Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in ...several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mesenchymal stem cells (MSCs) play an important role in the physiology and homeostasis of the hematopoietic system. Because MSCs generate most of the stromal cells present in the bone marrow (BM), ...form part of the hematopoietic stem cell (HSC) niche, and produce various molecules regulating hematopoiesis, their hematopoiesis-supporting capacity has been demonstrated. In the last decade, BM-MSCs have been proposed to be useful in some ex vivo protocols for HSC expansion, with the aim of expanding their numbers for transplant purposes (HSC transplant, HSCT). Furthermore, application of MSCs has been proposed as an adjuvant cellular therapy for promoting rapid hematopoietic recovery in HSCT patients. Although the MSCs used in preliminary clinical trials have come from the BM, isolation of MSCs from far more accessible sources such as neonatal tissues has now been achieved, and these cells have been found to possess similar biological characteristics to those isolated from the BM. Therefore, such tissues are now considered as a potential alternative source of MSCs for clinical applications. In this review, we discuss current knowledge regarding the biological characteristics of MSCs as related to their capacity to support the formation of hematopoietic stem and progenitor cells. We also describe MSC manipulation for ex vivo HSC expansion protocols used for transplants and their clinical relevance for hematopoietic recovery in HSCT patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sulfur dioxide (SO2) is an important preservative commonly used during winemaking. High concentrations of SO2 binding wine carbonyls limit sulfite efficacy resulting in higher total SO2 additions, ...which may exceed SO2 limits permitted by law and pose health risks for sensitive consumers. Major SO2 binding compounds (acetaldehyde, pyruvate, α-ketoglutaric acid, galacturonic acid, glucose and acetoin) were quantified in 237 red and white table wines by HPLC with pre-column derivatization to 2,4-dinitrophenylhydrazine. Average concentrations of SO2 binders in red and white wines (mean ± SE) were: acetaldehyde (red, 25 ± 3 mg/l; white, 40 ± 3 mg/l), pyruvic acid (red, 14 ± 2 mg/l; white, 25 ± 2 mg/l), α-ketoglutaric acid (red, 74 ± 4 mg/l; white, 31 ± 3 mg/l), galacturonic acids (red, 810 ± 51 mg/l; white, 267 ± 13 mg/l), glucose (red, 1400 ± 770 mg/l; white, 4750 ± 648 mg/l) and acetoin (red, 11 ± 1 mg/l; white, 10 ± 1 mg/l). Overall, acetaldehyde was identified as the most important SO2 binder. Acetaldehyde formation from the involuntary oxidation of ethanol during the post-fermentation stages likely is responsible for the large differences in acetaldehyde concentrations in products from different wineries and represents the most efficient target for efforts directed at reducing SO2 binders. Post-fermentation wine handling and bottling were identified as critical control points for the formation of acetaldehyde.
► An ultra high pressure HPLC method was used to quantify SO2 binding carbonyls in over 200 red and white cool climate table wines. ► Acetaldehyde, pyruvic acid and α-ketoglutaric acid caused 72, 17 and 8% of the bound SO2 in white wines, respectively. ► Acetaldehyde, pyruvic acid and α-ketoglutaric acid caused 55, 12 and 23% of the bound SO2 in red, respectively. ► The work provides frequency and winery-specific analyses to support regulatory and enological decisions. ► Critical control points for the formation of acetaldehyde in post-fermentative handling were identified.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adipocytes are the main cell type in adipose tissue, which is a critical regulator of metabolism, highly specialized in storing energy as fat. Adipocytes differentiate from multipotent mesenchymal ...stromal cells (hMSCs) through adipogenesis, a tightly controlled differentiation process involving close interplay between metabolic transitions and sequential programs of gene expression. However, the specific gears driving this interplay remain largely obscure. Additionally, the metabolite nicotinamide adenine dinucleotide (NAD+) is becoming increasingly recognized as a regulator of lipid metabolism, and a promising therapeutic target for dyslipidemia and obesity. Here, we explored how NAD+ bioavailability controls adipogenic differentiation from hMSC. We found a previously unappreciated repressive role for NAD+ on adipocyte commitment, while a functional NAD+-dependent deacetylase SIRT1 appeared crucial for terminal differentiation of pre-adipocytes. Repressing NAD+ biosynthesis during adipogenesis promoted the adipogenic transcriptional program, while two-photon microscopy and extracellular flux analyses suggest that SIRT1 activity mostly relies on the metabolic switch. Interestingly, SIRT1 controls subcellular compartmentalization of redox metabolism during adipogenesis.
Strains of Schizosaccharomyces pombe are being increasingly investigated with regards to their grape winemaking potential either in combination with the typical production yeast, Saccharomyces ...cerevisiae, or in monoseptic fermentations. Their ethanol tolerance and ability to degrade L-malic acid is oenologically convenient but contrasts with the comparatively high acetic acid and acetaldehyde formation potential which is considered undesirable, especially in white winemaking. The purpose of this work was to investigate the performance of a selected S. pombe strain in monoseptic femerntations of white grape must. Traditional batch fermentations were compared with an innovative and automated fed-batch fermentation technique were sugar concentrations are kept low during fermentations to decrease sugar induced osmotic stress. Because of its known effect on growth and ethanol tolerance, the effect of Mg was also tested. While Mg supplementation was not shown to significantly influence residual values of sugars, ethanol, glycerol, organic acids and acetaldehyde, the application of the fed-batch technique led to a fundamental change in yeast physiology. While glycerol values were only slightly reduced, the fed-batch approach allowed obtaining wines devoid of acetic acid whose levels were considerable in wines produced by the traditional batch technique (0.6 g/L). The work demonstrates that the acetic acid metabolism of S. pombe is associated to sugar induced osmotic stress such as for S. cerevisiae, too, and may be controlled by application of suitable fermentation techniques for winemaking.
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•Significant production of acetic acid in traditional batch fermentation•The fed-batch approach allos to prevent acetic acid formation by S. pombe.•Grape must supplementation with Mg did not affect metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory capacity; therefore, they have been used in different clinical protocols in which it is necessary to decrease the immune ...response. This capacity is mainly regulated by TNF-α and IFN-γ, and it has been observed that cell-cell contact, mainly mediated by ICAM-1, is important for MSCs to carry out efficient immunoregulation. Therefore, in the present work, we analyzed the effect of TNF-α alone or in combination with IFN-γ on the expression of ICAM-1. Besides, given the importance of cell contact in the immunoregulatory function of MSCs, we analyzed whether these cells release ICAM-1+ microvesicles (MVs). Our results show for the first time that TNF-α is capable of increasing the early expression of ICAM-1 in human BM-MSCs. Also, we observed that TNF-α and IFN-γ have a synergistic effect on the increase in the expression of ICAM-1. Furthermore, we found that BM-MSCs exposed to an inflammatory environment release MVs enriched in ICAM-1 (MVs-ICAM-1high). The knowledge generated in this study will contribute to the improvement of in vitro conditioning protocols that favor the therapeutic effect of these cells or their products.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
► Improved method for the quantification of major SO2 binders by DNPH derivatisation and UHPLC. ► Sample oxidation and artifacts decreased by inclusion of EDTA during sample pre-treatment. ► ...Derivatisation conditions and calibration ranges optimised and interferences identified. ► Method accuracy, precision, resolution and number of analytes exceed existing protocols. ► Method allows for rapid analysis of significant SO2 binders in wine.
Sulphur dioxide (SO2) is essential for the preservation of wines. The presence of SO2 binding compounds in musts and wines may limit sulphite efficacy leading to higher total SO2 additions, which may exceed SO2 limits permitted by law and pose health risks for sensitive individuals. An improved method for the quantification of significant wine SO2 binding compounds is presented that applies a novel sample treatment approach and rapid UHPLC separation.
Glucose, galacturonic acid, alpha-ketoglutarate, pyruvate, acetoin and acetaldehyde were derivatised with 2,4-dinitrophenylhydrazine and separated using a solid core C18 phase by ultra high performance liquid chromatography. Addition of EDTA to samples prevented de novo acetaldehyde formation from ethanol oxidation. Optimised derivatisation duration enhanced reproducibility and allowed for glucose and galacturonic acid quantification. High glucose residues were found to interfere with the recovery of other SO2 binders, but practical SO2 concentrations and red wine pigments did not affect derivatisation efficiency. The calibration range, method accuracy, precision and limits of detection were found to be satisfactory for routine analysis of SO2 binders in wines.
The current method represents a significant improvement in the comprehensive analysis of SO2 binding wine carbonyls. It allows for the quantification of major SO2 binders at practical analyte concentrations, and uses a simple sample treatment method that prevents treatment artifacts. Equipment utilisation could be reduced by rapid LC separation while maintaining analytical performance parameters. The improved method will be a valuable addition for the analysis of total SO2 binder pools in oenological samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Microbial biomass is an important biotechnological parameter. The traditional method for its determination involves an oven-drying step and equilibration to room temperature before weighing, and it ...is tedious and time consuming. This work studied the utilisation of a moisture analyser consisting of an efficient infrared-heating module and an analytical balance for the determination of microbial biomass by dry weight. The method duration depended on the sample volume and was between 7 and 40 min for sample volumes of 1-10 ml. The method precision depended on the total dry weight analysed - 10 mg of total dry weight being sufficient to achieve coefficients of variation of 5% or less. Comparison with the conventional oven method provided a correlation coefficient r² of 0·99. The recovery of an internal standard ranged between 94·2 and 106·4% with a precision of 1·39-4·53%CV. Validation revealed sufficient method accuracy, precision and robustness and was successfully applied to the study of yeast and bacterial growth kinetics. Techniques are discussed that allow for increased method precision at low biomass concentrations, and equations are provided to estimate required drying time and method precision based on sample volume and total sample dry weight, respectively. This work presents a rapid method for the determination of microbial biomass, allowing for the timely implementation of biomass-based information in biotechnological and laboratory protocols.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recently, the Galactic center has been reported to be a source of very high energy (VHE) g-rays by the CANGAROO, VERITAS, and HESS experiments. The energy spectra as measured by these experiments ...show substantial differences. In this Letter we present MAGIC observations of the Galactic center, resulting in the detection of a differential g-ray flux consistent with a steady, hard-slope power law, described as dN sub(g)/(dA dt dE) = (2.9 c 0.6) x 10 super(-12)(E/TeV) super(-2.2c0.2) cm super(-2) s super(-1) TeV super(-1). The g-ray source is centered at (R.A., decl.) = (17 super(h)45 super(m)20 super(s), -292'). This result confirms the previous measurements by the HESS experiment and indicates a steady source of TeV g-rays. We briefly describe the observational technique used and the procedure implemented for the data analysis, and we discuss the results in the perspective of different models proposed for the acceleration of the VHE g-rays.
Acetaldehyde is the major carbonyl compound formed during winemaking and has implications for sensory and colour qualities of wines as well as for the use of the wine preservative SO₂. The current ...work investigated the degradation of acetaldehyde and SO₂-bound acetaldehyde by two commercial Oenococcus oeni starters in white wine. Wines were produced by alcoholic fermentation with commercial yeast and adjusted to pH 3.3 and 3.6. While acetaldehyde was degraded rapidly and concurrently with malic acid at both pH values, SO₂-bound acetaldehyde caused sluggish bacterial growth. Strain differences were small. Efficient degradation of acetaldehyde can be achieved by commercial starters of O. oeni. According to the results, the degradation of acetaldehyde could not be separated from malolactic conversion by oenococci. While this may be desirable in white winemaking, it may be necessary to delay malolactic fermentation (MLF) in order to allow for colour development in red wines. SO₂-bound acetaldehyde itself maybe responsible for the sluggish or stuck MLF, and thus bound SO₂ should be considered next to free SO₂ in order to evaluate malolactic fermentability. The current study provides new results regarding the metabolism of acetaldehyde and SO₂-bound acetaldehyde during the MLF in white wine. The information is of significance to the wine industry and may contribute to reducing the concentration of wine preservative SO₂.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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