ストレス、癌及び老化関連病理の治療のための化合物探索における天然化学物質の細胞ベースのスクリーニング

筑波大学 (University of Tsukuba)201

ストレス、癌及び老化関連病理の治療のための化合物探索における天然化学物質の細胞ベースのスクリーニング

筑波大学 (University of Tsukuba)201

Identification and Functional Characterization of Anti-metastasis and Anti-angiogenic Activities of Triethylene Glycol Derivatives

We had previously reported anticancer activity in the water extract (WEX) of Ashwagandha leaves, and identified Triethylene glycol (TEG) as an active tumor suppressor component. In this study, we investigated anti-migratory and anti-angiogenesis activities of WEX and TEG. We conducted in vitro and in vivo experiments using TEG, and its two derivatives, Triethyleneglycol dimethacrylate (TD-10), and Tetraethyleneglycol dimethacrylate (TD-11). The data revealed strong anticancer and anti-metastasis potentials in the derivatives. Non-toxic, anti-migratory doses of the derivatives showed inhibition of canonical Wnt/β-catenin axis and consequent downregulation of EMT-signaling proteins (Vimentin, MMPs and VEGF). These results endorse that the TD-10 and TD-11 have potential to safely put a check on the aggressiveness of the metastatic cells and therefore represent promising candidates for the treatment of metastatic cancers

Public health expenditure, governance and health outcomes in Malaysia

According to the World Health Organization (WHO), government plays a crucial role in providing quality life for its citizens through good health system. There has been less attention given in analysing the relationship between government expenditure, governance and health outcomes particularly in developing countries. This paper aims to study the impact of public health expenditure and governance on health outcomes in Malaysia. An Autoregressive Distributed Lag (ARDL) cointegration framework has been used to analyse data from 1984 to 2009. The results based on the bounds testing procedure show that a stable, long-run relationship exists between health outcomes and their determinants; namely income level, public health expenditure, corruption and government stability. The results also reveal that public health expenditure and corruption affect long- and short run health outcomes in Malaysia. The findings are important to the policy makers in making decisions to improve the citizens’ quality of life. We suggest the Ministry of Health of Malaysia to conduct more consultations with other ministries and other stakeholders in health services as to identify the needs and emphasize on the importance of health program to the society. At the same time, attention should be given to reduce or eliminate the corruption rate as it has adverse effects on the country

Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression.

OBJECTIVES:Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats. METHODS:Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain. RESULTS:Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone. CONCLUSIONS:The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis

Integration of conventional cell viability assays for reliable and reproducible read-outs: experimental evidence

Abstract Objective Short-term viability assays of cultured cells in 96-well plates are routinely used to determine the cytotoxicity or safety of drugs. These are often based on the formation of chromogen, generated selectively in viable cells. The innate problems of such short-term cell viability assays include (i) effect of drugs is determined by cell density (ii) some drugs have slow/gradual effect and hence may escape such assays, (iii) cell morphology that reveal significant hints to molecular signaling underlining the effect of drugs cannot be effectively captured, (iv) long-term effect on viability and clonogenic potential of cells cannot be determined and (v) herbal extracts often possess intrinsic color that interferes with spectrophotometer estimation. In light of the ease and importance of cell culture-based assessment of drug safety and cytotoxicity, we attempted to combine the conventional cell-based assays in a way that allows multiple readouts (quantitative and qualitative) from a single experiment, and avoids the drawbacks of color interference. Results We have established and validated (using 16 types of cultured mammalian cells) a Quantitative and Qualitative Cell Viability assay in 12-well cell culture plates. It overcomes several shortcomings as discussed above and allows long-term observations on cell morphology and clonogenicity

Effect of curcumin, piperine and their combination on open field performance task.

<p>Values are expressed as mean ± SEM. For statistical significance,</p>a<p>P<0.05 as compared to sham group;</p>b<p>P<0.05 as compared to OBX control;</p>c<p>P<0.05 as compared to OBX+C1;</p>d<p>P<0.05 as compared to OBX+C2;</p>e<p>P<0.05 as compared to OBX+P (One-way ANOVA followed by Tukey’s test). OBX, Olfactory Bulbectomy; C1, curcumin (100 mg/kg); C2, curcumin (200 mg/kg); C3, curcumin (400 mg/kg); P, piperine (20 mg/kg); I, imipramine (10 mg/kg).</p

Effect of curcumin, piperine and their co-administration on lipid peroxidation (MDA), reduced glutathione (GSH), nitrite concentration and catalase enzymes levels.

<p>Values are expressed as mean ± SEM. For statistical significance,</p>a<p>P<0.05 as compared to sham group;</p>b<p>P<0.05 as compared to OBX control;</p>c<p>P<0.05 as compared to OBX+C1;</p>d<p>P<0.05 as compared to OBX+C2;</p>e<p>P<0.05 as compared to OBX+P (One-way ANOVA followed by Tukey’s test). OBX, Olfactory Bulbectomy; C1, curcumin (100 mg/kg); C2, curcumin (200 mg/kg); C3, curcumin (400 mg/kg); P, piperine (20 mg/kg); I, imipramine (10 mg/kg).</p