Differential Regulation of Decorin and Biglycan Gene Expression by Dexamethasone and Retinoic Acid in Cultured Human Skin Fibroblasts

Proteoglycans participate in the assembly of extracellular matrix, directly by interacting with other matrix components and indirectly by regulating cellular growth-factor responses. We have studied the regulation of gene expression of two small extracellular matrix chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, by dexamethasone and retinoic acid In cultured human skin fibroblasts. Dexamethasone increased decorin production, maximally 4,8- fold, and decorin mRNA levels up to 2.3-fold, but had no effect on biglycan production or mRNA levels. Dexamethasone also prevented transforming growth factor-β-elicited down-regulation of decorin mRNA levels and production by dermal fibroblasts. In addition, dexamethasone potently inhibited enhancement of biglycan production and mRNA levels by transforming growth factor-β. Retinoic acid dose dependently reduced decorin mRNA levels (by 51%) and production (by 72%), but had no effect on biglycan gene expression. Retinoic acid did not alter the effect of transforming growth factor-β on decorin or biglycan production or mRNA levels. These results provide evidence that tile effects of glucocorticoids and retinoids on dermal connective tissue are partially mediated via altered expression of decorin and biglycan, which both in turn regulate the activity of transforming growth factor-β, the most potent stimulator of connective tissue deposition

Volkswagen-huoltoprosessin kehittäminen lean menetelmin

Tämän opinnäytetyön tavoite oli kehittää Volkswagen Center Turun huoltoprosessia Leanmenetelmin, prosessin sujuvuutta vastaamaan yrityksen tavoitteita ja tulevaisuudennäkymiä sekä auttaa ymmärtämään syitä tuloksen takana. Menestyvä yritys syntyy motivoituneista ja tyytyväisistä työntekijöistä ja siksi työntekijöiden tyytyväisyys ja siihen panostaminen oli yksi tärkeimmistä kehityskohteista ja se vaatii myös jatkuvaa kehitystä ja ylläpitäviä toimintamalleja. Menetelmissä keskityttiin paljon henkilöstön hyvinvointiin sekä sitouttamiseen, jotka ovat jatkuvan muutoksen keskellä tärkeitä tehokkaan toiminnan kannalta. Opinnäytetyössä hyödynnettiin työntekijöiden kokemuksia keskusteluiden ja kysely- ja haastattelututkimuksien avulla. Opinnäytetyön aikana organisaatiossa toteutui organisaation rakennemuutoksia sekä mittava järjestelmämuutos. Uudet käyttöjärjestelmät ja tehostetumpi työtehtävien jaottelu mahdollistivat paremman keskittymisen yhteen osa-alueeseen. Yhdeksi laajemmaksi kehitys- ja tutkimuskohteeksi valittiin hallityönjohtajan rooli huollon toimihenkilöiden tiimissä. Hallityönjohdon esiselvityksen tavoitteena oli kartoittaa erillisen hallityönjohdon käyttöönoton mahdollisuutta Turun toimipisteessä. Esiselvitys toteutettiin tutustumalla hallityönjohdon toteutukseen muissa K-Caaran toimipisteissä. Vastuualueiden jako oli esiselvityksen mukaan yksi tärkeimmistä tekijöistä järjestelyn toimivuuden kannalta. Hallityönjohto ja vastuualueiden jako otettiin käyttöön ehdotelman mukaisesti, jolloin valittiin yksi vakituinen hallityönjohtaja sekä muiden toimihenkilöiden vastuualueet selkeytettiin. Henkilöstön sitouttaminen on avaintekijä muutoksen onnistumisessa. Tämä huomioitiin opinnäytetyötä tehdessä tutkimalla ja luomalla kehitysehdotuksia muun muassa kehityskeskusteluiden pitämiseen sekä palaverikäytäntöjen luomiseen ja tehostamiseen. Opinnäytetyön valmistuessa organisaatiossa on vielä suuria muutoksia meneillään. Opinnäytetyö toimi yrityksen huoltotoiminnan tarkastelun sekä muutoksen aloittajana, jonka keskeisin onnistuminen oli erillisen hallityönjohdon suunnittelu ja käyttöönotto, sekä toimihenkilöiden työtehtävien tarkastelun sekä uudelleenorganisoinnin ja käyttöönoton.The aim of the present Master’s thesis was to develop the VW service process in Volkswagen Center Turku with Lean methods, to help understand the reasons behind the result, to develop the fluency of the process and to meet the goals and future prospects of the company. Motivated and satisfied employees make a successful company. Therefore, employee satisfaction and investing in it was one of the main development targets and it requires continuous development. The methods used in the present study focus on the well-being and commitment of the employees. Employee well-being and commitment are important for an efficient way of working, especially in a situation characterized by a constant change. The employees’ experiences were studied through discussions, surveys and interviews. During the thesis process, a major system change as well as organizational changes took place in the company. New systems and a more efficient division of work allowed employees to focus on one area at a time. One of the broadest development and research targets was the position of the independent supervisor in the maintenance staff team. The aim of the preliminary study on the position was to survey the possibility of introducing an independent supervisor position at VW Turku. The preliminary study was carried out by exploring the implementation of the supervisor position in other K Caara services. According to the preliminary study, the clarity and division of the responsibilities was one of the most important factors for a successful way of working. The supervisor position and division of responsibilities were introduced in accordance with the plan. An independent supervisor was named and the responsibilities between the employees were clarified. The engagement of the employees is a key factor in the success of a change. This was taken into account in the thesis by researching and creating development proposals. The proposals include, among others, holding development discussions and enhancing meeting practices. As the thesis was completed, major changes were still taking place in the organization. The thesis was the initiator of the development and reviewing of the company’s service operations. The main success was the planning and implementation of an independent supervisor position as well as reviewing the work tasks of the employees, reorganization and introduction of the new ways of working

Expression of the ???6 integrin promotes migration and invasion in squamous carcinoma cells

The integrin αvβ6 is a fibronectin receptor whose expression is not detectable on normal oral epithelium but is increased significantly in healing and in oral epithelial dysplasia and oral squamous cell carcinoma, suggesting it may promote changes associated with tumor development. To study whether αvβ6 may drive invasive behavior we have used transfection and retroviral infection to create a panel of epithelial cell lines expressing various levels of αvβ6. We report that increased expression of αvβ6 in malignant keratinocytes promotes invasion and leads to an increased capacity for migration towards fibronectin. αvβ6 expression may have a significant role in contributing to the malignant behavior of epithelial cells

Transforming Growth Factor-β Induces Collagenase-3 Expression by Human Gingival Fibroblasts via p38 Mitogen-activated Protein Kinase

Human collagenase-3 (matrix metalloproteinase 13 (MMP-13)) is characterized by exceptionally wide substrate specificity and restricted tissue specific expression. Human skin fibroblasts in culture express MMP-13 only when they are in three-dimensional collagen (Ravanti, L., Heino, J., Lopez-Otin, C., and Kahari. V.-M. (1999) J. Biol. Chem. 274, 2446-2455). Here we show that MMP-13 is expressed by fibroblasts during normal human gingival wound repair. Expression of MMP-13 by human gingival fibroblasts cultured in monolayer or in collagen gel was induced by transforming growth factor-beta1 (TGF-beta1). Treatment of gingival fibroblasts with TGF-beta1 activated two distinct mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2) in 15 min and p38 MAPK in 1 and 2 h. Induction of MMP-13 expression by TGF-beta1 was blocked by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a selective inhibitor of ERK1/2 activation. Adenovirus-mediated expression of dominant negative p38alpha and c-Jun potently inhibited induction of MMP-13 expression in gingival fibroblasts by TGF-beta1. Infection of gingival fibroblasts with adenovirus for constitutively active MEK1 resulted in activation of ERK1/2 and JNK1 and up-regulation of collagenase-1 (MMP-1) and stromelysin-1 (MMP-3) production but did not induce MMP-13 expression. In addition, activation of p38 MAPK by constitutively active MKK6b or MKK3b was not sufficient to induce MMP-13 expression. These results show that TGF-beta-elicited induction of MMP-13 expression by gingival fibroblasts is dependent on the activity of p38 MAPK and the presence of functional AP-1 dimers. These observations demonstrate a fundamental difference in the regulation of collagenolytic capacity between gingival and dermal fibroblasts and suggest a role for MMP-13 in rapid turnover of collagenous matrix during repair of gingival wounds, which heal with minimal scarring

Benzoyl-arginine naphthylamide (BANA) hydrolysis by Treponema denticola and/or Bacteroides gingivalis in periodontal plaques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73624/1/j.1399-302X.1990.tb00425.x.pd

Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption-ionization-mass spectrometry imaging (MALDI-MSI).

Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids directly involved as potential biomarkers. These biomarkers may be used to determine whether an in vivo wound is going to heal for example if infected. An in vitro LSE model was wounded with a scalpel blade and assessed at day 4 post wounding by histology and MALDI-MSI. Samples were sectioned at wound site and were either formalin fixed paraffin embedded (FFPE) for histology or snapped frozen (FF) for MSI analysis. The combination of using an in vitro wounded skin model with MSI allowed the identification of lipids involved in the skin barrier repair/wound healing process. The technique was able to highlight lipids directly in the wound site and distinguish differences in lipid distribution between the epidermis and wound site. This novel method of coupling an in vitro LSE with MSI allowed in depth molecular analysis of the skin barrier repair/wound healing process. The technique allowed the identification of lipids directly involved in the skin barrier repair/wound healing process, indicating these biomarkers may be potentially be used within clinic. These biomarkers will help determine, which stage of the skin barrier repair/wound healing process the wound is in to provide the best treatment. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Suositus potilaan suojaamisesta röntgentutkimuksissa

Ulkoisia säteilysuojaimia on perinteisesti käytetty ionisoivaa säteilyä hyödyntävässä kuvantamisessa potilaan säteilyherkkien kudosten, elimien ja sikiön suojaamiseksi. Kuvantamistekniikoiden kehittymisen myötä säteilysuojainten käytön tarve on vähentynyt. Tieteellisten tutkimusten myötä myös tieto kudosten ja elimien säteilyherkkyyksistä on parantunut [1]. Terveydenhuollon yksiköissä säteilysuojainten käytön tulee perustua ajankohtaisiin tieteellisiin tutkimustuloksiin ja niiden perusteella laadittuihin suosituksiin. Tämä suositus pohjautuu vuonna 2022 julkaistuun eurooppalaiseen konsensukseen potilaiden suojaamisesta röntgentutkimuksissa [1] sekä muihin tieteellisiin julkaisuihin. Suosituksissa ei oteta kantaa henkilökunnan tai tukihenkilöiden säteilysuojaukseen

Biological effects of a root conditioning agent for dentin surface modification in vitro

Purpose: Connective tissue reattachment to periodontally damaged root surfaces is one of the most important goals of periodontal therapy. The aim of this study was to develop a root conditioning agent that can demineralize and detoxify the infected root surface. Methods: Dentin slices obtained from human teeth were treated with a novel root planing agent for 2 minutes and then washed with phosphate-buffered saline. Smear layer removal and type I collagen exposure were observed by scanning electron microscopy (SEM) and type I collagen immunostaining, respectively. Cell attachment and lipopolysaccharides (LPS) removal demonstrated the efficiency of the root conditioning agent. Results: SEM revealed that the smear layer was entirely removed and the dentinal tubules were opened by the experimental gel. Type I collagen was exposed on the surfaces of the dentin slices treated by the experimental gel, which were compared with dentin treated with other root planing agents. Dentin slices treated with the experimental gel showed the highest number of attached fibroblasts and flattened cell morphology. The agar diffusion assay demonstrated that the experimental gel also has effective antimicrobial activity. Escherichia coli LPS were effectively removed from well plates by the experimental gel. Conclusions: These results demonstrated that this experimental gel is a useful tool for root conditioning of infected root surfaces and can also be applied for detoxification of ailing implant surface threads. ⓒ 2010 Korean Academy of Periodontology.

Identification of a transcriptional signature for the wound healing continuum

There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post-serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF < NF < CWF are candidates for a negative/impaired healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group). Sixty-six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified. Overrepresentation analysis revealed pathways directly and indirectly associated with wound healing and aging and additional categories associated with differentiation, development, and morphogenesis. Knowledge of this wound healing continuum gene signature may in turn assist in the therapeutic assessment/treatment of a patient's wounds