@article{pasqui_cicaloni_tinti_guiotto_tinti_mori_bruttini_hayek_pecorelli_salvini_et al._2024, title={A proteomic approach to investigate the role of the MECP2 gene mutation in Rett syndrome redox regulatory pathways}, volume={752}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2023.109860}, abstractNote={Mutations in the X-linked methyl-CpG-binding 2 (MECP2) gene lead to Rett Syndrome (RTT; OMIM 312750), a devasting neurodevelopmental disorder. RTT clinical manifestations are complex and with different degrees of severity, going from autistic-like behavior to loss of acquired speech, motor skills and cardiac problems. Furthermore, the correlation between the type of MECP2 mutation and the clinical phenotype is still not fully understood. Contextually, different genotypes can differently affect the patient's phenotype and omics methodologies such as proteomics could be an important tool for a molecular characterization of genotype/phenotype correlation. The aim of our study was focused on evaluating RTT oxidative stress (OS) responses related to specific MECP2 gene mutations by using proteomics and bioinformatics approaches. Primary fibroblasts isolated from patients affected by R133C and R255× mutations were compared to healthy controls (HC). After clustering primary dermal fibroblasts based on their specific MECP2 mutations, fibroblast-derived protein samples were qualitative and quantitative analyzed, using a label free quantification (LFQ) analysis by mass spectrometry (MS), achieving a preliminary correlation for RTT genotype/phenotype. Among the identified proteins involved in redox regulation pathways, NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) was found to be absent in R255× cells, while it was present in R133C and in HC fibroblasts. Moreover, NQO1 aberrant gene regulation was also confirmed when cells were challenged with 100 μM hydrogen peroxide (H2O2). In conclusion, by employing a multidisciplinary approach encompassing proteomics and bioinformatics analyses, as well as molecular biology assays, the study uncovered phenotypic responses linked to specific MECP2 gene mutations. These findings contribute to a better understanding of the complexity of RTT molecular pathways, confirming the high heterogeneity among the patients.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Pasqui, Arianna and Cicaloni, Vittoria and Tinti, Laura and Guiotto, Anna and Tinti, Cristina and Mori, Alessia and Bruttini, Marco and Hayek, Joussef and Pecorelli, Alessandra and Salvini, Laura and et al.}, year={2024}, month={Feb} }
 @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{esposito_ferrara_drechsler_bortolini_ragno_toldo_bondi_pecorelli_voltan_secchiero_et al._2024, title={Nutlin-3 Loaded Ethosomes and Transethosomes to Prevent UV-Associated Skin Damage}, volume={14}, ISSN={["2075-1729"]}, DOI={10.3390/life14010155}, abstractNote={The skin’s protective mechanisms, in some cases, are not able to counteract the destructive effects induced by UV radiations, resulting in dermatological diseases, as well as skin aging. Nutlin-3, a potent drug with antiproliferative activity in keratinocytes, can block UV-induced apoptosis by activation of p53. In the present investigation, ethosomes and transethosomes were designed as delivery systems for nutlin-3, with the aim to protect the skin against UV damage. Vesicle size distribution was evaluated by photon correlation spectroscopy and morphology was investigated by cryogenic transmission electron microscopy, while nutlin-3 entrapment capacity was evaluated by ultrafiltration and HPLC. The in vitro diffusion kinetic of nutlin-3 from ethosomes and transethosomes was studied by Franz cell. Moreover, the efficiency of ethosomes and transethosomes in delivering nutlin-3 and its protective role were evaluated in ex vivo skin explants exposed to UV radiations. The results indicate that ethosomes and transethosomes efficaciously entrapped nutlin-3 (0.3% w/w). The ethosome vesicles were spherical and oligolamellar, with a 224 nm mean diameter, while in transethosome the presence of polysorbate 80 resulted in unilamellar vesicles with a 146 nm mean diameter. The fastest nutlin-3 kinetic was detected in the case of transethosomes, with permeability coefficients 7.4-fold higher, with respect to ethosomes and diffusion values 250-fold higher, with respect to the drug in solution. Ex vivo data suggest a better efficacy of transethosomes to promote nutlin-3 delivery within the skin, with respect to ethosomes. Indeed, nutlin-3 loaded transethosomes could prevent UV effect on cutaneous metalloproteinase activation and cell proliferative response.}, number={1}, journal={LIFE-BASEL}, author={Esposito, Elisabetta and Ferrara, Francesca and Drechsler, Markus and Bortolini, Olga and Ragno, Daniele and Toldo, Sofia and Bondi, Agnese and Pecorelli, Alessandra and Voltan, Rebecca and Secchiero, Paola and et al.}, 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{nieman_woo_sakaguchi_omar_tang_davis_pecorelli_valacchi_zhang_2023, title={Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins}, volume={10}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2023.1143385}, abstractNote={ObjectivesAstaxanthin is a dark red keto-carotenoid found in aquatic animals such as salmon and shrimp, and algae (Haematococcus pluvialis). Astaxanthin has a unique molecular structure that may facilitate anti-oxidative, immunomodulatory, and anti-inflammatory effects during physiological stress. The primary objective of this study was to examine the efficacy of 4-week ingestion of astaxanthin in moderating exercise-induced inflammation and immune dysfunction using a multi-omics approach.}, journal={FRONTIERS IN NUTRITION}, author={Nieman, David C. and Woo, Jongmin and Sakaguchi, Camila A. and Omar, Ashraf M. and Tang, Yang and Davis, Kierstin and Pecorelli, Alessandra and Valacchi, Giuseppe and Zhang, Qibin}, year={2023}, month={Mar} }
 @misc{ivarsson_pecorelli_lila_valacchi_2023, title={Blueberry Supplementation and Skin Health}, volume={12}, ISSN={["2076-3921"]}, url={https://doi.org/10.3390/antiox12061261}, DOI={10.3390/antiox12061261}, abstractNote={Environmental stressors such as air pollutants, ozone, and UV radiation are among the most noxious outdoor stressors affecting human skin and leading to premature skin aging. To prevent the extrinsic aging, the skin is equipped with an effective defensive system. However, cutaneous defense mechanisms can be overwhelmed through chronic exposure to environmental pollutants. Recent studies have suggested that the topical usage of natural compounds, such as blueberries, could be a good strategy to prevent skin damage from the environment. Indeed, blueberries contain bioactive compounds found to induce an active skin response against the environmental noxious effects. In this review, results from recent studies on this topic are discussed in order to build the argument for blueberries to possibly be an effective agent for skin health. In addition, we hope to highlight the need for further research to elucidate the mechanisms behind the use of both topical application and dietary supplementation with blueberries to bolster cutaneous systems and defensive mechanisms.}, number={6}, journal={ANTIOXIDANTS}, author={Ivarsson, John and Pecorelli, Alessandra and Lila, Mary Ann and Valacchi, Giuseppe}, year={2023}, month={Jun} }
 @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{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{hoskin_grace_guiotto_pecorelli_valacchi_lila_2023, title={Development of Spray Dried Spirulina Protein-Berry Pomace Polyphenol Particles to Attenuate Pollution-Induced Skin Damage: A Convergent Food-Beauty Approach}, volume={12}, ISSN={["2076-3921"]}, url={https://doi.org/10.3390/antiox12071431}, DOI={10.3390/antiox12071431}, abstractNote={Spray drying (SD) microencapsulation of phytochemicals from berry pomaces with Spirulina protein (SP) was incorporated into a cosmeceutical topical formulation to mitigate pollution skin damage. Initially, microparticles produced with SP and polyphenols recovered from fruit pomaces (elderberry SP-EB and muscadine grape SP-MG) were characterized regarding physicochemical and phytochemical content (polyphenol load, carotenoid and phycocyanin contents and antioxidant activity). SP had low total phenolic content (7.43 ± 0.23 mg GAE/g DW), but complexation with elderberry or muscadine grape pomaces polyphenols led to a substantial increase (27.63 ± 1.15 SP-EB and 111.0 ± 2.6 mg GAE/g DW SP-MG). SP-MG particles had higher anthocyanin (26.87 ± 1.25 mg/g) and proanthocyanidin (9.02 ± 0.74 mg/g) contents compared to SP-EB particles. SP-MG were prioritized to prepare a topical gel to attenuate skin oxinflammatory markers and prevent skin barrier disruption using ex vivo human biopsies exposed to diesel engine exhaust (DEE). The immunofluorescence results showed increased oxidative protein damage and inflammation associated with impaired skin barrier function after DEE exposure while topical application of gel formulated with SP-MG mitigated these effects. Overall, this study demonstrated that protein-polyphenol complexation is a synergistic strategy to stabilize and deliver residual fruit/algae phytoactives into cosmeceutical products for skin health applications.}, number={7}, journal={ANTIOXIDANTS}, author={Hoskin, Roberta Targino and Grace, Mary H. and Guiotto, Anna and Pecorelli, Alessandra and Valacchi, Giuseppe and Lila, Mary Ann}, year={2023}, month={Jul} }
 @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{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{pecorelli_2023, title={Mitochondria and inflammasome involvement in Autism Spectrum Disorder}, volume={198}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.12.020}, abstractNote={Geoffrey Burnstock is a purinergic signalling legend who’s discoveries and conceptualisation created and shaped the field. His scientific achievements were extraordinary and sustained. They included his demonstration that ATP can act as a neurotransmitter and hence extracellular signalling molecule, which he championed despite considerable initial opposition to his proposal that ATP acts outside of its role as an energy source inside cells. He led on purine receptor classification: initially of the P1 and P2 receptor families, then the P2X and P2Y receptor families, and then subtypes of P2X and P2Y receptors. This was achieved across several decades as he conceptualised and made sense of the emerging and growing evidence that there were multiple receptor subtypes for ATP and other nucleotides. He made discoveries about short term and long term/trophic purinergic signalling. He was a leader in the field for over 50 years. He inspired many and was a great colleague and mentor. I had the privilege of spending over 10 years (from 1985) with Geoff at the Department of Anatomy and Developmental Biology, University College London. This review is a personal perspective of some of Geoff’s research on P2 receptors carried out during that time. It is a tribute to Geoff who I regarded with enormous respect and admiration.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra}, year={2023}, month={Mar}, pages={S2–S2} }
 @article{vallese_cordone_pecorelli_valacchi_2023, title={Ox-inflammasome involvement in neuroinflammation}, volume={207}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.07.010}, abstractNote={Neuroinflammation plays a crucial role in the onset and the progression of several neuropathologies, from neurodegenerative disorders to migraine, from Rett syndrome to post-COVID 19 neurological manifestations. Inflammasomes are cytosolic multiprotein complexes of the innate immune system that fuel inflammation. They have been under study for the last twenty years and more recently their involvement in neuro-related conditions has been of great interest as possible therapeutic target. The role of oxidative stress in inflammasome activation has been described, however the exact way of action of specific endogenous and exogenous oxidants needs to be better clarified. In this review, we provide the current knowledge on the involvement of inflammasome in the main neuropathologies, emphasizing the importance to further clarify the role of oxidative stress in its activation including the role of mitochondria in inflammasome-induced neuroinflammation.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Vallese, Andrea and Cordone, Valeria and Pecorelli, Alessandra and Valacchi, Giuseppe}, year={2023}, month={Oct}, pages={161–177} }
 @article{garces_pecorelli_moretton_magnani_chiapetta_alvarez_evelson_valacchi_2023, title={Protective role of Ibuprofen-Curcumin co-load nanomicelles against oxidative stress and inflammasome activation mediated by indoor pollution exposure in A549 cells}, volume={208}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.10.345}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Garces, Mariana and Pecorelli, Alessandra and Moretton, Marcela and Magnani, Natalia and Chiapetta, Diego and Alvarez, Silvia and Evelson, Pablo Andres and Valacchi, Giuseppe}, year={2023}, month={Nov}, pages={S151–S152} }
 @article{silvestri_marcheggiani_orlando_cirilli_mengarelli_vallese_pecorelli_valacchi_tiano_2023, title={ROLE OF COENZYME Q10 IN MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE DAMAGE IN RETT SYNDROME}, volume={201}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2023.03.080}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Silvestri, Sonia and Marcheggiani, Fabio and Orlando, Patrick and Cirilli, Ilenia and Mengarelli, Francesco and Vallese, Andrea and Pecorelli, Alessandra and Valacchi, Giuseppe and Tiano, Luca}, year={2023}, month={May}, pages={16–16} }
 @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{pambianchi_hagenberg_pecorelli_pasqui_therrien_valacchi_2023, title={Tension as a key factor in skin responses to pollution}, volume={13}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-023-42629-6}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Pambianchi, Erika and Hagenberg, Zachary and Pecorelli, Alessandra and Pasqui, Arianna and Therrien, Jean-Philippe and Valacchi, Giuseppe}, year={2023}, month={Sep} }
 @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{pecorelli_francesca_cordone_guiotto_cervellati_hayek_valacchi_2022, title={Aberrant Mitochondrial Bioenergetics Fuels Inflammasome Machinery in Autism Spectrum Disorder}, volume={180}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.12.227}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Francesca, Ferrara and Cordone, Valeria and Guiotto, Anna and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe}, year={2022}, month={Feb}, pages={97–98} }
 @article{guiotto_cordone_benedusi_cervellati_cervellati_hayek_valacchi_pecorelli_2022, title={Involvement Of Ferroptosis In Rett Syndrome}, volume={192}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.10.054}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Guiotto, Anna and Cordone, Valeria and Benedusi, Mascia and Cervellati, Franco and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe and Pecorelli, Alessandra}, year={2022}, month={Nov} }
 @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{pasqui_cicaloni_tinti_mori_bruttini_pecorelli_tinti_dotta_laura_valacchi_2022, title={Mutations Specific Redox Regulation Pathway In Rett Syndrome By The Use Of Transcriptomics And Proteomics Approaches}, volume={192}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.10.062}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pasqui, Arianna and Cicaloni, Vittoria and Tinti, Laura and Mori, Alessia and Bruttini, Marco and Pecorelli, Alessandra and Tinti, Cristina and Dotta, Francesco and Laura, Salvini and Valacchi, Giuseppe}, year={2022}, month={Nov} }
 @misc{pecorelli_valacchi_2022, title={Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma}, volume={14}, ISSN={["2072-6694"]}, DOI={10.3390/cancers14133224}, abstractNote={Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain to be explored. Interestingly, redox-mediated signaling and perturbed microRNA (miRNA) profiles appear to be interconnected contributing factors able to act synergistically in melanoma initiation and progression. Since UV radiation can promote both redox imbalance and miRNA dysregulation, a harmful crosstalk between these two key cellular networks, with UV as central hub among them, is likely to occur in skin tissue. Therefore, decoding the complex circuits that orchestrate the interaction of UV exposure, oxidative stress, and dysregulated miRNA profiling can provide a deep understanding of the molecular basis of the melanomagenesis process. Furthermore, these mechanistic insights into the reciprocal regulation between these systems could have relevant implications for future therapeutic approaches aimed at counteracting UV-induced redox and miRNome imbalances for the prevention and treatment of malignant melanoma. In this review, we illustrate current information on the intricate connection between UV-induced dysregulation of redox-sensitive miRNAs and well-known signaling pathways involved in the malignant transformation of normal melanocytes to malignant melanoma.}, number={13}, journal={CANCERS}, author={Pecorelli, Alessandra and Valacchi, Giuseppe}, year={2022}, month={Jul} }
 @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{pambianchi_hagenberg_pecorelli_grace_therrien_lila_valacchi_2021, title={Alaskan Bog Blueberry (Vaccinium uliginosum) Extract as an Innovative Topical Approach to Prevent UV-Induced Skin Damage}, volume={8}, ISSN={["2079-9284"]}, url={https://doi.org/10.3390/cosmetics8040112}, DOI={10.3390/cosmetics8040112}, abstractNote={Our body is continuously exposed to various exogenous aggressors, and, in particular, the skin represents the main target for outdoor stressors, including ultraviolet (UV) radiation. UV exposure is well-known to be associated with the development/worsening of extrinsic photoaging and a multitude of skin conditions. Considering the role of photoprotection in skin health, the research of natural photoprotective molecules becomes of great importance. Therefore, in this work we wanted to evaluate the beneficial protective effects of ripe berries of Vaccinium uliginosum (Alaska bog blueberry (BB)) extract (100 μg/mL) for preventing the cutaneous oxidative, inflammatory, and structural damage induced by exposure to 200 mJ of UVA/UVB radiation. We observed that the topical application of BB extract on human ex vivo skin explants averted the UV-induced cutaneous OxInflammatory phenomenon by quenching the increase in the oxidative and inflammatory marker levels, such as 4-hydroxynonenal (4HNE), heme-oxygenase-1 (HO-1), cyclooxygenase-2 (COX2), and aryl hydrocarbon receptor (AhR); as well as by counteracting the loss of structural proteins (filaggrin and involucrin) induced by UV radiation. Our data propose the use of a topical application of Alaska bog blueberry extract as a natural and valuable approach to ensure photoprotection against UV-induced skin damage and premature aging.}, number={4}, journal={COSMETICS}, author={Pambianchi, Erika and Hagenberg, Zachary and Pecorelli, Alessandra and Grace, Mary and Therrien, Jean-Philippe and Lila, Mary Ann and Valacchi, Giuseppe}, year={2021}, month={Dec} }
 @article{guiotto_cordone_benedusi_cervellati_hayek_cervellati_valacchi_pecorelli_2021, title={Alteration of cellular defensive response and a possible involvement of ferroptosis cell death in Rett syndrome disorder}, volume={165}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2020.12.403}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Guiotto, Anna and Cordone, Valeria and Benedusi, Mascia and Cervellati, Franco and Hayek, Joussef and Cervellati, Carlo and Valacchi, Giuseppe and Pecorelli, Alessandra}, year={2021}, month={Mar} }
 @article{garces_magnani_pecorelli_calabro_marchini_caceres_pambianchi_galdoporpora_vico_salgueiro_et al._2021, title={Alterations in oxygen metabolism are associated to lung toxicity triggered by silver nanoparticles exposure}, volume={166}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.02.008}, abstractNote={Along with the AgNP applications development, the concern about their possible toxicity has increasingly gained attention. As the respiratory system is one of the main exposure routes, the aim of this study was to evaluate the harmful effects developed in the lung after an acute AgNP exposure. In vivo studies using Balb/c mice intranasally instilled with 0.1 mg AgNP/kg b.w, were performed. 99mTc-AgNP showed the lung as the main organ of deposition, where, in turn, AgNP may exert barrier injury observed by increased protein content and total cell count in BAL samples. In vivo acute exposure showed altered lung tissue O2 consumption due to increased mitochondrial active respiration and NOX activity. Both O2 consumption processes release ROS triggering the antioxidant system as observed by the increased SOD, catalase and GPx activities and a decreased GSH/GSSG ratio. In addition, increased protein oxidation was observed after AgNP exposure. In A549 cells, exposure to 2.5 μg/mL AgNP during 1 h resulted in augment NOX activity, decreased mitochondrial ATP associated respiration and higher H2O2 production rate. Lung 3D tissue model showed AgNP-initiated barrier alterations as TEER values decreased and morphological alterations. Taken together, these results show that AgNP exposure alters O2 metabolism leading to alterations in oxygen metabolism lung toxicity. AgNP-triggered oxidative damage may be responsible for the impaired lung function observed due to alveolar epithelial injury.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Garces, Mariana and Magnani, Natalia D. and Pecorelli, Alessandra and Calabro, Valeria and Marchini, Timoteo and Caceres, Lourdes and Pambianchi, Erika and Galdoporpora, Juan and Vico, Tamara and Salgueiro, Jimena and et al.}, year={2021}, month={Apr}, pages={324–336} }
 @misc{pecorelli_cordone_schiavone_caffarelli_cervellati_cerbone_gonnelli_hayek_valacchi_2021, title={Altered Bone Status in Rett Syndrome}, volume={11}, ISSN={["2075-1729"]}, DOI={10.3390/life11060521}, abstractNote={Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad spectrum of clinical phenotypes with various degrees of severity. In addition, as a complex multisystem disease, RTT shows several clinical manifestations ranging from neurological to non-neurological symptoms. The most common non-neurological comorbidities include, among others, orthopedic complications, mainly scoliosis but also early osteopenia/osteoporosis and a high frequency of fractures. A characteristic low bone mineral density dependent on a slow rate of bone formation due to dysfunctional osteoblast activity rather than an increase in bone resorption is at the root of these complications. Evidence from human and animal studies supports the idea that MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/β-catenin axis and RANKL/RANK/OPG system. More research is needed to better understand the role of MeCP2 in bone homeostasis. Indeed, uncovering the molecular mechanisms underlying RTT bone problems could reveal new potential pharmacological targets for the treatment of these complications that adversely affect the quality of life of RTT patients for whom the only therapeutic approaches currently available include bisphosphonates, dietary supplements, and physical activity.}, number={6}, journal={LIFE-BASEL}, author={Pecorelli, Alessandra and Cordone, Valeria and Schiavone, Maria Lucia and Caffarelli, Carla and Cervellati, Carlo and Cerbone, Gaetana and Gonnelli, Stefano and Hayek, Joussef and Valacchi, Giuseppe}, year={2021}, month={Jun} }
 @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{cordone_pecorelli_falone_hayek_amicarelli_valacchi_2021, title={Deregulated inflammasome response in Rett syndrome}, volume={177}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.08.158}, abstractNote={Pulmonary vein (PV) isolation is the cornerstone of catheter ablation in patients with atrial fibrillation (AF). “Single-shot” ablation devices have been recently engineered.We report on the safety and efficacy of a novel ablation catheter for PV isolation in patients with AF.One hundred eighty consecutive patients (58 ± 10 years, 125 male, 31% with structural heart disease) referred for paroxysmal (140) or persistent (40) AF underwent PV isolation by an open-irrigated mapping and radiofrequency (RF) decapolar ablation catheter in 7 centers. Ablation was guided by electroanatomic mapping, allowing RF energy delivery in the antral region of PVs from 10 irrigated electrodes simultaneously.Mean overall procedure time was 113 ± 53 minutes with a mean fluoroscopy time of 13.1 ± 8.4 minutes. The use of a preablation PV imaging related to a significant reduction in fluoroscopy time (from 14.7 ± 9.7 to 8.7 ± 6.6, P < .001). Mean ablation time was 12.5 ± 5.1 minutes, and 98% of the targeted veins were isolated with a mean of 23.4 ± 6.3 RF pulses per patient. In only 4 patients (2.2%) a single-point ablation strategy was required to achieve PV isolation. One groin hematoma and 1 PV stenosis were reported. During a mean follow-up of 13.9 ± 8.2 months 38 of 140 patients (27%) with paroxysmal AF and 12 of 40 patients (30%) with persistent AF had an atrial arrhythmia relapse (P = .671).In this multicenter registry, irrigated multielectrode RF ablation proved feasible, achieving a high rate of isolated PVs. Procedural and fluoroscopy times and success rates were comparable with other techniques, with a low complication rate.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cordone, Valeria and Pecorelli, Alessandra and Falone, Stefano and Hayek, Joussef and Amicarelli, Fernanda and Valacchi, Giuseppe}, year={2021}, month={Dec} }
 @article{crivellari_pecorelli_cordone_marchi_pinton_hayek_cervellati_valacchi_2021, title={Impaired mitochondrial quality control in Rett Syndrome}, volume={700}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2021.108790}, abstractNote={Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused in the 95% of cases by mutations in the X-linked MECP2 gene, affecting almost exclusively females. While the genetic basis of RTT is known, the exact pathogenic mechanisms that lead to the broad spectrum of symptoms still remain enigmatic. Alterations in the redox homeostasis have been proposed among the contributing factors to the development and progression of the syndrome. Mitochondria appears to play a central role in RTT oxidative damage and a plethora of mitochondrial defects has already been recognized. However, mitochondrial dynamics and mitophagy, which represent critical pathways in regulating mitochondrial quality control (QC), have not yet been investigated in RTT. The present work showed that RTT fibroblasts have networks of hyperfused mitochondria with morphological abnormalities and increased mitochondrial volume. Moreover, analysis of mitophagic flux revealed an impaired PINK1/Parkin-mediated mitochondrial removal associated with an increase of mitochondrial fusion proteins Mitofusins 1 and 2 (MFN1 and 2) and a decrease of fission mediators including Dynamin related protein 1 (DRP1) and Mitochondrial fission 1 protein (FIS1). Finally, challenging RTT fibroblasts with FCCP and 2,4-DNP did not trigger a proper apoptotic cell death due to a defective caspase 3/7 activation. Altogether, our findings shed light on new aspects of mitochondrial dysfunction in RTT that are represented by defective mitochondrial QC pathways, also providing new potential targets for a therapeutic intervention aimed at slowing down clinical course and manifestations in the affected patients.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Crivellari, Ilaria and Pecorelli, Alessandra and Cordone, Valeria and Marchi, Saverio and Pinton, Paolo and Hayek, Joussef and Cervellati, Carlo and Valacchi, Giuseppe}, year={2021}, month={Mar} }
 @article{guiotto_cordone_benedusi_cervellati_hayek_cervellati_valacchi_pecorelli_2021, title={Improper enzymatic defensive responses in Rett syndrome disorder}, volume={177}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.08.165}, abstractNote={Cobalt magnetic nanoparticles surface functionalised with iminodiacetic acid were evaluated as a nano-particulate solid phase extraction absorbent for copper ions (Cu2+) from environmental water samples. Using an external magnetic field, the collector nanoparticles could be separated from the aqueous phase, and adsorbed ions simply decomplexed using dilute HNO3. Effects of pH, buffer concentration, sample and sorbent volume, extraction equilibrium time, and interfering ion concentration on extraction efficiency were investigated. Optimal conditions were then applied to the extraction of Cu2+ ions from natural water samples, prior to their quantitation using high-performance chelation ion chromatography. The limits of detection (LOD) of the combined extraction and chromatographic method were ~0.1 ng ml−1, based upon a 100-fold preconcentration factor (chromatographic performance; LOD=9.2 ng ml−1 Cu2+), analytical linear range from 20 to 5000 ng mL−1, and relative standard deviations=4.9% (c=1000 ng ml−1, n=7). Accuracy and precision of the combined approach was verified using a certified reference standard estuarine water sample (SLEW-2) and comparison of sample determinations with sector field inductively coupled plasma mass spectrometry. Recoveries from the addition of Cu2+ to impacted estuarine and rain water samples were 103.5% and 108.5%, respectively. Coastal seawater samples, both with and without prior UV irradiation and dissolved organic matter removal were also investigated using the new methodology. The effect of DOM concentration on copper availability was demonstrated.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Guiotto, Anna and Cordone, Valeria and Benedusi, Mascia and Cervellati, Franco and Hayek, Joussef and Cervellati, Carlo and Valacchi, Giuseppe and Pecorelli, Alessandra}, year={2021}, month={Dec} }
 @article{pecorelli_guiotto_cordone_cervellati_benedusi_cervellati_hayek_valacchi_2021, title={Mitochondrial dynamics and quality control pathways impairment in Rett Syndrome and Autism Spectrum Disorder}, volume={177}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2021.08.070}, abstractNote={Furanodiene (FDE) possesses diverse pharmacological activities with high lipophilicity and poor stability. This study prepared FDE loaded PLGA nanoparticles (FDE-PLGA-NPs) and PEGylated PLGA nanoparticles (FDE-PEG-PLGA-NPs) by the spontaneous emulsion solvent diffusion method to improve the stability and bioavailability of FDE.FDE-PLGA-NPs and FDE-PEG-PLGA-NPs were characterized for size and size distribution, surface morphology, zeta-potential and entrapment efficiency. The stability of FDE, FDE-PLGA-NPs and FDE-PEG-PLGA-NPs in physiological fluids (PBS and artificial gastrointestinal fluids) was evaluated. In vitro cellular uptake and transport studies were performed using Caco-2 cell monolayers.The size of FDE-PLGA-NPs and FDE-PEG-PLGA-NPs ranged from 110-140 nm, the entrapment efficiencies were 87.3% and 89.2%, respectively, and the stabilities were enhanced significantly compared with FDE. FDE-PLGA-NPs and FDE-PEG-PLGA-NPs could be taken up by Caco-2 cells freely and transported across the monolayers. While FDE hardly reached to the receptor side, it could be taken up into Caco-2 cell monolayers.These results indicated that FDE-PLGA-NPs, especially FDE-PEG-PLGA-NPs, could enhance the stability and hydrophilicity of FDE and increase the permeation of FDE across Caco-2 cell monolayers.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Guiotto, Anna and Cordone, Valeria and Cervellati, Franco and Benedusi, Mascia and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe}, year={2021}, month={Dec}, pages={S17–S18} }
 @article{pecorelli_cordone_guiotto_cervellati_benedusi_cervellati_hayek_valacchi_2021, title={Mitochondrial dysfunction fuels inflammasome machinery in Autism Spectrum Disorder}, volume={165}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2020.12.410}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Cordone, Valeria and Guiotto, Anna and Cervellati, Franco and Benedusi, Mascia and Cervellati, Carlo and Hayek, Joussef and Valacchi, Giuseppe}, year={2021}, month={Mar} }
 @article{hoskin_pambianchi_pecorelli_grace_therrien_valacchi_lila_2021, title={Novel Spray Dried Algae-Rosemary Particles Attenuate Pollution-Induced Skin Damage}, volume={26}, ISSN={["1420-3049"]}, url={https://doi.org/10.3390/molecules26133781}, DOI={10.3390/molecules26133781}, abstractNote={The present study investigated the effect of spray-dried algae-rosemary particles against pollution-induced damage using ex-vivo human biopsies exposed to diesel engine exhaust (DEE). For this, the complexation of hydroalcoholic rosemary extract with Chlorella (RCH) and Spirulina (RSP) protein powders was conducted. The process efficiency and concentration of rosmarinic acid (RA), carnosic acid (CA), and carnosol (CR) phenolic compounds of both products were compared. The RSP spray-dried production was more efficient, and RSP particles presented higher CR and CA and similar RA concentrations. Therefore, spray-dried RSP particles were prioritized for the preparation of a gel formulation that was investigated for its ability to mitigate pollution-induced skin oxinflammatory responses. Taken altogether, our ex-vivo data clearly demonstrated the ability of RSP gel to prevent an oxinflammatory phenomenon in cutaneous tissue by decreasing the levels of 4-hydroxynonenal protein adducts (4HNE-PA) and active matrix metalloproteinase-9 (MMP-9) as well as by limiting the loss of filaggrin induced by DEE exposure. Our results suggest that the topical application of spirulina-rosemary gel is a good approach to prevent pollution-induced skin aging/damage.}, number={13}, journal={MOLECULES}, publisher={MDPI AG}, author={Hoskin, Roberta and Pambianchi, Erika and Pecorelli, Alessandra and Grace, Mary and Therrien, Jean-Philippe and Valacchi, Giuseppe and Lila, Mary Ann}, year={2021}, month={Jul} }
 @article{pecorelli_mcdaniel_wortzman_nelson_2021, title={Protective effects of a comprehensive topical antioxidant against ozone-induced damage in a reconstructed human skin model}, volume={313}, ISSN={["1432-069X"]}, DOI={10.1007/s00403-020-02083-0}, abstractNote={Abstract}, number={3}, journal={ARCHIVES OF DERMATOLOGICAL RESEARCH}, author={Pecorelli, Alessandra and McDaniel, David H. and Wortzman, Mitchell and Nelson, Diane B.}, year={2021}, month={Apr}, pages={139–146} }
 @article{grillo_fezza_chemi_colangeli_brogi_fazio_federico_papa_relitti_di maio_et al._2021, title={Selective Fatty Acid Amide Hydrolase Inhibitors as Potential Novel Antiepileptic Agents}, volume={12}, ISSN={["1948-7193"]}, DOI={10.1021/acschemneuro.1c00192}, abstractNote={Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a-m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a.}, number={9}, journal={ACS CHEMICAL NEUROSCIENCE}, author={Grillo, Alessandro and Fezza, Filomena and Chemi, Giulia and Colangeli, Roberto and Brogi, Simone and Fazio, Domenico and Federico, Stefano and Papa, Alessandro and Relitti, Nicola and Di Maio, Roberto and et al.}, year={2021}, month={May}, pages={1716–1736} }
 @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{cicaloni_pecorelli_cordone_tinti_rossi_hayek_salvini_tinti_valacchi_2020, title={A proteomics approach to further highlight the altered inflammatory condition in Rett syndrome}, volume={696}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2020.108660}, abstractNote={Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with perturbed redox homeostasis and inflammation, which appear as possible key factors in RTT pathogenesis. In this study, using primary dermal fibroblasts from control and RTT subjects, we performed a proteomic analysis that, together with data mining approaches, allowed us to carry out a comprehensive characterization of RTT cellular proteome. Functional and pathway enrichment analyses showed that differentially expressed proteins in RTT were mainly enriched in biological processes related to immune/inflammatory responses. Overall, by using proteomic data mining as supportive approach, our results provide a detailed insight into the molecular pathways involved in RTT immune dysfunction that, causing tissue and organ damage, can increase the vulnerability of affected patients to unknown endogenous factors or infections.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Cicaloni, Vittoria and Pecorelli, Alessandra and Cordone, Valeria and Tinti, Laura and Rossi, Marco and Hayek, Joussef and Salvini, Laura and Tinti, Cristina and Valacchi, Giuseppe}, year={2020}, month={Dec} }
 @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{pecorelli_cordone_messano_zhang_falone_amicarelli_hayek_valacchi_2020, title={Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation}, volume={28}, ISSN={["2213-2317"]}, DOI={10.1016/j.redox.2019.101334}, abstractNote={Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with an oxinflammatory status. Inflammasomes are multi-protein complexes, responsible for host immune responses against pathogen infections and redox-related cellular stress. Assembly of NLRP3/ASC inflammasome triggers pro-caspase-1 activation, thus, resulting in IL-1β and IL-18 maturation. However, an aberrant activation of inflammasome system has been implicated in several human diseases. Our aim was to investigate the possible role of inflammasome in the chronic subclinical inflammatory condition typical of RTT, by analyzing this complex in basal and lipopolysaccharide (LPS)+ATP-stimulated primary fibroblasts, as well as in serum from RTT patients and healthy volunteers. RTT cells showed increased levels of nuclear p65 and ASC proteins, pro-IL-1β mRNA, and NLRP3/ASC interaction in basal condition, without any further response upon the LPS + ATP stimuli. Moreover, augmented levels of circulating ASC and IL-18 proteins were found in serum of RTT patients, which are likely able to amplify the inflammatory response. Taken together, our findings suggest that RTT patients exhibited a challenged inflammasome machinery at cellular and systemic level, which may contribute to the subclinical inflammatory state feedback observed in this pathology.}, journal={REDOX BIOLOGY}, author={Pecorelli, Alessandra and Cordone, Valeria and Messano, Nicolo and Zhang, Changqing and Falone, Stefano and Amicarelli, Fernanda and Hayek, Joussef and Valacchi, Giuseppe}, year={2020}, month={Jan} }
 @article{sbardella_tundo_cunsolo_grasso_cascella_caputo_santoro_milardi_pecorelli_ciaccio_et al._2020, title={Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations}, volume={1866}, ISSN={["1879-260X"]}, DOI={10.1016/j.bbadis.2020.165793}, abstractNote={Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder which affects about 1: 10000 live births.In > 95% of subjects RTT is caused by a mutation in Methyl-CpG binding protein-2 (MECP2) gene, which encodes for a transcription regulator with pleiotropic genetic/epigenetic activities.The molecular mechanisms underscoring the phenotypic alteration of RTT are largely unknown and this has impaired the development of therapeutic approaches to alleviate signs and symptoms during disease progression.A defective proteasome biogenesis into two skin primary fibroblasts isolated from RTT subjects harbouring non-sense (early-truncating) MeCP2 mutations (i.e., R190fs and R255X) is herewith reported.Proteasome is the proteolytic machinery of Ubiquitin Proteasome System (UPS), a pathway of overwhelming relevance for postmitotic cells metabolism.Molecular, transcription and proteomic analyses indicate that MeCP2 mutations downregulate the expression of one proteasome subunit, α7, and of two chaperones, PAC1 and PAC2, which bind each other in the earliest step of proteasome biogenesis.Furthermore, this molecular alteration recapitulates in neuron-like SH-SY5Y cells upon silencing of MeCP2 expression, envisaging a general significance of this transcription regulator in proteasome biogenesis.girls start to lose cognitive, motor, language and social skills, further developing an autism-like behaviour, which led to prior categorizing of RTT among Autism Spectrum Disorders [1].In more than 95% of cases, RTT is due to a sporadic mutation in Methyl-CpG binding protein-2 (MECP2, Xq28) gene, which encodes a}, number={7}, journal={BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE}, author={Sbardella, Diego and Tundo, Grazia Raffaella and Cunsolo, Vincenzo and Grasso, Giuseppe and Cascella, Raffaella and Caputo, Valerio and Santoro, Anna Maria and Milardi, Danilo and Pecorelli, Alessandra and Ciaccio, Chiara and et al.}, year={2020}, month={Jul} }
 @article{sguizzato_valacchi_pecorelli_boldrini_simeliere_huang_cortesi_esposito_2020, title={Gallic acid loaded poloxamer gel as new adjuvant strategy for melanoma: A preliminary study}, volume={185}, ISSN={["1873-4367"]}, DOI={10.1016/j.colsurfb.2019.110613}, abstractNote={The present study describes the production and characterization of poloxamer gels containing the antioxidant molecule gallic acid. The gels were particularly designed in order to obtain a formulation suitable for administration on the skin to treat melanoma. The polymer concentration was selected after rheological characterization and determination of gel transition temperature. In order to study the gallic acid diffusion, in vitro experiments were performed using Franz cells associated to different membranes. As first approach the gallic acid diffusion was evaluated through synthetic membranes, such as cellulose, nylon, polycarbonate, polytetrafluoroethylene, polyvinylidene fluoride and the commercial Strat-M® membrane. The membranes were employed separately or in association and compared to stratum corneum epidermis membranes, in order to find a system able to reproduce the gallic acid diffusion through the skin. Selected membranes were used for studying gallic acid diffusion from poloxamer gel. It was found that the diffusion of gallic acid was dramatically influenced by the type of membrane, both in the case of the aqueous solution or poloxamer gel. Scratch wound healing and migration assays conducted on human keratinocytes and melanoma cells demonstrated the ability of gallic acid loaded gel to inhibit cellular migration, suggesting its potential as adjuvant strategy for melanoma.}, journal={COLLOIDS AND SURFACES B-BIOINTERFACES}, author={Sguizzato, Maddalena and Valacchi, Giuseppe and Pecorelli, Alessandra and Boldrini, Paola and Simeliere, Fanny and Huang, Nicolas and Cortesi, Rita and Esposito, Elisabetta}, year={2020}, month={Jan} }
 @article{cervellati_trentini_pecorelli_valacchi_2020, title={Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery}, volume={33}, ISSN={["1557-7716"]}, DOI={10.1089/ars.2020.8076}, abstractNote={SIGNIFICANCE
Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer disease (AD), vascular dementia (VAD), Parkinson's disease (PD), multiple sclerosis (MS) are fueled by neuroinflammation, which in turn is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the blood brain barrier loses its integrity as often occurs in the course of these diseases. It has been hypothesized the perpetual bidirectional flux of inflammatory mediators is not a mere "static" collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear.


RECENT ADVANCES
Solid recent evidence clearly suggest that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although at different extent, in the development in brain diseases CRITICAL ISSUE: Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammation-neuroinflammation-neurodegeneration in the pathogenesis of AD, VAD, PD and MS, highlighting the possible cause of the putative downstream component of the axis.


FUTURE DIRECTIONS
Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.}, number={3}, journal={ANTIOXIDANTS & REDOX SIGNALING}, author={Cervellati, Carlo and Trentini, Alessandro and Pecorelli, Alessandra and Valacchi, Giuseppe}, year={2020}, month={Jul}, pages={191–210} }
 @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{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{cicaloni_pecorelli_tinti_rossi_benedusi_cervellati_spiga_santucci_hayek_salvini_et al._2020, title={Proteomic pro fi ling reveals mitochondrial alterations in Rett syndrome}, volume={155}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2020.05.014}, abstractNote={Rett syndrome (RTT) is a pervasive neurodevelopmental disorder associated with mutation in MECP2 gene. Despite a well-defined genetic cause, there is a growing consensus that a metabolic component could play a pivotal role in RTT pathophysiology. Indeed, perturbed redox homeostasis and inflammation, i.e. oxinflammation, with mitochondria dysfunction as the central hub between the two phenomena, appear as possible key contributing factors to RTT pathogenesis and its clinical features. While these RTT-related changes have been widely documented by transcriptomic profiling, proteomics studies supporting these evidences are still limited. Here, using primary dermal fibroblasts from control and patients, we perform a large-scale proteomic analysis that, together with data mining approaches, allow us to carry out the first comprehensive characterization of RTT cellular proteome, showing mainly changes in expression of proteins involved in the mitochondrial network. These findings parallel with an altered expression of key mediators of mitochondrial dynamics and mitophagy associated with abnormal mitochondrial morphology. In conclusion, our proteomic analysis confirms the pathological relevance of mitochondrial dysfunction in RTT pathogenesis and progression.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Cicaloni, Vittoria and Pecorelli, Alessandra and Tinti, Laura and Rossi, Marco and Benedusi, Mascia and Cervellati, Carlo and Spiga, Ottavia and Santucci, Annalisa and Hayek, Joussef and Salvini, Laura and et al.}, year={2020}, month={Aug}, pages={37–48} }
 @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{woodby_penta_pecorelli_lila_valacchi_2020, title={Skin Health from the Inside Out}, volume={11}, ISSN={["1941-1421"]}, DOI={10.1146/annurev-food-032519-051722}, abstractNote={The skin is the main interface between the body and the environment, providing a biological barrier against an array of chemical and physical pollutants (e.g., ultraviolet light, ozone, etc.). Exposure of the skin to these outdoor stressors generates reactive oxygen species (ROS), which can overwhelm the skin's endogenous defense systems (e.g., catalase, vitamins C and E, etc.), resulting in premature skin aging due to the induction of DNA damage, mitochondrial damage, lipid peroxidation, activation of inflammatory signaling pathways, and formation of protein adducts. In this review, we discuss how topical application of antioxidants, including vitamins C and E, carotenoids, resveratrol, and pycnogenol, can be combined with dietary supplementation of these antioxidant compounds in addition to probiotics and essential minerals to protect against outdoor stressor-induced skin damage, including the damage associated with aging.}, journal={ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 11}, author={Woodby, Brittany and Penta, Kayla and Pecorelli, Alessandra and Lila, Mary Ann and Valacchi, Giuseppe}, year={2020}, pages={235–254} }
 @article{pecorelli_cervellati_cordone_amicarelli_hayek_valacchi_2019, title={13-HODE, 9-HODE and ALOX15 as potential players in Rett syndrome OxInflammation}, volume={134}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.02.007}, abstractNote={Mutations in the MECP2 gene are the main cause of Rett syndrome (RTT), a pervasive neurodevelopmental disorder, that shows also multisystem disturbances associated with a metabolic component. The aim of this study was to investigate whether an increased production of oxidized linoleic acid metabolites, specifically 9- and 13-hydroxyoctadecadienoic acids (HODEs), can contribute to the altered the redox and immune homeostasis, suggested to be involved in RTT. Serum levels of 9- and 13-HODEs were elevated in RTT and associated with the expression of arachidonate 15-Lipoxygenase (ALOX15) in peripheral blood mononuclear cells (PBMCs). Omega-3 polyunsaturated fatty acids supplementation has shown to lower HODEs levels in RTT. Statistically significant correlation was demonstrated between the increased plasma HODEs levels and the lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Collectively, these findings reinforce the concept of the key role played by lipid peroxidation in RTT, and the possible ability of omega-3 polyunsaturated fatty acids supplementation in improving the oxinflammation status in RTT.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Cervellati, Carlo and Cordone, Valeria and Amicarelli, Fernanda and Hayek, Joussef and Valacchi, Giuseppe}, year={2019}, month={Apr}, pages={598–603} }
 @article{cordone_pecorelli_benedusi_santini_falone_hayek_amicarelli_valacchi_2019, title={Antiglycative Activity and RAGE Expression in Rett Syndrome}, volume={8}, ISSN={["2073-4409"]}, DOI={10.3390/cells8020161}, abstractNote={Rett syndrome (RTT) is a human neurodevelopmental disorder, whose pathogenesis has been linked to both oxidative stress and subclinical inflammatory status (OxInflammation). Methylglyoxal (MG), a glycolytic by-product with cytotoxic and pro-oxidant power, is the major precursor in vivo of advanced glycation end products (AGEs), which are known to exert their detrimental effect via receptor- (e.g., RAGE) or non-receptor-mediated mechanisms in several neurological diseases. On this basis, we aimed to compare fibroblasts from healthy subjects (CTR) with fibroblasts from RTT patients (N = 6 per group), by evaluating gene/protein expression patterns, and enzymatic activities of glyoxalases (GLOs), along with the levels of MG-dependent damage in both basal and MG-challenged conditions. Our results revealed that RTT is linked to an alteration of the GLOs system (specifically, increased GLO2 activity), that ensures unchanged MG-dependent damage levels. However, RTT cells underwent more pronounced cell death upon exogenous MG-treatment, as compared to CTR, and displayed lower RAGE levels than CTR, with no alterations following MG-treatment, thus suggesting that an adaptive response to dicarbonyl stress may occur. In conclusion, besides OxInflammation, RTT is associated with reshaping of the major defense systems against dicarbonyl stress, along with an altered cellular stress response towards pro-glycating insults.}, number={2}, journal={CELLS}, author={Cordone, Valeria and Pecorelli, Alessandra and Benedusi, Mascia and Santini, Silvano, Jr. and Falone, Stefano and Hayek, Joussef and Amicarelli, Fernanda and Valacchi, Giuseppe}, year={2019}, month={Feb} }
 @article{pambianchi_francesca_pecorelli_woodby_lila_valacchi_2019, title={Blueberries Topical Application Prevents Ozone Induced Cutaneous Inflammasome Activation}, volume={145}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.10.393}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pambianchi, Erika and Francesca, Ferrara and Pecorelli, Alessandra and Woodby, Brittany and Lila, Mary and Valacchi, Giuseppe}, year={2019}, month={Dec}, pages={S148–S148} }
 @article{grillo_chemi_brogi_brindisi_relitti_fezza_fazio_castelletti_perdona_wong_et al._2019, title={Development of novel multipotent compounds modulating endocannabinoid and dopaminergic systems}, volume={183}, ISSN={["1768-3254"]}, DOI={10.1016/j.ejmech.2019.111674}, abstractNote={Polypharmacology approaches may help the discovery of pharmacological tools for the study or the potential treatment of complex and multifactorial diseases as well as for addictions and also smoke cessation. In this frame, following our interest in the development of molecules able to modulate either the endocannabinoid or the dopaminergic system, and given the multiple and reciprocal interconnections between them, we decided to merge the pharmacophoric elements of some of our early leads for identifying new molecules as tools able to modulate both systems. We herein describe the synthesis and biological characterization of compounds 5a-j inspired by the structure of our potent and selective fatty acid amide hydrolase (FAAH) inhibitors (3a-c) and ligands of dopamine D2 or D3 receptor subtypes (4a,b). Notably, the majority of the new molecules showed a nanomolar potency of interaction with the targets of interest. The drug-likeliness of the developed compounds (5a-j) was investigated in silico while hERG affinity, selectivity profile (for some proteins of the endocannabinoid system), cytotoxicity profiles (on fibroblast and astrocytes), and mutagenicity (Ames test) were experimentally determined. Metabolic studies also served to complement the preliminary drug-likeliness profiling for compounds 3a and 5c. Interestingly, after assessing the lack of toxicity for the neuroblastoma cell line (IMR 32), we demonstrated a potential anti-inflammatory profile for 3a and 5c in the same cell line.}, journal={EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY}, author={Grillo, Alessandro and Chemi, Giulia and Brogi, Simone and Brindisi, Margherita and Relitti, Nicola and Fezza, Filomena and Fazio, Domenico and Castelletti, Laura and Perdona, Elisabetta and Wong, Andrea and et al.}, year={2019}, month={Dec} }
 @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} }
 @misc{pecorelli_woodby_prieux_valacchi_2019, title={Involvement of 4-hydroxy-2-nonenal in pollution-induced skin damage}, volume={45}, ISSN={["1872-8081"]}, DOI={10.1002/biof.1513}, abstractNote={Abstract}, number={4}, journal={BIOFACTORS}, author={Pecorelli, Alessandra and Woodby, Brittany and Prieux, Roxane and Valacchi, Giuseppe}, year={2019}, month={Jul}, pages={536–547} }
 @article{ietta_valacchi_benincasa_pecorelli_cresti_maioli_2019, title={Multiple mechanisms of Rottlerin toxicity in A375 melanoma cells}, volume={45}, ISSN={["1872-8081"]}, DOI={10.1002/biof.1551}, abstractNote={Abstract}, number={6}, journal={BIOFACTORS}, author={Ietta, Francesca and Valacchi, Giuseppe and Benincasa, Linda and Pecorelli, Alessandra and Cresti, Laura and Maioli, Emanuela}, year={2019}, pages={920–929} }
 @article{pecorelli_valacchi_cordone_hayek_2019, title={OxInflammation as a Aossible new Player in Rett Syndrome Pathophysiology}, volume={145}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.10.396}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Valacchi, Giuseppe and Cordone, Valeria and Hayek, Joussef}, year={2019}, month={Dec}, pages={S149–S149} }
 @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{woodby_pambianchi_francesca_messano_pecorelli_therrien_valacchii_2019, title={Redox-Regulation of Antimicrobial Peptides}, volume={145}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.10.142}, abstractNote={Traditionally, clinical psychomotor skills are taught through videos and demonstration by faculty, which does not allow for the visualization of internal structures and anatomical landmarks that would enhance the learner skill performance.Sophomore and junior nursing students attending a large Midwestern institution (N = 69) participated in this mixed methods study. Students demonstrated their ability to place a nasogastric tube (NGT) after being randomly assigned to usual training (control group) or an iPad anatomy-augmented virtual simulation training module (augmented reality [AR] group). The ability of the participants to demonstrate competence in placing the NGT was assessed using a 17-item competency checklist. After the demonstration, students completed a survey to elicit information about students' level of training, prior experience with NGT placement, satisfaction with the AR technology, and perceptions of AR as a potential teaching tool for clinical skills training.The ability to correctly place the NGT through all the checklist items was statistically significant in the AR group compared with the control group (p = .011). Eighty-six percent of participants in the AR group rated AR as superior/far superior with other procedural training programs to which they had been exposed, whereas, only 5.9% of participants in the control group rated the control program as superior/far superior (p < .001).Overall, the AR module was better received compared with the control group with regard to realism, identifying landmarks, visualization of internal organs, ease of use, usefulness, and promoting learning and understanding.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Woodby, Brittany and Pambianchi, Erika and Francesca, Ferrara and Messano, Nicolo and Pecorelli, Alessandra and Therrien, Jean Philippe and Valacchii, Giuseppe}, year={2019}, month={Dec}, pages={S54–S55} }
 @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{pecorelli_cordone_falone_romani_benedusi_hayek_amicarelli_valacchi_2018, title={Inflammasome involvement in Rett syndrome subclinical inflammation}, volume={128}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2018.10.262}, abstractNote={Mutations in X-linked MECP2 gene cause most cases of Rett syndrome (RTT), a rare neurodevelopmental disorder typically affecting girls. Although RTT is mainly a neurological disorder, affected patients show many systemic abnormalities including redox imbalance, mitochondrial dysfunctions, metabolic alterations, gastrointestinal disorders, breathing disturbances and recurrent infections. Growing evidence highlights the importance of inflammation and immune system dysregulation in RTT pathophysiological mechanisms. Inflammasomes, cytoplasmic multi-protein complexes, regulate host immune response against pathogen infections and cellular stress. Assembly of NLRP3/ASC inflammasome leads to pro-caspase-1 activation and subsequent IL-1β and IL-18 maturation and secretion. Inflammasome dysregulation drives pathological conditions in a wide variety of human diseases. To investigate the possible role of inflammasome in the persistent and subclinical inflammatory status observed in RTT patients, we treated primary dermal fibroblasts from RTT and control subjects with LPS followed by ATP Analysis of confocal immunofluorescence showed a significant increased colocalization for NLRP3 and ASC signals in unstimulated RTT fibroblasts. This result parallels with a higher level of ASC-b isoform in untreated RTT cells, as determined by immunoblotting. Interestingly, while control fibroblasts responded to LPS/ATP with increased NLRP3/ASC colocalization, RTT fibroblasts appeared to be unresponsive to the treatment, showing a decreased NLRP3/ASC colocalization and no change in ASC-b levels. In addition, procaspase-1 and caspase-1 protein levels were significantly lower in unstimulated RTT, but casp-1/procasp-1 ratio was higher in RTT than control fibroblasts. Finally, IL-1β gene expression was higher in unstimulated RTT cells, but showing no change after LPS/ATP treatment. Taken together, our results suggest a possible basal activation of inflammasome in RTT cells that, on the other hand, appear to be unable to respond properly at the inflammatory stimulus. The dysregulated inflammasome activity could contribute to the subclinical inflammatory status of RTT, thereby identifying a new potential target for therapeutic intervention.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Pecorelli, Alessandra and Cordone, Valeria and Falone, Stefano and Romani, Arianna and Benedusi, Mascia and Hayek, Joussef and Amicarelli, Fernanda and Valacchi, Giuseppe}, year={2018}, month={Nov}, pages={S108–S109} }
 @article{romani_cervellati_muresan_belmonte_pecorelli_cervellati_benedusi_evelson_valacchi_2018, title={Keratinocytes oxidative damage mechanisms related to airbone particle matter exposure}, volume={172}, ISSN={["0047-6374"]}, DOI={10.1016/j.mad.2017.11.007}, abstractNote={Epidemiological evidences have correlated airbone particulate matter (PM) to adverse health effects, mainly linking to pulmonary and cardiovascular disease. Nevertheless, only recently, some studies reported detrimental effects of PM on other organs such as skin. In a recent work, we have reported increased oxidative and inflammatory responses in Reconstituted Human Epidermis (RHE) exposed to ambient particles (CAPs) and we also demonstrated the ability of CAPs to penetrate the skin tissue. The present study was aimed to better understand the cellular mechanisms beyond the oxidative changes induced by CAPs (5–10–25 μg/mL) in human immortalized keratinocytes (HaCaT). After 24 h of treatment, CAPs were able to enter the cells leading to a decrease in viability, increased levels of 4-hydroxinonenal products (4-HNE) and IL-1α release. Overall these data, suggest lipid and protein oxidative damage, as well as an increase of inflammatory response after being challenged with CAPs. In addition, 3 h after CAPs exposure we found a significant increase in NF-kB and Nrf2 translocation into the nucleus. In contrast, no differences in gene expression and enzymatic activity of Nrf2 target genes were detected. This last finding could be explained by the ability of CAPs to possibly alter the binding of Nrf2 to the ARE DNA sequence.}, journal={MECHANISMS OF AGEING AND DEVELOPMENT}, author={Romani, Arianna and Cervellati, Carlo and Muresan, Ximena M. and Belmonte, Giuseppe and Pecorelli, Alessandra and Cervellati, Franco and Benedusi, Mascia and Evelson, Pablo and Valacchi, G.}, year={2018}, month={Jun}, pages={86–95} }
 @misc{valacchi_virgili_cervellati_pecorelli_2018, title={OxInflammation: From Subclinical Condition to Pathological Biomarker}, volume={9}, ISSN={["1664-042X"]}, DOI={10.3389/fphys.2018.00858}, abstractNote={Inflammation is a complex systemic response evolved to cope with cellular injury, either due to infectious agents or, in general, with sporadic events challenging tissue integrity and function. Researchers involved in different fields have the tendency to look at the inflammatory response with different angles, according to their specific interest. Established its complexity, one of the most evident features of the inflammatory response is the generation of a pro-oxidative environment due to the production of high fluxes of pro-oxidant species. This production begins locally, close to the sites of tissue damage or infection, but eventually becomes a chronic challenge for the organism, if the inflammatory response is not properly controlled. In this review, we focus on this specific aspect of chronic, low-level sub-clinical inflammatory response. We propose the term “OxInflammation” as a novel operative term describing a permanent pro-oxidative feature that interact, in a positive feed-back manner, to a not yet clinically detectable inflammatory process, leading in a long run (chronically) to a systemic/local damage, as a consequence of the cross talk between inflammatory, and oxidative stress mediators. Therefore, it could be useful to analyze inflammatory markers in pathologies where there is an alteration of the redox homeostasis, although an inflammatory status is not clinically evident.}, journal={FRONTIERS IN PHYSIOLOGY}, author={Valacchi, Giuseppe and Virgili, Fabio and Cervellati, Carlo and Pecorelli, Alessandra}, year={2018}, month={Jul} }
 @article{sticozzi_pecorelli_romani_belmonte_cervellati_maioli_lila_gervellati_valacchi_2018, title={Tropospheric ozone affects SRB1 levels via oxidative post-translational modifications in lung cells}, volume={126}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2018.07.007}, abstractNote={Exposure to air pollution is associated with increased respiratory morbidities and susceptibility to lung dysfunction. Ozone (O3) is commonly recognized as one of the most noxious air pollutant and has been associated with several lung pathologies. It has been demonstrated that decreased lung disorder severity and incidence are connected with the consumption of a diet rich in fruits and vegetables, suggesting that higher intake of dietary micronutrients and phytoactive compounds can be beneficial. However, dietary supplementation - i.e. vitamin E (α-tocopherol) or vitamin A - has not always been effective in improving pulmonary function. Recently, research on the role of nutritional antioxidants on human health has focused more on studying their uptake at the cellular level rather than their effective ability to scavenge reactvive oxygen species (ROS). The Scavenger Receptor B1 (SRB1) has been shown to play a prominent role in the uptake, delivery and regulation of vitamin E in the lung. Given the importance of SRB1 in maintaining lung tissue in a healthy condition, we hypothesize that its expression could be modulated by pollution exposure, which thus could indirectly affect the uptake and/or delivery of lipophilic substances, such as vitamin E. To characterize the molecular mechanism involved in the redox modulation of SRB1, its cellular levels were assessed in human alveolar epithelial cells after O3 exposure. The results demonstrated that O3 induced the loss of SRB1 protein levels. This decline seems to be driven by hydrogen peroxide (H2O2) as a consequence of an increased activation of cellular NADPH oxidase (NOX), as demonstrated by the use of NOX inhibitors or catalase that reversed this effect. Furthermore, O3 caused the formation of SRB1-aldheyde adducts (4-hydroxy-2-nonenal) and the consequent increase of its ubiquitination, a mechanism that could account for SRB1 protein loss.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Sticozzi, Claudia and Pecorelli, Alessandra and Romani, Arianna and Belmonte, Giuseppe and Cervellati, Franco and Maioli, Emanuela and Lila, Mary Ann and Gervellati, Carlo and Valacchi, Giuseppe}, year={2018}, month={Oct}, pages={287–295} }
 @misc{valacchi_pecorelli_cervellati_hayek_2017, title={4-hydroxynonenal protein adducts: Key mediator in Rett syndrome oxinflammation}, volume={111}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2016.12.045}, abstractNote={In the last 15 years a strong correlation between oxidative stress (OxS) and Rett syndrome (RTT), a rare neurodevelopmental disorder known to be caused in 95% of the cases, by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, has been well documented. Here, we revised, summarized and discussed the current knowledge on the role of lipid peroxidation byproducts, with special emphasis on 4-hydroxynonenal (4HNE), in RTT pathophysiology. The posttranslational modifications of proteins via 4HNE, known as 4HNE protein adducts (4NHE-PAs), causing detrimental effects on protein functions, appear to contribute to the clinical severity of the syndrome, since their levels increase significantly during the subsequent 4 clinical stages, reaching the maximum degree at stage 4, represented by a late motor deterioration. In addition, 4HNE-PA are only partially removed due to the compromised functionality of the proteasome activity, contributing therefore to the cellular damage in RTT. All this will lead to a characteristic subclinical inflammation, defined “OxInflammation”, derived by a positive feedback loop between OxS byproducts and inflammatory mediators that in a long run further aggravates the clinical features of RTT patients. Therefore, in a pathology completely orphan of any therapy, aiming 4HNE as a therapeutic target could represent a coadjuvant treatment with some beneficial impact in these patients.‬‬‬}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Valacchi, Giuseppe and Pecorelli, Alessandra and Cervellati, Carlo and Hayek, Joussef}, year={2017}, month={Oct}, pages={270–280} }
 @article{brogi_ramunno_savi_chemi_alfano_pecorelli_pambianchi_galatello_compagnoni_focher_et al._2017, title={First dual AK/GSK-3 beta inhibitors endowed with antioxidant properties as multifunctional, potential neuroprotective agents}, volume={138}, ISSN={["1768-3254"]}, DOI={10.1016/j.ejmech.2017.06.017}, abstractNote={The manuscript deals with the design, synthesis and biological evaluation of novel benzoxazinone-based and indole-based compounds as multifunctional neuroprotective agents. These compounds inhibit human adenosine kinase (hAK) and human glycogen synthase kinase 3 beta (hGSK-3β) enzymes. Computational analysis based on a molecular docking approach underlined the potential structural requirements for simultaneously targeting both proteins' allosteric sites. In silico hints drove the synthesis of appropriately decorated benzoxazinones and indoles (5a-s, and 6a-c) and biochemical analysis revealed their behavior as allosteric inhibitors of hGSK-3β. For both our hit 4 and the best compounds of the series (5c,l and 6b) the potential antioxidant profile was assessed in human neuroblastoma cell lines (IMR 32, undifferentiated and neuronal differentiated), by evaluating the protective effect of selected compounds against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Results showed a strong efficacy of the tested compounds, even at the lower doses, in counteracting the induced oxidative stress (50 μM of H2O2) and in preventing ROS formation. In addition, the tested compounds did not show any cytotoxic effect determined by the LDH release, at the concentration range analyzed (from 0.1 to 50 μM). This study allowed the identification of compound 5l, as the first dual hAK/hGSK-3β inhibitor reported to date. Compound 5l, which behaves as an effective antioxidant, holds promise for the development of new series of potential therapeutic agents for the treatment of neurodegenerative diseases characterized by an innovative pharmacological profile.}, journal={EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY}, author={Brogi, Simone and Ramunno, Anna and Savi, Lida and Chemi, Giulia and Alfano, Gloria and Pecorelli, Alessandra and Pambianchi, Erika and Galatello, Paola and Compagnoni, Giulia and Focher, Federico and et al.}, year={2017}, month={Sep}, pages={438–457} }
 @article{fallacara_vertuani_panozzo_pecorelli_valacchi_manfredini_2017, title={Novel Artificial Tears Containing Cross-Linked Hyaluronic Acid: An In Vitro Re-Epithelialization Study}, volume={22}, ISSN={["1420-3049"]}, DOI={10.3390/molecules22122104}, abstractNote={Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing, improving tissue health. To the best of our knowledge, only a few recent studies have investigated cross-linked HA (HA-CL) in eye drops for human applications. This work consists in an in vitro evaluation of the re-epithelialization ability of two different preparations containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5-diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE) staining were evaluated. In addition, to understand the molecular basis of the re-epithelialization properties, cyclin D1 levels were assessed by western blot. The results showed no cellular toxicity, a slight decrease in IL-8 release, and restoration of epithelium integrity when the wounded 3D model was treated with S1 and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and S2.}, number={12}, journal={MOLECULES}, author={Fallacara, Arianna and Vertuani, Silvia and Panozzo, Giacomo and Pecorelli, Alessandra and Valacchi, Giuseppe and Manfredini, Stefano}, year={2017}, month={Dec} }
 @article{cavicchio_benedusi_pambianchi_pecorelli_cervellati_savelli_calamandrei_maellaro_rispoli_maioli_et al._2017, title={Potassium Ascorbate with Ribose: Promising Therapeutic Approach for Melanoma Treatment}, volume={2017}, ISSN={["1942-0994"]}, DOI={10.1155/2017/4256519}, abstractNote={While surgery is the definitive treatment for early-stage melanoma, the current therapies against advanced melanoma do not yet provide an effective, long-lasting control of the lesions and a satisfactory impact on patient survival. Thus, research is also focused on novel treatments that could potentiate the current therapies. In the present study, we evaluated the effect of potassium ascorbate with ribose (PAR) treatment on the human melanoma cell line, A375, in 2D and 3D models. In the 2D model, in line with the current literature, the pharmacological treatment with PAR decreased cell proliferation and viability. In addition, an increase in Connexin 43 mRNA and protein was observed. This novel finding was confirmed in PAR-treated melanoma cells cultured in 3D, where an increase in functional gap junctions and a higher spheroid compactness were observed. Moreover, in the 3D model, a remarkable decrease in the size and volume of spheroids was observed, further supporting the treatment efficacy observed in the 2D model. In conclusion, our results suggest that PAR could be used as a safe adjuvant approach in support to conventional therapies for the treatment of melanoma.}, journal={OXIDATIVE MEDICINE AND CELLULAR LONGEVITY}, author={Cavicchio, Carlotta and Benedusi, Mascia and Pambianchi, Erika and Pecorelli, Alessandra and Cervellati, Franco and Savelli, Vinno and Calamandrei, Duccio and Maellaro, Emilia and Rispoli, Giorgio and Maioli, Emanuela and et al.}, year={2017} }