Hsa_circ_0003596 enhances the development of cell renal clear cell carcinoma through the miR-502-5p/IGF1/PI3K/AKT axis

Accumulating research findings have shown that circular RNAs (circRNAs) play an indispensable role in tumorigenesis and tumor progression. The current study aimed to explore the role and modulatory mechanism of hsa_circ_0003596 in clear cell renal cell carcinoma (ccRCC). Quantitative real-time polymerase chain reaction was adopted to detect the expression of hsa_circ_0003596 in ccRCC tissue and cell lines. 5-Ethynyl-2′-deoxyuridine, cell counting kit 8 and the colony formation assay were utilized to assess the proliferation potential of the ccRCC cells. Transwell along with wound healing assays were adopted to quantify infiltration coupled with the migration potential of the cells. The current research study found that the circRNA hsa_circ_0003596 was overexpressed in ccRCC tissue and cell lines. Further, result showed that hsa_circ_0003596 was associated with distant metastasis of renal cancer. Notably, the knockdown of hsa_circ_0003596 can lower the proliferation, infiltration and migration potential of ccRCC cells. The results of in vivo experiments found that the reduction of hsa_circ_0003596 significantly hampered the growth of tumors in mice. In addition, it was evident that hsa_circ_0003596 acts as a “molecular sponge” for miR-502-5p to upregulate the expression of the microRNA-502-5p (miR-502-5p) target insulin-like growth factor 1 (IGF1R). Furthermore, it was found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling was the downstream cascade of hsa_circ_0003596/miR-502-5p/IGF1R cascade, which is partly responsible for the cancer-promoting effect. Overall, the results of the present study showed that hsa_circ_0003596 facilitated the proliferation, infiltration and migration of ccRCC through the miR-502-5p/IGF1R/PI3K/AKT axis. Therefore, it was evident that hsa_circ_0003596 can serve as a possible biomarker and therapeutic target against ccRCC.     

环境激素DBP对拟南芥试管形态发生的影响

报道了酞酸酯类化合物DBP对拟南芥试管形态发生的影响。利用不同浓度的DBF处理拟南芥茎段外植体,切片观察拟南芥茎段试管形态发生过程中脱分化、分化及再分化的变化情况。结果发现：拟南芥茎段外植体在对照组培养基上生长良好,首先是愈伤组织产生,而后愈伤组织块增大,颜色呈淡绿色,生长旺盛,并有分化出芽现象;添加0．01mg／L、0．1mg／L和1．0mg／LDBP,茎段愈伤组织诱导率低,且高浓度时愈伤组织出现褐化、活力差的现象;培养12h、24h、2d、3d、7d、14d、21d和28d茎段显微切片结果显示,DBP具有抑制拟南芥试管形态发生的作用,随着DBP浓度的增加呈现剂量抑制效应。     

ATM pathway is essential for ionizing radiation-induced autophagy

BackgroundATM plays an important role in response to DNA damage, while the roles of ATM in radiation-induced autophagy are still unclear in cervical cancer cells.MethodsHuman cervical cancer cells, Hela, were used, and cell models with ATM^?/? and MAPK14^?/? were established by gene engineering. Western blot was implemented to detect protein expression. MDC staining and GFP-LC3 relocalization were used to detect autophagy. CCK-8 was used to detect cell viability. Radiosensitivity was analyzed by colony formation assays. Co-immunoprecipitation was used to detect the interaction between different proteins, and apoptosis was detected by flow cytometry.ResultsAfter radiation autophagy was induced, illustrated by the increase of MAPLC3-II/MAPLC3-I ratio and decrease of p62, and phosphorylation of ATM simultaneously increased. ATM^?/? cells displayed hypersensitivity but had no influence on IR-induced apoptosis. Then inhibitor of ATM, KU55933, ATM and MAPK14 silencing were used, and autophagy was induced by IR more than 200% in control, and only by 35.72%, 53.18% and 24.76% in KU55933-treated cells, ATM^?/? and MAPK14^?/? cells, respectively. KU55933 inhibited IR-induced autophagy by activating mTOR pathways. ATM silencing decreased the expression of MAPK14 and mTOR signals significantly. Beclin's bond to PI3KIII and their interaction increased after IR, while in ATM^?/? and MAPK14^?/? cells this interaction decreased after IR. Both ATM and MAPK14 interacted with Beclin, while ATM^?/? and MAPK14^?/? cells showed no interaction.ConclusionsATM could promote IR-induced autophagy via the MAPK14 pathway, the mTOR pathway, and Beclin/PI3KIII complexes, which contributed to the effect of ATM on radiosensitivity.     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration     

Ferritinophagy is Involved in Experimental Subarachnoid Hemorrhage-Induced Neuronal Ferroptosis

Ferroptosis is a novel form of regulated cell death involved in the pathophysiological process of experimental subarachnoid hemorrhage (SAH), but how neuronal ferroptosis occurs remains unknown. In this study, we report that SAH-induced ferroptosis is macroautophagy/autophagy dependent because the inhibition of autophagy by knocking out autophagy-related gene 5 (ATG5) apparently mitigated SAH-induced ferroptosis. We created an experimental SAH model in Sprague–Dawley rats to determine the possible mechanism. We found that SAH can trigger neuronal ferroptosis, as evidenced by the disruption of iron homeostasis, elevation of intracellular lipid peroxidation (LPO) and decreased expression of ferroptosis–protective proteins. Then, we inhibited autophagy by ATG5 gene knockout, showing that autophagy inhibition can reduce the intracellular iron level and LPO, improve the expression of ferroptosis–protective proteins, and subsequently alleviate SAH-induced cell death. Additionally, autophagy inhibition also attenuated SAH prognostic indicators, such as brain edema, blood–brain barrier permeability, and neurological deficits. These findings not only present an opinion that SAH triggers neuronal ferroptosis via activation of ferritinophagy but also indicate that regulating ferritinophagy and maintaining iron homeostasis could provide clues for the prevention of early brain injury.

     

Bioremediation of Polyaromatic Hydrocarbon-Contaminated Sediments in Aerated Bioslurry Reactors

Treatment of dredged sediments contaminated by polyaromatic hydrocarbons (PAHs) is a significant problem in the New York/New Jersey (NY/NJ) Harbor. 0.5 m³-scale slurry-phase bioreactors were used to determine whether bioaugmentation with a PAH-degradative bacterial consortium, or with the salt marsh grass S. alterniflora, could enhance the biodegradation of PAHs added to dredged estuarine sediments from the NY/NJ Harbor. The results were compared to biodegradation effected by the indigenous sediment microbial community. Sediments were diluted 1:1 in tap water and spiked to a final concentration of 20 mg/kg dry weight sediment of phenanthrene, anthracene, acenaphthene, fluorene, fluoranthene, and pyrene. The sediment slurry was then continuously sparged with air over 3 months. In all bioreactors a rapid reduction of greater than 95% of the initial phenanthrene, acenaphthene, and fluorene occurred within 14 days. Pyrene and fluoranthene reductions of 70 to 90% were achieved by day 77 of treatment. Anthracene was more recalcitrant and reductions ranged from 30 to 85%. Separate experiments showed that the sediment microbial communities mineralized ¹⁴C-pyrene and ¹⁴C-phenanthrene. PAH degradation, and the number of phenanthrene-degrading bacteria, were not enhanced by microbial or plant bioaugmentation. These data demonstrate that bioaugmentation is not required to effect efficient remediation of PAH-contaminated dredged sediments in slurry-phase bioreactors.     

Exogenous silicon (Si) increases antioxidant enzyme activity and reduces lipid peroxidation in roots of salt-stressed barley (Hordeum vulgare L.)

Two contrasting barley (Hordeum vulgare L.) cultivars, i.e. Kepin No.7 (salt sensitive) and Jian 4 (salt tolerant), were grown hydroponically to study the effect of exogenous silicon (Si) on time dependent changes of the activities of major antioxidant enzymes and of lipid peroxidation in roots under salt stress. Enzymes included: superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione reductase (GR). Three treatments with three replicates were investigated consisting of a control (basal nutrients with neither NaCl nor Si added), 120 mmol/L-1 NaCl, and 120 mmol/L-1 NaCl +1.0 mmol/L-1 Si. Plant roots were harvested 2, 4 and 6 days after treatment and assayed for activities of the antioxidant enzymes and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), and electrolytic leakage percentage (ELP). The activities of SOD, POD and CAT in roots of salt-stressed plants were significantly stimulated at Day 2 compared to control plants, but considerably decreased at Day 4 and onward. GR activity in roots of salt-stressed plants remained unchanged at Day 2, but significantly decreased at Day 4 and onward. However, exogenous Si significantly enhanced these enzyme activities in roots of salt-stressed plants compared to Si-deprived salt treatments. This Si effect was time-dependent and became stronger as the experiments continued. The tendency of change in the activities of antioxidant enzymes and the concentration of GSH coincided with the concentration of MDA, the end product of lipid peroxidation, and the ELP. Higher activities of antioxidant enzymes, and higher concentration of GSH, but lower concentration of MDA and lower ELP were noted in cultivar Jian 4 compared to Kepin No. 7, implying genotypic differences with Jian 4 being less susceptible to stress-dependent membrane lipid peroxidation. The effects of Si-enhanced salt tolerance are discussed with respect to cell membrane integrity, stability and function in barley.