Daiva Bironaite - Academia.edu (original) (raw)

Papers by Daiva Bironaite

Research paper thumbnail of Fibrillogenic C-terminal fragment of alpha-1-antitrypsin activates human monocytes via oxidative mechanisms

Cell and Tissue Research, Jul 1, 2001

Production of alpha-1-antitrypsin by human monocytes is an important factor in controlling tissue... more Production of alpha-1-antitrypsin by human monocytes is an important factor in controlling tissue damage by proteases in the microenvironment of inflammation. Increases of four- to eightfold in levels of native and fragmented forms of alpha-1-antitrypsin have been detected in inflammatory loci in vivo. In this study we have extended our previous observation that the carboxyl-terminal peptide (C-36) of alpha-1-antitrypsin produced by specific proteinase cleavage, when added in its fibrillar form at concentrations of 5 microM or more to monocytes in culture, induces cytotoxic effects. Experiments with synthetic amyloid-forming peptides suggest fibril cytotoxicity to be mediated via a common oxidative stress mechanism. We undertook to determine whether C-36 fibril cytotoxicity also involves this common pathway. Monocytes stimulated with C-36 fibrils for 1 h showed significant elevation in monocyte chemoattractant protein-1 expression, induced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, increased intracellular lipid peroxidation, altered mitochondrial membrane potential, and increased cytosolic cytochrome c and caspase-3 activity. Treatment of monocytes with C-36 fibrils after 24 h also resulted in increased cytosolic cathepsin D activity, suggesting that lysosomes may also be destabilized over longer periods of time. In contrast, native alpha-1-antitrypsin only showed concentration and time-dependent effects on chemoattractant protein-1 expression, and these appear to be independent of oxidative stress. These results indicate that the cytotoxicity of the fibrillar fragment is mediated via oxidative mechanisms and support important multiple roles for native and also for cleaved forms of alpha-1-antitrypsin in monocyte recruitment and activation during inflammatory processes such as atherosclerosis.

Research paper thumbnail of P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

European Heart Journal, Oct 1, 2019

Research paper thumbnail of The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes

International Journal of Molecular Sciences, Apr 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Oxidative Properties of Blood-Derived Extracellular Vesicles in 15 Patients After Myocardial Infarction

Medical Science Monitor, Jan 31, 2022

BackgroundIn this study, we investigated the yield and composition of extracellular vesicles (EVs... more BackgroundIn this study, we investigated the yield and composition of extracellular vesicles (EVs) derived from 40- to 60-year-old healthy male controls and post-myocardial infarction (post-MI) patients’ blood samples and assessed their pro-inflammatory and oxidative-related properties. Our study aimed to determine the EV yield and composition differences between both groups and to find out if there were differences between EV-mediated oxidative stress reactions.Material/MethodsFifteen post-MI patients and 25 healthy individuals were included. EVs were isolated by ultracentrifugation and analyzed using nanotracking analysis (NTA), western blotting and fluorescent flow cytometry (FFC). Oxidative stress (OS) in blood samples was identified by measuring malondialdehyde concentration from serum, while EVs-induced OS was measured in the human vein endothelium cells (HUVEC) using H2DCFDA (2′,7′-dichlorodihydrofluorescein diacetate) fluorescence as a marker.ResultsWe found higher EVs concentration in healthy controls than in the post-MI group (7.07±3.1 E+10 ml vs 3.1±1.9 E+10 ml, P<0.001) and a higher level of CD9-positive exosomes (MFI 275±39.5 vs 252±13, P<0.001). Post-MI patients’ EVs carry pro-oxidative nicotinamide adenine dinucleotide phosphate (NADPH) oxidases isoforms NOX1 (NADPH oxidase 1), NOX5 (NADPH oxidase 5) and NOX2 (NADPH oxidase 2) and anti-oxidative thioredoxin, extracellular signal-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt B). In the post-MI EVs, there was a higher predominance of enzymes with anti-oxidative effects, leading to weaker OS-inducing properties in the HUVEC cells.ConclusionsWe conclude that post-MI patient blood sample EVs have stronger anti- than pro-oxidative properties and these could help fight against post-MI consequences.

Research paper thumbnail of The Inhibition of Glutathione Reductase by Quinones

Zeitschrift für Naturforschung C, Oct 1, 1991

Glutathione Reductase, Inhibition, Quinones Fully substituted quinones including som e naturally ... more Glutathione Reductase, Inhibition, Quinones Fully substituted quinones including som e naturally occurring oxyquinones acted as inhibitors o f yeast gluta thione reductase (EC 1.6.4.2). They were competitive, mixed or uncompetitive inhibitors for N A D P H , possess ing K j in the range o f 1-2 0 0 |iM and uncompetitive in hibitors for glutathione. Rhein (4,5-dioxy-9,10-anthraquinone-2-carbonic acid) and 9,10-phenanthrenequinone were the most effective inhibitors. It is concluded that certain quinones can bind to the N A D P(H)-binding site and to the heteroaromatics binding site at the inter face domain (P. A. Karplus, E. F. Pai, and G. E. Schulz, Eur. J. Biochem. 178, 6 9 3-7 0 3 (1989)) o f the enzyme.

Research paper thumbnail of Scanning electrochemical microscopy for the stimulation and investigation of human skeletal muscle-derived mesenchymal stem/stromal cells

Research paper thumbnail of Pacemaker functions of NCN2-expressing human mesenchymal stem cells

Research paper thumbnail of The Electron-Transfer Reactions of NADPH-Cytochrome P450 Reductase with Nonphysiological Oxidants

Archives of Biochemistry and Biophysics, 1994

Research paper thumbnail of Fungal quinone pigments as oxidizers and inhibitors of mitochondrial NADH:ubiquinone reductase

Archives of Biochemistry and Biophysics, 1992

Research paper thumbnail of The Role of Serum Adiponectin for Outcome Prediction in Patients with Dilated Cardiomyopathy and Advanced Heart Failure

BioMed Research International, 2017

Clinical interpretation of patients’ plasma adiponectin (APN) remains challenging; its value as b... more Clinical interpretation of patients’ plasma adiponectin (APN) remains challenging; its value as biomarker in dilated cardiomyopathy (DCM) is equivocal. We evaluated whether circulating APN level is an independent predictor of composite outcome: death, left ventricle assist device (LVAD) implantation, and heart transplantation (HT) in patients with nonischemic DCM. 57 patients with nonischemic DCM (average LV diastolic diameter 6.85 cm, LV ejection fraction 26.63%, and pulmonary capillary wedge pressure 22.06 mmHg) were enrolled. Patients underwent echocardiography, right heart catheterization, and endomyocardial biopsy. During a mean follow-up of 33.42 months, 15 (26%) patients died, 12 (21%) patients underwent HT, and 8 (14%) patients were implanted with LVAD. APN level was significantly higher in patients who experienced study endpoints (23.4 versus 10.9 ug/ml, p=0.01). APN was associated with worse outcome in univariate Cox proportional hazards model (HR 1.04, CI 1.02–1.07, p=0....

Research paper thumbnail of Benzene-induced cytotoxicity and apoptosis in TrHBMEC and HL-60 cell lines

Research paper thumbnail of The toxicity of aromatic nitrocompounds to bovine leukemia virus-transformed fibroblasts: the role of single-electron reduction

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1995

Bovine leukemia virus-transformed lamb embryo fibroblasts (line FLK) possess activity of DT-diaph... more Bovine leukemia virus-transformed lamb embryo fibroblasts (line FLK) possess activity of DT-diaphorase of ca. 260 U/mg protein and similar levels of other NADP(H)-oxidizing enzymes: NADH:oxidase, 359 U/mg; NADPH:oxidase, 43 U/mg; NADH:cytochrome-c reductase, 141 U/mg; NADPH:cytochrome-c reductase, 43 U/mg. In general, the toxicity of aromatic nitrocompounds towards FLK cells increases on increase of single-electron reduction potentials (E~) of nitrocompounds or the log of their reduction rate constants by single-electron-transferring enzymes, microsomal NADPH:cytochrome P-450 reductase (EC 1.6.2.4) and mitochondrial NADH:ubiquinone reductase (EC 1.6.99.3). No correlation between the toxicity and reduction rate of nitrocompounds by rat liver DT-diaphorase (EC 1.6.99.2) was observed. The toxicity is not significantly affected by dicumarol, an inhibitor of DT-diaphorase. Nitrocompounds examined were poor substrates for DT-diaphorase, being 10 4 times less active than menadione. Their poor reactivity is most probably determined by their preferential binding to a NADPH binding site, but not to menadione binding site of diaphorase. These data indicate that at comparable activities of DT-diaphorase and single-electron-transferring NAD(P)H dehydrogenases in the cell, the toxicity of nitrocompounds will be determined mainly by their single-electron reduction reactions.

Research paper thumbnail of The Effect of Heat Shock on Myogenic Differentiation of Human Skeletal-Muscle-Derived Mesenchymal Stem/Stromal Cells

Cells

Muscle injuries, degenerative diseases and other lesions negatively affect functioning of human s... more Muscle injuries, degenerative diseases and other lesions negatively affect functioning of human skeletomuscular system and thus quality of life. Therefore, the investigation of molecular mechanisms, stimulating myogenic differentiation of primary skeletal-muscle-derived mesenchymal stem/stromal cells (SM-MSCs), is actual and needed. The aim of the present study was to investigate the myogenic differentiation of CD56 (neural cell adhesion molecule, NCAM)-positive and -negative SM-MSCs and their response to the non-cytotoxic heat stimulus. The SM-MSCs were isolated from the post operation muscle tissue, sorted by flow cytometer according to the CD56 biomarker and morphology, surface profile, proliferation and myogenic differentiation has been investigated. Data show that CD56(+) cells were smaller in size, better proliferated and had significantly higher levels of CD146 (MCAM) and CD318 (CDCP1) compared with the CD56(−) cells. At control level, CD56(+) cells significantly more express...

Research paper thumbnail of Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair

International Journal of Molecular Sciences

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant los... more The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher relea...

Research paper thumbnail of Non-Physiological Redox Agents Are Reduced in the Nadp(H) Binding Site of Glutathione Reductase

Research paper thumbnail of Benzene-induced cytotoxicity and apoptosis in TrHBMEC and HL-60 cell lines

Research paper thumbnail of The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel

International Journal of Molecular Sciences

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesio... more Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-β3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type cha...

Research paper thumbnail of Human airway and lung microbiome at the crossroad of health and disease (Review)

Experimental and Therapeutic Medicine

Research paper thumbnail of Proteomic and biochemical analysis of R399E, a recombinant and mutant form of GDF5 on the secretome of human articular cartilage and meniscal explants from osteoarthritic joints

Osteoarthritis and Cartilage, 2021

Research paper thumbnail of Scanning electrochemical microscopy for the investigation of redox potential of human myocardium-derived mesenchymal stem cells grown at 2D and 3D conditions

Electrochimica Acta, 2020

Three-dimensional (3D) cell cultivation systems in vitro are promising biomodels to study the met... more Three-dimensional (3D) cell cultivation systems in vitro are promising biomodels to study the metabolic processes of healthy and diseased human heart cells. Cardiac 3D-spheroids are mimicking cell living conditions and, therefore, they can be employed to investigate processes that occur in both extra-cellular and intra-cellular environments. In this study, human healthy and dilated left ventricle myocardiumderived mesenchymal stem cells (hmMSCs) were grown for 5 days in two different cell cultivation systems in vitro : (i) attached to the cell culture flask (2D-cultivation) and (ii) in spheres (3D-cultivation). Then 2D-and 3D-cultivated healthy and pathological hmMSCs have been investigated by generationcollection mode of scanning electrochemical microscopy (GC-SECM) using 2-methylnaphthalene-1,4-dione (menadione or MD) as a redox mediator. Healthy 2D-cultivated hmMSCs were more redox active, therefore, faster responded to MD and were more sensitive to the high MD concentrations compared to the pathological hmMSCs. 3D-cultivation of pathological cells improved their redox activity and made healthy hmMSCs more resistant to the MD. Data of this study show that SECM measurements, using redox mediator MD, can be applied to investigate changes of intra-cellular redox status of human healthy and dilated hmMSCs grown under different conditions. Moreover, the intra-cellular redox status of dilated hmMSCs can be purposefully improved by 3D-cultivation with further their application for therapeutic purposes.

Research paper thumbnail of Fibrillogenic C-terminal fragment of alpha-1-antitrypsin activates human monocytes via oxidative mechanisms

Cell and Tissue Research, Jul 1, 2001

Production of alpha-1-antitrypsin by human monocytes is an important factor in controlling tissue... more Production of alpha-1-antitrypsin by human monocytes is an important factor in controlling tissue damage by proteases in the microenvironment of inflammation. Increases of four- to eightfold in levels of native and fragmented forms of alpha-1-antitrypsin have been detected in inflammatory loci in vivo. In this study we have extended our previous observation that the carboxyl-terminal peptide (C-36) of alpha-1-antitrypsin produced by specific proteinase cleavage, when added in its fibrillar form at concentrations of 5 microM or more to monocytes in culture, induces cytotoxic effects. Experiments with synthetic amyloid-forming peptides suggest fibril cytotoxicity to be mediated via a common oxidative stress mechanism. We undertook to determine whether C-36 fibril cytotoxicity also involves this common pathway. Monocytes stimulated with C-36 fibrils for 1 h showed significant elevation in monocyte chemoattractant protein-1 expression, induced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, increased intracellular lipid peroxidation, altered mitochondrial membrane potential, and increased cytosolic cytochrome c and caspase-3 activity. Treatment of monocytes with C-36 fibrils after 24 h also resulted in increased cytosolic cathepsin D activity, suggesting that lysosomes may also be destabilized over longer periods of time. In contrast, native alpha-1-antitrypsin only showed concentration and time-dependent effects on chemoattractant protein-1 expression, and these appear to be independent of oxidative stress. These results indicate that the cytotoxicity of the fibrillar fragment is mediated via oxidative mechanisms and support important multiple roles for native and also for cleaved forms of alpha-1-antitrypsin in monocyte recruitment and activation during inflammatory processes such as atherosclerosis.

Research paper thumbnail of P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

European Heart Journal, Oct 1, 2019

Research paper thumbnail of The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes

International Journal of Molecular Sciences, Apr 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Oxidative Properties of Blood-Derived Extracellular Vesicles in 15 Patients After Myocardial Infarction

Medical Science Monitor, Jan 31, 2022

BackgroundIn this study, we investigated the yield and composition of extracellular vesicles (EVs... more BackgroundIn this study, we investigated the yield and composition of extracellular vesicles (EVs) derived from 40- to 60-year-old healthy male controls and post-myocardial infarction (post-MI) patients’ blood samples and assessed their pro-inflammatory and oxidative-related properties. Our study aimed to determine the EV yield and composition differences between both groups and to find out if there were differences between EV-mediated oxidative stress reactions.Material/MethodsFifteen post-MI patients and 25 healthy individuals were included. EVs were isolated by ultracentrifugation and analyzed using nanotracking analysis (NTA), western blotting and fluorescent flow cytometry (FFC). Oxidative stress (OS) in blood samples was identified by measuring malondialdehyde concentration from serum, while EVs-induced OS was measured in the human vein endothelium cells (HUVEC) using H2DCFDA (2′,7′-dichlorodihydrofluorescein diacetate) fluorescence as a marker.ResultsWe found higher EVs concentration in healthy controls than in the post-MI group (7.07±3.1 E+10 ml vs 3.1±1.9 E+10 ml, P<0.001) and a higher level of CD9-positive exosomes (MFI 275±39.5 vs 252±13, P<0.001). Post-MI patients’ EVs carry pro-oxidative nicotinamide adenine dinucleotide phosphate (NADPH) oxidases isoforms NOX1 (NADPH oxidase 1), NOX5 (NADPH oxidase 5) and NOX2 (NADPH oxidase 2) and anti-oxidative thioredoxin, extracellular signal-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt B). In the post-MI EVs, there was a higher predominance of enzymes with anti-oxidative effects, leading to weaker OS-inducing properties in the HUVEC cells.ConclusionsWe conclude that post-MI patient blood sample EVs have stronger anti- than pro-oxidative properties and these could help fight against post-MI consequences.

Research paper thumbnail of The Inhibition of Glutathione Reductase by Quinones

Zeitschrift für Naturforschung C, Oct 1, 1991

Glutathione Reductase, Inhibition, Quinones Fully substituted quinones including som e naturally ... more Glutathione Reductase, Inhibition, Quinones Fully substituted quinones including som e naturally occurring oxyquinones acted as inhibitors o f yeast gluta thione reductase (EC 1.6.4.2). They were competitive, mixed or uncompetitive inhibitors for N A D P H , possess ing K j in the range o f 1-2 0 0 |iM and uncompetitive in hibitors for glutathione. Rhein (4,5-dioxy-9,10-anthraquinone-2-carbonic acid) and 9,10-phenanthrenequinone were the most effective inhibitors. It is concluded that certain quinones can bind to the N A D P(H)-binding site and to the heteroaromatics binding site at the inter face domain (P. A. Karplus, E. F. Pai, and G. E. Schulz, Eur. J. Biochem. 178, 6 9 3-7 0 3 (1989)) o f the enzyme.

Research paper thumbnail of Scanning electrochemical microscopy for the stimulation and investigation of human skeletal muscle-derived mesenchymal stem/stromal cells

Research paper thumbnail of Pacemaker functions of NCN2-expressing human mesenchymal stem cells

Research paper thumbnail of The Electron-Transfer Reactions of NADPH-Cytochrome P450 Reductase with Nonphysiological Oxidants

Archives of Biochemistry and Biophysics, 1994

Research paper thumbnail of Fungal quinone pigments as oxidizers and inhibitors of mitochondrial NADH:ubiquinone reductase

Archives of Biochemistry and Biophysics, 1992

Research paper thumbnail of The Role of Serum Adiponectin for Outcome Prediction in Patients with Dilated Cardiomyopathy and Advanced Heart Failure

BioMed Research International, 2017

Clinical interpretation of patients’ plasma adiponectin (APN) remains challenging; its value as b... more Clinical interpretation of patients’ plasma adiponectin (APN) remains challenging; its value as biomarker in dilated cardiomyopathy (DCM) is equivocal. We evaluated whether circulating APN level is an independent predictor of composite outcome: death, left ventricle assist device (LVAD) implantation, and heart transplantation (HT) in patients with nonischemic DCM. 57 patients with nonischemic DCM (average LV diastolic diameter 6.85 cm, LV ejection fraction 26.63%, and pulmonary capillary wedge pressure 22.06 mmHg) were enrolled. Patients underwent echocardiography, right heart catheterization, and endomyocardial biopsy. During a mean follow-up of 33.42 months, 15 (26%) patients died, 12 (21%) patients underwent HT, and 8 (14%) patients were implanted with LVAD. APN level was significantly higher in patients who experienced study endpoints (23.4 versus 10.9 ug/ml, p=0.01). APN was associated with worse outcome in univariate Cox proportional hazards model (HR 1.04, CI 1.02–1.07, p=0....

Research paper thumbnail of Benzene-induced cytotoxicity and apoptosis in TrHBMEC and HL-60 cell lines

Research paper thumbnail of The toxicity of aromatic nitrocompounds to bovine leukemia virus-transformed fibroblasts: the role of single-electron reduction

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1995

Bovine leukemia virus-transformed lamb embryo fibroblasts (line FLK) possess activity of DT-diaph... more Bovine leukemia virus-transformed lamb embryo fibroblasts (line FLK) possess activity of DT-diaphorase of ca. 260 U/mg protein and similar levels of other NADP(H)-oxidizing enzymes: NADH:oxidase, 359 U/mg; NADPH:oxidase, 43 U/mg; NADH:cytochrome-c reductase, 141 U/mg; NADPH:cytochrome-c reductase, 43 U/mg. In general, the toxicity of aromatic nitrocompounds towards FLK cells increases on increase of single-electron reduction potentials (E~) of nitrocompounds or the log of their reduction rate constants by single-electron-transferring enzymes, microsomal NADPH:cytochrome P-450 reductase (EC 1.6.2.4) and mitochondrial NADH:ubiquinone reductase (EC 1.6.99.3). No correlation between the toxicity and reduction rate of nitrocompounds by rat liver DT-diaphorase (EC 1.6.99.2) was observed. The toxicity is not significantly affected by dicumarol, an inhibitor of DT-diaphorase. Nitrocompounds examined were poor substrates for DT-diaphorase, being 10 4 times less active than menadione. Their poor reactivity is most probably determined by their preferential binding to a NADPH binding site, but not to menadione binding site of diaphorase. These data indicate that at comparable activities of DT-diaphorase and single-electron-transferring NAD(P)H dehydrogenases in the cell, the toxicity of nitrocompounds will be determined mainly by their single-electron reduction reactions.

Research paper thumbnail of The Effect of Heat Shock on Myogenic Differentiation of Human Skeletal-Muscle-Derived Mesenchymal Stem/Stromal Cells

Cells

Muscle injuries, degenerative diseases and other lesions negatively affect functioning of human s... more Muscle injuries, degenerative diseases and other lesions negatively affect functioning of human skeletomuscular system and thus quality of life. Therefore, the investigation of molecular mechanisms, stimulating myogenic differentiation of primary skeletal-muscle-derived mesenchymal stem/stromal cells (SM-MSCs), is actual and needed. The aim of the present study was to investigate the myogenic differentiation of CD56 (neural cell adhesion molecule, NCAM)-positive and -negative SM-MSCs and their response to the non-cytotoxic heat stimulus. The SM-MSCs were isolated from the post operation muscle tissue, sorted by flow cytometer according to the CD56 biomarker and morphology, surface profile, proliferation and myogenic differentiation has been investigated. Data show that CD56(+) cells were smaller in size, better proliferated and had significantly higher levels of CD146 (MCAM) and CD318 (CDCP1) compared with the CD56(−) cells. At control level, CD56(+) cells significantly more express...

Research paper thumbnail of Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair

International Journal of Molecular Sciences

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant los... more The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher relea...

Research paper thumbnail of Non-Physiological Redox Agents Are Reduced in the Nadp(H) Binding Site of Glutathione Reductase

Research paper thumbnail of Benzene-induced cytotoxicity and apoptosis in TrHBMEC and HL-60 cell lines

Research paper thumbnail of The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel

International Journal of Molecular Sciences

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesio... more Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-β3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type cha...

Research paper thumbnail of Human airway and lung microbiome at the crossroad of health and disease (Review)

Experimental and Therapeutic Medicine

Research paper thumbnail of Proteomic and biochemical analysis of R399E, a recombinant and mutant form of GDF5 on the secretome of human articular cartilage and meniscal explants from osteoarthritic joints

Osteoarthritis and Cartilage, 2021

Research paper thumbnail of Scanning electrochemical microscopy for the investigation of redox potential of human myocardium-derived mesenchymal stem cells grown at 2D and 3D conditions

Electrochimica Acta, 2020

Three-dimensional (3D) cell cultivation systems in vitro are promising biomodels to study the met... more Three-dimensional (3D) cell cultivation systems in vitro are promising biomodels to study the metabolic processes of healthy and diseased human heart cells. Cardiac 3D-spheroids are mimicking cell living conditions and, therefore, they can be employed to investigate processes that occur in both extra-cellular and intra-cellular environments. In this study, human healthy and dilated left ventricle myocardiumderived mesenchymal stem cells (hmMSCs) were grown for 5 days in two different cell cultivation systems in vitro : (i) attached to the cell culture flask (2D-cultivation) and (ii) in spheres (3D-cultivation). Then 2D-and 3D-cultivated healthy and pathological hmMSCs have been investigated by generationcollection mode of scanning electrochemical microscopy (GC-SECM) using 2-methylnaphthalene-1,4-dione (menadione or MD) as a redox mediator. Healthy 2D-cultivated hmMSCs were more redox active, therefore, faster responded to MD and were more sensitive to the high MD concentrations compared to the pathological hmMSCs. 3D-cultivation of pathological cells improved their redox activity and made healthy hmMSCs more resistant to the MD. Data of this study show that SECM measurements, using redox mediator MD, can be applied to investigate changes of intra-cellular redox status of human healthy and dilated hmMSCs grown under different conditions. Moreover, the intra-cellular redox status of dilated hmMSCs can be purposefully improved by 3D-cultivation with further their application for therapeutic purposes.