HSPs, heat shock proteins

  • 文章类型: Journal Article
    肿瘤免疫治疗已成为新一代抗肿瘤治疗,但是它的适应症仍然集中在对免疫系统敏感的几种类型的肿瘤上。因此,扩大适应证、提高疗效的有效策略成为肿瘤免疫治疗进一步发展的关键要素。据报道,天然产物对癌症免疫疗法有这种作用,包括癌症疫苗,免疫检查点抑制剂,和过继免疫细胞疗法。其机制主要归因于肿瘤免疫抑制微环境的重塑,是帮助肿瘤避免免疫系统和癌症免疫疗法识别和攻击的关键因素。因此,这篇综述总结并总结了据报道可改善癌症免疫治疗的天然产物,并研究了其机制。我们发现皂苷,多糖,黄酮类化合物主要是三类天然产物,这反映了通过逆转肿瘤免疫抑制微环境与癌症免疫治疗相结合的显着效果。此外,这篇综述还收集了有关纳米技术用于改善天然产物缺点的研究。所有这些研究都显示了天然产物在癌症免疫疗法中的巨大潜力。
    Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.
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  • 文章类型: Journal Article
    阿拉伯骆驼是已知最大的哺乳动物,可以在炎热的气候条件下生存。我们为骆驼颗粒细胞暴露于45°C2(急性热休克)或20h(慢性热休克)后的耐热性提供了分子解释。细胞对急性热应激反应的共同特征是热休克蛋白和DNA修复酶表达的增加。肌动蛋白聚合和Rho信号传导被严格激活,作为抵抗热休克的细胞防御。暴露于慢性热休克的细胞显示出改变的细胞结构,检测到的总蛋白质减少,代谢酶,和细胞骨架蛋白表达。用转化生长因子β(TGFβ)途径抑制剂SB-431542治疗可抑制暴露于慢性热休克的细胞的形态改变。此外,在38°C的恢复阶段24小时,随着HSP70表达的指数增加,蛋白质组变化部分恢复,细胞在恢复的第9天恢复正常的细胞形态。完整的蛋白质组学数据可通过具有标识符PXD012159的ProteomeXchange获得。细胞防御和对两种热条件的耐受性策略反映了骆驼体细胞在极热条件下保存生命的灵活适应性。
    The Arabian camel is the largest known mammal that can survive in severe hot climatic conditions. We provide the molecular explanation for the thermotolerance of camel granulosa somatic cells after exposure to 45 °C for 2 (acute heat shock) or 20 h (chronic heat shock). The common features of the cellular responses to acute heat stress were the increase of heat shock proteins and DNA repair enzymes expression. Actin polymerization and Rho signaling were critically activated as a cellular defense against heat shock. Cells exposed to chronic heat shock showed altered cell architecture with a decrease in total detected proteins, metabolic enzymes, and cytoskeletal protein expression. Treatment with transforming growth factor beta (TGFβ) pathway inhibitor SB-431542 suppressed the morphological alterations of cells exposed to chronic heat shock. Moreover, during the recovery stage at 38 °C for 24 h, proteomic changes were partially restored with an exponential increase in HSP70 expression, and the cells restored their normal cellular morphology on the 9th day of recovery. Full proteomics data are available via ProteomeXchange with identifier PXD012159. The strategies of cellular defense and tolerance to both thermal conditions reflect the flexible adaptability of camel somatic cells to conserve life under extremely hot conditions.
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  • 文章类型: Journal Article
    原生动物寄生虫病的治疗具有挑战性,因此,识别和分析新药靶标非常重要。寄生虫在宿主生物体内存活,有些需要中间宿主来完成它们的生命周期。改变宿主环境会给寄生虫带来压力,适应通常伴随着大量热休克蛋白(Hsps)的表达。在Hsps中,Hsp90蛋白在应激环境中起重要作用。然而,很少有关于Hsp90蛋白的计算研究来比较分析它们作为潜在的寄生虫药物靶标。这里,试图详细了解主机之间的差异,载体和寄生Hsp90蛋白进行大规模生物信息学分析。总共104个Hsp90序列根据其细胞定位分为三组;即细胞溶质,线粒体和内质网(ER)。Further,寄生虫蛋白根据寄生虫的类型(原生动物,蠕虫和外寄生虫)。一级序列分析,系统发育树计算,Hsp90蛋白的基序分析和理化性质表明,尽管这些蛋白的整体结构保守,寄生Hsp90蛋白具有独特的特征,可以将它们与人类区分开来,因此令人鼓舞的想法,即应该进一步分析原生动物Hsp90蛋白作为潜在的药物靶标。
    The treatment of protozoan parasitic diseases is challenging, and thus identification and analysis of new drug targets is important. Parasites survive within host organisms, and some need intermediate hosts to complete their life cycle. Changing host environment puts stress on parasites, and often adaptation is accompanied by the expression of large amounts of heat shock proteins (Hsps). Among Hsps, Hsp90 proteins play an important role in stress environments. Yet, there has been little computational research on Hsp90 proteins to analyze them comparatively as potential parasitic drug targets. Here, an attempt was made to gain detailed insights into the differences between host, vector and parasitic Hsp90 proteins by large-scale bioinformatics analysis. A total of 104 Hsp90 sequences were divided into three groups based on their cellular localizations; namely cytosolic, mitochondrial and endoplasmic reticulum (ER). Further, the parasitic proteins were divided according to the type of parasite (protozoa, helminth and ectoparasite). Primary sequence analysis, phylogenetic tree calculations, motif analysis and physicochemical properties of Hsp90 proteins suggested that despite the overall structural conservation of these proteins, parasitic Hsp90 proteins have unique features which differentiate them from human ones, thus encouraging the idea that protozoan Hsp90 proteins should be further analyzed as potential drug targets.
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  • 文章类型: Journal Article
    负载有肿瘤相关抗原(TAA)的自体树突状细胞(DC)是用于癌症治疗的有希望的免疫工具。这些刺激抗肿瘤反应和免疫记忆的产生。然而,许多患者仍然难以接受DC治疗。抗原(Ag)递送到DCs与疫苗成功有关,和抗原肽,肿瘤相关蛋白,肿瘤细胞,自体肿瘤裂解物,和肿瘤来源的mRNA已被测试为Ag来源。最近,负载有同种异体肿瘤细胞裂解物的DC用于诱导有效的免疫应答。这种策略提供了一个可重现的几乎所有适用于患者使用的潜在Ags库。独立于MHC单倍型或自体肿瘤组织可用性。然而,优化自体肿瘤细胞裂解液的制备对提高疗效至关重要。这篇综述认为癌细胞来源的裂解物作为抗原的相关来源和能够响应肿瘤细胞的离体治疗性DC的激活因子的作用。这些有希望的疗法与晚期癌症患者的生存期延长有关。
    Autologous dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are a promising immunological tool for cancer therapy. These stimulate the antitumor response and immunological memory generation. Nevertheless, many patients remain refractory to DC approaches. Antigen (Ag) delivery to DCs is relevant to vaccine success, and antigen peptides, tumor-associated proteins, tumor cells, autologous tumor lysates, and tumor-derived mRNA have been tested as Ag sources. Recently, DCs loaded with allogeneic tumor cell lysates were used to induce a potent immunological response. This strategy provides a reproducible pool of almost all potential Ags suitable for patient use, independent of MHC haplotypes or autologous tumor tissue availability. However, optimizing autologous tumor cell lysate preparation is crucial to enhancing efficacy. This review considers the role of cancer cell-derived lysates as a relevant source of antigens and as an activating factor for ex vivo therapeutic DCs capable of responding to neoplastic cells. These promising therapies are associated with the prolonged survival of advanced cancer patients.
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  • 文章类型: Journal Article
    Sugarcane is an important tropical cash crop meeting 75% of world sugar demand and it is fast becoming an energy crop for the production of bio-fuel ethanol. A considerable area under sugarcane is prone to waterlogging which adversely affects both cane productivity and quality. In an effort to elucidate the genes underlying plant responses to waterlogging, a subtractive cDNA library was prepared from leaf tissue. cDNA clones were sequenced and annotated for their putative functions. Major groups of ESTs were related to stress (15%), catalytic activity (13%), cell growth (10%) and transport related proteins (6%). A few stress-related genes were identified, including senescence-associated protein, dehydration-responsive family protein, and heat shock cognate 70 kDa protein. A bioinformatics search was carried out to discover novel microRNAs (miRNAs) that can be regulated in sugarcane plants subjected to waterlogging stress. Taking advantage of the presence of miRNA precursors in the related sorghum genome, seven candidate mature miRNAs were identified in sugarcane. The application of subtraction technology allowed the identification of differentially expressed sequences and novel miRNAs in sugarcane under waterlogging stress. The comparative global transcript profiling in sugarcane plants undertaken in this study suggests that proteins associated with stress response, signal transduction, metabolic activity and ion transport play important role in conferring waterlogging tolerance in sugarcane.
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