The role of puff volume in vaping emissions, inhalation risks, and metabolic perturbations: a pilot study.

Secondhand vaping exposure is an emerging public health concern that remains understudied. In this study, saliva and exhaled emissions from ENDS users (secondhand) and non-ENDS users (baseline) were collected, firsthand emissions were generated using an automated ENDS aerosol generation system programmed to simulate puffing topography profiles collected from ENDS users. Particulate concentrations and sizes along with volatile organic compounds were characterized. We revealed puffing topography metrics as potential mediators of firsthand and secondhand particle and chemical exposures, as well as metabolic and respiratory health outcomes. Particle deposition modeling revealed that while secondhand emissions displayed smaller deposited mass, total and pulmonary particle deposition fractions were higher than firsthand deposition levels, possibly due to smaller secondhand emission particle diameters. Lastly, untargeted metabolomic profiling of salivary biomarkers of lung injury due to firsthand ENDS exposures revealed potential early indicators of respiratory distress that may also be relevant in bystanders exposed to secondhand vaping scenarios. By leveraging system toxicology, we identified 10 metabolites, including leukotriene D4, that could potentially serve as biomarkers for ENDS use, exposure estimation, and the prediction of vaping-related disease. This study highlights characterization of vaping behavior is an important exposure component in advancing our understanding of potential health effects in ENDS users and bystanders.

Inhalation exposure-induced toxicity and disease mediated via mTOR dysregulation.

Environmental air pollution is a global health concern, associated with multiple respiratory and systemic diseases. Epidemiological supports continued urbanization and industrialization increasing the prevalence of inhalation exposures. Exposure to these inhaled pollutants induces toxicity via activation of numerous cellular mechanisms including oxidative stress, autophagy, disrupted cellular metabolism, inflammation, tumorigenesis, and others contributing to disease development. The mechanistic target of rapamycin (mTOR) is a key regulator involved in various cellular processes related to the modulation of metabolism and maintenance of homeostasis. Dysregulation of mTOR occurs following inhalation exposures and has also been implicated in many diseases such as cancer, obesity, cardiovascular disease, diabetes, asthma, and neurodegeneration. Moreover, mTOR plays a fundamental role in protein transcription and translation involved in many inflammatory and autoimmune diseases. It is necessary to understand inhalation exposure-induced dysregulation of mTOR since it is key regulator which may contribute to numerous disease processes. This mini review evaluates the available literature regarding several types of inhalation exposure and their impacts on mTOR signaling. Particularly we focus on the mTOR signaling pathway related outcomes of autophagy, lipid metabolism, and inflammation. Furthermore, we will examine the implications of dysregulated mTOR pathway in exposure-induced diseases. Throughout this mini review, current gaps will be identified related to exposure-induced mTOR dysregulation which may enable the targeting of mTOR signaling for the development of therapeutics.

Autophagy and Mitochondria: Targets in Neurodegenerative Disorders.

BACKGROUND & OBJECTIVE: Cellular physiology and energy metabolism are maintained by the constant supply of energy furnished by the powerhouses of the cell called mitochondria. Cellular homeostasis depends on the timely clearance of damaged cellular organelles and proteins via pathways including autophagy. Mitochondria and mitochondrial autophagy play a vital role in cellular health and failure of these pathways can have a devastating effect on cellular homeostasis. Amongst the various cell types, neuronal cells are more vulnerable to bioenergetic depletion since most of their functions critically depend on the availability of energy derived from mitochondrial metabolism, thus making neurodegenerative disorders an obstinate issue. Research in the past few decades has shown that these neurodegenerative disorders are associated with mitochondrial dysfunction and compromised mitophagy leading to accumulation of protein aggregates which ultimately culminate in neurodegeneration. CONCLUSION: Thus, targeting mitochondria and autophagy-related proteins and enzymes in neurodegenerative disorders may open the avenues for potential targets for discovering effective therapies. Here, we review the involvement of mitochondrial and autophagy dysfunction in neurodegenerative disorders specifically focusing on Alzheimer's, Parkinson's and Huntington's disease.