甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。     

Clinical features and hematological findings of COVID-19 patients with blood transfusion

This paper aims to illustrate the clinical characteristics, hematological findings, and blood transfusion information of Coronavirus disease 2019 (COVID-19) patients. Twenty-three COVID-19 patients were treated and transfused with blood products in Wuhan First Hospital from February 12 to March 20, 2020. The patients were divided into a survivor group and a non-survivor group, respectively, according to whether the patient had been discharged or died. The results demonstrated at the time of initial blood transfusion, that the non-survivor group possessed a lower platelet (PLT) than that of the survivor group (P<0.001), and PLT were below the normal range in 6 (85.7%) non-survivor group and in 2 (12.5%) survivor group (P<0.01). Over half of these patients had abnormalities in fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT), and international normalized ratio (INR), but no significant difference was found between the non-survivor group and survivor group. The non-survivor group had a dramatically higher D-Dimers and disseminated intravascular coagulation (DIC) scores than those of the survivor group (P<0.01). Six (85.7%) non-survivors but none of the survivors had a DIC score greater than 6 (P<0.001). Fifteen (93.8%) survivors and 2 (28.6%) non-survivors were transfused with RBC (P<0.01). The non-survivors (5/7) possessed a higher proportion for using AP than the survivors (2/16). The study suggests that COVID-19 patients who undergo blood transfusion usually possess coagulation dysfunction, and DIC may be closely related to deteriorating clinical outcomes.     

Efficient Editing of an Adenoviral Vector Genome with CRISPR/Cas9

Immunotherapy based on genetic modification of T cells has played an important role in the treatment of tumors and viral infections. Moreover, adenoviral vectors engineered with improved safety due to their inability to integrate into the host genome have been key in the clinical application of T cell therapy. However, the commonly used adenoviral vector Ad5 exhibits low efficiency of infection of human T cells and the details of the intracellular trafficking pathway of adenoviral vectors in human primary T cells remains unclear. Resolution of these issues will depend on successful modification of the adenoviral vector. To this end, here we describe the successful establishment of a simple and efficient method for editing adenoviral vectors in vitro using the CRISPR-Cas9 gene editing system to target the adenoviral fiber gene. Electronic supplementary materialThe online version of this article (10.1007/s12088-020-00905-3) contains supplementary material, which is available to authorized users.     

Phosphorylation of Novel Interactors of Wild Soybean GsSnRK1 Protein Kinase

Plant Molecular Biology Reporter - Plant SnRK1 kinases have been reported to participate in regulating many aspects of plant biology including resistance to biotic and abiotic stresses. Wild...     

High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities

Cell Biology and Toxicology - Autophagy is a conserved lysosomal degradation process, and abnormal autophagy has been associated with various pathological processes, e.g., neurodegeneration,...     

SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling

ObjectivesCutaneous wound healing is one of the major medical problems worldwide. Epigenetic modifiers have been identified as important players in skin development, homeostasis and wound repair. SET domain–containing 2 (SETD2) is the only known histone H3K36 tri‐methylase; however, its role in skin wound healing remains unclear.Materials and MethodsTo elucidate the biological role of SETD2 in wound healing, conditional gene targeting was used to generate epidermis‐specific Setd2‐deficient mice. Wound‐healing experiments were performed on the backs of mice, and injured skin tissues were collected and analysed by haematoxylin and eosin (H&E) and immunohistochemical staining. In vitro, CCK8 and scratch wound‐healing assays were performed on Setd2‐knockdown and Setd2‐overexpression human immortalized keratinocyte cell line (HaCaT). In addition, RNA‐seq and H3K36me3 ChIP‐seq analyses were performed to identify the dysregulated genes modulated by SETD2. Finally, the results were validated in functional rescue experiments using AKT and mTOR inhibitors (MK2206 and rapamycin).ResultsEpidermis‐specific Setd2‐deficient mice were successfully established, and SETD2 deficiency resulted in accelerated re‐epithelialization during cutaneous wound healing by promoting keratinocyte proliferation and migration. Furthermore, the loss of SETD2 enhanced the scratch closure and proliferation of keratinocytes in vitro. Mechanistically, the deletion of Setd2 resulted in the activation of AKT/mTOR signalling pathway, while the pharmacological inhibition of AKT and mTOR with MK2206 and rapamycin, respectively, delayed wound closure.ConclusionsOur results showed that SETD2 loss promoted cutaneous wound healing via the activation of AKT/mTOR signalling.     

Fitness of F1 hybrids between 10 maternal wild soybean populations and transgenic soybean

Transgenic Research - The releasing of transgenic&nbsp;soybeans (Glycine max (L.) Merr.) into farming systems raises concerns that transgenes might escape from the soybeans via pollen into...