Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells

BACKGROUND Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally.Cisplatin(DDP)is one of the most common and effective chemotherapies for patients with gastric cancer,but DDP resistance remains a severe clinical challenge.AIM To explore the function of M2 polarized macrophages-derived exosomal microRNA(miR)-588 in the modulation of DDP resistance of gastric cancer cells.METHODS M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis.The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers.The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells.The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay,apoptosis analysis,colony formation assay,Western blot analysis,qPCR analysis,and luciferase reporter assay in SGC7901 and SGC7901/DDP cells,and by tumorigenicity analysis in nude mice.RESULTS M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin(IL)-13 and IL-4.Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance.M2 polarized macrophagesderived exosomes could transfer in gastric cancer cells to enhance DDP resistance.Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells.miR-588 promoted DDP-resistant gastric cancer cell growth in vivo.miR-588 was able to target cylindromatosis(CYLD)in gastric cancer cells.The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP.CONCLUSION In conclusion,we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD.miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.

Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury

Propofol has been shown to exert neuroprotective effects on the injured spinal cord.However,the effect of propofol on the blood-spinal cord barrier（BSCB） after ischemia/reperfusion injury（IRI） is poorly understood.Therefore,we investigated whether propofol could maintain the integrity of the BSCB.Spinal cord IRI（SCIRI） was induced in rabbits by infrarenal aortic occlusion for 30 minutes.Propofol,30 mg/kg,was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion.Then,48 hours later,we performed histological and m RNA/protein analyses of the spinal cord.Propofol decreased histological damage to the spinal cord,attenuated the reduction in BSCB permeability,downregulated the m RNA and protein expression levels of matrix metalloprotease-9（MMP-9） and nuclear factor-κB（NF-κB）,and upregulated the protein expression levels of occludin and claudin-5.Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression,by inhibiting the NF-κB signaling pathway,and by maintaining expression of tight junction proteins.

Cellulose synthesis genes CESA6 and CSI1 are important for salt stress tolerance in Arabidopsis

Soil salinity is a widespread abiotic stress constraint threatening agricultural production, as it severely inhibits growth and development of crops. Several salt stress signaling pathways have been discovered in the model plant Arabidopsis thaliana, which include components for sensing the stress, transmitting the signal and regulating the downstream genes （Deinlein et al. 2o14; Julkowska and Testerink 2015）. In nature, plant roots directly encounter heterogeneous soils and therefore their responses to saline environments require dynamic changes in growth, a process in which plant cell walls play important roles （Tenhaken 2o15）. However, the molecular mechanisms underlying cell wall remodeling under stress conditions are still unclear.

Cytotoxicity of six copper-bearing intrauterine devices on Chinese hamster ovary cells: the influence of frame, shape and copper surface area

Objective To evaluate the cytotoxicity of six commonly used copper-bearing intrauterine devices （Cu-IUDs） on Chinese hamster ovary （CHO-K1） cells and to investigate the influence of frame, shape and copper surface area of Cu-IUDs on cell toxicity.Methods Cu-IUDs were incubated in 10% FBS-DMEM/F12 culture medium at 37 ℃ for 24 h. The extracts were analyzed by flame atomic absorption spectrometer and were then diluted into different concentrations with culture medium. Finally, cytotoxicity of these original and diluted extracts on CHO-K1 cells was detected by cell counting kit-8 （CCK-8） assay.Results The viabilities of cells treated with the original extracts of six Cu-IUDs （TCu220C bulb, TCu220C, GCu220, GCu300, Yuangong Cu270 and Yuangong Ⅱ- 300） were all below 10% and the cupric ion concentrations in these extracts were 28.22 mg/L, 31.80 mg/L, 92.80 mg/L, 99.74 mg/L, 114.90 mg/L and 119.20 mg/L, respectively. After these original extracts were diluted, significant differences in cytotoxicity were exhibited. IUDs with larger copper surface areas （GCu300 and Yuangong Ⅱ-300） showed more cytotoxicity than those with smaller areas （GCu220 and Yuangong Cu270） respectively; When different shapes of Cu-IUDs were compared, TCu220C bulb showed lower cytotoxicity than TCu220C, and GCu300 exhibited higher toxicity than Yuangong Ⅱ-300; TCu220C displayed significantly lower cytotoxicity than GCu220 due to their differences in frames.Conclusion We presented evidence on the cytotoxic effects of copper ions released from Cu-IUDs on CHO-K1 cells and found that shape, frame together with copper surface area of Cu-IUDs had obvious influence on the cytotoxicity.