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Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase (ALOX5) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase (5-LO). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men’s and an increase in women’s serum levels of 5-LO and LTB4. These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.

Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs’ specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response. © 2022 by the authors.

Rationale: Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear.Methods: In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: 1) via cutting-edge digital spatial proteomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n=19); and 2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract.Results: PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from global initiative for chronic lung disease (GOLD) 1-2 COPD patients compared to patients with GOLD 3-4 COPD and controls. Within all the COPD patients, PD-L1 protein expression was strongly directly correlated with the FEV1 % predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels vs. all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD (GOLD 3-4) had reduced AM PD-L1 expression compared to GOLD 1-2 COPD patients. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Conclusions: Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

Ancient pozzolanic mortars show the high technological quality achieved by Roman construction workers, due to their ‘excellent state’ of preservation in every environment. These workers well knew that thanks to the combination of lime with specific volcanic products (pozzolana), mortar and concrete become hydraulic, allowing underwater hardening and increasing mechanical strength. The use of pozzolana in a mortar provides the underwater curing (hydraulic limes) of whatever construction with higher speed compared to carbonation processes of slaked lime. Whenever pozzolana is not available, it is substituted by ceramic fragments, which possess similar hydraulic properties. This research focuses, for the first time, on the detailed characterization of mortars coming from the Thermal Complex of Baia, which represents one of the most important archaeological sites in the Campania region. Thanks to several thermal springs, the ancient city of Baiae (Campi Flegrei) was the holiday resort of the Roman aristocracy. The former Soprintendenza Archeologia della Campania, allowed us to perform non-invasive, but representative, sampling of mortars that were characterised by multianalytical methodologies (POM, XRPD, SEM-EDS, TGA, and MIP) providing useful information on possible future activities of restoration. Results confirmed the expertise of Roman workers, who skilfully combined volcanic tuff aggregate, hydrated lime, and ceramic fragments. In particular, the typical zeolitic mineral association of phillipsite > chabazite > analcime found in the tuff aggregate pointed out their provenance from the Neapolitan Yellow Tuff related to the volcanic activity of Campi Flegrei of ca. 15 ka BP. The most relevant characteristic detected in all studied samples is the mortar hydraulicity testified by evidences such as reaction rims between pozzolana and binder, Hydraulicity Index (HI), and thermal analyses investigation. Also, composition of secondary mineralogical phases in the cementiceous matrix is particularly relevant. Distinctive is the contemporary presence of C-A-S-H gel, calcite and gypsum. C-A-S-H gel is derived from lime/ceramic fragments reaction; calcite is likely related to the partial reaction of underburned lime; and gypsum could be ascribable to the sulphation process of calcite. These secondary minerogenetic products fill pore space and enhance bonding in pumice fragments, thus contributing to long-term durability of mortars.

Background: Anti-leukotriene anti-(LT) drugs induce a more effective control of asthma in female much more than in male subjects, partially due to genetic factors. However, the well-known correlations between “single nucleotide polymorphism” (SNPs) and asthma are still poor investigated in gender difference. Aims and Objectives: The first aim of this study is to characterize the effectiveness of an anti-LT therapy, in sex-matched asthmatic subjects. The second one is to investigate the distribution of SNPs involved in the LTs pathway in female and male asthmatic patients. Methods: In a prospective cohort study of sex-matched asthmatic subjects, pulmonary function tests (higher forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC]) and asthma control tests [ACT] were performed. The fraction of exhaled nitric oxide (FeNO) and blood levels of both 5- lipoxygenase (5-LO) and LTs were also measured. Moreover, 13 SNPs involved in LTs pathway were genotyped in saliva samples. Results: In the first part of the study, female subjects treated with anti-LT have been better control of the asthmatic symptoms and improvement of pulmonary function, compared with male subjects. Interestingly, treated female patients had significantly lower levels of FeNO compared with male patients in the same group. In the second part of the study, 5-LO, LTs blood levels and SNPs have been evaluated, but need to be confirmed. Conclusions: The better control of asthmatic symptoms, lung function and inflammation in females compared to males induced by anti-LT could potentially reflect a different distribution of SNPs according to sex. This evidence could contribute to the development of personalized asthma therapy.

Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse responses to drugs. However, there are knowledge gaps on the effectiveness of anti-leukotrienes drugs on lung function, symptoms, and pulmonary and systemic inflammation in adult asthmatic women compared with men. We conducted a prospective cohort study to characterize the effectiveness of an anti-leukotrienes drug, montelukast (MS), in asthmatic adult women and men. Methods: Twenty-one asthmatic subjects (11 women and 10 men), who were on low-dose inhaled corticosteroids (ICS), were treated with MS. The optimal control of the symptoms was achieved in both groups according to the Global Initiative for Asthma guidelines. At enrollment, and after 13 weeks from the beginning of MS, pulmonary function tests and asthma control tests were performed, and the fraction of exhaled nitric oxide and blood eosinophils levels were measured. Results: From baseline until the end of the study, women treated with MS + ICS had better control of the asthmatic symptoms, defined as higher asthma control test (ACT) score (17.00 ± 1.07 to 23.36 ± 0.45; p < 0.0015), improved pulmonary function [with higher forced expiratory volume in 1 s (from 77.25 ± 6.79 to 103.88 ± 6.24; p < 0.0077)], and forced vital capacity (from 91.95 ± 6.81 to 113.17 ± 4.79; p < 0.0183) compared with men. Interestingly, MS + ICS-treated women had significantly lower levels of blood eosinophils (from 5.27 ± 0.30 to 3.30 ± 0.31; p < 0.0449) and exhaled nitric oxide (from 44.70 ± 7.30 to 25.20 ± 3.90; p < 0.0294) compared with men. Conclusion: The treatment with MS, added to ICS, in women leads to better control of symptoms, better management of lung function, and decreased inflammation levels compared with ICS + MS treatment in men. Copyright © 2019 Esposito, Spaziano, Giannattasio, Ferrigno, Liparulo, Rossi, Roviezzo, Sessa, Falciani, Berrino, Polverino, Polverino and D'Agostino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse responses to drugs. However, there are knowledge gaps on the effectiveness of anti-leukotrienes drugs on lung function, symptoms, and pulmonary and systemic inflammation in adult asthmatic women compared with men. We conducted a prospective cohort study to characterize the effectiveness of an anti-leukotrienes drug, montelukast (MS), in asthmatic adult women and men.Methods: Twenty-one asthmatic subjects (11 women and 10 men), who were on low-dose inhaled corticosteroids (ICS), were treated with MS. The optimal control of the symptoms was achieved in both groups according to the Global Initiative for Asthma guidelines. At enrollment, and after 13 weeks from the beginning of MS, pulmonary function tests and asthma control tests were performed, and the fraction of exhaled nitric oxide and blood eosinophils levels were measured.Results: From baseline until the end of the study, women treated with MS + ICS had better control of the asthmatic symptoms, defined as higher asthma control test (ACT) score (17.00 +/- 1.07 to 23.36 +/- 0.45; p < 0.0015), improved pulmonary function [with higher forced expiratory volume in 1 s (from 77.25 +/- 6.79 to 103.88 +/- 6.24; p < 0.0077)], and forced vital capacity (from 91.95 +/- 6.81 to 113.17 +/- 4.79; p < 0.0183) compared with men. Interestingly, MS + ICS-treated women had significantly lower levels of blood eosinophils (from 5.27 +/- 0.30 to 3.30 +/- 0.31; p < 0.0449) and exhaled nitric oxide (from 44.70 +/- 7.30 to 25.20 +/- 3.90; p < 0.0294) compared with men.Conclusion: The treatment with MS, added to ICS, in women leads to better control of symptoms, better management of lung function, and decreased inflammation levels compared with ICS + MS treatment in men.

Asthma is a heterogeneous chronic inflammatory disease of the airways. The most prevalent form is atopic asthma, which is initiated by the exposure to (inhaled) allergens. Intermittent attacks of breathlessness, airways hyperresponsiveness, wheezing, coughing, and resultant allergen-specific immune responses characterize the disease. Nociceptin/OFQ-NOP receptor system is able to combine anti-hyperresponsiveness and immunomodulatory actions. In particular, N/OFQ is able to inhibit airways microvascular leakage and bronchoconstriction through a presynaptic and non-opioid mechanism of action that blocks tachykinin release. Moreover, it also acts on allergenic sensitization because it is able to modulate the immune response that triggers the development of airway hyperresponsiveness through an interaction on cell membranes of dendritic cells (DCs) that are generally responsible to start and sustain allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. In asthmatic patients, sputum showed elevated N/OFQ levels that are related to increased eosinophil counts. The addition of exogenous N/OFQ in sputum obtained from patients with severe asthma attenuated eosinophils migration and release of inflammatory mediators. These observations confirmed that elevated endogenous N/OFQ levels in asthmatic sputum were lower than the ones required to exert beneficial effects, suggesting that supplementation with exogenous N/OFQ may need. In conclusion, the innovative role of N/OFQ in counteracting airways inflammation/hyperresponsiveness opens new potential targets/strategies in asthma treatment.

The topic of this study is the archaeometric characterization of mortars from Villa del Pezzolo, a Roman Villa located in Seiano (Napoli-Campania, Italy), dated between the 1st century B.C. and the 3rd century A.D. Mortars were analyzed by means of a multi-analytical approach (polarized optical microscopy, X-ray powder diffraction, scanning electron microscopy and energy-dispersed spectrometry, thermal analyses and mercury intrusion porosimetry) according to existing recommendations. Analytical results evidenced the use of local geomaterials composed of sedimentary and volcanic aggregates in the mix design and confirmed the three distinct building phases identified by archaeologists. Volcanic tuff fragments, identified in the 1st building phase can be ascribed to Campanian Ignimbrite formation, widely cropping out in the Sorrento Peninsula, as confirmed by the presence of glassy shards, partially devitrified and replaced by authigenic feldspar, a typical feature of welded grey ignimbrite lithofacies (WGI). Volcanic aggregates in samples of the 2nd and 3rd building phases show, instead, the presence of leucite-bearing volcanic scoriae and garnet crystal fragments related to Somma-Vesuvius products. Study of these mortars allowed us to: (1) understand the production technologies, (2) highlight use of materials with hydraulic behavior, such as volcanic and fictile fragments, (3) confirm the three building phases from compositional features of mortars and (4) highlight the change over time of the volcanic aggregate for mortars mix-design.

This work is the result of a geoarchaeological investigation on the Anfiteatro Flavio, one of the most important archaeological sites in the Campania region (southern Italy), situated in an area of great geological and archaeological interest, the Campi Flegrei volcanic field. The aim of this research was to characterise building stones employed for structural use, focusing on the type of materials and their provenance. The mineralogical-petrographic characterization of 27 samples from corbels and pillars involved X-ray powder diffraction analyses (XRPD), thin section optical microscopy observations (OM) and energy dispersive spectrometry microanalyses (EDS). The results revealed that the source materials are represented by two distinctive trachytic/phonolitic lava deposits. Pillar light grey block samples are made of a feldspar-phyric (F-p) lava type that shares many petrographic and mineral chemical features with the Campi Flegrei Accademia lava dome, cropping out in the immediate proximities of the Anfiteatro Flavio. On the other hand, pillar grey block and corbel samples are made of an alkali feldspar and sodalite-phyric (KS-p) lava that has been correlated to an Ischian lava deposit based mainly of the peculiar composition of the observed amphibole crystals. Previous data attesting for the use of the Piperno welded tuff for the pillar grey blocks were likely driven by the “eutaxitic-like” fluidal oriented texture and by the alveolitization alteration displayed by the samples. This however does not exclude that the Piperno had been employed as a building stone for other structural elements of the amphitheatre. The use of the Ischia lavas as an exported building material had been never reported before, possibly suggesting that current knowledges about the use and trade of building materials in the Campania area during the Roman period need to be reconsidered.

This research provides a characterization of ancient Roman mortars from “Villa del Capo di Sorrento” (commonly known as “Villa di Pollio Felice” or “Bagni della Regina Giovanna”). A deepened analysis of cementitious binding matrix and aggregates was conducted with the aims of determining possible sources of raw materials and the mix recipe, and to evaluate the minerogenetic secondary processes. Twenty samples taken from the Villa were investigated by means of a multi-analytical approach, including polarized optical microscopy on thin sections, X-ray powder diffraction, scanning electron microscopy analysis, energy dispersed spectrometry, simultaneous thermal analyses, and mercury intrusion porosimetry. Bedding mortars were made with slaked lime mixed with volcanic materials, whereas coating mortars were made adding to previous recipe as ceramic fragments. All samples were classified as hydraulic mortars. Cementitious binding matrix was characterized by gel-like C-A-S-H, calcite, hydrocalumite, and gypsum, deriving from lime/pozzolanic material. Geomaterials used for mortar production had a local origin. Pozzolanic materials, such as volcanic fragments, scoriae, pumice, and crystal fragments derived from both pyroclastic rocks of the Campi Flegrei district and from rocks of the Somma-Vesuvio complex, porosity test suggest that the products related to minerogenetic secondary processes, make mortars more resistant.

It is widely recognized that airway inflammation and remodeling play a key role not only in the central airway but also small airway pathology during asthma. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide, and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). We studied a murine model of AHR in order to understand the role of N/OFQ in the inflammation and remodeling of the small airways. Balb/c mice were sensitized to ovalbumin (OVA). At days 0 and 7 (pre-OVA sensitization) or from day 21 to 23 (post-OVA sensitization), the mice were treated intraperitoneally with N/OFQ or saline solution. After the last OVA challenge, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS for 48h, and then euthanized. Small airway compliance (sCaw) was measured and lung samples were collected for histological and molecular evaluations such as perimeter and diameter of small airway, total wall area, airway smooth muscle (ASM) thickness and number of alveolar attachments. Both pre- and post-OVA sensitization N/OFQ treatments induced: (1) increases in sCaw; (2) reduction of the bronchial wall thickness; (3) attenuation of the hyperplastic phase of airway smooth muscle mass; and (4) protection against loss of alveolar attachments compared with saline solution treatments. These results suggest that N/OFQ protects against inflammation, and mechanical damage and remodeling of small airways caused by OVA sensitization, suggesting a new potential therapeutic target for asthma. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. It is widely recognized that airway inflammation and remodeling play a key role not only in the central airway but also small airway pathology during asthma. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide, and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). We studied a murine model of AHR in order to understand the role of N/OFQ in the inflammation and remodeling of the small airways. Balb/c mice were sensitized to ovalbumin (OVA). At days 0 and 7 (pre-OVA sensitization) or from day 21 to 23 (post-OVA sensitization), the mice were treated intraperitoneally with N/OFQ or saline solution. After the last OVA challenge, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS for 48h, and then euthanized. Small airway compliance (sCaw) was measured and lung samples were collected for histological and molecular evaluations such as perimeter and diameter of small airway, total wall area, airway smooth muscle (ASM) thickness and number of alveolar attachments. Both pre- and post-OVA sensitization N/OFQ treatments induced: (1) increases in sCaw; (2) reduction of the bronchial wall thickness; (3) attenuation of the hyperplastic phase of airway smooth muscle mass; and (4) protection against loss of alveolar attachments compared with saline solution treatments. These results suggest that N/OFQ protects against inflammation, and mechanical damage and remodeling of small airways caused by OVA sensitization, suggesting a new potential therapeutic target for asthma.