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81.
Wu‐Xia Qiu Xiao‐Li Ma Xiao Lin Fan Zhao Di‐Jie Li Zhi‐Hao Chen Ke‐Wen Zhang Ru Zhang Pai Wang Yun‐Yun Xiao Zhi‐Ping Miao Kai Dang Xiao‐Yang Wu Ai‐Rong Qian 《Journal of cellular and molecular medicine》2020,24(1):317-327
Microtubule actin cross‐linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3‐E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast‐specific Osterix (Osx) promoter‐driven Macf1 conditional knockout mice (Macf1f/fOsx‐Cre). The Macf1f/fOsx‐Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/fOsx‐Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/fOsx‐Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/fOsx‐Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease. 相似文献
82.
Simon Borna Ales Drobek Jarmila Kralova Daniela Glatzova Iva Splichalova Matej Fabisik Jana Pokorna Tereza Skopcova Pavla Angelisova Veronika Kanderova Julia Starkova Petr Stanek Orest V. Matveichuk Nataliia Pavliuchenko Katarzyna Kwiatkowska Majd B. Protty Michael G. Tomlinson Meritxell Alberich‐Jorda Vladimir Korinek Tomas Brdicka 《Journal of cellular and molecular medicine》2020,24(2):1980-1992
WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis. 相似文献
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Jiheng Zhan Xing Li Dan Luo Yu Hou Yonghui Hou Shudong Chen Zhifeng Xiao Jiyao Luan Dingkun Lin 《Journal of cellular and molecular medicine》2020,24(9):5317-5329
Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 μmol/L) markedly facilitated BMSC differentiation into neuron‐like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI. 相似文献
85.
目的:探讨小骨窗显微手术治疗基底节区高血压脑出血的效果及对血清gaspase切割的细胞角蛋白18(CCCK-18)、补体C1q肿瘤坏死因子相关蛋白3(CTRP-3)水平的影响。方法:选取2016年5月至2018年5月我院收治的160例基底节区高血压脑出血患者,按照随机数表法将其分为观察组(n=82)和对照组(n=78)。对照组采用传统大骨瓣开颅术治疗,观察组采用小骨窗显微手术治疗。观察和比较两组的临床疗效,血肿清除率、术中出血量、术后意识恢复时间、住院时间,治疗前后NIHSS、ADL评分、血清CCCK-18、CTRP-3水平的变化及并发症的发生情况。结果:治疗后,观察组总有效率显著高于对照组[95.12%vs. 79.48%](P0.05);血肿清除率、术中出血量、术后意识恢复时间、住院时间均显著优于对照组[(93.62±3.58)%vs.(85.40±2.19)%,(92.47±12.56)mL vs.(189.25±26.47) mL,(2.01±0.58) d vs.(8.69±2.03) d,(13.39±2.08) d vs.(19.45±3.76) d](P0.05);NIHSS评分显著低于对照组[(9.76±1.42)分vs.(20.57±3.26)分](P0.05);ADL评分显著高于对照组[(86.42±8.64)分vs.(75.39±7.02)分](P0.05);血清CCCK-18水平显著低于对照组[(201.76±32.59) U/L vs.(237.57±39.20) U/L,(29.59±5.19) ng/mL vs.(42.97±7.94)ng/mL](P0.05);CTRP-3水平显著高于对照组[(289.59±35.19)ng/mL vs.(232.97±27.94)ng/mL](P0.05);并发症总发生率显著低于对照组[3.65%(3/82) vs. 14.10%(11/78)](P0.05)。结论:小骨窗显微手术治疗基底节区高血压脑出血的疗效显著,可更有效清除血肿,缓解血肿压迫,改善神经功能,减少继发性损伤,安全性高,可能与其降低血清CCCK-18水平及升高CTRP-3水平有关。 相似文献
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Nicholas M. Wragg Diogo Mosqueira Lia Blokpeol‐Ferreras Andrew Capel Darren J. Player Neil R. W. Martin Yang Liu Mark P. Lewis 《Biotechnology journal》2020,15(1)
In vitro 3D tissue‐engineered (TE) structures have been shown to better represent in vivo tissue morphology and biochemical pathways than monolayer culture, and are less ethically questionable than animal models. However, to create systems with even greater relevance, multiple integrated tissue systems should be recreated in vitro. In the present study, the effects and conditions most suitable for the co‐culture of TE skeletal muscle and bone are investigated. High‐glucose Dulbecco's modified Eagle medium (HG‐DMEM) supplemented with 20% fetal bovine serum followed by HG‐DMEM with 2% horse serum is found to enable proliferation of both C2C12 muscle precursor cells and TE85 human osteosarcoma cells, fusion of C2C12s into myotubes, as well as an upregulation of RUNX2/CBFa1 in TE85s. Myotube formation is also evident within indirect contact monolayer cultures. Finally, in 3D co‐cultures, TE85 collagen/hydroxyapatite constructs have significantly greater expression of RUNX2/CBFa1 and osteocalcin/BGLAP in the presence of collagen‐based C2C12 skeletal muscle constructs; however, fusion within these constructs appears reduced. This work demonstrates the first report of the simultaneous co‐culture and differentiation of 3D TE skeletal muscle and bone, and represents a significant step toward a full in vitro 3D musculoskeletal junction model. 相似文献
89.