The role of osteoblasts in regulating hematopoietic stem cell activity and tumor metastasis

Bone marrow stromal cells are critical regulators of hematopoiesis. Osteoblasts are part of the stromal cell support system in bone marrow and may be derived from a common precursor. Several studies suggested that osteoblasts regulate hematopoiesis, yet the entire mechanism is not understood. It is clear, however, that both hematopoietic precursors and osteoblasts interact for the production of osteoclasts and the activation of resorption. We observed that hematopoietic stem cells (HSCs) regulate osteoblastic secretion of various growth factors, and that osteoblasts express some soluble factors exclusively in the presence of HSCs. Osteoblasts and hematopoietic cells are closely associated with each other in the bone marrow, suggesting a reciprocal relationship between them to develop the HSC niche. One critical component regulating the niche is stromal-derived factor-1 (SDF-1) and its receptor CXCR4 which regulates stem cell homing and, as we have recently demonstrated, plays a crucial role in facilitating those tumors which metastasize to bone. Osteoblasts produce abundant amounts of SDF-1 and therefore osteoblasts play an important role in metastasis. These findings are discussed in the context of the role of osteoblasts in marrow function in health and disease.

Livets källa kärleken : hälsans urkraft

This basic research focuses on the ethos of health and the human being's becoming in health. The theoretical perspective consists of the caring tradition within caring science developed at Åbo Akademy University. The aim of the present doctoral thesis is to uncover a new understanding as well as to deepen and attain a more nuanced understanding of the ethos of health, the essence of health, by penetrating to the core of what gives the human being the strength for experiencing a becoming in health. The research questions are as follows: l) What is the human being's source of strength? and 2) What reveals the source of strength so that the human being can perceive it and dedicate its strength in order to experience a becoming in health? The primary methodology used in the dissertation is hermeneutical. The material consists of the work Kärlekens gerningar by Kierkegaard, texts from focused interviews with respondents who have lived through severe personal suffering, as well as the book Det bländande mörkret by Wikström. These texts are interpreted through hermeneutical reading. The new horizon of understanding that emerges is reflected towards Eriksson's caritative theory, towards prior research within the tradition of caring science at Åbo Akademy University and towards previous national and international studies within this field. The new understanding shows that the human being's source of strength is love, the essence and origin of life. The substance of health is love, which, through the trinity of faith, hope and love, also makes possible the existence of the source of strength. Love has a deeper dignity than faith and hope, is connected with eternity and is the uniting link between temporality and eternity. The human being's inner longing entails an ontological attraction towards the source of strength. This source of strength is hidden, which provides and maintains its force, like a mystery connected with the darkness of suffering that hides the secret representing the source of strength, life's mystery, bu t w hi ch is revealed in both the darkness of suffering and in the light of joy. The dedication of strength requires freedom, willingness and courage to see the light, despite awareness of shame and guilt. Creative acts liberate the human being for the dedication of strength, which is preceded by a holy presence where, in solitude, the human being makes sacrifices for the sake of his or her human smallness and weakness, and allows himself or herself to be enclosed by the darkness of suffering to discover the light from the source. This entails being enraptured in a quiet "doing" in order to experience the beauty that bears witness to the holy which creates unity. The source of strength is revealed through beauty. The ethos of the human being and the ethos of health have the same fundamental substance, whilst the ethos of life possesses the deepest dimension and concerns the mysterious and infinite eternity. The ethos of life, eternity, which is a wellspring of strength, is not in itself strength-giving unless it is allied with love. Health can be understood in the light of life, of which death is an inevitable part. Life itself constitutes and creates the source which, through its alliance with eternity' s primordial wellspring of strength, generates strength from which the human being's source of strength, love, receives its eternal fervour. The human being is fundamentally interconnected with an abstract other, the first love, a universal wellspring of strength. Through Communion with this abstract other a dedication of the strength to experience a becoming in health becomes possible. Love for one's neighbour is the fundamental substance in the movement of becoming in health. Becoming in health presupposes a simultaneous movement in which the human being practices the human calling through ethos. As one loves one's neighbour through actions the still forces of eternity are in motion. When life emerges in the foreground and becomes the home of the human being, a dedication of the power of love is possible. Life itself determines the human being's becoming in health. A humble fundamental attitude towards life constitutes the basis for a continuous dedication of vitality from this source.

Auringon asemaa seuraavan aurinkopaneelijärjestelmän kehittäminen

Tässä diplomityössä käsitellään Aurinkoa seuraavan aurinkopaneelijärjestelmän kehittämistä Suomen olosuhteisiin. Työ on tehty osana Lappeenrannan teknillisen yliopiston Green Campus-projektia, jossa tarkoituksena on tuottaa yliopistolle energiaa uusiutuvilla menetelmillä ja käyttää niitä apuna tutkimuksessa sekä opetuksessa. Tavoitteena työssä on ymmärtää Auringon seuraamisen hyödyt sekä mahdolliset haitat aurinkopaneeli sovellutuksissa. Aikaisemman tutkimustiedon ollessa vähäistä, on työssä pyritty löytämään laskentamalli tuottavuuden laskentaan riippumatta siitä, missä päin maapalloa aurinkopaneelijärjestelmä sijaitsee. Työ alkaa kirjallisuustutkimuksella, jossa käydään läpi aurinkopaneelien toimintaperiaate, aurinkoenergian ja auringonpaistetuntien suuruusluokat Suomessa, sekä Suomen sääoloista johtuvat vaatimukset aurinkopaneelijärjestelmille. Tämän jälkeen on vertailtu kaupallisia järjestelmiä. Lopuksi järjestelmällistä tuotesuunnittelua hyväksikäyttäen suunnitellaan oma versio Aurinkoa seuraavasta aurinkopaneelijärjestelmästä. Oman suunnitelman järkevyyttä simuloidaan pienoismallilla Matlab-Arduino ympäristössä ja pyritään löytämään mahdollisia heikkouksia. Suomessa aurinkoenergiasta 90 % saadaan maalis – syyskuun aikana. Nykyisillä akkujärjestelmillä aurinkoenergia Suomessa ei sovellu kuin täydentäväksi energianlähteeksi. Aurinkoa seuraamalla voidaan saavuttaa 25-30 % tuottavuuden lisäys kesäaikana verrattuna staattiseen järjestelmään. Talvella hyöty tippuu 0-10 % luokkaan. Pienoismallilla simuloidut ohjaustavat osoittivat, että Aurinkoa on mahdollista seurata ilman sensoreita laskemalla Auringon paikka tähtitieteen kaavoista.

Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70% hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.

Primary mechanism of apoptosis induction in a leukemia cell line by fraction FA-2-b-ß prepared from the mushroom Agaricus blazei Murill

Agaricus blazei Murill is a native Brazilian mushroom which functions primarily as an anticancer substance in transplanted mouse tumors. However, the mechanism underlying this function of A. blazei Murill remains obscure. The present study was carried out to investigate the effect of fraction FA-2-b-ß, an RNA-protein complex isolated from A. blazei Murill, on human leukemia HL-60 cells in vitro. Typical apoptotic characteristics were determined by morphological methods using DNA agarose gel electrophoresis and flow cytometry. The growth suppressive effect of fraction FA-2-b-ß on HL-60 cells in vitro occurred in a dose- (5-80 µg/mL) and time-dependent (24-96 h) manner. The proliferation of HL-60 cells (1 x 10(5) cells/mL) treated with 40 µg/mL of fraction FA-2-b-ß for 24-96 h and with 5-80 µg/mL for 96 h resulted in inhibitory rates ranging from 8 to 54.5%, and from 4.9 to 86.3%, respectively. Both telomerase activity determined by TRAP-ELISA and mRNA expression of the caspase-3 gene detected by RT-PCR were increased in HL-60 cells during fraction FA-2-b-ß treatment. The rate of apoptosis correlated negatively with the decrease of telomerase activity (r = 0.926, P < 0.05), but correlated positively with caspase-3 mRNA expression (r = 0.926, P < 0.05). These data show that fraction FA-2-b-ß can induce HL-60 cell apoptosis and that the combined effect of down-regulation of telomerase activity and up-regulation of mRNA expression of the caspase-3 gene could be the primary mechanism of induction of apoptosis. These findings provide strong evidence that fraction FA-2-b-ß could be of interest for the clinical treatment of acute leukemia.

Estrogens and male reproduction: a new concept

The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ß) in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.

Meditationes sancti evangelii 66

Invokaatio: Sun Theo.

Theoremata nonnulla miscellanea (1668)

Variantti A.

De magistratu

Invokaatio: Sun to Theo.

De triplici juris objecto

Invokaatio: Sun Theo Trismegisto.

De axiomate in genere

Arkit: A-B4.

De Spiritu Sancto, et aeterna eius divinitate ac processione; nec non officio atque donis

Invokaatio: Sun to Theo trisbeltiso kai megiso.

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Axiomata miscellanea

Arkit: A4.

De mundo sive totius universi constitutione

Invokaatio: Sun to Theo.