SET protein as an epigenetics target.

The SET gene has four transcripts reported in NCBI, coding two isoforms of SET proteins. The most known function of SET protein is inhibiting protein phosphatase 2A, a tumor suppressor, which has been associated with different biological processes. In this review, our focus was on exploring the other SET functions related to epigenetic mechanisms, which impact cellular migration, cell cycle and apoptosis.

Interplay between EZH2/ß-catenin in stemness of cisplatin-resistant HNSCC and their role as therapeutic targets.

The Wnt/ß-catenin signaling pathway is associated with the regulation of cancer stem cells, and it can be driven by epigenetic modifications. Here, we aim to identify epigenetic modifications involved in the control of the Wnt/ß-catenin signaling and investigate the role of this pathway in the accumulation of cancer stem cells (CSC) and chemoresistance of Head and Neck Squamous Cell Carcinoma (HNSCC). Quantitative-PCR, western blot, shRNA assay, viability assay, flow cytometry assay, spheres formation, xenograft model, and chromatin immunoprecipitation were employed to evaluate the Wnt/ß-catenin pathway and EZH2 in wild-type and chemoresistant oral carcinoma cell lines, and in the populations of CSC and non-stem cells. We demonstrated that ß-catenin and EZH2 were accumulated in cisplatin-resistant and CSC population. The upstream genes of the Wnt/ß-catenin signaling (APC and GSK3ß) were decreased, and the downstream gene MMP7 was increased in the chemoresistant cell lines. The inhibition of ß-catenin and EZH2 combined effectively decreased the CSC population in vitro and reduced the tumor volume and CSC population in vivo. EZH2 inhibition increased APC and GSK3ß, and the Wnt/ß-catenin inhibition reduced MMP7 levels. In contrast, EZH2 overexpression decreased APC and GSK3ß and increased MMP7. EZH2 and ß-catenin inhibitors sensitized chemoresistant cells to cisplatin. EZH2 and H3K27me3 bounded the promoter of APC, leading to its repression. These results suggest that EZH2 regulates ß-catenin by inhibiting the upstream gene APC contributing to the accumulation of cancer stem cells and chemoresistance. Moreover, the pharmacological inhibition of the Wnt/ß-catenin combined with EZH2 can be an effective strategy for treating HNSCC.

Photoinitiated Intramolecular Proton Transfer in Deprotonated para-Coumaric Acid.

Deprotonated para-coumaric acid is commonly considered as a model for the chromophore in photoactive yellow protein, which undergoes E → Z isomerization following absorption of blue light. Here, tandem ion mobility mass spectrometry is coupled with laser excitation to study the photochemistry of deprotonated para-coumaric acid, to show that the E isomers of the phenoxide and carboxylate forms have distinct photochemical responses with maxima in their action spectra at 430 and 360 nm, respectively. The E isomer of the phenoxide anion undergoes efficient autodetachment upon excitation of its lowest ππ* transition. For the E isomer of the carboxylate deprotomer, a one-way photoinitiated proton transfer generates the phenoxide deprotomer through a mechanism postulated to involve an excited-state enol-keto tautomerism followed by a series of ground-state rearrangements including a second proton transfer. This mechanism is supported by experiments in which the relevant intermediate keto isomer is prepared and spectroscopically probed and through master equation modeling of possible ground-state isomerization processes. The Z isomer of the carboxylate deprotomer shows a weak Z → E photoisomerization response that occurs in competition with photodestruction (presumably electron detachment), demonstrating that the E and Z isomers undergo different processes in their excited states. The study highlights the utility of isomer-selective spectroscopy for characterizing the photochemistry of isolated anions possessing multiple deprotonation sites.

Spinocerebellar ataxia: Functional analysis of the stomatognathic system

Background: Neurodegenerative diseases that affect the cerebellum, especially in elderly individuals, cause impairment of motor coordination and quality of life. The presente study evaluated the electromyographic activity and thickness of the right and left masseter and temporal muscles, and the maximum molar bite force of individuals with spinocerebellar ataxia. Material and Methods: Twenty-eight individuals were divided into two groups: those with (n=14) and without (n=14) spinocerebellar ataxia. Data on the masticatory muscles obtained from the electromyographic activity (resting, right and left laterality and protrusion), muscle thickness (maximal voluntary contraction and tensile strength) and maximum bite force (right and left) were tabulated and descriptive analysis using Student’s t-test (P ≤ 0.05). Results: In the comparison between groups, greater electromyographic activity was demonstrated for individuals with spinocerebellar ataxia, with a statistically significant difference in protrusion and laterality for the temporal muscles (P = 0.05). T here was no statistically significant d ifference b etween t he g roups for m asticatory muscles thickness in the conditions evaluated. For maximum molar bite force, the group with spinocerebellar ataxia showed lower bite force (P ≤ 0.05). Conclusions: The data obtained suggest that spinocerebellar ataxia promotes functional reduction in the stomatognathic system, mainly affecting the electromyographic activity and bite force, hindering chewing, with a resultant alteration of nutritional intake and a decrease of quality of life

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Quantum chemical study of the thermal decomposition of o-quinone methide (6-methylene-2,4-cyclohexadien-1-one).

o-Quinone methide (o-QM), or 6-methylene-2,4-cyclohexadiene-1-one, has been identified as an important intermediate in lignin and alkyl benzene combustion, and the thermal decomposition of o-QM is therefore relevant to the combustion of transportation fuels (which contain toluene) and of biomass and low-rank coals (which contain lignin). We present a comprehensive reaction mechanism for the unimolecular conversion of o-QM to the reaction intermediates tropone and fulvene, calculated using theoretical quantum chemical techniques. Enthalpies of formation for all reactants, products, and intermediates are calculated using the CBS-QB3 theoretical method. Transition states are determined with the CBS-QB3 method, which we use to obtain rate constants as a function of temperature from transition-state theory, with Wigner tunneling corrections applied to hydrogen-shift reactions. Barrier heights are also calculated with the BB1K density functional theory (DFT) method for thermochemical kinetics. Reaction pathways are identified leading to tropone (which rapidly decomposes to benzene + CO) and to fulvene + CO, via initial hydrogen transfer to 2-hydroxyphenylcarbene and via ring opening to 1,3,5,6-heptatetraen-1-one, respectively. Quantum Rice-Ramsperger-Kassel (QRRK) theory analysis of the reaction kinetics indicates that the dominant reaction pathway is formation of tropone via 2-hydroxyphenylcarbene; the formation of fulvene + CO via initial ring opening constitutes a secondary pathway, which becomes more important with increasing temperature. Our calculations, using BB1K barrier heights, yield the rate equation k(T) [s(-1)] = 2.64 x 10(14) exp(-35.9/T [K]) for o-QM decomposition, which is in relatively good agreement with the experimental rate equation. Calculations provide an apparent activation energy of 71.3 kcal mol(-1), versus 67.2 kcal mol(-1) from experiment.