Upregulation of p72 enhances malignant migration and invasion of glioma cells by repressing Beclin1 expression

p72 is the member of the DEAD-box RNA helicase family, which can unwind double-stranded RNA and is efficient for microRNA (miRNA, miR) processing. However, its specific role in glioma has not been elucidated. First, the expression of p72 in glioma cell lines and tissues was explored using Western blot. To explore the role of p72 on glioma progression, adenovirus inhibiting p72 was transfected into A172 and T98G cells. Cell autophagy was determined using GFPLC3 dots, and cell apoptosis was determined using flow cytometry. The effect of Beclin1 was explored using GFP-LC3 dots, flow cytometry, and colony formation. The possible miRNAs that target the 3′-untranslated region (3′-UTR) of Beclin1 were predicted using TargetScan. Dual luciferase reporter assay was applied to determine whether these miRNAs bind to the 3′-UTR of Beclin1. The expression of p72 was significantly increased in glioma cell lines and tissues. Autophagy-related protein Beclin1 was found to be significantly enhanced when p72 was inhibited. The accumulation of GFP-LC3 dots was significant in cells transfected with ad-sh-p72 compared with ad-con. Colony formation capacity and cell apoptosis were also found to be significantly decreased with p72 inhibition. Furthermore, upregulation of Beclin1 contributes to A172 cell autophagy, invasion, and apoptosis. Overexpression of p72 induces increased miR-34-5p and miR-5195-3p expression in A172 and T98G cells. Beclin1 was the target gene of miR-34-5p and miR-5195-3p. In conclusion, we found for the first time that overexpression of p72 decreased Beclin1 expression partially by increasing miR-34-5p and miR-5195-3p expression in A172 and T98G cells.     

Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways

Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS. Consistent findings were obtained in vivo. Additionally, IV inhibited H₂O₂-induced cytotoxicity and apoptosis. However, these effects were partially reversed following the use of an HO-1 inhibitor in vitro. Further studies revealed that IV significantly inhibited MAPK phosphorylation, reduced NF-κB nuclear translocation, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in RAW 264.7 cells. In vivo, pretreatment with IV attenuated histopathological changes, infiltration of polymorphonuclear granulocytes and endothelial activation, decreased the expression of ICAM-1 and VCAM-1, reduced the levels of MPO and MDA, and increased the content of GSH and SOD in ALI. Furthermore, IV treatment effectively increased Nrf2 and HO-1 expression in lung tissues. Therefore, IV may offer a protective role against LPS-induced ALI by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.     

淹水胁迫下江南牡丹生长及光合特性研究

以3年生江南牡丹品种‘凤丹白’为材料,利用盆栽淹水法,设置正常管理、轻度胁迫和重度胁迫3个水平,研究不同淹水胁迫水平对牡丹生长和光合特性的影响。结果表明：经过30 d胁迫后,正常管理、轻度胁迫和重度胁迫下的江南牡丹苗高生长量分别为3.6、1.1和0.73 cm,地径生长量分别为0.21、0.11和0.06 cm,植株总生物量增加量分别为7.0、3.0和2.75 g,淹水胁迫和正常生长差异显著,淹水胁迫严重影响了江南牡丹的生长。同时,在正常管理时,牡丹总叶绿素含量升高,而在淹水胁迫下呈下降趋势。淹水胁迫不同时间根系活力均呈下降趋势且随着胁迫程度的增加下降越大。正常管理下光合速率逐渐增加而胁迫条件下光合速率逐渐降低。同时胁迫条件下,牡丹蒸腾速率、气孔导度均明显下降;轻度淹水胁迫下胞间CO2浓度先升高后降低;而重度胁迫下胞间CO2浓度呈现逐渐升高的变化趋势。淹水胁迫对牡丹根系活力、茎段生长和叶片光合特性影响较大。该研究结果为江南牡丹耐涝胁迫机理研究奠定了理论基础。     

BI-RADS 3级对乳腺病灶患者的诊断结果及影响因素分析

目的:回顾性分析超声BI-RADS 3级对乳腺病灶患者的诊断结果及影响因素。方法:选择2014年8月至2017年8月上海交通大学医学院附属第九人民医院和复旦大学附属华山医院北院收治的168例乳腺病灶患者,回顾性分析其影像学资料及病理分析结果。分析BI-RADS 3级对乳腺病灶的阴性诊断率,采用Kim分级对BI-RADS 3级结果进行重新分级,分析影响BI-RADS分级及重新分级的主要因素。结果:168例BI-RADS 3级乳腺病灶中,159例为良性病变,9例为恶性。168例BI-RADS 3级乳腺病灶的阳性预测值为5.4%(9/168),阴性预测值为94.6%(159/168)。病灶数目、年龄、医师年资、病灶大小对BI-RADS 3级良恶性乳腺病灶判断无明显影响,而BI-RADS 3级恶性乳腺病灶较良性病灶更易触诊(P 0.05)。重新分级发现,124例仍为BI-RADS 3级,44例上升至BI-RADS 4级,重新分级恶性病灶的检出率为100%(9/9),假阳性率为20.8%(35/168)。病灶多发、年龄≥40岁更可能评估为BI-RADS 4级(P0.05),医师年资、病灶大小、病灶触及情况对重新分级无明显影响(P0.05)。结论:BI-RADS 3级对乳腺良性病灶有较高的阴性诊断率,重新分级可提高乳腺恶性病灶的检出率,但会造成较高的假阳性率,影响BI-RADS分级的主要因素为病灶可否扪及,影响重新分级的主要因素为患者年龄及乳腺病灶是否多发。     

Genome Characteristics and Evolution of Pseudorabies Virus Strains in Eastern China from 2017 to 2019

Since late 2011, outbreaks of pseudorabies virus(PRV) have occurred in southern China causing major economic losses to the pig industry. We previously reported that variant PRV forms and recombination in China could be the source of continued epidemics. Here, we analyzed samples from intensive pig farms in eastern China between 2017 and 2019, and sequenced the main glycoproteins(gB, gC, gD, and gE) to study the evolution characteristics of PRV. Based on the g C gene, we found that PRV variants belong to clade 2 and detected a founder effect during by the PRV epidemic. In addition,we detected inter-and intra-clade recombination; in particular, inter-clade recombination in the g B genes of strains FJ-ZXF and FJ-W2, which were recombinant with clade 1 strains. We also found specific amino-acid changes and positively selected sites, possibly associated with functional changes. This analysis of the emergence of PRV in China illustrates the need for continuous monitoring and the development of vaccines against specific variants of PRV.     

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12‐dimethylbenz(a)anthracene (DMBA)‐treated mammary carcinogenesis in Sprague‐Dawley (SD) rats and MCF‐7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA‐induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt‐b₅ and CYP₄₅₀) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl‐2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA‐induced mammary cancer in SD animals and Michigan cancer foundation‐7 mammary cancer cells.     

HMGB1 release from trophoblasts contributes to inflammation during Brucella melitensis infection

Brucella melitensis infection causes acute necrotizing inflammation in pregnant animals; however, the pathophysiological mechanisms leading to placentitis are unknown. Here, we demonstrate that high‐mobility group box 1 (HMGB1) acts as a mediator of placenta inflammation in B. melitensis‐infected pregnant mice model. HMGB1 levels were increased in trophoblasts or placental explant during B. melitensis infection. Inhibition of HMGB1 activity with neutralising antibody significantly reduced the secretion of inflammatory cytokines in B. melitensis‐infected trophoblasts or placenta, whereas administration of recombinant HMGB1 (rHMGB1) increased the inflammatory response. Mechanistically, this decreased inflammatory response results from inhibition of HMGB1 activity, which cause the suppression of both mitogen‐activated protein kinases and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activation. Moreover, neutralising antibody to HMGB1 prevented B. melitensis infection‐induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in trophoblasts. In contrast, in vitro stimulation of trophoblasts with rHMGB1 caused activation of NADPH oxidase and increased the production of ROS, which contributes to high bacterial burden within trophoblasts or placenta. In vivo, treatment with anti‐HMGB1 antibody increases the number of Brucella survival within placenta in B. melitensis‐infected pregnant mice but successfully reduced the severity of placentitis and abortion.     

长链非编码RNA RLM通过影响AMPK的磷酸化调节HepG2细胞中的脂质沉积

长非编码RNAs（long noncoding RNAs,lncRNAs）是一类长度大于200 nt、不能编码蛋白质的RNA分子,可通过AMPK、胰岛素受体等多种信号通路,调节细胞糖脂代谢。本研究发现,HepG2细胞中一条未报道的长链非编码RNA,命名为lnc-RLM（lnc-regulate lipid metabolism）。通过敲低HepG2细胞中lnc RLM,检测细胞中甘油三脂含量及脂质代谢相关调节因子表达量。结果显示,实验组较对照组甘油三酯含量显著升高（P<0.05）;AMPK磷酸化水平显著下调,脂质合成相关因子SREBP 1c和FAS表达量上调;同时,细胞中乙酰辅酶A羧化酶（ACC）活性较对照组显著上调（P<0.05）。在lnc RLM敲低的HepG2细胞中,利用AMPK激动剂（A-769662）作用细胞24 h,结果显示,降低的AMPK磷酸化水平并不会因AMPK激动剂的作用而显著升高。本研究结果说明,HepG2细胞中敲低lnc-RLM表达量,可通过影响AMPK磷酸化水平,调节HepG2细胞中脂质沉积。这为今后研究AMPK活性调节提供新的可能,也为代谢性疾病的治疗提供了新思路。     

长非编码RNA THOR在肿瘤中的作用

长非编码RNA（long non-coding RNA,lncRNA）是一类长度超过200 nt并且缺乏蛋白质编码潜能的RNA分子。最初lncRNA被认为是由RNA聚合酶Ⅱ转录的副产物,且无生物学功能。随着转录组测序技术的发展,大规模的lncRNA被鉴定出来。越来越多的证据表明,lncRNA参与多种生物学过程,包括基因印记、基因组重排、染色质修饰、细胞周期调控、转录、剪接、mRNA降解和翻译。lncRNA异常表达与人类多种疾病相关,尤其是增生性疾病,包括胃癌、肝癌和直肠癌等。其中,睾丸相关的高度保守的致癌长非编码RNA（testis-associated highly-conserved oncogenic long non-coding RNA,THOR）是一种非常保守的非编码RNA,在睾丸中特异性表达,并广泛存在于人的多种肿瘤组织中,如肝癌、胃癌、鼻咽癌、肾细胞癌、骨肉瘤、视网膜母细胞瘤、黑色素瘤、非小细胞肺癌和舌鳞状细胞癌中,在其发生和发展过程中发挥重要作用。在鼻咽癌、肾细胞癌、骨肉瘤、黑色素瘤、非小细胞肺癌和舌鳞状细胞癌中,THOR主要通过与胰岛素样生长因子2 mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1,IGF2BP1）相互作用,促进肿瘤细胞的增殖。在肝癌中,THOR分别通过PTEN/AKT和β-联蛋白信号促进癌细胞的增殖和肝肿瘤干细胞的扩增。在胃癌和骨肉瘤中,THOR主要通过提高SOX9的表达增强癌细胞的干性。在视网膜母细胞瘤中,THOR主要通过提高c-myc的表达促进癌细胞增殖。在鼻咽癌中,THOR主要通过提高YAP的表达增强癌细胞的干性。