Quercetin-3-O-β-d-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells

Cellular senescence is known to contribute to tissue aging, a variety of age-related diseases, tissue regeneration, and cancer. Therefore, aging intervention might be useful for prevention of aging as well as age-related disease. In this study, we investigated compounds from Polygonum aviculare to determine if they inhibited cellular senescence in human primary cells, human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Ten compounds from P. aviculare were purified and their inhibitory effects on adriamycin-induced cellular senescence were measured by observing senescence-associated β-galactosidase (SA-β-gal) activity and reactive oxygen species. Among them, compound 9 (quercetin-3-O-β-d-glucuronide) showed inhibitory effects against cellular senescence in HDFs and HUVECs treated with adriamycin. Additionally, compound 9 rescued replicative senescence in HDFs and HUVECs. These data imply that compound 9 represses cellular senescence in human primary cells and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or aging-associated diseases.     

Homoegonol attenuates the asthmatic responses induced by ovalbumin challenge

Homoegonol is a lignan derived from styraxlignolide A, which was isolated from Styrax japonica, a medicinal plant widely used for treatment of inflammatory diseases in Korea. We investigated the efficacy of homoegonol for the treatment of allergic asthma using an ovalbumin (OVA)-induced murine asthma model. The mice were sensitized through intraperitoneal injections of OVA on days 0 and 14. On days 21, 22 and 23 after the initial OVA sensitization, the mice were received OVA airway challenge. Homoegonol was administered by oral gavage at a dose of 30 mg/kg 1 h prior to the OVA challenge. The homoegonol-treated mice exhibited reduced inflammatory cell counts and Th2 cytokines in BALF, AHR, and IgE in the serum compared with the OVA-sensitized/challenged mice. The histological analysis of the lung tissue revealed that the administration of homoegonol attenuated the airway inflammation and the mucus overproduction in airway epithelial lesions induced by OVA through a reduction in expression of inducible nitric oxide synthase and matrix metalloproteinase-9. These findings indicate that homoegonol effectively suppresses the asthmatic responses induced by OVA challenge and suggests that homoegonol exhibits potential as therapeutic drug for allergic asthma.     

Quantitative and pattern recognition analyses of magnoflorine,spinosin, 6′′′-feruloyl spinosin and jujuboside A by HPLC in Zizyphi Semen

Two rapid and simple HPLC methods with UV detector to determine three main compounds (magnoflorine, spinosin and 6′′′-feruloyl spinosin) and evaporative light scattering detector (ELSD) to determine jujuboside A were developed for the chemical analyses of Zizyphi Semen. Magnoflorine, spinosin, and 6′′′-feruloyl spinosin were separated with an YMC J’sphere ODS-H80 column (250 mm × 4.6 mm, 4 μm) by the gradient elution followed by the isocratic elution using methanol with 0.1 % formic acid and water with 0.1 % formic acid as the mobile phase. The flow rate was 1.0 mL/min. Jujuboside A was separated by HPLC–ELSD with YoungJinBioChrom Aegispak C18-L column (250 mm × 4.6 mm, 5 μm) column in a gradient elution using methanol with 0.1 % formic acid (A) and water with 0.1 % formic acid as the mobile phase. These two methods were fully validated with respect to linearity, precision, accuracy, stability, and robustness. These HPLC methods were applied successfully to quantify four compounds in a Zizyphi Semen extract. The HPLC analytical methods were validated for pattern recognition analysis by repeated analysis of 91 seed samples corresponding to 48 Zizyphus jujuba var. spinosa (J01–J48) and 43 Zizyphus mauritiana (M01–M43). The results indicate that these methods are suitable for a quality evaluation of Zizyphi Semen.     

Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB

In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC⁵⁰ value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.     

Development of Vorinostat-Loaded Solid Lipid Nanoparticles to Enhance Pharmacokinetics and Efficacy against Multidrug-Resistant Cancer Cells

Purpose

To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its bioavailability and effects on multidrug-resistant cancer cells.

Methods

VOR-loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an emulsification-sonication technique, and the formulation parameters were optimized. The cytotoxicity of the optimized formulation was evaluated in cancer cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were examined following oral and intravenous (IV) administration to rats.

Results

VOR-SLNs were spherical, with a narrowly distributed average size of ~100 nm, and were physically stable for 3 months. Drug release showed a typical bi-phasic pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231) cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA-MB-231 cells at low doses, suggesting an ability to effectively counter the P-glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and decreased its elimination rate constant. The areas under the VOR concentration-time curve produced by oral and IV administration of VOR-SLNs were significantly greater than those produced by free drug administration. These in vivo results clearly highlighted the remarkable potential of SLNs to augment the bioavailability of VOR.

Conclusions

VOR-SLNs successfully enhanced the oral bioavailability, circulation half-life, and chemotherapeutic potential of VOR.     

Development of a scale to measure individuals’ ratings of peace

Background

The evolving concept of peace-building and the interplay between peace and health is examined in many venues, including at the World Health Assembly. However, without a metric to determine effectiveness of intervention programs all efforts are prone to subjective assessment. This paper develops a psychometric index that lays the foundation for measuring community peace stemming from intervention programs.

Methods

After developing a working definition of ‘peace’ and delineating a Peace Evaluation Across Cultures and Environments (PEACE) scale with seven constructs comprised of 71 items, a beta version of the index was pilot-tested. Two hundred and fifty subjects in three sites in the U.S. were studied using a five-point Likert scale to evaluate the psychometric functioning of the PEACE scale. Known groups validation was performed using the SOS-10. In addition, test-retest reliability was performed on 20 subjects.

Results

The preliminary data demonstrated that the scale has acceptable psychometric properties for measuring an individual’s level of peacefulness. The study also provides reliability and validity data for the scale. The data demonstrated internal consistency, correlation between data and psychological well-being, and test-retest reliability.

Conclusions

The PEACE scale may serve as a novel assessment tool in the health sector and be valuable in monitoring and evaluating the peace-building impact of health initiatives in conflict-affected regions.

     

Selective Effects of D- and L-Govadine in Preclinical Tests of Positive,Negative, and Cognitive Symptoms of Schizophrenia

There is a critical need to develop novel pharmacotherapeutics capable of addressing the positive, negative, and cognitive symptoms of schizophrenia. Building on recent studies with a racemic mixture of the synthetic tetrahydroprotoberberine, D,L-Govadine, we isolated the D- and L-stereoisomers and employed a battery of behavioral, neurochemical, and electrophysiological procedures to assess their individual therapeutic potential. Rodent models predictive of antipsychotic efficacy and those that model positive symptoms were employed and we found that L-Govadine, but not D-Govadine, improved these measures. Pretreatment with either stereoisomer during CS pre-exposure prevented the disruption of latent inhibition by amphetamine. Moreover, pretreatment with either stereoisomer also improved deficits in social interaction in the neonatal ventral hippocampal lesioned rat. Improved cognitive performance in two different prefrontal cortex-dependent tasks was observed with D-, but not L-Govadine, which strongly suggests that the D-steroisomer may be an effective cognitive enhancer. Alterations in dopamine efflux were also assessed and L-Govadine increased dopamine efflux in both the prefrontal cortex and nucleus accumbens. However, D-Govadine only increased dopamine efflux in the prefrontal cortex and not in the nucleus accumbens. Electrophysiological studies confirmed that L-Govadine is a DA-D2 antagonist, whereas D-Govadine shows no appreciable physiological effects at this receptor. Collectively these data show that L-Govadine performs well on measures predictive of antipsychotic efficacy and rodent models of positive symptoms through antagonism of DA-D2 receptors, whereas D-Govadine improves impairments in compromised memory function in delayed response tasks possibly through selective increases in DA efflux in the frontal cortex.     

Effects of Deposition Strategy and Preheating Temperature on Thermo-Mechanical Characteristics of Inconel 718 Super-Alloy Deposited on AISI 1045 Substrate Using a DED Process

Thermomechanical characteristics are highly dependent on the deposition strategy of the directed energy deposition (DED) process, including the deposition path, the interpass time, the deposition volume, etc., as well as the preheating condition of the substrate. This paper aims to investigate the effects of the deposition strategy and the preheating temperature on thermomechanical characteristics of Inconel 718 super-alloy deposited on an AISI 1045 substrate using a DED process via finite element analyses (FEAs). FE models for different deposition strategies and preheating temperatures are created to examine the thermomechanical behavior. Sixteen deposition strategies are adopted to perform FEAs. The heat sink coefficient is estimated from a comparison of temperature histories of experiments and those of FEAs to obtain appropriate FE models. The influence of deposition strategies on residual stress distributions in the designed model for a small volume deposition is examined to determine feasible deposition strategies. In addition, the effects of the deposition strategy and the preheating temperature on residual stress distributions of the designed part for large volume deposition are investigated to predict a suitable deposition strategy of the DED head and appropriate preheating temperature of the substrate.     

Evaluation of Dynamic Properties of Sodium-Alginate-Reinforced Soil Using A Resonant-Column Test

Ground reinforcement is a method used to reduce the damage caused by earthquakes. Usually, cement-based reinforcement methods are used because they are inexpensive and show excellent performance. Recently, however, reinforcement methods using eco-friendly materials have been proposed due to environmental issues. In this study, the cement reinforcement method and the biopolymer reinforcement method using sodium alginate were compared. The dynamic properties of the reinforced ground, including shear modulus and damping ratio, were measured through a resonant-column test. Also, the viscosity of sodium alginate solution, which is a non-Newtonian fluid, was also explored and found to increase with concentration. The maximum shear modulus and minimum damping ratio increased, and the linear range of the shear modulus curve decreased, when cement and sodium alginate solution were mixed. Addition of biopolymer showed similar reinforcing effect in a lesser amount of additive compared to the cement-reinforced ground, but the effect decreased above a certain viscosity because the biopolymer solution was not homogeneously distributed. This was examined through a shear-failure-mode test.