Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells

Much evidence indicates that various naturally occurring compounds have an anti-cancer effect, but the detailed mechanisms are not well understood. In this study, we selected anti-cancer phytochemicals such as epigallocatechin-3-gallate (EGCG), resveratrol (RES) and α-mangostin (α-M), all of which are well-characterized chemopreventive agents. We sought to elucidate the mechanism of their anti-cancer effects and the synergistic effects obtained by combined treatment with the anti-cancer drug 5-fluorouracil (5-FU) in three human colon cancer cell lines. The numbers of viable cells were consistently decreased by the treatment with EGCG, RES or α-M at more than 10 μM in all three cell lines tested. All compounds mainly induced apoptosis and suppressed the PI3K/Akt signaling pathway. Additionally, α-M, which had the greatest PI3K/Akt-suppressing activity, also suppressed MAP kinase (MAPK)/Erk1/2 signaling. Importantly, the combination treatment with RES and 5-FU induced a remarkably synergistic enhancement of growth inhibition and apoptosis through the additional suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells. Interestingly, RES increased the intracellular expression level of miR-34a, which down-regulated the target gene E2F3 and its downstream Sirt1, resulting in growth inhibition. These findings indicate that these compounds functioned as chemosensitizers when combined with anti-cancer drugs through the modulation of apoptotic and growth-related signaling pathways. Also, RES exerted its anti-cancer activity in part through a newly defined mechanism, i.e., the miR-34a/E2F3/Sirt1 cascade.     

Landslide-facilitated species diversity in a beech-dominant forest

To evaluate the extent to which landslides affect community dynamics and consequent species diversity in a beech-dominated forest, differences in the composition and size structure of tree species were compared between landslide and adjacent stable (control) stands. Demography and changes in size were compared between the two stands over a 5-year period about 60 years after a landslide. In the control stand, replacement occurred even amongst late-successional species, with beech (Fagus crenata)—the most dominant species—increasing in relative abundance. In the landslide stand, very few large individuals of late-successional species occurred, whereas large individuals of early-successional species occurred only in the landslide stand. The traits indicate that the landslide strongly facilitated species diversity, not only by reducing the dominance of late-successional species, but also by promoting recruitment of early-successional species. However, new recruitment of early-successional species was inhibited in the landslide stand, although we observed succeeding regeneration and subsequent population growth of late-successional species there. As a result, the relative dominance of late-successional species increased with succession after the landslide, thus decreasing future species diversity. In beech-dominant forest landscapes in Japan that include communities with different developmental stages, the mosaic of serial stages may facilitate species diversity after a landslide.     

Production and Properties of Alkaline Lipase from Alcaligenes sp. Strain No. 679

For the production of extracellular lipase by Alcaligenes species No. 679, NaNO₃, polyoxyethylene alkyl ether, Fe⁺⁺, sodium citrate and fructose were found to be effective. The enzyme was prepared by acetone precipitation from the filtrate of the culture broth of this strain. The enzyme was most active at pH 9.0 and 50°C, while 35% of its activity was lost on heat treatment at 60°C for 10 min. Sodium salts of bile acids stimulated the enzyme activity. This lipase could hydrolyse natural fats and oils as well as olive oil. During the hydrolysis of olive oil, monoglyceride was found to accumulate up to 70 mol percent. This lipase possesses special properties similar to those of pancreatic lipase as shown in the comparative experiments.     

Intermolecular Forces Involved in the Gelation and Gel Stability of Sesame 13S Globulin

The effect of various reagents on the formation and stability of heat-induced gels of sesame 13S globulins were investigated. Electrostatic interaction, the hydrophobic bond and the disulfide bond were important for forming the network structure of gels, and the hydrogen bond also had an influence on the formation of the gel. Hydrophobic bonds mainly contributed to the stability of the gel. Subunit analyses of the proteins solubilized from the gels showed the presence of a free acidic subunit (AS) and basic subunit (BS), a polymer of AS, a dimer of BS and the dimer of a fragment from AS or BS. From the results, sulfhydryl-disulfide exchange reactions during gelation are suggested.     

Modification of Proteinase Inhibitor II in Adzuki Beans during Germination

We investigated the effects of compounds isolated from a methanolic extract of rose hips on melanin biosynthesis in B16 mouse melanoma cells and the possible mechanisms responsible for the inhibition of melanin biosynthesis. We found that, among the isolated compounds, quercetin was a particularly potent melanogenesis inhibitor. To reveal the mechanism for this inhibition, the effects on tyrosinase of B16 mouse melanoma were measured. Quercetin decreased the intracellular tyrosinase activity as well as the tyrosinase activity in a cell culture-free system. We also examined the cellular level of tyrosinase protein and found that quercetin dose-dependently inhibited tyrosinase protein expression. We consider from these results that the inhibition of melanogenesis by quercetin was due to the inhibition of both tyrosinase activity and of the protein expression.     

The Biosynthetic Pathway of (Z)-11-Hexadecenal,the Sex Pheromone Component of the Rice Stem Borer,Chilo sappressalis WALKER (Lepidoptera: Pyralidae)

Lipoxygenase-3, the major component of the enzyme in rice grain, was purified 2980-fold with a yield of 7% from embryos. The purified enzyme had a specific activity of 280 μmol O₂ formed/min per mg protein. This enzyme was inactivated by SH compounds, such as cysteine and glutathione. The inactivation was prevented by the addition of catalase or replacement of the air by N₂ gas. These two treatments were also effective for the stable storage of the purified enzyme. The molecular weights measured by sodium dodecyl sulfate gel and gradient gel electrophoresis were 93,000 and 89,000, respectively, indicating that the enzyme is a single polypeptide chain. The purified enzyme contained 0.73 Fe atom per molecule. The absorption spectrum suggested that the enzyme is a non-heme iron protein. Some similarities in amino-acid composition were observed between rice, soybean, and pea lipoxygenases. The purified enzyme specifically produced 9-d-hydroperoxy-10,12(E,Z)-octadecadienoic acid when linoleic acid was used as a substrate.     

Purification and Properties of Phospholipase D from Actinomadura sp. Strain No. 362

An extracellular phospholipase D from Actinomadura sp. Strain No. 362 was purified about 430-fold from the culture filtrate. The purified enzyme preparation was judged to be homogeneous on polyacrylamide gel electrophoresis. The molecular weight and isoelectric point of the enzyme were estimated to be about 50,000—60,000 and 6.4, respectively. The enzyme was most active at pH 5.5 and 50°C in the presence of Triton X-100, but showed the highest activity at pH 7.0 and 60 — 70°C in its absence. The enzyme was stable up to 30°C at pH 7.2 and also stable in the pH range of 4.0 to 8.0 on 2 hr incubation at 25°C. With regard to substrate specificity, this enzyme hydrolysed lecithin best among the phospholipids tested. It was activated by Fe^{3 +}, Al³⁺, Mn^{2 +}, Ca^{2 +}, diethyl ether, sodium deoxycholate and Triton X-100, but was inhibited by cetyl pyridinium chloride and dodecylsulfate.     

Psychological and physiological effect in humans of touching plant foliage - using the semantic differential method and cerebral activity as indicators

Background

Numerous studies have reported on the healing powers of plants and nature, but there have not been so many instances of experimental research. In particular, there are very few psychological and physiological studies using tactile stimuli. This study examines the psychological and physiological effects of touching plant foliage by using an evaluation profile of the subjects’ impressions and investigating cerebral blood flow.

Methods

The subjects were 14 young Japanese men aged from 21 to 27 years (mean ± standard deviation: 23.6 ± 2.4). With their eyes closed, the subjects touched four different tactile samples including a leaf of natural pothos (Epipremnum aureum). The physiological indices were compared before and after each stimulus. Psychological indices were obtained using a ‘semantic differential’ method.

Results

The fabric stimulus gave people ‘soft’ and ‘rough’ impressions, ‘kind’, ‘peaceful’ and ‘pleasant’ feelings psychologically, and a sense of physiological calm. On the other hand, the metal stimulus gave people ‘cold’, ‘smooth’ and ‘hard’ impressions and an image of something ‘artificial’. The metal stimulus caused a stress response in human cerebral blood flow although its evaluation in terms of ‘pleasant or unpleasant’ was neutral. There were no remarkable differences between the stimuli of natural and artificial pothos compared with other types of stimulus psychologically. However, only the natural pothos stimulus showed a sense of physiological calm in the same appearance as the fabric stimulus.

Conclusions

This study shows that people experience an unconscious calming reaction to touching a plant. It is to be concluded that plants are an indispensable element of the human environment.     

Linking leaf veins to growth and mortality rates: an example from a subtropical tree community

A fundamental goal in ecology is to link variation in species function to performance, but functional trait–performance investigations have had mixed success. This indicates that less commonly measured functional traits may more clearly elucidate trait–performance relationships. Despite the potential importance of leaf vein traits, which are expected to be related to resource delivery rates and photosynthetic capacity, there are few studies, which examine associations between these traits and demographic performance in communities. Here, we examined the associations between species traits including leaf venation traits and demographic rates (Relative Growth Rate, RGR and mortality) as well as the spatial distributions of traits along soil environment for 54 co‐occurring species in a subtropical forest. Size‐related changes in demographic rates were estimated using a hierarchical Bayesian approach. Next, Kendall's rank correlations were quantified between traits and estimated demographic rates at a given size and between traits and species‐average soil environment. Species with denser venation, smaller areoles, less succulent, or thinner leaves showed higher RGR for a wide range of size classes. Species with leaves of denser veins, larger area, cheaper construction costs or thinner, or low‐density wood were associated with high mortality rates only in small size classes. Lastly, contrary to our expectations, acquisitive traits were not related to resource‐rich edaphic conditions. This study shows that leaf vein traits are weakly, but significantly related to tree demographic performance together with other species traits. Because leaf traits associated with an acquisitive strategy such as denser venation, less succulence, and thinner leaves showed higher growth rate, but similar leaf traits were not associated with mortality, different pathways may shape species growth and survival. This study suggests that we are still not measuring some of key traits related to resource‐use strategies, which dictate the demography and distributions of species.     

Age at Transition from Pediatric to Adult Care Has No Relationship with Mortality for Childhood-Onset Type 1 Diabetes in Japan: Diabetes Epidemiology Research International (DERI) Mortality Study

Objective

To follow up Japanese patients with type 1 diabetes for a maximum of 40 years to examine when they transitioned from pediatric care to adult care and to explore whether the attending physician, i.e., pediatrician or internist, was associated with prognosis.

Methods

Participants consisted of 1,299 patients who had been diagnosed as having type 1 diabetes at less than 15 years old between 1965 and 1979 identified through two nationwide surveys. Patients were classified as having received either pediatric care or adult care at the age of 15 and 30, and were compared for differences in mortality associated with the attending physician.

Results

The attending physicians were confirmed for a total of 1,093 patients at the age of 15. Of these patients, 43.8% and 40.3% received pediatric care and adult care, respectively. Of the 569 patients receiving pediatric care, 74.2%, 56.6%, 53.4%, and 51.3% continued with pediatric care at 20, 30, 40, and 50 years old, respectively. The attending physicians (pediatrician or internist) at the age of 15 and 30 had no significant impact on their survival (P = 0. 892, 0.411, respectively).

Conclusions

More than half of the patients who had received pediatric care at the age of 15 continued to receive pediatric care even after the age of 30, suggesting that their transition was far from smooth, while the attending physician at the age of both 15 and 30 was not a prognostic factor for mortality. Thus, the timing for transition to adult care in these patients has no relationship with mortality in Japan.