[National Survey on the Activity of Lung Function Laboratories. Effects During the SARS-COV-2 Pandemic]. / Encuesta sobre la actividad de los laboratorios de función pulmonar. Efectos durante la pandemia por SARS-CoV-2.

Introduction: Following the SARS-CoV-2 pandemic in March 2020, pulmonary function testing (PFT) laboratories underwent a transformation, with a reduction in the number of tests or closure in some cases. The aim of this work was to know the activity of PFT in Spain and the modification of this activity due to the pandemic. Material and methods: A protocolised survey was carried out to members of the PFT laboratories through the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Results: Thirty-nine hospitals in Spain responded. The pulmonary function tests most frequently performed in the PFT laboratories were forced spirometry with bronchodilator test (100%), body plethysmography (97.4%), CO transfer capacity (97.4%), respiratory muscle strength measured in the mouth (97.4%), 6-minute walking test (94.7%), measurement of exhaled fraction of nitric oxide (92.3%) and incremental exercise test (71.8%).The pandemic led to a significant decrease in the number of tests (35.4%) during 2020 with subsequent recovery in 2021, without reaching pre-pandemic values.The most important changes were increased examination times, working with personal protective equipment and ventilation of the rooms. The performance of the nasopharyngeal swab for SARS-CoV2 testing prior to the tests was not homogeneous in the PFT laboratories. Conclusions: Most hospitals are sufficiently equipped to perform the most common pulmonary function tests. The pandemic resulted in a loss of activity in all hospitals.

Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach.

Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization.In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored. A mixed hidden-Markov model (MHMM) was developed to characterize the underlying (hidden) formation of ADA against the biologic, using certolizumab pegol (CZP), as a test drug. CZP is a PEGylated Fc free TNF-inhibitor used in the treatment of rheumatoid arthritis and other chronic inflammatory diseases.The bivariate MHMM used information from plasma drug concentrations and ADA measurements, from six clinical studies (n = 845), that were correlated through a bivariate Gaussian function to infer about two hidden states; production and no-production of ADA influencing PK. Estimation of inter-individual variability was not supported in this case. Parameters associated with the observed part of the model were reasonably well estimated while parameters associated with the hidden part were less precise. Individual state sequences obtained using a Viterbi algorithm suggested that the model was able to determine the start of ADA production for each individual, being a more assay-independent methodology than traditional population PK. The model serves as a basis for identification of covariates influencing the ADA formation, and thus has the potential to identify aspects that minimize its impact on PK and/or efficacy.

Nontoxic effects of thymol, carvacrol, cinnamaldehyde, and garlic oil on dung beetles: A potential alternative to ecotoxic anthelmintics.

The sustainability of the traditional extensive livestock sector will only be possible if healthy dung-decomposing insect communities are preserved. However, many current pharmaceutical anthelmintics are harmful to dung beetles, their presence can have a negative impact on biological systems. Phytochemical anthelmintics are an alternative to ecotoxic synthetic pharmaceutical anthelmintics, although ecotoxicological tests of their possible indirect effects on dung beetles are required to demonstrate their viability. In this study, the potential ecotoxicity of thymol, carvacrol, cinnamaldehyde and garlic oil (diallyl disulfide and diallyl trisulfide) were tested for the first time. Inhibition of antennal response was measured as a relevant parameter by obtaining relevant toxicity thresholds derived from concentration‒response curves, such as the IC50. All phytochemical compounds tested were demonstrated to be suitable alternative candidates to the highly ecotoxic compound ivermectin, considering their non-toxicity to nontarget organisms. Residues of the phytochemical antiparasitics found in cattle droppings were extremely low, even undetectable in the case of diallyl disulfide and diallyl trisulfide. Furthermore, our results showed that none of the phytochemical compounds have ecotoxic effects, even at extremely high concentrations, including those almost 1000 times higher than what is most likely to be found in dung susceptible to ingestion by dung beetles in the field. We can conclude that the four selected phytochemical compounds meet the requirements to be considered reliable alternatives to ecotoxic veterinary medicinal products, such as ivermectin.

Effectiveness of Dry Needling versus Manual Therapy in Myofascial Temporomandibular Disorders: A Single-Blind Randomized Controlled Trial.

Dry needling (DN) is an invasive physiotherapy technique employed for reducing myofascial pain. To compare the effectiveness of dry needling (DN) versus manual therapy (MT) in improving pain, active maximal mouth opening (AMMO) and cervical disability in patients with myofascial pain from temporomandibular disorders (TMDs) were investigated against these treatments. A single-blind, randomized controlled trial was carried out. Individuals (n = 50) with TMDs were randomly allocated in a 1:1 ratio to the DN (n = 25) or MT group (n = 25). Each group received three sessions, separated by 4 days, of either DN or MT. Outcomes were assessed according to pain intensity (Numeric Pain Rating Scale), AMMO (cm), disability (Neck Disability Index), and pressure-pain threshold (PPT) (digital algometry) from the active myofascial trigger points. In both groups, pain and neck disability were significantly lower at the end of treatment compared with those measured at baseline (pain: -2.52 with 95% CI: -3.43 to -1.60 for DN group; pain: -2.92 with 95% CI: -3.77 to -2.07 for MT group; disability: -3.2 with 95% CI: -4.31 to -2.09 for DN group; disability: -2.68 with 95% CI: -3.56 to -1.79 for MT group), but not were not lower after the first session, without differences between the groups. AMMO was significantly higher after the first session (0.16 with 95% CI: 0.03 to 0.29 for DN group; 0.30 with 95% CI: 0.20 to 0.41 for MT group) and at the end of treatment in both groups (0.27 with 95% CI: 0.14 to 0.41 for DN group; 0.37 with 95% CI: 0.22 to 0.52 for MT group) compared with the baseline measurements. Finally, PPT results for the masseter and pterygoid muscles were significantly higher at the end of treatment in both groups (without statistically significant differences between groups), but not after the first session. The assessed therapies, DN and MT, are equally effective in improving pain, AMMO, cervical disability, and PPT in the muscles directly involved in the temporomandibular joint biomechanics of patients with myofascial TMDs.

(R)-8-Methylsulfinyloctyl isothiocyanate from Nasturtium officinale inhibits LPS-induced immunoinflammatory responses in mouse peritoneal macrophages: chemical synthesis and molecular signaling pathways involved.

The aim of this study was to develop an optimal synthetic route to obtain natural (R)-8-methylsulfinyloctyl isothiocyanate ((R)-8-OITC), present in watercress, based on the "DAG methodology" as well as to evaluate its potential antioxidant and immunomodulatory effects, exploring possible signaling pathways that could be involved in an ex vivo model of murine peritoneal macrophages stimulated with LPS. Treatment with (R)-8-OITC inhibited the levels of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-17 and IL-18), intracellular ROS production and expression of pro-inflammatory enzymes (COX-2, iNOS and mPGES-1) through modulation of the expression of Nrf2, MAPKs (p38, JNK and ERK) and JAK/STAT, and the canonical and non-canonical pathways of the inflammasome. Taking all these together, our results provide a rapid and cost-effective synthetic route to obtain natural (R)-8-OITC and demonstrate that it could be a potential nutraceutical candidate for managing immuno-inflammatory pathologies. Therefore, further in vivo trials are warranted.

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice.

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.

Pruebas de función pulmonar en el asma, más allá del protocolo diagnóstico / Pulmonary function tests in asthma, beyond the diagnostic protocol

Las pruebas funcionales respiratorias son imprescindibles para el diagnóstico y el seguimiento de los pacientes asmáticos,principalmente la espirometría forzada junto a la prueba broncodilatadora. Sin embargo, en determinados grupos de pacien-tes pueden ser necesarias o complementarias otras pruebas funcionales que no están incluidas en los protocolos diagnós-ticos de las guías de práctica clínica. Si bien estas pruebas suelen ser más complejas y no están disponibles en todos losniveles asistenciales, hay pacientes en los que hay que descartar otras posibles enfermedades respiratorias o incluso ca-racterizar mejor el asma mediante un estudio más completo de la afectación de la vía aérea. También hay que contemplarla posibilidad de la medición de la función pulmonar en el domicilio en algunos pacientes, lo que puede optimizar sucontrol y disminuir la sobrecarga de recursos sanitarios. En esta revisión describimos la evidencia actual que apoyaría enpacientes con asma el uso de la telemedicina, así como las posibles indicaciones de otras pruebas funcionales como laoscilometría, la pletismografía, la prueba de difusión y las pruebas de esfuerzo.(AU)

Respiratory function tests are essential for the diagnosis and follow-up of asthmatic patients, mainly forced spirometry toge-ther with bronchodilator testing. However, in certain groups of patients, other functional tests that are not included in thediagnostic protocols of clinical practice guidelines may be necessary or complementary. Although these tests are usuallymore complex and are not available at all levels of care, there are patients in whom other possible respiratory diseases mustbe ruled out or even to better characterize asthma through a more complete study of airway involvement. It is also necessaryto consider the possibility of measuring lung function at home in some patients, which can optimize its control and reducethe overload of health resources. In this review we describe the current evidence that would support the use of telemedici-ne in people with asthma, as well as possible indications of other functional tests such as oscillometry, plethysmography,diffusion test, and stress tests.(AU)

Diferencias e influencia en la Conducta Adaptativa por las regiones colombianas

La presente investigación tuvo por objetivo describir las diferencias e influencia de las regiones colombianas en las Habilidades Adaptativas Específicas y Dominios de la Conducta Adaptativa en niños colombianos entre 0-15 años, sin alteraciones en el neurodesarrollo y sin etiología de daño cerebral. Participaron padres y profesores de 2081 niños, divididos por 4 regiones geográficas: Andina, Caribe, Orinoquía y Pacífico. Se aplicó el cuestionario de conducta adaptativa ABAS-II en sus versiones Infantil padres a los padres de niños de 0 a 1,11 años, y las versiones escolar padres y escolar profesores a los padres y profesores de niños de 2 a 15 años. Los resultados indicaron que existen diferencias estadísticamente significativas entre los menores de las diferentes regiones, siendo los resultados más altos los de la región Pacífico y los más bajos los de la región Orinoquía. Con estos resultados se considera que es importante tener en cuenta los aspectos culturales, sociales, ambientales e históricos de cada región del país para la evaluación de su conducta adaptativa, entendiendo que estas diferencias no marcan o indican mayor susceptibilidad a patología, sino variaciones culturales dentro de los términos considerados como lo esperado.

The present research aimed to describe the differences and influence of Colombia geographic regions on Specific Adaptive Skills and Domains of Adaptive Behavior in Colombian children between 0-15 years of age without neurodevelopmental alterations and without etiology of cerebral disease. 2081 Colombian children´s parents and teachers participated, divided into 4 regions: Andean, Caribbean, Orinoquía and Pacific. The ABAS-II questionnaire was applied the chindren´s parent version to parents of children from 0 to 1,11 years and the school parents`and school teachers` versions to parents and teachers of children from 2 to 15 years of age. The results indicated that there are statistically significance differences between the children of the different regions, the highest results being those of the Pacific region and the lowest those of the Orinoquía region. It is considered with the results that it is important to take into account the cultural, social, environmental and historical aspects of each region of the country for the evaluation of their adaptive behavior; these differences do not mark or indicate greater susceptibility to pathology, but rather cultural variations within of the terms considered as the expected.

Allergen exposure boosts peripheral Th9 responses in patients with local allergic rhinitis.

KEY POINTS: Intranasal allergen exposure increases peripheral total Th2 and Th9 cells in patients with local allergic rhinitis (LAR). Peripheral T-cell response seems dominated by Th9 cells in patients with LAR, whereas Th2 responses prevail in patients with allergic rhinitis. Our results identify Th9 cells as potential therapeutic targets for patients with LAR.

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates.

Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. This review focuses on the scientific evidence of exposure to OPs and their toxic effects on the immune system of non-target organisms (invertebrates and vertebrates) from a descriptive perspective of the immuno-toxic mechanisms associated with susceptibility to the development of bacterial, viral, and fungal infectious diseases. During the exhaustive review, we found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.

Lateralized overgrowth as a guiding sign of abdominal neoplasms for pediatric orthopedic surgeons.

OBJECTIVES: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center. PATIENTS AND METHODS: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted. RESULTS: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis. CONCLUSION: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Hematologic analysis of hospitalized patients and outpatients infected with SARS-CoV-2 and possible use as a prognostic biomarker.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem; this has caused thousands of deaths around the world. This infection induces hematologic alterations, and it is necessary to recognize predictive biomarkers to address the need for hospitalization or the severity of the disease. This study aimed to analyze different parameters in outpatients and hospitalized patients infected with SARS-CoV-2 and determine whether hematic biometry can be used for prognosis rapidly. We analyzed 689 patients, of whom 355 were outpatients (162 women and 193 men) and 334 required hospitalization (197 men and 137 women). The average age of the hospitalized patients was 46 years (men, 49 years; women, 52 years), whereas the average age of the outpatients was 49 years (men, 51 years; women, 44 years). Hematologic parameters were analyzed and compared between the outpatients and hospitalized patients. The patients were divided into groups by age and sex. We found that in the hospitalized patients, the erythrocyte, hematocrit, and hemoglobin levels decreased, whereas the outpatients did not experience changes in the erythroid series. In leukocytes, these increased significantly, as they did in neutrophils; however, lymphocytopenia was observed. In the outpatients, we observed normal levels of neutrophils and lymphopenia. We can conclude that hematic biometry can be used as a biomarker, and the relation between neutrophils and lymphocytes is indicated for understanding the development and prognosis of the disease.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH): A Review of Another Sequel of Severe Post-Covid-19 Pneumonia.

The spectrum of pulmonary parenchymal and vascular pathologies related to the COVID-19 have emerged. There is evidence of a specific susceptibility related to thrombotic microangiopathy in situ and a complex immune-inflammatory cascade, especially in the pulmonary vascular bed. The potential to lead to transient or self-correcting sequelae of pulmonary vascular injury will only become apparent with longer-term follow-up. In this review, we aimed to present the findings in a group of patients with severe pneumonia due to covid-19 complicated by acute pe documented by chest angiography, who during a follow-up of more than 3 months with oral anticoagulant met clinical, hemodynamic, and imaging criteria of chronic thromboembolic pulmonary hypertension. We present a brief review of the epidemiology, pathophysiology, clinical findings, comorbidities, treatment, and imaging findings of chronic thromboembolic pulmonary hypertension as a sequel of severe post-covid-19 pneumonia; and compared and discussed these findings with similar reports from the medical literature.

A Review of the Usefulness of Catheter-Directed Thrombolysis for Pulmonary Embolism.

Venous thromboembolic disease (VTE) is a health problem; around 10 million cases occur yearly with substantial morbidity and mortality. Those who survive may be left with long-term sequelae. Those sequelae might include chronic thromboembolic pulmonary hypertension, persistent right ventricular dysfunction, exercise intolerance, and reduced quality of life. Current PE management consists of anticoagulation alone, systemic thrombolysis, catheter-directed thrombolysis, and surgical embolectomy. The severity of patients with pulmonary embolism (PE) depends on the clinic and not exclusively on the extent of radiological or anatomical involvement. In this review, we present the main clinical and functional characteristics of patients in whom thrombotic fragmentation plus catheter-guided thrombolysis is used to manage acute PE of intermediate-high risk and torpid evolution within the first hours of admission.

Pulmonary Embolism (PE) Prevalence in Mexican-Mestizo Patients With Severe SARS-COV-2 (COVID-19) Pneumonia At A Tertiary-Level Hospital: A Review.

Since the report of the first case of COVID-19 in Wuhan, China, on December 31, 2019, several associated thrombotic complications have been reported, mainly venous thromboembolic events, and myocardial infarctions, in addition to peripheral arterial thrombosis and cerebral vascular events, which have been attributed to a hypercoagulable state. We aimed to know the prevalence and prognostic biomarkers in patients with pulmonary thromboembolism (PE) and SARS Cov-2 pneumonia. Hospitalized patients with SARS Cov-2 pneumonia who have had clinical, biomarker, and imaging data (chest angiography) of pulmonary thromboembolism were included. Descriptive statistics and prevalence rates were calculated. For the analysis between the groups, the paired Student's t and the Wilcoxon test were performed. CT angiography was performed on 26 patients at our institution, with a diagnosis of severe pneumonia secondary to SARS-CoV2. 9 of the patients (34.6%) had a venous thromboembolic disease. Type 2 DM was the most frequent comorbidity up to 55.5% of the total; it was followed by obesity and overweight in 55.5%, and in third place, by systemic arterial hypertension in 33.3% of the cases, 1 (11.1%) patient had chronic kidney disease and 1 (11.1%) patient with a history of cancer, only 1 patient met criteria and was treated with thrombolysis. 6 (66.6%) of the patients had segmental PE, 3 (33.3%) patients had subsegmental PE, and 4 (44.4%) patients presented pulmonary infarction.

Epigenetic linkage of systemic lupus erythematosus and nutrition.

The term 'epigenetics' refers to a series of meiotically/mitotically inheritable alterations in gene expression, related to environmental factors, without disruption on DNA sequences of bases. Recently, the pathophysiology of autoimmune diseases (ADs) has been closely linked to epigenetic modifications. In fact, epigenetic mechanisms can modulate gene expression or repression of targeted cells and tissues involved in autoimmune/inflammatory conditions acting as keys effectors in regulation of adaptive and innate responses. ADs, as systemic lupus erythematosus (SLE), a rare disease that still lacks effective treatment, is characterised by epigenetic marks in affected cells. Taking into account that epigenetic mechanisms have been proposed as a winning strategy in the search of new, more specific and personalised therapeutics agents, pharmacology and pharmaco-epigenetic studies about epigenetic regulations of ADs may provide novel individualised therapies. Focusing on possible implicated factors on development and predisposition of SLE, diet is feasibly one of the most important factors since it is linked directly to epigenetic alterations and these epigenetic changes may augment or diminish the risk of SLE. Nevertheless, several studies have suggested that dietary therapy could be promising to SLE patients via prophylactic actions deprived of side effects of pharmacology, decreasing co-morbidities and improving lifestyle of SLE sufferers. Herein, we review and discuss the cross-link between epigenetic mechanisms on SLE predisposition and development, as well as the influence of dietary factors on regulation of epigenetic modifications that may eventually make a positive impact on SLE patients.

Reversed priapism, thrombosis of the dorsal penile vein: A case report.

Priapism is an unintentional prolonged penile erection, lasting equal to or greater than 4 hours, in the absence of sexual stimulation or after having finished it. It is a rare pathology that can represent a urological emergency. The present report describes the case of a 25-year-old patient who presented priapism after suffering a one-meter fall on the genital area. Patient is a 25-year-old male with macroscopic hematuria without clots, testicular pain 4/10 on the numerical pain scale, stabbing type, without irradiation, secondary to a fall that occurred 3 months earlier, which resulted in a blow to the genital area. He presented an evolution of 20 days with detumescence and erectile dysfunction. Penile Doppler was performed and inverted priapism, arteriolacunar fistula at the base of the left corpus cavernosum, plus severe erectile dysfunction, were diagnosed. After a cavernography and an arteriography, a thrombolysis was performed. The patient continued with anticoagulant treatment with clopidogrel and enoxaparin and did not present complications after thrombolysis. A detailed clinical history, physical examination and a Doppler ultrasound study can provide a clear and timely diagnosis for the patient. Cavernography and arteriography have shown satisfactory results. In the present case, thrombolysis treatment with alteplase provided favorable results.

Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells.

The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 µg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.