The expression of clock genes, regulating the synchronization of metabolic and behavioral processes with environmental light/dark cycles, is regulated by methylation and might be influenced by short-term exposure to airborne particulate matter (PM), especially in individuals that are hypersensitive to proinflammatory cues. The present study aimed to evaluate the effects of PM_2.5 and PM₁₀ on the methylation profile of the clock genes ARNTL, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 in a population of 200 women with obesity. A significant association between PM₁₀ exposure and the methylation of clock genes was found, namely, this was negative for PER2 gene and positive for the CLOCK, CRY1, CRY2, and PER3 genes. PM_2.5 was negatively associated with methylation of PER2 gene and positively with methylation of CRY2 gene. Evidence was observed for effect modification from body mass index (BMI) regarding the PER1 gene: as PM_2.5/10 increases, DNA methylation increases significantly for relatively low BMI values (BMI = 25), while it decreases in participants with severe obesity (BMI = 51). PM may therefore alter the epigenetic regulation of clock genes, possibly affecting circadian rhythms. Future studies are needed to clarify how alterations in clock gene methylation are predictive of disease development and how obesity can modulate the adverse health effects of PM.

Neurodegenerative disorders (NDs) are highly prevalent conditions with genetic and environmental causes. Recently, air pollution has emerged as an important contributor to NDs, causing oxidative stress and neuronal damage in the brain. Identifying early molecular alterations mediating the effects of air pollution on ND pathogenesis would be crucial for implementing personalized medicine approaches, especially for the monitoring of specific categories of highly exposed workers. Epigenetic modifications might be suitable candidates in that sense, since they are highly responsive to environmental stressors, they modulate the expression of multiple ND-related genes, and offer technical advantages as they can be studies in peripheral tissues and are relatively stable in biological samples after collection.

Background: Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity. Methods: Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO₂), and apparent temperature (AT) were estimated based on subjects’ residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT. Results: Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO₂ exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41–3.47]; GAF: β = −1.93, 95% CI [−3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups. Conclusions: Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

Environmental and lifestyle exposures have a huge impact on cancer risk; nevertheless, the biological mechanisms underlying this association remain poorly understood. Extracellular vesicles (EVs) are membrane-enclosed particles actively released by all living cells, which play a key role in intercellular communication. EVs transport a variegate cargo of biomolecules, including non-coding RNA (ncRNA), which are well-known regulators of gene expression. Once delivered to recipient cells, EV-borne ncRNAs modulate a plethora of cancer-related biological processes, including cell proliferation, differentiation, and motility. In addition, the ncRNA content of EVs can be altered in response to outer stimuli. Such changes can occur either as an active attempt to adapt to the changing environment or as an uncontrolled consequence of cell homeostasis loss. In either case, such environmentally-driven alterations in EV ncRNA might affect the complex crosstalk between malignant cells and the tumor microenvironment, thus modulating the risk of cancer initiation and progression. In this review, we summarize the current knowledge about EV ncRNAs at the interface between environmental and lifestyle determinants and cancer. In particular, we focus on the effect of smoking, air and water pollution, diet, exercise, and electromagnetic radiation. In addition, we have conducted a bioinformatic analysis to investigate the biological functions of the genes targeted by environmentally-regulated EV microRNAs. Overall, we draw a comprehensive picture of the role of EV ncRNA at the interface between external factors and cancer, which could be of great interest to the development of novel strategies for cancer prevention, diagnosis, and therapy.

Major depressive disorder (MDD) is a serious and disabling condition, whose etiological mechanisms are not fully understood. The aim of the DeprAir study is to verify the hypothesis that air pollution exposure may exacerbate neuroinflammation with consequent alterations in DNA methylation of genes involved in circadian rhythms and hormonal dysregulation, resulting in the worsening of depressive symptoms. The study population consists of 420 depressed patients accessing the psychiatry unit of the Policlinico Hospital (Milan, Italy), from September 2020 to December 2022. Data collection is still ongoing for about 100 subjects. For each participant demographic and lifestyle information, depression history and characteristics, as well as blood samples, were collected. MDD severity was assessed through five rating scales commonly used in clinical practice to assess the severity of affective symptoms. Exposure to particulate and gaseous air pollutants is assigned to each subject using both air pollution monitoring station measurements and estimates derived from a chemical transport model. DeprAir is the first study investigating in a comprehensive picture whether air pollution exposure could be an important modifiable environmental factor associated with MDD severity and which biological mechanisms mediate the negative effect of air pollution on mental health. Its results will represent an opportunity for preventive strategies, thus entailing a tremendous impact on public health.