Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia ...inducible factor 1 alpha (Hif1α) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin.
HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT-qPCR and western blot. Melatonin-induced anti-angiogenic activity was confirmed by in vivo human umbilical vein endothelial cells (HUVECs) tube formation assay. Secreted VEGF was measured by ELISA. Immunofluorescence was performed to analyse Hif1α cellular localisation. Physical interaction between Hif1α and its co-activators was analysed by immunoprecipitation and chromatin immunoprecipitation (ChIP).
Melatonin at a pharmacological concentration (1 mM) decreases cellular and secreted VEGF levels, and prevents HUVECs tube formation under hypoxia, associated with a reduction in Hif1α protein expression, nuclear localisation, and transcriptional activity. While hypoxia increases phospho-STAT3, Hif1α, and CBP/p300 recruitment as a transcriptional complex within the VEGF promoter, melatonin 1 mM decreases their physical interaction. Melatonin and the selective STAT3 inhibitor Stattic show a synergic effect on Hif1α, STAT3, and VEGF expression.
Melatonin exerts an anti-angiogenic activity in HepG2 cells by interfering with the transcriptional activation of VEGF, via Hif1α and STAT3. Our results provide evidence to consider this indole as a powerful anti-angiogenic agent for HCC treatment.
The alkali activation of fly ashes is a chemical process by which the glassy component of these powdered materials is transformed into very well-compacted cement. In the present work the relationship ...between the mineralogical and microstructural characteristics of alkaline activated fly ash mortars (activated with NaOH, Na
2CO
3 and waterglass solutions) and its mechanical properties has been established. The results of the investigation show that in all cases (whatever the activator used) the main reaction product formed is an alkaline aluminosilicate gel, with low-ordered crystalline structure. This product is responsible for the excellent mechanical-cementitious properties of the activated fly ash. However the microstructure as well as the Si/Al and Na/Al ratios of the aluminosilicate gel change as a function of the activator type used in the system. As a secondary reaction product some zeolites are formed. The nature and composition of these zeolites also depend on the type of activator used.
The primary aim of the present paper was to determine the variations over time (one year) in the main cementitious gels forming during the alkaline activation of hybrid cements (70% FA/30% OPC). The ...28 and 365 day hydration products were characterised by different techniques. The findings showed that the C-S-H/N-A-S-H mix of gels precipitating did not precipitate in a pure state, but rather that their composition was affected by the presence of dissolved species. In the presence of aluminium C-S-H gel development was: C-S-H→C–(A)–S–H→C-A-S-H, whilst in the presence of calcium, N-A-S-H gel evolved as follows: N-A-S-H→(N,C)-A-S-H→C-A-S-H. This last conversion is not complete in these systems because the amount of calcium present is thought to be insufficient. On the grounds of the findings, a microstructural model is proposed to describe the development of the reaction products forming in these hybrid cements.
Infrared spectroscopic techniques were used in the present study to acquire a deeper understanding of mid-range order in the alkaline aluminosilicate (zeolite precursor) formed in the alkali ...activation of fly ash. Experiments were conducted with three type F fly ashes containing different proportions of vitreous and crystalline (primarily mullite and quartz) phases, activated with an 8
M solution of NaOH. All the mixes were alkali activated at 85
°C for the following reaction times: 2
h, 5
h, 8
h, 20
h and 7
days. The results indicate that the amount of alkaline silicoaluminate formed as the main reaction product, and its Si/Al ratio, induce a shift in the T–O stretching band appearing at 950–1100
cm
−1. Moreover, the presence of zeolite-type crystalline phases generates substantial changes in the 800–500
cm
−1 area of the spectra. Selective chemical attacks were used to facilitate identification of the spectra bands.
This book provides an updated state-of-the-art review on new developments in alkali-activation. The main binder of concrete, Portland cement, represents almost 80% of the total CO2 emissions of ...concrete which are about 6 to 7% of the Planet's total CO2 emissions. This is particularly serious in the current context of climate change and it could get even worse because the demand for Portland cement is expected to increase by almost 200% by 2050 from 2010 levels, reaching 6000 million tons/year. Alkali-activated binders represent an alternative to Portland cement having higher durability and a lower CO2 footprint. * Reviews the chemistry, mix design, manufacture and properties of alkali-activated cement-based concrete binders * Considers performance in adverse environmental conditions. * Offers equal emphasis on the science behind the technology and its use in civil engineering.
Activated blends of Portland cement and fly ash with a high ash content (>70%) are a new alternative to traditional OPCs. A number of papers have been published on C–S–H and N–A–S–H, the two gels ...that constitute the main cementitious products generated by the alkaline activation of these cements, and the elements that may be taken up into their structure. Very little is known about the kinetics of these systems, however, particularly during the early stages of the reaction. The present study used isothermal conduction calorimetry to explore hydration kinetics during the first 72h in a cement containing 30% OPC and 70% fly ash. Two activating solutions were used: a mix of NaOH+Na2SiO3 and a Na2CO3 solution. The findings showed that hydration kinetics were substantially modified by the type of alkaline activator used, particularly with respect to the secondary phases generated. In both cases the main reaction product appeared to be a mix of C–A–S–H and (N,C)–A–S–H gels, whose proportions were clearly impacted by the type of activator used.
This review undertakes rigorous analysis of much of the copious literature available to the scientific community on the use of alkali-activated binders (AABs) in construction. The authors’ main ...intention is to categorically refute arguments of that part of the scientific community underestimating or even dismissing the actual potential of AABs as alternatives to Portland cement (PC). The main premise invoked in support of those arguments is a presumed lack of material resources for precursors that would make AAB industrial-scale production unfeasible anywhere on the planet (a substantial number of scientific papers show that the raw materials required for AAB manufacture are in abundance worldwide). The review also analyses the role of alkaline activators in the chemistry of AABs; it is important to clarify and highlight that alkaline activators are not, by any means, confined to the two synthetic products (caustic soda and waterglass) mostly employed by researchers; other sustainable and efficient products are widely available. Finally, the review deals with the versatility of AAB production processes. The technologies required for the large scale manufacturing of AABs are mostly already in place in PC factories; actually no huge investment is required to transform a PC plant in a AAB factory; and quality and compositional uniformity of Alkaline Cements (binders produced through an industrial process) would be guaranteed. The last conclusions extracted from this review-paper are related with: i) the low carbon footprint of one-part AABs and ii) the urgent need of exploring standardization formulas allowing the commercial development of (sustainable) binders different from PC.
In this section, the speaker will present the results from a recent longitudinal study performed by the work group, in which a cohort of 265 patients admitted with a manic episode were followed up ...during three years after hospital discharge to identify acute readmissions due to affective relapses. The study of different sociodemographic and clinical variables potentially implicated in a higher risk of readmission over three years is presented, including adherence to treatment, substance use, number of previous episodes, family history, predominant polarity, treatments used and number of visits to the Emergency Department.Disclosure of InterestNone Declared
This paper deals with the alkaline activation of fly ashes for the production of a novel cementitious material and with the effect of curing conditions on the nature of the reaction products. Curing ...procedures favouring carbonation process negatively affects the development of mechanical strength of this new alkaline cement. Carbonation of the system involves its pH modification and consequently the modification of the nature of the reaction products and the kinetics of reactions.
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