Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion

<p>Abstract</p> <p>Background</p> <p>Neural recognition molecule L1CAM, which is a key protein involved in early nervous system development, is known to be abnormally expressed and shed in several types of cancers where it participates in metastasis and progression. The distinction of L1CAM presence in cancerous vs. normal tissues has suggested it to be a new target for cancer treatment. Our current study focused on the potential role of soluble L1CAM in breast cancer cell adhesion to extracellular matrix proteins, migration, and invasion.</p> <p>Results</p> <p>We found L1 expression levels were correlated with breast cancer stage of progression in established data sets of clinical samples, and also were high in more metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435, but low in less migratory MDA-MB-468 cells. Proteolysis of L1 into its soluble form (sL1) was detected in cell culture medium from all three above cell lines, and can be induced by PMA activation. Over-expression of the L1 ectodomain in MDA-MB-468 cells by using a lentiviral vector greatly increased the amount of sL1 released by those cells. Concomitantly, cell adhesion to extracellular matrix and cell transmigration ability were significantly promoted, while cell invasion ability through Matrigel™ remained unaffected. On the other hand, attenuating L1 expression in MDA-MB-231 cells by using a shRNA lentiviral vector resulted in reduced cell-matrix adhesion and transmigration. Similar effects were also shown by monoclonal antibody blocking of the L1 extracellular region. Moreover, sL1 in conditioned cell culture medium induced a directional migration of MDA-MB-468 cells, which could be neutralized by antibody treatment.</p> <p>Conclusions</p> <p>Our data provides new evidence for the function of L1CAM and its soluble form in promoting cancer cell adhesion to ECM and cell migration. Thus, L1CAM is validated further to be a potential early diagnostic marker in breast cancer progression and a target for breast cancer therapy.</p

Current-cycle iterative learning control for high-precision position tracking of piezoelectric actuator system via active disturbance rejection control for hysteresis compensation

As a typical smart structure, piezoelectric actuator (PEA) is an essential constituent component in piezoelectric-driven positioning stages. Nevertheless, the positioning precision is severely degraded by its innate rate-dependent hysteretic nonlinearity. In this paper, an innovative control method which combines active disturbance rejection control (ADRC) and current-cycle iterative learning control (CILC) is proposed by constructing PEA as a second-order disturbance-based (SODB) structure to handle both hysteretic nonlinearities and dynamic uncertainties of PEA. The proposed method differs from the prevalent model-inverse solution in hysteresis compensation, where the control performance of the latter extremely relies on the accurateness of the hysteretic model while the former does not require a mathematical model of hysteresis since it is considered as a general disturbance and eliminated. Compared with the existing hysteresis compensation via pure ADRC method, the proposed method has improved robustness by incorporating an additional ILC loop to ADRC. Comparative experimentations are executed on a PEA system and results imply that the proposed approach has better control performance than pure proportionalintegral (PI) control and ADRC

A new framework for the analysis of finite element methods for fluid-structure interaction problems

Finite element methods and kinematically coupled schemes that decouple the fluid velocity and structure's displacement have been extensively studied for incompressible fluid-structure interaction (FSI) over the past decade. While these methods are known to be stable and easy to implement, optimal error analysis has remained challenging. Previous work has primarily relied on the classical elliptic projection technique, which is only suitable for parabolic problems and does not lead to optimal convergence of numerical solutions to the FSI problems in the standard $L^2$ norm. In this article, we propose a new kinematically coupled scheme for incompressible FSI thin-structure model and establish a new framework for the numerical analysis of FSI problems in terms of a newly introduced coupled non-stationary Ritz projection, which allows us to prove the optimal-order convergence of the proposed method in the $L^2$ norm. The methodology presented in this article is also applicable to numerous other FSI models and serves as a fundamental tool for advancing research in this field

Dexmedetomidine preconditioning alleviates apoptosis in rat cardiomyocytes by suppressing programmed cell death 4 (PDCD4) after myocardial ischemia-reperfusion injury

Purpose: To determine the role of dexmedetomidine (Dex) in hypoxia/reoxygenation (H/R)-induced myocardial cell injury and the possible involvement of the programmed cell death 4 (Pdcd4) gene in Dex-mediated myocardial cell apoptosis after ischemia-reperfusion (I/R) injury. Methods: An in vivo I/R-injured rat model and in vitro H/R rat cell model were evaluated to ascertain the role of Dex in apoptosis. Programmed cell death 4 (PDCD4) gene expression levels were measured after Dex preconditioning. The effects of Pdcd4 knockdown or overexpression on Dex-mediated apoptosis during H/R injury were determined. Results: Dex pretreatment alleviated myocardial infarction in rats, suppressed myocardial cell apoptosis, and inhibited PDCD4 expression (p &lt; 0.05). Treatment with Dex also alleviated H/R-induced apoptosis in rat cardiomyocytes, while PDCD4 expression decreased after Dex treatment (p &lt; 0.05). Moreover, PDCD4 overexpression reversed the inhibitory effect of Dex on H/R myocardial cell apoptosis. Conclusion: Dex alleviates myocardial infarction in rats via its effect on PDCD4 expression. Therefore, Dex can potentially be used for the treatment but this has to clinical studies

Trifolirhizin mitigates ovalbumin-induced lung inflammation and tissue damage in neonatal rats via inhibition of the NF-κB signaling pathway

Purpose: To investigate the effect of trifolirhizin on neonatal rat model of asthma, and the mechanism of action involved. Methods: Neonatal rats (n = 50) were randomly assigned to 5 groups (10 pups/group): sham, asthma and three treatment groups. With the exception of sham group, the rat pups were sensitized intraperitoneally with ovalbumin (OVA) at a dose of 20 µg/kg on days 7 and 21 postpartum. Rats in the treatment groups received trifolirhizin intragastrically at doses of 2, 4 and 5 mg/kg on day 7 postpartum. Eosinophils in bronchoalveolar lavage fluid (BALF) were counted using hematological analyzer. Serum immunoglobulin (Ig)E and interleukin (IL)-4, IL-5 and IL-13 levels in BALF were determined using their respective enzyme-linked immunosorbent assay (ELISA) kits. Messenger RNA (mRNA) expressions of mucin 5AC (Muc5AC), mucin 5B (Muc5B), tumor necrosis factor α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) were determined using immunohistochemical staining, while the protein expression of inhibitor of nuclear factor of kappa light polypeptide gene enhancer in B-cells alpha (IκBα) was assayed by Western blotting. Results: Serum IgE level was significantly higher in asthma group than in sham group, but was significantly and dose-dependently reduced after treatment with trifolirhizin (p &lt; 0.05). Lung tissue damage was also significantly mitigated in the treatment groups, relative to asthma group (p &lt; 0.05). Trifolirhizin treatment significantly and dose-dependently downregulated the mRNA expressions of Muc5AC, Muc5B, TNF-α and ICAM-1, but upregulated IκBα protein expression significantly and dosedependently (p &lt; 0.05). Bronchoalveolar lavage fluid (BALF) levels of IL-4, IL-5 and IL-13 were significantly higher in asthma group, but were significantly and dose-dependently reduced after treatment with trifolirhizin (p &lt; 0.05). Conclusion: These results indicate that trifolirhizin mitigates OVA-induced lung inflammation and tissue damage in neonatal rats via inhibition of NF-κB signaling pathway, thus affording a potential therapeutic strategy for the management of asthma&nbsp

Linking PHYTOCHROME-INTERACTING FACTOR to Histone Modification in Plant Shade Avoidance

Shade avoidance syndrome (SAS) allows a plant grown in a densely populated environment to maximize opportunities to access to sunlight. Although it is well established that SAS is accompanied by gene expression changes, the underlying molecular mechanism needs to be elucidated. Here, we identify the H3K4me3/H3K36me3-binding proteins, Morf Related Gene (MRG) group proteins MRG1 and MRG2, as positive regulators of shade-induced hypocotyl elongation in Arabidopsis (Arabidopsis thaliana). MRG2 binds PHYTOCHROME-INTERACTING FACTOR7 (PIF7) and regulates the expression of several common downstream target genes, including YUCCA8 and IAA19 involved in the auxin biosynthesis or response pathway and PRE1 involved in brassinosteroid regulation of cell elongation. In response to shade, PIF7 and MRG2 are enriched at the promoter and gene-body regions and are necessary for increase of histone H4 and H3 acetylation to promote target gene expression. Our study uncovers a mechanism in which the shade-responsive factor PIF7 recruits MRG1/MRG2 that binds H3K4me3/H3K36me3 and brings histone-acetylases to induce histone acetylations to promote expression of shade responsive genes, providing thus a molecular mechanistic link coupling the environmental light to epigenetic modification in regulation of hypocotyl elongation in plant SAS

Toxicity of kadsura coccinea (Lem.) A. C. Sm. essential oil to the bed bug, cimex lectularius L. (hemiptera: Cimicidae)

Copyright © 2019 American Society for Microbiology. All Rights Reserved. We sought to define trends in and predictors of carbapenem consumption across community, teaching, and university-affiliated hospitals in the United States and Canada. We conducted a retrospective multicenter survey of carbapenem and broad-spectrum noncarbapenem beta-lactam consumption between January 2011 and December 2013. Consumption was tabulated as defined daily doses (DDD) or as days of therapy (DOT) per 1,000 patient days (PD). Multivariate mixed-effects models were explored, and final model goodness of fit was assessed by regressions of observed versus predicted values and residual distributions. A total of 20 acute-care hospitals responded. The centers treated adult patients (n 19/20) and pediatric/neonatal patients (n 17/20). The majority of the centers were nonprofit (n 17/20) and not affiliated with medical/teaching institutions (n 11/20). The median (interquartile range [IQR]) carbapenem consumption rates were 38.8 (17.4 to 95.7) DDD/1,000 PD and 29.7 (19.2 to 40.1) DOT/1,000 PD overall. Carbapenem consumption was well described by a multivariate linear mixed-effects model (fixed effects, R2 0.792; fixed plus random effects, R2 0.974). Carbapenem consumption increased by 1.91-fold/quarter from 48.6 DDD/1,000 PD (P 0.004) and by 0.056-fold/quarter from 45.7 DOT/ 1,000 PD (P 0.93) over the study period. Noncarbapenem consumption was independently related to increasing carbapenem consumption (beta 0.31 for increasing noncarbapenem beta-lactam consumption; P 0.001). Regular antibiogram publication and promotion of conversion from intravenous (i.v.) to oral (p.o.) administration independently affected carbapenem consumption rates. In the final model, 58.5% of the observed variance in consumption was attributable to between-hospital differences. Rates of carbapenem consumption across 20 North American hospitals differed greatly, and the observed differences were correlated with hospital-specific demographics. Additional studies focusing on the drivers of hospital-specific carbapenem consumption are needed to determine whether these rates are justifiable