Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

Abstract Background Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.</p

Nanoscale Metallic Iron for Environmental Remediation: Prospects and Limitations

The amendment of the subsurface with nanoscale metallic iron particles (nano-Fe0) has been discussed in the literature as an efficient in situ technology for groundwater remediation. However, the introduction of this technology was controversial and its efficiency has never been univocally established. This unsatisfying situation has motivated this communication whose objective was a comprehensive discussion of the intrinsic reactivity of nano-Fe0 based on the contemporary knowledge on the mechanism of contaminant removal by Fe0 and a mathematical model. It is showed that due to limitations of the mass transfer of nano-Fe0 to contaminants, available concepts cannot explain the success of nano-Fe0 injection for in situ groundwater remediation. It is recommended to test the possibility of introducing nano-Fe0 to initiate the formation of roll-fronts which propagation would induce the reductive transformation of both dissolved and adsorbed contaminants. Within a roll-front, FeII from nano-Fe0 is the reducing agent for contaminants. FeII is recycled by biotic or abiotic FeIII reduction. While the roll-front concept could explain the success of already implemented reaction zones, more research is needed for a science-based recommendation of nano- Fe0 for subsurface treatment by roll-front

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

A simple new hydrazine-free synthesis of methyl 1,4,5-trisubstituted 1H-pyrazole-3-carboxylates

Conditions for successful syntheses of poly- substituted pyrazole-3-carboxylates have been found. The methodology consists in mixing equimolar amounts of diazonium tetrafluoroborates and enaminoesters in pres- ence of sodium acetate. 1-Methylpyrrolidone has appeared to be the solvent of choice. The compounds prepared have been characterized by means of nuclear magnetic reso- nance (NMR) spectroscopy, elemental analysis, and in two cases, also by X-ray diffraction. The advantage of the methodology is a simple implementation without necessity of working under inert atmosphere. The presence of other functional groups enables further synthetic transformations of the products

Evaluation of mulched drip irrigation for cotton in arid Northwest China

Field experiments were conducted in arid Southern Xinjiang, Northwest China, for 3 years to evaluate sustainable irrigation regimes for cotton. The experiments involved mulched drip irrigation during the growing season and flood irrigation afterward. The drip irrigation experiments included control experiments, experiments with deficit irrigation during one crop growth stage, and alternative irrigation schemes in which freshwater was used during one growth stage and relatively saline water in the others. The average cotton yield over 3 years varied between 3,575 and 5,095 kg/ha, and the irrigation water productivity between 0.91 and 1.16 kg/m3. Crop sensitivities to water stress during the different growth stages ranged from early flowering-belling (most sensitive) > seedling > budding > late flowering-belling (least sensitive), while sensitivities to salt stress ranged from late flowering-belling > budding > seedling > early flowering-belling. Although mulched drip irrigation during the growing season caused an increase in salinity in the root zone, flood irrigation after harvesting leached the accumulated salts to below background levels. Numerical simulations, based on the 3-year experiments and extended by another 20 years, suggest that mulched drip irrigation using alternatively fresh and brackish water during the growing season and flood irrigation with freshwater after harvesting is a sustainable irrigation practice that should not lead to soil salinization

Evaluation of mulched drip irrigation for cotton in arid Northwest China

Field experiments were conducted in arid Southern Xinjiang, Northwest China, for 3 years to evaluate sustainable irrigation regimes for cotton. The experiments involved mulched drip irrigation during the growing season and flood irrigation afterward. The drip irrigation experiments included control experiments, experiments with deficit irrigation during one crop growth stage, and alternative irrigation schemes in which freshwater was used during one growth stage and relatively saline water in the others. The average cotton yield over 3 years varied between 3,575 and 5,095 kg/ha, and the irrigation water productivity between 0.91 and 1.16 kg/m3. Crop sensitivities to water stress during the different growth stages ranged from early flowering-belling (most sensitive) > seedling > budding > late flowering-belling (least sensitive), while sensitivities to salt stress ranged from late flowering-belling > budding > seedling > early flowering-belling. Although mulched drip irrigation during the growing season caused an increase in salinity in the root zone, flood irrigation after harvesting leached the accumulated salts to below background levels. Numerical simulations, based on the 3-year experiments and extended by another 20 years, suggest that mulched drip irrigation using alternatively fresh and brackish water during the growing season and flood irrigation with freshwater after harvesting is a sustainable irrigation practice that should not lead to soil salinization

Tree rings of european beech (Fagus sylvatica l.) indicate the relationship with solar cycles during climate change in central and southern europe

The impact of solar cycles on forest stands, while important in the development of the forest environment during climate change, has not yet been sufficiently researched. This work eval-uates the radial growth of European beech (Fagus sylvatica L.) in the mountain areas of southern Italy and central Europe (Czech Republic, Poland) in correlation to solar cycles (sunspot number), extreme climatic events, air temperatures and precipitation totals. This research is focused on the evaluation of the radial growth of beech (140 dendrochronological samples with 90–247 years of age) from 1900 to 2019. The time span was divided into the following three periods: 1) a period of regular harvesting (1900–1969), 2) a period of air pollution crisis (1970–1985) and 3) a period of forest protection (1986–2019). The results indicate that the solar cycle was significantly involved in radial growth on all research plots. With regard to the evaluated precipitation totals, seasonal temperatures and the sunspot number, the latter was the most significant. Temperatures had a positive effect and precipitation had a negative effect on the radial increment of beech in central Europe, while in southern Italy, the effect of temperature and precipitation on the increment is reversed. In gen-eral, the limiting factor for beech growth is the lack of precipitation during the vegetation season. The number of negative pointer years (NPY) with an extremely low increment rose in relation to the decreasing southward latitude and the increasing influence of climate change over time, while a higher number of NPY was found in nutrient‐richer habitats compared to nutrient‐poorer ones. Precipitation and temperature were also reflected in the cyclical radial growth of European beech. The relationship between solar cycles and the tree ring increment was reversed in southern Italy and central Europe in the second and third (1970–2019) time periods. In the first time period (1900– 1969), there was a positive relationship of the increment to solar cycles on all research plots. In the tree rings of European beech from southern Italy and central Europe, a relationship to the 11‐year solar cycle has been documented. This study will attempt to describe the differences in beech growth within Europe, and also to educate forest managers about the relevant influence of solar cycles. Solar activity can play an important role in the growth of European beech in central and southern Europe, especially during the recent years of global climate change