Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.     

Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis; however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.     

Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T₀) and after (T₁) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC–MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.     

The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology,Liver Fatty Acids,Plasma Glucose,and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague–Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.     

BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization

Mechanical forces acting on cell–cell adhesion modulate the barrier function of endothelial cells. The actively remodeled actin cytoskeleton impinges on cell–cell adhesion to counteract external forces. We applied stress on endothelial monolayers by mechanical stretch to uncover the role of BRAF in the stress-induced response. Control cells responded to external forces by organizing and stabilizing actin cables in the stretched cell junctions. This was accompanied by an increase in intercellular gap formation, which was prevented in BRAF knockdown monolayers. In the absence of BRAF, there was excess stress fiber formation due to the enhanced reorganization of actin fibers. Our findings suggest that stretch-induced intercellular gap formation, leading to a decrease in barrier function of blood vessels, can be reverted by BRAF RNAi. This is important when the endothelium experiences changes in external stresses caused by high blood pressure, leading to edema, or by immune or cancer cells in inflammation or metastasis.     

Prolonged corneal anaesthesia by proxymetacaine hydrochloride detected by a thermal cooling stimulus

Purpose

To assess the duration, depth and recovery time of anaesthesia produced by 0.5% proxymetacaine hydrochloride (proparacaine), using a thermal cooling stimulus.

Methods

Seventeen non-contact lens-wearing subjects were recruited (mean age = 26 ± 3.6 years, range = 23-39; blue iris = 8, brown iris = 9). Central corneal sensitivity was measured in the right eye of each patient to establish a baseline, before 20 μl of either 0.5% proxymetacaine hydrochloride (p) or 0.9% unpreserved saline (s) was instilled under four experimental conditions (right eye-left eye): p-p, p-s, s-p, s-s. Corneal sensitivity was re-measured at 2, 5, 10, 15, 20, 30, 45 and 60 min post-instillation.

Results

The onset of anaesthesia was observed at 2 min (Wilcoxon, p < 0.001), with the maximum anaesthesia occurring at 15 min (Wilcoxon, p < 0.001). Recovery of corneal sensitivity to baseline levels did not occur by 60 min (Wilcoxon, p < 0.001). No difference in onset time, depth of anaesthesia, or recovery time was noted between the blue and brown iris subjects (Mann-Whitney, p > 0.05).

Conclusions

Although the anaesthetic effect of 0.5% proxymetacaine hydrochloride continues for more than 60 min, this finding does not alter current clinical practice. The extended duration, however, is of relevance to studies that use corneal anaesthesia to investigate the role of corneal nerves in the blink mechanism.     

Effect of drying temperature on polyphenolic content and antioxidant activity of apricots

This study was carried out in order to check for the influence of drying parameters on the phenolic compounds and antioxidant activity on two apricot cultivars (Pelese and Cafona) using two sets of air drying temperatures: (1) air temperature at 55 °C; (2) air temperature at 75 °C. Whole fresh and dried fruits were assessed for: phenolics, ascorbic acid, antioxidant activity and redox potential (all parameters were calculated on a dry matter basis). Analysis of data shows that the decrease in chlorogenic and neochlorogenic acid in Cafona cultivar is higher at the lower drying temperature. Catechin showed the same behaviour of hydroxycinnamic acids in both cultivars, while the decrease in the other compounds was significantly more marked in the sample dried at 75 °C. The antioxidant activity increased significantly in Cafona fruits and this increase was confirmed by a diminution of the redox potential.     

燕麦片加工品质评价及其品种相关性研究

拟通过燕麦品种间品质性状的差异来寻求燕麦片加工品质的客观评价方法,并从中筛选出适宜加工燕麦片的优良品种.结果显示,燕麦品种间在粗脂肪、粗纤维、千粒重及β-葡聚糖含量等理化指标上存在较大变异;燕麦片的理化和感官评价指标中以汤汁黏度、口感、色泽等指标对产品整体品质影响最为显著.从燕麦片的营养和食用品质综合考虑,从34个国产燕麦品种中筛选出适宜加工燕麦片的5个优质品种-坝莜1号(河北产)、白燕2号(山西产)、坝莜3号、张莜1号、定莜2号.     

Modeling stimulus‐driven attentional selection in dynamic natural scenes

In this paper we have developed a neuromorphic model of bottom‐up (BU) visual attentional selection. The output of a recently developed neuromorphic multi‐channel retina model has represented the input of our model. As a first step, a saliency map has been calculated for each retinal channel which, next, has been integrated into a master saliency map. Model parameters have been optimized based on human eye movement data measured during viewing dynamic natural scenes. We have tested two different strategies for weighting the channel‐specific saliency maps during integration into a master map. In the first case, channel weights have been kept constant throughout the verification measurements, whereas, in the other case, they have been updated on each frame, according to the specific properties of the visual input. Surprisingly, the constant channel weighting strategies have performed better than the continually updated ones. We have measured the model's accuracy by defining the hit ratio (concurrence) between the first few predicted locations (the most salient locations) and the measured fixation locations. Constant weighting methods have achieved ～74% hit ratio on four predictions. For a comparison, the accidental chance for this case has been less than 20%. This pure BU approach has performed surprisingly well on dynamic natural input. Some practical applications have already been made with task‐dependent simplifications. Copyright © 2008 John Wiley & Sons, Ltd.     

Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.