OBJECTIVE 1) To study the efficacy of GSPs on the migration of highly metastatic mammary carcinoma cells and 2) To investigate inhibition mechanisms. METHODS Cell migration was assessed using a ...24-well transwell assay. Cells with diff erent concentrations of GSPs were suspended (5 × 105cell/mL) in RPMI 1640 media in the upper chamber, and RPMI 1640 media with 10% FBS was supplemented in the lower chamber. Then, cells were allowed to migrate for 24 h.RESULTS GSPs inhibited the migration of 4T1 cells in a dose-dependent manner. The migration of 4T1 cells was obviously inhibited by GSPs, even at a very low concentration (5 μg/mL), and was totally inhibited when the concentration was 20 μg/mL. Also, 20 μg/mL of GSPs inhibited cell viability by only 11.4% and induced early apoptosis by only 5.6% compared with a percentage of 4.0% in control cells. GSPs suppressed the activation of PDK1, Akt and Erk1/2 in a dose- dependent manner.CONCLUSION GSPs significantly inhibit the migration of highly metastatic mammary carcinoma 4T1 cells in vitro. This inhibition is independent of decreased cell viability or apoptosis induction. The inhibition of migration by GSPs is involved in blocking the PI3k/Akt and MAPK pathways.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Objective The rostral anterior cingulate cortex (rACC) is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors (NMDARs) are highly expressed in the rACC and ...mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate (cAMP)/protein ki- nase A (PKA) and/or extracellular regulated kinase (ERK)/cAMP-response element-binding protein (CREB). The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK (pERK) and phospho-CREB (pCREB) in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Extracting B2O3 from calcined boron mud(CBM) was studied. The effect of factors such as reaction temperature and NaO H-to-CBM mass ratio on B2O3 extraction efficiency was investigated. The results ...show that increasing reaction temperature and NaO H-to-CBM mass ratio increases B2O3 extraction efficiency. There are two stages for the B2O3 extracting process: 0–20 min is the first stage, which is rapid; 20–50 min is the second stage, which is slower than the first stage. The overall extracting process follows the shrinking core model, and the first and second stages are determined to obey the surface chemical reaction model and the diffusion through the products layer model,respectively. The activation energies of the first and second stages are calculated to be 41.74 and 15.43 kJ·mol-1,respectively. The B2O3 extracting kinetics equations of the first and second stages are also obtained.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective: To introduce the imaging characteristics of moyamoya disease (MMD) using high-resolution magnetic resonance imaging (HR-MRI) and to discuss the role of HR-MRI in differentiating MMD from ...other intracranial artery diseases, especially intracranial atherosclerotic disease (ICAD). Data Sources: This review was based on the data in articles published between 2005 and 2015, which were obtained from PubMed. The keywords included HR-MRI, MMD, ICAD, and intracranial artery diseases. Study Selection: Articles related to HR-MRI for MMD or other intracranial artery diseases were selected for review. Results: There are differences between the characteristic patterns of HR-MRI in MMD and ICAD. MMD is associated with inward remodeling, smaller outer diameters, concentric occlusive lesions and homogeneous signal intensity, while ICAD is more likely to be associated with outward remodeling, normal outer diameters, eccentric occlusive lesions, and heterogeneous signal intensity. Other intracranial artery diseases, such as dissection and vasculitis, also have distinctive characteristics in HR-MRI. HR-MRI may become a useful tool for the differential diagnosis of MMD in the future. Conclusions: HR-MRI of MMD provides a more in-depth understanding of MMD, and it is helpful in evaluating pathological changes in the vessel wall and in differentiating MMD from other intracranial artery steno-occlusive diseases, particularly ICAD.以
Background: Current treatments for scoliosis have some defects and complications. To study spinal deformities and test novel scoliosis treatments, many animal models of scoliosis have been developed. ...These models applied a single load to the spine and could not precisely modulate the spinal growth in different dimensions. In this study, we applied posterior tethering in various directions with the application of nickel-titanium (NT) coil springs in dog's spine to modulate spinal growth in the coronal, sagittal, and transverse planes and create a scoliosis model possess curves that mimic adolescent idiopathic scoliosis (AIS) three dimensionally. Methods: Scoliosis was surgically induced in eight 8-week-old female dogs (weight: 1.95–2.30 kg) using bone screws and NT coil springs. The deformity was induced through the placement of posterior NT coil springs that tethered the spine by bone screw fixation. All dogs were monitored with serial radiographs to document changes in deformities. Results: All experimental animals developed scoliotic curves convex to the left in the lumbar segment. The mean coronal Cobb angle was 18.0° immediately postoperatively and 54.5° at 22 weeks. The mean lordosis increased from 6.2° postoperatively to 35.0° at final follow-up. Apical axial rotation increased from 4.5° postoperatively to 31.2° at 22 weeks. Conclusions: With the application of NT springs in dogs that allowed posterior tethering in various directions, lumbar spinal deformity was achieved in three planes: coronal, sagittal, and transverse planes. Notably, the lumbar spine in surgically treated dogs developed lordoscoliosis with obvious rotation and the curves mimic AIS three dimensionally well. This method allows lumbar scoliosis to develop without deep dissection of muscle and maintains the essential anatomical elements along the spinal curve. Moreover, the spinal growth modulation technique could yield information that would provide a basis for developing novel early-stage treatments for children with scoliosis.
AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic mouse model was established by ...intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 rain before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated. RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT. CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
Miniaturized channel filters are in high demand for many applications such as photonic integrated circuits, information-based technology, and platforms for investigation of light–matter ...interactions.Recently, several photonic schemes have been proposed to achieve nanofilters, which require sophisticated growth techniques. Here, we have fabricated microdisk whispering-gallery-mode(WGM) resonators through controlled assembly of organic materials with an emulsion-solventevaporation method. Based on this emulsion assembly method, the diameters of microdisks can be easily controlled, and more importantly, a microwire-disk interconnected structure is able to be constructed via one-step assembly. This microwire-waveguide-connected microdisk heterostructure can be utilized as a channel drop filter. Our results have demonstrated a facile way to achieve flexible WGM-based photonic components which can be integrated with other functional devices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The aetiology of inflammatory bowel disease (IBD) is a multifactorial interplay between heredity and environment
. Here we report that deficiency in SETDB1, a histone methyltransferase that mediates ...the trimethylation of histone H3 at lysine 9, participates in the pathogenesis of IBD. We found that levels of SETDB1 are decreased in patients with IBD, and that mice with reduced SETDB1 in intestinal stem cells developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability
, and the loss of SETDB1 in intestinal stem cells released repression of endogenous retroviruses (retrovirus-like elements with long repeats that, in humans, comprise approximately 8% of the genome). Excessive viral mimicry generated by motivated endogenous retroviruses triggered Z-DNA-binding protein 1 (ZBP1)-dependent necroptosis, which irreversibly disrupted homeostasis of the epithelial barrier and promoted bowel inflammation. Genome instability, reactive endogenous retroviruses, upregulation of ZBP1 and necroptosis were all seen in patients with IBD. Pharmaceutical inhibition of RIP3 showed a curative effect in SETDB1-deficient mice, which suggests that targeting necroptosis of intestinal stem cells may represent an approach for the treatment of severe IBD.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We revisit the proposed extended Schmidt law, which posits that the star formation efficiency in galaxies depends on the stellar mass surface density, by investigating spatially resolved star ...formation rates (SFRs), gas masses, and stellar masses of star formation regions in a vast range of galactic environments, from the outer disks of dwarf galaxies, to spiral disks and to merging galaxies, as well as individual molecular clouds in M33. We find that these regions are distributed in a tight power law as ∝ , which is also valid for the integrated measurements of disk and merging galaxies at high-z. Interestingly, we show that star formation regions in the outer disks of dwarf galaxies with down to 10−5 yr−1 kpc−2, which are outliers of both the Kennicutt-Schmidt and Silk-Elmegreen laws, also follow the extended Schmidt law. Other outliers in the Kennicutt-Schmidt law, such as extremely metal-poor star formation regions, also show significantly reduced deviation from the extended Schmidt law. These results suggest an important role for existing stars in helping to regulate star formation through the effect of their gravity on the midplane pressure in a wide range of galactic environments.