Suppressive Effect of Liposomes Containing DNA Coding for Diphtheria Toxin A-Chain on Cells Transformed with Bovine Leukemia Virus

A recombinant plasmid which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (BLV-LTR) was constructed to test a novel application of liposomes as antiviral agents. The promoter activity of BLV-LTR was estimated by the chloramphenicol acetyltransferase (CAT) assay using a plasmid which contains the coding sequence of CAT under the control of BLV-LTR (pBLVCAT). When BLV-infected cells were transfected with pBLVCAT, CAT activity was detected. BLV-uninfected cell lines, however, showed no detectable CAT activity. The plasmid DNA entrapped in liposomes was added to BLV-infected cells in culture. Syncytium formation induced by BLV-infected cells was effectively suppressed by the liposomes containing the gene for DT-A under the control of BLV-LTR. Conversely, liposomes containing the gene for DT-A without a promoter showed no such effect. DT-A gene-containing liposomes with BLV-LTR did not affect formation of syncytium induced by bovine immunodeficiency virus. These observations indicate that BLV-infected cells were readily targeted on the level of gene expression. This strategy could be applied to the treatment of BLV-induced B-cell proliferation of cattle, and further to other viral/neoplastic diseases where specific gene expression is exerted.     

基于益生菌治疗帕金森病的研究进展

帕金森病是常见的神经退行性疾病,其发病原因至今尚未明确,目前的治疗方法价格昂贵、效果差且副作用大。帕金森病患者常见胃肠道功能障碍,帕金森病和肠道菌群之间的关联已得到实验证实,患者有望通过益生菌改善肠道菌群达到治疗的目的。工程益生菌的出现使得人们可以按照自己的意愿改造益生菌,提高其稳定性和靶向性,展现出其特有的应用潜力。本文将从益生菌治疗帕金森病的研究现状出发,阐述益生菌治疗帕金森病的可能机制,进一步分析工程益生菌治疗帕金森病的可行性,为该疾病的安全治疗提供新的思路。     

An interdisciplinary approach to the treatment of a hyperfunctional voice disorder

The purpose of this article is to describe the treatment of a 45-year-old male with a hyperfunctional voice disorder by a biofeedback therapist and a speech-language pathologist. The interdisciplinary approach to the treatment of this voice disorder involved the combined use of traditional voice therapy techniques and EMG biofeedback procedures together with cognitive behavioral therapy. Voice therapy was facilitated through the use of a computer-based, speech-monitoring system. The remediation of this voice disorder was attributed to the collaborative efforts of two professionals representing diverse professional training and treatment protocols. The results showed reductions in muscle activity in the infrahyoid and laryngeal areas as well as improved use of proper breathing and voicing onset behaviors. Follow-up at 10 and 15 months posttreatment intervals indicated that the client had retained all target voice skills and the tension reduction/biofeedback skills. Results suggest that interdisciplinary, collaborative efforts using biofeedback and voice therapy can prove beneficial in the treatment of hyperfunctional voice disorders.Note: Neither author has been compensated in any way for the use of the CAFET System nor does either have any financial interest in the company.     

PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target

Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.     

毛乌素沙地杨柴灌木林恢复演替过程中土壤活性有机碳组分变化特征

土壤活性有机碳是土壤有机碳(SOC)的活性部分,是衡量土壤质量和健康状况的重要指标,能够反映植被恢复演替过程中土壤环境的早期变化。但在SOC贫瘠的沙地,长期恢复演替如何影响土壤活性有机碳组分尚不清楚。本研究以毛乌素沙地杨柴人工灌木林为研究对象,分别选取未造林(CK)与造林年限9 a、18 a和30 a的杨柴人工灌木林,探究毛乌素沙地杨柴人工灌木林恢复演替过程中土壤可溶性有机碳(DOC)、微生物量碳(MBC)、易氧化有机碳(ROC)和SOC变化规律。结果表明：(1)毛乌素沙地杨柴灌木林随恢复演替年限增加土壤固碳能力增强,但在恢复演替18 a时出现转折点,恢复演替18—30 a时土壤固碳速率相对减缓;(2)表层0—10 cm土壤DOC、MBC和ROC对恢复演替响应较为敏感,恢复演替过程中表层土壤活性有机碳各组分含量逐渐升高;(3)恢复演替年限并未对土壤活性有机碳占SOC比例产生显著影响,同时也未显著改变碳库活度。综上所述,毛乌素沙地杨柴灌木林恢复演替有助于土壤活性有机碳和SOC积累,但长期恢复演替是否持续对土壤活性有机碳固持产生积极作用仍需进一步研究。     

基于转录组测序的宁夏枸杞不同品种果实活性成分合成差异表达基因分析

为探究不同品种宁夏枸杞果实活性成分生物合成相关基因的表达水平,筛选关键差异表达基因(differentially expressed genes,DEGs),揭示宁夏枸杞品种间活性成分含量差异的分子机制,本研究采用Illumina NovaSeq 6000高通量测序技术,对宁夏枸杞‘宁杞1号’和‘宁杞7号’青果期、转色期及成熟期果实进行转录组测序,比较2个品种果实不同发育期相关基因表达谱的变化。结果显示:转录组测序共获得811818178条clean reads,有121.76 Gb有效数据。‘宁杞1号’和‘宁杞7号’在青果期、转色期和成熟期差异表达基因分别有2827、2552和2311个;分别有2153、2050和1825个差异基因在基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析和同源蛋白簇(clusters of orthologous groups of proteins,KOG)分析等6个数据库中被成功注释。青果期、转色期和成熟期果实的差异表达基因,在GO数据库分别有1307、865和624个被富集到生物学过程、细胞组分及分子功能3个部分中;KEGG通路富集结果均集中在代谢途径、次生代谢物生物合成和植物-病原互作过程;在KOG数据库,3个发育期分别注释了1775、1751和1541个差异表达基因。对注释的基因进行PubMed数据库检索,在青果期、转色期和成熟期分别筛选到与枸杞活性成分合成相关的差异表达基因18、26和24个,这些基因主要参与类胡萝卜素、类黄酮、萜类、生物碱和维生素等代谢途径。选取7个差异表达基因进行RT-qPCR验证,结果与转录组测序数据表达趋势一致。本研究从转录水平为不同品种宁夏枸杞活性成分含量差异提供了初步证据,为进一步挖掘枸杞活性成分生物合成的关键基因及解析其表达调控机制提供了研究基础。     

基于碳酸酐酶IX的肿瘤成像和治疗研究进展

碳酸酐酶IX (carbonic anhydrase IX, CAIX)是一种在乏氧肿瘤细胞表面特异性过表达的跨膜蛋白,具有调节肿瘤细胞内外酸碱度的功能,与肿瘤增殖、侵袭和转移息息相关。因此,CAIX是一个很有潜力的肿瘤成像和治疗靶点。本文详细阐述了基于CAIX的肿瘤成像、治疗和诊疗一体化的研究进展,并对CAIX作为抗肿瘤靶点的应用前景进行了展望。     

Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound

Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l -lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy.