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991.
Mohammadhossein Hassanshahi Yu-Wen Su Samira Khabbazi Chia-Ming Fan Qian Tang Xuesen Wen Jian Fan Ke-Ming Chen Cory J. Xian 《Journal of cellular physiology》2019,234(9):16549-16561
Methotrexate (MTX), a widely used antimetabolite in paediatric cancer to treatment, has been widely reported to cause bone loss and bone marrow (BM) microvascular (particularly sinusoids) damage. Investigations must now investigate how MTX-induced bone loss and microvasculature damage can be attenuated/prevented. In the present study, we examined the potency of icariin, an herbal flavonoid, in reducing bone loss and the dilation/damage of BM sinusoids in rats caused by MTX treatment. Groups of young rats were treated with five daily MTX injections (0.75 mg/kg) with and without icariin oral supplementation until Day 9 after the first MTX injection. Histological analyses showed a significant reduction in the bone volume/tissue volume (BV/TV) fraction (%) and trabecular number in the metaphysis trabecular bone of MTX-treated rats, but no significant changes in trabecular thickness and trabecular spacing. However, the BV/TV (%) and trabecular number were found to be significantly higher in MTX + icariin-treated rats than those of MTX alone-treated rats. Gene expression analyses showed that icariin treatment maintained expression of osteogenesis-related genes but suppressed the induction of adipogenesis-related genes in bones of MTX-treated rats. In addition, icariin treatment attenuated MTX-induced dilation of BM sinusoids and upregulated expression of endothelial cell marker CD31 in the metaphysis bone of icariin + MTX-treated rats. Furthermore, in vitro studies suggest that icariin treatment can potentially enhance the survival of cultured rat sinusoidal endothelial cells against cytotoxic effect of MTX and promote their migration and tube formation abilities, which is associated with enhanced production of nitric oxide. 相似文献
992.
993.
Shupeng Shi Mimi Tang Honglei Li Hui Ding Yangfan Lu Lijuan Gao Qian Wu Luo Zhou Yujiao Fu Bo Xiao Mengqi Zhang 《Journal of cellular physiology》2019,234(6):9316-9327
Angiogenesis is positively correlated with the survival rate of stroke patients. Therefore, studying factors that initiate and promote angiogenesis after ischemic stroke is crucial for finding novel and effective treatment targets that improve the prognosis of stroke. X-box binding protein l splicing (XBP1s) plays a positive regulatory role in cell proliferation and angiogenesis. However, the role and mechanism of XBP1s on the proliferation of brain microvascular endothelial cells (BMECs) and angiogenesis after cerebral ischemia remains unclear. In the current study, we investigated the role XBP1s plays in BMEC proliferation and angiogenesis following cerebral ischemia. In this study, the roles of XBP1s on cell survival, apoptosis, cycle migration, and angiogenesis were determined in oxygen-glucose deprivation (OGD) treated BMECs. The expression of XBP1s in BMECs, which were exposed to OGD at 0, 2, 4, and 6 hr, increased in a time-dependent manner. The overexpression of XBP1s promoted cell survival, cell cycle, migration, and angiogenesis of BMECs, and inhibited the apoptosis in OGD-treated BMECs. In addition, the overexpression of XBP1s promoted the expression of cyclin D1, matrix metalloproteinase (MMP-2), and MMP-9, but inhibited cleaved Caspase-3 and cleaved Caspase-9 expression in OGD-treated BMECs. The overexpression of XBP1s also promoted the expression of hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, phosphatidylinositol-4,5-bisphosphate 3-kinase, p-AKT, p-mTOR, p-GSK3β, and p-extracellular signal-regulated kinase1/2 in OGD-treated BMECs. The effect of XBP1s silencing was opposite to that of XBP1s overexpression. In conclusion, using an in vitro OGD model, we demonstrated that XBP1s may be a promising target for ischemic stroke therapy to maintain BMECs survival and induce angiogenesis. 相似文献
994.
995.
Hui-Bo Wang Si-Hui Huang Man Xu Jun Yang Jian Yang Ming-Xin Liu Chun-Xia Wan Hai-Han Liao Di Fan Qi-Zhu Tang 《Journal of cellular physiology》2019,234(9):15654-15667
Cardiac remodeling is associated with inflammation and apoptosis. Galangin, as a natural flavonol, has the potent function of regulating inflammation and apoptosis, which are factors related to cardiac remodeling. Beginning 3 days after aortic banding (AB) or Sham surgery, mice were treated with galangin for 4 weeks. Cardiac remodeling was assessed according to echocardiographic parameters, histological analyses, and hypertrophy and fibrosis markers. Our results showed that galangin administration attenuated cardiac hypertrophy, dysfunction, and fibrosis response in AB mice and angiotensin II-treated H9c2 cells. The inhibitory action of galangin in cardiac remodeling was mediated by MEK1/2–extracellular-regulated protein kinases 1/2 (ERK1/2)–GATA4 and phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT)–glycogen synthase kinase 3β (GSK3β) activation. Furthermore, we found that galangin inhibited inflammatory response and apoptosis. Our findings suggest that galangin protects against cardiac remodeling through decreasing inflammatory responses and apoptosis, which are associated with inhibition of the MEK1/2–ERK1/2–GATA4 and PI3K–AKT–GSK3β signals. 相似文献
996.
Multiple studies have reported different methods in treating gestational diabetes mellitus (GDM); however, the relationship between miR-335-5p and GDM still remains unclear. Here, this study explores the effect of miR-335-5p on insulin resistance and pancreatic islet β-cell secretion via activation of the TGFβ signaling pathway by downregulating VASH1 expression in GDM mice. The GDM mouse model was established and mainly treated with miR-335-5p mimic, miR-335-5p inhibitor, si-VASH1, and miR-335-5p inhibitor + si-VASH1. Oral glucose tolerance test (OGTT) was conducted to detect fasting blood glucose (FBG) fasting insulin (FINS). The OGTT was also used to calculate a homeostasis model assessment of insulin resistance (HOMA-IR). A hyperglycemic clamp was performed to measure the glucose infusion rate (GIR), which estimated β-cell function. Expressions of miR-335-5p, VASH1, TGF-β1, and c-Myc in pancreatic islet β-cells were determined by RT-qPCR, western blot analysis, and insulin release by ELISA. The miR-335-5p mimic and si-VASH1 groups showed elevated blood glucose levels, glucose area under the curve (GAUC), and HOMA-IR, but a reduced GIR and positive expression of VASH1. Overexpression of miR-335-5p and inhibition of VASH1 contributed to activated TGFβ1 pathway, higher c-Myc, and lower VASH1 expressions, in addition to downregulated insulin and insulin release levels. These findings provided evidence that miR-335-5p enhanced insulin resistance and suppressed pancreatic islet β-cell secretion by inhibiting VASH1, eventually activating the TGF-β pathway in GDM mice, which provides more clinical insight on the GDM treatment. 相似文献
997.
【目的】对滇金丝猴粪便微生物来源的β-半乳糖苷酶进行异源表达和纯化,并研究其酶学性质。【方法】从滇金丝猴粪便微生物的宏基因组中克隆出一个β-半乳糖苷酶基因galRBM20_1,对该基因进行异源表达和酶学性质分析。构建含有T7强启动子的pEASY-E2-galRBM20_1质粒,转化至大肠杆菌BL21(DE3),经IPTG诱导表达后进行酶学性质研究。【结果】滇金丝猴粪便来源的β-半乳糖苷酶(galRBM20_1)最适pH为5.0,在pH 4–7之间能保留70%及其以上的活性。最适温度为45°C,在37°C和45°C下耐受1 h,酶活不变。特别的是,该酶具有良好的Na Cl稳定性,经1–5 mol/L的Na Cl作用1 h后,相对酶活均能超过初始酶活:当NaCl的作用浓度为4 mol/L时,β-半乳糖苷酶相对酶活最高(146%);当NaCl的作用浓度为5mol/L时,β-半乳糖苷酶的相对酶活仍达到135%。【结论】本研究从滇金丝猴粪便微生物的宏基因库中克隆得到β-半乳糖苷酶基因galRBM20_1,并成功在大肠杆菌BL21(DE3)表达,首次从动物胃肠道宏基因组中获得具有耐盐和转糖基产Galactooligosaccharides(GOS)性能的β-半乳糖苷酶。该酶具有良好的耐盐性,和较广的pH作用范围,使其在食品、生物技术领域和环保方面的发展具有良好的应用价值。 相似文献
998.
999.
Wei Liu Dandan Tang Rui Shi Jiazhang Lian Lei Huang Jin Cai Zhinan Xu 《Biotechnology and bioengineering》2019,116(12):3312-3323
S-Adenosyl-l -methionine (SAM) is an important small molecule compound widely used in treating various diseases. Although l -methionine is generally used, the low-cost dl -methionine is more suitable as the substrate for industrial production of SAM. However, d -methionine is inefficient for SAM formation due to the substrate-specificity of SAM synthetase. In order to increase the utilization efficiency of dl -methionine, intracellular conversion of d -methionine to l -methionine was investigated in the type strain Saccharomyces cerevisiae BY4741 and an industrial strain S. cerevisiae HDL. Firstly, via disruption of HPA3 encoding d -amino acid-N-acetyltransferase, d -methionine was accumulated in vivo and no N-acetyl-d -methionine production was observed. Further, codon-optimized d -amino acid oxidase (DAAO) gene from Trigonopsis variabilis (Genbank MK280686) and l -phenylalanine dehydrogenase gene (l -PheDH) from Rhodococcus jostii (Genbank MK280687) were introduced to convert d -methionine to l -methionine, SAM concentration and content was increased by 110% and 72.1% in BY4741 (plasmid borne) and increased by 38.2% and 34.1% in HDL (genome integrated), by feeding 0.5 g/L d -methionine. Using the recently developed CRISPR tools, the DAAO and l -PheDH expression cassettes were integrated into the HPA3 and SAH1 loci while SAM2 expression was integrated into the SPE2 and GLC3 loci of HDL, and the resultant strain HDL-R2 accumulated 289% and 192% more SAM concentration and content, respectively, by feeding 0.5 g/L dl -methionine. Further, in a 10 L fed-batch fermentation process, 10.3 g/L SAM were accumulated with the SAM content of 242 mg/g dry cell weight by feeding 16 g/L dl -methionine. The strategies used here provided a promising approach to enhance SAM production using low-cost dl -methionine. 相似文献
1000.
Plant and Soil - Improving our understanding of ecosystem responses to land-use intensification requires explicit consideration of linkages between aboveground and belowground communities. Here, we... 相似文献