1,720,994 research outputs found
Data about a rat embryonic stem cell model at pre- and post-implantation stage to reduce in vivo developmental toxicity testing
No full textThe present dataset file contains data about the characterization of an in vitro model based on a line of Rat Embryonic Stem Cells (RESCs) line. The RESCs culture is easy to use and suitable for wide-scale screening, mimicking two different developmental stages: i) pre-implant model, as undifferentiated pluripotent cells, and ii) post-implant model, driving cell differentiation toward the neuroectodermal lineage. The in vitro platform model was validated by using 2,2',6,6'-tetrabromobisphenol A (TBBPA) as test compound, a toxic flame retardant which acts as an endocrine disruptor chemical, targeting the thyroid hormone (TH) signal. The in vitro platform was validated by using 2,2',6,6'-tetrabromobisphenol A (TBBPA) as test compound, a toxic flame retardant which acts as an endocrine disruptor chemical, targeting the thyroid hormone (TH) signal. The dataset contains all the characterization data, the PCRarray full expression data and functional experiments
Data about the role of RXRγ in T3-mediated oligodendrocyte precursor cell differentiation
No full textThis dataset contains data describing the effect of the knock-out of the Rxrg gene in neral stem cell (NSC)-derived oligodendrocyte precursor cells (OPCs) differentiation and maturation. Data has been obtained by transcriptomic analysis using RNAseq in cells isolated by WT and Rxrg-/- animals cultured as indifferentiated precursors and 24 hours after the differentiation induction by triiodotironine (T3) exposure, mimiking the physiologic differentiation/maturation molecular machinery.
RNAseq data has been validated using morphological analysis. Molecular tools has been used to inhibit (cyclopamine, GANT61) or activate (SAG, purmorphamine) the sonic hadgehog (SHH) pathway in differentiating WT and Rxrg-/- OPC cultures. Specific markers (NG2, MBP) have been used to quantify the differentiation/maturation of the OPC culture, measuring the percentage of precursors and mature oligodendrocytes
RNAseq analysis on the foot of mediterranean mussels experimentally exposed to heat waves for 3 and 30 days
No full textThis dataset contains RNAseq data to measure gene expression and identify differentially expressed genes (DEGs) in Mediterranean mussels (Mytilus galloprovincialis) exposed for 3 and 30 days to experimental heat waves (28°C), mimiking the temperature increase expected in 2050. The control group was maintained at a temperature of 20.0 ± 0.5 ◦C, while the exposed group was brought to 28.0 ± 0.5 °C by warming the water at a rate of 0.5 °C·h-1. The water temperatures were kept constant for 30 days using electronic thermostats and heat exchangers. Seawater parameters (temperature, salinity, and pH) were checked daily
Data about the effect of short-chain PFAS exposure during gestation and breastfeeding on alteration of learning and memory in adulthood
No full textThe dataset includes detailed outcomes of in vivo and ex vivo tests, aimed to investigate the effect of short-chain Per- and polyfluoroalkyl substances (PFAS) maternal exposure on neurodevelopment in rats. Animals have been exposed to two different contaminants (PFBA, Perfluorobutanoic acid; and GenX, Ammonium Perfluoro, 2-methyl-3-oxahexanoate) at two different doses (indicated as LD, low dose, and HD, high dose) indirectly, through the maternal exposure (4 weeks pre-gestation, gestation, and lactation periods). Tests include a battery of standardized behavioral performed during adult life (9 weeks after weaning), assays designed to probe distinct facets of neurological function. Motor coordination and balance were quantitatively assessed via the Rotarod test. Spontaneous locomotion, reflecting exploratory behavior and anxiety-like states, was evaluated through open-field activity. Cognitive and mnemonic abilities were thoroughly investigated using the Morris water maze.
In vivo analysis have been implemented with quantification of circulating hormones and gene expression data of neurogenesis marker in the hippocampus. Furthermore, the dataset integrates cell culture data from ex vivo studies, using primary hippocampl neurons (isolated from P0 pups exposed to PFBA during gestation) providing a comprehensive view.
This dataset also includes quantitative analyses of short-chain PFAS residues in key tissues (liver, kidneys, brain, and thyroid)
Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia
Full text linkIntroduction: Nerve growth factor (NGF) is a pleiotropic molecule acting on different cell types in physiological and pathological conditions. However, the effect of NGF on the survival, differentiation and maturation of oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), the cells responsible for myelin formation, turnover, and repair in the central nervous system (CNS), is still poorly understood and heavily debated. Methods: Here we used mixed neural stem cell (NSC)-derived OPC/astrocyte cultures to clarify the role of NGF throughout the entire process of OL differentiation and investigate its putative role in OPC protection under pathological conditions. Results: We first showed that the gene expression of all the neurotrophin receptors (TrkA, TrkB, TrkC, and p75(NTR)) dynamically changes during the differentiation. However, only TrkA and p75(NTR) expression depends on T3-differentiation induction, as Ngf gene expression induction and protein secretion in the culture medium. Moreover, in the mixed culture, astrocytes are the main producer of NGF protein, and OPCs express both TrkA and p75(NTR). NGF treatment increases the percentage of mature OLs, while NGF blocking by neutralizing antibody and TRKA antagonist impairs OPC differentiation. Moreover, both NGF exposure and astrocyte-conditioned medium protect OPCs exposed to oxygenglucose deprivation (OGD) from cell death and NGF induces an increase of AKT/pAKT levels in OPCs nuclei by TRKA activation. Discussion: This study demonstrated that NGF is implicated in OPC differentiation, maturation, and protection in the presence of metabolic challenges, also suggesting implications for the treatment of demyelinating lesions and diseases
Neuroprotection and neuroregeneration: roles for the white matter
Full text linkEfficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system. Over the last few decades, a great deal of attention has been focused on white matter as a potential therapeutic target, mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system, a cell type able to fully repair myelin damage, and to the development of advanced imaging techniques to visualize and measure white matter lesions. The combination of these two events has greatly increased the body of research into white matter alterations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair, thus indirectly contributing to neuroprotection. This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system. Pivot conditions are discussed, specifically multiple sclerosis as a white matter disease; spinal cord injury, the acute lesion of a central nervous system component where white matter prevails over the gray matter, and Alzheimer’s disease, where the white matter was considered an ancillary component until recently. We first describe oligodendrocyte precursor cell biology and developmental myelination, and its regulation by thyroid hormones, then briefly describe white matter imaging techniques, which are providing information on white matter involvement in central nervous system lesions and degenerative diseases. Finally, we discuss pathological mechanisms which interfere with myelin repair in adulthood
New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich's Ataxia Patient
Full text linkIron homeostasis in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron homeostasis occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich's ataxia (FRDA, OMIM no. 229300), a hereditary neurodegenerative disorder. Exploiting the induced pluripotent stem cells (iPSCs) technology and the iPSC capacity to differentiate into specific cell types, we derived cardiomyocytes of a FRDA patient and of a healthy control subject in order to study the cardiac iron homeostasis and the HAMP-FPN axis. Both CTR and FRDA iPSCs-derived cardiomyocytes express cardiac differentiation markers; in addition, FRDA cardiomyocytes maintain the FRDA-like phenotype. We found that FRDA cardiomyocytes show an increase in the protein expression of HAMP and FPN. Moreover, immunofluorescence analysis revealed for the first time an unexpected nuclear localization of FPN in both cm and FRDA cardiomyocytes. However, the amount of the nuclear FPN was less in FRDA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis
Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain
Full text linkHaemangiosarcoma is a highly metastatic and lethal cancer of blood vessel-forming cells that commonly spreads to the brain in both humans and dogs. Dysregulations in phosphatase and tensin (PTEN) homologue have been identified in various types of cancers, including haemangiosarcoma. MicroRNAs (miRNAs) are short noncoding single-stranded RNA molecules that play a crucial role in regulating the gene expression. Some miRNAs can function as oncogenes or tumour suppressors, influencing important processes in cancer, such as angiogenesis. This study aimed to investigate whether miRNAs targeting PTEN were disrupted in canine haemangiosarcoma and its corresponding brain metastases (BM). The expression levels of miRNA-10b, miRNA-19b, miRNA-21, miRNA-141 and miRNA-494 were assessed in samples of primary canine cardiac haemangiosarcomas and their matched BM. Furthermore, the miRNA profile of the tumours was compared to samples of adjacent non-cancerous tissue and healthy control tissues. In primary cardiac haemangiosarcoma, miRNA-10b showed a significant increase in expression, while miRNA-494 and miRNA-141 exhibited downregulation. Moreover, the overexpression of miRNA-10b was retained in metastatic brain lesions. Healthy tissues demonstrated significantly different expression patterns compared to cancerous tissues. In particular, the expression of miRNA-10b was nearly undetectable in both control brain tissue and perimetastatic cerebral tissue. These findings can provide a rationale for the development of miRNA-based therapeutic strategies, aimed at selectively treating haemangiosarcoma
Brain susceptibility to hypoxia/hypoxemia and metabolic dysfunction in Alzheimer's disease
No full textPhotobiomodulation at Defined Wavelengths Regulates Mitochondrial Membrane Potential and Redox Balance in Skin Fibroblasts
Full text linkStarting from the discovery of phototherapy in the beginning of the last century, photobiomodulation (PBM) has been defined in late 1960s and, since then, widely described in different in vitro models. Robust evidence indicates that the effect of light exposure on the oxidative state of the cells and on mitochondrial dynamics, suggesting a great therapeutic potential. The translational scale-up of PBM, however, has often given contrasting and confusing results, mainly due to light exposure protocols which fail to adequately control or define factors such as emitting device features, emitted light characteristics, exposure time, cell target, and readouts. In this in vitro study, we describe the effects of a strictly controlled light-emitting diode (LED)-based PBM protocol on human fibroblasts, one of the main cells involved in skin care, regeneration, and repair. We used six emitter probes at different wavelengths (440, 525, 645, 660, 780, and 900 nm) with the same irradiance value of 0.1 mW/cm2, evenly distributed over the entire surface of the cell culture well. The PBM was analyzed by three main readouts: (i) mitochondrial potential (MitoTracker Orange staining), (ii) reactive oxygen species (ROS) production (CellROX staining); and (iii) cell death (nuclear morphology). The assay was also implemented by cell-based high-content screening technology, further increasing the reliability of the data. Different exposure protocols were also tested (one, two, or three subsequent 20 s pulsed exposures at 24 hr intervals), and the 645 nm wavelength and single exposure chosen as the most efficient protocol based on the mitochondrial potential readout, further confirmed by mitochondrial fusion quantification. This protocol was then tested for its potential to prevent H2O2-induced oxidative stress, including modulation of the light wave frequency. Finally, we demonstrated that the controlled PBM induced by the LED light exposure generates a preconditioning stimulation of the mitochondrial potential, which protects the cell from oxidative stress damage
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