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51.
Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD+) declining over time. The decrease in NAD+ production has been linked to the age‐related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate‐limiting enzyme in the NAD+ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues. Currently, the physiological cause for the release of eNAMPT is unknown, and how it may be affected by age and physical exercise. Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV‐eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD+ and SIRT1 activity in recipient cells compared to pre‐exercise EVs, indicating a pathway for inter‐tissue signalling promoted through exercise. Our results suggest a mechanism to limit age‐related NAD+ decline, through the systemic delivery of eNAMPT via EVs released during exercise. 相似文献
52.
With the development of mass spectrometry (MS)-based proteomics technologies, patient-derived xenograft (PDX), which is generated from the primary tumor of a patient, is widely used for the proteome-wide analysis of cancer mechanism and biomarker identification of a drug. However, the proteomics data interpretation is still challenging due to complex data deconvolution from the PDX sample that is a cross-species mixture of human cancerous tissues and immunodeficient mouse tissues. In this study, by using the lab-assembled mixture of human and mouse cells with different mixing ratios as a benchmark, we developed and evaluated a new method, SPA (shared peptide allocation), for protein quantitation by considering the unique and shared peptides of both species. The results showed that SPA could provide more convenient and accurate protein quantitation in human–mouse mixed samples. Further validation on a pair of gastric PDX samples (one bearing FGFR2 amplification while the other one not) showed that our new method not only significantly improved the overall protein identification, but also detected the differential phosphorylation of FGFR2 and its downstream mediators (such as RAS and ERK) exclusively. The tool pdxSPA is freely available at https://github.com/Li-Lab-Proteomics/pdxSPA. 相似文献
53.
Jia Xuan Leong Margot Raffeiner Daniela Spinti Gautier Langin Mirita FranzWachtel Andrew R Guzman JungGun Kim Pooja Pandey Alyona E Minina Boris Macek Anders Hafrn Tolga O Bozkurt Mary Beth Mudgett Frederik Brnke Daniel Hofius Suayib Üstün 《The EMBO journal》2022,41(13)
Beyond its role in cellular homeostasis, autophagy plays anti‐ and promicrobial roles in host–microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well‐described in animals, the extent to which xenophagy contributes to plant–bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type‐III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense‐related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense‐related autophagy in plant–bacteria interactions. 相似文献
54.
看家基因Actin常被用作定量、半定量PCR试验的内参基因.为研究其他基因在南美蟛蜞菊响应环境变化的表达调控机制,根据GenBank上已登录的肌动蛋白基因(Actin)的同源核苷酸保守序列,设计特异性引物,利用RT-PCR的方法克隆获得了南美蟛蜞菊Actin基因的全长序列,并将该序列命名为WtAct.序列分析结果表明W... 相似文献
55.
Zirui Liu Yiquan Li Yilong Zhu Nan Li Wenjie Li Chao Shang Gaojie Song Shanzhi Li Jianan Cong Tingyu Li Zhiru Xiu Jing Lu Chenchen Ge Xia Yang Yaru Li Lili Sun Xiao Li Ningyi Jin 《International journal of biological sciences》2022,18(2):717
Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy. 相似文献
56.
57.
天然产物的主要来源之一是微生物,不同于其他的生物资源,真菌菌种相对容易选育和保藏、适应力较强,可通过大规模发酵获取产物,更具有利于自然资源的可持续发展性和利用价值。篮状菌(Talaromyces sp.)及其次级代谢产物在天然色素上的研究受到科学家的青睐,同时在食品、环境、农业和医药等方面发挥了重要作用,尤其是海洋来源的篮状菌及其次级代谢物表现出显著的生物活性,例如杀虫、抗肿瘤、抗菌、抗病毒等。近来研究表明,篮状菌次级代谢产物根据生物合成的方式可以分为六大类:萜类(terpenes)、生物碱类(fumiquinazolines)、聚酮类(polyketides)、聚酯类(lactones)、醌类(quinones)和甾体类(steroids),这些活性物质对促进药物的先导物质挖掘与开发具有重要意义。本文通过对文献和资料的查阅,总结了近年来篮状菌及其次级代谢物的研究开发进展,希望为后续研究和应用提供参考。 相似文献
58.
目的:冠心病的发病率越来越高,成为临床上常见的心血管疾病。冠心病的发生、发展与冠状动脉病变程度直接相关。通过手术引起冠脉狭窄,探讨冠脉狭窄与骨保护素(OPG)的相关性,从而为临床冠心病的预测提供理论依据。方法:(1)20头巴马小型猪,在胸腔镜直视下手术丝线永久性结扎左前降支近端建立轻度(狭窄程度20-49%)、中度(狭窄程度50-69%)和重度(狭窄程度≥70%)狭窄的冠状动脉狭窄模型;(2)各组小型猪分别在其手术处理前后1 min留取静脉血和分离血浆,测定骨保护素的含量。结果:(1)手术对各组小型猪血浆OPG的影响差异无统计学意义(P0.05),同时,各组之间冠脉狭窄模型猪手术后血浆OPG的浓度较对照组升高,但无统计学差异(P0.05)。结论:(1)手术作为一种应激性损伤,导致OPG升高。(2)骨保护素与冠状动脉硬化和血管钙化有关,但与没有动脉硬化和钙化引起的的冠脉狭窄无关。 相似文献
59.
综述拟寄生蜂搜索产卵过程中对寄主竞争的最新研究进展.这类竞争具有四种方式,即标记寄主、杀卵和杀幼、守护寄主和捕食寄主.(1)标记寄主常涉及寄主标记信息素,这是由雌蜂在产卵前、产卵时或产卵后分泌的化学物质.寄主标记信息素常介导拟寄生蜂对已寄生和健康寄主的辨别、减少过寄生和多寄生、减轻种内和种间竞争压力.(2)雌蜂遇到已寄生寄主时,很多种类杀死前一雌蜂遗留的卵和幼虫,再产下自己的卵.雌蜂使用三种方法杀卵和杀幼,即产卵器穿刺、取食和使用有毒物质.通过杀卵和杀幼,产卵雌蜂清除了前一雌蜂遗留的后代,主动改善了寄主品质,从而有利于自身后代的生存.(3)守护寄主在肿腿蜂科、缘腹细蜂科、金小蜂科、缨小蜂科和茧蜂科中均有报道,守护者驱逐入侵者以保护后代及健康寄主.(4)捕食寄主不仅减少了健康寄主数量,且直接导致已寄生寄主中拟寄生蜂卵和幼虫的死亡.雌蜂一般在体内成熟卵量较少时捕食寄主.讨论了研究拟寄生蜂搜索产卵过程中竞争寄主的理论意义和实际应用价值. 相似文献
60.