@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={Cutaneous tissues is among the main target of outdoor stressors such as ozone (O3 ), particulate matter (PM), and ultraviolet radiation (UV) all involved in inducing extrinsic skin aging. Only a few reports have studied the multipollutant interaction and its effect on skin damage. In the present work, we intended to evaluate the ability of pollutants such as O3 and PM to further aggravate cutaneous UV damage. In addition, the preventive properties of a cosmeceutical formulation mixture (AOX mix) containing 15% vitamin C (L-ascorbic acid), 1% vitamin E (α-tocopherol) and 0.5% ferulic acid was also investigated. Skin explants obtained from three different subjects were exposed to 200 mJ UV light, 0.25 ppm O3 for 2 h, and 30 min of diesel engine exhaust (DEE), alone or in combination for 4 days (time point D1 and D4). The results showed a clear additive effect of O3 and DEE in combination with UV in terms of keratin 10, Desmocollin and Claudin loss. In addition, the multipollutant exposure significantly induced the inflammatory response measured as NLRP1/ASC co-localization suggesting the activation of the inflammasome machinery. Finally, the loss of Aquaporin3 was also affected by the combined outdoor stressors. Furthermore, daily topical pre-treatment with the AOX Mix significantly prevented the cutaneous changes induced by the multipollutants. In conclusion, this study is among the first to investigate the combined effects of three of the most harmful outdoor stressors on human skin and confirms that daily topical of an antioxidant application may prevent pollution-induced skin damage.}, 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{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{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 Being the more apparent organ exposed to the outdoor stressors, the effect of pollution on the skin has been widely studied in the last few decades. Although UV light is known as the most aggressive stressor to which our cutaneous tissue is daily exposed, other components of the tropospheric pollution have also shown to affect skin health and functionality. Among them, ozone has been proven to be one of the most toxic due to its high reactivity with the epidermal lipids. Studying the cutaneous effect of pollution in a laboratory setting presents challenges, therefore it becomes critical to employ appropriate and tailored models that aim to answer specific questions. Several skin models are available nowadays: in vitro models (2D cell lines and 3D cutaneous tissues), ex vivo skin explants and in vivo approaches (animals and humans). Although in the last 20 years researchers developed skin models that closely resemble human skin (3D cutaneous tissues), ex vivo skin explants still remain one of the best models to study cutaneous responses. Unfortunately, one important cutaneous property that is not present in the traditional ex vivo human skin explants is the physiological tension, which has been shown to be a cardinal player in skin structure, homeostasis, functional properties and responses to external stimuli. For this reason, in this study, to confirm and further comprehend the harmful mechanism of ozone exposure on the integumentary system, we have performed experiments using the state of art in cutaneous models: the innovative TenSkin™ model in which ex vivo human skin explants are cultured under physiologically relevant tension during the whole experimental procedure. Specifically, we were interested in corroborating previous findings showing that ozone exposure modulates the expression of cutaneous antimicrobial peptides (AMPs). The present work demonstrates that cutaneous exposure to ozone induces AMPs gene and protein levels (CAMP/LL-37, hBD2, hBD3) and that the presence of tension can further modulate their expression. In addition, different responses between tension and non-tension cultured skin were also observed during the evaluation of OxInflammatory markers [cyclooxygenase-2 (COX2), aryl hydrocarbon receptor (AhR), matrix-metallo-proteinase 9 (MMP9) and 4-hydroxy-nonenal (4HNE)]. This current study supports our previous findings confirming the ability of pollution to induce the cutaneous expression of AMPs via redox signaling and corroborates the principle that skin explants are a good and reliable model to study skin responses even though it underlines the need to holistically consider the role of skin tension before extrapolating the data to real life.}, 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{benedusi_kerob_guiotto_cervellati_ferrara_pambianchi_2023, title={Topical Application of M89PF Containing Vichy Mineralising Water and Probiotic Fractions Prevents Cutaneous Damage Induced by Exposure to UV and O3}, volume={16}, ISSN={["1178-7015"]}, DOI={10.2147/CCID.S414011}, abstractNote={Purpose Exposure of the skin to ultraviolet radiation (UV) or ozone (O3) results in stressed skin, leading to the alteration of the skin physical barrier and defence functions. In this work, the preventive benefit of a dermocosmetic, M89PF, containing Vichy mineralising water, probiotic fractions, antioxidant vitamins and hyaluronic acid, in the alteration of skin physical barrier and skin defence functions after exposure to O3 and UV, alone or combined, was assessed. Methods Untreated and treated (M89PF) skin explants were exposed to O3, to UV rays or to O3+UV. Immunofluorescence was performed for skin barrier, oxidative stress, and inflammatory markers after one and four days of exposure to the pollutants. Results M89PF significantly (p≤0.05) prevented the decrease of the expression level of different skin barrier markers, and significantly (p≤0.05) prevented the induction of OxInflammatory markers and inflammasome components by UV, O3, or both combined. Conclusion M89PF prevents skin barrier damage, as well as oxidative stress and inflammatory markers induced by exposome factors, such as UV, O3, or both combined.}, journal={CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY}, author={Benedusi, Mascia and Kerob, Delphine and Guiotto, Anna and Cervellati, Franco and Ferrara, Francesca and Pambianchi, Erika}, year={2023}, pages={1769–1776} }
 @article{valacchi_pambianchi_coco_pulliero_izzotti_2022, title={MicroRNA Alterations Induced in Human Skin by Diesel Fumes, Ozone, and UV Radiation}, volume={12}, ISSN={["2075-4426"]}, DOI={10.3390/jpm12020176}, abstractNote={Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants.}, number={2}, journal={JOURNAL OF PERSONALIZED MEDICINE}, author={Valacchi, Giuseppe and Pambianchi, Erika and Coco, Simona and Pulliero, Alessandra and Izzotti, Alberto}, year={2022}, month={Feb} }
 @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{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} }
 @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{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{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{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{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_sticozzi_pambianchi_villetti_civelli_valacchi_facchinetti_2020, title={The PDE4 inhibitor CHF6001 affects keratinocyte proliferation via cellular redox pathways}, volume={685}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2020.108355}, abstractNote={Psoriasis is a skin disease characterized by abnormal keratinocyte proliferation and inflammation. Currently, there are no cures for this disease, so the goal of treatment is to decrease inflammation and slow down the associated rapid cell growth and shedding. Recent advances have led to the usage of phosphodiesterase 4 (PDE4) inhibitors for treatment of this condition. For example, apremilast is an oral, selective PDE4 inhibitor that is able to reduce skin inflammation and is Food and Drug Administration (FDA)-approved to treat adults with moderate to severe psoriasis and/or psoriatic arthritis. However, common target-related adverse events, including diarrhea, nausea, headache, and insomnia limit the usage of this drug. To circumvent these effects, the usage of PDE4 inhibitors specifically designed for topical treatment, such as CHF6001, may combine local anti-inflammatory activity with limited systemic exposure, improving tolerability. In this study, we showed that CHF6001, currently undergoing clinical development for COPD, suppresses human keratinocyte proliferation as assessed via BrdU incorporation. We also observed decreased re-epithelialization in a scratch-wound model after CHF6001 treatment. At the molecular level, CHF6001 inhibited translocation of phosphorylated NF-κB subunit p65, promoting loss of nuclear cyclin D1 accumulation and an increase of cell cycle inhibitor p21. Furthermore, CHF6001 decreased oxidative stress, measured by assessing lipid peroxidation (4-HNE adduct formation), through the inactivation of the NADPH oxidase. These results suggest that CHF6001 has the potential to treat skin disorders associated with hyperproliferative keratinocytes, such as psoriasis by targeting oxidative stress, abnormal re-epithelization, and inflammation.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Woodby, Brittany and Sticozzi, Claudia and Pambianchi, Erika and Villetti, Gino and Civelli, Maurizio and Valacchi, Giuseppe and Facchinetti, Fabrizio}, year={2020}, month={May} }
 @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{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{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{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} }