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    Wyświetlanie 1-13 z 13
    Tytuł:
    Stem cells: applications, perspectives, misunderstandings
    Autorzy:
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/704245.pdf
    Data publikacji:
    2020
    Wydawca:
    Polska Akademia Nauk. Czytelnia Czasopism PAN
    Tematy:
    stem cells
    cellular therapies
    gene therapy
    embryonic stem cells
    induced pluripotent stem cells
    Opis:
    Stem cells exist and can do a lot. For several decades, bone marrow and umbilical cord blood transplants containing haematopoietic stem cells have been used in the treatment of blood diseases. Genetic modifications (gene therapy) of such cells help to cure complex immunodeficiencies and severe anaemias. The limbal stem cells taken from the eye and properly multiplied can regenerate the damaged cornea, and the epidermal stem cells help in the treatment of severe burns and some hereditary, severe skin diseases. Promising experimental research is under way on other uses of stem cells. However, these cells are appropriately selected, having real ability to differentiate into specialized cells whose malfunction is the cause of the disease. Therapeutic applications of stem cells are apparently limited to date. Meanwhile, the Internet is full of advertisements for supposedly miraculous treatments for almost any disease. Stem cells have become a modern synonym of the Holy Grail. A wonderful dish, transforming every drink into elixir of health, youth and long life. Stem cells from a single source, e.g., umbilical cord blood, or so-called cells, although without proven properties of stem cells, are offered in commercial private clinics as a panacea for autism, cerebral palsy, spina bifida, eye diseases, amyotrophic lateral sclerosis and dozens other disorders. Without justification for their action in these diseases, without convincing evidence of safety, but for a high fee. This article discusses stem cells and misunderstandings about including any cells among them. It draws attention to the real possibilities and confirmed uses of stem cells and presents the problems, doubts and dangers for patients associated with commercial offers of treatments using “stem” cells. The author cites the positions of scientific institutions and societies warning against premature commercialization of unjustified and potentially dangerous therapies
    Źródło:
    Nauka; 2020, 1
    1231-8515
    Pojawia się w:
    Nauka
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    HIF-1: the knowns and unknowns of hypoxia sensing.
    Autorzy:
    Zagórska, Anna
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/1041533.pdf
    Data publikacji:
    2004
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    angiogenesis
    prolyl and asparaginyl hydroxylases
    hypoxia inducible factor-1
    carbon monoxide
    reactive oxygen species
    nitric oxide
    heme oxygenase
    Opis:
    Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions as a master regulator of cellular and systemic oxygen homeostasis. It consists of two constitutively produced subunits: HIF-1α and HIF-1β. Under normoxic conditions HIF-1α undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the α subunit. Additionally, hydroxylation of an asparaginyl residue blocks the transcriptional activity of HIF-1 due to inhibition of its interaction with co-activators. In contrast, under hypoxic conditions, abolition of prolyl hydroxylation results in HIF-1α stabilization, whereas the lack of asparaginyl hydroxylation allows the transcriptional activity. Additionally, the transcriptional activity may be modulated by phosphorylation or redox modification of HIF-1. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, various growth factors, or direct inhibitors of prolyl and asparaginyl hydroxylases. Therefore, it seems to be a crucial transcription factor elicited by a wide range of stresses such as impaired oxygenation, inflammation, energy deprivation, or intensive proliferation. However, the mechanisms of normoxic activation, as well as of oxygen sensing, are not yet fully known. Further understanding of the processes that control HIF-1 activity will be crucial for the development of new diagnostic and therapeutic strategies.
    Źródło:
    Acta Biochimica Polonica; 2004, 51, 3; 563-585
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Helper-dependent adenoviral vectors in experimental gene therapy
    Autorzy:
    Józkowicz, Alicja
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/1041362.pdf
    Data publikacji:
    2005
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    helper-dependent adenoviral vectors
    adenoviruses
    gene therapy
    Opis:
    In the majority of potential applications gene therapy will require an effective transfer of a transgene in vivo resulting in high-level and long-term transgene expression, all in the absence of significant toxicity or inflammatory responses. The most efficient vehicles for delivery of foreign genes to the target tissues are modified adenoviruses. Adenoviral vectors of the first generation, despite the high infection efficacy, have an essential drawback: they induce strong immune response, which leads to short term expression of the transgene, and limits their usefulness in clinical trials. In contrast, helper-dependent adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal immunogenicity and negligible side-effects, allowing for long-term transgene expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral vector-mediated experimental gene therapy, effectively used in animal models for delivery of transgenes into the liver, skeletal muscle, myocardium or brain. Strong and long-lasting expression of therapeutic genes has allowed for successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia, and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb, facilitates the use of physiologically regulated, endogenous promoters, instead of artificial viral promoter sequences. This enables also generation of the single vectors expressing multiple genes, which can be potentially useful for treatment of polygenic diseases. In this review we characterize the basic features of HdAd vectors and describe some of their experimental and potential clinical applications.
    Źródło:
    Acta Biochimica Polonica; 2005, 52, 3; 589-599
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Carbon monoxide - a "new" gaseous modulator of gene expression.
    Autorzy:
    Dulak, Józef
    Józkowicz, Alicja
    Powiązania:
    https://bibliotekanauki.pl/articles/1043644.pdf
    Data publikacji:
    2003
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    angiogenesis
    vascular endothelial growth factor
    atherosclerosis
    nitric oxide
    oxidative stress
    Opis:
    Carbon monoxide (CO) is an odorless, tasteless and colorless gas which is generated by heme oxygenase enzymes (HOs). HOs degrade heme releasing equimolar amounts of CO, iron and biliverdin, which is subsequently reduced to bilirubin. CO shares many properties with nitric oxide (NO), an established cellular messenger. Both CO and NO are involved in neural transmission and modulation of blood vessel function, including their relaxation and inhibition of platelet aggregation. CO, like NO, binds to heme proteins, although CO binds only ferrous (FeII) heme, whereas NO binds both ferrous and ferric (FeIII). CO enhances the activity of guanylate cyclase although it is less potent than NO. In contrast, CO inhibits other heme proteins, such as catalase or cytochrome P450. The effects of CO on gene expression can be thus varied, depending on the cellular microenvironment and the metabolic pathway being influenced. In this review the regulation of gene expression by HO/CO in the cardiovascular system is discussed. Recent data, derived also from our studies, indicate that HO/CO are significant modulators of inflammatory reactions, influencing the underlying processes such as cell proliferation and production of cytokines and growth factors.
    Źródło:
    Acta Biochimica Polonica; 2003, 50, 1; 31-47
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages.
    Autorzy:
    Józkowicz, Alicja
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/1043649.pdf
    Data publikacji:
    2003
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    cell viability
    metalloporphyrins
    vascular endothelial growth factor
    nitric oxide
    heme oxygenase
    Opis:
    Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 μM protoporphyrins. Some cells were additionally stimulated with IL-1β or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant. Generation of nitric oxide by iNOS was significantly increased by SnPPIX but strongly decreased by ZnPPIX. Similar differences were observed when cell viability was compared. SnPPIX improved the cell survival rate, whereas the same doses of ZnPPIX exerted some cytotoxic effects. In summary, SnPPIX and ZnPPIX can be used as HO-1 inhibitors in some experimental models. However, these compounds produce also HO-independent effects, which can make the interpretation of experiments very uncertain. Thus the involvement of the HO-1 pathway should be always confirmed by more specific methods.
    Źródło:
    Acta Biochimica Polonica; 2003, 50, 1; 69-79
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Adult stem cells: hopes and hypes of regenerative medicine
    Autorzy:
    Dulak, Józef
    Szade, Krzysztof
    Szade, Agata
    Nowak, Witold
    Józkowicz, Alicja
    Powiązania:
    https://bibliotekanauki.pl/articles/1038957.pdf
    Data publikacji:
    2015
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    embryonic stem cells
    induced pluripotent stem cells
    myocardial infarction
    very small embryonic-like stem cells
    heme oxygenase-1
    Opis:
    Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology.
    Źródło:
    Acta Biochimica Polonica; 2015, 62, 3; 329-337
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Ligands of peroxisome proliferator-activated receptor-γ increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages.
    Autorzy:
    Jozkowicz, Alicja
    Dulak, Jozef
    Piatkowska, Ewa
    Placha, Wojciech
    Dembinska-Kiec, Aldona
    Powiązania:
    https://bibliotekanauki.pl/articles/1044268.pdf
    Data publikacji:
    2000
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    angiogenesis
    ciglitazone
    vascular endothelial growth factor
    thiazolidinediones
    prostaglandin-J2
    peroxisome proliferator-activated receptor-γ
    Opis:
    Peroxisome proliferator-activated receptors-γ (PPARγ) are ligand-inducible transcription factors of the nuclear hormone receptor superfamily. We examined the effect of PPARγ activation on the generation of vascular endothelial growth factor (VEGF), one of the major angiogenic agents. Rat vascular smooth muscle cells (VSMC) and murine macrophages RAW264.7 were incubated for 24 h with PPARγ activators: prostaglandin J2 and ciglitazone. PPARγ were expressed in VSMC and RAW cells and their activity was upregulated in the presence of PGJ2 and ciglitazone. Incubation of the cells with PPARγ activators significantly augmented the release of VEGF protein into the media, both in resting and in IL-1β- or LPS-stimulated cultures. The higher protein generation was connected with the increased expression of mRNA and transcriptional activation of VEGF promoter. We conclude that the activation of PPARγ upregulates the generation of VEGF and may be involved in the regulation of angiogenesis.
    Źródło:
    Acta Biochimica Polonica; 2000, 47, 4; 1147-1157
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Prostaglandin-J2 upregulates expression of matrix metalloproteinase-1 independently of activation of peroxisome proliferator-activated receptor-γ.
    Autorzy:
    Józkowicz, Alicja
    Huk, Ihor
    Nigisch, Anneliese
    Cisowski, Jarosław
    Weigel, Guenter
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/1043441.pdf
    Data publikacji:
    2003
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    matrix metalloproteinase-1
    urokinase plasminogen activator
    prostaglandin-J2
    peroxisome proliferator-activated receptor-γ
    endothelial cells
    Opis:
    Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-inducible nuclear receptor that functions as a transcription factor involved in lipid metabolism, inflammatory response and angiogenesis. The most potent endogenous PPARγ activator is 15-deoxy-Δ12,14prostaglandin-J2 (15d-PGJ2), whereas synthetic ligands include the oral antidiabetic drugs thiazolidinediones (TZDs). Activation of PPARγ was reported to decrease the synthesis of matrix metalloproteinases (MMPs) in vascular smooth muscle cells and macrophages. We aimed to investigate the effect of PPARγ ligands on expression of MMP-1 and urokinase plasminogen activator (uPA) in human microvascular endothelial cells (HMEC-1). We found that treatment of HMEC-1 with 15d-PGJ2 increased the synthesis of MMP-1 protein up to 168% comparing to untreated cells. TZDs (ciglitazone and troglitazone), more potent activators of PPARγ in HMEC-1, did not influence MMP-1 production, arguing against the involvement of PPARγ in this process. Importantly, the stimulatory effect of 15d-PGJ2 was reversed by the antioxidant N-acetyl-cysteine (NAC), suggesting a contribution of oxidative stress. We demonstrated also that 15d-PGJ2 did not change the activity of MMP-1 promoter, but increased the stability of MMP-1 mRNA. In contrast, 15d-PGJ2 very potently inhibited the synthesis of uPA. This effect was in part mimicked by ciglitazone and troglitazone implying an involvement of PPARγ. Accordingly, NAC did not modify the inhibitory effect of 15d-PGJ2 on uPA expression. In conclusion, we postulate that 15d-PGJ2 may differently regulate the synthesis of proteases involved in angiogenesis : it upregulates MMP-1 expression in HMEC-1 through induction of oxidative stress, and inhibits uPA synthesis partly by activation of PPARγ.
    Źródło:
    Acta Biochimica Polonica; 2003, 50, 3; 677-689
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells
    Autorzy:
    Józkowicz, Alicja
    Pankiewicz, Joanna
    Dulak, Józef
    Partyka, Łukasz
    Wybrańska, Iwona
    Huk, Igor
    Dembińska-Kieć, Aldona
    Powiązania:
    https://bibliotekanauki.pl/articles/1044482.pdf
    Data publikacji:
    1999
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Źródło:
    Acta Biochimica Polonica; 1999, 46, 3; 703-715
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Elastic, electrically conductive, cytocompatible and bioprintable composites
    Autorzy:
    Benko, Aleksandra
    Wilk, Sabastian
    Martyniak, Alicja
    Stępniewski, Jacek
    Zambrzycki, Marcel
    Pietryga, Krzysztof
    Stedncel, Marek
    Dulak, Józef
    Powiązania:
    https://bibliotekanauki.pl/articles/1844753.pdf
    Data publikacji:
    2021
    Wydawca:
    Akademia Górniczo-Hutnicza im. Stanisława Staszica w Krakowie. Polskie Towarzystwo Biominerałów
    Źródło:
    Engineering of Biomaterials; 2021, 24, 163; 108
    1429-7248
    Pojawia się w:
    Engineering of Biomaterials
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Expression of cellular retinoic acid-binding protein I and II (CRABP I and II) in embryonic mouse hearts treated with retinoic acid
    Autorzy:
    Stachurska, Emilia
    Loboda, Agnieszka
    Niderla-Bielińska, Justyna
    Szperl, Małgorzata
    Juszyński, Michał
    Jozkowicz, Alicja
    Dulak, Jozef
    Ratajska, Anna
    Powiązania:
    https://bibliotekanauki.pl/articles/1039942.pdf
    Data publikacji:
    2011
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    CRABP I
    embryonic mouse heart
    CRABP II
    retinoic acid
    neural crest
    Opis:
    Cellular retinoic acid binding proteins are considered to be involved in retinoic acid (RA) signaling pathways. Our aim was to compare the expression and localization of cellular retinoic acid binding proteins I and II (CRABP I and II) in embryonic mouse hearts during normal development and after a single teratogenic dose of RA. Techniques such as real-time PCR, RT-PCR, Western blots and immunostaining were employed to examine hearts from embryos at 9-17 dpc. RA treatment at 8.5dpc affects production of CRABP I and II in the heart in the 48-h period. Changes in expression of mRNA for retinaldehyde dehydrogenase II (Raldh2), Crabp1 and Crabp2 genes also occur within the same time window (i.e. 10-11dpc) after RA treatment. In the embryonic control heart these proteins are localized in groups of cells within the outflow tract (OT), and the atrioventricular endocardial cushions. A gradient of labeling is observed with CRABP II but not for CRABP I along the myocardium of the looped heart at 11 dpc; this gradient is abolished in hearts treated with RA, whereas an increase of RALDH2 staining has been observed at 10 dpc in RA-treated hearts. Some populations of endocardial endothelial cells were intensively stained with anti-CRABP II whereas CRABP I was negative in these structures. These results suggest that CRABP I and II are independently regulated during heart development, playing different roles in RA signaling, essential for early remodeling of the heart tube and alignment of the great arteries to their respective ventricles.
    Źródło:
    Acta Biochimica Polonica; 2011, 58, 1; 19-29
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Pharmacological versus genetic inhibition of heme oxygenase-1 - the comparison of metalloporphyrins, shRNA and CRISPR/Cas9 system
    Autorzy:
    Mucha, Olga
    Podkalicka, Paulina
    Czarnek, Maria
    Biela, Anna
    Mieczkowski, Mateusz
    Kachamakova-Trojanowska, Neli
    Stepniewski, Jacek
    Jozkowicz, Alicja
    Dulak, Jozef
    Loboda, Agnieszka
    Powiązania:
    https://bibliotekanauki.pl/articles/1038402.pdf
    Data publikacji:
    2018
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    CRISPR/Cas9
    shRNA
    inhibitors
    heme oxygenase-1
    HO-1
    off-target
    Opis:
    Inhibition of heme oxygenase-1 (HO-1, encoded by HMOX1), a cytoprotective, anti-apoptotic and anti-inflammatory enzyme, may serve as a valuable therapy in various pathophysiological processes, including tumorigenesis. We compared the effect of chemical inhibitors - metalloporphyrins, with genetic tools - shRNA and CRISPR/Cas9 systems, to knock-down (KD)/knock-out (KO) HO-1 expression/activity. 293T cells were incubated with metalloporphyrins, tin and zinc protoporphyrins (SnPPIX and ZnPPIX, respectively) or were either transduced with lentiviral vectors encoding different shRNA sequences against HO-1 or were modified by CRISPR/Cas9 system targeting HMOX1. Metalloporphyrins decreased HO activity but concomitantly strongly induced HO-1 mRNA and protein in 293T cells. On the other hand, only slight basal HO-1 inhibition in shRNA KD 293T cell lines was confirmed on mRNA and protein level with no significant effect on enzyme activity. Nevertheless, silencing effect was much stronger when CRISPR/Cas9-mediated knock-out was performed. Most of the clones harboring mutations within HMOX1 locus did not express HO-1 protein and failed to increase bilirubin concentration after hemin stimulation. Furthermore, CRISPR/Cas9-mediated HO-1 depletion decreased 293T viability, growth, clonogenic potential and increased sensitivity to H2O2 treatment. In summary, we have shown that not all technologies can be used for inhibition of HO activity in vitro with the same efficiency. In our hands, the most potent and comprehensible results can be obtained using genetic tools, especially CRISPR/Cas9 approach.
    Źródło:
    Acta Biochimica Polonica; 2018, 65, 2; 277-286
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-13 z 13

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