| 40201. |
- Talkhoncheh, Mehrnaz Safaee, et al.
(författare)
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Transient inhibition of NF-κB signaling enhances ex vivo propagation of human hematopoietic stem cells
- 2018
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:9, s. 1444-1450
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded ex vivo has been challenging. Here we show that chemical inhibition of the NF- κB signaling pathway leads to a significant improvement of hematopoietic stem cell function from ex vivo cultured human umbilical cord blood derived CD34+ cells. We found a distinct peak of activation of the NF-κB pathway shortly after cells were put in culture, and consequently inhibition of the pathway was both necessary and sufficient during the first 24 hours of culture where it reduced the levels of several pro-inflammatory cytokines. Taken together, NF-κB pathway inhibition facilitates propagation of hematopoietic stem cells in culture and may complement other strategies for hematopoietic stem cell expansion by relieving stress signals that are induced as an immediate response to culture initiation.
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| 40202. |
- Tallheden, Tommi, 1972, et al.
(författare)
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Phenotypic plasticity of human articular chondrocytes.
- 2003
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Ingår i: The Journal of bone and joint surgery. American volume. - 0021-9355. ; 85-A Suppl 2, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Progenitor cells in mesenchymal tissues are important in the maintenance of tissue homeostasis and regeneration capacity. Articular cartilage is a tissue with a very low capacity for repair. One explanation could be the lack of chondrogenic progenitor cells within the adult tissue. As a test of chondrogenic differentiation potential, we examined the ability of isolated chondrocytes to take on several phenotypic identities within the mesenchymal lineage by applying culture techniques and markers used in the study of the phenotypic plasticity of marrow-derived mesenchymal stem cells (MSCs).
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| 40203. |
- Tallroth, G, et al.
(författare)
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Regional cerebral blood flow in normal man during insulin-induced hypoglycemia and in the recovery period following glucose infusion
- 1992
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 41:7, s. 717-721
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Tidskriftsartikel (refereegranskat)abstract
- The effect of moderate hypoglycemia (p-glucose, 2.0 +/- 0.3 mmol/L; mean +/- SD) on regional cerebral blood flow (rCBF) was studied in a group of 10 healthy, right-handed men (aged 23 to 28 years) using an intravenous xenon 133 single photon emission computed tomography technique (SPECT). After 10 minutes of hypoglycemia, global CBF had increased to 46.3 +/- 9.6 mL/100 g/min compared with the initial normoglycemic flow of 38.6 +/- 6.8 mL/100 g/min (P less than .01). The relative distribution of the rCBF changed significantly (P less than .05, ANOVA) from before to during hypoglycemia. Of the 10 regions analyzed, the highest increments in rCBF during hypoglycemia were found in the frontal (21.5% +/- 15.2%) and parietal (20.6% +/- 14.2%) lobes, and the lowest (10.7% +/- 9.4%) were found in the pons/brainstem regions. The increase in rCBF persisted for 15 minutes after normalization of blood glucose. The persisting high flow after hypoglycemia affected all regions, but a further 10.1% +/- 7.2% increase was observed in the pons/brainstem area (P less than .05). The CBF was significantly higher in the right compared with the left hemisphere (2.8%, 1.2%, and 3.9%, respectively; P less than .05) in all measurements. A decrease in brain volume was found at the final examination, compared with the hypoglycemic state (2.6%; P less than .05). It is concluded that moderate hypoglycemia leads to a marked increase in CBF and in the relative distribution of rCBF, which persists in the immediate period after normalization of the blood glucose level.
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| 40204. |
- Talvik, M, et al.
(författare)
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A cross-validation study on the relationship between central D-2 receptor occupancy and serum perphenazine concentration
- 2004
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Ingår i: Psychopharmacology. - Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Glostrup Univ Hosp, Dept Clin Biochem, Glostrup, Denmark. : SPRINGER. - 0033-3158 .- 1432-2072. ; 175:2, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: There is a need for laboratory measures to guide clinical treatment with antipsychotic drugs. For serum concentration of the classical antipsychotic drug perphenzine an optimal therapeutic interval has been identified between 2 and 6 nmol/l. Positron emission tomography (PET) studies have suggested an optimal interval in central dopamine D-2 receptor occupancy of between 65 and 80%. Objectives: The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D-2 receptor occupancy and the therapeutic window for serum perphenazine concentration. Methods: Six patients who had responded to maintenance treatment with perphenazine decanoate were examined with PET and [C-11]raclopride during steady-state conditions. Blood sampling was carried out for minimum serum perphenazine concentration and during the PET examination. Results: The serum perphenazine concentration was between 1.8 and 9 nmol/l and the D-2 receptor occupancy varied between 66 and 82%. The relationship between central receptor occupancy and serum drug concentration was curvilinear. Mild extrapyramidal symptoms were present in the patient with the highest D-2 receptor occupancy. Conclusions: The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D-2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.
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| 40205. |
- Talvio, Karo, et al.
(författare)
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Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
- 2022
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Lack of FMR1 protein results in fragile X syndrome (FXS), which is the most common inherited intellectual disability syndrome and serves as an excellent model disease to study molecular mechanisms resulting in neuropsychiatric comorbidities. We compared the transcriptomes of human neural progenitors (NPCs) generated from patient-derived induced pluripotent stem cells (iPSCs) of three FXS and three control male donors. Altered expression of RAD51C, PPIL3, GUCY1A2, MYD88, TRAPPC4, LYNX1, and GTF2A1L in FXS NPCs suggested changes related to triplet repeat instability, RNA splicing, testes development, and pathways previously shown to be affected in FXS. LYNX1 is a cholinergic brake of tissue plasminogen activator (tPA)-dependent plasticity, and its reduced expression was consistent with augmented tPA-dependent radial glial process growth in NPCs derived from FXS iPSC lines. There was evidence of human iPSC line donor-dependent variation reflecting potentially phenotypic variation. NPCs derived from an FXS male with concomitant epilepsy expressed differently several epilepsy-related genes, including genes shown to cause the auditory epilepsy phenotype in the murine model of FXS. Functional enrichment analysis highlighted regulation of insulin-like growth factor pathway in NPCs modeling FXS with epilepsy. Our results demonstrated potential of human iPSCs in disease modeling for discovery and development of therapeutic interventions by showing early gene expression changes in FXS iPSC-derived NPCs consistent with the known pathophysiological changes in FXS and by revealing disturbed FXS progenitor growth linked to reduced expression of LYNX1, suggesting dysregulated cholinergic system.
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| 40206. |
- Tamás, Markus J., 1970, et al.
(författare)
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Heavy Metals and Metalloids As a Cause for Protein Misfolding and Aggregation
- 2014
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 4:1, s. 252-267
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Tidskriftsartikel (refereegranskat)abstract
- While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.
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| 40207. |
- Tamás, Markus J., 1970, et al.
(författare)
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Misfolding and aggregation of nascent proteins: a novel mode of toxic cadmium action in vivo.
- 2018
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Ingår i: Current genetics. - : Springer Science and Business Media LLC. - 1432-0983 .- 0172-8083. ; 64:1
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Forskningsöversikt (refereegranskat)abstract
- Cadmium is a highly poisonous metal and a human carcinogen, but the molecular mechanisms underlying its cellular toxicity are not fully understood. Recent findings in yeast cells indicate that cadmium exerts its deleterious effects by inducing widespread misfolding and aggregation of nascent proteins. Here, we discuss this novel mode of toxic heavy metal action and propose a mechanism by which molecular chaperones may reduce the damaging effects of heavy metal ions on protein structures.
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| 40208. |
- Tamm, Christoffer, et al.
(författare)
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Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents
- 2016
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Ingår i: Stem Cell Reviews. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:5, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- Reliable and efficient DNA and RNA transfection methods are required when studying the role of individual genes in mouse pluripotent stem cells. However, these cells usually grow in tight clusters and are therefore more difficult to transfect than many other cell lines. We have found that transfection is especially challenging when mouse embryonic stem (mES) cells are cultured in the newly described 2i medium, which is based on two chemical inhibitors of differentiation pathways. In the present study we have performed a side-by-side comparison of commercially available, non-viral transfection reagents with regard to their ability to deliver plasmid DNA and siRNA into adherent and/or trypsinized mES cells cultured in 2i medium, assessing transfection rates, plasmid gene expression, siRNA mediated knockdown of Oct4 and viability. Finally, we present a fast and efficient method for transfection of trypsinized mES cells using the liposomal-based Lipofectamine 2000. With only a five-minute long transfection time we obtained at least 85 % transfected cells with 80 % maintained viability. Moreover, this protocol saves up to a day of experimental time since the cells are in suspension at the time of transfection, which allows for immediately re-plating into the appropriate format. This fast, simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications.
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| 40209. |
- Tammi, Markku, et al.
(författare)
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EGF regulates HAS-2 expression, controls epidermal thickness and stimulates keratinocyte migration
- 2002
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Ingår i: Hyaluronan, Vol 1: Chemical, Biochemical and Biological Aspects. - Great Britain : Woodhead Publishing Limited. - 1855735709 ; , s. 561-570
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Konferensbidrag (refereegranskat)abstract
- High concentrations of hyaluronan reside in the small space between the vital kertinocyte layers of human and animal epidermis and influence keratinocyte interactions, including growth, mobility and differentiation. We have previously found that the content of epidermal hyaluronan in human skin organ cultures is decreased and increased by cortisol and retinoic acid, and associated with enhanced and retarded terminal differentiation, respectively. To further substantiate this idea, we incubated epidermal keratinocytes with epidermal growth factor (EGF), and found a marked increase in hyaluronan synthesis which correlated with faster migration in an in vitro wounding assay of keratinocyte monolayers. EGF increased hyaluronan also in stratified, differentiated organotypic cultures, and increased the height of vital epidermis and reduced the thickness of the cornified layers, findings in line with an inhibition of terminal differentiation of keratinocytes. The stimulation of hyaluronan synthesis by EGF was due to upregulation of hyaluronan synthase 2 (HAS2) but not HAS1 or HAS3. A part of the EGF influence on the structure of epidermis, and on skin wound healing, is thus mediated through its control of HAS2 expression.
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| 40210. |
- Tamura, K, et al.
(författare)
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Fibronectin stimulates transcription of the platelet-derived growth factor beta-receptor in cultured rat aortic smooth muscle cells.
- 1998
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 251:3, s. 677-80
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Tidskriftsartikel (refereegranskat)abstract
- Fibronectin seems to play an important role in promoting the characteristic changes of vascular smooth muscle cells in diabetes mellitus including overexpression of the platelet-derived growth factor beta-receptor. To determine the regulatory mechanism of the beta-receptor by fibronectin, we have analyzed the effect of fibronectin on the expression of the beta-receptor in cultured rat aortic smooth muscle cells using the beta-receptor promoter/luciferase expression vector system. Fibronectin was found to stimulate the expression of the beta-receptor at the transcriptional level. Both a MEK1 inhibitor PD98059 and a tyrosine kinase inhibitor herbimycin A significantly inhibited the fibronectin-stimulated receptor transcription. Herbimycin A also completely inhibited the fibronectin-stimulated increase in tyrosine phosphorylation of focal adhesion kinase. These data suggest the involvement of the integrin-mediated mitogen-activated protein kinase pathway downstream of fibronectin stimulation in the activation process of the beta-receptor promoter.
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