The aim of this study was to analyze the cytotoxicity and genotoxicity of titanium oxide (TiO
2) and aluminium oxide (Al
2O
3) nanoparticles (NPs) on Chinese hamster ovary (CHO-K1) cells using ...neutral red (NR), mitochondrial activity (by MTT assay), sister chromatid exchange (SCE), micronucleus (MN) formation, and cell cycle kinetics techniques. Results showed a dose-related cytotoxic effect evidenced after 24
h by changes in lysosomal and mitochondrial dehydrogenase activity. Interestingly, transmission electronic microscopy (TEM) showed the formation of perinuclear vesicles in CHO-K1 cells after treatment with both NPs during 24
h but no NP was detected in the nuclei. Genotoxic effects were shown by MN frequencies which significantly increased at 0.5 and 1
μg/mL TiO
2 and 0.5–10
μg/mL Al
2O
3. SCE frequencies were higher for cells treated with 1–5
μg/mL TiO
2. The absence of metaphases evidenced cytotoxicity for higher concentrations of TiO
2. No SCE induction was achieved after treatment with 1–25
μg/mL Al
2O
3. In conclusion, findings showed cytotoxic and genotoxic effects of TiO
2 and Al
2O
3 NPs on CHO-K1 cells. Possible causes of controversial reports are discussed further on.
Lung carcinoma is often incurable and remains the leading cancer killer in both men and women. Recent evidence indicates that tumors contain a small population of cancer stem cells that are ...responsible for tumor maintenance and spreading. The identification of the tumorigenic population that sustains lung cancer may contribute significantly to the development of effective therapies. Here, we found that the tumorigenic cells in small cell and non-small cell lung cancer are a rare population of undifferentiated cells expressing CD133, an antigen present in the cell membrane of normal and cancer-primitive cells of the hematopoietic, neural, endothelial and epithelial lineages. Lung cancer CD133(+) cells were able to grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. The injection of 10(4) lung cancer CD133(+) cells in immunocompromised mice readily generated tumor xenografts phenotypically identical to the original tumor. Upon differentiation, lung cancer CD133(+) cells acquired the specific lineage markers, while loosing the tumorigenic potential together with CD133 expression. Thus, lung cancer contains a rare population of CD133(+) cancer stem-like cells able to self-renew and generates an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may provide valuable information to be exploited in the clinical setting.
Soil nitrogen mineralisation (N
), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net N
) ...varies with soil properties and climate. However, because most global-scale assessments of net N
are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net N
across 30 grasslands worldwide. We find that realised N
is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential N
only weakly correlates with realised N
, but contributes to explain realised net N
when combined with soil and climatic variables. We provide novel insights of global realised soil net N
and show that potential soil net N
data available in the literature could be parameterised with soil and climate data to better predict realised N
.
AIMS: To evaluate the antibacterial efficacy of silicate bioactive glass nanoparticles/collagen composites functionalized with tetracycline hydrochloride (TCH). METHODS AND RESULTS: Different ...concentrations of tetracycline hydrochloride (TCH) were incorporated on silicate bioactive glass nanoparticles/collagen composites by dipping these biomaterials for 48 h at 37°C in a solution of simulated body fluid (SBF) plus 0·05, 0·20 or 0·35 mg ml⁻¹of the antibiotic. TCH release was assessed in double‐distilled water at 37°C up to 72 h. The antibacterial activity of the samples has been evaluated in two ways: inhibition zone test and plate count method. The experiments were performed in vitro up to 48 h on four staphylococci strains (Staphylococcus aureus ATCC29213, ATCC25923, ATCC6538P and Staphylococcus epidermidis ATCC12228). The new composites were also tested for cytotoxicity on MG‐63 human osteosarcoma cells. The results showed that the incorporation and release of TCH was dependent on the initial concentration of TCH in SBF. The biomaterials also inhibited the Staph. aureus cell growth even though the efficacy was similar for all concentration. On the other hand, no cytotoxic effects were found on osteoblast‐like cells, even at the highest concentration. CONCLUSIONS: Considering all results, it can be concluded that the new composite acts as a suitable bioactive carrier of TCH and could have potential in the prevention of biomaterial related infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest a potential application as wound dressing.
Two ternary copper(II) complexes with 2,2′-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulae are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl·CH
3
OH, in what ...follows SMTCu and SDQCu, respectively, induced oxidative stress by increasing ROS level from 1.0 μM and the reduction potential of the couple GSSG/GSH
2
. The co-treatment with
l
-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the effect of copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks given by—at least partially—the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. These phenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine and loss of cell integrity from 1.0 μM. The combination with BSO induced a marked increase in the apoptotic population. On the other hand, an improved cell proliferation effect was observed when combining SDQCu with a radiation dose of 2 Gy from 1.0 μM or with 6 Gy from 1.5 μM. Finally, studies in multicellular spheroids demonstrated that even though copper(II) complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellular resistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor effect of both complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, only SDQCu was the best adjuvant of ionizing radiation treatment.
Graphical abstract
We report herein the antitumor actions of three oxidovanadium(IV) complexes on MG-63 human osteosarcoma cell line. The three complexes: VO(oda), VO(oda)bipy and VO(oda)phen (oda=oxodiacetate), caused ...a concentration dependent inhibition of cell viability. The antiproliferative action of VO(oda)phen could be observed in the whole range of concentrations (at 2.5μM), while VO(oda)bipy and VO(oda) showed a decrease of cell viability only at higher concentrations (at 50 and 75μM, respectively) (p<0.01). Moreover, VO(oda)phen caused a decrease of lysosomal and mitochondrial activities at 2.5μM, while VO(oda) and VO(oda)bipy affected neutral red uptake and mitochondrial metabolism at 50μM (p<0.01). On the other hand, no DNA damage studied by the Comet assay could be observed in MG-63 cells treated with VO(oda) at 2.5–10μM. Nevertheless, VO(oda)phen and VO(oda)bipy induced DNA damage at 2.5 and 10μM, respectively (p<0.01). The generation of reactive oxygen species increased at 10μM of VO(oda)phen and only at 100μM of VO(oda) and VO(oda)bipy (p<0.01). Besides, VO(oda)phen and VO(oda)bipy triggered apoptosis as determined by externalization of the phosphatidylserine. The determination of DNA cleavage by agarose gel electrophoresis showed that the ability of VO(oda)(bipy) is similar to that of VO(oda), while VO(oda)(phen) showed the highest nuclease activity in this series. Overall, our results showed a good relationship between the bioactivity of the complexes and their structures since VO(oda)phen presented the most potent antitumor action in human osteosarcoma cells followed by VO(oda)bipy and then by VO(oda) according to the number of intercalating heterocyclic moieties.
Bioactivity of three oxovanadium(IV) complexes with oxodiacetate (oda) (a multiple oxygen donor) and intercalating DNA related ligands: odabipy and odaphen, was evaluated in the human osteosarcoma cell line (MG-63). Cytotoxicity, genotoxicity, and mechanisms of action correlated with the chemical structures. VO(oda)phen was the most potent antitumoral complex of this series. Display omitted
•The bioactivity of three vanadyl complexes was investigated in osteosarcoma cells.•Compounds were screened for their anticancer activity against MG-63 cell line.•The complexes induced cyto- and genotoxicity that caused impaired cell viability.•Oxidative stress, apoptosis and DNA cleavage were the main mechanisms of action.•The antitumoral potency was: VO(oda)phen>VO(oda)bipy>VO(oda).
Early competition between native and non-native species can greatly influence ecosystem integrity through its effect on species regeneration, which can be further modulated by environmental context.
...Bromus tectorum
(cheatgrass
,
winter annual grass) has recently invaded the temperate grasslands of Patagonia Argentina ecosystems mainly used for extensive livestock raising. We evaluated the relative impact of competition from
B. tectorum
on two native species with different life-forms, from the seedling stage:
Vulpia australis
, the only winter annual grass in the community, and
Bromus setifolius
, a perennial grass highly palatable to livestock. The effect of asymmetric competition between
B. tectorum
(seedling or adult individuals) on
B. setifolius
was also assessed. A greenhouse experiment was conducted to simulate interspecific competition (two species per pot), and control (one species per pot) treatments. We regulated the recruitment timing of all studied species to represent realistic competition dynamics in the field.
Bromus tectorum
had a greater negative impact on the growth of both native species relative to the effect produced by a co-occurring native, even when that native was ecologically equivalent to the invader. Also, the impact of
B. tectorum
on
B. setifolius
depended on the invader’s developmental stage, with bigger individuals having the largest impact. In contrast, native species hardly affected
B. tectorum
development. Our findings indicate that native grasses may not hinder the spread of
B. tectorum
through competition. Moreover,
B. tectorum
could have a negative impact at the community level through its effect on the recruitment of native species, probably exacerbating degradation in overgrazed areas.
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