Puzianowska-Kuznicka M.,Mossakowski Medical Research Center
Clinica Chimica Acta | Year: 2012
Women live longer than men; this can be attributed in part to the function of estrogens. In premenopausal women 17β-estradiol (E2) is produced mainly by the ovaries. Extra-ovarian sources of this hormone comprise adipose tissue, breast tissue, bone, leukocytes, heart, testes, prostate, adrenal tissues, and some brain structures. E2 exerts the majority of its biological functions by interacting with the nuclear receptors ERα and ERβ, encoded by the ESR1 and ESR2 genes, respectively. The genomic mechanism of ER action is the regulation of the activity of target genes. In addition, E2 induces rapid cellular effects in transcription-independent, non-genomic mechanisms, acting via receptors localized in the plasma membrane, in the cytoplasm, and in the mitochondria. Notably, ERα commonly serves as an extra-nuclear receptor of E2. In wild type animal models of cardiac ischemia ERα activation reduces infarct size, apoptosis of cardiomyocytes, inflammation, and oxidative stress, induces vasodilatation and increases neovascularization. The cardioprotective role of ERα in human is not fully elucidated. An individual with disruptive ESR1 mutation had dysfunctional epithelium and suffered from early cardiovascular disease. An association of the common ESR1 - 397T>C and - 351A>G polymorphisms and of other polymorphisms with cardiovascular disease and with myocardial infarction is still not firmly established. © 2011 Elsevier B.V.
Mossakowska M.,International Institute of Molecular and Cell Biology |
Broczek K.,Medical University of Warsaw |
Wieczorowska-Tobis K.,Poznan University of Medical Sciences |
Klich-Raczka A.,Jagiellonian University |
And 5 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014
Background: Clinical and biochemical predictors of extreme longevity would be useful in geriatric practice but have still not been clearly defined. Methods: To identify the best nongenetic predictors of survival in centenarians, we examined 340 individuals aged 100+ years. A detailed questionnaire was completed, and comprehensive geriatric assessment and blood analyses were performed. Survival of study participants was checked annually over the period of 10 years. Results: In the univariate Cox proportional hazards model, a longer survival of centenarians was correlated with a higher adjusted Mini-Mental State Examination (MMSEadj) score (p < .000001), higher Activities of Daily Living (ADL) and adjusted Instrumental Activities of Daily Living (IADLadj) scores (p < .000001 and p = .00008, respectively), and younger age at the time of testing (p = .005). Blood pressure, lipid profile, and C-reactive protein and hemoglobin concentrations were not associated with survival. Multivariate analysis including age, sex, and the MMSEadj and ADL scores showed that both MMSEadj and ADL predicted survival (HR = 0.978 per each MMSEadj point, 95% CI: 0.964-0.993, p = .004; HR = 0.900 per each ADL point, 95% CI: 0.842-0.962, p = .002, respectively). In multivariate analysis with the ADL score substituted by the IADLadj score, the only predictor of survival was MMSEadj (HR = 0.973 per each MMSEadj point, 95% CI: 0.958-0.988, p = .0006). Conclusions: Cognitive and functional performances are predictors of survival in centenarians. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.
Mubki T.,Imam Muhammad ibn Saud Islamic University |
Rudnicka L.,Medical University of Warsaw |
Rudnicka L.,Mossakowski Medical Research Center |
Olszewska M.,Medical University of Warsaw |
And 2 more authors.
Journal of the American Academy of Dermatology | Year: 2014
Hair loss (alopecia) is a common problem and is often a major source of distress for patients. The differential diagnosis of alopecia includes both scarring and nonscarring alopecias. In addition, many hair shaft disorders can produce hair shaft fragility, resulting in different patterns of alopecia. Therefore, an organized and systematic approach is needed to accurately address patients' complaints to achieve the correct diagnosis. Part 1 of this 2-part continuing medical education article on alopecia describes history taking and the clinical examination of different hair loss disorders. It also provides an algorithmic diagnostic approach based on the most recent knowledge about different types of alopecia. © 2014 by the American Academy of Dermatology, Inc.
Gawinkowski S.,Polish Academy of Sciences |
Walewski L.,The Interdisciplinary Center |
Vdovin A.,University of Regensburg |
Slenczka A.,University of Regensburg |
And 5 more authors.
Physical Chemistry Chemical Physics | Year: 2012
Combined use of IR, Raman, neutron scattering and fluorescence measurements for porphycene isolated in helium nanodroplets, supersonic jet and cryogenic matrices, as well as for solid and liquid solutions, resulted in the assignments of almost all of 108 fundamental vibrations. The puzzling feature of porphycene is the apparent lack of the N-H stretching band in the IR spectrum, predicted to be the strongest of all bands by standard harmonic calculations. Theoretical modeling of the IR spectra, based on ab initio molecular dynamics simulations, reveals that the N-H stretching mode should appear as an extremely broad band in the 2250-3000 cm -1 region. Coupling of the N-H stretching vibration to other modes is discussed in the context of multidimensional character of intramolecular double hydrogen transfer in porphycene. The analysis can be generalized to other strongly hydrogen-bonded systems. © the Owner Societies 2012.
Janowski M.,Johns Hopkins University |
Janowski M.,Mossakowski Medical Research Center
Neuromethods | Year: 2016
The CSF is increasingly considered as an attractive gateway to the central nervous system (CNS). It is warranted by the direct delivery of therapeutic agents beyond the blood-brain barrier (BBB) and widespread access to the large areas of the brain and the spinal cord. In small animals access to CSF is not trivial. The cisterna magna is the largest CSF fluid compartment; thus it was selected as a target. Here, I describe the surgical procedure for efficient and reproducible access and injection of therapeutic agents such as stem cells to cisterna magna. Due to hydromechanics, the method is distinct from previously described techniques for CSF withdrawal. Finally, I describe the method for CNS dissection within intact dura for evaluation of cell distribution. © Springer Science+Business Media New York 2016.
Cui L.,University of Eastern Finland |
Kerkela E.,Red Cross |
Bakreen A.,University of Eastern Finland |
Nitzsche F.,Fraunhofer Institute for Cell Therapy and Immunology |
And 7 more authors.
Stem Cell Research and Therapy | Year: 2015
Introduction: Intra-arterial cell infusion is an efficient delivery route with which to target organs such as the ischemic brain. However, adverse events including microembolisms and decreased cerebral blood flow were recently reported after intra-arterial cell delivery in rodent models, raising safety concerns. We tested the hypothesis that cell dose, infusion volume, and velocity would be related to the severity of complications after intra-arterial cell delivery. Methods: In this study, 38 rats were subjected to a sham middle cerebral artery occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow mesenchymal stem cells at different cell doses (0 to 1.0 × 106), infusion volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group (n = 4) was infused with 1.0 × 106 cells labeled with iron oxide for in vivo tracking of cells. Cells were infused through the external carotid artery under laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral embolisms or hemorrhage. Limb placing, cylinder, and open field tests were conducted to assess sensorimotor functions before the rats were perfused for histology. Results: A cell dose-related reduction in cerebral blood flow was noted, as well as an increase in embolic events and concomitant lesion size, and sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes) was associated with high rate of complications. Lesions on MRI were confirmed with histology and corresponded to necrotic cell loss and blood-brain barrier leakage. Conclusions: Particularly cell dose but also infusion velocity contribute to complications encountered after intra-arterial cell transplantation. This should be considered before planning efficacy studies in rats and, potentially, in patients with stroke. © 2015 Cui et al.; licensee BioMed Central.
Boltze J.,Fraunhofer Institute for Cell Therapy and Immunology |
Lukomska B.,Mossakowski Medical Research Center |
Jolkkonen J.,University of Eastern Finland
Journal of Cerebral Blood Flow and Metabolism | Year: 2014
Experimental stroke treatment by mesenchymal stem cell (MSC) populations is an attractive paradigm in stroke research. There are many studies describing improved functional outcomes after MSC delivery in stroke, but the mechanisms through which the transferred cells exert these effects are less well understood. Moreover, commonly applied functional tests may not be suitable for discriminating real functional recovery from compensation, which is a frequently encountered phenomenon in rodents. This commentary highlights some of the potential risks for the translational process associated with these tests and proposes some alternative test arrays which may achieve more specific functional phenotyping. © 2014 ISCBFM.
Koronkiewicz M.,Polish National Medicines Institute |
Chilmonczyk Z.,Polish National Medicines Institute |
Kazimierczuk Z.,Mossakowski Medical Research Center
Medicinal Chemistry Research | Year: 2012
A series of new pentabromobenzylisothioureas [ZKK-1-ZKK-5; (ZKKs)] carrying additional substituents on nitrogen atoms has been synthesized. The ZKKs were found to induce apoptosis in HL-60 (human promyleocytic leukemia) and K-562 (human chronic erythromyeloblastoid leukemia) cell lines in a concentration-dependent manner at low micromolar concentrations. ZKK-3 [(N,N'- dimethyl-S-2,3,4,5,6-pentabromobenzyl)isothiouronium bromide] showed the highest proapoptotic activity in HL-60 cells, whereas ZKK-2 [N-methyl-S-(2,3,4,5,6- pentabromobenzyl)isothiouronium bromide] was most effective in this respect in K-562 cells. During the ZKKsinduced apoptosis, an 85 kDa fragment of cleaved PARP (caspase-3 and caspase-7 substrate) was detected in both cell lines tested. The studied compounds also decreased mitochondrial transmembrane potential in both these cell lines and caused the cells to accumulate in G 1 and at the G 1/S border of the cell cycle in a concentration-dependent manner. These results show promise for their study as new compounds in the treatment of leukemia, after an appropriate preclinical toxicity profile. © Springer Science+Business Media, LLC 2011.
Buzanska L.,Mossakowski Medical Research Center
Postepy biochemii | Year: 2013
Maintenance of developmental and regenerative capability of the tissue highly depends upon mutual interaction of the stem cells with the components of their microenvironment (niche). The nature of this interaction is determined by the biochemical and biophysical properties of the niche constituencies. Although knowledge about the components of the stem cell microenvironment and their architecture is growing quickly, we still need to unravel the mechanisms underlying the control of the niche functioning, enabling stem cells differentiation and homeostasis of the tissue. Advancement in biotechnology provides tools to build up in vitro "biomimetic" microenvironments resembling a natural stem cell niche, where the cell is provided with diverse extracellular signals exerted by soluble and structural cues, mimicking those found in vivo. To obtain such microenvironment in vitro emerging nano/biotechnology methods were applied, using biomaterials of new generation, which enable controlling of the stem cell differentiation by time and special related release of the active factors. This article is providing an overview of the new research strategies for the bioengineering of the stem cell niche and gives the examples of the cell/biomaterial 2D and 3D complex systems used for basic and preclinical research as well as entering clinical applications for the therapy of the nervous system.
Dobrzyn P.,Nencki Institute of Experimental Biology |
Pyrkowska A.,Nencki Institute of Experimental Biology |
Jazurek M.,Nencki Institute of Experimental Biology |
Szymanski K.,Nencki Institute of Experimental Biology |
And 2 more authors.
Journal of Applied Physiology | Year: 2010
Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsat-urated fatty acids, has recently been shown to be a critical control point in regulation of liver and skeletal muscle metabolism. Herein, we demonstrate that endurance training significantly increases both SCD1 mRNA and protein levels in the soleus muscle, whereas it does not affect SCD1 expression in the EDL muscle and liver. Desaturation index (18:1Δ9/18:0 ratio), an indirect indicator of SCD1 activity, was also significantly higher (3.6-fold) in soleus of trained rats compared with untrained animals. Consistent with greater SCD1 expression/activity, the contents of free fatty acids, diacylglycerol, and triglyceride were elevated in soleus of trained rats. However, training did not affect lipid concentration in EDL and liver. Additionally, endurance training activated the AMP-activated protein kinase pathway as well as increased peroxisome proliferator-activated receptor (PPAR)-§ and PPARα gene expression and activity in soleus and liver. Increased lipid accumulation in soleus was coupled with elevated protein levels of fatty acid synthase, mRNA levels of diacylglycerol acyltransferase and glycerol-3-phosphate transferase, as well as increased levels of proteins involved in fatty acid transport (fatty acid translocase/CD36, fatty acid transport protein 1). Interestingly, sterol regulatory element-binding protein (SREBP)-1c expression and SREBP-1 protein levels were not affected by exercise training. Together, the obtained data suggest that SCD1 upregulation plays an important role in adaptation of oxidative muscle to endurance training. Copyright © 2010 the American Physiological Society.