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While health effects of conventional tobacco are well defined, data on vaping devices, including one of the most popular e-cigarettes which have high nicotine levels, are less established. Prior acute e-cigarette studies have demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies have demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated the impact of inhalation of aerosols produced from pod-based, flavored e-cigarettes (JUUL) aerosols three times daily for 3 months on inflammatory markers in the brain, lung, heart, and colon. JUUL aerosol exposure induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens in the central nervous system. Inflammatory gene expression increased in the colon, while gene expression was more broadly altered by e-cigarette aerosol inhalation in the lung. Cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-specific findings were detected across these studies. Our findings suggest that daily e-cigarette use may cause neuroinflammation, which may contribute to behavioral changes and mood disorders. In addition, e-cigarette use may cause gut inflammation, which has been tied to poor systemic health, and cardiac inflammation, which leads to cardiovascular disease.

In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-0-desmethylnaproxen (0-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, 7 (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1) displayed 0-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 [micro]mol x [L.sup.-1]) together with 14[micro] mol x [L.sup.-1] of the sulfate donor, 3'-phosphoadenosine-5'phosphosulfate (PAPS). At 10 [micro]mol x [L.sup.-1] 0-DMN concentration, however, only SULT1A1 and SULT1A3 displayed detectable activity, with the former being nearly 2 orders of magnitude more active than the latter. A pH-dependence study indicated that SULT1A1 exhibited a broad pH optimum spanning pH 5.5-7. Kinetic parameters of the sulfation of 0-DMN by SULT1A1 were determined. The production and release of sulfated 0-DMN was demonstrated using cultured human HepG2 hepatoma cells and Caco-2 colon carcinoma cells. Moreover, assays using human organ specimens revealed that the 0-DMN-sulfating activities present in the cyto-sols of liver and small intestine (at 502.5 and 497.2 [micro]mol x [min.sup.-1-][(mg protein).sup.1], respectively) were much higher than those detected for the cyto-sols of lung and kidney. Taken together, these results provided relevant information concerning the sulfation of 0-DMN both in vitro and in vivo. Key words: naproxen, 6-0-desmethylnaproxen, sulfation, cytosolic sulfotransferase, SULTs. Dans cette etude, nous visions a obtenir un registre detaille des sulfotransferases (SULT) cytosoliques humaines, qui permettent de sulfater le 6-0-demethyle naproxene (0-DMN), un des principaux metabolites du naproxene. Des 13 SULT humains connus analyses, la SULT1A1, la SULT1A2, la SULT1A3, la SULT1B1, la SULT1C2, la SULT1C4 et la SULT1E1 ont presente une activite 0-DMN sulfatante a l'analyse de concentrations elevees de substrat (500 [micro]mol x [L.sup.-1]) avec le donneur de sulfates PAPS (pour 3'-phosphoadenosine 5'-phosphosulfate) a 14 [micro]mol x [L.sup.-1]. Ce-pendant, avecle 0-DMN a 10 [micro]mol x [L.sup.-1], seules l'activite de la SULT1A1 et l'activite de la SULT1A3 etaient detectables, et la premiere etait presque deux fois plus elevee que la seconde. Une etude de dependance au pH a montre que l'expression de la SULT1A1 etait optimale a l'interieur d'une large plage de pH (de 5,5 a 7). Nous avons etabli les parametres cinetiques de la sulfatation du 0-DMN par la SULT1A1. Nous avons montre la production et la liberation d'0-DMN sulfate a l'aide de cellules humaines d'hepatome (HepG2) et de cancer du colon (Caco-2) en culture. De surcroit, des analyses sur des echantillons d'organes humains ont revele que l'activite sulfatante de l'0-DMN presente dans le cytosol de cellules de foie et d'intestin grele (502,5 et 497,2 [micro]mol x [min.sup.-1]-[(mg de proteines).sup.-1], respectivement) etait beaucoup plus elevee que dans le cytosol de cellules de poumon et de rein. En somme, ces resultats ont permis d'obtenir des renseignements pertinents quant a la sulfatation de l'0-DMN, tant in vitro qu'in vivo. [Traduit par la Redaction] Mots-cles: naproxene, 6-0-demethyle naproxene, sulfatation, sulfotransferase cytosolique, SULT., Introduction Naproxen is a widely used non-steroidal anti-inflammatory drug (Duggan et al. 2010). It exerts its antipyretic, anti-inflammatory, and analgesic activity via reversible inhibition of COX-1 and COX-2 enzymes, and [...]

Intracerebral hemorrhage (ICH) is a subtype of stroke associated with higher rates of mortality. Currently, no effective drug treatment is available for ICH. The molecular pathways following ICH are complicated and diverse. Nucleic acid therapeutics such as gene knockdown by small interfering RNAs (siRNAs) have been developed in recent years to modulate ICH's destructive pathways and mitigate its outcomes. However, siRNAs delivery to the central nervous system is challenging and faces many roadblocks. Existing barriers to systemic delivery of siRNA limit the use of naked siRNA; therefore, siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain, or cell types seem quite promising. Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases. This review discusses the obstacles to siRNA delivery, including the advantages and disadvantages of viral and nonviral vectors. Additionally, we provide a comprehensive overview of recent progress in nanotherapeutics areas, primarily focusing on the delivery system of siRNA for ICH treatment., Competing Interests: None