Anti-Inflammatory activity of a polyphenolic extract from Arabidopsis thaliana in in vitro and in vivo models of Alzheimer's Disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aβ. BV2 murine microglia cells treated with both Aβ25⁻35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1β, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aβ only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aβ-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aβ1⁻42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed

Spotlight on dupilumab in the treatment of atopic dermatitis: Design, development, and potential place in therapy

Atopic dermatitis (AD) is among the most common inflammatory skin diseases in children and adults in industrialized countries. Up to one-third of adults (probably a smaller proportion in childhood) suffer from moderate-to-severe AD, whose recommended treatment is usually based on systemic therapies. The currently available therapeutics are limited, and AD management becomes challenging in most cases. Over the last few years, new advances in the understanding of AD pathogenic mechanisms and inflammatory pathways have led to the identification of specific therapeutic targets and new molecules have been tested. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that is able to block the signaling of both IL-4 and IL-13 and achieve rapid and significant improvements in adults with moderate-to-severe AD. Dupilumab is ready to inaugurate a long and promising biological target treatment option for Th2 cell-mediated atopic immune response that characterizes AD

Erythema multiforme-like irritant contact dermatitis after application of an antiscabies treatment.

We describe the case of an irritant contact dermatitis due to an antiscabies treatment in a man who presented to our clinic with an important cutaneous reaction with many hemorrhagic, "target" erythema multiforme-like lesions, as the result of an acute toxic insult of the skin by permethrin 5%. This is a possible, but very uncommon symptom of non-eczematous contact dermatitis and an unusual drug causing the acute hypersensitivity reaction typical of erythema multiforme

Oriente/Occidente: un’unità culturale non (più) percepita

The notion of “Europe” is geographically and culturally controversial. While of Greek origins, this unsteady concept also has other progenitors, unwilling to recognize any “external” contributions to their own culture. One of these progenitors is Denis de Rougemont’s L’Amour et l’Occident, whose “Protestant” approach to the problems posed by the sudden emergence of Troubadour poetry is just as fanciful and untenable as the “Catholic” one. The Troubadour passion, indeed, is a sort of gnostic fever to be seen in a much bigger context than the “Cis-Dardanellian” Europe. If we compare the works of the Troubadours and Dante, for instance, we find unsurprising similarities – if little known – but when a likeness of this sort appears to connect Dante to the Persian Hafez, poet of the fourteenth century, it is quite staggering: the resemblance lies not only in general concepts, but in rhetorical images and the wording too. This paper provides evidence of these and other literary contacts between “Europe” and “Asia”. The sense of alienation we purport to feel when encountering Asian cultures appears, in fact, to be a rather recent affair.  “Europa” è un concetto geograficamente e culturalmente controverso, di origine greca, anche se altri genitori vanno riconosciuti alla balzana idea che essa sia sorta e si sia sviluppata senza apporti esterni. Uno di questi padri è sicuramente L’amour et l’Occidentdi Denis de Rougemont, il cui approccio “protestante” ai problemi posti dal subito apparire della poesia trobadorica è altrettanto fantasioso e insostenibile di quello “cattolico”. Invero, la passione trobadorica è una sorta di febbre gnostica reperibile in un’area più vasta dell’Europa “Cis-Dardanellica”. Ponendo a confronto i lavori dei Trovatori e di Dante, per esempio, troviamo somiglianze forse non sorprendenti – benché malnote – ma quando scorgiamo analoghe similarità tra Dante e il poeta persiano Hâfez, allora trasaliamo, anche perché l’affinità non si limita ai concetti generali, ma si estende alle immagini retoriche e all’espressione verbale. Qualche prova viene esposta circa questi (e altri) contatti letterari tra “Europa” e “Asia”. Il senso di estraneità che pretendiamo spesso di provare di fronte alle culture d’Asia è fatto abbastanza recente

Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality

Potential Infectious Etiology of Behçet's Disease

Behçet's disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçet's disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçet's disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçet's disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role

COVID-19 infection in chronic spontaneous urticaria treated with omalizumab: two case reports

Letter to the edito

Green route for the isolation and purification of hyrdoxytyrosol, tyrosol, oleacein and oleocanthal from extra virgin olive oil

Extra virgin olive oil (EVOO) phenols represent a significant part of the intake of antioxidants and bioactive compounds in the Mediterranean diet. In particular, hydroxytyrosol (HTyr), tyrosol (Tyr), and the secoiridoids oleacein and oleocanthal play central roles as anti-inflammatory, neuro-protective and anti-cancer agents. These compounds cannot be easily obtained via chemical synthesis, and their isolation and purification from EVOO is cumbersome. Indeed, both processes involve the use of large volumes of organic solvents, hazardous reagents and several chromatographic steps. In this work we propose a novel optimized procedure for the green extraction, isolation and purification of HTyr, Tyr, oleacein and oleocanthal directly from EVOO, by using a Natural Deep Eutectic Solvent (NaDES) as an extracting phase, coupled with preparative high-performance liquid chromatography. This purification method allows the total recovery of the four components as single pure compounds directly from EVOO, in a rapid, economic and ecologically sustainable way, which utilizes biocompatible reagents and strongly limits the use or generation of hazardous substances

Preliminary study of the mechanical and hygrothermal performance of concrete reinforced with fibrillated cellulose

Cement, being the most widely used building material, is the responsible for a large share of greenhouse gas emissions. To reduce the environmental impact of its production, natural fibres can be used as eco-friendly additives. Moreover, their potential use in traditional lime-based mortars makes them an ideal choice for green buildings as well as for the retrofit of historical buildings. An innovative cementitious composite reinforced with fibrillated cellulose (hereafter called «green concrete») was tested to assess its mechanical and physical properties. Samples were casted using Portland cement and natural hydraulic lime and varying the ratios among the constituents. Viscosity and setting time of the fresh pastes were determined with a viscosimeter and a Vicat apparatus, while their hydration was studied by thermal analysis. The influence of the fibres on the flexural strength of the final composite was determined through mechanical tests. The expected hygrothermal performance of the «green concrete» was explored through dynamic hygrothermal simulation to investigate its potential use as a retrofit material. A sensitivity analysis (SA), based on the hygrothermal properties of natural-based building materials similar to the «green concrete», was conducted to identify the parameters influencing more the simulation of annual internal temperature and moisture variations. The preliminary assessment of the mechanical properties of the «green concrete» showed that at higher percentages the cellulose fibres can negatively affect the workability/setting time of the fresh pastes and the flexural strength. The most promising samples were identified and will undergo further investigation. The SA results outlined that the «green concrete» might not be effective for thermal insulation, although it might be used as a moisture-buffering layer by adjusting the values of the free water saturation moisture content, the equilibrium moisture content at RH=80% and the dry vapour diffusion resistance factor of the final composite