1,721,008 research outputs found
Nadph oxidases: Redox regulators of stem cell fate and function
Full text linkOne of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative
I glicosidi della Stevia come nutraceutici ad effetto insulino simile
No full textStevia rebaudiana Bertoni è una pianta perenne appartenente alla famiglia delle Asteracee (Compositae), nativa delle regioni subtropicali del Brasile e del Paraguay. Fin dai tempi più antichi le sue foglie sono state impiegate dalle popolazioni native in virtù del loro potere dolcificante. Questa caratteristica ha sollevato l’interesse dei nutrizionisti e dell’industria, sempre alla ricerca di nuovi dolcificanti naturali, privi di potere calorico e alternativo al saccarosio. Tale esigenza è da imputarsi al preoccupante aumento di diabete mellito di tipo 2 e obesità, sia nei paesi industrializzati sia in quelli in via di sviluppo, che costituisce attualmente il principale problema di sanità pubblica a livello mondiale. Oltre al potere dolcificante, i glicosidi estratti dalla Stevia rebaudiana Bertoni possiedono diversi effetti benefici sulla salute umana, tra i quali i più interessanti sono quelli anti-iperglicemici, insulinotropici ed insulino-simili, che li rendono potenziali coadiuvanti nel trattamento del diabete mellito e dei dismetabolismi ad esso associati.
Studi in vivo sia su animali che su volontari umani hanno dimostrato che i glicosidi della Stevia non sono genotossici né carcinogenici, pertanto la Food and Drug Administration statunitense (FDA) e l’Ente Europeo per la Sicurezza Alimentare (EFSA) hanno autorizzato l’uso dei glicosidi della Stevia come dolcificanti commerciali e additivi alimentari. La dose giornaliera consentita è stata stabilita a 4 mg/Kg di peso.
Lo scopo di questa ricerca è stato quello di studiare il meccanismo molecolare sotteso agli effetti esercitati dai glicosidi della Stevia sul metabolismo del glucosio. A tal fine è stato valutato l’effetto di alcuni estratti commerciali di Stevia sull’attività di trasporto di glucosio in diverse linee cellulari, confrontandolo con quello dell’insulina per validarne l’attività come nutraceutico ad azione ipoglicemizzant
Comparison of the therapeutic effect of amniotic fluid stem cells and their exosomes on monoiodoacetate-induced animal model of osteoarthritis
Full text linkThe cartilage tissue engineering associated with stem cell-related therapies is becoming very interesting since adult articular cartilage has limited intrinsic capacity for regeneration upon injury. Amniotic fluid stem cells (AFSC) have been shown to produce exosomes with growth factors and immunomodulating molecules that could stop tissue degradation and induce cartilage repair. Based on this state of the art, the main aim of this study was to explore the efficacy of the secreted exosomes, compared to their AFSC source, in MIA-induced animal model of osteoarthritis mimicking a chronic and degenerative process, where inflammation is also involved and lead to irreversible joint damage. Exosomes, obtained by the use of a commercial kit, prior to the injection in animal knee joints, were characterized for the presence of typical markers and HGF, TGFβ, and IDO. Then, analyses were performed by histology, immunohistochemistry, and behavioral scoring up to 3 weeks after the treatment. Exosome-treated defects showed enhanced pain tolerance level and improved histological scores than the AFSC-treated defects. Indeed by 3 weeks, TGFβ-rich exosome samples induced an almost complete restoration of cartilage with good surface regularity and with the characteristic of hyaline cartilage. Moreover, cells positive for resolving macrophage marker were more easily detectable into exosome-treated joints. Therefore, a modulating role for exosomes on macrophage polarization is conceivable, as demonstrated also by experiments performed on THP1 macrophages. In conclusion, this study demonstrates for the first time the efficacy of human AFSC exosomes in counteract cartilage damage, showing a positive correlation with their TGFβ content
Exosomes Derived from Human Amniotic Fluid Mesenchymal Stem Cells Preserve Microglia and Neuron Cells from Aβ
No full textBackground: Neuroinflammation is involved in neuronal cell death that occurs in neurodegenerative diseases such as Alzheimer’s disease (AD). Microglia play important roles in regulating the brain amyloid beta (Aβ) levels, so immunomodulatory properties exerted by mesenchymal stem cells may be exploited to treat this pathology. The evidence suggests that the mechanism of action of human amniotic fluid stem cells (hAFSCs) is through their secretome, which includes exosomes (exo). Methods: We examined the effect of exosomes derived from human amniotic fluid stem cells (hAFSCs-exo) on activated BV-2 microglia cells by lipopolysaccharide (LPS) as a neuroinflammation model. To investigate the exo effect on the interplay between AD neurons and microglia, SH-SY5Y neuroblastoma cells treated with Aβ were exposed to a conditioned medium (CM) obtained from activated BV-2 or co-culture systems. Results: We found that the upregulation of the markers of pro-inflammatory microglia was prevented when exposed to hAFSC-exo whereas the markers of the anti-inflammatory macrophage phenotype were not affected. Interestingly, the hAFSC-exo pretreatment significantly inhibited the oxidative stress rise and apoptosis occurring in the neurons in presence of both microglia and Aβ. Conclusion: We demonstrated that hAFSC-exo mitigated an inflammatory injury caused by microglia and significantly recovered the neurotoxicity, suggesting that hAFSC-exo may be a potential therapeutic agent for inflammation-related neurological conditions, including AD
Dietary polyphenols and their effects on cell biochemistry and pathophysiology
Full text linkPolyphenols, occurring in fruit and vegetables, wine, tea, extra virgin olive oil, chocolate, and other cocoa products, have been demonstrated to exert beneficial effects in a large array of disease states, including cancer, cardiovascular disease, and neurodegenerative disorders. Many of the biological effects of polyphenols have been attributed to their antioxidant properties, either through their reducing capacities per se or through their possible influences on intracellular redox status. As such, polyphenols may protect cell constituents against oxidative damage and have been reported to limit the risk of various degenerative diseases associated with oxidative stress, including cardiovascular diseases, type 2 diabetes, and cancer. However, accumulating evidence suggests that the classical hydrogen-donating antioxidant activity is unlikely to be the sole explanation for their cellular effects in vivo. Indeed, it has recently become clear that, in complex biological systems, polyphenols are able to exhibit several additional properties which are yet poorly understood. It is evident that polyphenols are potent bioactive molecules and a clear understanding of their precise mechanisms of action as either antioxidants or modulators of cell signaling is crucial to the evaluation of their potential as chemopreventive or anticancer agents and inhibitors of neurodegeneration
Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration
Full text linkNeurodegenerative diseases include a variety of pathologies such as Alzheimer’s
disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and so forth,
which share many common characteristics such as oxidative stress, glycation, abnormal protein
deposition, inflammation, and progressive neuronal loss. The last century has witnessed significant
research to identify mechanisms and risk factors contributing to the complex etiopathogenesis of
neurodegenerative diseases, such as genetic, vascular/metabolic, and lifestyle-related factors, which
often co-occur and interact with each other. Apart from several environmental or genetic factors,
in recent years, much evidence hints that impairment in redox homeostasis is a common mechanism
in different neurological diseases. However, from a pharmacological perspective, oxidative stress is a
difficult target, and antioxidants, the only strategy used so far, have been ineffective or even provoked
side effects. In this review, we report an analysis of the recent literature on the role of oxidative stress
in Alzheimer’s and Parkinson’s diseases as well as in amyotrophic lateral sclerosis, retinal ganglion
cells, and ataxia. Moreover, the contribution of stem cells has been widely explored, looking at their
potential in neuronal differentiation and reporting findings on their application in fighting oxidative
stress in different neurodegenerative diseases. In particular, the exposure to mesenchymal stem cells
or their secretome can be considered as a promising therapeutic strategy to enhance antioxidant
capacity and neurotrophin expression while inhibiting pro-inflammatory cytokine secretion, which
are common aspects of neurodegenerative pathologies. Further studies are needed to identify a
tailored approach for each neurodegenerative disease in order to design more effective stem cell
therapeutic strategies to prevent a broad range of neurodegenerative disorder
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Combination of Epigallocatechin Gallate and Sulforaphane Counteracts In Vitro Oxidative Stress and Delays Stemness Loss of Amniotic Fluid Stem Cells
Full text linkAmniotic fluid stem cells (AFSCs) are characterized in vivo by a unique niche guarantying their homeostatic role in the body. Maintaining the functionality of stem cells ex vivo for clinical applications requires a continuous improvement of cell culture conditions. Cellular redox status plays an important role in stem cell biology as long as reactive oxygen species (ROS) concentration is finely regulated and their adverse effects are excluded. The aim of this study was to investigate the protective effect of two antioxidants, sulforaphane (SF) and epigallocatechin gallate (EGCG), against in vitro oxidative stress due to hyperoxia and freeze-thawing cycles in AFSCs. Human AFSCs were isolated and characterized from healthy subjects. Assays of metabolic function and antioxidant activity were performed to investigate the effect of SF and EGCG cotreatment on AFSCs. Real-time PCR was used to investigate the effect of the cotreatment on pluripotency, senescence, osteogenic and adipogenic markers, and antioxidant enzymes. Alkaline phosphatase assays and Alizarin Red staining were used to confirm osteogenic differentiation. The cotreatment with SF and EGCG was effective in reducing ROS production, increasing GSH levels, and enhancing the endogenous antioxidant defences through the upregulation of glutathione reductase, NAD(P)H:quinone oxidoreductase-1, and thioredoxin reductase. Intriguingly, the cotreatment sustained the stemness state by upregulating pluripotency markers such as OCT4 and NANOG. Moreover, the cotreatment influenced senescence-associated gene markers in respect to untreated cells. The cotreatment upregulated osteogenic gene markers and promoted osteogenic differentiation in vitro. SF and EGCG can be used in combination in AFSC culture as a strategy to preserve stem cell functionality
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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