@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_prieux_woodby_valacchi_2021, title={Inflammasome Activation in Pollution-Induced Skin Conditions}, volume={147}, ISSN={["1529-4242"]}, DOI={10.1097/PRS.0000000000007617}, abstractNote={SUMMARY
Exposure to air pollutants has been now associated with detrimental effects on a variety of organs, including the heart, lungs, GI tract, and brain. However, recently it has become clear that pollutant exposure can also promote the development/exacerbation of a variety of skin conditions, including premature aging, psoriasis, acne, and atopic dermatitis. Although the molecular mechanisms by which pollutant exposure results in these cutaneous pathological manifestations, it has been noticed that an inflammatory status is a common denominator of all those skin conditions. For this reason, recently, the activation of a cytosolic multiprotein complex involved in inflammatory responses (the inflammasome) that could promote the maturation of proinflammatory cytokines interleukin-1β and interleukin-18 has been hypothesized to play a key role in pollution-induced skin damage. In this review, we summarize and propose the cutaneous inflammasome as a novel target of pollutant exposure and the eventual usage of inflammasome inhibitor as new technologies to counteract pollution-induced skin damage. Possibly, the ability to inhibit the inflammasome activation could prevent cutaneous inflammaging and ameliorate the health and appearance of the skin.}, number={1S-2}, journal={PLASTIC AND RECONSTRUCTIVE SURGERY}, author={Ferrara, Francesca and Prieux, Roxane and Woodby, Brittany and Valacchi, Giuseppe}, year={2021}, month={Jan}, pages={15S–24S} }
 @misc{woodby_arnold_valacchi_2021, title={SARS-CoV-2 infection, COVID-19 pathogenesis, and exposure to air pollution: What is the connection?}, volume={1486}, ISSN={["1749-6632"]}, DOI={10.1111/nyas.14512}, abstractNote={Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS‐CoV‐2 infection and COVID‐19–associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID‐19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD‐19–associated immunopathology, enhancing virus‐induced tissue inflammation and damage.}, number={1}, journal={ANNALS OF THE NEW YORK ACADEMY OF SCIENCES}, author={Woodby, Brittany and Arnold, Michelle M. and Valacchi, Giuseppe}, year={2021}, month={Feb}, pages={15–38} }
 @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{scott_woodby_ulicny_raikhy_orr_songock_bodily_2020, title={Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance}, volume={94}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.01582-19}, abstractNote={Persistent human papillomavirus infections can cause a variety of significant cancers. The ability of HPV to persist depends on evasion of the host immune system. In this study, we show that the HPV16 E5 protein can suppress an important aspect of the host immune response. In addition, we find that the E5 protein is important for helping the virus avoid integration into the host genome, which is a frequent step along the pathway to cancer development. ABSTRACT Human papillomaviruses (HPVs) infect keratinocytes of stratified epithelia. Long-term persistence of infection is a critical risk factor for the development of HPV-induced malignancies. Through the actions of its oncogenes, HPV evades host immune responses to facilitate its productive life cycle. In this work, we discovered a previously unknown function of the HPV16 E5 oncoprotein in the suppression of interferon (IFN) responses. This suppression is focused on keratinocyte-specific IFN-κ and is mediated through E5-induced changes in growth factor signaling pathways, as identified through phosphoproteomics analysis. The loss of E5 in keratinocytes maintaining the complete HPV16 genome results in the derepression of IFNK transcription and subsequent JAK/STAT-dependent upregulation of several IFN-stimulated genes (ISGs) at both the mRNA and protein levels. We also established a link between the loss of E5 and the subsequent loss of genome maintenance and stability, resulting in increased genome integration. IMPORTANCE Persistent human papillomavirus infections can cause a variety of significant cancers. The ability of HPV to persist depends on evasion of the host immune system. In this study, we show that the HPV16 E5 protein can suppress an important aspect of the host immune response. In addition, we find that the E5 protein is important for helping the virus avoid integration into the host genome, which is a frequent step along the pathway to cancer development.}, number={2}, journal={JOURNAL OF VIROLOGY}, author={Scott, Matthew L. and Woodby, Brittany L. and Ulicny, Joseph and Raikhy, Gaurav and Orr, A. Wayne and Songock, William K. and Bodily, Jason M.}, year={2020}, month={Jan} }
 @article{ercoli_finetti_woodby_belmonte_miracco_valacchi_trabalzini_2020, title={KRIT1 as a possible new player in melanoma aggressiveness}, volume={691}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2020.108483}, abstractNote={Krev interaction trapped protein 1 (KRIT1) is a scaffold protein known to form functional complexes with distinct proteins, including Malcavernin, PDCD10, Rap1 and others. It appears involved in several cellular signaling pathways and exerts a protective role against inflammation and oxidative stress. KRIT1 has been studied as a regulator of endothelial cell functions and represents a determinant in the pathogenesis of Cerebral Cavernous Malformation (CCM), a cerebrovascular disease characterized by the formation of clusters of abnormally dilated and leaky blood capillaries, which predispose to seizures, neurological deficits and intracerebral hemorrhage. Although KRIT1 is ubiquitously expressed, few studies have described its involvement in pathologies other than CCM including cancer. Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic propensity. Despite the numerous efforts made to define the signaling pathways activated during melanoma progression, the molecular mechanisms at the basis of melanoma growth, phenotype plasticity and resistance to therapies are still under investigation.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Ercoli, Jasmine and Finetti, Federica and Woodby, Brittany and Belmonte, Giuseppe and Miracco, Clelia and Valacchi, Giuseppe and Trabalzini, Lorenza}, year={2020}, month={Sep} }
 @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{valacchi_magnani_woodby_maria ferreira_evelson_2020, title={Particulate Matter Induces Tissue OxInflammation: From Mechanism to Damage}, volume={33}, ISSN={["1557-7716"]}, DOI={10.1089/ars.2019.8015}, abstractNote={SIGNIFICANCE
Oxidative stress and oxidative damage are central hypothetical mechanisms for the adverse effects of airborne particulate matter (PM). Activation of inflammatory cells capable of generating reactive oxygen and nitrogen species is another proposed damage pathway. Understanding the interplay between these responses can help us understand the adverse health effects attributed to breathing polluted air.


CRITICAL ISSUES
Reactive oxygen species (ROS) are generated during phagocytosis of the particles, leading to enhancement of oxidative stress and triggering the inflammatory response. The activation of inflammatory signaling pathways results in the release of cytokines, and other mediators that can further induce ROS production by activating endogenous enzymes, leading to a positive feedback loop, which can aggravate the effects triggered by PM exposure. Recent advances: The consequences of PM exposure on different organs results in oxidative damage, decreased function, and inflammation, which can lead to the development/exacerbation of proinflammatory disorders. Mitochondrial damage is also an important event in PM-induced cytotoxicity.


FUTURE DIRECTIONS
Further research is required to elucidate the exact mechanisms by which PM exposure results in adverse health effects, in terms of the relationship between the redox responses triggered by the presence of the particles and the inflammation observed in the different organs, so the development/exacerbation of PM-associated health problems can be prevented.}, number={4}, journal={ANTIOXIDANTS & REDOX SIGNALING}, author={Valacchi, Giuseppe and Magnani, Natalia and Woodby, Brittany and Maria Ferreira, Sandra and Evelson, Pablo}, year={2020}, month={Aug}, pages={308–326} }
 @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's d = 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's d = 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's d = 0.450). The patterns of change in plasma IL-18 and IL-37 did not differ between the FLAV and PL trials (interaction effects, p = .388, .716, respectively). These data indicate that 2-week FLAV ingestion mitigated inflammasome activation, with a corresponding decrease in IL-1β release in cyclists after a 75-km cycling time trial. The data from this study support the strategy of ingesting high amounts of FLAV to mitigate postexercise inflammation.}, number={6}, journal={INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM}, author={Nieman, David C. and Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Hoyle, Andrew T. and Simonson, Andrew and Valacchi, Giuseppe}, year={2020}, month={Nov}, pages={396–404} }
 @article{ferrara_pambianchi_pecorelli_woodby_messano_therrien_lila_valacchi_2020, title={Redox regulation of cutaneous inflammasome by ozone exposure}, volume={152}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2019.11.031}, abstractNote={Several pollutants have been shown to affect skin physiology, among which ozone (O3) is one of the most toxic. Prolonged exposure to O3 leads to increased oxidative damage and cutaneous inflammation. The correlation between O3 exposure and inflammatory cutaneous conditions (atopic dermatitis, psoriasis, acne and eczema) has been already suggested, although the mechanism involved is still unclear. In the last few decades, a new multiprotein complex, the inflammasome, has been discovered and linked to tissue inflammation, including inflammatory skin conditions. The inflammasome activates inflammatory responses and contributes to the maturation of cytokines such as interleukin 1β (IL-1β) and interleukin 18. This complex is also responsive to reactive oxygen species (ROS), which plays a role in triggering the activation of the complex. On this basis it is possible hypothesize that the activation of the inflammasome could be the link between the inflammatory skin conditions associated to O3 exposure. In the present work, the ability of O3 to induce inflammasome activation was determined in different skin models, ranging from 2D (human keratinocytes) to 3D models in vitro and ex vivo. Results clearly showed that O3 exposure increased both transcript and protein levels of the main inflammasome complex, such as ASC and caspase-1. Furthermore, by using both immunofluorescence and an ASC oligomerization assay the formation of the complex was determined together with increased secreted levels of both IL-18 and IL-1β. Of note is that H2O2 and to a less extent 4HNE (both considered the main mediators of O3 interaction with cellular membranes) were also able to activate skin inflammasome while the use of catalase prevents the activation. This study demonstrated that O3 can activate cutaneous inflammasome in a redox dependent manner suggesting a possible role of this new pathway in pollution induced inflammatory skin conditions.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Ferrara, Francesca and Pambianchi, Erika and Pecorelli, Alessandra and Woodby, Brittany and Messano, Nicolo and Therrien, Jean-Philippe and Lila, Mary Ann and Valacchi, Giuseppe}, year={2020}, month={May}, pages={561–570} }
 @article{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. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 11 is March 25, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, 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{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{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={The effects of environmental insults on human health are a major global concern. Some of the most noxious pollutants that humans are exposed to include ozone (O3), particulate matter (PM), and cigarette smoke (CS). Since the skin is the first line of defense against environmental insults, it is considered one of the main target organs for the harmful insults of air pollution. Thus, there is solid evidence that skin pathologies such as premature aging, atopic dermatitis (AD), and psoriasis are associated with pollutant exposure; all of these skin conditions are also associated with an altered redox status. Therefore, although the mechanisms of action and concentrations of O3, PM, and CS that we are exposed to differ, exposure to all of these pollutants is associated with the development of similar skin conditions due to the fact that all of these pollutants alter redox homeostasis, increasing reactive oxygen species production and oxidative stress. A main product of oxidative stress, induced by exposure to the aforementioned pollutants, is 4‐hydroxy‐2‐nonenal (HNE), which derives from the oxidation of ω‐6 polyunsaturated fatty acids. HNE is a highly reactive compound that can form adducts with cellular proteins and even DNA; it is also an efficient cell signaling molecule able to regulate mitogen‐activated protein kinase pathways and the activity of redox‐sensitive transcription factors such as Nrf2, AP1, and NFκB. Therefore, increased levels of HNE in the skin, in response to pollutants, likely accelerates skin aging and exacerbates existing skin inflammatory conditions; thus, targeting HNE formation could be an innovative cosmeceutical approach for topical applications.}, number={4}, journal={BIOFACTORS}, author={Pecorelli, Alessandra and Woodby, Brittany and Prieux, Roxane and Valacchi, Giuseppe}, year={2019}, month={Jul}, pages={536–547} }
 @article{muresan_narzt_woodby_ferrara_gruber_valacchi_2019, title={Involvement of cutaneous SR-B1 in skin lipid homeostasis}, volume={666}, ISSN={["1096-0384"]}, DOI={10.1016/j.abb.2019.03.005}, abstractNote={The main functions of the skin are to protect against environmental insults and prevent water loss, which are performed by the complex lipid- and protein matrix present in the outermost layers of the epithelium. The lipidome of these outer layers is mainly composed of ceramides, fatty acids, and cholesterol, which regulates keratinocyte differentiation and skin barrier function. SR-B1 is a multifunctional scavenger receptor that is best known for facilitating uptake of cholesterol from HDL particles in the liver, but it is also expressed in the skin.To determine the role of SR-B1 in keratinocyte differentiation.We investigated the relationship between SR-B1 and keratinocyte differentiation using a physiologically relevant model, organotypic skin equivalents (SEs), wherein SR-B1 was knocked down via siRNA transfection. To assess effects of SR-B1 knockdown on keratinocyte differentiation, we performed hematoxylin/eosin staining, RT-PCR, western blotting, and immunohistochemistry. We also examined the effect of SR-B1 knockdown on lipid production by performing Oil Red O staining and thin layer chromatography.SR-B1 knockdown resulted in decreased lipid levels in SEs, specifically ceramides, and in decreased transcript levels of LDLR, PPAR-α and PPAR-γ, which are factors involved in regulating ceramide synthesis. In addition, filaggrin levels increased in SR-B1 KD tissues, but neither keratin 14 nor keratin 10 were affected.We conclude that one of the main functions of SR-B1 in the skin is to regulate ceramide levels and thereby maintain the barrier function of the skin, resulting in the protection of cutaneous tissues from outdoor insults.}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Muresan, Ximena Maria and Narzt, Marie-Sophie and Woodby, Brittany and Ferrara, Francesca and Gruber, Florian and Valacchi, Giuseppe}, year={2019}, month={May}, pages={1–7} }
 @misc{lim_lee_woodby_valacchi_2019, title={Ozonated Oils and Cutaneous Wound Healing}, volume={25}, ISSN={["1873-4286"]}, DOI={10.2174/1381612825666190702100504}, abstractNote={Wound tissue repair is a complex and dynamic process of restoring cellular structures and tissue layers. Improvement of this process is necessary to effectively treat several pathologies characterized by chronic delayed wound closure, such as diabetes, and the investigation of new approaches aimed to ameliorate the wound healing process is under continuous evolution. Recently, the usage of vegetable matrices in the form of ozonated oils has been proposed, and several researchers have shown positive effects on wound healing, due to the bactericidal, antiviral, and antifungal properties of these ozonated oils. In the present review, we intend to summarize the actual state of the art of the topical usage of ozonated oil in cutaneous wounds with special emphasis to the importance of the ozonated degree of the oil.}, number={20}, journal={CURRENT PHARMACEUTICAL DESIGN}, author={Lim, Yunsook and Lee, Heaji and Woodby, Brittany and Valacchi, Giuseppe}, year={2019}, pages={2264–2278} }
 @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{fuks_woodby_valacchi_2019, title={Skin damage by tropospheric ozone}, volume={70}, ISSN={["1432-1173"]}, DOI={10.1007/s00105-019-4361-4}, abstractNote={Tropospheric (ground level) ozone (O 3 ) is a secondary pollutant, emerging from other pollutants in the sunshine. Exposure to O 3  correlates with higher pulmonary and cardiovascular mortality and affects reproductive health and the central nervous system acutely and chronically. Skin might be a potentially overlooked target organ of ambient O 3 . The experimental evidence suggests a positive correlation of O 3  exposure with oxidative damage, impaired antioxidant defence and proinflammatory response in the skin. In time series studies it was observed that acute rises in O 3  levels correlated with seeking medical help for skin conditions; however, whether these findings are specific to O 3 , is not yet clear. There is preliminary epidemiological evidence that long-term exposure to O 3  is associated with premature skin aging. This finding was independent of co-exposure to other environmental factors affecting skin (e.g. ultraviolet radiation and air pollution). As concentrations of O 3  are rising in many regions of the world, adverse cutaneous effects of O 3  present a relevant public health concern.}, number={3}, journal={HAUTARZT}, author={Fuks, K. B. and Woodby, B. and Valacchi, G.}, year={2019}, month={Mar}, pages={163–168} }
 @article{raikhy_woodby_scott_shin_myers_scott_bodily_2019, title={Suppression of Stromal Interferon Signaling by Human Papillomavirus 16}, volume={93}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.00458-19}, abstractNote={The persistence of high-risk human papillomavirus (HPV) infections is the key risk factor for developing HPV-associated cancers. The ability of HPV to evade host immunity is a critical component of its ability to persist. The environment surrounding a tumor is increasingly understood to be critical in cancer development, including immune evasion. Our studies show that HPV can suppress the expression of immune-related genes in neighboring fibroblasts in a three-dimensional (3D) model of human epithelium. This finding is significant, because it indicates that HPV can control innate immunity not only in the infected cell but also in the microenvironment. In addition, the ability of HPV to regulate stromal gene expression depends in part on the viral oncogene E5, revealing a new function for this protein as an immune evasion factor. ABSTRACT Human papillomaviruses (HPVs) infect squamous epithelia and cause several important cancers. Immune evasion is critical for viral persistence. Fibroblasts in the stromal microenvironment provide growth signals and cytokines that are required for proper epithelial differentiation, maintenance, and immune responses and are critical in the development of many cancers. In this study, we examined the role of epithelial-stromal interactions in the HPV16 life cycle using organotypic (raft) cultures as a model. Rafts were created using uninfected human foreskin keratinocytes (HFKs) and HFKs containing either wild-type HPV16 or HPV16 with a stop mutation to prevent the expression of the viral oncogene E5. Microarray analysis revealed significant changes in gene expression patterns in the stroma in response to HPV16, some of which were E5 dependent. Interferon (IFN)-stimulated genes (ISGs) and extracellular matrix remodeling genes were suppressed, the most prominent pathways affected. STAT1, IFNAR1, IRF3, and IRF7 were knocked down in stromal fibroblasts using lentiviral short hairpin RNA (shRNA) transduction. HPV late gene expression and viral copy number in the epithelium were increased when the stromal IFN pathway was disrupted, indicating that the stroma helps control the late phase of the HPV life cycle in the epithelium. Increased late gene expression correlated with increased late keratinocyte differentiation but not decreased IFN signaling in the epithelium. These studies show HPV16 has a paracrine effect on stromal innate immunity, reveal a new role for E5 as a stromal innate immune suppressor, and suggest that stromal IFN signaling may influence keratinocyte differentiation. IMPORTANCE The persistence of high-risk human papillomavirus (HPV) infections is the key risk factor for developing HPV-associated cancers. The ability of HPV to evade host immunity is a critical component of its ability to persist. The environment surrounding a tumor is increasingly understood to be critical in cancer development, including immune evasion. Our studies show that HPV can suppress the expression of immune-related genes in neighboring fibroblasts in a three-dimensional (3D) model of human epithelium. This finding is significant, because it indicates that HPV can control innate immunity not only in the infected cell but also in the microenvironment. In addition, the ability of HPV to regulate stromal gene expression depends in part on the viral oncogene E5, revealing a new function for this protein as an immune evasion factor.}, number={19}, journal={JOURNAL OF VIROLOGY}, author={Raikhy, Gaurav and Woodby, Brittany L. and Scott, Matthew L. and Shin, Grace and Myers, Julia E. and Scott, Rona S. and Bodily, Jason M.}, year={2019}, month={Oct} }