急性髓系白血病mRNA与非编码RNA差异表达谱及CeRNA调控网络分析

利用GEO数据库(gene expression omnibus database)通过生物信息学分析方法探讨急性髓系白血病(acute myelogenous leukemia,AML)的发病机制。检索GEO数据库中AML相关芯片数据集GSE142698、GSE142699和GSE96535。利用GEO2R分析得到差异mRNAs、miRNAs以及差异lncRNAs。利用在线生物信息学分析工具DAVID对差异mRNAs进行GO富集分析和KEGG通路分析。利用miRWalk数据库预测AML相关miRNAs的靶向mRNAs,利用Spongescan数据库预测AML相关miRNAs的靶向lncRNAs,构建lncRNA-miRNA-mRNA竞争性内源RNA （competing endogenous RNA,ceRNA）调控网络。共筛选出29个显著差异mRNAs、70个显著差异miRNAs和20 005个显著差异lncRNAs。GO富集分析和KEGG通路分析显示,差异表达基因主要涉及蛋白磷酸化、细胞分裂、细胞增殖的负调控、基因表达的正向调节、周期蛋白依赖的丝氨酸/苏氨酸激酶活性的调节等生物过程以及细胞周期、细胞衰老、癌症通路、PI3K-Akt通路等信号通路。将miRWalk数据库预测的靶向mRNAs与差异mRNAs取交集,Spongescan数据库预测的靶向lncRNAs与差异lncRNAs取交集,分别确定了25个mRNAs、6个lncRNAs参与AML相关ceRNA调控网络的构建。结果表明,lncRNAs可能作为关键的ceRNA,通过调控miRNA和相关靶基因参与AML的发生与发展,研究结果为AML诊断和治疗的分子生物学研究提供了新的依据。     

N-Heterocyclic Carbene-Palladium Polymers Network: Recyclable Pre-catalyst for Effective Suzuki–Miyaura Coupling Reaction in Water

Rational design of high-efficiency N-heterocyclic carbene (NHC) palladium catalyst is of great importance to modern organic synthesis, especially in chemical and pharmaceutical industries. Herein, we fabricate a polymer network containing N-heterocyclic carbene palladium (PNNHC-Pd) catalytic active sites via an immobilization process. The N-heterocyclic carbene palladium can serve as a promising linkage of polymer network as well as an effective catalytic active site owing to its structural preference and strong σ-donating ability with palladium species. The results display that N-heterocyclic carbene palladium disperses homogeneously in polymer network, thus rendering PNNHC-Pd excellent catalytic activity, high stability and superior reusability in palladium-catalyzed Suzuki–Miyaura coupling reaction in aqueous medium. This work provides a new insight into the development of heterogenization of homogeneous catalysts based on polymer network.     

Five New Phenolic Glycosides from Viburnum luzonicum

Viburnum luzonicum is widely distributed in China. Its branch extracts showed potential α-amylase and α-glucosidase inhibitory activities. In order to discover new bioactive constituents, five undescribed phenolic glycosides, viburozosides A−E ( 1 – 5 ), were obtained by bioassay-guided isolation coupled with HPLC-QTOF-MS/MS analysis. Their structures were elucidated by spectroscopic analyses, including 1D NMR, 2D NMR, ECD, and ORD. All compounds were tested for their α-amylase and α-glucosidase inhibitory potency. Compound 1 showed significantly competitive inhibition against α-amylase (IC₅₀=17.5 μM) and α-glucosidase (IC₅₀=13.6 μM).     

Engeletin alleviates cerebral ischemia reperfusion-induced neuroinflammation via the HMGB1/TLR4/NF-κB network

High-mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti-inflammatory activity. Herein, we examined the mechanism of engeletin-mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose-dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL-1β, TNF-α, IL-6 and IFN-γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl-2 protein levels, while suppressing Bax and Cleaved Caspase-3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF-κB and attenuated nuclear transfer of nuclear factor kappa B (NF-κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF-κB inflammatory network.     

CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C-X3-C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1-induced cell motility is upregulated through intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre-treated with CX3CR1 monoclonal antibody (mAb) and small-interfering RNA (siRNA). The CX3CL1-CX3CR1 axis activates promoted PLCβ/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCβ, PKCα, c-Src inhibitors reduced CX3CL1-induced c-Jun phosphorylation, c-Jun translocation into the nucleus and c-Jun binding to the ICAM-1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM-1 expression through the CX3CR1 and the PLCβ/PKCα/c-Src signal pathway, suggesting that CX3CL1-CX3CR1-mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.     

Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.     

山东省假性肥大型肌营养不良的RFLP分析 Ⅰ．可疑携带者的基因型确定

本文选用10个DMD基因内部和桥探针,对山东省9个地区的21个DMD／BMD家系的173名成员进行RFLP分析,其中可疑携带者55人,多数家系应用1－3个探针,有基因重组家庭选用4－5个探针,便可完成多态分析,RFLP分析可以确定85．45％的可疑携带者（≥95％可信限）,即13人确定为携带者,30人排除携带者,另有4人风险大幅提高,通过这些探针的群体多态检测和不同家庭结构和类型的应用分析,我们提出了在中国人群中DMD／SMD基因诊断的基本程序。     

杂交试验中的最佳样本含量

杂交试验是一项费时费钱的工作,因此在进行试验之前如能进行严密的设计,给出试验所需的样本大小是十分必要的,统计学中常见的估计样本容理的公式不宜应用于杂交试验,本文分两种情况给出了杂交试验中样本容量的估计公式,据此估计出的样本容量安排杂交试验,可在满足试验者要求的条件下,使试验的总成本最低或使试畜的总头数最少。     

Research Progress on Anti-Inflammatory Mechanisms of Black Ginseng

In recent years, black ginseng, a new type of processed ginseng product, has attracted the attention of scholars globally. Ginsenoside and ginseng polysaccharide, the main active substances of black ginseng, have been shown to carry curative effects for many diseases. This article focuses on the mechanism of their action in anti-inflammatory response, which is mainly divided into three aspects: activation of immune cells to exert immune regulatory response; participation in inflammatory response-related pathways and regulation of the expression level of inflammatory factors; effect on the metabolic activity of intestinal flora. This study identifies active anti-inflammatory components and an action mechanism of black ginseng showing multi-component, multi-target, and multi-channel characteristics, providing ideas and a basis for a follow-up in-depth study of its specific mechanism.