Thymic epithelial cells (TECs) help orchestrate thymopoiesis, and TEC differentiation relies on bidirectional interactions with thymocytes. Although the molecular mediators that stimulate medullary ...thymic epithelial cell (mTEC) maturation are partially elucidated, the signals that regulate cortical thymic epithelial cell (cTEC) homeostasis remain elusive. Using IL-7 reporter mice, we show that TECs coexpressing high levels of IL-7 (Il7(YFP+) TECs) reside within a subset of CD205(+)Ly51(+)CD40(low) cTECs that coexpresses Dll4, Ccl25, Ccrl1, Ctsl, Psmb11, and Prss16 and segregates from CD80(+)CD40(high) mTECs expressing Tnfrsf11a, Ctss, and Aire. As the frequency of Il7(YFP+) TECs gradually declines as mTEC development unfolds, we explored the relationship between Il7(YFP+) TECs and mTECs. In thymic organotypic cultures, the thymocyte-induced reduction in Il7(YFP+) TECs dissociates from the receptor activator of NF-κB-mediated differentiation of CD80(+) mTECs. Still, Il7(YFP+) TECs can generate some CD80(+) mTECs in a stepwise differentiation process via YFP(-)Ly51(low)CD80(low) intermediates. Il7(YFP+) TECs are sustained in Rag2(-/-) mice, even following in vivo anti-CD3ε treatment that mimics the process of pre-TCR β-selection of thymocytes to the double positive (DP) stage. Using Marilyn-Rag2(-/-) TCR transgenic, we find that positive selection into the CD4 lineage moderately reduces the frequency of Il7(YFP+) TECs, whereas negative selection provokes a striking loss of Il7(YFP+) TECs. These results imply that the strength of MHC/peptide-TCR interactions between TECs and thymocytes during selection constitutes a novel rheostat that controls the maintenance of IL-7-expressing cTECs.
Agmatine is an endogenous neuromodulator that has been shown to have beneficial effects in the central nervous system, including antidepressant-like effects in animals. In this study, we investigated ...the ability of agmatine (0.1mg/kg, p.o.) and the conventional antidepressant fluoxetine (10mg/kg, p.o.) to reverse the behavioral effects and morphological alterations in the hippocampus of mice exposed to chronic corticosterone (20mg/kg, p.o.) treatment for a period of 21days as a model of stress and depressive-like behaviors. Chronic corticosterone treatment increased the immobility time in the tail suspension test (TST), but did not cause anhedonic-like and anxiety-related behaviors, as assessed with the splash test and the open field test (OFT), respectively. Of note, the depressive-like behaviors induced by corticosterone were accompanied by a decrease in hippocampal cell proliferation, although no changes in hippocampal neuronal differentiation were observed. Our findings provide evidence that, similarly to fluoxetine, agmatine was able to reverse the corticosterone-induced depressive-like behaviors in the TST as well as the deficits in hippocampal cell proliferation. Additionally, fluoxetine but not agmatine, increased hippocampal differentiation. Agmatine, similar to fluoxetine, was capable of increasing both dendritic arborization and length in the entire dentate hippocampus, an effect more evident in the ventral portion of the hippocampus, as assessed with the modified Sholl analysis. Altogether, our results suggest that the increase in hippocampal proliferation induced by agmatine may contribute, at least in part, to the antidepressant-like response of this compound in this mouse model of stress induced by chronic exposure to corticosterone.
•Chronic corticosterone administration increased the immobility time in the TST.•Agmatine and fluoxetine reversed behavioral alterations elicited by corticosterone.•Corticosterone reduced hippocampal cell proliferation, but not differentiation.•Agmatine reversed corticosterone-induced deficit in hippocampal cell proliferation.•Agmatine improved dendritic arborization and length in hippocampal dentate gyrus.
Smart cities aim to improve the citizens' quality of life by leveraging information about urban scale processes extracted from heterogeneous data sources collected on citywide deployments. The ...Internet-of-Things (IoT) is, thus, the enabler of smart city technologies at urban scale. In this paper, we present PortoLivingLab, a multisource sensing infrastructure that leverages IoT technology to achieve city-scale sensing of four phenomena: weather, environment, public transport, and people flows. To sense these processes on a city scale, we deployed a vehicular network with over 600 vehicles and 19 static environmental sensors. We also developed an easily reconfigurable crowdsensing platform and carried out several crowdsensing campaigns with more than 600 participants. The data is collected in a common backend and stored using similar spatio-temporal data models to simplify sharing and joint analysis for the characterization of urban dynamics. We describe the architecture and composing elements of PortoLivingLab, highlighting the IoT technologies, and challenges faced. We present several proof-of-concept use cases (e.g., passenger flows from WiFi connections) that provide new insights into different components of an evolving and moving city. Finally, we lay out the future lines of work that will strive for finding hidden phenomena by leveraging data from the three complementary platforms.
L. is a subshrub used in traditional medicine in different parts of the world, namely in Europe and the Iberian Peninsula. According to reported folk knowledge, the aerial parts are mainly used as ...diuretics and the underground organs are used for the treatment of disorders of the urinary system and as a laxative. In this work, the aerial part and the roots and rhizomes of
were chemically characterized with regard to the content of phenolic compounds and bioactive properties. Aqueous (infusions and decoctions) preparations and hydroethanolic extracts from the two mentioned parts of the plant were prepared. Nine phenolic compounds were detected in all the extracts. Apigenin-
-hexoside-
-pentoside isomer II was the major compound in aqueous extracts and, in the hydroethanolic extract was quercetin-
-deoxyhexoside-hexoside followed by apigenin-
-hexoside-
-pentoside isomer II. All extracts revealed antioxidant activity and potential to inhibit some of the assayed bacteria; aqueous extracts of the aerial part and infusions of roots and rhizomes did not show cytotoxic effects on a non-tumor primary cell culture. This preliminary study provides suggestions of the biological potential associated with the empirical uses and knowledge of this species, in particular its bioactivities.
Stem cell therapy is a strategy far from being satisfactory and applied in the clinic. Poor survival and differentiation levels of stem cells after transplantation or neural injury have been major ...problems. Recently, it has been recognized that cell death-relevant proteins, notably those that operate in the core of the executioner apoptosis machinery are functionally involved in differentiation of a wide range of cell types, including neural cells.
This article will review recent studies on the mechanisms underlying the non-apoptotic function of mitochondrial and death receptor signaling pathways during neural differentiation. In addition, we will discuss how these major apoptosis-regulatory pathways control the decision between differentiation, self-renewal and cell death in neural stem cells and how levels of activity are restrained to prevent cell loss as final outcome.
Emerging evidence suggests that, much like p53, caspases and Bcl-2 family members, the two prime triggers of cell death pathways, death receptors and mitochondria, may influence proliferation and differentiation potential of stem cells, neuronal plasticity, and astrocytic versus neuronal stem cell fate decision.
A better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation as an alternative to cell death will surely contribute to improve neuro-replacement strategies.
► Cell death-relevant proteins are functionally involved in neural differentiation. ► Understanding differentiation will improve neuro-replacement strategies. ► Mitochondrial and death receptor pathways influence stem cell fate. ► Neuronal plasticity and astrocytic versus neuronal fate decision are also modulated. ► Cell fate switch involves regulation of redox stage and Bcl-2 family proteins.
Conducting fibres are essential to the development of e-textiles. We demonstrate a method to make common insulating textile fibres conductive, by coating them with graphene. The resulting fibres ...display sheet resistance values as low as 600 Ωsq
, demonstrating that the high conductivity of graphene is not lost when transferred to textile fibres. An extensive microscopic study of the surface of graphene-coated fibres is presented. We show that this method can be employed to textile fibres of different materials, sizes and shapes, and to different types of graphene. These graphene-based conductive fibres can be used as a platform to build integrated electronic devices directly in textiles.
The presentation of nutrition information on a serving size basis is a strategy that has been adopted by several countries to promote healthy eating. Variation in serving size, however, can alter the ...nutritional values reported on food labels and compromise the food choices made by the population. This narrative review aimed to discuss (1) current nutrition labelling legislation regarding serving size and (2) the implications of declared serving size for nutrition information available on packaged foods. Most countries with mandatory food labelling require that serving size be presented on food labels, but variation in this information is generally allowed. Studies have reported a lack of standardisation among serving sizes of similar products which may compromise the usability of nutrition information. Moreover, studies indicate that food companies may be varying serving sizes as a marketing strategy to stimulate sales by reporting lower values of certain nutrients or lower energy values on nutrition information labels. There is a need to define the best format for presenting serving size on food labels in order to provide clear and easily comprehensible nutrition information to the consumer.
Salacia impressifolia (Miers) A. C. Smith (family Celastraceae) is a traditional medicinal plant found in the Amazon Rainforest known as “miraruíra”, "cipó-miraruíra" or “panu” and is traditionally ...used to treat dengue, flu, inflammation, pain, diabetes, male impotency, renal affections, rheumatism and cancer. Aim of the study: The aim of this study was to investigate in vitro and in vivo anti-leukemia activity of the stem bark of S. impressifolia in experimental models. Materials and methods: The in vitro cytotoxic activity of extracts, fractions and quinonemethide triterpenes (22-hydroxytingenone, tingenone and pristimerin) from the stem bark of S. impressifolia in cultured cancer cells was determined. The in vivo antitumor activity of the ethyl acetate extract (EAE) and of its fraction (FEAE.3) from the stem bark of S. impressifolia was assessed in C.B-17 severe combined immunodeficient (SCID) mice engrafted with human promyelocytic leukemia HL-60 cells. Results: The extract EAE, its fraction FEAE.3, and quinonemethide triterpenes exhibited potent cytotoxicity against cancer cell lines, including in vitro anti-leukemia activity against HL-60 and K-562 cells. Moreover, extract EAE and its fraction FEAE.3 inhibited the in vivo development of HL-60 cells engrafted in C.B-17 SCID mice. Tumor mass inhibition rates were measured as 40.4% and 81.5% for the extract EAE (20 mg/kg) and for its fraction FEAE.3 (20 mg/kg), respectively. Conclusions: Ethyl acetate extract and its fraction from the stem bark of S. impressifolia exhibit in vitro and in vivo anti-leukemia activity that can be attributed to their quinonemethide triterpenes. These data confirm the ethnopharmacological use of this species and may contribute to the development of a novel anticancer herbal medicine.
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The relationship between depression and monoaminergic systems has been hypothesized for many years. In this study, we have investigated the possible antidepressant-like effect of scopoletin, a ...coumarin from
Polygala sabulosa in the tail suspension test and forced swimming test. Moreover, the ability of scopoletin to reverse the depression-like behavior in the forced swimming test induced by immobility stress in mice was evaluated. Scopoletin reduced the immobility time in the tail suspension test (10–100
mg/kg, p.o.), but not in the forced swimming test. Fluoxetine (positive control) decreased the immobility time in the forced swimming and tail suspension tests (20
mg/kg, p.o. and 10
mg/kg. p.o., respectively). Immobility stress caused an increase in the immobility time in the forced swimming test (depression-like behavior), which was reversed by scopoletin (1–100
mg/kg, p.o.) and fluoxetine (10
mg/kg, p.o.). Scopoletin produced no psychostimulant effect in the open-field test. The pretreatment of mice with ketanserin (5
mg/kg, i.p., a preferential 5-HT
2A receptor antagonist), prazosin (1
mg/kg, i.p., an α
1-adrenoceptor antagonist), yohimbine (1
mg/kg, i.p., an α
2-adrenoceptor antagonist), haloperidol (0.2
mg/kg, i.p., a dopaminergic receptor antagonist), SCH23390 (0.05
mg/kg, s.c., a dopamine D
1 receptor antagonist) or sulpiride (50
mg/kg, i.p., a dopamine D
2 receptor antagonist), but not WAY100635 (0.1
mg/kg, s.c., a selective 5-HT
1A receptor antagonist) prevented the antidepressant-like effect of scopoletin (10
mg/kg, p.o.) in the tail suspension test. The results indicate that its antidepressant-like effect is dependent on the serotonergic (5-HT
2A receptors), noradrenergic (α
1- and α
2-adrenoceptors) and dopaminergic (dopamine D
1 and D
2 receptors) systems.
Introduction
Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) ...among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology.
Methods and results
Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC
50
= 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC
50
= 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC
50
= 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for
111
In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to
111
In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor).
Discussion
In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology.
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