Vitamin E Inhibits Osteoclastogenesis in Protecting Osteoporosis

The most common orthopedic condition affecting senior adults is osteoporosis, which is defined by a decrease in bone mass and strength as well as microstructural degradation that leads to fragility fractures. Bone remodeling is a well-planned, ongoing process that replaces deteriorated, old bone with new, healthy bone. Bone resorption and bone creation work together during the cycle of bone remodeling to preserve the bone’s volume and microarchitecture. The only bone-resorbing cells in the human body, mononuclear preosteoclasts fuse to form osteoclasts, are multinucleated cells. In numerous animal models or epidemiological studies, vitamin E’s anti-osteoporotic characteristics have been extensively described. This review aims to summarize recent developments in vitamin E’s molecular features as a bone-protective agent. In RANKL/RANK/OPG signaling pathway, vitamin E inhibits synthesis of RANKL, stimulation of c-Fos, and increase level of OPG. Vitamin E also inhibits inflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-27, and MCP-1, negative regulating the JAK–STAT, NF-κB, MAPK signaling pathways. Additionally, vitamin E decreases malondialdehyde and increases superoxide dismutase, GPx and heme oxygenase-1, in suppressing osteoclasts. In this article, we aim to give readers the most recent information on the molecular pathways that vitamin E uses to enhance bone health

SCF/c-KIT Signaling Increased Mucin2 Production by Maintaining Atoh1 Expression in Mucinous Colorectal Adenocarcinoma

Mucinous colorectal adenocarcinoma (MCA) patients often a show high risk of malignant potential and a poorer survival rate. Given that the pathological feature and oncobiological characteristics of MCA are correlated with its abundant extracellular mucin2 (MUC2), we paid interest toward investigating the key factor that promotes MUC2 production exposure to highly-activated stem cell factor (SCF)/c-KIT signaling, which we believed to contribute to MCA formation. Long-term azoxymethane and dextran sodium sulfate treatment successfully induced MCA only in wild-type (WT) mice at week 37 and 43, while all c-kit loss-of-function mutant mice (Wadsm/m) developed non-MCA. Significantly, MUC2 and its key transcriptional factor Atonal homologue 1 (Atoh1) were remarkably expressed in MCA mice compared with non-MCA mice. Atoh1 was significantly elevated in colorectal cancer (CRC) cells stimulated by exogenous SCF or overexpressing c-KIT in vitro, while decreased by the blockage of SCF/c-KIT signaling with Imatinib. Furthermore, the maintained Atoh1 protein level was due to the inactive glycogen synthase kinase 3β (p-GSK3β) by virtue of the activated SCF/c-KIT-Protein Kinase B (AKT) signaling. Similar results were obtained from the ONCOMINE database and CRC patients. In conclusion, we suggested that SCF/c-KIT signaling promoted MUC2 production and MCA tumorigenesis by maintaining Atoh1 expression. Therefore, targeting the related key molecules might be beneficial for treating MCA patients

Lipopolysaccharide induces the early enhancement of mice colonic mucosal paracellular permeability mainly mediated by mast cells

The alteration of intestinal mucosal barrier is considered to be the central pathophysiological process in response to gastrointestinal infections, and mucosal microstructural damage is a major factor for enhancing epithelial permeability in persistent bacterial infections. However, the mechanism involved in hyperpermeability in the early stage of acute bacterial infections is not fully understood. In the present study, fluorescein isothiocyanate-dextran across and transepithelial resistance measured in Ussing chambers were used to assess the intestinal paracellular permeability. Mast cell activation was evaluated by western blotting for the presence of tryptase released from mast cells. Serum levels of interleukin-6 were evaluated using enzymelinked immunosorbent assay. Our results indicated that mast cells played a pivotal role in colonic mucosal hyperpermeability in wild type mice treated with lipopolysaccharide (LPS) for 2 h. And the effect of LPS was mainly dependent on mast cell degranulation, while no change in permeability was observed in the mast celldeficient mice (Wads-/- ) after LPS administration. No obvious changes of the mucosal structure including histomorphological architecture and expression of intercellular junction proteins were obtained in either wild type or Wads-/- mice after LPS stimulation by hematoxylin and eosin staining, immunofluorescence staining and western blot analysis. Furthermore, the selfrenewal of intestinal epithelia, detected by using proliferation marker 5’-bromo-2’-deoxyuridine, was not involved in increased permeability. Collectively, activation of mast cells induced by LPS mediated intestinal hyperpermeability in the initial stage, and played a crucial role in barrier dysfunction rather than mucosal microstructural damage in acute enterogenous bacterial infection

Stimulus categories and the quality score (QS) of sound exemplars averaged within each category.

<p>Stimulus categories and the quality score (QS) of sound exemplars averaged within each category.</p

Selective brain maps for (a) English and (b) Music categories based on MSVM-RFE classification results.

<p>Panels (a1) – (a4) show the four largest clusters from voxels selected for the English category. Panel (a5) shows the cluster on the left Heschl’s gyrus. Panels (b1) – (b5) show the five largest clusters from voxels selected for the Music category. For each panel, the axial, sagittal and coronal slices are centered at the corresponding cluster. The left side of the brain is on the left side of the figure.</p

Classification accuracies across subjects for all seven sound categories using MSVM-RFE.

<p>Based on within-subject analysis results, the data from subject 4 was not included for the across-subject analysis. “leave sub1 out” means leaving subject 1 out. That means the model is trained on data from the 2nd, 3rd, 5th, and 6th subjects and is tested on data from the 1st subject.</p

Classification accuracies for seven-sound category classifiers built for each subject separately using MSVM-RFE.

<p>Error bars represent one standard deviation of the mean accuracy.</p

Comparison of seven-sound category classification accuracies obtained by four different MVPA models.

<p>Error bars represent one standard deviation of the mean accuracy.</p

The relationship chart of four different fMRI data analysis cases.

<p>(A) Case WithinSub: Classifiers are trained and tested for each subject separately; (B) Case AcrossSub: Classifiers are built across subjects, that is, leaving out the complete data of one subject for testing and using the data from all other subjects for training; (C) Case AvgItem: fMRI data are averaged over items and classifiers are built across subjects on the averaged data; (D) Case AvgSub: fMRI data are averaged over subjects and classifiers are built for this “averaged subject”. For each fMRI data analysis case, if a red rectangle contains only one subject, it indicates a within-subject analysis. Otherwise, the analysis is done across subjects.</p

Conjunction brain maps for common voxels between Cases WithinSub and each of the other three.

<p>Brain maps of the largest clusters formed by selected voxels that are common between Cases WithinSub and AvgSub, Cases WithinSub and AvgItem, and Cases WithinSub and AcrossSub are shown in parts (a), (b), and (c) respectively. The left side of the brain is on the left side of the figure.</p