inflammation model

炎症模型
  • 文章类型: Journal Article
    亚硫酸盐是生命体系中二氧化硫(SO2)的主要存在形式之一,已被认为是炎症中的内源性介质。积累的证据表明,亚硫酸盐的异常水平与许多炎症性疾病有关,包括神经系统疾病和癌症。在这里,设计并合成了一种新型的荧光探针QX-OA来检测亚硫酸盐。QX-OA是通过选择喹啉-xanthene作为荧光团和乙酰丙酸酯作为特异性和相对稳定的识别反应来构建的。探针在550nm处显示出显著的绿色开启信号,与其他可能的干扰物种相比,具有高灵敏度(90倍)和对亚硫酸盐的出色选择性。同时,QX-OA已成功应用于Hela细胞中内源性和外源性亚硫酸盐的可视化。在LPS诱导的炎症模型中,QX-OA可以观察到亚硫酸盐水平的剂量依赖性增加(0-2mg/mL)。因此,QX-OA被确定为在临床前诊断中检测亚硫酸盐的潜在方法。
    Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.
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  • 文章类型: Journal Article
    目前治疗大软骨缺损的金标准是自体软骨细胞移植(ACT)。软骨再生作为一种新的手术方法,切碎的软骨植入(MCI)越来越成为人们关注的焦点。这项研究的目的是研究在使用促炎细胞因子TNFα的标准化炎症模型中,与软骨芯片相比,分离和培养的软骨细胞之间软骨形成的影响。根据ACT方法培养来自牛软骨的关节软骨细胞至第3代,并转移到球体培养中。同时,将软骨片段化(<1mm3)以产生软骨碎片。补充TNFα(20ng/mL)以模拟炎症过程。与未传代的软骨细胞相比,TNFα对传代的软骨细胞有更强的影响,影响分离的软骨细胞和软骨芯片之间的基因表达谱不同。MCI对TNFα的敏感性较低,IL-6释放减少,对炎症标志物的影响较小。生化和组织学分析支持这些发现,与未传代的细胞和MCI构建体相比,TNFα对传代的沉淀培养物具有更大的负面影响。这项研究证明了TNFα对软骨细胞球体培养和软骨片段模型中软骨形成的负面影响。与未传代的细胞和软骨相比,传代的软骨细胞对细胞因子的影响更敏感。这表明与ACT相比,MCI在骨关节炎病症中可能具有优异的再生潜力。需要进一步的调查才能将这些发现转化为临床实践。
    The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm3) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.
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  • 文章类型: Journal Article
    国际抗癫痫联盟/美国癫痫学会(ILAE/AES)联合转化工作组发起了TASK3工作组,为临床前癫痫研究的各个方面创建通用数据元素(CDE)。这可以帮助提高实验设计的标准化。本文讨论了啮齿动物癫痫模型中与癫痫发作和癫痫相关的神经病理变化。我们讨论CDE用于神经变性的组织病理学参数,星形胶质细胞形态和功能的变化,炎症的机制,以及大鼠和小鼠反复发作导致的血脑屏障和髓磷脂/少突胶质细胞的变化。我们提供详细的CDE表和病例报告表(CRF),有了这份伴随的手稿,我们讨论了个别神经病理学检查的基本原理和方法学方面。CDEs,CRFs,所有研究人员都可以获得配套论文,它们的使用将有利于转化性临床前癫痫研究的协调性和可比性。最终的希望是促进治疗癫痫的理性治疗概念的发展,癫痫发作,和合并症以及评估疾病病理状态的生物标志物的发展。
    The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force initiated the TASK3 working group to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve the standardization of experimental designs. This article addresses neuropathological changes associated with seizures and epilepsy in rodent models of epilepsy. We discuss CDEs for histopathological parameters for neurodegeneration, changes in astrocyte morphology and function, mechanisms of inflammation, and changes in the blood-brain barrier and myelin/oligodendrocytes resulting from recurrent seizures in rats and mice. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript, we discuss the rationale and methodological aspects of individual neuropathological examinations. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of rational therapy concepts for treating epilepsies, seizures, and comorbidities and the development of biomarkers assessing the pathological state of the disease.
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  • 文章类型: Journal Article
    Along with modern new drugs, many therapeutic schemes also include known effective drugs, particularly, glucocorticoids. One of the most distributed of them is prednisolone that has pronounced anti-inflammatory properties. Its disadvantage is short-term circulation, resulting in a number of side effects. For this reason the development of its more effective and safe formulations is carried out. We have obtained the formulation of prednisolone included in nanoparticles from soy phosphatidylcholine with an average diameter of 20 nm. With oral administration to rats and analysis by HPLC an increase in prednisolone maximal concentration in of plasma and the duration of circulation as compared with free drug administration were shown. The experiment with mice with conconavalin A induced inflammation was also carried out: conconavalin A was injected subplantary in an hour after oral administration of both prednisolone formulations in several doses. The index of the inflammatory reaction (determined by the edema degree) was suppressed more effectively in the case of prednisolone in nanoparticles. Maximal suppression (62.2% as compared with 49.6% for free prednisolone) was observed even at a minimal dose (2.5 mg/kg), at which the free drug did not act at all. The results indicate an increase in the efficiency of prednisolone included in phospholipid nanoparticles, that makes it possible to diminish its administered doses and thereby reduce the risk of side effects.
    Nariadu s novymi lekarstvennymi preparatami, mnogie terapevticheskie skhemy ispol\'zuiut izvestnye éffektivnye lekarstvennye sredstva, v chastnosti, gliukokortikoidy. Sredi nikh odnim iz naibolee rasprostranennykh iavliaetsia prednizolon, obladaiushchiĭ vyrazhennymi protivovospalitel\'nymi svoĭstvami. Nedostatkom étogo lekarstva iavliaetsia kratkovremennaia tsirkuliatsiia v krovi, trebuiushchaia povtornykh vvedeniĭ i privodiashchaia k riadu pobochnykh éffektov. V sviazi s étim provodiatsia razrabotki bolee éffektivnykh i bezopasnykh lekarstvennykh form étogo preparata. Nami poluchena kompozitsiia prednizolona, vkliuchennogo v nanochastitsy iz soevogo fosfatidilkholina, so srednim diametrom 20 nm. Pri peroral\'nom vvedenii étoĭ kompozitsii pokazano uvelichenie maksimal\'noĭ kontsentratsii prednizolona v plazme i dlitel\'nosti ego tsirkuliatsii po sravneniiu so svobodnym lekarstvom. Na myshakh s model\'iu vospaleniia, indutsirovannogo vvedeniem konkonavalina A, indeks reaktsii vospaleniia (opredeliaemyĭ po oteku konechnosti) snizhalsia v sluchae kompozitsii prednizolona v nanochastitsakh sushchestvenno aktivnee, chem pri vvedenii svobodnogo lekarstva: maksimal\'noe snizhenie indeksa (62,2% po sravneniiu s 49,6%) nabliudalos\' uzhe pri minimal\'noĭ doze vvodimogo prednizolona (2,5 mg/kg), pri kotoroĭ svobodnoe lekarstvo voobshche ne deĭstvovalo. Poluchennye rezul\'taty ukazyvaiut na povyshenie éffektivnosti prednizolona pri vkliuchenii v fosfolipidnye nanochastitsy, chto daet vozmozhnost\' umen\'sheniia vvodimykh doz i snizhaet risk pobochnogo deĭstviia.
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  • 文章类型: Journal Article
    The difficulty of near-infrared (NIR) ratiometric detection imaging lies in the lack of high-efficiency NIR probes and the overlapping interference between two emission peaks. To achieve more accurate detection in living organisms, dual NIR-emissive luminescent nanoprobes were designed under the same excitation at 808 nm. The Er3+ ion-doped nanoparticles were employed as a reference with their fluorescence emission at 1525 nm. Meanwhile, a cyanine dye molecule (Cy925) was combined on the surface of nanoparticles as the ClO- recognition site with its NIR emission at 925 nm. The ratiometric nanoprobe relied on the ratio of aforementioned two separated NIR peaks ( I925nm/ I1525nm), featuring deeper imaging penetration depth and low autofluorescence. This nanoprobe was verified to be sensitive and highly selective to ClO- through photoluminescence titration. The in vitro detection experiment developed reasonable work curves, guaranteeing that we can detect the change in concentration of ClO- in mice limbs with arthritis through in vivo imaging experiments.
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