Identification and validation of Temozolomide resistance hub gene LncRNA MOCS2-DT in glioblastoma

Background:Temozolomide(TMZ)is an important adjuvant chemotherapy drug after glioma surgery.However,with the progress of treatment,most patients will gradually develop drug resistance.Long non-coding RNA(lncRNA)in the prediction and reversal of chemotherapy drug resistance possesses great potential.Methods:1.The clinical data and RNA expression matrix of glioma patients were downloaded from the Chinese Glioma Genome Atlas(CGGA),and the clinical data and RNA expression profiles of 47 patients who only received TMZ chemotherapy after surgery were selected;2.WGCNA was performed on RNA expression profiles to find modules highly correlated with survival time and lncRNAs with high connectivity in modules.Core lncRNA were further screened from the GEO database(P<0.05);survival analysis,correlation analysis,enrichment analysis and co-expression analysis were performed;and 3.A TMZ concentration gradient induced glioma-resistant cells(U251TR).Cell proliferation toxicity assays and real-time quantitative PCR were used to verify the core lncRNA and identify the biological characteristics of U251TR.Results:1.According to the WGCNA analysis,it was found that the pink module is highly correlated with survival time and that there are 17 core lncRNAs with high connectivity in the pink module.2.The expression of the core lncRNA MOCS2-DT in the U251 resistant strain was significantly lower than that in the sensitive strain(P<0.05).3.U251TR cells had significantly larger cell bodies with irregular shapes.U251TR cells had a stronger tolerance to TMZ than U251 cells,and the resistance index was about four times higher(P<0.05).4.The expression levels of MGMT and ABCG2 in U251TR cells were significantly higher than those in parental U251 cells(P<0.05),and the expression levels of MOCS2-DT in U251TR cells were significantly lower than those in parental U251 cells(P<0.05).5.The survival time and survival rate of patients with low expression of MOCS2-DT were significantly lower than those of patients with high expression of MOCS2-DT in patients who only received TMZ chemotherapy after surgery.6.The enrichment analysis results show that the mRNA co-expressed with MOCS2-DT is enriched in synapse organization,regulation of membrane potential and signal release,indicating that MOCS2-DT is closely related to these functions.Conclusion:Targeted regulation of MOCS2-DT may reverse the drug resistance of glioma,improve the prognosis of patients and prolong the survival time of patients.

Effects of Mangiferin on the Expression of TNF-α,iNos,ICAM-1 and Its mRNA in the Heart,Brain and Kidneys of SHR

[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.

Mangiferin alleviates renal infammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway

Objective: Hypertension is a low-grade infammation state of the disease and was easily complicated by kidneys’ infammatory response. Mangiferin(MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-infammatory activity. However, the effects of MGF on renal infammatory injury in spontaneously hypertensive rats(SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal infammatory injury in SHRs.Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological,immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR(RT-PCR) analysis.Results: The results showed that the levels of interleukin 6(IL-6), tumor necrosis factor-a(TNF-a), monocyte chemoattractant protein-1(MCP-1) and recombinant chemokine C-C-Motif receptor 2(CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen(BUN) and serum uric acid(SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.Conclusion: Our study proved that the kidneys of SHRs had significant infammatory injury, and MGF had the protective effects on renal infammatory injury in SHRs;The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤

高血压是一种低度炎症状态的疾病,通常伴有心脏炎症。芒果苷(MGF)是一种天然糖基蒽酮,具有很强的抗炎活性。然而,MGF对高血压患者心脏炎症损伤的作用尚不清楚。本文研究MGF对自发性高血压大鼠(SHRs)心脏炎症损伤的保护作用及其机制。采用10周龄雄性SHRs和10周龄正常雄性Wistar-Kyoto(WKY)大鼠,对SHRs使用10、20、40 mg/kg剂量的MGF,连续8周。测量其收缩压(SBP)水平,采集心脏组织进行形态学、免疫组化、ELISA、western blot和实时反转录PCR分析。结果表明模型组大鼠收缩压水平均较对照组显著升高,SHRs自发升高收缩压水平,各剂量MGF对收缩压水平无显著影响。模型组大鼠心脏组织形态学结果显示有明显的炎症性损伤,MGF对这种损伤有显著的抑制作用。同时,MGF显著抑制了SHRs IL-6和TNF-α含量的升高。此外,MGF还显著抑制了SHRs MCP-1、CCR2蛋白以及其mRNA表达的增加。研究表明MGF并不会降低SHRs大鼠的SBP水平,但MGF对SHRs大鼠的心脏炎症损伤具有保护作用,这可能是因为MGF部分抑制了MCP-1/CCR2信号通路表达的原因。

Crystalline mesoporous transition metal oxides： hard-templating synthesis and application in environmental catalysis

象 MCM-41 和 SBA-15 那样的 Mesoporous 硅石拥有高表面区域，订的 nanopores，和优秀热稳定性，并且有经常用作催化剂支持。尽管 mesoporous 金属氧化物与 mesoporous 硅石相比有更低的表面区域，他们通常有更多样化的功能。Mesoporous 金属氧化物能经由一条软模板或难模板的途径被综合，并且这些材料最近在环境催化作用发现了一些应用，例如器官的污染物质的公司氧化， N2O 分解，和消除。在这评论，我们作为难模板用 mesoporous 硅石总结 mesoporous 转变金属氧化物的合成，在环境催化作用加亮这些材料的申请，并且供应为未来开发的一些前景。

New Cassane Diterpenoids from the Seed Kernels of Caesalpinia cucullata, Exhibit Anti-inflammatory Effect in vitro by Inhibiting iNOS Enzymatic Activity

Inflammation is a complex biological response to stimulation.Natural cassane diterpenoids from Caesalpinia genus exhibit significant anti-inflammation activity.Eight new cassane diterpenoids(1-8)along with seven known ones(9-15)were obtained from the seed kernels of Caesalpinia cucullata Roxb.This is the first report on chemical investigation of the seed kernels of C.cucullata,and the cassane diterpenes were found in this plant for the first time.Their structures were elucidated based on the extensive spectroscopic analyses,and the absolute configurations were identified by ECD calculation and X-ray crystallography.All compounds were evaluated for their anti-inflammation activity by inhibiting NO production in LPS-induced RAW 264.7 cells.Compounds 1-2 and 9-11 exhibited effective inhibitory activity with inhibition rate more than 50%.The iNOS enzyme activity and molecular docking experiments were performed to explore the preliminary mechanism.Eventually,a potential anti-inflammatory mechanism revealed that the bioactive cassane inhibited overproduction of NO by targeting key residues in the iNOS active cavity to reduce iNOS enzymatic activation.

P2-type layered high-entropy oxides as sodium-ion cathode materials

P2-type layered oxides with the general Na-deficient composition Na_(x)TMO_(2)(x<1,TM:transition metal)are a promising class of cathode materials for sodium-ion batteries.The open Na+transport pathways present in the structure lead to low diffusion barriers and enable high charge/discharge rates.However,a phase transition from P2 to O2 structure occurring above 4.2 V and metal dissolution at low potentials upon discharge results in rapid capacity degradation.In this work,we demonstrate the positive effect of configurational entropy on the stability of the crystal structure during battery operation.Three different compositions of layered P2-type oxides were synthesized by solid-state chemistry,Na_(0.67)(Mn_(0.55)Ni_(0.21)Co_(0.24))O_(2),Na_(0.67)(Mn_(0.45)Ni_(0.18)Co_(0.24)Ti_(0.1)Mg_(0.03))O_(2) and Na_(0.67)(Mn_(0.45)Ni_(0.18)Co_(0.18)Ti_(0.1)Mg_(0.03)Al_(0.04)Fe_(0.02))O_(2) with low,medium and high configurational entropy,respectively.The high-entropy cathode material shows lower structural transformation and Mn dissolution upon cycling in a wide voltage range from 1.5 to 4.6 V.Advanced operando techniques and post-mortem analysis were used to probe the underlying reaction mechanism thoroughly.Overall,the high-entropy strategy is a promising route for improving the electrochemical performance of P2 layered oxide cathodes for advanced sodium-ion battery applications.

高分辨率核磁共振在颅颈大动脉狭窄介入治疗中的临床应用进展

介入治疗是颅颈大动脉狭窄患者预防缺血性脑卒中事件发生的重要手段,精确地评估未来发生脑卒中的风险和预判介入治疗后并发症的发生可以最大限度地使患者获益。高分辨率核磁共振(HR-MRI)具有优越的空间分辨率和无创的特点,被广泛应用于介入诊疗活动中。本文围绕HR-MRI在介入治疗颅颈大动脉狭窄中的应用进展进行综述。