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Simple Summary: Extrahepatic cholangiocarcinoma (EHCC) is an aggressive tumor. The five-year survival rate for patients who undergo surgical resection is only 20–40% due to recurrences. Therefore, elucidating the molecular mechanisms underlying invasion and metastasis in EHCC is crucial for developing adjuvant therapy. The epithelial–mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in two EHCC cell lines. CCR7 mediates cell invasion and migration in EHCC by inducing EMT, which was abrogated by a CCR7 antagonist. CCR7 may be a potential target for adjuvant therapy in EHCC. The epithelial–mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC. [ABSTRACT FROM AUTHOR]

Background and Objective The periodontal ligament ( PDL) is characterized by rapid turnover, high remodeling capacity and high inherent regenerative potential compared with other connective tissues. Periostin, which is highly expressed in the fibroblasts in the PDL, has been widely discussed in relation to collagen fibrillogenesis in the PDL. Recently, several reports have indicated periostin in cell migration. The aim of this study was to examine whether human PDL fibroblasts ( hPDLFs) with high levels of periostin expression promote the migration of human bone marrow mesenchymal stem cells ( hMSCs). Material and Methods The migration of hMSCs was examined by transwell chamber migration assay under different conditions: medium alone, hPDLFs, human dermal fibroblasts, recombinant periostin, integrin αvβ3 blocking antibody (anti- CD51/61 antibody) and inhibitors of FAK ( PF431396) and PI3 K ( LY294002). Phosphorylation of FAK and Akt in hMSCs under stimulation of periostin was examined by western blotting. Results The migration assay revealed that the number of migrated hMSCs by hPDLFs was significantly larger than those by dermal fibroblasts, periostin small interfering RNA hPDLFs and medium alone. Furthermore, recombinant periostin also strongly induced hMSC migration. The addition of anti- CD51/61 antibody, PF431396 and LY294002 caused a significant reduction in the number of migrated hMSCs respectively. The anti- CD51/61 antibody inhibited both FAK and Akt phosphorylations under periostin stimulation. PF431396 inhibited both FAK and Akt phosphorylations. LY294002 inhibited only Akt phosphorylation, and FAK phosphorylation was not influenced under periostin stimulation. Conclusion Periostin expression in hPDLFs promotes the migration of hMSCs through the αvβ3 integrin/ FAK/ PI3 K/ Akt pathway in vitro. [ABSTRACT FROM AUTHOR]

Background and Objective Epithelial cells are recognized as the first line of defense against bacterial infection and environmental harmful stimuli such as cigarette smoke ( CS). Although previous studies explored the effects of nicotine on host cells, mechanisms by which CS affects cellular functions remain uncertain. The present study investigated the effects of CS condensate ( CSC) on in vitro wound closure of gingival epithelial cells and their potential interactions with a major periodontal pathogen, Porphyromonas gingivalis. Material and Methods Human gingival epithelial cells (Ca9-22) were treated with CSC for 24 h. Cell proliferation was determined using a WST-1 assay. Cell migration was assessed using a wound closure model. The expression of integrins was analyzed by confocal scanning laser microscopy and real-time PCR. Intracellular invasion of P. gingivalis was evaluated by confocal scanning laser microscopy and an antibiotic protection assay. Results Low concentrations (1-10 μg/mL) of CSC showed no significant effect on cell proliferation. CSC demonstrated dual effects on epithelial wound closure of Ca9-22 cells: high concentrations (i.e. 250 μg/mL) significantly inhibited the wound closure whereas low concentrations (i.e. 10 μg/mL) promoted it ( p < 0.01). CSC induced distinct changes in cytoskeleton. When CSC-exposed cells were infected with P. gingivalis for 2 h, a significant inhibition of wound closure was observed concurrent with a decrease in integrin α3 expression near the wound area. A significantly increased P. gingivalis invasion into Ca9-22 was observed when exposed to low concentrations of CSC. Conclusion Low concentrations of CSC increased invasion of human gingival epithelial cells by P. gingivalis and induced changes in cytoskeleton and integrin expression, thereby modulating the cell migration. [ABSTRACT FROM AUTHOR]

Background: The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels. Methods: We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS). Results: In subjects with BMI below 25 kg/m2, both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m2, smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS. Conclusions: Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than nonsmokers. [ABSTRACT FROM AUTHOR]

Abstract: To better understand the mechanism underlying the bloom outbreaks of dinoflagellates, Ceratium furca, and Ceratium fusus in the temperate coastal area of Sagami Bay, we investigated the diel changes of vertical migration, swimming speed, cell volume, and cell division. Our results from both the field and laboratory indicate that C. furca and C. fusus can migrate vertically between surface and sub-surface layers to avoid strong sunlight (>1000μmolm−2 s−1). Diel vertical migration (DVM) of C. furca was observed in the laboratory, while that of C. fusus was not observed. C. furca demonstrated a constant DVM rhythm, i.e., their cells began to descend from the surface before the light was extinguished, and ascended into the surface before the light was turned on. The downward and upward migrations of the cells occurred at every 3h before turning on and off the light, suggesting that the DVM pattern was independent of nutrient concentration. The swimming speeds of C. furca (avg. 250μms−1) were always faster than those of C. fusus (avg. 75μms−1). In addition, the speeds of C. furca during light periods were faster than those during dark periods, whereas the speeds of C. fusus remained relatively constant. A higher proportion of dividing cells was recorded near dawn (05:00–07:00h). Cell volumes of C. furca and C. fusus did not markedly change between 12:00 and 21:00h, but gradually increased until 03:00h and then sharply decreased. Furthermore, the cell volume of the two Ceratium species was significantly shifted to the temporal pattern of cell division. Combined with the DVM manner of two Ceratium and cell division timing, only C. furca divided at the bottom, and then moved toward the surface shortly before the dark to light transition. Based on our observations, C. furca has an ecological advantage due to their DVM activity, since nutrients can be obtained well in the near bottom layers, while during the daytime, light present in nutrient-depleted surface water can be obtained using their high swimming speed. On the other hand, C. fusus stimulated by low salinity conditions, might be dependent on external environmental conditions such as additional nutrients following freshwater discharge by heavy rainfall because they may not perform active DVM due to a slow swimming ability. Our findings support that specific characteristics, including the DVM behavior in C. furca, yield a competitive advantage over C. fusus in Sagami Bay. [Copyright &y& Elsevier]

Pholiota nameko, a type of edible and medicinal fungus, is currently grown extensively for food and traditional medicine in China and Japan. It possesses various biological activities, such as anti-inflammatory, anti-hyperlipidemia and antitumor activities. However, P. nameko has rarely been discussed in the field of dermatology; identifying its biological activities could be beneficial in development of a new natural ingredient used in wound care. To evaluate its in vitro wound healing activities, the present study assessed the antioxidant and anti-collagenase activities of P. nameko polysaccharides (PNPs) prepared through fractional precipitation (40%, 60% and 80% (v/v)); the assessments were conducted using reducing power, hydroxyl radical scavenging activity, dichloro-dihydro-fluorescein diacetate and collagenase activity assays. The ability of PNPs to facilitate L929 fibroblast cell proliferation and migration was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch assays. The findings indicated that, among all fractions, PNP-80 showed the best antioxidant and anti-collagenase activity, as measured by their reducing power (IC50 of PNP-80 was 2.43 ± 0.17 mg/mL), the hydroxyl radical scavenging (IC50 of PNP-80 was 2.74 ± 0.11 mg/mL) and collagenase activity assay, and significantly reduced cellular ROS content, compared with that of H2O2-induced L929 cells. Moreover, PNP-80 significantly promoted L929 fibroblast proliferation and migration, compared with the control group. Overall, we suggested that PNP-80 could be a promising candidate for further evaluation of its potential application on wound healing. [ABSTRACT FROM AUTHOR]

The article focuses on a study which found that nucleus is not pulled by centrosome in migrating neurons conducted by Hiroki Umeshima and colleagues at RIKEN Brain Science Institute in Japan. The imaging study of mouse cerebellar slices revealed that nucleus passed in front of centrosome. The research indicated that inhibition of LIS1, which regulates microtubule motor dynein, hindered the migration of nucleus without interfering with centrosome.

The appendicularian, Oikopleura dioica, is a planktonic chordate. Its simple and transparent body, invariant cell lineages and short life cycle of 5 days make it a promising model organism for studies of chordate development. Here we describe the cell migration that occurs during development of the O. dioica larva. Using time-lapse imaging facilitated by florescent labeling of cells, three cell populations exhibiting long-distance migration were identified and characterized. These included (i) a multinucleated oral gland precursor that migrates anteriorly within the trunk region and eventually separates into the left and right sides, (ii) endodermal strand cells that are collectively retracted from the tail into the trunk in a tractor movement, and (iii) two subchordal cell precursors that individually migrate out from the trunk to the tip of the tail. The migration of subchordal cell precursors starts when all of the endodermal strand cells enter the trunk, and follows the same path but in a direction opposite to that of the latter. Labeling of these cells with a photoconvertible fluorescent protein, Kaede, demonstrated that the endodermal strand cells and subchordal cell precursors have distinct origins and eventual fates. Surgical removal of the trunk from the tail demonstrated that the endodermal strand cells do not require the trunk for migration, and that the subchordal cell precursors would be attracted by the distal part of the tail. This well-defined, invariant and traceable long-distance cell migration provides a unique experimental system for exploring the mechanisms of versatile cell migration in this simple organism with a chordate body plan., (Copyright © 2014 Elsevier Inc. All rights reserved.)