27 research outputs found
Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.
FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer
Control of a coupled tank system using PI controller with advanced control methods
The liquid level control in tanks and flow control between cascaded or coupled tanks are the basic control problems exist in process industries nowadays. Liquids are to be pumped, stored or mixed in tanks for various types of chemical processes and all these require essential control and regulation of flow and liquid level. In this paper, different types of tuning methods are proposed for Proportional-Integral (PI) controller and are further improved with integration of Advanced Process Control (APC) method such as feedforward and gain scheduling to essentially control the liquid level in Tank 2 of a coupled tank system. The MATLAB/Simulink tools are used to design PI controller using pole-placement, Ciancone, Cohen Coon and modified Ziegler-Nichols tuning method with Cohen Coon tuning method found to have a better performance. Advanced process control such as feedforward-plus-PI, Gain Scheduling (GS) based PI, Internal Model Control (IMC) based PI, feedforward-plus-GS-based PI and feedforward-plus-IMC-based PI controllers are further tested as improvement version to further compare the significance of the advanced process control outcomes hence GS-PI, improved GI-base PI-plus FF found to have better performance. The GS method is built over five operating points to approximate the system’s nonlinearity and is eventually combined with feedforward control to yield a much better performance
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Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.
ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN
An unexpected journey of a suction catheter in a preterm neonate
Foreign bodies are extremely rare in preterm neonates. The majority are iatrogenic. We describe a neonate of 27 weeks gestation who was found to have an 18Â mm long suction catheter at the right main bronchi after resuscitation in another hospital. It was first detected by chest X-ray after endotracheal intubation. Repeat X-ray revealed the catheter moved to the stomach and migrated to the lower gastrointestinal tract in a few hours. The patient was treated conservatively and the catheter was passed out on day 14. Newborn resuscitation may result in iatrogenic foreign body in neonates. Serious complications such as respiratory compromise, perforations or abscess may occur. Early referral to a specialized tertiary center with pediatric surgical service is recommended. We hope our experience demonstrated the importance of preventing iatrogenic foreign body in clinical setting. Access to endoscopic instrumentation for foreign body removal in preterm neonates should be available at all times
Cornu Cervi Pantotrichum Supplementation Improves Exercise Performance and Protects against Physical Fatigue in Mice
Cornu cervi pantotrichum (CCP) is a well-known yang-invigorating agent used in traditional Chinese medicine that can nourish the blood, tonify qi, and invigorate bones and tendons with multifunctional bioactivities. However, evidence on the effects of CCP on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of ethanolic extract from CCP on ergogenic and antifatigue functions following a physiological challenge. Male ICR mice from four groups (n = 8 per group) were orally administered CCP for 14 days at 0, 2054, and 4108 mg/kg/day, and were respectively designated as the vehicle, CCP-1X, and CCP-2X groups. The physical performance and antifatigue function were evaluated using forelimb grip strength and exhaustive swimming time as well as serum levels of lactate, ammonia, glucose, and creatine kinase after a 15-min swimming exercise. The results indicated that CCP-1X supplementation significantly improved grip strength; reduced fatigue-associated biochemical indices, including lactate and ammonia levels; and ameliorated skeletal muscle injury induced by acute exercise challenge. A trend analysis revealed that CCP supplementation significantly increased grip strength and dose-dependently reduced serum alkaline phosphatase, uric acid, triacylglycerol, and glucose levels in healthy mice. Therefore, CCP is a potential agent with an antifatigue pharmacological effect
Towards binder jetting and sintering of AZ91 magnesium powder
The inherent properties of magnesium (Mg) make it one of the most challenging metals to process with additive manufacturing (AM), especially with fusion-based techniques. Binder jetting is a two-step AM method in which green Mg objects print near room temperature, then the as-printed green object sinters at a high temperature. Thus far, a limited number of studies have been reported on the binder jetting of Mg powder. This study aimed to push the knowledge base of binder jetting and sintering for AZ91D powder. To this end, the principle of capillary-mediated binderless printing was used to determine the ink saturation level (SL) required for the binder jetting of a green AZ91 object. The effects of various SLs on forming interparticle bridges between AZ91 powder particles and the dimensional accuracy of the resultant as-printed objects were investigated. Green AZ91 objects sintered at different temperatures ranging from 530 °C to 575 °C showed a marginal increment in density with an increase in sintering temperature (i.e., 1.5% to 5.1%). The root cause of such a low sintering densification rate in the presence of up to 54.5 vol. % liquid phase was discussed in the context of the powder packing density of as-printed objects and swelling occurring at sintering temperatures ≥ 45 °C. Overall, this work demonstrates the great potential of binderless printing for AM of Mg powder and the need for pushing sintering boundaries for further densification of as-printed Mg components.Published versionThis research was funded by the first Singapore–Germany academic–industry (2 + 2) international collaboration grant (Grant no. A1890b0050)
How Do Acquired Political Identities Influence Our Neural Processing toward Others within the Context of a Trust Game?
Trust is essential for mutually beneficial human interactions in economic exchange and politics and people’s social identities notably have dramatic effects on trust behaviors toward others. Previous literature concerning social identities generally suggests that people tend to show in-group favoritism toward members who share the same identity. However, how our brains process signals of identity while facing uncertain situations in interpersonal interactions remains largely unclear. To address this issue, we performed an fMRI experiment with 54 healthy adults who belonged to two identity groups of opposing political orientations. The identity information of participants was extracted from a large-scale social survey on the 2012 Taiwan presidential election. Accordingly, participants were categorized as either the Kuomintang (KMT) or the Democratic Progressive Party (DPP) supporters. During the experiment, participants played trust games with computer agents with labels of the same or the opposing political identity. Interestingly, our results suggest that the behaviors of the two groups cannot be equally attributed to in-group favoritism. Behaviorally, only the DPP supporter group showed a significant trust preference toward in-group members, which did not hold for the KMT supporter group. Consistently, neurophysiological findings further revealed that only the DPP supporter group showed neuronal responses to both unexpected negative feedback from in-group members in anterior insula, temporoparietal junction, and dorsal lateral prefrontal cortex, as well as to unexpected rewards from out-group members in caudate. These findings therefore suggest that acquired identities play a more complex role in modulating people’s social expectation in interpersonal trust behaviors under identity-relevant contexts
Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.
BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation