ABSTRACTHouse geckos share living quarters with humans in the tropical and subtropical regions inhabited by these reptiles. Gecko behavior, biological traits, continuous exposure to suspended particulate matter 0 µm in diameter (PM10) and dust, as well as status as exotic species, motivated the choice of these species to examine environmental exposure to ambient air pollutants, in particular metals, and subsequent accumulation in these organisms. One part of the study was conducted in Tamaulipas (Mexico) where Hemydactylus frenatus is abundant in urban and industrial environments, the other part was conducted in Andalucia (Spain) where Tarentola mauritanica is found in similar environments. Adult geckos were collected on buildings in locations affected by various air pollution sources. For both species, higher metal contents were observed in whole-body (including digestive tracts) analysis and were markedly different between collection sites. Contents in tails, digestive tracts, and carcasses without digestive tracts were not correlated. Based on contamination factor values, bioaccumulation in H. frenatus tissues occurred for 12 of the 15 metals analyzed. Data suggest that H. frenatus might serve as a biomonitor for Cu, Ni, Pb, Cr, Li, and V, whereas T. mauritanica might be a biomonitor for Cu, Ni, Pb, and Cr. To our knowledge, metal contents for H. frenatus are reported here for the first time. House gecko data could be integrated into a highly representative monitoring system and health risk assessments related to air quality in residential areas.

ABSTRACTCroton heliotropiifolius Kunth, popularly known as “quince” and “velame,” contains a high concentration of volatile oils in the leaves, and widely used in folk medicine as an antiseptic, analgesic, sedative, anti-inflammatory, spasmolytic and local anesthetic. The objectives of this investigation were to (1) identify the phytochemical compounds and (2) assess the cytogenotoxicity of the essential oil extracted from the leaves of C. heliotropiifolius Kunth. The oil was extracted utilizing hydrodistillation and phytochemical profile determined using gas chromatography and mass spectrometry (GCMS). In the toxicogenetics analysis, Allium cepa roots were exposed to 1% dimethylsulfoxide or methylmethanesulfonate (MMS, 10 µg/ml) negative and positive controls, respectively, and to C. heliotropiifolius oil at 6 concentrations (0.32; 1.6; 8; 40; 200 or 1000 µg/ml). The phytochemical profile exhibited 40 chromatographic bands, and 33 compounds identified. α-pinene (16.7%) and 1,8-cineole (13.81%) were identified as the major compounds. Some of these identified secondary metabolites displayed biological and pharmacological activities previously reported including antiseptic, analgesic, sedative, anti-inflammatory as well insecticidal, antiviral, anti-fungal actions. In the A. cepa test, C. heliotropiifolius leaves oil induced cytotoxicity at concentrations of 0.32, 1.6 or 200 µg/ml and genotoxicity at 200 or 1000 µg/ml as evidenced by increased presence of micronuclei and significant chromosomal losses. Based upon our observations data demonstrated that the essential oil of C. heliotropiifolius leaves contain monoterpene hydrocarbons, and oxygenated monoterpenes, sesquiterpenes, and oxygenated sesquiterpenes which are associated with cytotoxic and genotoxic responses noted in on A. cepa cells.

ABSTRACTDaminozide (alar), a plant growth retardant, is used in different fruit orchard to make fruits attractive and reduce pre-harvest losses. Previously data demonstrated that acute daminozide exposure affected reproductive fitness and produced neurodegeneration in Drosophila melanogaster. The goal of this study was to determine whether continuous exposure to daminozide affects neuromuscular co-ordination in D. melanogaster as manifested in various behavioral responses. Fruit flies were exposed to 200 or 400 mg/L concentration of daminozide for two successive generations. Treated D. melanogaster were examined for the behaviors indicative of neuromuscular coordination and cognitive abilities, that include climbing, social interaction, adult grooming, migration, flight, male aggression, and adult courtship. Aberrant behavioral responses were noted among treated D. melanogaster of both sexes as evidenced by the following parameters: reduction in flight duration, abnormal social interaction, altered copulatory acts, and over-aggressiveness. Data suggest that daminozide produces impairment in neuromuscular coordination and cognitive ability in Drosophila, which was reflected as altered behavioral patterns. As Drosophila is considered as a reliable in vivo model utilized in toxicity testing, our findings may help us to anticipate and monitor potential daminozide-induced toxicity in animals and humans.

ABSTRACTOne of the main problems related to ferruginous-asbestos bodies (ABs) exposure is their potential pathogenetic role in asbestos-related diseases. The aim of this study was to examine whether purified ABs, might stimulate inflammatory cells. ABs were isolated by exploiting their magnetic properties, therefore avoiding the strong chemical treatment usually employed for this purpose. This latter treatment, which is based upon the digestion of organic matter with concentrated hypochlorite, may markedly modify the AB structure and consequently also their “in vivo” manifestations. ABs were found to induce secretion of human neutrophil granular component myeloperoxidase, as well as stimulate rat mast cell degranulation. Data demonstrated that by triggering secretory processes in inflammatory cells, purified ABs may play a role in the pathogenesis of asbestos-related diseases by continuing and enhancing the pro-inflammatory activity of the asbestos fibers.

Chimarrão is a typical beverage made from the infusion of dried and ground leaves and stems of Ilex paraguariensis (popularly known as Yerba mate or mate herb) which is widely consumed in parts of South America. The aim of this study was to examine the effects of the chimarrão against nephrotoxicity and oxidative stress induced by the potassium dichromate (PD) salt in male Wistar rats. The experiment lasted 17 days, and in the first 15 days animals ingested a chimarrão infusion or control drinking water and then submitted to an intraperitoneal injection (15 mg/kg) of PD (or saline solution) and euthanized after 48 hr at which time animals still received infusion or drinking water. Blood plasma and 24 hr-urine samples were collected to measure creatinine levels as an estimate of glomerular filtration rate (GFR). Concomitantly oxidative stress was determined in the kidneys as evidenced by levels of carbonyl groups, malondialdehyde (MDA) and antioxidant capacity against peroxyl radicals. Potassium dichromate induced oxidative stress in the kidneys and reduced GFR. Treatment with chimarrão during the 15 days prior to PD injection reduced PD salt-mediated oxidative stress. Further, treatment with post-injection chimarrão to PD-administered rats improved the GFR. Our findings support that the use of the chimarrão beverage may be considered as an important nephroprotective substance.

ABSTRACTHymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC50 of 3.12 μg/ml. The extract at concentrations of 400 and 800 μg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 μg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 μg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 μl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.

ABSTRACTThe measurement of fine (diameter: 100 nanometers–2.5 micrometers) and ultrafine (UF: < 100 nanometers) titanium dioxide (TiO2) particles is instrument dependent. Differences in measurements exist between toxicological and field investigations for the same exposure metric such as mass, number, or surface area because of variations in instruments used, operating parameters, or particle-size measurement ranges. Without appropriate comparison, instrument measurements create a disconnect between toxicological and field investigations for a given exposure metric. Our objective was to compare a variety of instruments including multiple metrics including mass, number, and surface area (SA) concentrations for assessing different concentrations of separately aerosolized fine and UF TiO2 particles. The instruments studied were (1) DustTrak™ DRX, (2) personal DataRAMs™ (PDR), (3) GRIMMTM, and (4) diffusion charger (DC). Two devices of each field-study instrument (DRX, PDR, GRIMM, and DC) were used to measure various metrics while adjusting for gravimetric mass concentrations of fine and UF TiO2 particles in controlled chamber tests. An analysis of variance (ANOVA) was used to apportion the variance to inter-instrument (between different instrument-types), inter-device (within instrument), and intra-device components. Performance of each instrument-device was calculated using root mean squared error compared to reference methods: close-faced cassette and gravimetric analysis for mass and scanning mobility particle sizer (SMPS) real-time monitoring for number and SA concentrations. Generally, inter-instrument variability accounted for the greatest (62.6% or more) source of variance for mass, and SA-based concentrations of fine and UF TiO2 particles. However, higher intra-device variability (53.7%) was observed for number concentrations measurements with fine particles compared to inter-instrument variability (40.8%). Inter-device variance range(0.5–5.5%) was similar for all exposure metrics. DRX performed better in measuring mass closer to gravimetric than PDRs for fine and UF TiO2. Number concentrations measured by GRIMMs and SA measurements by DCs were considerably (40.8–86.9%) different from the reference (SMPS) method for comparable size ranges of fine and UF TiO2. This information may serve to aid in interpreting assessments in risk models, epidemiologic studies, and development of occupational exposure limits, relating to health effect endpoints identified in toxicological studies considering similar instruments evaluated in this study.

ABSTRACTCassia fistula L. is well known for its traditional medicinal properties as an anti-inflammatory, hepatoprotective, antifungal, antibacterial, antimutagenic, and wound healing agent. The aim of the present study was to determine antioxidant, genoprotective, and cytotoxic potential of different fractions of C. fistula bark including hexane (CaMH), chloroform (CaMC), ethyl acetate (CaME), and methanol (CaMM). Among all the fractions studied, CaMM exhibited maximal radical scavenging activity in antioxidant DPPH assay, Superoxide anion radical scavenging assay and nitric oxide radical scavenging assay displayed an IC50 value of 18.95, 29.41, and 13.38 µg/ml, respectively. CaMM fraction possessed the highest phenolic (130.37 mg gallic acid equivalent/g dry weight of extract) and flavonoid (36.96 mg rutin equivalent/g dry weight of fraction) content. Data demonstrated significant positive correlation between polyphenol levels and radical scavenging activity. Single cell gel electrophoresis (Comet assay) exhibited genoprotective potential of C. fistula bark fractions against DNA damage induced by hydrogen peroxide (H2O2) in human lymphocytes. CaMM fraction displayed highest protective ability against H2O2 induced-toxicity as evidenced by significant decrease in % tail DNA content from 30 to 7% at highest concentration (200 µg/ml). CaMM was found to be rich in catechin, gallic acid, chlorogenic acid, and kaempferol. The phenolic content and antioxidant ability of the fractions was markedly negatively correlated with H2O2- induced DNA damage in human lymphocytes. Cytotoxic potential was evaluated against dermal epidermoid carcinoma (A431), pancreatic (MIA PaCa-2) and brain glioblastoma (LN-18) cancer cell lines using MTT assay. Results showed that C. fistula bark fractions possessed highest toxicity against the skin carcinoma cells. CaMM fraction reduced over 50% cell growth at the concentration of 76.72 µg/ml in A431 cells. These findings suggest that fractions of C. fistula bark exhibit potential to be considered as therapeutic agents in various carcinomas.

ABSTRACTAsbestos fibers interact with many different proteins and may affect either their structure or functions. The aim of this study was to determine whether ferritin absorbed onto fibers might modify its ferroxidase activity. By measuring apo-ferritin ferroxidase activity, data demonstrated that ferritin in the presence of fibers did not significantly modify this enzymatic activity. However, fibers in the absence of ferritin promoted ferrous iron oxidation. Evidence suggests that asbestos fibers may promote iron oxidation and subsequently affect cellular iron homeostatic mechanisms.

ABSTRACTFluopsin C is an antibiotic compound derived from secondary metabolism of different microorganisms, which possesses antitumor, antibacterial, and antifungal activity. Related to fluopsin C antiproliferative activity, the aim of this study was to examine the following parameters: cytotoxicity, genotoxicity, cell cycle arrest, cell death induction (apoptosis), mitochondrial membrane potential (MMP), colony formation, and mRNA expression of genes involved in adaptive stress responses and cellular death utilizing a monolayer. In addition, a three-dimensional cell culture was used to evaluate the effects on growth of tumor spheroids. Fluopsin C was cytotoxic (1) producing cell division arrest in the G1 phase, (2) elevating expression of mRNA of the CDKN1A gene and (3) decrease in expression of mRNA H2AFX gene. Further, fluopsin C enhanced DNA damage as evidenced by increased expression of mRNA of GADD45A and GPX1 genes, indicating that reactive oxygen species (ROS) may be involved in the observed genotoxic response. Reticulum stress was also detected as noted from activation of the ribonuclease inositol-requiring protein 1 (IRE1) pathway, since a rise in mRNA expression of the ERN1 and TRAF2 genes was observed. During the cell death process, an increase in mRNA expression of the BBC3 gene was noted, indicating participation of this antibiotic in oncotic (ischemic) cell death. Data thus demonstrated for the first time that fluopsin C interferes with the volume of tumor spheroids, in order to attenuate their growth. Our findings show that fluopsin C modulates essential molecular processes in response to stress and cell death.

ABSTRACTCancer and infectious diseases are among the leading causes of death in the world. Despite the diverse array of treatments available, challenges posed by resistance, side effects, high costs, and inaccessibility persist. In the Solanaceae plant family, few studies with Vassobia breviflora species relating to biological activity are known, but promising results have emerged. The phytochemicals present in the ethyl acetate fraction were obtained using ESI-MS-QTOF, and the antioxidants assays 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical capture (ABTS), plasma ferric reduction capacity (FRAP), and total antioxidant capacity (TAC). Cytotoxic activity was evaluated by MTT, Neutral Red, and lactate dehydrogenase (LDH) released. The production of reactive oxygen species, nitric oxide, and purinergic enzymes was also investigated. Antibacterial activity was measured through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibiofilm activity, in addition to genotoxicity in plasmid DNA. Five major masses were identified D-glucopyranose II, allyl disulfide, γ-lactones, pharbilignoside, and one mass was not identified. V. breviflora exhibited relevant antioxidant and cytotoxic activity against the HeLa cell line and enhanced expression effect in modulation of purinergic signaling. Antibacterial activities in the assays in 7 ATCC strains and 8 multidrug-resistant clinical isolates were found. V. breviflora blocked biofilm formation in producing bacteria at the highest concentrations tested. However, there was no plasmid DNA cleavage at the concentrations tested. Data demonstrated that V. breviflora exhibited an antioxidant effect through several methods and proved to be a promising therapeutic alternative for use against tumor cells via purinergic signaling and multidrug-resistant microorganisms, presenting an anti-biofilm effect.

ABSTRACTThe development of agroecology has promoted the discovery of new bioactive compounds that might act as biocides to control infections and microbial contamination. Algae belonging to Lyngbya genus produce several allelochemicals, which are compounds with crop protection potential. The present study aimed to examine primary and secondary compounds derived from Lyngbya sp. extracts (aqueous and hydroethanolic) on phytotoxic, cytogenotoxic, and insecticidal activities. Determination of compounds indicated the presence predominantly of proteins and flavonoids. The extracts presented physicochemical characteristics that produced (1) 89% germination inhibition using hydroethanolic extract and (2) diminished development of seedlings of L. sativa by hydroethanolic extract as evidenced by reduced radicles length in 83.54%. Aqueous and hydroethanolic Lyngbya sp. extracts significantly interfered with meristematic cells of A. cepa, as evidenced by chromosomal alterations and aberrant mitotic phases in cells. Extracts also exhibited pro-oxidative activity and a potent insecticidal potential on S. zeamais, indicating that the hydroethanolic extract produced 100% insect mortality at 75 mg/ml after 48 hr while the aqueous extract initiated 90% mortality at the same concentration after 82 hr. Therefore, data demonstrate that Lyngbya genus provides basic information for new environmental and ecotoxicological studies to seek a possible source of proteins and flavonoids to be used in agroecological management.

ABSTRACTThe aim of this study was to determine the biological effects of dietary supplementation with 0.05% and 0.1% cinnamon essential oil extracted from Cinnamomum cassia on silver catfish (Rhamdia quelen). The final body weight, weight gain, and specific growth rate were significantly higher in fish supplemented with 0.05% cinnamon essential oil than in the control(untreated) group. Muscle reactive oxygen species and lipid peroxidation levels were significantly lower in fish supplemented with 0.05% cinnamon essential oil but higher at the 0.1% concentration. Muscle antioxidant capacity against peroxyl radicals (ACAP) and superoxide dismutase activity were significantly higher in fish supplemented with 0.05% cinnamon essential oil, while ACAP levels were lower in fish supplemented with 0.1%. The total saturated fatty acid content was significantly higher in the muscle of supplemented fish than in controls, while the total monounsaturated fatty acid content was significantly higher only in fish fed 0.1% cinnamon essential oil. Finally, the total content of polyunsaturated fatty acids was significantly lower in fish fed 0.1% essential oil. Thus, data demonstrated that 0.05% C. cassia essential oil improves fish health by improving performance and muscle oxidant/antioxidant status. Higher doses of cinnamon essential oil produced oxidative stress in muscle, suggesting toxicity at the 0.1% level. Although this cinnamon essential oil diet exerted positive health effects, this diet impaired the muscle fatty acid profile, suggesting adverse impacts on human health.

ABSTRACTFish early life stages are well known for their sensitivity to crude oil exposure. However, the effect of crude oil exposure on adults and their gametes during their spawning period is not well studied. Polar cod, a key arctic fish, may be at risk for crude oil exposure during this potentially sensitive life stage. Additionally, this species experiences lower food availability during their spawning season, with unknown combined consequences. In the present study, wild-caught polar cod were exposed to decreasing levels of a water-soluble fraction (WSF) of crude oil or control conditions and fed either at a low or high feed ration to assess the combined effect of both stressors. Samples were taken during late gonadal development, during active spawning (spawning window), and in the post-spawning period. Histology analysis of gonads from fish sampled during the spawning window showed that oil-exposed polar cod were more likely to have spawned compared to controls. Oil-exposed females had 947 differentially regulated hepatic genes, and their eggs had a higher polycyclic aromatic hydrocarbon body burden compared to controls. Feed ration did not consistently affect polar cod’s response to oil exposure for the endpoints measured, however, did alone result in decreases in some sperm motility parameters. These results suggest that polar cod’s spawning period is a sensitive life event to crude oil exposure, while feed limitation may play a minor role for this supposedly capital breeder. The effects of adult exposure to crude oil on gamete quality and the next generation warrant further investigation.

ABSTRACTCoumarins and chalcones are compounds widely found in plants or obtained by synthetic methods which possess several biological properties including antioxidant, anti-inflammatory, and antitumor effects. A series of coumarin-chalcone hybrids were synthesized to improve their biological actions and reduce potential adverse effects. Considering the applications of these molecules, a coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl) acryloyl-2 H-chromen-2-one] (4-MET) was synthesized and the genotoxic, cytotoxic, and protective effects assessed against damage induced by different mutagens. First, in silico tools were used to predict biological activity of 4-MET which indicated a chemopreventive potential. Subsequently, the genotoxic/antigenotoxic activities of 4-MET were determined both in vitro (Ames test) and in vivo (micronucleus (MN) test and comet assay). In addition, molecular docking simulations were performed between 4-MET and glutathione reductase, an important cellular detoxifying enzyme. Our results indicated that 4-MET was not mutagenic in the Ames test; however, when co-treated with sodium azide or 4-nitroquinoline 1-oxide (4-NQO), 4-MET significantly reduced the harmful actions of these mutagens. Except for a cytotoxic effect after 120 hr treatment, 4-MET alone did not produce cytotoxicity or genotoxicity in the MN test and comet assay. Nonetheless, all treatments of 4-MET with cyclophosphamide (CPA) showed a chemoprotective effect against DNA damage induced by CPA. Further, molecular docking analysis indicated a strong interaction between 4-MET and the catalytic site of glutathione reductase. These effects may be related to (1) damage prevention, (2) interaction with detoxifying enzymes, and (3) DNA-repair induction. Therefore, data demonstrated that 4-MET presents a favorable profile to be used in chemopreventive therapies.

ABSTRACTThe aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible mushrooms belonging to the Boletaceae family mushrooms. In addition, methanol extracts of mushrooms were tested for in vitro protective effect by the cytochalasin-B blocked micronucleus (CBMN) assay using chromosome aberrations in human peripheral lymphocytes as a model. The genotoxic activity of methanol extracts prepared at 4 different concentrations (1, 2, 3 or 6 µg/ml) was examined using amifostine and mitomycin C as positive controls. Extracts of species B. regius and B. edulis exhibited the greatest reduction in the frequency of micronuclei (MN). Extract of B. regius at concentrations of 2 µg/ml showed the highest decrease in number of MN. In comparison, extract of mushroom B. edulis at a concentration of 3 µg/ml displayed less reduction. However, as heavy metals and metalloids are found in mushrooms, another aim was to examine whether these agents affected genotoxicity. Principal component analysis (PCA) identified clustering differences between control and heavy metals and metalloids groups and might explain the influence of heavy element content and genotoxic activity in mushrooms.

ABSTRACTAccording to the International Agency for Research on Cancer (IARC), airborne fine particulate matter (PM2.5), which is categorized as a Group I carcinogen, was found to lead to predominantly lung as well as other cancer types in humans. Hepatocellular carcinoma (HCC) is endemic in Taiwan where it is the second and fourth foremost cause of cancer deaths in men and women, respectively. Taiwan’s mortality rates for liver cancer vary considerably from one region to another, suggesting that the environment may exert some influence on deaths attributed to liver cancer. The aim of this investigation was to perform an ecologic study to examine the possible link between ambient PM2.5 levels and risk of liver cancer in 66 in Taiwan municipalities. To undertake this investigation, annual PM2.5 levels and age-standardized liver cancer mortality rates were calculated for male and female residents of these areas from 2010 to 2019. Data were tested using weighted-multiple regression analyses to compute adjusted risk ratio (RR) controlling for urbanization level and physician density. Annual PM2.5 levels of each municipality were divided into tertiles. The adjusted RRs for males residing in those areas with intermediate tertile levels (21.85 to 28.21 ug/m3) and the highest tertiles levels (28.22–31.23 ug/m3) of PM2.5 were 1.29 (95% CI = 1.25–1.46) and 1.41 (95% CI = 1.36–1.46), respectively. Women in these locations shared a similar risk, 1.32 (1.25–1.4) and 1.41 (1.34–1.49), respectively. Evidence indicated that PM2.5 increased risk of mortality rates attributed to liver cancer in both men and women in Taiwan.

ABSTRACTWelding fumes contain harmful metals and gas by-products associated with development of lung dysfunction, asthma, bronchitis, and lung cancer. Two prominent welding fume particulate metal components are nanosized iron (Fe) and manganese (Mn) which might induce oxidative stress and inflammation resulting in pulmonary injury. Welding fume toxicity may be dependent upon metal nanoparticle (NP) components. To examine toxicity of welding fume NP components, a system was constructed for controlled and continuous NP generation from commercial welding and customized electrodes with varying proportions of Fe and Mn. Aerosols generated consisted of nanosized particles and were compositionally consistent with each electrode. Human alveolar lung A459 epithelial cells were exposed to freshly generated metal NP mixtures at a target concentration of 100 µg/m3 for 6 hr and then harvested for assessment of cytotoxicity, generation of reactive oxygen species (ROS), and alterations in the expression of genes and proteins involved in metal regulation, inflammatory responses, and oxidative stress. Aerosol exposures decreased cell viability and induced increased ROS production. Assessment of gene expression demonstrated variable up-regulation in cellular mechanisms related to metal transport and storage, inflammation, and oxidative stress based upon aerosol composition. Specifically, interleukin-8 (IL-8) demonstrated the most robust changes in both transcriptional and protein levels after exposure. Interleukin-8 has been determined to serve as a primary cytokine mediating inflammatory responses induced by welding fume exposures in alveolar epithelial cells. Overall, this study demonstrated variations in cellular responses to metal NP mixtures suggesting compositional variations in NP content within welding fumes may influence inhalation toxicity.

ABSTRACTPressure from expanding populations has resulted in a need for protection, reclamation, and restoration of damaged land to productive, beneficial health uses. The objective of this investigation was to 1) compare land cover on the Department of Energy (DOE) Oak Ridge Reservation (ORR) with the surrounding region, 2) select an indicator to evaluate ORR’s protection of ecological resources, and 3) develop and implement a method to compare the amount of the indicator on ORR with the regions using National Land Cover Database (NLCD). Data demonstrated that ORR has a higher % of forests (deciduous, coniferous, mixed) than the 10 km and 30 km areas surrounding ORR, suggesting that obligations are being met to protect the ecology and environment. The findings also indicate that the interior forest at ORR is fragmented more than is the interior forest in the 30 km buffer zone, suggesting a need for DOE and managers of other lands to take into consideration the importance of intact interior forest when developing land or planning roads. The study describes the basis for specific ecological parameters such as interior forest that are important to consider when planning and executing remediation, restoration, and other management actions.

ABSTRACTVassobia breviflora belongs to the Solanaceae family, possessing biological activity against tumor cells and is a promising alternative for therapy. The aim of this investigation was to determine the phytochemical properties V. breviflora using ESI-ToF-MS. The cytotoxic effects of this extract were examined in B16-F10 melanoma cells and the relationship if any to purinergic signaling was involved. The antioxidant activity of total phenols, (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) was analyzed, as well as production of reactive oxygen species (ROS) and nitric oxide (NO) was determined. Genotoxicity was assessed by DNA damage assay. Subsequently, the structural bioactive compounds were docked against purinoceptors P2X7 and P2Y1 receptors. The bioactive compounds found in V. breviflora were N-methyl-(2S,4 R)-trans-4-hydroxy-L-proline, calystegine B, 12-O-benzoyl- tenacigenin A and bungoside B. In vitro cytotoxicity was demonstrated at concentration ranges of 0.1–10 mg/ml, and plasmid DNA breaks only at the concentration of 10 mg/ml. V. breviflora extracts affected hydrolysis by ectoenzymes, such as ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ectoadenosine deaminase (E-ADA) which control levels of degradation and formation of nucleosides and nucleotides. In the presence of substrates ATP, ADP, AMP and adenosine, the activities of E-NTPDase, 5´-NT or E-ADA were significantly modulated by V. breviflora. N-methyl-(2S,4 R)-trans-4-hydroxy-L-proline presented higher binding affinity (according to receptor-ligand complex estimated binding affinity as evidenced by ∆G values) to bind to both P2X7 and P2Y1purinergic receptors.Our results suggest a putative interaction of V. breviflora bioactive compounds with growth inhibitory potential in B16-F10 melanoma and suggest that may be considered as promising compounds in melanoma and cancer treatment