Synergistic effect of dietary betaines on sirt1-mediated apoptosis in human oral squamous cell carcinoma cal 27

Betaines are food components widely distributed in plants, animals, microorganisms, and dietary sources. Among betaines, δ-valerobetaine (N,N,N-trimethyl-5-aminovaleric acid, δVB) shares a metabolic pathway common to γ-butyrobetaine (γBB). The biological properties of δVB are particularly attractive, as it possesses antioxidant, anti-inflammatory and anticancer activities. Here, we investigated the possible synergism between δVB and the structurally related γBB, to date unexplored, by testing the in vitro anticancer activity in head and neck squamous cell carcinoma cell lines, FaDu, UM-SCC-17A and Cal 27. Among cell lines tested, results indicated that betaines showed the highest effect in reducing Cal 27 cell proliferation up to 72 h (p < 0.01). This effect was enhanced when betaines were administered in combination (δVB plus γBB) (p < 0.001). Inhibition of cell growth by δVB plus γBB involved reactive oxygen species (ROS) accumulation, upregulation of sirtuin 1 (SIRT1), and apoptosis (p < 0.001). SIRT1 gene silencing by small interfering RNA decreased the apoptotic effect of δVB plus γBB by modulating downstream procaspase-3 and cyclin B1 (p < 0.05). These findings might have important implications for novel prevention strategies for tongue squamous cell carcinoma by targeting SIRT1 with naturally occurring betaines

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p < 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p < 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3+) suppressed the PA-induced autophagy (mimic NC+PA) (p < 0.01), inflammation, and pyroptosis (p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Pool boiling of nanofluids on biphilic surfaces: An experimental and numerical study

This study addresses the combination of customized surface modification with the use of nanofluids, to infer on its potential to enhance pool-boiling heat transfer. Hydrophilic surfaces patterned with superhydrophobic regions were developed and used as surface interfaces with different nanofluids (water with gold, silver, aluminum and alumina nanoparticles), in order to evaluate the effect of the nature and concentration of the nanoparticles in bubble dynamics and consequently in heat transfer processes. The main qualitative and quantitative analysis was based on extensive post-processing of synchronized high-speed and thermographic images. To study the nucleation of a single bubble in pool boiling condition, a numerical model was also implemented. The results show an evident benefit of using biphilic patterns with well-established distances between the superhydrophobic regions. This can be observed in the resulting plot of the dissipated heat flux for a biphilic pattern with seven superhydrophobic spots, δ = 1/d and an imposed heat flux of 2132 w/m2. In this case, the dissipated heat flux is almost constant (except in the instant t* ≈ 0.9 when it reaches a peak of 2400 W/m2), whilst when using only a single superhydrophobic spot, where the heat flux dissipation reaches the maximum shortly after the detachment of the bubble, dropping continuously until a new necking phase starts. The biphilic patterns also allow a controlled bubble coalescence, which promotes fluid convection at the hydrophilic spacing between the superhydrophobic regions, which clearly contributes to cool down the surface. This effect is noticeable in the case of employing the Ag 1 wt% nanofluid, with an imposed heat flux of 2132 W/m2, where the coalescence of the drops promotes a surface cooling, identified by a temperature drop of 0.7 °C in the hydrophilic areas. Those areas have an average temperature of 101.8 °C, whilst the average temperature of the superhydrophobic spots at coalescence time is of 102.9 °C. For low concentrations as the ones used in this work, the effect of the nanofluids was observed to play a minor role. This can be observed on the slight discrepancy of the heat dissipation decay that occurred in the necking stage of the bubbles for nanofluids with the same kind of nanoparticles and different concentration. For the Au 0.1 wt% nanofluid, a heat dissipation decay of 350 W/m2 was reported, whilst for the Au 0.5 wt% nanofluid, the same decay was only of 280 W/m2. The results of the numerical model concerning velocity fields indicated a sudden acceleration at the bubble detachment, as can be qualitatively analyzed in the thermographic images obtained in this work. Additionally, the temperature fields of the analyzed region present the same tendency as the experimental results.This work was funded by Portuguese national funds of FCT/MCTES (PIDDAC) through the base funding from the following research units: UIDB/00532/2020 (Transport Phenomena Research Center, CEFT), UIDB/04077/2020 (MEtRICs) and UIDP/04436/2020. The authors are also grateful for the funding of FCT through the projects LISBOA-01-0145-FEDER-030171/NORTE-01-0145-FEDER-030171 (PTDC/EME-SIS/30171/2017), funded by COMPETE2020, NORTE2020, PORTUGAL2020 and FEDER. The authors also acknowledge FCT for partially financing the research under the framework of the project UTAP-EXPL/CTE/0064/2017, financiado no ambito do Projeto 5665-Parcerias Internacionais de Ciencia e Tecnologia, UT Austin Programme. Mr Pedro Pontes also acknowledgesFCT for his fellowship ref. SFRH/BD/149286/2019

Treatment of male sexual deviation by use of a vibrator: Case report

A new technique of enhancement of heterosexual responsiveness is described. This uses a classical conditioning paradigm with heterosexual photographic material as the CS and erections elicited by a vibrator as the UCS. A 44-year-old fetishist was treated in this manner. His response to treatment was favorable and details of change are presented. The timing of physiological and diary measure changes is in line with an explanation in terms of the treatment procedure. However, attitude changes began before treatment commenced

«La relation de limitation et d’exception dans le français d’aujourd’hui : excepté, sauf et hormis comme pivots d’une relation algébrique »

L’analyse des emplois prépositionnels et des emplois conjonctifs d’ “excepté”, de “sauf” et d’ “hormis” permet d’envisager les trois prépositions/conjonctions comme le pivot d’un binôme, comme la plaque tournante d’une structure bipolaire. Placées au milieu du binôme, ces prépositions sont forcées par leur sémantisme originaire dûment métaphorisé de jouer le rôle de marqueurs d’inconséquence systématique entre l’élément se trouvant à leur gauche et celui qui se trouve à leur droite. L’opposition qui surgit entre les deux éléments n’est donc pas une incompatibilité naturelle, intrinsèque, mais extrinsèque, induite. Dans la plupart des cas (emplois limitatifs), cette opposition prend la forme d’un rapport entre une « classe » et le « membre (soustrait) de la classe », ou bien entre un « tout » et une « partie » ; dans d’autres (emplois exceptifs), cette opposition se manifeste au contraire comme une attaque de front portée par un « tout » à un autre « tout ». De plus, l’inconséquence induite mise en place par la préposition/conjonction paraît, en principe, tout à fait insurmontable. Dans l’assertion « les écureuils vivent partout, sauf en Australie » (que l’on peut expliciter par « Les écureuils vivent partout, sauf [qu’ils ne vivent pas] en Australie »), la préposition semble en effet capable d’impliquer le prédicat principal avec signe inverti, et de bâtir sur une telle implication une sorte de sous énoncé qui, à la rigueur, est totalement inconséquent avec celui qui le précède (si « les écureuils ne vivent pas en Australie », le fait qu’ils « vivent partout » est faux). Néanmoins, l’analyse montre qu’alors que certaines de ces oppositions peuvent enfin être dépassées, d’autres ne le peuvent pas. C’est, respectivement, le cas des relations limitatives et des relations exceptives. La relation limitative, impliquant le rapport « tout » - « partie », permet de résoudre le conflit dans les termes d’une somme algébrique entre deux sous énoncés pourvus de différent poids informatif et de signe contraire. Les valeurs numériques des termes de la somme étant déséquilibrées, le résultat est toujours autre que zéro. La relation exceptive, au contraire, qui n’implique pas le rapport « tout » - « partie », n’est pas capable de résoudre le conflit entre deux sous énoncés pourvus du même poids informatif et en même temps de signe contraire : les valeurs numériques des termes de la somme étant symétriques et égales, le résultat sera toujours équivalent à zéro