其用于骨缺损修复具有重要意义。
目的:探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。
方法:体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片,选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片,CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度;然后对骨髓间充质干细胞膜片进行成骨诱导,通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。
结果与结论:单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性,最佳质量浓度为100 μg/L(P < 0.001),单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖,最佳质量浓度为20 μg/L(P < 0.001),而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001);经成骨诱导后,4组膜片在形态学上无明显差异,均能诱导骨髓间充质干细胞膜片的成骨分化,其中联合组钙结节最明显(P < 0.001),可显著促进膜片晚期成骨分化并抑制其早期成骨分化,具有明显的协同促进作用(P < 0.001)。结果表明,骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用,既可以促进骨髓间充质干细胞膜片增殖,又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇)
中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程 相似文献
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Seyed Mehdi BagheriMofidi Majid Pouladian Seyed Behnamedin Jameie Ali Abbaspour Tehrani-Fard 《Australasian physical & engineering sciences in medicine / supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine》2016,39(3):717-726
Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm3. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation. 相似文献