A Quick Method for the Determination of the Fraction of Freebase Nicotine in Electronic Cigarettes.

Recently, many electronic cigarettes (ECIGs) manufacturers have begun offering e-liquids, known as "nicotine salts". These salts that have started gaining big popularity among users can be formed by adding weak acid to e-liquid mixtures consisting of propylene glycol (PG), vegetable glycerin (VG), flavors, and nicotine. The latter can exist in two forms: monoprotonated (mp) and freebase (fb) based on the pH of the matrix. Over the years, the determination of the fraction of fb was found important to policymakers as the prevalence of this form in ECIGs has been associated with the harshness sensory of inhalable aerosols. Liquid-liquid extraction (LLE), 1H NMR, and Henderson-Hasselback have been developed to deduce the fraction of fb; however, these methods were found to be time-consuming and have shown some challenges mainly due to the presence of a non-aqueous matrix consisting of PG and VG. This paper presents a quick non-aqueous pH measurement-based method that allows a quick determination of the fraction fb by just measuring the pH and the dielectric constant of the e-liquid. Then, by inputting these values into an established mathematical relationship, the fraction fb can be deduced. The relationship between pH, dielectric constant, and fb relies on knowing the values of the acidity dissociation constants of nicotine, which were determined for the first time in various PG/VG mixtures using a non-aqueous potentiometric titration. To validate the proposed method, the fraction fb was determined for commercials and lab-made nicotine salts utilizing the pH and LLE methods. The variation between the two methods was (<8.0%) for commercial e-liquids and lab-made nicotine salts containing lactic acid and salicylic acid. A larger discrepancy of up to 22% was observed for lab-made nicotine salts containing benzoic acid, which can be attributed to the stronger affinity of benzoic acid to toluene in the LLE method.

Carrier Solvents of Electronic Nicotine Delivery Systems Alter Pulmonary Surfactant.

In late 2019, hundreds of users of electronic products that aerosolize a liquid for inhalation were hospitalized with a variety of respiratory and gastrointestinal symptoms. While some investigations have attributed the disease to the presence of vitamin E acetate in liquids that also contained tetrahydrocannabinol, some evidence suggests that chronic inhalation of two common solvents used in electronic nicotine delivery systems (ENDS), propylene glycol (PG) and vegetable glycerin (VG), can interfere with the lipid components of pulmonary surfactant and cause or exacerbate pulmonary injury. The interaction between PG, VG, and lung surfactant is not yet understood. This study presents an examination of the molecular interactions of PG and VG with lung surfactant mimicked by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The interaction of DPPC and PG-VG is studied by attenuated total reflectance fourier transform infrared spectroscopy. The results showed that PG and VG altered the molecular alignment of the DPPC surfactant. The orientation of the surfactant at the surface of the lung affects the surface tension at the air-water interface, thereby influencing breathing. These findings suggest that chronic aerosolization of the primary solvents in ENDS might alter the function of pulmonary surfactant.

The Effect of Different Ester Chain Modifications of Two Guaianolides for Inhibition of Colorectal Cancer Cell Growth.

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide-A (Sal-A) and salograviolide-B (Sal-B) are two STLs that have been isolated from Centaurea ainetensis, an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal-A and Sal-B were modified and successfully prepared into eight novel guaianolide-type STLs (compounds 1-8) bearing ester groups of different geometries. Sal-A, Sal-B, and compounds 1-8 were tested against a human colorectal cancer cell line model with differing p53 status; HCT116 with wild-type p53 and HCT116 p53-/- null for p53, and the normal-like human colon mucosa cells with wild-type p53, NCM460. IC50 values indicated that derivatization of Sal-A and Sal-B resulted in potentiation of HCT116 cell growth inhibition by 97% and 66%, respectively. The effects of the different molecules on cancer cell growth were independent of p53 status. Interestingly, the derivatization of Sal-A and Sal-B molecules enhanced their anti-growth properties versus 5-Fluorouracil (5-FU), which is the drug of choice in colorectal cancer. Structure-activity analysis revealed that the enhanced molecule potencies were mainly attributed to the position and number of the hydroxy groups, the lipophilicity, and the superiority of ester groups over hydroxy substituents in terms of their branching and chain lengths. The favorable cytotoxicity and selectivity of the potent molecules, to cancer cells versus their normal counterparts, pointed them out as promising leads for anti-cancer drug design.

Free-Base and Total Nicotine, Reactive Oxygen Species, and Carbonyl Emissions From IQOS, a Heated Tobacco Product.

INTRODUCTION: IQOS is an emerging heated tobacco product marketed by Philip Morris International (PMI). Because the tobacco in IQOS is electrically heated and not combusted, PMI claims that it generates significantly lower toxicant levels than combustible cigarettes. To date, a few independent studies have addressed IQOS toxicant emissions, and none have reported reactive oxygen species (ROS), and the form of the nicotine emitted by the device. METHODS: In this study, IQOS aerosol was generated using a custom-made puffing machine. Two puffing regimens were used: Health Canada Intense and ISO. ROS, carbonyl compounds (CCs), and total nicotine and its partitioning between free-base and protonated forms were quantified in the IQOS aerosol by fluorescence, high-performance liquid chromatography, and gas chromatography, respectively. The same toxicants were also quantified in combustible cigarette aerosols for comparison. In addition, propylene glycol and vegetable glycerin were also measured in the IQOS tobacco and aerosol. RESULTS: IQOS and combustible cigarettes were found to emit similar quantities of total and free-base nicotine. IQOS total ROS (6.26 ± 2.72 nmol H2O2/session) and CC emissions (472 ± 19 µg/session) were significant, but 85% and 77% lower than levels emitted by combustible cigarettes. CONCLUSIONS: IQOS emits harmful constituents that are linked to cancer, pulmonary disease, and addiction in cigarette smokers. For a given nicotine intake, inhalation exposure to ROS and CCs from IQOS is likely to be significantly less than that for combustible cigarettes. IMPLICATIONS: IQOS is PMI's new heated tobacco product. PMI claims that because IQOS heats and does not burn tobacco it generates low toxicant yields. We found that one IQOS stick can emit similar free-base and total nicotine yields as a combustible cigarette. A pack-a-day equivalent user of IQOS may experience significant inhalation exposure of ROS and CCs compared to background air. However, substituting IQOS for combustible cigarettes will likely result in far lower ROS and carbonyl inhalation exposure for a given daily nicotine intake.

Toxicant inhalation among singleton waterpipe tobacco users in natural settings.

BACKGROUND: Studies that assess waterpipe tobacco smoking behaviour and toxicant exposure generally use controlled laboratory environments with small samples that may not fully capture real-world variability in human behaviour and waterpipe products. This study aimed to conduct real-time sampling of waterpipe tobacco use in natural environments using an in situ device. METHODS: We used the REALTIME sampling instrument: a validated, portable, self-powered device designed to sample automatically a fixed percentage of the aerosol flowing through the waterpipe mouthpiece during every puff. We recruited participants at café and home settings in Jordan and measured puffing behaviour in addition to inhalation exposure of total particulate matter (TPM), carbon monoxide (CO), nicotine, polycyclic aromatic hydrocarbons and volatile aldehydes. We correlated total inhaled volume with five selected toxicants and calculated the regression line of this relationship. RESULTS: Averaged across 79 singleton sessions (52% male, mean age 27.0, 95% home sessions), sessions lasted 46.9 min and participants drew 290 puffs and inhaled 214 L per session. Mean quantities of inhaled toxicants per session were 1910 mg TPM, 259 mg CO, 5.0 mg nicotine, 117 ng benzo[a]pyrene and 198 ng formaldehyde. We found positive correlations between total inhaled volume and TPM (r=0.472; p<0.001), CO (r=0.751; p<0.001), nicotine (r=0.301, p=0.035) and formaldehyde (r=0.526; p<0.001), but a non-significant correlation for benzo[a]pyrene (r=0.289; p=0.056). CONCLUSIONS: In the natural environment, waterpipe tobacco users inhale large quantities of toxicants that induce tobacco-related disease, including cancer. Toxicant content per waterpipe session is at least equal, but for many toxicants several magnitudes of order higher, than that of a cigarette. Health warnings based on early controlled laboratory studies were well founded; if anything our findings suggest a greater exposure risk.

Nicotine and Carbonyl Emissions From Popular Electronic Cigarette Products: Correlation to Liquid Composition and Design Characteristics.

Introduction: Available in hundreds of device designs and thousands of flavors, electronic cigarette (ECIG) may have differing toxicant emission characteristics. This study assesses nicotine and carbonyl yields in the most popular brands in the U.S. market. These products included disposable, prefilled cartridge, and tank-based ECIGs. Methods: Twenty-seven ECIG products of 10 brands were procured and their power outputs were measured. The e-liquids were characterized for pH, nicotine concentration, propylene glycol/vegetable glycerin (PG/VG) ratio, and water content. Aerosols were generated using a puffing machine and nicotine and carbonyls were, respectively, quantified using gas chromatograph and high-performance liquid chromatography. A multiregression model was used to interpret the data. Results: Nicotine yields varied from 0.27 to 2.91 mg/15 puffs, a range corresponding to the nicotine yield of less than 1 to more than 3 combustible cigarettes. Nicotine yield was highly correlated with ECIG type and brand, liquid nicotine concentration, and PG/VG ratio, and to a lower significance with electrical power, but not with pH and water content. Carbonyls, including the carcinogen formaldehyde, were detected in all ECIG aerosols, with total carbonyl concentrations ranging from 3.72 to 48.85 µg/15 puffs. Unlike nicotine, carbonyl concentrations were mainly correlated with power. Conclusion: In 15 puffs, some ECIG devices emit nicotine quantities that exceed those of tobacco cigarettes. Nicotine emissions vary widely across products but carbonyl emissions showed little variations. In spite of that ECIG users are exposed to toxicologically significant levels of carbonyl compounds, especially formaldehyde. Regression analysis showed the importance of design and e-liquid characteristics as determinants of nicotine and carbonyl emissions. Implications: Periodic surveying of characteristics of ECIG products available in the marketplace is valuable for understanding population-wide changes in ECIG use patterns over time.

Oxidative Potential of Ambient Particulate Matter in Beirut during Saharan and Arabian Dust Events.

In this study, we examine the oxidative potential of airborne particulate matter (PM) in Beirut, Lebanon, as influenced by dust events originating in the Sahara and Arabian deserts. Segregated fine (< 2.5 µm) and coarse (2.5-10 µm) PM samples collected during dust events, as well as during non-dust periods, were analyzed for chemical composition, and the in vitro alveolar macrophage (AM) assay was utilized to determine the oxidative potential of both types of samples. We performed Spearman rank-order correlation analysis between individual chemical components and the oxidative potential of PM to examine the impact of the changes in PM chemical composition due to the occurrence of dust events on overall PM oxidative potential. Our findings revealed that the oxidative potential of Beirut's urban PM during non-dust periods was much higher than during dust episodes for fine PM. Our findings also indicated that tracers of tailpipe emissions (i.e., elemental (EC) and organic carbon (OC)), non-tailpipe emissions (i.e., heavy metals including Cu, Zn, As, Cd, and Pb), and secondary organic aerosols (SOA) (i.e., water-soluble organic carbon, WSOC) were significantly associated with the oxidative potential of PM during dust days and non-dust periods. However, the contribution of desert dust aerosols to Beirut's indigenous PM composition did not exacerbate its oxidative potential, as indicated by the negative correlations between the oxidative potential of PM and the concentrations of crustal elements that were enriched during the dust days. This suggests that aerosols generated during Saharan and Arabian dust events pose no additional health risk to the population due to PM-triggered reactive oxygen species formation. These results significantly contribute to our understanding of the effects of desert dust aerosols on the composition and oxidative potential of PM in several countries throughout the entire Middle East region that are impacted by dust events in the Sahara and Arabian deserts.

Surface Chemistry of Electronic Cigarette Electrical Heating Coils: Effects of Metal Type on Propylene Glycol Thermal Decomposition.

INTRODUCTION: Carbonyls, a class of compounds strongly linked to pulmonary disease in smokers, are probably the most reported non-nicotine toxicants found aerosols. Reported emissions vary from negligible quantities to those far exceeding combustible cigarettes. Observations of high emissions are commonly attributed to "dry puffing", whereby the ECIG heating filament runs dry of liquid and reaches temperatures that induce thermal degradation of the ECIG vapor components at the filament's metal surface. Using a pyrolysis flow reactor, in this study we examined the potential role of surface chemistry in the formation of carbonyl compounds in ECIGs, and whether the different commercially available filament materials could potentially impact their toxicant emissions through catalysis. This information could inform nascent efforts to regulate the design of ECIGs for public health ends. METHODS: Nitrogen or air saturated with propylene glycol vapor was drawn through a temperature and residence time controlled tubular quartz pyrolysis flow reactor in which nichrome, Kanthal, or stainless steel ECIG heating filament wires were inserted. A control condition with no inserted wire was also included. Concentrations of carbonyl products at the reactor outlet were measured as a function of temperature, heating filament wire material, and carrier gas composition (N2 vs air). Carbonyls were sampled using DNPH cartridges and analyzed by HPLC. RESULTS: ECIG heating filament wires were found to have a strong catalytic effect. Carbonyl formation initiated at temperatures lower than 250°C in the presence of the metallic wires, compared to 460°C without them. Carbonyl formation was found to be a function of the material of construction, and whether the wire was new or aged. New nichrome wires were the least reactive, but when aged they exhibited the highest reactivity. Carbonyls were formed via dehydration or oxidation reactions of PG. CONCLUSIONS: Carbonyl formation chemistry is catalyzed by commonly used ECIG heating filament materials, at temperatures that are well below those expected during "dry puffing". The variability in the distribution and yield of carbonyl compounds across ECIG filament materials suggests that this heretofore unaccounted variable may partially explain the wide ranges reported in the literature to date. More importantly, it suggests that ECIG construction materials may be an important variable for regulations designed to protect public health.

Biomarkers of exposure to new and emerging tobacco delivery products.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

Carboxylate Counteranions in Electronic Cigarette Liquids: Influence on Nicotine Emissions.

The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine is normally associated with counteranions in tobacco products. The chemical and physical properties of counteranions may differently influence the nicotine form and emissions in ECIG aerosols. In this study, we examined how these anions influence nicotine emissions and their evaporation behavior and potential decomposition during ECIG operation. ECIG liquid solutions with equal nicotine concentration and pH but different counteranions (formate, acetate, and citrate) were prepared from analytical standards to assess the effect of the counteranion on nicotine partitioning. High performance liquid and gas chromatography methods were developed to determine the counteranions and the two protonated (NicH+) and free base (Nic) forms of nicotine in commercially available and standard solutions of ECIG liquids and aerosols. In commercial samples, acetate and citrate anions were detected. In standard solutions, both formate and acetate ions were found to evaporate intact, but citrate ion decomposed into formic acid and other products. This study also shows that the identity of the counteranion has no effect on total nicotine emission from ECIG in agreement with previous reports on tobacco cigarettes. However, the partitioning of aerosolized nicotine into NicH+ and Nic is anion-dependent even when the parent liquid pH is held constant. These results indicate that the anions found in a given ECIG product may influence the nicotine delivery profile to the user by enriching aerosols with free-base nicotine as in the case of polycarboxylic acids such as citric acid.

Detection of 5-hydroxymethylfurfural and furfural in the aerosol of electronic cigarettes.

SIGNIFICANCE: The wide availability of sweet flavours has been hypothesised as a factor in the popularity of electronic cigarette (ECIG), especially among youth. Saccharides, which are commonly used to impart a sweet flavour to ECIG liquids, thermally degrade to produce toxic compounds, like aldehydes and furans. This study investigates the formation of furanic compounds in aerosols when ECIG liquid solutions of varying sweetener concentrations are vaped under different power and puff duration. METHODS: Liquids are prepared by mixing aqueous sucrose, glucose or sorbitol solutions to a 70/30 propylene glycol/glycerin solution. Aerosols are generated and trapped on filter pads using a commercially available ECIG operating at 4.3 and 10.8 W and 4 and 8 s puff duration. Extraction, elimination of matrix interference and quantification are achieved using novel solid phase extraction and gas chromatography tandem mass spectrometry methods (GC-MS). RESULTS: Well-resolved GC peaks of 5-hydroxymethylfurfural (HMF) and furfural (FA) are detected. Both HMF and FA are quantified in the aerosols of sweet-flavoured e-liquids under various vaping conditions. Levels of furan emissions are significantly correlated with electric power and sweetener concentration and not with puff duration. Unlike saccharides, the formation of HMF and FA from a sugar alcohol is negligible. CONCLUSIONS: The addition of sweeteners to ECIG liquids exposes ECIG user to furans, a toxic class of compounds. Under certain conditions, the per-puff yield of HMF and FA in ECIG emissions is comparable to values reported for combustible cigarettes.

Free-Base and Protonated Nicotine in Electronic Cigarette Liquids and Aerosols.

As with other tobacco aerosols, nicotine delivery from e-cigarettes (ECIG) depends on the total nicotine and its partitioning between free-base (Nic) and protonated (NicH(+)) forms. Previous studies of ECIG nicotine emissions have generally reported "nicotine yield" without attention to whether the methods employed resulted in quantification of the total nicotine or only one of its forms, making reported results difficult to compare across studies or to evaluate against reported blood exposure. This study reports a convenient solvent extraction method for determining total nicotine and its partitioning in ECIG liquids and aerosols by gas chromatography. Commercial ECIG liquids and aerosols were analyzed, and it was found that most of the nicotine was in the Nic form, with aerosols exhibiting higher Nic fraction than the parent liquids. Apparent pH was found to correlate with nicotine partitioning and can provide a useful indirect measure when chromatography is unavailable. Finally, labeled ECIG liquid nicotine concentration in commercial products was often inconsistent with measured nicotine.

Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives.

OBJECTIVES: Waterpipe smoking using sweetened, flavoured tobacco products has become a widespread global phenomenon. In this paper, we review chemical, physical and biological properties of waterpipe smoke. DATA SOURCES: Peer-reviewed publications indexed in major databases between 1991 and 2014. Search keywords included a combination of: waterpipe, narghile, hookah, shisha along with names of chemical compounds and classes of compounds, in addition to terms commonly used in cellular biology and aerosol sizing. STUDY SELECTION: The search was limited to articles published in English which reported novel data on waterpipe tobacco smoke (WTS) toxicant content, biological activity or particle size and which met various criteria for analytical rigour including: method specificity and selectivity, precision, accuracy and recovery, linearity, range, and stability. DATA EXTRACTION: Multiple researchers reviewed the reports and collectively agreed on which data were pertinent for inclusion. DATA SYNTHESIS: Waterpipe smoke contains significant concentrations of toxicants thought to cause dependence, heart disease, lung disease and cancer in cigarette smokers, and includes 27 known or suspected carcinogens. Waterpipe smoke is a respirable aerosol that induces cellular responses associated with pulmonary and arterial diseases. Except nicotine, smoke generated using tobacco-free preparations marketed for 'health conscious' users contains the same or greater doses of toxicants, with the same cellular effects as conventional products. Toxicant yield data from the analytical laboratory are consistent with studies of exposure biomarkers in waterpipe users. CONCLUSIONS: A sufficient evidence base exists to support public health interventions that highlight the fact that WTS presents a serious inhalation hazard.

Phenolic compounds in particles of mainstream waterpipe smoke.

INTRODUCTION: Waterpipe tobacco smoking has in recent years become a popular international phenomenon, particularly among youth. While it has been shown to deliver significant quantities of several carcinogenic and toxic substances, phenols, an important class of chemical compounds thought to promote DNA mutation and cardiovascular diseases, however, has not been studied. Due to the relatively low temperature characteristic of waterpipe tobacco during smoking (i.e., <450 °C), it was hypothesized that phenolic compounds, which form at approximately 300 °C, will be found in abundance in waterpipe smoke. METHODS: In this study, phenolic compounds in the particle phase of waterpipe mainstream smoke were quantified. Waterpipe and cigarette mainstream smoke generated using standard methods were collected on glass fiber pads and analyzed using gas chromatography/mass spectroscopy selected ion current profile chromatogram method for quantification. RESULTS: We found that relative to a single cigarette, a waterpipe delivers at least 3 times greater quantities of the 7 analyzed phenols (phenol, o-cresol, m-cresol, p-cresol, catechol, resorcinol, and hydroquinone). Moreover, phenol derivatives such as methylcatechol, and flavorings such as vanillin, ethyl vanillin, and benzyl alcohol were found in quantities up to 1,000 times greater than the amount measured in the smoke of a single cigarette. CONCLUSION: The large quantities of phenols and phenol derivatives in waterpipe smoke add to the growing evidence that habitual waterpipe use may increase the risk of cancer and cardiovascular diseases.

Road versus roadside particle size distribution in a hot Mediterranean summer--estimation of fleet emission factors.

UNLABELLED: Particle size distribution at major on-road, roadside, and university-ground sites in Lebanon were studied in summer 2011. In a predominant old traffic fleet, it is shown that calculated PM2.5 mass emission factors (EFs) conform to those of heavy duty vehicles. When compared to roads in California, higher PM2.5 mass but similar particle number EFs are obtained for the average fleet of the on-road sites. This confirms the observed particle size distribution pattern, rich in particles in the accumulation range mainly between 0.425 and 0.675 microm with a prevalent peak at 0.475 microm. Corresponding total particle counts (TC) measured on the roadside are as high as 14,050 particles/cm3 and are up to 67% higher than particle counts measured at the university-ground site. In a hot, dry and humid summer weather with consistent temperature oscillations, particle dispersion is shown to be a function of meteorological factors, mainly the effect of the boundary-layer thickness, with particle counts measured during the morning being around 40% higher than particle counts measured during the afternoon. IMPLICATIONS: In a hot and humid Mediterranean summer, high emission factors are associated with an old car fleet. The observed diurnal variation in the particle count is attributed to the change in the thickness boundary layer in summer. In comparison to road sites, the particle size distribution shows the prevalence of larger size particles. Particle counts measured at the roadside sites are at least 20% higher than those of the road sites. The findings call for the reinforcement of local regulations on car age. Furthermore, the high number of particles can cause or aggravate a number of health and ecosystem problems.

Differential growth inhibitory effects of highly oxygenated guaianolides isolated from the Middle Eastern indigenous plant Achillea falcata in HCT-116 colorectal cancer cells.

Medicinal plants play a crucial role in traditional medicine and in the maintenance of human health worldwide. Sesquiterpene lactones represent an interesting group of plant-derived compounds that are currently being tested as lead drugs in cancer clinical trials. Achillea falcata is a medicinal plant indigenous to the Middle Eastern region and belongs to the Asteraceae family, which is known to be rich in sesquiterpene lactones. We subjected Achillea falcata extracts to bioassay-guided fractionation against the growth of HCT-116 colorectal cancer cells and identified four secotanapartholides, namely 3-ß-methoxy-isosecotanapartholide (1), isosecotanapartholide (2), tanaphallin (3), and 8-hydroxy-3-methoxyisosecotanapartholide (4). Three highly oxygenated guaianolides were isolated for the first time from Achillea falcata, namely rupin A (5), chrysartemin B (6), and 1ß, 2ß-epoxy-3ß,4α,10α-trihydroxyguaian-6α,12-olide (7). These sesquiterpene lactones showed no or minor cytotoxicity while exhibiting promising anticancer effects against HCT-116 cells. Further structure-activity relationship studies related the bioactivity of the tested compounds to their skeleton, their lipophilicity, and to the type of functional groups neighboring the main alkylating center of the molecule.

Effects of Desert Dust and Sandstorms on Human Health: A Scoping Review.

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross-tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time-series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health.

Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.

BACKGROUND: Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-ß-methoxy-iso-seco-tanapartholide (ß-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how ß-tan and Sal A modulate their signaling pathways in JB6P + cells. METHODS: The effects of ß-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. RESULTS: ß-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. CONCLUSIONS: These results highlight the anti-tumor promoting properties of ß-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary medicine practices.

Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention.

INTRODUCTION: Sesquiterpene lactones (SLs) are one of the most diverse bioactive secondary metabolites found in plants and exhibit a broad range of therapeutic properties . SLs have been showing promising potential in cancer clinical trials, and the molecular mechanisms underlying their anticancer potential are being uncovered. Recent evidence also points to a potential utility of SLs in cancer prevention. AREAS COVERED: This work evaluates SLs with promising anticancer potential based on cell, animal, and clinical models: Artemisinin, micheliolide, thapsigargin dehydrocostuslactone, arglabin, parthenolide, costunolide, deoxyelephantopin, alantolactone, isoalantolactone, atractylenolide 1, and xanthatin as well as their synthetic derivatives. We highlight actionable molecular targets and biological mechanisms underlying the anticancer therapeutic properties of SLs. This is complemented by a unique assessment of SL mechanisms of action that can be exploited in cancer prevention. We also provide insights into structure-activity and pharmacokinetic properties of SLs and their potential use in combination therapies. EXPERT OPINION: We extract seven major lessons learned and present evidence-based solutions that can circumvent some scientific limitations or logistic impediments in SL anticancer research. SLs continue to be at the forefront of cancer drug discovery and are worth a joint interdisciplinary effort in order to leverage their potential in cancer therapy and prevention.

Updated national emission inventory and comparison with the Emissions Database for Global Atmospheric Research (EDGAR): case of Lebanon.

Physically based computational modeling is an effective tool for estimating and predicting the spatial distribution of pollutant concentrations in complex environments. A detailed and up-to-date emission inventory is one of the most important components of atmospheric modeling and a prerequisite for achieving high model performance. Lebanon lacks an accurate inventory of anthropogenic emission fluxes. In the absence of a clear emission standard and standardized activity datasets in Lebanon, this work serves to fill this gap by presenting the first national effort to develop a national emission inventory by exhaustively quantifying detailed multisector, multi-species pollutant emissions in Lebanon for atmospheric pollutants that are internationally monitored and regulated as relevant to air quality. Following the classification of the Emissions Database for Global Atmospheric Research (EDGAR), we present the methodology followed for each subsector based on its characteristics and types of fuels consumed. The estimated emissions encompass gaseous species (CO, NOx, SO2), and particulate matter (PM2.5 and PM10). We compare totals per sector obtained from the newly developed national inventory with the international EDGAR inventory and previously published emission inventories for the country for base year 2010 presenting current discrepancies and analyzing their causes. The observed discrepancies highlight the fact that emission inventories, especially for data-scarce settings, are highly sensitive to the activity data and their underlying assumptions, and to the methodology used to estimate the emissions.