Evidence for the involvement of sphingosine-1-phosphate in the homing and engraftment of hematopoietic stem cells to bone marrow.

The α-chemokine stromal-derived factor 1 (SDF-1), which binds to the CXCR4 receptor, directs migration and homing of CXCR4+ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) stem cell niches. Nevertheless, it is also known that CXCR4-/- fetal liver-derived hematopoietic stem cells engraft into BM and that blockade of CXCR4 by its antagonist AMD3100 does not prevent engraftment of HSPCs. Because of this finding of SDF-1-CXCR4-independent BM homing, the unique role of SDF-1 in HSPC homing has recently been challenged.

Caloric restriction increases ratio of estrogen to androgen receptors expression in murine ovaries--potential therapeutic implications.

Both estrogens and androgens are involved in the development and normal functioning of the ovaries. It is also known that ovarian function is regulated by diet. The goal of this study was to estimate the expression of sex hormone receptors in ovaries of mice that were on a 9-month caloric restriction (alternate-day feeding) as compared to normal control animals fed ad libitum.

Microbiological quality of non-sterile pharmaceutical products.

In microbiological terms, pharmaceutical products can be divided into two groups: sterile and non-sterile. Non-sterile drugs must satisfy the appropriate microbiological purity criteria which are included in pharmacopoeial monographs. Pharmacopoeial studies are prepared specifically with a view to ensuring that the medicinal product is therapeutically effective and safe for the patient.

Evidence of a Pivotal Role for the Distal Part of the Complement Cascade in the Diurnal Release of Hematopoietic Stem Cells Into Peripheral Blood.

We found that diurnal activation of the three evolutionarily ancient proteolytic cascades in peripheral blood (PB), namely, the complement, coagulation, and fibrinolytic cascades, late at night or in the early morning hours, precedes the diurnal release of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into PB in wild-type mice. Moreover, activation of the distal part of the complement cascade (ComC), involving cleavage of the fifth component (C5), seems to play a crucial role in pharmacological mobilization of HSPCs. In order to shed more light on the role of diurnal rhythms in the egress of HSPCs, we studied diurnal changes in the number of circulating HSPCs in C5-deficient mice and did not observe diurnal changes in the number of these cells circulating in PB in C5(-/-) animals.

Further evidence that paroxysmal nocturnal haemoglobinuria is a disorder of defective cell membrane lipid rafts.

The glycolipid glycosylphosphatidylinositol anchor (GPI-A) plays an important role in lipid raft formation, which is required for proper expression on the cell surface of two inhibitors of the complement cascade, CD55 and CD59. The absence of these markers from the surface of blood cells, including erythrocytes, makes the cells susceptible to complement lysis, as seen in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). However, the explanation for why PNH-affected hematopoietic stem/progenitor cells (HSPCs) expand over time in BM is still unclear.

Effects of Endurance and Endurance Strength Training on Body Composition and Physical Capacity in Women with Abdominal Obesity.

Aims: To compare the effects of endurance training with endurance strength training on the anthropometric, body composition, physical capacity, and circulatory parameters in obese women.

Methods: 44 women with abdominal obesity were randomized into groups A and B, and asked to perform endurance (A) and endurance strength training (B) for 3 months, 3 times/week, for 60 min. Dual-energy X-ray absorptiometry and Graded Exercise Test were performed before and after training.

The cell cycle- and insulin-signaling-inhibiting miRNA expression pattern of very small embryonic-like stem cells contributes to their quiescent state.

Murine Oct4(+), very small embryonic-like stem cells (VSELs), are a quiescent stem cell population that requires a supportive co-culture layer to proliferate and/or to differentiate in vitro. Gene expression studies have revealed that the quiescence of these cells is due to changes in expression of parentally imprinted genes, including genes involved in cell cycle regulation and insulin and insulin-like growth factor signaling (IIS). To investigate the role of microRNAs (miRNAs) in VSEL quiescence, we performed miRNA studies in highly purified VSELs and observed a unique miRNA expression pattern in these cells.

Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy.

Background: One of side effects of chemotherapy and radiotherapy is the induction of several factors in various tissues and organs that create a pro-metastatic microenvironment for cancer cells that survive initial treatment.

Methods: In the present study, we employed human ovarian cancer cell line A2780 and immunodeficient mice xenograft model to test effect of both ibuprofen and dexamethasone to ameliorate the therapy-induced pro-metastatic microenvironment in bone marrow, liver, and lung.

Results: In our studies, we found that total body irradiation or administration of cisplatin increases the metastatic spread of human ovarian cancer cells transplanted into immunodeficient mice compared with animals unexposed to irradiation or cisplatin.

Vancomycin-modified silica: Synthesis, controlled release and biological activity of the drug.

Vancomycin was immobilized on three different organically functionalized silicas. The materials obtained were used for a controlled release of the antibiotic. The influence of the type of chemical bond on the in vitro drug release was investigated.

Membrane lipid rafts, master regulators of hematopoietic stem cell retention in bone marrow and their trafficking.

Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein microdomains, known as lipid rafts, which float freely in the membrane bilayer. These structures have an important role in assembling signaling molecules (e.g.

[Stem cell research and its growing impact on contemporary psychiatry].

The expanding field of stem cell research is now beginning to help with the problems of modern psychiatry. On the one hand, induced pluripotent stem cells (iPSCs) can now be used to generate neural cell lines from patients suffering from psychiatric disorders, which can then serve as models for studying changes in gene expression pattern involved in the pathogenesis of these diseases. These artificially generated neural cells are also employed in studying the efficacy of newly developed antipsychotic treatments.

5‑Azacytidine inhibits human rhabdomyosarcoma cell growth by downregulating insulin‑like growth factor 2 expression and reactivating the H19 gene product miR‑675, which negatively affects insulin‑like growth factors and insulin signaling.

Insulin-like growth factor 2 (IGF2) and 1 (IGF1) and insulin (INS) promote proliferation of rhabdomyosarcoma (RMS) cells by interacting with the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor (INSR). Loss of imprinting (LOI) by DNA hypermethylation at the differentially methylated region (DMR) for the IGF2‑H19 locus is commonly observed in RMS cells and results in an increase in the expression of proliferation-promoting IGF2 and downregulation of proliferation-inhibiting non-coding H19 miRNAs. One of these miRNAs, miR‑675, has been reported in murine cells to be a negative regulator of IGF1R expression.

Hematopoietic stem/progenitor cells express several functional sex hormone receptors-novel evidence for a potential developmental link between hematopoiesis and primordial germ cells.

Evidence has accumulated that hematopoietic stem progenitor cells (HSPCs) share several markers with the germline, a connection supported by reports that prolactin, androgens, and estrogens stimulate hematopoiesis. To address this issue more directly, we tested the expression of receptors for pituitary-derived hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), on purified murine bone marrow (BM) cells enriched for HSPCs and tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. We also tested whether administration of pituitary- and gonad-derived sex hormones (SexHs) increases incorporation of bromodeoxyuridine (BrdU) into HSPCs and expansion of hematopoietic clonogenic progenitors in mice and promotes recovery of blood counts in sublethally irradiated animals.

A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation.

The molecular nature of very small embryonic-like stem cells in adult tissues.

Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs).

Withaferin a alone and in combination with cisplatin suppresses growth and metastasis of ovarian cancer by targeting putative cancer stem cells.

Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs).

Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment.

Our current understanding of stem cells suffers from a lack of precision, as the stem cell compartment is a broad continuum between early stages of development and adult postnatal tissues, and it is not fully understood how this transition occurs. The definition of stem cell pluripotency is adapted from embryology and excludes the possibility that some early-development stem cells with pluri- and/or multipotential differentiation potential may reside in postnatal tissues in a dormant state in which they are protected from uncontrolled proliferation and thus do not form teratomas or have the ability to complement blastocyst development. We will discuss the concept that a population of very small embryonic-like stem cells (VSELs) could be a link between early-development stages and adult stem cell compartments and reside in a quiescent state in adult tissues.

LM and TEM study of the orthokeratinized and parakeratinized epithelium of the tongue in the domestic duck (Anas platyrhynchos f. domestica).

The previous histological studies of the lingual mucosa in birds characterized two types of keratinized epithelium, i.e. orthokeratinized and parakeratinized.

Identification of heme oxygenase 1 (HO-1) as a novel negative regulator of mobilization of hematopoietic stem/progenitor cells.

Activation of complement cascade (ComC) play and important role in mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). While there are vast experimental data on the mechanisms and factors that induce or promote mobilization of HSPCs, there is relatively less data on negative regulators of this process. We demonstrate for the first time that heme oxygenase-1 (HO-1) that has a well-documented anti-inflammatory potential plays an important and heretofore unrecognized role in retention of HSPCs in BM niches by i) modulating negatively activation of mobilization promoting ComC, ii) maintaining stromal derived factor-1 (SDF-1) level in the BM microenvironment and iii) attenuating chemotactic responsiveness of HSPCs to SDF-1 and sphingosine-1 phosphate (S1P) gradients in PB.

DOCK2 is critical for CD8(+) TCR(-) graft facilitating cells to enhance engraftment of hematopoietic stem and progenitor cells.

CD8(+) TCR(-) graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function.

Bioactive lipids, LPC and LPA, are novel prometastatic factors and their tissue levels increase in response to radio/chemotherapy.

Unlabelled: Bioactive lipids are fundamental mediators of a number of critical biologic processes such as inflammation, proliferation, and apoptosis. Rhabdomyosarcoma (RMS) is common in adolescence with histologic subtypes that favor metastasis. However, the factors that influence metastasis are not well appreciated.

Positive effects of prolonged caloric restriction on the population of very small embryonic-like stem cells - hematopoietic and ovarian implications.

Background: Low calorie intake, or calorie restriction (CR) without malnutrition, has been demonstrated in several animal species, including mice, to increase both median and maximum lifespan as well as delay reproductive senescence. Our previous work demonstrated a positive correlation between life span and the number of very small embryonic-like stem cells (VSELs) in long living Laron dwarf mice. These animals have very low levels of circulating insulin-like growth factor 1 (IGF-1) in peripheral blood (PB), maintain higher numbers of hematopoietic stem cells (HSPCs) in bone marrow (BM), and display prolonged fecundity compared with wild type littermates.

Expression of the erythropoietin receptor by germline-derived cells - further support for a potential developmental link between the germline and hematopoiesis.

Background: Expressing several markers of migrating primordial germ cells (PGCs), the rare population of quiescent, bone marrow (BM)-residing very small embryonic-like stem cells (VSELs) can be specified like PGCs into hematopoietic stem/progenitor cells (HSPCs). These two properties of VSELs support the possibility of a developmental origin of HSPCs from migrating PGCs.

Methods: To address a potential link between VSELs and germ line cells we analyzed by RT-PCR and FACS expression of erythropoietin receptor (EpoR) on murine bone marrow- and human umbilical cord blood-derived VSELs, murine and human teratocarcinoma cell lines and human ovarian cancer cells.