It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes ...in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes progressively with chronological age. According to our results, the age range from 47 to 54 is critical given that it is the period when the expression trend (increasing or decreasing) of age-related small non-coding RNAs is more pronounced. Furthermore, age-related miRNAs regulate genes that are involved in immune, cell cycle and cancer-related processes, which had already been associated to human aging. Therefore, human aging could be studied as a result of progressive molecular changes, and different age ranges should be analysed to cover the whole aging process.
Yerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related inflammation. The aim of this work was to study ...the effect of YM on cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells in vitro with phytohemagglutinin (PHA) in the presence of yerba mate and determined their activation by measuring the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells' (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in the inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component.
Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro ...manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.
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•Human dermis-derived cultures show two types of SOX2+ cells: Schwann and perivascular•p75NTR+CD56+ Schwann cells are responsible for neural progeny•SOX2 expression levels regulate the neural competence of dermal precursors•p75NTR+CD56+ neural precursor cells similarly arise from human cardiospheres
In this article, Izeta and colleagues show that neural precursor cell (NPC) cultures from adult human dermis include two SOX2+ cell subpopulations (Schwann and perivascular), and neural progeny is derived only from Schwann cells in a process regulated by their SOX2 expression levels. NPCs similarly arise from human cardiospheres, potentially elucidating the origin of seemingly unrelated NPCs observed in multiple organs.
Many factors may converge in healthy aging in the oldest old, but their association and predictive power on healthy or functionally impaired aging has yet to be demonstrated. By detecting healthy ...aging and in turn, poor aging, we could take action to prevent chronic diseases associated with age. We conducted a pilot study comparing results of a set of markers (peripheral blood mononuclear cell or PBMC telomere length, circulating Aβ peptides, anti-Aβ antibodies, and ApoE status) previously associated with poor aging or cognitive deterioration, and their combinations, in a cohort of "neurologically healthy" (both motor and cognitive) nonagenarians (
= 20) and functionally impaired, institutionalized nonagenarians (
= 38) recruited between 2014 and 2015. We recruited 58 nonagenarians (41 women, 70.7%; mean age: 92.37 years in the neurologically healthy group vs. 94.13 years in the functionally impaired group). Healthy nonagenarians had significantly higher mean PBMC telomere lengths (mean = 7,
= 0.001), this being inversely correlated with functional impairment, and lower circulating Aβ40 (total in plasma fraction or TP and free in plasma fraction or FP), Aβ42 (TP and FP) and Aβ17 (FP) levels (FP40 131.35,
= 0.004; TP40 299.10,
= 0.007; FP42 6.29,
= 0.009; TP42 22.53,
= 0.019; FP17 1.32
= 0.001; TP17 4.47,
= 0.3), after adjusting by age. Although healthy nonagenarians had higher anti-Aβ40 antibody levels (net adsorbed signal or NAS ± SD: 0.211 ± 0.107), the number of participants that pass the threshold (NAS > 3) to be considered as positive did not show such a strong association. There was no association with ApoE status. Additionally, we propose a "
combining TP40 and mean PBMC telomere length, the strongest correlation of measured biomarkers with neurologically healthy status in nonagenarians (AUC = 0.904).
Yerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related inflammation. The aim of this work was to study ...the effect of YM on cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells
in vitro
with phytohemagglutinin (PHA) in the presence of yerba mate and determined their activation by measuring the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells' (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in the inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component.
In the presence of yerba mate lymphocyte activation is reduced without affecting cell viability in a dose-dependent manner.
Background: Multiple sclerosis is an autoimmune and demyelinating disease of the central nervous system. Commercially available treatments are focused in the attenuation of the immune response, but ...up to now, none of them are focused in improving remyelination. Nevertheless, alternative strategies are being studied. MicroRNAs have been shown to work as remyelination inductors. More concretely, miR-219 has been shown to be involved in the differentiation of oligodendrocyte precursor cells (OPCs) and therefore remyelination. In this work, nanoparticles (NPs), liposomes (LPs) and exosomes (EXs) were compared as miR-219 delivery systems in an OPC culture where the ability of miR-219 to induce OPC differentiation was also analysed. Methods: OPCs were obtained from P-1 mice brains and cultured in laminin-coated P24 plates prior to the treatment. PLGA nanoparticles and DSPC liposomes were loaded with miRIDIAN microRNA mmu-miR-219a-5p. Exosomes were obtained from HEK293T cells infected with pLKO-mmu-miR219a-5p plasmid. All the respective controls were done. For uptake experiments, NPs were loaded with coumarin and LP with DiOC18. In addition, miRIDIAN microRNA mimic transfection control with Dy547 was used for NP and LP. Exosomes were labelled with Celltracker CM-Dil. In order to quantify the differentiation degree of OPCs and the levels of miR-219 in the vehicles, qPCR was carried out. Results: Preliminary results showed higher levels of miR-219 and a better uptake for LPs and NPs in comparison with EXs. However, LPs and NPs were not able to induce OPCs differentiation whereas EXs did. Summary/conclusion: EX, which showed the lowest miR-219 and uptake levels, were able to induce OPCs differentiation. These results might indicate that EX are extremely efficient as microRNA delivery systems. In addition, we hypothesized that the additional cargo that EXs may carry could favour the shown effects.