BACKGROUNDThe immune system of many invertebrates, including insects, has been shown to comprise memory, or specific immune priming. However, knowledge of the molecular mechanisms especially the candidate immune-related genes mediated the specificity of the immune priming are still very scarce and fragmentary. We therefore used two closely related Gram-negative pathogenic bacteria (Photorhabdus luminescens TT01 and P. luminescens H06) as the priming agents and employed Illumina/Solexa platform to investigate the transcriptional changes of the haemocytes of Bombyx mori larvae after priming.RESULTSIn total, 23.0 Gbp of sequence data and 153,331,564 reads were generated, representing 10,496 genes. Approximately 89% of the genes or sequenced reads could be aligned to the silkworm reference genome. The differentially expressed genes (DEGs) of PBS-vs-TT01 (up-regulated expression of TT01 relative to PBS), PBS-vs-H06 (up-regulated expression of H06 relative to PBS) and TT01-vs-H06 (up-regulated expression of H06 relative to TT01) were 707, 159 and 461 respectively. In addition, expression patterns of 25 selected DEGs derived from quantitative real-time polymerase chain reaction (qRT-PCR) were consistent with their transcript abundance changes obtained by transcriptomic analyses. The DEGs are mainly related to pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), signaling molecular, effector molecules, phagosome and spliceosome, indicating that they have participated in the regulation of the specific immune priming in the B. mori larvae.CONCLUSIONSThe transcriptome profiling data sets from this study will provide valuable resources to better understand the molecular and biological mechanisms regulating the specificity of invertebrates' immune priming. All these will shed light on controlling insect pests or preventing epidemic of infectious diseases in economic invertebrates.

2018-12-01·BMC Genomics2区 · 生物学

Phenotypic and genomic comparison of Photorhabdus luminescens subsp. laumondii TT01 and a widely used rifampicin-resistant Photorhabdus luminescens laboratory strain

2区 · 生物学

ArticleOA

作者: Heermann, Ralf ; Pfeiffer, Friedhelm ; Habermann, Bianca ; Langer, Angela ; Gazanis, Athanasios ; Eckstein, Simone ; Zamora-Lagos, Maria-Antonia

BACKGROUNDPhotorhabdus luminescens is an enteric bacterium, which lives in mutualistic association with soil nematodes and is highly pathogenic for a broad spectrum of insects. A complete genome sequence for the type strain P. luminescens subsp. laumondii TT01, which was originally isolated in Trinidad and Tobago, has been described earlier. Subsequently, a rifampicin resistant P. luminescens strain has been generated with superior possibilities for experimental characterization. This strain, which is widely used in research, was described as a spontaneous rifampicin resistant mutant of TT01 and is known as TT01-Rif^R.RESULTSUnexpectedly, upon phenotypic comparison between the rifampicin resistant strain and its presumed parent TT01, major differences were found with respect to bioluminescence, pigmentation, biofilm formation, haemolysis as well as growth. Therefore, we renamed the strain TT01-Rif^R to DJC. To unravel the genomic basis of the observed differences, we generated a complete genome sequence for strain DJC using the PacBio long read technology. As strain DJC was supposed to be a spontaneous mutant, only few sequence differences were expected. In order to distinguish these from potential sequencing errors in the published TT01 genome, we re-sequenced a derivative of strain TT01 in parallel, also using the PacBio technology. The two TT01 genomes differed at only 30 positions. In contrast, the genome of strain DJC varied extensively from TT01, showing 13,000 point mutations, 330 frameshifts, and 220 strain-specific regions with a total length of more than 300 kb in each of the compared genomes.CONCLUSIONSAccording to the major phenotypic and genotypic differences, the rifampicin resistant P. luminescens strain, now named strain DJC, has to be considered as an independent isolate rather than a derivative of strain TT01. Strains TT01 and DJC both belong to P. luminescens subsp. laumondii.

2018-02-01·Toxicon3区 · 医学

Combinatorial effect of Photorhabdus luminescens TT01 and Bacillus thuringiensis Vip3Aa16 toxin against Agrotis segetum

3区 · 医学

Article

作者: Boukedi, Hanen ; Abdelkefi-Mesrati, Lobna ; Sellami, Sameh ; Jallouli, Wafa ; Frikha, Fakher ; Tounsi, Slim

The entomopathogenic Photorhabdus luminescens TT01 is a promoting bacterium that controls effectively many insect pests. Indeed, it exhibited a mortality rate of 32.36% against the first instar larvae of the turnip moth Agrotis segetum, when it was used at a concentration of 5 × 10⁷ cells/ml but no toxicity against the second instar larvae in the same condition. P. luminescens TT01 oral toxicity is associated to septicaemia since cells fraction exhibited the highest mortality rate of 34%. In order to enhance P. luminescens TT01 insecticidal potential, combination with Bacillus thuringiensis Vip3Aa16 toxin was tested. An improvement of insecticidal activity was shown. Indeed, 100% mortality of A. segetum first instar larvae was obtained after 2 days of treatment, when using TT01 cells and Vip3Aa16 toxin at a concentration of 5 × 10⁷ cells/ml and 9.025 ng/cm², respectively. Moreover, growth inhibition rate of 45% of the second instar larvae was observed, when using the same combination. A. segetum mortality could be the result of several alterations in the midgut epithelium caused by Vip3Aa16 toxin, allowing a rapid invasion of the hemocoel by TT01 cells as demonstrated by histopathological study. Clear symptoms of intoxication were observed for all combinations tested, including swelling, vesicle formation, cytoplasm vacuolization and brush border membrane lysis. Taken together, these results promote the use of P. luminescens TT01 as a potent bioinsecticide to control effectively A. segetum by oral treatment in a mixture with Vip3Aa16 toxin.

项与 TT-01 相关的新闻（医药）

2022-11-10

·生物谷

CD：南京医科大学汪强虎团队，揭示胶质母细胞瘤进化关键

，此项研究找到了处于不同演化阶段的IDH野生型GBM病灶的分子“标记“NES。具有高NES特征的肿瘤细胞也拥用更高的可塑性，能更好的“制造”对自己有利的微环境。比如，招募并驯化巨噬细胞，而这些被驯化的免疫细胞是我们人体免疫系统的重要组成部分。如果把我们的免疫系统想象成一支军队，那免疫细胞就是这支军队中的一个个士兵，他们分工合作守护着我们的健康。谁能想到兢兢业业的免疫细胞居然会在我们体内的“异己”——肿瘤细胞的策反下，成为自己的敌人呢？今天就给大家讲讲肿瘤细胞是如何“劫持“免疫细胞成为“帮凶”并一起成长的。近日，由南京医科大学汪强虎领衔的研究团队，在国际顶尖肿瘤学期刊Cancer Discovery发表最新研究成果[1]。他们首次利用异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤（GBM）多发病灶模型，揭示了肿瘤与免疫微环境协同自然演化的过程，为GBM的治疗提供了新的潜在靶点。文章首页截图 IDH野生型GBM是成人中最常见和最具侵袭性的脑肿瘤。目前，患者平均生存期仅为15个月，且易复发[2]。免疫治疗的发展和临床应用为多种癌症带来了希望，但似乎还未给GBM患者带来福音，其中的一个重要原因就是GBM中存在明显的免疫抑制肿瘤微环境[3]。比如肿瘤浸润巨噬细胞，它们不但不消灭肿瘤细胞，反而通过分泌各种细胞因子促进肿瘤的生长和耐药[4]。因此，系统地描述GBM进展过程中肿瘤免疫微环境的形成及其特点，对研发GBM的治疗新方法、新靶点来说至关重要。为此，研究人员收集了4名诊断为多发病灶IDH野生型GBM患者（NJ01、NJ02、TT01和TT02）的肿瘤组织，每位患者采集2个GBM病变。从这些肿瘤组织中共分离得到61062个单细胞，开展单细胞RNA测序（scRNA-seq），并对测序数据进行了深入分析。多发病灶GBM是指患者同时发生一个以上的肿瘤病变，在临床上较罕见。大多数多发病灶GBM在早期阶段是从一个肿瘤前体细胞克隆开始，经历长期的平行遗传演化而成。这些多发病灶可能会反应肿瘤进展的各个阶段，是研究GBM与肿瘤微环境协同自然演化的好模型[5]。多发病灶GBM的单细胞测序及其他数据分析流程图测序结果表明，同一患者的不同病灶具有共同的祖先，并在空间上相互隔离独自演化，存在潜在的演化顺序。第一病灶更古老，而第二病灶相对“年轻”；第二病灶中的肿瘤细胞就像新生的“竹笋”，最终可能发展为第一病灶中肿瘤细胞的表型。为了寻找具有不同演化顺序病灶的分子“标记”，研究人员通过比较不同基因在第一、二病灶间的表达情况，最终筛选得到12个基因作为GBM的自然进化特征（NES）。这些特征基因与凋亡、血管生成和缺氧等途径相关。与“年轻”病灶相比，“年老”病灶中有更多的肿瘤细胞表达NES基因（P<0.001）。不同演化顺序GBM病灶中表达NES的肿瘤细胞百分比随后，研究人员发现处于不同发展阶段、不同状态的肿瘤细胞，NES表达存在明显差异，进一步证明NES可以作为GBM肿瘤不同演化阶段的“标记”。而且，NES还能预测GBM患者的临床结局，具有低NES（lNES）特征的GBM患者总生存期比高NES（hNES）患者长（P=0.027）。 TCGA数据库中具有低NES和高NES特征的IDH野生型GBM患者的总生存期比较接下来，研究人员对NES如何影响GBM与肿瘤微环境协同演化进行了探索。在GBM的演化过程中，缺氧事件可能是导致肿瘤快速演化的重要始动因素之一，其可通过激活肿瘤内低氧诱导因子HIF1A，从而促进其下游FOSL2等基因高表达。而研究人员也的确发现，NES中促进肿瘤进展的关键调节因子FOSL2在“较老”的病灶中高表达。缺氧和常氧条件下肿瘤细胞NES评分比较（左）； siHIF1A处理对肿瘤细胞FOSL2等NES基因表达量的影响（右） FOSL2可调节NES中的另一个基因ANXA1的表达，而ANXA1可招募并诱导单核细胞分化为处于免疫抑制状态的极化巨噬细胞，从而促进肿瘤细胞生长。对GBM病灶中非肿瘤细胞的聚类分析表明，骨髓来源的巨噬细胞（BMDM）的确是GBM中最主要的非肿瘤细胞群体。在4个患者中，第一个病灶中BMDMs显著高于第二个病灶（P<0.001）。也就是说，具有hNES特征的“较老”的GBM病灶中，也存在更多的BMDM。 GBM中不同非肿瘤细胞的占比（左）；同一患者不同病灶中不同来源巨噬细胞的占比（MG，microglia；右）这些被肿瘤细胞招募而来的，处于免疫抑制状态的极化巨噬细胞，能显著降低CD8阳性T细胞的增殖和IFN-γ的产生，给GBM的免疫治疗带来困难。研究人员进一步利用小鼠肿瘤模型证实，在小鼠GBM细胞系中敲低ANXA1可有效抑制肿瘤生长，延长小鼠存活时间，提示ANXA1可能是GBM治疗的潜在靶点。 ANXA1敲低对小鼠肿瘤生长和存活时间的影响此外，研究人员还发现与极化巨噬细胞共培养的肿瘤细胞NES表达量增加。而且，极化巨噬细胞产生的CCL2使肿瘤更易发生转移。这些发现与临床观察吻合，提示CCL2可能是减缓肿瘤进展的潜在治疗靶点。总的来说，此项研究找到了处于不同演化阶段的IDH野生型GBM病灶的分子“标记“NES。具有高NES特征的肿瘤细胞也拥用更高的可塑性，能更好的“制造”对自己有利的微环境。比如，招募并驯化巨噬细胞，而这些被驯化的巨噬细胞还能够进一步协同促进肿瘤演化，提高肿瘤侵袭能力。 GBM肿瘤自然演化过程中与巨噬细胞相互作用示意图总之，正常的细胞一旦变异为肿瘤细胞后，就会变得异常狡猾，不但自己疯狂生长，还会“引诱”和“劫持”本来充满“正义”的免疫细胞成为他们的“帮凶”。我们一定要保持好的生活习惯，少接触致癌危险因素，尽量远离肿瘤君哦。参考文献： 1.Wu L, Wu W, Zhang J, et al. Natural coevolution of tumor and immunoenvironment in glioblastoma[J]. Cancer Discov. 2022, CD-22-0196. 2.Jiang T, Nam DH, Ram Z, et al. Clinical practice guidelines for the management of adult diffuse gliomas[J]. Cancer Lett. 2021, 499:60-72 3.McGranahan T, Therkelsen KE, Ahmad S, et al. Current State of Immunotherapy for Treatment of Glioblastoma[J]. Curr Treat Options Oncol. 2019, 20(3):24 4.Hao NB, Lu MH, Fan YH, et al. Macrophages in tumor microenvironments and the progression of tumors[J]. Clin Dev Immunol. 2012, 2012:948098 5.Abou-El-Ardat K, Seifert M, Becker K, et al. Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas[J]. Neuro Oncol. 2017, 19(4):546-57

免疫疗法

2021-06-04

·GlobeNewswire

Vitiligo Pipeline - Current Treatments, Drug Pipeline and Clinical Trial Outlook | Insights by DelveInsight

Los Angeles, June 03, 2021 (GLOBE NEWSWIRE) -- Vitiligo Pipeline - Current Treatments, Drug Pipeline and Clinical Trial Outlook | Insights by DelveInsight Prominent companies such as Incyte Corporation, TWi Biotechnology, Amgen, Pfizer, Arcutis Biotherapeutics, AnaptysBio, and others are developing potential drug candidates to boost the Vitiligo treatment scenario. Out of all the emerging therapies, the late-stage product Ruxolitinib has shown promising results and will have a major impact on the Vitiligo treatment market. DelveInsight’s ‘Vitiligo Pipeline Insights’ report offers a holistic coverage of the current treatments and pipeline therapies and landscape in different stages of development from pre-clinical till late-stage, along with dormant, inactive and abandoned therapeutic agents. Some of the key pointers from the Vitiligo Pipeline report: Request for Sample to know more about the key pharma company and therapy expected to grab maximum share @ Vitiligo Emerging Therapies and Forecast The Vitiligo Pipeline reports a panoramic view of the ongoing clinical trials, mergers & partnerships taking place in the domain, recent happenings in space and growth prospects across the Vitiligo domain that continue to attract the pharma companies. Vitiligo: Overview Vitiligo is a complex pigment disorder that affects the skin, hair, and occasionally the mucous membranes leading to the development of white patches and discoloration. The condition is due to a lack of pigment melanin that is produced by the skin cells known as melanocytes. For more information on emerging drugs, visit Vitiligo Pipeline Analysis Vitiligo Drug Pipeline Assessment Request for Sample to know more @ Vitiligo Pipeline Analysis, Key Companies and Futuristic Trends Vitiligo Therapeutics Assessment The Vitiligo Pipeline report proffers comprehensive coverage of the active pipeline candidates segmented by Stage, Product Type, Route of Administration, Molecule Type, Target, and Mechanism of Action. By Product Type By Stage By Molecule Type By Route of Administration By Mechanism of Action By Targets Connect with our Business Executive for Asset Prioritization Services and Consulting Solutions Scope of the Vitiligo Pipeline Report Coverage: GlobalKey Players: Dermavant Sciences, Incyte Corporation, TWi Biotechnology, Aclaris Therapeutics, Dermira, Amgen, Pfizer, Arcutis Biotherapeutics, AnaptysBio, Bioniz Therapeutics, and others. Key Vitiligo Pipeline Therapies: Cerdulatinib, Ruxolitinib, Brepocitinib, AC-1101, ATI-1777, QLT-450, AMG 714, PF-06651600, ANB030, ARQ-252, BNZ-1, TT-01, and others. Reach out @ Vitiligo Pipeline: Novel therapies and Emerging technologies Table of Contents Learn more about the report offerings @ Vitiligo Emerging Therapies, Treatments and Ongoing Clinical Trials Related Reports Vitiligo MarketDelveInsight's "Vitiligo Market Insights, Epidemiology, and Market Forecast-2030" report. Vitiligo Epidemiology ForecastDelveInsight's 'Vitiligo Epidemiology Forecast to 2030' report. Dyschromia MarketDelveInsight's "Dyschromia Market Insights, Epidemiology, and Market Forecast-2030" report. Dystrophic Epidermolysis Bullosa MarketDelveInsight's "Dystrophic Epidermolysis Bullosa Market Insights, Epidemiology, and Market Forecast-2030" report. Exanthema MarketDelveInsight's "Exanthema Market Insights, Epidemiology, and Market Forecast-2030" report. Eczema MarketDelveInsight's "Eczema Market Insights, Epidemiology, and Market Forecast-2030" report. Generalized Pustular Psoriasis MarketDelveInsight's "Generalized Pustular Psoriasis Market Insights, Epidemiology, and Market Forecast-2030" report. Related Posts Most Common Foods AllergiesAtopic Dermatitis Market About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. For more insights, visit Pharma, Healthcare, and Biotech News

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100 项与 TT-01 相关的药物交易

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