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The olfactory nuisance, due to the emissions of active molecules, is mainly associated with unproperly managed waste disposal and animal farming. Volatile compounds e.g., aromatics, organic and inorganic sulfide compounds, as well as nitrogen and halogenated compounds are the major contributor to odor pollution generated by waste management plants; the most important source of atmospheric ammonia is produced by livestock farming. Although an odorous compound may represent a nuisance rather than a health risk, long-term exposure to a mixture of volatile compounds may represent a risk for different diseases, including asthma, atopic dermatitis, and neurologic damage. Workers and communities living close to odor-producing facilities result directly exposed to irritant air pollutants through inhalation and for this reason the cumulative health risk assessment is recommended. Health effects are related to the concentration and exposure duration to the odorants, as well as to their irritant potency and/or biotransformation in hazardous metabolites. The health effects of a single chemical are well known, while the interactions between molecules with different functional groups have still to be extensively studied. Odor emissions are often due to airborne pollutants at levels below the established toxicity thresholds. The relationship between odor and toxicity does not always occurs but depends on the specific kind of pollutant involved. Indeed, some toxic agents does not induce odor nuisance while untoxic agents do. Accordingly, the relationship between toxicity and odor nuisance should be always analyzed in detail evaluating on the characteristics of the airborne mixture and the type of the source involved.

Human papillomavirus (HPV) is causatively associated with cervical cancer, the fourth most common malignant disease of women worldwide: (1) The aim of the proposed study is to implement routine diagnostics of HPV precancerous cervical lesions by introducing new molecular diagnostic tools. (2) Methods: This is a retrospective cohort study with a total of twenty-two formalin-fixed paraffin-embedded (FFPE) cervical samples of various sample type (nine biopsy and thirteen conization) each patient had a previous abnormal results of pap test or HPV DNA test. Genotyping, viral load and co-infections were determined. For each patient, the individual expression of 2549 microRNAs were evaluated by microarray and qPCR. (3) Results: Our data demonstrates that the microRNAs were commonly expressed in tissues biopsies. miR 4485-5p, miR4485-3p and miR-4497 were highly down-regulated in tissue biopsies with HPV precancerous cervical lesions. (4) Conclusions: the introduction of a microRNA analysis panel can improve early diagnosis, understand the nature of the lesion and, consequently, improve the clinical management of patients with HPV precancerous cervical lesions.

The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term.

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

Fanconi anemia (FA) is a complex tumor-prone disease defined by an entangled genotype and phenotype. Despite enormous efforts in the last 20 years, a comprehensive and integrated view of the disease is still missing. The aim of this pilot study was to establish whether a global microRNA (miRNA) analysis approach could be helpful in defining aspects in FA phenotype, which might deserve future attention with the perspective to develop miRNA-based therapies.miRNA array were employed to characterize the global miRNA (miRNoma) profile of FA RNA samples with respect to normal samples.We report and compare miRNA profile from two FA established cell lines and three FA patients. This analysis reveals that 36 and 64 miRNAs, respectively, are found differentially expressed (2-fold variation and P 0.05) in the samples from FA cell lines and FA patients. Overlap of these data results in 24 miRNAs as shared in the two sample populations. Available bioinformatics methods were used to predict target genes for the differentially expressed miRNAs and to perform pathway enrichment analysis.Seven pathway results associated with the FA phenotype. It is interesting to note that some of these pathways were previously unrelated to FA phenotype. It might be important to focus on these pathways not previously emerged as dysfunctional in FA to better define the pathophysiological context of this disease. This is the first report of a global miRNA analysis in FA.

Particulate matter (PM) pollution is one of the major public health problems worldwide, given the high mortality attributable to exposure to PM pollution and the high pathogenicity that is found above all in the respiratory, cardiovascular, and neurological systems. The main sources of PM pollution are the daily use of fuels (wood, coal, organic residues) in appliances without emissions abatement systems, industrial emissions, and vehicular traffic. This review aims to investigate the causes of PM pollution and classify the different types of dust based on their size. The health effects of exposure to PM will also be discussed. Particular attention is paid to the measurement method, which is unsuitable in the risk assessment process, as the evaluation of the average PM compared to the evaluation of PM with punctual monitoring significantly underestimates the health risk induced by the achievement of high PM values, even for limited periods of time.

Background: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. Methods: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. Results: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. Conclusions: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.

Background: The COVID-19 pandemic continues to ravage the human population, therefore, multiple prevention and intervention protocols are being rapidly developed. The aim of our study was to develop a new chemo-prophylactic/-therapeutic strategy that effectively prevents COVID-19 and related complications. Methods: In in vitro studies, COVID-19 infection-sensitive cells were incubated with human oropharyngeal fluids containing high SARS-CoV-2 loads. Levels of infection were determined via intra-cellular virus loads using quantitative PCR (qPCR). Efficacies for infection prevention were determined using several antiviral treatments: lipid-encapsulated ozonized oil (HOO), water-soluble HOO (HOOws), UV, and hydrogen peroxide. In in vivo studies, safety and efficacy of HOO in fighting COVID-19 infection was evaluated in human subjects. Results: HOO in combination with HOOws was the only treatment able to fully neutralize SARS-CoV-2 as well as its capacity to penetrate and reproduce inside sensitive cells. Accordingly, the feasibility of using HOO/HOOws was tested in vivo. Analysis of expired gas in healthy subjects indicates that HOO administration increases oxygen availability in the lung. For our human studies, HOO/HOOws was administered to 52 cancer patients and 21 healthy subjects at high risk for COVID-19 infection, and all of them showed clinical safety. None of them developed COVID-19 infection, although an incidence of at least 11 cases was expected. Efficacy of HOO/HOOws was tested in four COVID-19 patients obtaining recovery and qPCR negativization in less than 10 days. Conclusions: Based on our experience, the HOO/HOOws treatment can be administered at standard doses (three pills per day) for chemo-prophylactic purposes to healthy subjects for COVID-19 prevention and at high doses (up to eight pills per day) for therapeutic purposes to infected patients. This combined prevention strategy can provide a novel protocol to fight the COVID-19 pandemic.

The aim of this research was to evaluate the effects of different lens types on the availability and efficacy of anti-inflammatory and antibiotic drugs. Three lens types were examined: (1) nonionic hydrogel lenses, (2) ionic hydrogel lenses, and (3) silicone hydrogel lenses. The lenses were incubated with (a) dexamethasone, (b) betamethasone, (c) bromophenacyl bromide, and (d) chloramphenicol. Drug availability was quantified by gradient HPLC, and chloramphenicol antibacterial activity was quantified by testing the inhibition of Salmonella typhimurium growth on agar. The lens allowing the most abundant passage of betamethasone was the ionic hydrogel lens, followed by the silicone hydrogel lens and nonionic hydrogel lens. The lens allowing the most abundant passage of dexamethasone was the ionic hydrogel lens, but only at 0.5 h and 1 h. Regarding chloramphenicol, the ionic hydrogel lens and silicone hydrogel lens allowed more abundant passage than the nonionic hydrogel lens. These results highlight the relevance of adapting lenses to anti-inflammatory therapy, thus allowing a personalized medical approach.

Background: Military personnel are frequently exposed to environmental pollutants that can cause a variety of diseases. Methods: This review analyzed publications regarding epidemiological and biomonitoring studies on occupationally-exposed military personnel. Results: The exposures include sulfur mustard, organ chlorines, combustion products, fuel vapors, and ionizing and exciting radiations. Important factors to be considered are the lengths and intensities of exposures, its proximity to the sources of environmental pollutants, as well as confounding factors (cigarette smoke, diet, photo-type, healthy warrior effect, etc.). Assessment of environmental and individual exposures to pollutants is crucial, although often omitted, because soldiers have often been evaluated based on reported health problems rather than on excessive exposure to pollutants. Biomarkers of exposures and effects are tools to explore relationships between exposures and diseases in military personnel. Another observation from this review is a major problem from the lack of suitable control groups. Conclusions: This review indicates that only studies which analyzed epidemiological and molecular biomarkers in both exposed and control groups would provide evidence-based conclusions on exposure and disease risk in military personnel.

Environmental pollutants can influence microbiota variety, with important implications for the general wellbeing of organisms. In subjects at high-risk of cancer, gut, and lung microbiota are distinct from those of low-risk subjects, and disease progression is associated with microbiota alterations. As with many inflammatory diseases, it is the combination of specific host and environmental factors in certain individuals that provokes disease outcomes. The microbiota metabolites influence activity of epigenetic enzymes. The knowledge of the mechanisms of action of environmental pollution now includes not only the alteration of the gut microbiota but also the interaction between different human microbiota niches such as the lung–gut axis. The epigenetic regulations can reprogram differentiated cells in response to environmental changes. The microbiota can play a major role in the progression and suppression of several epigenetic diseases. Accordingly, the maintenance of a balanced microbiota by monitoring the environmental stimuli provides a novel preventive approach for disease prevention. Metagenomics technologies can be utilized to establish new mitigation approaches for diseases induced by polluted environments. The purpose of this review is to examine the effects of particulate matter exposure on the progression of disease outcomes as related to the alterations of gut and lung microbial communities and consequent epigenetic modifications.

Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue—in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice.

Bulky DNA adducts are a combined sign of aromatic chemical exposure, as well as an individual’s ability to metabolically activate carcinogens and repair DNA damage. The present study aims to investigate the association between PM exposure and DNA adducts in blood cells, in a population of 196 adults with an unhealthy BMI (≥25). For each subject, a DNA sample was obtained for quantification of DNA adducts by sensitive32P post-labelling methods. Individual PM10 exposure was derived from daily mean concentrations measured by single monitors in the study area and then assigned to each subject by calculating the mean of the 30 days (short-term exposure), and of the 365 (long-term exposure) preceding enrolment. Multivariable linear regression models were used to study the association between PM10 and DNA adducts. The majority of analysed samples had bulky DNA adducts, with an average value of 3.7 ± 1.6 (mean ± SD). Overall, the findings of the linear univariate and multiple linear regression showed an inverse association between long-term PM10 exposure and adduct levels; this unexpected result might be since the population consists of subjects with an unhealthy BMI, which might show an atypical reaction to airborne urban pollutants; a hermetic response which happens when small amounts of pollutants are present. Pollutants can linger for a long time in the adipose tissue of obese persons, contributing to an increase in oxidative DNA damage, inflammation, and thrombosis when exposure is sustained.

I. Dans un « Curriculum vitae » rédigé à l’occasion du baccalauréat (l’Abitur), Benjamin souligne l’influence décisive de son séjour à Haubinda (l’internat fondé par Hermann Lietz, en 1901) sur sa première formation intellectuelle : « Ce séjour fut très important, outre le rétablissement de ma santé, car c’est ici que je reçus, en particulier dans l’enseignement de l’allemand, les impulsions décisives, qui depuis ont accompagné ma recherche et mes intérêts. Mon penchant pour la littérature, q...

Aloe vera extracts have been used for drug therapy due to their antimicrobial, anti-inflammatory, and epithelia-regenerative actions. Considering the possible adverse side effects on the corneal surface of anti-microbial agent administration after ocular surgery, it is of interest to identify the ability of Aloe vera extract release from a therapeutic lens to prevent ocular irritation. The aim of this research was to evaluate the effects of different lens types on the availability and efficacy of releasing Aloe vera extracts in which they are soaked. Two lens types were examined: (1) non-ionic hydrogel lenses and (2) ionic hydrogel lenses. Aloe vera availability was quantified by LC&ndash, MS, and activity was quantified by a spectrophotometer (Nanodrop) at different times: (a) 30 min, (b) 60 min, (c) 2 h, (d) 6 h, and (e) 24 h. The lens allowing for the most abundant passage of Aloe vera extracts was the ionic hydrogel lens, followed by the non-ionic hydrogel lens. The obtained results demonstrate that the best lens allowing for the high and stable release of Aloe vera extract to the corneal surface are those composed of ionic hydrogels.

The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as “hormesis”. Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.

Celecoxib, a nonsteroidal anti-inflammatory drug that selectively targets cyclooxygenase-2, is a promising cancer chemopreventive agent. However, safety concerns have been raised in clinical trials evaluating its ability to prevent colorectal adenomas. The rationale for the herein reported studies was to analyze genomic and epigenetic end-points aimed at investigating both the chemopreventive properties of celecoxib towards cigarette smoke-associated molecular alterations and its possible adverse effects. We carried out three consecutive studies in mice treated with either smoke and/or celecoxib. Study 1 investigated early DNA alterations (DNA adducts, oxidative DNA damage, and systemic genotoxic damage) and epigenetic alterations (expression of 1,135 microRNAs) in lung and blood of Swiss H mice; Study 2 evaluated the formation of DNA adducts in lung, liver, and heart; and Study 3 evaluated the expression of microRNAs in 10 organs and 3 body fluids of ICR (CD-1) mice. Surprisingly, the oral administration of celecoxib to smoke-free mice resulted in the formation of DNA adducts in both lung and heart and in dysregulation of microRNAs in mouse organs and body fluids. On the other hand, celecoxib attenuated smoke-related DNA damage and dysregulation of microRNA expression. In conclusion, celecoxib showed pleiotropic properties and multiple mechanisms by counteracting the molecular damage produced by smoke in a variety of organs and body fluids. However, administration of celecoxib to non-smoking mice resulted in evident molecular alterations, also including DNA and RNA alterations in the heart, which may bear relevance in the pathogenesis of the cardiovascular adverse effects of this drug.

Purpose: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures. Experimental design: Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR. Results: The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively. Conclusions: microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies.