(1) Background: Autophagy, the major cytoplasmic process of substrate turnover, declines with age, contributing to proteostasis decline, accumulation of harmful protein aggregates, damaged ...mitochondria and to ROS production. Accordingly, abnormalities in the autophagic flux may contribute to many different pathophysiological conditions associated with ageing, including neurodegeneration. Recent data have shown that extra-virgin olive oil (EVOO) polyphenols stimulate cell defenses against plaque-induced neurodegeneration, mainly, through autophagy induction. (2) Methods: We carried out a set of in vitro experiments on SH-SY5Y human neuroblastoma cells exposed to toxic Aβ1–42 oligomers to investigate the molecular mechanisms involved in autophagy activation by two olive oil polyphenols, oleuropein aglycone (OleA), arising from the hydrolysis of oleuropein (Ole), the main polyphenol found in olive leaves and drupes and its main metabolite, hydroxytyrosol (HT). (3) Results: Our data show that the mixture of the two polyphenols activates synergistically the autophagic flux preventing cell damage by Aβ1–42 oligomers., in terms of ROS production, and impairment of mitochondria. (4) Conclusion: Our results support the idea that EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration. These data confirm and provide the rationale to consider these molecules, alone or in combination, as promising candidates to contrast ageing-associated neurodegeneration.
Heavy metal (HM) pollution, specifically cadmium (Cd) contamination, is a worldwide concern for its consequences for plant health and ecosystem stability. This review sheds light on the intricate ...mechanisms underlying Cd toxicity in plants and the various strategies employed by these organisms to mitigate its adverse effects. From molecular responses to physiological adaptations, plants have evolved sophisticated defense mechanisms to counteract Cd stress. We highlighted the role of phytochelatins (PCn) in plant detoxification, which chelate and sequester Cd ions to prevent their accumulation and minimize toxicity. Additionally, we explored the involvement of glutathione (GSH) in mitigating oxidative damage caused by Cd exposure and discussed the regulatory mechanisms governing GSH biosynthesis. We highlighted the role of transporter proteins, such as ATP-binding cassette transporters (ABCs) and heavy metal ATPases (HMAs), in mediating the uptake, sequestration, and detoxification of Cd in plants. Overall, this work offered valuable insights into the physiological, molecular, and biochemical mechanisms underlying plant responses to Cd stress, providing a basis for strategies to alleviate the unfavorable effects of HM pollution on plant health and ecosystem resilience.
(1) Background: In recent years, numerous studies have highlighted the beneficial effects of extra virgin olive oil (EVOO) as an active ingredient against chronic diseases. The properties of EVOO are ...due to its peculiar composition, mainly to its rich content of polyphenols. In fact, polyphenols may contribute to counteract oxidative stress, which often accompanies chronic diseases. In this work, the antioxidant effects of high-value polyphenol oleocanthal (OC) and its main metabolites, tyrosol (Tyr) and oleocanthalic acid (OA), respectively, have been investigated along with their impact on cell viability. (2) Methods: OC, Tyr, and OA have been evaluated regarding antiradical properties in term of scavenging capacity towards biologically relevant reactive species, including O
, HOCl, and ROO
, as well as their antioxidant/antiradical capacity (FRAP, DPPH
, ABTS
). Moreover, the ability to permeate the intestinal membrane was assessed by an intestinal co-culture model composed by Caco-2 and HT29-MTX cell lines. (3) Results: The capacity of OC and Tyr as radical oxygen species (ROS) scavengers, particularly regarding HOCl and O
, was clearly demonstrated. Furthermore, the ability to permeate the intestinal co-culture model was plainly proved by the good permeations (>50%) achieved by all compounds. (4) Conclusions: OC, OA, and Tyr revealed promising properties against oxidative diseases.
We took advantage of the fluorescent features of a serotonin-derived fluorophore to develop a simple and low-cost assay for copper in urine. The quenching-based fluorescence assay linearly responds ...within the concentration range of clinical interest in buffer and in artificial urine, showing very good reproducibility (CV
% = 4% and 3%) and low detection limits (16 ± 1 μg L
and 23 ± 1 μg L
). The Cu
content was also estimated in human urine samples, showing excellent analytical performances (CV
% = 1%), with a limit of detection of 59 ± 3 μg L
and a limit of quantification of 97 ± 11 μg L
, which are below the reference value for a pathological Cu
concentration. The assay was successfully validated through mass spectrometry measurements. To the best of our knowledge, this is the first example of copper ion detection exploiting the fluorescence quenching of a biopolymer, offering a potential diagnostic tool for copper-dependent diseases.
Robotics and AI-based applications (RAI) are often said to be so technologically advanced that they should be held responsible for their actions, instead of the human who designs or operates them. ...The paper aims to prove that this thesis ("the exceptionalist claim")-as it stands-is both theoretically incorrect and practically inadequate. Indeed, the paper argues that such claim is based on a series of misunderstanding over the very notion and functions of "legal responsibility", which it then seeks to clarify by developing and interdisciplinary conceptual taxonomy. In doing so, it aims to set the premises for a more constructive debate over the feasibility of granting legal standing to robotic application. After a short Introduction setting the stage of the debate, the paper addresses the ontological claim, distinguishing the philosophical from the legal debate on the notion of i) subjectivity and ii) agency, with their respective implications. The analysis allows us to conclude that the attribution of legal subjectivity and agency are purely fictional and technical solutions to facilitate legal interactions, and is not dependent upon the intrinsic nature of the RAI. A similar structure is maintained with respect to the notion of responsibility, addressed first in a philosophical and then legal perspective, to demonstrate how the latter is often utilized to both pursue ex ante deterrence and ex post compensation. The focus on the second objective allows us to bridge the analysis towards functional (law and economics based) considerations, to discuss how even the attribution of legal personhood may be conceived as an attempt to simplify certain legal interactions and relations. Within such a framework, the discussion whether to attribute legal subjectivity to the machine needs to be kept entirely within the legal domain, and grounded on technical (legal) considerations, to be argued on a functional, bottom-up analysis of specific classes of RAI. That does not entail the attribution of animacy or the ascription of a moral status to the entity itself.
Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). All these pathologies ...are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM's effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediated inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1, and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells turned out to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDDs.
Robots are slowly, but certainly, entering people's professional and private lives. They require the attention of regulators due to the challenges they present to existing legal frameworks and the ...new legal and ethical questions they raise. This paper discusses four major regulatory dilemmas in the field of robotics: how to keep up with technological advances; how to strike a balance between stimulating innovation and the protection of fundamental rights and values; whether to affirm prevalent social norms or nudge social norms in a different direction; and, how to balance effectiveness versus legitimacy in techno-regulation. The four dilemmas are each treated in the context of a particular modality of regulation: law, market, social norms, and technology as a regulatory tool; and for each, we focus on particular topics - such as liability, privacy, and autonomy - that often feature as the major issues requiring regulatory attention. The paper then highlights the role and potential of the European framework of rights and values, responsible research and innovation, smart regulation and soft law as means of dealing with the dilemmas.
Background: Agrifood waste products are often considered rich sources of bioactive compounds that can be conveniently recovered. Due to these peculiar characteristics, the study of these waste ...products is attracting great interest in nutraceutical research. Olive mill wastewaters (OMWWs) are generated by extra virgin olive oil (EVOO) production, and they pose environmental challenges due to their disposal. This study aimed to characterize the polyphenolic profile and to evaluate the nutraceutical properties of OMWW extracts from two Tuscan olive cultivars, Leccino (CL) and Frantoio (CF), collected during different time points in EVOO production. Method: After a liquid–liquid extraction, the HPLC and LC–MS/MS analysis of OMWW extracts confirmed the presence of 18 polyphenolic compounds. Results: The polyphenol composition varied between the cultivars and during maturation stages. Notably, oleacein was detected at remarkably high levels in CL1 and CF1 extracts (314.628 ± 19.535 and 227.273 ± 3.974 μg/mg, respectively). All samples demonstrated scavenging effects on free radicals (DPPH and ABTS assays) and an anti-inflammatory potential by inhibiting cyclooxygenase (COX) enzymes. Conclusions: This study highlights the nutraceutical potential of OMWW extracts, emphasizing their antioxidant, antiradical, and anti-inflammatory activities. The results demonstrate the influence of olive cultivar, maturation stage, and extraction process on the polyphenolic composition and the bioactivity of OMWW extracts. These findings support a more profitable reuse of OMWW as an innovative, renewable, and low-cost source of dietary polyphenols with potential applications as functional ingredients in the development of dietary supplements, as well as in the pharmaceutical and cosmetics industries.
Short-chain fatty acids (SCFAs) are the main by-products of microbial fermentations occurring in the human intestine and are directly involved in the host's physiological balance. As impaired gut ...concentrations of acetic, propionic, and butyric acids are often associated with systemic disorders, the administration of SCFA-producing microorganisms has been suggested as attractive approach to solve symptoms related to SCFA deficiency.
In this research, nine probiotic strains (
NR, OC, SIN, and T,
ATCC 7050,
DSM 16604,
DSM 17938,
ATCC 53103, and
CNCM I-745) commonly included in commercial formulations were tested for their ability to secrete SCFAs by using an improved protocol in high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS).
The developed method was highly sensitive and specific, showing excellent limits of detection and quantification of secreted SCFAs. All tested microorganisms were shown to secrete acetic acid, with only
and
additionally able to produce propionic and butyric acids. Quantitative differences in the secretion of SCFAs were also evidenced.
The experimental approach described in this study may contribute to the characterization of probiotics as SCFA-producing organisms, a crucial stage toward their application to improve SCFA deficiency.
Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not ...bring 3-iodothyronamine (T1AM) brain levels back to normal. T1AM is a thyroid hormone derivative with cognitive effects. Using a pharmacological hypothyroid mouse model, we investigated whether augmenting levothyroxine (L-T4) with T1AM improves behavioural correlates of depression, anxiety, and memory and has an effect on hippocampal neurogenesis. Hypothyroid mice showed impaired performance in the novel object recognition test as compared to euthyroid mice (discrimination index (DI): 0.02 ± 0.09 vs. 0.29 ± 0.06; t = 2.515, p = 0.02). L-T4 and L-T4+T1AM rescued memory (DI: 0.27 ± 0.08 and 0.34 ± 0.08, respectively), while T1AM had no effect (DI: −0.01 ± 0.10). Hypothyroidism reduced the number of neuroprogenitors in hippocampal neurogenic niches by 20%. L-T4 rescued the number of neuroprogenitors (mean diff = 106.9 ± 21.40, t = 4.99, pcorr = 0.003), while L-T4+T1AM produced a 30.61% rebound relative to euthyroid state (mean diff = 141.6 ± 31.91, t = 4.44, pcorr = 0.004). We performed qPCR analysis of 88 genes involved in neurotrophic signalling pathways and found an effect of treatment on the expression of Ngf, Kdr, Kit, L1cam, Ntf3, Mapk3, and Neurog2. Our data confirm that L-T4 is necessary and sufficient for recovering memory and hippocampal neurogenesis deficits associated with hypothyroidism, while we found no evidence to support the role of non-canonical TH signalling.
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