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"My biggest motivation is to make creative and significant discoveries in my research fields. I chose chemistry as a career because of a high score for chemistry in my college entrance examination …" Find out more about Hai-Long Jiang in his Author Profile. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Centrosome amplification (CA) is a common phenomenon in cancer, promotes genomic stability and cancer evolution, and has been reported to promote metastasis. CA promotes a stochastic gain/loss of chromosomes during cell division, known as chromosomal instability (CIN). However, it is unclear whether CA is present in circulating tumor cells (CTCs), the seeds for metastasis. Here, we surveyed CA in CTCs from human subjects with metastatic breast cancer. CTCs were captured by CD45-exclusion and selection of EpCAM-positive cells using an exclusion-based sample preparation technology platform known as VERSA (Versatile Exclusion-based Rare Sample Analysis). Centriole amplification (centrin foci >4) is the definitive assay for CA. However, determination of centrin foci is technically challenging and incompatible with automated analysis. To test if the more technically accessible centrosome marker pericentrin could serve as a surrogate for centriole amplification in CTCs, cells were stained with pericentrin and centrin antibodies to evaluate CA. This assay was first validated using breast cancer cell lines and a non-transformed epithelial cell line model of inducible CA, then translated to CTCs. Pericentrin area and pericentrin area x intensity correlate well with centrin foci, validating pericentrin as a surrogate marker of CA. CA is found in CTCs from 75% of subjects, with variability in the percentage and extent of CA in individual circulating cells in a given subject, similar to the variability previously seen in primary tumors and cell lines. In summary, we created, validated, and implemented a novel method to assess CA in CTCs from subjects with metastatic breast cancer. Such an assay will be useful for longitudinal monitoring of CA in cancer patients and in prospective clinical trials for assessing the impact of CA on response to therapy. This article is protected by copyright. All rights reserved.Malignant gliomas are a heterogeneous group of brain tumors with a poor prognosis, which is largely due to its aggressive invasiveness and angiogenesis. In recent years, it has been found that multiple long non-coding RNAs (lncRNAs) participate in a wide range of biological functions including angiogenesis through the regulation of gene expression in cancers. In this study, we investigate and report the novel role of lncRNA SLC26A4-AS1 in gliomas, with a novel mechanism involving transcription factors NFKB1 and NPTX1. We determined that SLC26A4-AS1 was downregulated in human glioma tissues and cells. selleckchem Furthermore, overexpression of SLC26A4-AS1 or NPTX1 restrained the aggressiveness of glioma cells and their pro-angiogenic ability. SLC26A4-AS1 was also found to upregulate NPTX1 by recruiting NFKB1 into the NPTX1 promoter. Moreover, silencing of either NPTX1 or NFKB1 restored the aggressive and pro-angiogenic properties of glioma cells in the presence of SLC26A4-AS1. Taken together, we demonstrate that SLC26A4-AS1 promotes NPTX1 transcriptional activity by recruiting NFKB1 and thus exerting antiangiogenic effects on glioma cells. This study provides an experimental basis for the intervention of SLC26A4-AS1 in the treatment of gliomas. This article is protected by copyright. All rights reserved.The inflammatory response involves the activation of several cell types to fight insults caused by a plethora of agents, and to maintain the tissue homeostasis. On the one hand, cells involved in the pro-inflammatory response, such as inflammatory M1 macrophages, Th1 and Th17 lymphocytes or activated microglia must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production. On the other hand, regulatory T cells or M2 macrophages, which are involved in immune regulation and resolution of inflammation, preferentially use fatty acid oxidation through the TCA cycle as a main source for energy production. Here we discuss the impact of glycolytic metabolism at the different steps of the inflammatory response. Finally, we review a wide variety of molecular mechanisms which could explain the relationship between glycolytic metabolites and the pro-inflammatory phenotype, including signalling events, epigenetic remodelling, post-transcriptional regulation and post-translational modifications. Inflammatory processes are a common feature of many age-associated diseases, such as cardiovascular and neurodegenerative disorders. The finding that immunometabolism could be a master regulator of inflammation broadens the avenue for treating inflammation-related pathologies through the manipulation of the vascular and immune cell metabolism. This article is protected by copyright. All rights reserved.BACKGROUND Evaluating effectiveness of stellate ganglion blockades (SGBs) proves challenging as criteria defining a successful blockade, are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients benefit from blockade series, are not yet available. OBJECTIVES Objectives are to evaluate through a clinical approach SGBs' effectiveness performed under ultrasound-guidance (us-SGB) and to identify factors to predict effectiveness. METHODS This study retrospectively analyzes 809 us-SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner's syndrome or complications were assessed. RESULTS Pain reduction after blockade series was highly significant and showed no significant correlation with either change of temperature, vital signs, or Horner's syndrome. For patients with neuropathic pain, predictive potential for pain reduction following a series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9 %, dysphagia 3.4 %, hematoma 0.6 %) were lower than in non-ultrasound-guided techniques. CONCLUSIONS Data indicate that us-SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness. This article is protected by copyright. All rights reserved.
Homepage: https://www.selleckchem.com/
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