@article{ferrara_yan_pecorelli_guiotto_colella_pasqui_ivarrson_lynch_anderias_choundhary_et al._2024, title={Combined exposure to UV and PM affect skin oxinflammatory responses and it is prevented by antioxidant mix topical application: Evidences from clinical study}, volume={4}, ISSN={["1473-2165"]}, DOI={10.1111/jocd.16321}, abstractNote={Abstract Background Exposure to environmental stressors like particulate matter (PM) and ultraviolet radiation (UV) induces cutaneous oxidative stress and inflammation and leads to skin barrier dysfunction and premature aging. Metals like iron or copper are abundant in PM and are known to contribute to reactive oxygen species (ROS) production. Aims Although it has been suggested that topical antioxidant may be able to help in preventing and/or reducing outdoor skin damage, limited clinical evidence under real‐life exposure conditions have been reported. The aim of the present study was to evaluate the ability of a topical serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (CF Mix) to prevent oxinflammatory skin damage and premature aging induced by PM + UV in a human clinical trial. Methods A 4‐day single‐blinded, clinical study was conducted on the back of 15 females (18–40 years old). During the 4 consecutive days, the back test zones were treated daily with or without the CF Mix, followed by with/without 2 h of PM and 5 min of UV daily exposure. Results Application of the CF Mix prevented PM + UV‐induced skin barrier perturbation (Involucrin and Loricrin), lipid peroxidation (4HNE), inflammatory markers (COX2, NLRP1, and AhR), and MMP9 activation. In addition, CF Mix was able to prevent Type I Collagen loss. Conclusion This is the first human study confirming the multipollutants cutaneous damage and suggesting the utility of a daily antioxidant topical application to prevent pollution induced skin damage.}, journal={JOURNAL OF COSMETIC DERMATOLOGY}, author={Ferrara, Francesca and Yan, Xi and Pecorelli, Alessandra and Guiotto, Anna and Colella, Sante and Pasqui, Arianna and Ivarrson, John and Lynch, Stephen and Anderias, Sara and Choundhary, Hina and et al.}, year={2024}, month={Apr} }
 @article{beggiato_ferrara_romani_cassano_trentini_valacchi_cervellati_ferraro_2024, title={Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease}, volume={388}, ISSN={["1872-7786"]}, DOI={10.1016/j.cbi.2023.110839}, abstractNote={Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD. To address this hypothesis, the levels of 4-hydroxynonenal (4-HNE; i.e. a marker of oxidative stress damage) along with the protein expression and enzymatic activity of PON1 and PON2 have been investigated in the brain and serum of young [Postnatal day (PD)8-10, 20-25 and 60-65] asymptomatic 3xTg-AD female mice, one of the most used transgenic models of AD. At PD 8-10, there were no differences in hippocampus and prefrontal cortex (PFC) 4-HNE expression levels between 3xTg-AD mice compared to controls (Non-Tg mice). On the other hand, significant increased levels of 4-HNE were detected in PD 20-30 3xTg-AD mice hippocampus, while a significant reduction was observed in 3xTg-AD group at PD 60-65. In the PFC, 4-HNE levels were significantly reduced in 3xTg-AD mice brain at PD 20-30, while no differences in 4-HNE levels were detected at PD 60-65. No significant differences in arylesterase and lactonase activities were observed in the plasma of 3xTg-AD and Non-Tg mice at the different considered ages. Compared to Non-Tg mice, a reduction of brain arylesterase activity was found in 3xTg-AD female at PD 20-30 and PD 60-65, but it was significant only in the younger group. Finally, a similar trend was observed also for PON1 and PON2 protein levels, with both significantly, and solely, decreased in 3xTg-AD mice brain at PD 20-30. Overall, these findings suggest that the altered oxidative stress homeostasis in the 3xTg-AD female mice may be related to an early reduction in activity and expression of PONs enzymes most likely via a reduced brain arylesterases activity.}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Beggiato, Sarah and Ferrara, Francesca and Romani, Arianna and Cassano, Tommaso and Trentini, Alessandro and Valacchi, Giuseppe and Cervellati, Carlo and Ferraro, Luca}, year={2024}, month={Jan} }
 @article{ferrara_pecorelli_pambianchi_white_choudhary_casoni_valacchi_2024, title={Vitamin C compounds mixture prevents skin barrier alterations and inflammatory responses upon real life multi pollutant exposure}, volume={33}, ISSN={["1600-0625"]}, DOI={10.1111/exd.15000}, abstractNote={Abstract}, number={1}, journal={EXPERIMENTAL DERMATOLOGY}, author={Ferrara, Francesca and Pecorelli, Alessandra and Pambianchi, Erika and White, Stacy and Choudhary, Hina and Casoni, Alice and Valacchi, Giuseppe}, year={2024}, month={Jan} }
 @article{sguizzato_ferrara_baraldo_bondi_guarino_drechsler_valacchi_cortesi_2023, title={Bilosomes and Biloparticles for the Delivery of Lipophilic Drugs: A Preliminary Study}, volume={12}, ISSN={["2076-3921"]}, DOI={10.3390/antiox12122025}, abstractNote={In this study, bile acid-based vesicles and nanoparticles (i.e., bilosomes and biloparticles) are studied to improve the water solubility of lipophilic drugs. Ursodeoxycholic acid, sodium cholate, sodium taurocholate and budesonide were used as bile acids and model drugs, respectively. Bilosomes and biloparticles were prepared following standard protocols with minor changes, after a preformulation study. The obtained systems showed good encapsulation efficiency and dimensional stability. Particularly, for biloparticles, the increase in encapsulation efficiency followed the order ursodeoxycholic acid < sodium cholate < sodium taurocholate. The in vitro release of budesonide from both bilosytems was performed by means of dialysis using either a nylon membrane or a portion of Wistar rat small intestine and two receiving solutions (i.e., simulated gastric and intestinal fluids). Both in gastric and intestinal fluid, budesonide was released from bilosystems more slowly than the reference solution, while biloparticles showed a significant improvement in the passage of budesonide into aqueous solution. Immunofluorescence experiments indicated that ursodeoxycholic acid bilosomes containing budesonide are effective in reducing the inflammatory response induced by glucose oxidase stimuli and counteract ox-inflammatory damage within intestinal cells.}, number={12}, journal={ANTIOXIDANTS}, author={Sguizzato, Maddalena and Ferrara, Francesca and Baraldo, Nada and Bondi, Agnese and Guarino, Annunziata and Drechsler, Markus and Valacchi, Giuseppe and Cortesi, Rita}, year={2023}, month={Dec} }
 @article{casoni_benedusi_cervellati_pecorelli_ferrara_vallese_valacchi_2023, title={CADMIUM EXPOSURE AFFECTS THE PROGRESSION OF HUMAN METASTATIC MELANOMA BY INDUCING A DEREGULATION OF ANTIOXIDANT CELL RESPONSE}, volume={201}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2023.03.174}, DOI={10.1016/j.freeradbiomed.2023.03.174}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Casoni, Alice and Benedusi, Mascia and Cervellati, Franco and Pecorelli, Alessandra and Ferrara, Francesca and Vallese, Andrea and Valacchi, Giuseppe}, year={2023}, month={May}, pages={42–43} }
 @article{cordone_pecorelli_ferrara_guiotto_hayek_cervellati_amicarelli_valacchi_2023, title={CONSTITUTIVE ACTIVATION OF NLRP3 INFLAMMASOME MACHINERY IN EX-VIVO MODELS OF RETT SYNDROME: FROM PATHOGENETIC ROLE TO NEW POTENTIAL THERAPEUTIC TARGET}, volume={201}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.03.068}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cordone, Valeria and Pecorelli, Alessandra and Ferrara, Francesca and Guiotto, Anna and Hayek, Joussef and Cervellati, Carlo and Amicarelli, Fernanda and Valacchi, Giuseppe}, year={2023}, month={May}, pages={12–12} }
 @article{sguizzato_ferrara_valacchi_cortesi_esposito_2023, title={Caffeic acid-loaded lipid nanoparticles as a tool to protect skin against oxidative stress: formulation and evaluation on human skin explants}, volume={198}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.12.068}, abstractNote={Nanomaterials possess outstanding attributes due to nanoscale effects and increased surface area, which influence interactions with biomolecules, cells, and the biological system. They have been envisaged to play an important role in biosensors, bioimaging, and gene and drug delivery applications. Properties, including size, morphology, composition, zeta potential, and structure, control their specific interactions on the cellular level. Calcium phosphates (CPs), the primary component of natural hard tissue, are bequeathed with commendable properties, including biocompatibility, bioactivity, tunable biodegradability, that depends on the Ca/P molar ratio and nontoxicity. In addition, the dissolution rate of CPs can be contained by adjusting its crystallinity, thereby potentially promoting the development of efficient and controlled delivery systems. This chapter focuses on the biological properties of CP nanoparticles, including their limited toxicity. It also describes the various mechanisms in drug loading, targetability, and the uses of CPs as drug and gene delivery agents. The chapter also includes a brief overview of CPs as theranostic agents.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Sguizzato, Maddalena and Ferrara, Francesca and Valacchi, Giuseppe and Cortesi, Rita and Esposito, Elisabetta}, year={2023}, month={Mar}, pages={S19–S19} }
 @article{ivarsson_ferrara_vallese_guiotto_colella_pecorelli_valacchi_2023, title={Comparison of Pollutant Effects on Cutaneous Inflammasomes Activation}, volume={24}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms242316674}, DOI={10.3390/ijms242316674}, abstractNote={The skin is the outermost layer of the body and, therefore, is exposed to a variety of stressors, such as environmental pollutants, known to cause oxinflammatory reactions involved in the exacerbation of several skin conditions. Today, inflammasomes are recognized as important modulators of the cutaneous inflammatory status in response to air pollutants and ultraviolet (UV) light exposure. In this study, human skin explants were exposed to the best-recognized air pollutants, such as microplastics (MP), cigarette smoke (CS), diesel engine exhaust (DEE), ozone (O3), and UV, for 1 or 4 days, to explore how each pollutant can differently modulate markers of cutaneous oxinflammation. Exposure to environmental pollutants caused an altered oxidative stress response, accompanied by increased DNA damage and signs of premature skin aging. The effect of specific pollutants being able to exert different inflammasomes pathways (NLRP1, NLRP3, NLRP6, and NLRC4) was also investigated in terms of scaffold formation and cell pyroptosis. Among all environmental pollutants, O3, MP, and UV represented the main pollutants affecting cutaneous redox homeostasis; of note, the NLRP1 and NLRP6 inflammasomes were the main ones modulated by these outdoor stressors, suggesting their role as possible molecular targets in preventing skin disorders and the inflammaging events associated with environmental pollutant exposure.}, number={23}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Ivarsson, John and Ferrara, Francesca and Vallese, Andrea and Guiotto, Anna and Colella, Sante and Pecorelli, Alessandra and Valacchi, Giuseppe}, year={2023}, month={Dec} }
 @article{cordone_vallese_pecorelli_guiotto_ferrara_benedusi_cervellati_hayek_valacchi_2023, title={Deregulated NLRP3 inflammasome response due to a constitutive activation of NF-kappa B p65 pro-inflammatory pathway in lymphomonocytes of Rett syndrome patients}, volume={198}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2022.12.075}, DOI={10.1016/j.freeradbiomed.2022.12.075}, abstractNote={Elevated levels of the type III (III) isoforms of neuregulin 1 (NRG1) have been observed in the brains of schizophrenia patients that carry NRG1 HapICE risk alleles, which is thought to contribute to the aetiology of the disease. We generated transgenic mice with forebrain driven Nrg1 III overexpression (Nrg1 III tg) and previously found that male heterozygous Nrg1 type III tg mice exhibit several schizophrenia-relevant behaviours including social and cognitive deficits as well as impaired sensorimotor gating. A number of mouse models for other Nrg1 isoform types exhibit sex-specific phenotypes yet sex-specific effects of Nrg1 III overexpression had not been evaluated. Thus, in this study we tested female Nrg1 III transgenic mice using a comprehensive behavioural phenotyping battery relevant to positive, negative and cognitive symptoms of schizophrenia. Firstly, forebrain Nrg1 III mRNA overexpression was confirmed in female transgenic mice using by qPCR. In the open field test, female Nrg1 III mice exhibited a blunted response to an acute challenge with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801. Female Nrg1 III tg mice also exhibited moderately impaired short-term memory. Other behavioural domains including sensory abilities, motor functions, baseline locomotion, anxiety, sociability, social recognition memory, fear conditioning and prepulse inhibition were unperturbed in Nrg1 III tg females. Together these results illustrate that overexpressing forebrain Nrg1 III in female mice modifies the locomotive response to NMDA receptor antagonism without causing severe alterations to a number of other schizophrenia-related behavioural domains. The data suggest that behavioural effects of Nrg1 III overexpression may be sex-dependent.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cordone, Valeria and Vallese, Andrea and Pecorelli, Alessandra and Guiotto, Anna and Ferrara, Francesca and Benedusi, Mascia and Cervellati, Franco and Hayek, Joussef and Valacchi, Giuseppe}, year={2023}, month={Mar}, pages={S21–S22} }
 @article{sarkar_pecorelli_woodby_pambianchi_ferrara_duary_valacchi_2023, title={Evaluation of Anti-Oxinflammatory and ACE-Inhibitory Properties of Protein Hydrolysates Obtained from Edible Non-Mulberry Silkworm Pupae (Antheraea assama and Philosomia ricinii)}, volume={15}, ISSN={["2072-6643"]}, DOI={10.3390/nu15041035}, abstractNote={Food-derived bioactive peptides (BAPs) obtained from edible insect-protein hold multiple activities promising the potential to target complex pathological mechanisms responsible for chronic health conditions such as hypertension development. In this study, enzymatic protein hydrolysates from non-mulberry edible silkworm Antheraea assama (Muga) and Philosomia ricini (Eri) pupae, specifically Alcalase (A. assama) and Papain (P. ricini) hydrolysates obtained after 60 and 240 min, exhibited the highest ACE-inhibitory and antioxidant properties. The hydrolysates’ fractions (<3, 3–10 and >10 kDa), specifically Alc_M60min_F3 (≤3 kDa) and Pap_E240min_F3 (≤3 kDa), showed the highest antioxidant and ACE-inhibitory activities, respectively. Further RP-HPLC purified sub-fractions F4 and F6 showed the highest ACE inhibition as well as potent anti-oxinflammatory activities in lipopolysaccharide (LPS)-treated endothelial cells. Indeed, F4 and F6 ACE-inhibitory peptide fractions were effective in preventing p65 nuclear translocation after 3 h of LPS stimulation along with the inhibition of p38 MAPK phosphorylation in HUVEC cells. In addition, pretreatment with F4 and F6 ACE-inhibitory peptide fractions significantly prevented the LPS-induced upregulation of COX-2 expression and IL-1β secretion, while the expression of NRF2 (nuclear factor erythroid 2-related factor 2)-regulated enzymes such as HO-1 and NQO1 was induced by both peptide fractions. The derived peptides from edible pupae protein hydrolysates have potentialities to be explored as nutritional approaches against hypertension and related cardiovascular diseases.}, number={4}, journal={NUTRIENTS}, author={Sarkar, Preeti and Pecorelli, Alessandra and Woodby, Brittany and Pambianchi, Erika and Ferrara, Francesca and Duary, Raj Kumar and Valacchi, Giuseppe}, year={2023}, month={Feb} }
 @article{ferrara_pecorelli_guiotto_vallese_cordone_benedusi_cervellati_valacchi_2023, title={INFLAMMASOMES REGULATION BY ENVIRONMENTAL POLLUTANTS IN HUMAN SKIN}, volume={201}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2023.03.158}, DOI={10.1016/j.freeradbiomed.2023.03.158}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Ferrara, Francesca and Pecorelli, Alessandra and Guiotto, Anna and Vallese, Andrea and Cordone, Valeria and Benedusi, Mascia and Cervellati, Franco and Valacchi, Giuseppe}, year={2023}, month={May}, pages={38–39} }
 @article{sguizzato_ferrara_drechsler_baldisserotto_montesi_manfredini_valacchi_cortesi_2023, title={Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study}, volume={15}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics15071940}, abstractNote={In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.}, number={7}, journal={PHARMACEUTICS}, author={Sguizzato, Maddalena and Ferrara, Francesca and Drechsler, Markus and Baldisserotto, Anna and Montesi, Leda and Manfredini, Stefano and Valacchi, Giuseppe and Cortesi, Rita}, year={2023}, month={Jul} }
 @article{vallese_pecorelli_cordone_ferrara_benedusi_cervellati_hayek_valacchi_2023, title={MITOCHONDRIAL DYSFUNCTION AND NLRP3 INFLAMMASOME ACTIVATION IN AUTISM SPECTRUM DISORDER}, volume={201}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.03.094}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Vallese, Andrea and Pecorelli, Alessandra and Cordone, Valeria and Ferrara, Francesca and Benedusi, Mascia and Cervellati, Franco and Hayek, Joussef and Valacchi, Giuseppe}, year={2023}, month={May}, pages={20–20} }
 @article{benedusi_canella_vallese_casoni_guerra_rispoli_ferrara_cervellati_valacchi_2023, title={THE POSSIBLE MODULATION OF NRF2 AND NF-KB CROSSTALK BY SULFORAPHANE IN THE PROGRESSION OF HUMAN MELANOMA}, volume={201}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2023.03.230}, DOI={10.1016/j.freeradbiomed.2023.03.230}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Benedusi, Mascia and Canella, Rita and Vallese, Andrea and Casoni, Alice and Guerra, Martina and Rispoli, Giorgio and Ferrara, Francesca and Cervellati, Franco and Valacchi, Giuseppe}, year={2023}, month={May}, pages={57–57} }
 @article{cordone_pecorelli_ferrara_guiotto_hayek_cervellati_amicarelli_valacchi_2023, title={THE PROTECTIVE ROLE OF ENDOTHELIAL alpha 1AMPK IN AIRCRAFT NOISE-INDUCED VASCULAR DYSFUNCTION AND OXIDATIVE STRESS IS MEDIATED BY FASTING, EXERCISE AND PHARMACOLOGICAL TREATMENT}, volume={201}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.03.067}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cordone, Valeria and Pecorelli, Alessandra and Ferrara, Francesca and Guiotto, Anna and Hayek, Joussef and Cervellati, Carlo and Amicarelli, Fernanda and Valacchi, Giuseppe}, year={2023}, month={May}, pages={11–12} }
 @article{vallese_pecorelli_cordone_ferrara_benedusi_cervellati_hayek_valacchi_2023, title={The pathogenic axis between mitochondrial dysfunction and NLRP3 inflammasome activation in Autism Spectrum Disorder}, volume={208}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2023.10.112}, DOI={10.1016/j.freeradbiomed.2023.10.112}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Vallese, Andrea and Pecorelli, Alessandra and Cordone, Valeria and Ferrara, Francesca and Benedusi, Mascia and Cervellati, Franco and Hayek, Joussef and Valacchi, Giuseppe}, year={2023}, month={Nov}, pages={S49–S49} }
 @article{benedusi_kerob_guiotto_cervellati_ferrara_pambianchi_2023, title={Topical Application of M89PF Containing Vichy Mineralising Water and Probiotic Fractions Prevents Cutaneous Damage Induced by Exposure to UV and O3}, volume={16}, ISSN={["1178-7015"]}, DOI={10.2147/CCID.S414011}, abstractNote={Purpose Exposure of the skin to ultraviolet radiation (UV) or ozone (O3) results in stressed skin, leading to the alteration of the skin physical barrier and defence functions. In this work, the preventive benefit of a dermocosmetic, M89PF, containing Vichy mineralising water, probiotic fractions, antioxidant vitamins and hyaluronic acid, in the alteration of skin physical barrier and skin defence functions after exposure to O3 and UV, alone or combined, was assessed. Methods Untreated and treated (M89PF) skin explants were exposed to O3, to UV rays or to O3+UV. Immunofluorescence was performed for skin barrier, oxidative stress, and inflammatory markers after one and four days of exposure to the pollutants. Results M89PF significantly (p≤0.05) prevented the decrease of the expression level of different skin barrier markers, and significantly (p≤0.05) prevented the induction of OxInflammatory markers and inflammasome components by UV, O3, or both combined. Conclusion M89PF prevents skin barrier damage, as well as oxidative stress and inflammatory markers induced by exposome factors, such as UV, O3, or both combined.}, journal={CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY}, author={Benedusi, Mascia and Kerob, Delphine and Guiotto, Anna and Cervellati, Franco and Ferrara, Francesca and Pambianchi, Erika}, year={2023}, pages={1769–1776} }
 @article{ferrara_benedusi_sguizzato_cortesi_baldisserotto_buzzi_valacchi_esposito_2022, title={Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells}, volume={14}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics14051038}, abstractNote={The present study is aimed to design ethosomes and transethosomes for topical administration of quercetin. To overcome quercetin low bioavailability, scarce solubility and poor permeability that hamper its pharmaceutical use, the drug was loaded in ethosomes and transethosomes based on different concentrations of phosphatidylcholine. Vesicle morphology was studied by cryogenic transmission electron microscopy, while size distribution and quercetin entrapment capacity were evaluated up to 3 months, respectively, by photon correlation spectroscopy and high-performance liquid chromatography. The antioxidant property was studied by photochemiluminescence test. Quercetin release and permeation was investigated in vitro, using Franz cells associated to different membranes. In vitro assays were conducted on human keratinocytes and melanoma cells to study the behavior of quercetin-loaded nano-vesicular forms with respect to cell migration and proliferation. The results evidenced that both phosphatidylcholine concentration and quercetin affected the vesicle size. Quercetin entrapment capacity, antioxidant activity and size stability were controlled using transethosomes produced by the highest amount of phosphatidylcholine. In vitro permeation studies revealed an enhancement of quercetin permeation in the case of transethosomes with respect to ethosomes. Notably, scratch wound and migration assays suggested the potential of quercetin loaded-transethosomes as adjuvant strategy for skin conditions.}, number={5}, journal={PHARMACEUTICS}, author={Ferrara, Francesca and Benedusi, Mascia and Sguizzato, Maddalena and Cortesi, Rita and Baldisserotto, Anna and Buzzi, Raissa and Valacchi, Giuseppe and Esposito, Elisabetta}, year={2022}, month={May} }
 @article{pozzetti_ferrara_marotta_gemma_butini_benedusi_fusi_ahmed_pomponi_ferrari_et al._2022, title={Extra Virgin Olive Oil Extracts of Indigenous Southern Tuscany Cultivar Act as Anti-Inflammatory and Vasorelaxant Nutraceuticals}, volume={11}, ISSN={["2076-3921"]}, DOI={10.3390/antiox11030437}, abstractNote={Extra virgin olive oil (EVOO) is the typical source of fats in the Mediterranean diet. While fatty acids are essential for the EVOO nutraceutical properties, multiple biological activities are also due to the presence of polyphenols. In this work, autochthonous Tuscany EVOOs were chemically characterized and selected EVOO samples were extracted to obtain hydroalcoholic phytocomplexes, which were assayed to establish their anti-inflammatory and vasorelaxant properties. The polar extracts were characterized via 1H-NMR and UHPLC-HRMS to investigate the chemical composition and assayed in CaCo-2 cells exposed to glucose oxidase or rat aorta rings contracted by phenylephrine. Apigenin and luteolin were found as representative flavones; other components were pinoresinol, ligstroside, and oleuropein. The extracts showed anti-inflammatory and antioxidant properties via modulation of NF-κB and Nrf2 pathways, respectively, and good vasorelaxant activity, both in the presence and absence of an intact endothelium. In conclusion, this study evaluated the nutraceutical properties of autochthonous Tuscany EVOO cv., which showed promising anti-inflammatory and vasorelaxant effects.}, number={3}, journal={ANTIOXIDANTS}, author={Pozzetti, Luca and Ferrara, Francesca and Marotta, Ludovica and Gemma, Sandra and Butini, Stefania and Benedusi, Mascia and Fusi, Fabio and Ahmed, Amer and Pomponi, Serena and Ferrari, Stefano and et al.}, year={2022}, month={Mar} }
 @article{pecorelli_ferrara_guiotto_vallese_cordone_belmonte_hayek_cervellati_valacchi_2022, title={Loss of Scavenger Receptor B1 (SR-B1) in Brain of a Rett Syndrome Mouse Model}, volume={192}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2022.10.159}, DOI={10.1016/j.freeradbiomed.2022.10.159}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, publisher={Elsevier BV}, author={Pecorelli, Alessandra and Ferrara, Francesca and Guiotto, Anna and Vallese, Andrea and Cordone, Valeria and Belmonte, Giuseppe and Hayek, Joussef and Cervellati, Carlo and Valacchi, Giuseppe}, year={2022}, month={Nov} }
 @article{cordone_ferrara_pecorelli_guiotto_vitale_amicarelli_cervellati_hayek_valacchi_2022, title={The constitutive activation of TLR4-IRAK1-NF kappa B axis is involved in the early NLRP3 inflammasome response in peripheral blood mononuclear cells of Rett syndrome patients}, volume={181}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.01.017}, abstractNote={Rett syndrome (RTT), a devastating neurodevelopmental disorder, is caused in 95% of the cases by mutations in the X-chromosome-localized MECP2 gene. To date, RTT is considered a broad-spectrum disease, due to multisystem disturbances affecting patients, associated with mitochondrial dysfunctions, subclinical inflammation and an overall OxInflammatory status. Inflammasomes are multi-protein complexes crucially involved in innate immune responses against pathogens and oxidative stress mediators. The assembly of NLRP3:ASC inflammasome lead to pro-caspase 1 activation, maturation of interleukins (IL)-1β and 18 and proteolytic cleavage of Gasdermin D leading eventually to pyroptosis and systemic inflammation. The possible de-regulation of this system, in parallel with upstream nuclear factor (NF)-κB p65 pathway, were analyzed in peripheral blood mononuclear cells (PBMCs) and plasma isolated from RTT patients and matching controls. RTT PBMCs showed a constitutive activation of the axis TLR4 (Toll-like receptor 4)-IRAK1 (interleukin-1 receptor associated kinase 1)-NF-κB p65, together with augmented ROS generation and enhanced IL-18 mRNA levels and NLRP3:ASC co-localization. The deregulation of inflammasome components was even found in THP-1 cells silenced for MECP2 and importantly, in plasma compartment of RTT subjects, from the earliest stages of the pathology or in correlation with the severity of MeCP2 mutations. Taken together, these data provide new insights into the mechanisms involved in RTT sub-clinical inflammatory status present in RTT patients, thus helping to reveal new targets for future therapeutic approaches.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cordone, Valeria and Ferrara, Francesca and Pecorelli, Alessandra and Guiotto, Anna and Vitale, Antonio and Amicarelli, Fernanda and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe}, year={2022}, month={Mar}, pages={1–13} }
 @article{ferrara_cordone_pecorelli_benedusi_pambianchi_guiotto_vallese_cervellati_valacchi_2022, title={Ubiquitination as a key regulatory mechanism for O-3-induced cutaneous redox inflammasome activation}, volume={56}, ISSN={["2213-2317"]}, url={http://dx.doi.org/10.1016/j.redox.2022.102440}, DOI={10.1016/j.redox.2022.102440}, abstractNote={NLRP1 is one of the major inflammasomes modulating the cutaneous inflammatory responses and therefore linked to a variety of cutaneous conditions. Although NLRP1 has been the first inflammasome to be discovered, only in the past years a significant progress was achieved in understanding the molecular mechanism and the stimuli behind its activation. In the past decades a crescent number of studies have highlighted the role of air pollutants as Particulate Matter (PM), Cigarette Smoke (CS) and Ozone (O3) as trigger stimuli for inflammasomes activation, especially via Reactive Oxygen Species (ROS) mediators. However, whether NLRP1 can be modulated by air pollutants via oxidative stress and the mechanism behind its activation is still poorly understood. Here we report for the first time that O3, one of the most toxic pollutants, activates the NLRP1 inflammasome in human keratinocytes via oxidative stress mediators as hydrogen peroxide (H2O2) and 4-hydroxy-nonenal (4HNE). Our data suggest that NLRP1 represents a target protein for 4HNE adduction that possibly leads to its proteasomal degradation and activation via the possible involvement of E3 ubiquitin ligase UBR2. Of note, Catalase (Cat) treatment prevented inflammasome assemble and inflammatory cytokines release as well as NLRP1 ubiquitination in human keratinocytes upon O3 exposure. The present work is a mechanistic study that follows our previous work where we have showed the ability of O3 to induce cutaneous inflammasome activation in humans exposed to this pollutant. In conclusion, our results suggest that O3 triggers the cutaneous NLRP1 inflammasome activation by ubiquitination and redox mechanism.}, journal={REDOX BIOLOGY}, publisher={Elsevier BV}, author={Ferrara, Francesca and Cordone, Valeria and Pecorelli, Alessandra and Benedusi, Mascia and Pambianchi, Erika and Guiotto, Anna and Vallese, Andrea and Cervellati, Franco and Valacchi, Giuseppe}, year={2022}, month={Oct} }
 @article{ferrara_cordone_pecorelli_benedusi_pambianchi_guiotto_vallese_cervellati_valacchi_2022, title={Ubiquitination as a key regulatory mechanism for O3-induced cutaneous redox Inflammasome activation}, volume={192}, ISSN={["1873-4596"]}, url={http://dx.doi.org/10.1016/j.freeradbiomed.2022.10.033}, DOI={10.1016/j.freeradbiomed.2022.10.033}, abstractNote={Redox signaling is an important emerging mechanism of cellular function. Dysfunctional redox signaling is increasingly implicated in numerous pathologies, including atherosclerosis, diabetes, and cancer. The molecular messengers in this type of signaling are reactive species which can mediate the post-translational modification of specific groups of proteins, thereby effecting functional changes in the modified proteins. Electrophilic compounds comprise one class of reactive species which can participate in redox signaling. Electrophiles modulate cell function via formation of covalent adducts with proteins, particularly cysteine residues.This review will discuss the commonly used methods of detection for electrophile-sensitive proteins, and will highlight the importance of identifying these proteins for studying redox signaling and developing novel therapeutics.There are several methods which can be used to detect electrophile-sensitive proteins. These include the use of tagged model electrophiles, as well as derivatization of endogenous electrophile–protein adducts.In order to understand the mechanisms by which electrophiles mediate redox signaling, it is necessary to identify electrophile-sensitive proteins and quantitatively assess adduct formation. Strengths and limitations of these methods will be discussed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, publisher={Elsevier BV}, author={Ferrara, Francesca and Cordone, Valeria and Pecorelli, Alessandra and Benedusi, Mascia and Pambianchi, Erika and Guiotto, Anna and Vallese, Andrea and Cervellati, Franco and Valacchi, Giuseppe}, year={2022}, month={Nov} }
 @article{sguizzato_ferrara_mariani_pepe_cortesi_huang_simeliere_boldrini_baldisserotto_valacchi_et al._2021, title={"Plurethosome" as Vesicular System for Cutaneous Administration of Mangiferin: Formulative Study and 3D Skin Tissue Evaluation}, volume={13}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics13081124}, abstractNote={Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status.}, number={8}, journal={PHARMACEUTICS}, author={Sguizzato, Maddalena and Ferrara, Francesca and Mariani, Paolo and Pepe, Alessia and Cortesi, Rita and Huang, Nicolas and Simeliere, Fanny and Boldrini, Paola and Baldisserotto, Anna and Valacchi, Giuseppe and et al.}, year={2021}, month={Aug} }
 @article{pambianchi_ferrara_pecorelli_benedusi_choudhary_therrien_valacchi_2021, title={Deferoxamine Treatment Improves Antioxidant Cosmeceutical Formulation Protection against Cutaneous Diesel Engine Exhaust Exposure}, volume={10}, ISSN={["2076-3921"]}, DOI={10.3390/antiox10121928}, abstractNote={Skin is one of the main targets of the outdoor stressors. Considering that pollution levels are rising progressively, it is not surprising that several cutaneous conditions have been associated with its exposure. Among the pollutants, diesel engine exhaust (DEE) represents one of the most toxic, as it is composed of a mixture of many different noxious chemicals generated during the compression cycle, for ignition rather than an electrical spark as in gasoline engines. The toxic chemicals of most concern in DEE, besides the oxides of nitrogen, sulfur dioxide and various hydrocarbons, are metals that can induce oxidative stress and inflammation. The present study aimed to evaluate the effects of topical application, singularly or in combination, of the iron-chelator deferoxamine and a commercially available formulation, CE Ferulic, in up to 4-day DEE-exposed skin. DEE induced a significant increase in the oxidative marker 4-hydroxy-nonenal (4HNE) and matrix-metallopeptidase-9 (MMP-9), the loss of cutaneous-barrier-associated proteins (filaggrin and involucrin) and a decrease in collagen-1, while the formulations prevented the cutaneous damage in an additive manner. In conclusion, this study suggests that iron plays a key role in DEE-induced skin damage and its chelation could be an adjuvant strategy to reinforce antioxidant topical formulations.}, number={12}, journal={ANTIOXIDANTS}, author={Pambianchi, Erika and Ferrara, Francesca and Pecorelli, Alessandra and Benedusi, Mascia and Choudhary, Hina and Therrien, Jean-Philippe and Valacchi, Giuseppe}, year={2021}, month={Dec} }
 @article{ferrara_prieux_woodby_valacchi_2021, title={Inflammasome Activation in Pollution-Induced Skin Conditions}, volume={147}, ISSN={["1529-4242"]}, DOI={10.1097/PRS.0000000000007617}, abstractNote={Summary:Exposure to air pollutants has been now associated with detrimental effects on a variety of organs, including the heart, lungs, GI tract, and brain. However, recently it has become clear that pollutant exposure can also promote the development/exacerbation of a variety of skin conditions, including premature aging, psoriasis, acne, and atopic dermatitis. Although the molecular mechanisms by which pollutant exposure results in these cutaneous pathological manifestations, it has been noticed that an inflammatory status is a common denominator of all those skin conditions. For this reason, recently, the activation of a cytosolic multiprotein complex involved in inflammatory responses (the inflammasome) that could promote the maturation of proinflammatory cytokines interleukin-1β and interleukin-18 has been hypothesized to play a key role in pollution-induced skin damage. In this review, we summarize and propose the cutaneous inflammasome as a novel target of pollutant exposure and the eventual usage of inflammasome inhibitor as new technologies to counteract pollution-induced skin damage. Possibly, the ability to inhibit the inflammasome activation could prevent cutaneous inflammaging and ameliorate the health and appearance of the skin.}, number={1S-2}, journal={PLASTIC AND RECONSTRUCTIVE SURGERY}, author={Ferrara, Francesca and Prieux, Roxane and Woodby, Brittany and Valacchi, Giuseppe}, year={2021}, month={Jan}, pages={15S–24S} }
 @article{prieux_benedusi_ferrara_guiotto_cervellati_valacchi_2021, title={NALP1 involvement in cigarette smoke induces cutaneous inflammation}, volume={165}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2020.12.370}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Prieux, Roxane and Benedusi, Mascia and Ferrara, Francesca and Guiotto, Anna and Cervellati, Franco and Valacchi, Giuseppe}, year={2021}, month={Mar} }
 @article{ferrara_pecorelli_benedusi_pambianchi_guiotto_cervellati_valacchi_2021, title={Ubiquitination as a key regulatory mechanism for O-3-induced cutaneous redox inflammasome activation}, volume={165}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2020.12.303}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Ferrara, Francesca and Pecorelli, Alessandra and Benedusi, Mascia and Pambianchi, Erika and Guiotto, Anna and Cervellati, Franco and Valacchi, Giuseppe}, year={2021}, month={Mar} }
 @article{pecorelli_ferrara_messano_cordone_schiavone_cervellati_woodby_cervellati_hayek_valacchi_2020, title={Alterations of mitochondrial bioenergetics, dynamics, and morphology support the theory of oxidative damage involvement in autism spectrum disorder}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fj.201902677R}, abstractNote={Autism spectrum disorder (ASD) has been hypothesized to be a result of the interplay between genetic predisposition and increased vulnerability to early environmental insults. Mitochondrial dysfunctions appear also involved in ASD pathophysiology, but the mechanisms by which such alterations develop are not completely understood. Here, we analyzed ASD primary fibroblasts by measuring mitochondrial bioenergetics, ultrastructural and dynamic parameters to investigate the hypothesis that defects in these pathways could be interconnected phenomena responsible or consequence for the redox imbalance observed in ASD. High levels of 4‐hydroxynonenal protein adducts together with increased NADPH (nicotinamide adenine dinucleotide phosphateoxidase) activity and mitochondrial superoxide production coupled with a compromised antioxidant response guided by a defective Nuclear Factor Erythroid 2‐Related Factor 2 pathway confirmed an unbalanced redox homeostasis in ASD. Moreover, ASD fibroblasts showed overactive mitochondrial bioenergetics associated with atypical morphology and altered expression of mitochondrial electron transport chain complexes and dynamics‐regulating factors. We suggest that many of the changes observed in mitochondria could represent compensatory mechanisms by which ASD cells try to adapt to altered energy demand, possibly resulting from a chronic oxinflammatory status.}, number={5}, journal={FASEB JOURNAL}, author={Pecorelli, Alessandra and Ferrara, Francesca and Messano, Nicolo and Cordone, Valeria and Schiavone, Maria Lucia and Cervellati, Franco and Woodby, Brittany and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe}, year={2020}, month={May}, pages={6521–6538} }
 @article{kremslehner_miller_nica_nagelreiter_narzt_golabi_vorstandlechner_mildner_lachner_tschachler_et al._2020, title={Imaging of metabolic activity adaptations to UV stress, drugs and differentiation at cellular resolution in skin and skin equivalents Implications for oxidative UV damage}, volume={37}, ISSN={["2213-2317"]}, DOI={10.1016/j.redox.2020.101583}, abstractNote={The epidermis is a multi-layered epithelium that consists mainly of keratinocytes which proliferate in its basal layer and then differentiate to form the stratum corneum, the skin's ultimate barrier to the environment. During differentiation keratinocyte function, chemical composition, physical properties, metabolism and secretion are profoundly changed. Extrinsic or intrinsic stressors, like ultraviolet (UV) radiation thus may differently affect the epidermal keratinocytes, depending on differentiation stage. Exposure to UV elicits the DNA damage responses, activation of pathways which detoxify or repair damage or induction of programmed cell death when the damage was irreparable. Recently, rapid diversion of glucose flux into the pentose phosphate pathway (PPP) was discovered as additional mechanism by which cells rapidly generate reduction equivalents and precursors for nucleotides – both being in demand after UV damage. There is however little known about the correlation of such metabolic activity with differentiation state, cell damage and tissue localization of epidermal cells. We developed a method to correlate the activity of G6PD, the first and rate-limiting enzyme of this metabolic UV response, at cellular resolution to cell type, differentiation state, and cell damage in human skin and in organotypic reconstructed epidermis. We thereby could verify rapid activation of G6PD as an immediate UVB response not only in basal but also in differentiating epidermal keratinocytes and found increased activity in cells which initiated DNA damage responses. When keratinocytes had been UVB irradiated before organotypic culture, their distribution within the skin equivalent was abnormal and the G6PD activity was reduced compared to neighboring cells. Finally, we found that the anti-diabetic and potential anti-aging drug metformin strongly induced G6PD activity throughout reconstructed epidermis. Activation of the protective pentose phosphate pathway may be useful to enhance the skin's antioxidant defense systems and DNA damage repair capacity on demand.}, journal={REDOX BIOLOGY}, author={Kremslehner, Christopher and Miller, Anne and Nica, Robert and Nagelreiter, Ionela-Mariana and Narzt, Marie-Sophie and Golabi, Bahar and Vorstandlechner, Vera and Mildner, Michael and Lachner, Julia and Tschachler, Erwin and et al.}, year={2020}, month={Oct} }
 @article{schiavone_pecorelli_woodby_ferrara_pambianchi_santucci_valacchi_2020, title={Mechanisms involved in the unbalanced redox homeostasis in osteoblastic cellular model of Alkaptonuria}, volume={690}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2020.108416}, abstractNote={Alkaptonuria (AKU) is a rare metabolic disease correlated with the deficiency of homogentisate 1,2-dioxygenase and leading to an accumulation of the metabolite homogentisic acid (HGA) which can be subjected to oxidation and polymerization reactions. These events are considered a trigger for the induction of oxidative stress in AKU but, despite the large description of an altered redox status, the underlying pathogenetic processes are still unstudied. In the present study, we investigated the molecular mechanisms responsible for the oxidative damage present in an osteoblast-based cellular model of AKU. Bone, in fact, is largely affected in AKU patients: severe osteoclastic resorption, osteoporosis, even for pediatric cases, and an altered rate of remodeling biomarkers have been reported. In our AKU osteoblast cell model, we found a clear altered redox homeostasis, determined by elevated hydrogen peroxide (H2O2) levels and 4HNE protein adducts formation. These findings were correlated with increased NADPH oxidase (NOX) activity and altered mitochondrial respiration. In addition, we observed a decreased activity of superoxide dismutase (SOD) and reduced levels of thioredoxin (TRX) that parallel the decreased Nrf2-DNA binding. Overall, our results reveal that HGA is able to alter the cellular redox homeostasis by modulating the endogenous ROS production via NOX activation and mitochondrial dysfunctions and impair the cellular response mechanism. These findings can be useful for understanding the pathophysiology of AKU, not yet well studied in bones, but which is an important source of comorbidities that affect the life quality of the patients.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Schiavone, Maria Lucia and Pecorelli, Alessandra and Woodby, Brittany and Ferrara, Francesca and Pambianchi, Erika and Santucci, Annalisa and Valacchi, Giuseppe}, year={2020}, month={Sep} }
 @article{nieman_valacchi_wentz_ferrara_pecorelli_woodby_sakaguchi_simonson_2020, title={Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes}, volume={30}, ISSN={["1543-2742"]}, DOI={10.1123/ijsnem.2019-0171}, abstractNote={This double-blinded, placebo controlled, randomized crossover trial investigated the influence of 2-week mixed flavonoid versus placebo supplementation on oxinflammation markers after a 75-km cycling time trial in 22 cyclists (42.3 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr post 75-km cycling (176 ± 5.4 min, 73.4 ±2.0% maximal oxygen consumption). The supplement provided 678-mg flavonoids with quercetin (200 mg), green tea catechins (368 mg, 180-mg epigallocatechin gallate), and anthocyanins (128 mg) from bilberry extract, with caffeine, vitamin C, and omega-3 fatty acids added as adjuvants. Blood samples were analyzed for blood leukocyte counts, oxinflammation biomarkers, including 4-hydroxynonenal, protein carbonyls, and peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and glutathione peroxidase. Each of the blood biomarkers was elevated postexercise (time effects, all ps < .01), with lower plasma levels for 4-hydroxynonenal (at 21-hr postexercise) in flavonoid versus placebo (interaction effect, p = .008). Although elevated postexercise, no trial differences for the neutrophil/lymphocyte ratio (p = .539) or peripheral blood mononuclear mRNA expression for cyclooxygenease-2 (p = .322) or glutathione peroxidase (p = .839) were shown. Flavonoid supplementation prior to intensive exercise decreased plasma peroxidation and oxidative damage, as determined by 4-hydroxynonenal. Postexercise increases were similar between the flavonoid and placebo trials for peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and the nuclear factor erythroid 2-related factor 2 related gene glutathione peroxidase (NFE2L2). The data support the strategy of flavonoid supplementation to mitigate postexercise oxidative stress in endurance athletes.}, number={2}, journal={INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM}, author={Nieman, David C. and Valacchi, Giuseppe and Wentz, Laurel M. and Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Sakaguchi, Camila A. and Simonson, Andrew}, year={2020}, month={Mar}, pages={112–119} }
 @article{sguizzato_mariani_ferrara_drechsler_hallan_huang_simeliere_khunti_cortesi_marchetti_et al._2020, title={Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid}, volume={10}, ISSN={["2079-4991"]}, DOI={10.3390/nano10050961}, abstractNote={Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.}, number={5}, journal={NANOMATERIALS}, author={Sguizzato, Maddalena and Mariani, Paolo and Ferrara, Francesca and Drechsler, Markus and Hallan, Supandeep Singh and Huang, Nicolas and Simeliere, Fanny and Khunti, Nikul and Cortesi, Rita and Marchetti, Nicola and et al.}, year={2020}, month={May} }
 @article{nieman_ferrara_pecorelli_woodby_hoyle_simonson_valacchi_2020, title={Postexercise Inflammasome Activation and IL-1 beta Production Mitigated by Flavonoid Supplementation in Cyclists}, volume={30}, ISSN={["1543-2742"]}, DOI={10.1123/ijsnem.2020-0084}, abstractNote={Inflammasomes are multiprotein signaling platforms of the innate immune system that detect markers of physiological stress and promote the maturation of caspase-1 and interleukin 1 beta (IL-1β), IL-18, and gasdermin D. This randomized, cross-over trial investigated the influence of 2-week mixed flavonoid (FLAV) versus placebo (PL) supplementation on inflammasome activation and IL-1β and IL-18 production after 75-km cycling in 22 cyclists (42 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr postexercise (176 ± 5.4 min, 73.4 ± 2.0 %VO2max). The supplement (678 mg FLAVs) included quercetin, green tea catechins, and bilberry anthocyanins. The pattern of change in the plasma levels of the inflammasome adaptor oligomer ASC (apoptosis-associated speck-like protein containing caspase recruitment domain) was different between the FLAV and PL trials, with the FLAV ASC levels 52% lower (Cohen’sd = 1.06) than PL immediately following 75-km cycling (interaction effect,p = .012). The plasma IL-1β levels in FLAV were significantly lower than PL (23–42%; Cohen’sd = 0.293–0.644) throughout 21 hr of recovery (interaction effect,p = .004). The change in plasma gasdermin D levels were lower immediately postexercise in FLAV versus PL (15% contrast,p = .023; Cohen’sd = 0.450). The patterns of change in plasma IL-18 and IL-37 did not differ between the FLAV and PL trials (interaction effects,p = .388, .716, respectively). These data indicate that 2-week FLAV ingestion mitigated inflammasome activation, with a corresponding decrease in IL-1β release in cyclists after a 75-km cycling time trial. The data from this study support the strategy of ingesting high amounts of FLAV to mitigate postexercise inflammation.}, number={6}, journal={INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM}, author={Nieman, David C. and Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Hoyle, Andrew T. and Simonson, Andrew and Valacchi, Giuseppe}, year={2020}, month={Nov}, pages={396–404} }
 @article{ferrara_pambianchi_pecorelli_woodby_messano_therrien_lila_valacchi_2020, title={Redox regulation of cutaneous inflammasome by ozone exposure}, volume={152}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.11.031}, abstractNote={Several pollutants have been shown to affect skin physiology, among which ozone (O3) is one of the most toxic. Prolonged exposure to O3 leads to increased oxidative damage and cutaneous inflammation. The correlation between O3 exposure and inflammatory cutaneous conditions (atopic dermatitis, psoriasis, acne and eczema) has been already suggested, although the mechanism involved is still unclear. In the last few decades, a new multiprotein complex, the inflammasome, has been discovered and linked to tissue inflammation, including inflammatory skin conditions. The inflammasome activates inflammatory responses and contributes to the maturation of cytokines such as interleukin 1β (IL-1β) and interleukin 18. This complex is also responsive to reactive oxygen species (ROS), which plays a role in triggering the activation of the complex. On this basis it is possible hypothesize that the activation of the inflammasome could be the link between the inflammatory skin conditions associated to O3 exposure. In the present work, the ability of O3 to induce inflammasome activation was determined in different skin models, ranging from 2D (human keratinocytes) to 3D models in vitro and ex vivo. Results clearly showed that O3 exposure increased both transcript and protein levels of the main inflammasome complex, such as ASC and caspase-1. Furthermore, by using both immunofluorescence and an ASC oligomerization assay the formation of the complex was determined together with increased secreted levels of both IL-18 and IL-1β. Of note is that H2O2 and to a less extent 4HNE (both considered the main mediators of O3 interaction with cellular membranes) were also able to activate skin inflammasome while the use of catalase prevents the activation. This study demonstrated that O3 can activate cutaneous inflammasome in a redox dependent manner suggesting a possible role of this new pathway in pollution induced inflammatory skin conditions.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Ferrara, Francesca and Pambianchi, Erika and Pecorelli, Alessandra and Woodby, Brittany and Messano, Nicolo and Therrien, Jean-Philippe and Lila, Mary Ann and Valacchi, Giuseppe}, year={2020}, month={May}, pages={561–570} }
 @article{schiavone_pecorelli_woodby_ferrara_santucci_valacchi_2019, title={HGA Induces Oxidative Damage in an Ostcoblastic Cellular Model of Alkaptonuria: Sources and Mechanisms HGA Induces Oxidative Damage in an Osteoblastic Cellular Model of Alkaptonuria: Sources and Mechanisms}, volume={145}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.10.095}, abstractNote={Excessive fatty acid uptake-induced oxidative stress causes liver injury and the consecutive recruitment of inflammatory immune cells, thereby promoting the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Lycopene, the most effective singlet oxygen scavenger of the antioxidant carotenoids, has anti-inflammatory activity. Here, we investigated the preventive and therapeutic effects of lycopene in a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet. Lycopene alleviated excessive hepatic lipid accumulation and enhanced lipolysis, decreased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis, and subsequently reduced the recruitment of CD4+ and CD8+ T cells in the liver. Importantly, lycopene reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. In parallel, lycopene decreased LPS-/IFN-γ-/TNFα-induced M1 marker mRNA levels in peritoneal macrophages, as well as TGF-β1-induced expression of fibrogenic genes in a stellate cell line, in a dose-dependent manner. These results were associated with decreased oxidative stress in cells, which might be mediated by the expression of NADPH oxidase subunits. In summary, lycopene prevented and reversed lipotoxicity-induced inflammation and fibrosis in NASH mice by reducing oxidative stress. Therefore, it might be a novel and promising treatment for NASH.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Schiavone, Maria Lucia and Pecorelli, Alessandra and Woodby, Brittany and Ferrara, Francesca and Santucci, Annalisa and Valacchi, Giuseppe}, year={2019}, month={Dec}, pages={S37–S38} }
 @article{muresan_narzt_woodby_ferrara_gruber_valacchi_2019, title={Involvement of cutaneous SR-B1 in skin lipid homeostasis}, volume={666}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2019.03.005}, abstractNote={The main functions of the skin are to protect against environmental insults and prevent water loss, which are performed by the complex lipid- and protein matrix present in the outermost layers of the epithelium. The lipidome of these outer layers is mainly composed of ceramides, fatty acids, and cholesterol, which regulates keratinocyte differentiation and skin barrier function. SR-B1 is a multifunctional scavenger receptor that is best known for facilitating uptake of cholesterol from HDL particles in the liver, but it is also expressed in the skin.To determine the role of SR-B1 in keratinocyte differentiation.We investigated the relationship between SR-B1 and keratinocyte differentiation using a physiologically relevant model, organotypic skin equivalents (SEs), wherein SR-B1 was knocked down via siRNA transfection. To assess effects of SR-B1 knockdown on keratinocyte differentiation, we performed hematoxylin/eosin staining, RT-PCR, western blotting, and immunohistochemistry. We also examined the effect of SR-B1 knockdown on lipid production by performing Oil Red O staining and thin layer chromatography.SR-B1 knockdown resulted in decreased lipid levels in SEs, specifically ceramides, and in decreased transcript levels of LDLR, PPAR-α and PPAR-γ, which are factors involved in regulating ceramide synthesis. In addition, filaggrin levels increased in SR-B1 KD tissues, but neither keratin 14 nor keratin 10 were affected.We conclude that one of the main functions of SR-B1 in the skin is to regulate ceramide levels and thereby maintain the barrier function of the skin, resulting in the protection of cutaneous tissues from outdoor insults.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Muresan, Ximena Maria and Narzt, Marie-Sophie and Woodby, Brittany and Ferrara, Francesca and Gruber, Florian and Valacchi, Giuseppe}, year={2019}, month={May}, pages={1–7} }
 @article{ferrara_pecorelli_woodby_pambianchi_messano_therrien_valacchi_2019, title={Redox Regulation of Cutaneous Inflammasome Pathway by Ozone Exposure}, volume={145}, ISBN={1873-4596}, DOI={10.1016/j.freeradbiomed.2019.10.055}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Pambianchi, Erika and Messano, Nicole and Therrien, Jean Philippe and Valacchi, Giuseppe}, year={2019}, month={Dec}, pages={S22–S23} }
 @article{valacchi_pecorelli_pambianchi_ferrara_lila_2018, title={AtmO(3)spheric skin damage: The oxInflammation phenomena}, volume={138}, ISSN={["1523-1747"]}, DOI={10.1016/j.jid.2018.06.089}, abstractNote={Atmospheric factors such as air pollution have been implicated in premature skin aging and also being associated with several skin pathologies. Among the pollutants to which cutaneous tissues is daily exposed, ozone has been shown to be one of the most noxious. The skin damage caused by ozone exposure is largely related to its ability to generate a complex cascade of oxidative stress related reactions. Indeed ozone is not able to penetrate the skin and although it is not a radical per se it is able to react with the stratum corneum fatty acids and generate oxidized lipids that can act as second messengers. This cascade of effects is able to initiate a pro-inflammatory skin response that, with the altered redox homeostasis, leads to a vicious cycle where inflammation and ROS aliment each other. In this contest the fine regulated balance between NFkB and Nrf2 activation is also compromise and the defensive ability of cutaneous cells is corrupted. In addition, the insufficient activation of NRF2 lead to the arousal of the inflammasome pathway that can eventually lead to cells damage and death. The action by which ozone affect skin has been evidenced in several cutaneous model (2D, 3D, biopsies) and also in human subjects. Therefore, knowing the exact mechanism by which ozone is able to affect skin can bring new insights on possible therapeutic and preventive interventions.}, number={9}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Valacchi, G. and Pecorelli, A. and Pambianchi, E. and Ferrara, F. and Lila, M.}, year={2018}, month={Sep}, pages={B15–B15} }
 @article{muresan_sticozzi_belmonte_cervellati_ferrara_lila_valacchi_2018, title={SR-B1 involvement in keratinocytes in vitro wound closure}, volume={658}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2018.09.014}, abstractNote={Skin represents the most extended organ of human body, having as main function the protection of our body from outdoor stressors. Its protective ability is compromised when the skin is disrupted as a consequence of mechanical insults. For this purpose, cutaneous tissue is equipped with an efficient and fine mechanism involved in repairing the wounded area. Among the numerous players that take part in the wound healing process, SR-B1 has been recently shown to have a role in keratinocyte re-epithelialization. SR-B1 is a mediator of cholesterol uptake from HDLs, whereas it is implicated in other cellular processes such as vitamins absorption, vesicle trafficking or pathogen identification. The aim of this study was to investigate the mechanisms involved in SR-B1 role in skin wound closure. Our in vitro data demonstrated that SR-B1 influenced keratinocyte proliferation and migration through a downregulation of nuclear cyclin D1 levels and active MMP9 expression respectively possibly in an NF-kB-dependent mechanism. In addition, SR-B1 was also able to modulate keratinocyte morphology into a pro-migratory cytoskeleton rearrangement. The present in vitro study suggests a new role of SRB1 as a possible new key player in cutaneous wound healing mechanism.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Muresan, Ximena M. and Sticozzi, Claudia and Belmonte, Giuseppe and Cervellati, Franco and Ferrara, Francesca and Lila, Mary Ann and Valacchi, Giuseppe}, year={2018}, month={Nov}, pages={1–6} }