Investigation of DNA damage, oxidative stress, and inflammation in synthetic cannabinoid users.

BACKGROUND: The widespread use of synthetic cannabinoids (SCs) among youth has become an important public health problem. Several life-threatening side effects of SC have been reported, including cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, and pulmonary effects, besides skin toxicity and hepatotoxicity. METHODS: Given that high levels of SC can lead to oxidative stress, DNA damage, and inflammation, it has been aimed in this study to investigate the effects of SC in aspects of primary DNA damage, plasma total oxidant status (TOS)/total antioxidant status (TAS), thiol-disulfide homeostasis, myeloperoxidase (MPO) level, and cytokine levels (interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) of 40 SC users (SCUs) in Turkey. RESULTS: Mean plasma TOS levels were significantly higher in the SCUs group than in the healthy group (HG). Similarly, mononuclear leukocyte DNA damage, plasma TOS, MPO activity, disulfide, oxidative stress index levels, IL-1ß, IL-6, and TNF-α levels were significantly higher in the SCU group than in the HG, whereas plasma TAS, total, and native thiol levels were significantly lower in the SCU group than in the HG. CONCLUSION: It is concluded that SC can cause increase in oxidative stress and in inflammatory processes in addition to its potential for DNA damage. Additional studies with larger sample sizes and longer durations should be held to understand more specific outcomes of SC use.

Optimization of thermosonication conditions for cloudy strawberry nectar with using of critical quality parameters.

The optimum thermosonication parameters, temperature and ultrasound energy density (UED), determined by using response surface methodology to inactivate polyphenol oxidase (PPO) and protecting the quality parameters, especially color of strawberry nectar. The PPO inactivation was successfully achieved by thermosonication treatment. Increasing of temperature resulted with decreasing of browning index and increasing of hydroxymethyl furfural. High temperature-low UED combination can be applied to obtain minimum change in ΔE∗ and maximum protection of ascorbic acid. Thermosonication at mild temperature (∼50 °C) and UED (∼230 J/g) ensured the maximum levels of total monomeric anthocyanin and total phenolic content. The combination of 59 °C and 455 J/g was the conditions of optimum thermosonication to minimize quality parameters which cause undesirable changes like color degradation in nectar and maximize desirable ones which have beneficial effects on characteristics of nectar or on human health like phenolic content of nectar.

Optimization of anthocyanins extraction from black carrot pomace with thermosonication.

A study was conducted to identify optimal ultrasound processing conditions (ultrasound energy density and temperature) to maximize the extraction of anthocyanin colorants from black carrot pomace. The treatment maximized the yield of five different anthocyanin compounds from black carrot pomace with cyanidin-3-xyloside-galactoside-glucoside-ferrulic acid (C3XGGF, 60.85-74.22mg/L) as the most abundant anthocyanin compound, followed by cyanidin-3-xyloside-galactoside (C3XG, 49.56-70.12mg/L). The response surface models predicted that if extraction conditions were conducted at 183.1J/g energy density and 50°C, the yield of various anthocyanin compounds would be maximized from the black carrot pomace. Response surface models were developed correlating anthocyanin yield with ultrasonication treatment parameters. The study showed the synergy of combining ultrasonication and temperature for the extraction of anthocyanin pigments from black carrot pomace. Results of the study also further demonstrate the potential of ultrasonication technology as a tool for the extraction of valuable components waste products from fruits and vegetables juice industry.

Effects of PEF and heat pasteurization on PME activity in orange juice with regard to a new inactivation kinetic model.

The inactivation kinetics of pectin methyl esterase (PME) during the shelf life (4°C-180 days) of freshly squeezed orange juice samples processed by both pulsed electric fields (PEF) and heat pasteurization (HP) was evaluated in the study. The PME inactivation level after the PEF (25.26 kV/cm-1206.2 µs) and HP (90°C-20s) treatments were 93.8% and 95.2%, respectively. The PME activity of PEF-processed samples decreased or did not change, while that of HP samples increased during storage (p<0.01). A kinetic model was developed expressing PME inactivation as a function of the PEF treatment conditions, and this enabled the estimation of the reaction rate constant (587.8-2375.4s(-1)), and the time required for a 90% reduction (De, 3917.7-969.5s). Quantification of the increase in PEF energy to ensure a ten-fold reduction in De (ze, 63.7 J), activation electric fields (-921.2 kV cm(-1)mol(-1)), and electrical activation energy (12.9 kJ mol(-1)) was also carried out. Consequently, PEF processing was very effective for the inactivation of PME and for providing stability of orange juice during storage.

Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques.

The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation.

Comparison of phenolic compounds of orange juice processed by pulsed electric fields (PEF) and conventional thermal pasteurisation.

Processing of orange juice by pulsed electric fields (PEF) and thermal pasteurisation was carried out to compare changes in total phenolic concentration, hydroxybenzoic acid, hydroxycinnamic acids, flavonols, flavones and flavonones before and after being stored at 4°C for 180days. Changes in the initial total phenolic concentration of the samples varied depending on the applied electric field intensity and thermal pasteurisation. Hesperidin and chlorogenic acids were detected as the most abounded flavonoid and phenolic acids in the orange juice, respectively. Except for syringic acid and neoeriocitrin, the concentration of the phenolic compounds indentified in the orange juice samples enhanced after the PEF or thermal pasteurisation. The samples treated with PEF had more stable flavonoids and phenolic acids than those treated with the thermal pasteurisation. The PEF-treated samples had higher sensory scores than the heat-treated samples.

The influence of axial image resolution on atherosclerotic plaque stress computations.

Biomechanical models are used extensively to study risk factors, such as peak stresses, for vulnerable atherosclerotic plaque rupture. Typically, 3D patient-specific arterial models are reconstructed by interpolating between cross sectional contour data which have a certain axial sampling, or image, resolution. The influence of the axial sampling resolution on computed stresses, as well as the comparison of 3D with 2D simulations, is quantified in this study. A set of histological data of four atherosclerotic human coronary arteries was used which were reconstructed in 3D with a high sampling (HS) and low sampling (LS) axial resolution, and 4 slices were treated separately for 2D simulations. Stresses were calculated using finite element analysis (FEA). High stresses were found in thin cap regions and regions of thin vessel walls, low stresses were found inside the necrotic cores and media and adventitia layers. Axial sampling resolution was found to have a minor effect on general stress distributions, peak plaque/cap stress locations and the relationship between peak cap stress and minimum cap thickness. Axial sampling resolution did have a profound influence on the error in computed magnitude of peak plaque/cap stresses (±15.5% for HS vs. LS geometries and ±24.0% for HS vs. 2D geometries for cap stresses). The findings of this study show that axial under sampling does not influence the qualitative stress distribution significantly but that high axially sampled 3D models are needed when accurate computation of peak stress magnitudes is required.

Initial stress in biomechanical models of atherosclerotic plaques.

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.

Although dysregulation of tight junction (TJ) proteins is observed in epithelial malignancy, their participation in epithelial transformation is poorly understood. Recently we demonstrated that expression of oncogenic Raf 1 in Pa4 epithelial cells disrupts TJs and induces an oncogenic phenotype by downregulating expression of the TJ protein, occludin. Here we report the mechanism by which Raf 1 regulates occludin expression. Raf 1 inhibited occludin transcription by repressing a minimal segment of the occludin promoter in concert with upregulation of the transcriptional repressor, Slug without influencing the well-documented transcriptional repressor, Snail. Overexpression of Slug in Pa4 cells recapitulated the effect of Raf 1 on occludin expression, and depletion of Slug by small interfering RNA abrogated the effect of Raf 1 on occludin. Finally, chromatin immunoprecipitation assays and site-directed mutagenesis demonstrated a direct interaction between Slug and an E-box within the minimal Raf 1-responsive segment of the occludin promoter. These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition.