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  • 1
    Online Resource
    Online Resource
    The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma
    Hindawi Limited ; 2022
    In:  Journal of Immunology Research Vol. 2022 ( 2022-11-16), p. 1-18
    Details
    In: Journal of Immunology Research, Hindawi Limited, Vol. 2022 ( 2022-11-16), p. 1-18
    Abstract: Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.
    Type of Medium: Online Resource
    ISSN: 2314-7156 , 2314-8861
    URL: Article
    DOI: 10.1155/2022/7945884
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2817541-4
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  • 2
    Online Resource
    Online Resource
    Neutrophil-to-Lymphocyte Ratio (NLR) and Monocyte-to-Lymphocyte Ratio (MLR) Predict Clinical Outcome in Patients with Stage IIB Cervical Cancer
    Hindawi Limited ; 2021
    In:  Journal of Oncology Vol. 2021 ( 2021-9-8), p. 1-14
    Details
    In: Journal of Oncology, Hindawi Limited, Vol. 2021 ( 2021-9-8), p. 1-14
    Abstract: Introduction. Stage IIB cervical cancer (CC) is an advanced stage CC with poor prognosis. Inflammatory response plays a crucial role in the development of CC, and systemic inflammatory indexes were related to the prognosis in several cancers. The objective of the study was to determine the prognostic value of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and systemic inflammation response index (SIRI) as inflammatory indexes in patients with stage IIB CC. Materials and Methods. A retrospective study was performed in 260 patients with stage IIB CC. PLR, NLR, MLR, BLR, and SIRI were obtained from routine blood tests. Prognosis information of the patients was acquired from regular clinical follow-up. Recurrence and response to therapy were determined through electronic medical records (EMRs). Correlations of the inflammatory indexes with overall survival (OS), progression-free survival (PFS), recurrence, and response to therapy were analyzed using SPSS version 26.0 software. Results. Receiver operating characteristic (ROC) curve analyses suggested that NLR, MLR, and SIRI had better predictive value than PLR as well as BLR in the prognosis and recurrence risk. Both univariate and multivariate survival analyses showed that higher NLR and MLR were significantly associated with shorter OS as well as PFS, whereas SIRI was not an independent predictive factor of PFS. Chi-square test results revealed that increased NLR was significantly correlated with higher recurrence rate ( P = 0.046 ), and increased MLR showed significant correlation with elevated recurrence risk ( P = 0.002 ). Univariate and binary logistic regression analyses for response to therapy indicated that elevated NLR was associated with decreased complete remission (CR) rate ( P = 0.031 ), and the P value lost statistical significance while being adjusted by tumor size ( P = 0.108 ). Conclusions. For patients with stage IIB CC, both NLR and MLR are independent prognostic factors as well as risk factors for recurrence; NLR serves as a potential marker for therapeutic response.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    URL: Article
    DOI: 10.1155/2021/2939162
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2461349-6
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  • 3
    Online Resource
    Online Resource
    Melatonin Ameliorates the Progression of Atherosclerosis via Mitophagy Activation and NLRP3 Inflammasome Inhibition
    Hindawi Limited ; 2018
    In:  Oxidative Medicine and Cellular Longevity Vol. 2018 ( 2018-09-04), p. 1-12
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2018 ( 2018-09-04), p. 1-12
    Abstract: The NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediated inflammatory responses are critically involved in the progression of atherosclerosis (AS), which is the essential cause for cardiovascular diseases. Melatonin has anti-inflammatory properties. However, little is known about the potential effects of melatonin in the pathological process of AS. Herein, we demonstrate that melatonin suppressed prolonged NLRP3 inflammasome activation in atherosclerotic lesions by reactive oxygen species (ROS) scavenging via mitophagy in macrophages. The atherosclerotic mouse model was induced with a high-fat diet using ApoE −/− mice. Melatonin treatment markedly attenuated AS plaque size and vulnerability. Furthermore, melatonin decreased NLRP3 inflammasome activation and the consequent IL-1 β secretion within atherosclerotic lesions. Despite the unchanged protein expression, the silent information regulator 3 (Sirt3) activity was elevated in the atherosclerotic lesions in melatonin-treated mice. In ox-LDL-treated macrophages, melatonin attenuated the NLRP3 inflammasome activation and the inflammatory factors secretion, while this protective effect was abolished by either Sirt3 silence or autophagy inhibitor 3-MA. Mitochondrial ROS (mitoROS), which was a recognized inducer for NLRP3 inflammasome, was attenuated by melatonin through the induction of mitophagy. Both Sirt3-siRNA and autophagy inhibitor 3-MA partially abolished the beneficial effects of melatonin on mitoROS clearance and NLRP3 inflammasome activation, indicating the crucial role of Sirt3-mediated mitophagy. Furthermore, we demonstrated that melatonin protected against AS via the Sirt3/FOXO3a/Parkin signaling pathway. In conclusion, the current study demonstrated that melatonin prevented atherosclerotic progression, at least in part, via inducing mitophagy and attenuating NLRP3 inflammasome activation, which was mediated by the Sirt3/FOXO3a/Parkin signaling pathway. Collectively, our study provides insight into melatonin as a new target for therapeutic intervention for AS.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    URL: Article
    DOI: 10.1155/2018/9286458
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2455981-7
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  • 4
    Online Resource
    Online Resource
    Effect of Nitric Acid on the Low Fluorescing Performance of Drilling Fluid Lubricant Based Animal and Vegetable Oils
    Hindawi Limited ; 2013
    In:  Journal of Spectroscopy Vol. 2013 ( 2013), p. 1-7
    Details
    In: Journal of Spectroscopy, Hindawi Limited, Vol. 2013 ( 2013), p. 1-7
    Abstract: After synthesis of mixed fatty acid triethanolamine ester surfactant based on animal and vegetable mixed oils, the reaction solution was added into 4% (wt/wt) liquid nitric acid or 9% (wt/wt) solid nitric acid as eliminating fluorescent agent continuing to react from 1 to 2 hours. The low fluorescence lubricant named E167 for drilling fluid was prepared, in which maximum fluorescence intensity ( F m a x ) was less than 10 in three-dimensional fluorescence spectra of excitation wavelength range. When the E167 was added into fresh water based drilling fluid at the dosage of 0.5% (wt/wt), the sticking coefficient reduced rate ( Δ K f ) is 78% and the extreme pressure (E-P) friction coefficient reduced rate ( Δ f ) is 79%. In the case of 4% brine mud with 0.5% (wt/wt) E167 in it, the Δ K f and Δ f are 75% and 62%, respectively. After the hot rolling ageing test 180°C × 16 h with the E167 was added into fresh water based drilling fluid at the dosage of 1% (wt/wt), the Δ K f and Δ f are greater than 70%, which shows a much better lubrication properties of strong resistance to high temperature. The fresh water based drilling fluid which contains 1% (wt/wt) E167 is almost nonfoaming even after hot rolling ageing 120°C × 16 h.
    Type of Medium: Online Resource
    ISSN: 2314-4920 , 2314-4939
    URL: Article
    DOI: 10.1155/2013/269280
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
    detail.hit.zdb_id: 2068433-2
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Effects of Se‐enriched Chrysanthemum morifolium on lifespan and antioxidant defense‐related gene expression of Drosophila melanogaster model
    Hindawi Limited ; 2022
    In:  Journal of Food Biochemistry Vol. 46, No. 12 ( 2022-12)
    Details
    In: Journal of Food Biochemistry, Hindawi Limited, Vol. 46, No. 12 ( 2022-12)
    Type of Medium: Online Resource
    ISSN: 0145-8884 , 1745-4514
    URL: Issue
    URL: Article
    DOI: 10.1111/jfbc.v46.12
    DOI: 10.1111/jfbc.14503
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2174913-9
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  • 6
    Online Resource
    Online Resource
    Effect of Corilagin on the Proliferation and NF- κ B in U251 Glioblastoma Cells and U251 Glioblastoma Stem-Like Cells
    Hindawi Limited ; 2016
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2016 ( 2016), p. 1-9
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2016 ( 2016), p. 1-9
    Abstract: Background . This study is to explore the effect of corilagin on the proliferation and NF- κ B signaling pathway in U251 glioblastoma cells and U251 glioblastoma stem-like cells. Methods . CD133 positive U251 glioblastoma cells were separated by immunomagnetic beads to isolate glioblastoma stem-like cells. U251 cells and stem-like cells were intervened by different corilagin concentrations (0, 25, 50, and 100  μ g/mL) for 48 h, respectively. Cell morphology, cell counting kit-8 assay, flow cytometry, dual luciferase reporter assay, and a western blot were used to detect and analyze the cell proliferation and cell cycle and investigate the expression of IKB α protein in cytoplasm and NF- κ B/p65 in nucleus. Results . Corilagin inhibited the cell proliferation of U251 cells and their stem-like cells and the inhibition role was stronger in U251 stem-like cells ( P 〈 0.05 ). The cell cycle was arrested at G2/M phase in the U251 cells following corilagin intervention; the proportion of cells in G2/M phase increased as the concentration of corilagin increased ( P 〈 0.05 ). The U251 stem-like cells were arrested at the S phase following treatment with corilagin; the proportion of cells in the S phase increased as the concentration of corilagin increased ( P 〈 0.05 ). The ratio of dual luciferase activities of U251 stem-like cells was lower than that of U251 cells in the same corilagin concentration. With increasing concentrations of corilagin, the IKB α expression in cytoplasm of U251 cells and U251 stem-like cells was increased, but the p65 expression in nucleus of U251 cells and U251 stem-like cells was decreased ( P 〈 0.05 ). Conclusion . Corilagin can inhibit the proliferation of glioblastoma cells and glioblastoma stem-like cells; the inhibition on glioblastoma stem-like cell proliferation is stronger than glioblastoma cells. This different result indicates that the effect of corilagin on U251 cells and U251 stem-like cells may have close relationships with mechanism of cell cycle and NF- κ B signaling pathway; however, the real antitumor mechanism of corilagin is not yet clear and requires further study.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1155/2016/1418309
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2148302-4
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  • 7
    Online Resource
    Online Resource
    SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice
    Hindawi Limited ; 2017
    In:  Oxidative Medicine and Cellular Longevity Vol. 2017 ( 2017), p. 1-15
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2017 ( 2017), p. 1-15
    Abstract: Background . Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results . Cardiac-specific SIRT1 knockout (SIRT1 KO ) mice were generated using Cre-loxP system. SIRT1 KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1 KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1 KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF-1), NRF-2, estrogen-related receptor-α (ERR-α), and mitochondrial transcription factor A (TFAM). Conclusions . Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC-1α-mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    URL: Article
    DOI: 10.1155/2017/4602715
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2455981-7
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  • 8
    Online Resource
    Online Resource
    PADI1 and Its Co-Expressed Gene Signature Unveil Colorectal Cancer Prognosis and Immunotherapy Efficacy
    Hindawi Limited ; 2022
    In:  Journal of Oncology Vol. 2022 ( 2022-11-26), p. 1-18
    Details
    In: Journal of Oncology, Hindawi Limited, Vol. 2022 ( 2022-11-26), p. 1-18
    Abstract: Peptidyl arginine deiminase 1 (PADI1) catalyzes protein citrullination and has a role in regulating immune responses. The tumor immune microenvironment has been reported to be important in colorectal cancer (CRC), which was correlated with the ability of CRC patients to benefit from immunotherapy. However, there is a lack of molecular markers for matching CRC immunotherapy. Previously, single-gene risk models have only considered the effect of individual genes on intrinsic tumor properties, ignoring the role of genes and their co-expressed genes as a whole. In this study, we analyzed the differential expression of PADI1 in colorectal cancer (CRC). We found that PADI1 was highly expressed in CRC. Subgroup survival analysis revealed a prognostic survival difference for PADI1 in CRC patients aged less than 65 years, male, T stage, N0, M0, and stage I-II ( p 〈 0.05 ). In addition, we analyzed the functions and signaling pathways associated with PADI1 in CRC and found that it was highly enriched in several immune-related functions and pathways. Then, a set of PADI1 co-expressed genes (PCGs) risk-prognosis scores was developed with PADI1 as the core, which could accurately predict the prognosis of CRC ( p 〈 0.05 ). PCGs risk score can be an independent prognostic factor for CRC. A new set of Norman plot models were developed for clinical characteristics with age, sex, and TNM stage, which can accurately predict CRC 1, 3, and 5 years survival, and calibration curves and decision curve analysis (DCA) validated the accuracy of the models. The risk score assessed the immune microenvironment of CRC and found that the immune score was higher in the low-risk group, and CD4+ T cells, helper T cells, and eosinophils were more infiltrated in the low-risk group ( p 〈 0.05 ). Immunotherapy efficacy was better in the low-risk group ( p 〈 0.05 ). The underlying mechanism may be that the high-risk group of PCGs was enriched in some pathways that promote immune escape and immune dysfunction. In conclusion, PCGs may better predict CRC prognosis and immunotherapeutic response.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    URL: Article
    DOI: 10.1155/2022/8394816
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2461349-6
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  • 9
    Online Resource
    Online Resource
    The Impact of Electroacupuncture at Hegu, Shousanli, and Quchi Based on the Theory “Treating Flaccid Paralysis by Yangming Alone” on Stroke Patients’ EEG: A Pilot Study
    Hindawi Limited ; 2020
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2020 ( 2020-11-24), p. 1-9
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2020 ( 2020-11-24), p. 1-9
    Abstract: Background. In China, electroacupuncture based on meridians theory “treating flaccid paralysis by Yangming alone” has been widely used for stroke rehabilitation in clinical practice. The aim of this study was to explore the electroencephalography change of electroacupuncture intervention on strokes patients with flaccid paralysis. Methods. Twenty-three stroke patients with flaccid paralysis and six stroke patients with spasticity accepted electroacupuncture with the acupoints Hegu [LI4], Shousanli [LI10] , and Quchi [LI11] for 20 minutes and their EEG data were recorded before, during, and after the electroacupuncture intervention. Results. Compared with the baseline EEG signals before electroacupuncture, the ipsilesional and contralesional beta-band average power of patients with flaccid paralysis and spasticity were significantly increased during the needles retention stage and decreased slightly after removing the needles. The significant decrease of the ipsilesional and contralesional delta band average power in patients with flaccid paralysis occurred during the electroacupuncture stimulation, and they increased after the removal of the needles. The ipsilesional delta band average power of patients with spasticity significantly decreased during the electroacupuncture stimulation. Conclusion. From this pilot electrophysiological study, we provided a possible electrophysiological mechanism of the curative effect of electroacupuncture for stroke reha bilitation.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    URL: Article
    DOI: 10.1155/2020/8839491
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2148302-4
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  • 10
    Online Resource
    Online Resource
    N -Butanol Extract from Melilotus suaveolens Ledeb Affects Pro- and Anti-Inflammatory Cytokines and Mediators
    Hindawi Limited ; 2010
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 7, No. 1 ( 2010), p. 97-106
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 7, No. 1 ( 2010), p. 97-106
    Abstract: Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n -butanol extract from M. suaveolens Ledeb . Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-α, IL-1β, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-κB and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-κB activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1093/ecam/nem165
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2010
    detail.hit.zdb_id: 2148302-4
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