Icaritin Synergistically Enhances the Radiosensitivity of 4T1 Breast Cancer Cells

Icaritin (ICT) is a hydrolytic form of icariin isolated from plants of the genus Epimedium. This study was to investigate the radiosensitization effect of icaritin and its possible underlying mechanism using murine 4T1 breast cancer cells. The combination of Icaritin at 3 µM or 6 µM with 6 or 8 Gy of ionizing radiation (IR) in the clonogenic assay yielded an ER (enhancement ratio) of 1.18 or 1.28, CI (combination index) of 0.38 or 0.19 and DRI (dose reducing index) of 2.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a synergistic killing (?) effect with radiation on the tumor cells. This effect might relate with bioactivities of ICT: 1) exert an anti-proliferative effect in a dose- and time-dependent manner, which is different from IR killing effect but likely work together with the IR effect; 2) suppress the IR-induced activation of two survival paths, ERK1/2 and AKT; 3) induce the G2/M blockage, enhancing IR killing effect; and 4) synergize with IR to enhance cell apoptosis. In addition, ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM) assay. Taken together, ICT is a new radiosensitizer and can enhance anti-cancer effect of IR or other therapies.     

III - Prostaglandin hyperalgesia: Relevance of the peripheral effect for the analgesic action of opioid-antagonists

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE₂ or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.     

On the evolution of pure winner and loser effects: A game-theoretic model

The persistence of linear dominance hierarchies is often attributed to higher probabilities of a win after a win or a loss after a loss in agonistic interactions, yet there has been no theory on the evolution of such prior-experience effects. Here an analytic model, based on the idea that contests are determined by subjective perceptions of resource-holding potential (RHP) which animals may revise in the light of experience, demonstrates that winner and loser effects can evolve through round-robin competition among triads of animals drawn randomly from their population, and that the probability of a hierarchy increases with the strength of the combined effect. The effects are pure, in the sense that a contestant observes neither its own RHP nor its opponent’s RHP or RHP perception or win—loss record; and so the strength of an effect is unmodified by the RHPs of particular individuals, but depends on the distribution of RHP among the population at large. The greater the difference between an individual’s and its opponent’s RHP perception, the more likely it is to win a contest; however, if it overestimates its RHP, then the cost of fighting increases with the overestimate. A winner or loser effect exists only if the fitness gain of the beta individual in a hierarchy, relative to that of the alpha, is less than 0.5. Then a loser effect can exist alone, or it can coexist with a winner effect; however, there cannot exist a winner effect without a loser effect.     

Digitalis receptor desensitization in rat ventricle: Ouabain produces two inotropic effects

In rat ventricular strips at 35° and 37°C, at 1 Hz and 3 Hz stimulation rate and in Krebs-Henseleit and Tyrode solution, cumulative dose/response curves of ouabain revealed two apparent positive inotropic effects, a “low-dose” effect with a half maximal increase in contractile force (ED₅₀) of 0.5 μM ouabain representing about 30% of the total inotropy and a “high-dose” effect of 19 to 35 μM ouabain representing about 70% of total inotropy. The overall or combined ED₅₀ was 16 μM ouabain. The “low-dose” effect was not prevented by α or β adrenergic blockade, by reserpinization, or by histamine H₂ antagonist. However, when the tissue preparations were washed for 60 to 120 min after completion of the first dose/response experiment, a second dose/response curve with ouabain revealed an absence or disappearance of the “low-dose” effect and a normal “high-dose” effect. The “low-dose” effect is apparently related to pretreatment with ouabain. We refer to this phenomenon as “desensitization”.     

In vitro bactericidal activity of the N-terminal fragment of the frog peptide esculentin-1b (Esc 1–18) in combination with conventional antibiotics against Stenotrophomonas maltophilia

In this study the bactericidal effect of the N-terminal fragment of the frog skin peptide esculentin-1b [Esc(1–18)] in combination with clinically used antimicrobial agents was evaluated against Stenotrophomonas maltophilia, either in standard conditions (phosphate buffer) or in the presence of human serum. A synergistic bactericidal effect was observed after a 24 h incubation when combinations of Esc(1–18) and amikacin or colistin were used against clinical strains of S. maltophilia with or without resistance to these antibiotics, both in buffer and in the presence of serum. An indifferent effect was observed when the peptide was combined with levofloxacin or ceftazidime. A synergistic effect was also observed at earlier time points when the peptide was used in combination with colistin. Sequential exposure of bacterial cells to Esc(1–18) and amikacin or colistin, or vice versa, indicated that while Esc(1–18) and colistin cooperated in enhancing the bactericidal effect of their combination, when Esc(1–18) was combined with amikacin, the peptide had a major role in initiating the bactericidal effect, while amikacin was required for the subsequent effector phase. Altogether, the results obtained indicate that exposure of S. maltophilia to sub-bactericidal concentrations of Esc(1–18) increases its susceptibility to amikacin or colistin and may also render resistant strains susceptible to these antibiotics.     

Antifungal Properties of Cranberry Juice

Cranberry juice exerts a significant in vitro antifungal effect on eight representative species of dermatophytes, whereas it has no apparent effect on Candida albicans. The antifungal effect is fungistatic. Benzoic acid or other small molecular weight components, or both, were responsible for the fungistatic action. Studies with C. albicans on the effect of pH alone and the effect of pH on the ionization of benzoic acid indicate that cranberry juice would exert an even more significant antifungal action if the pH were left at its native value of 2.8; not adjusted to 5.6. This would probably be due to pH and a larger amount of free benzoic acid. Further investigation suggested that benzoic acid loses some of its antifungal properties in cranberry juice at pH 5.6. This investigation suggests that the dermatophytes may have a higher sensitivity to benzoic acid or other small molecular weight components of cranberry juice, or to both.     

Effect of a cytokinin antagonist on cytokinin and light-dependent amaranthin synthesis inAmaranthus Tricolor seedlings

InAmaranthus tricolor seedlings, amaranthin synthesis can be induced under the effect either of a cytokinin or of white light. The 3-methyl-7-(n-pentylamino)pyrazolo(4,3-d)pyrimidine (PAMPP), a cytokinin analog that strongly inhibits the growth of tobacco callus, antagonizes the stimulating effect of cytokinin as well as stimulation by light. In dose-response terms, the inhibitory effect of PAMPP was described as competitive with respect to N⁶-benzyladenine (b⁶Ade) or light. The inhibition by PAMPP of the b⁶Ade amaranthin test response or the inhibition by this cytokinin analog of the light amaranthin test response were both reversed by either subsequent light or b⁶Ade treatment.     

Mimicry Enhances Observational Learning in 16-Month-Old Infants

We examined the effect of mimicry on how 16-month-old infants learn by observation a novel tool use action, which consisted of using a rake to retrieve a toy. Across four conditions, we manipulated whether during an initial play phase, an adult mimicked the infant''s play or not (testing the effect of mimicry), the infant played with the adult or played alone (controlling the effect of interacting with a contingent partner) and whether the infant saw a demonstration of the tool''s use or not (evaluating baseline performance). We found that infants who had been mimicked learned best from a demonstration of the rake''s use and performed better than infants who only played with the experimenter without mimicry or played by themselves before the demonstration. As expected, infants did not learn from a demonstration of the rake''s use when they played by themselves and thus had no previous interaction with an experimenter. The mechanisms driving this powerful learning effect of mimicry are discussed.     

3-Hydroxy-3-methylglutaryl CoA reductase of Hevea latex: The occurrence of a heat-stable activator in the C-serum

The effect of the C-serum (the cytosol) on the activity of 3-hydroxy-3-methylglutaryl CoA reductase in the latex of $\text{Hevea}\text{brasiliensis}$ was investigated. Depending on the clone from which the latex was obtained, the C-serum was found to depress or activate or have little effect on the enzyme activity. Boiling the C-serum however, resulted in a consistent activation effect in all the clones examined. Optimal activation was obtained with 20 μl boiled C-serum. Dialysis or EDTA (40 mM) treatment of the boiled C-serum did not diminish the activation effect. Although not essential, dithiothreitol complemented the activation effect of the boiled C-serum and the optimal concentration was 10 mM. Trypsin digestion of the boiled C-serum resulted in the complete loss of the activation effect. The activator in the boiled C-serum was salted out by ammonium sulphate at 25 – 100% saturation. Hevein had no effect on reductase activity.     

Effect of sodium fluoride on radiation sensitivity of barley seeds

Barley seeds soaked in 0.01 M sodium fluoride (NaF) in phosphate buffer (pH7) or in buffer alone for 18 h were dried and equilibrated to 10% moisture, either in air or in nitrogen. Pre-treated and re-dried seeds were irradiated in air or in nitrogen with 0, 13, 20, 26 and 32 kR of γ rays, and were immediately hydrated in oxygen- or nitrogen-bubbled water. Parameters of radiation effect considered were seedling injury, mitotic and meiotic cells with bridge aberrations at anaphase and pollen fertility in M₁, and the frequency of chlorophyll mutations in M₂. NaF at 0.01 M was not mutagenic by itself. Pre-treatment with NaF significantly enhanced the radiation effect, when the irradiation was done in air, in comparison with the buffer soaked seeds. The increased effect due to NaF was additional to the oxygen effect. In nitrogen, NaF pre-treatment increased the mutagenic effect but it was not always significant. Post-soaking of irradiated seeds in 0.01 M NaF for 5 h increased seedling injury in comparison with the irradiated seeds soaked in buffer alone or in 0.01 M NaCl. At least a part of the sensitizing effect of NaF may be due to the inhibition of repair.     

Chemometric variance analysis of <Superscript>1</Superscript>H NMR metabolomics data on the effects of oral rinse on saliva

In order to investigate exposure end effect markers of fruit and fruit fibre intake we investigated how fresh apple or apple-pectin affects the urinary metabolome of rats. Twenty-four Fisher 344 male rats were randomized into three groups and fed a standard diet with different supplementations added in two of the groups (7% apple-pectin or 10 g raw apple). After 24 days of feeding, 24 h urine was collected and analyzed by UPLC-QTOF-MS in positive and negative ionization mode. Metabolites that responded to the apple or pectin diets were selected and classified as either potential exposure or effect markers based on the magnitude and pattern of their response. An initial principal component analysis (PCA) of all detected metabolites showed a clear separation between the groups and during marker identification several new apple and/or pectin markers were found. Quinic acid, m-coumaric acid and (-)epicatechin were identified as exposure markers of apple intake whereas hippuric acid behaved as an effect marker. Pyrrole-2-carboxylic acid and 2-furoylglycine behaved as pectin exposure markers while 2-piperidinone was recognized as a potential pectin effect marker. None of them has earlier been related to intake of pectin or other fibre products. We discuss these new potential exposure and effect markers and their interpretation.     

Effect of a cytokinin antagonist on cytokinin and light-dependent amaranthin synthesis inAmaranthus Tricolor seedlings

InAmaranthus tricolor seedlings, amaranthin synthesis can be induced under the effect either of a cytokinin or of white light. The 3-methyl-7-(n-pentylamino)pyrazolo(4,3-d)pyrimidine (PAMPP), a cytokinin analog that strongly inhibits the growth of tobacco callus, antagonizes the stimulating effect of cytokinin as well as stimulation by light. In dose-response terms, the inhibitory effect of PAMPP was described as competitive with respect to N⁶-benzyladenine (b⁶Ade) or light. The inhibition by PAMPP of the b⁶Ade amaranthin test response or the inhibition by this cytokinin analog of the light amaranthin test response were both reversed by either subsequent light or b⁶Ade treatment.     

Characteristics of Inhibition of a Taiwanese Soil Suppressive to Fusarium oxysporum f. sp. raphani

Germination of nutrient-amended chlamydospores of the three formae speciales of Fusarium oxysporum tested were inhibited in a suppressive soil collected from central Taiwan. The suppressive soil released a volatile substance when moistened with alkaline solution. The inhibition spectrum of the volatile substance was different from that of the suppressive soil. The inhibitory effect of the suppressive soil was greatly reduced when it was heat-treated for 30 min at 40°C or higher. The inhibitory effect of the heat-treated suppressive soil was restored after infestation with 1% conducive or suppressive soil for 14 days. However, infestation of heat-treated conducive soil even with 1% suppressive soil did not render it suppressive. Amendment of suppressive soil with rose bengal, streptomycin or Rubigan completely or partially reduced the inhibitory effect. Increasing the total population of indigenous microorganisms in conducive soil by amendment with rice germ or soybean meal to about the same level as that in suppressive soil did not render it suppressive. Results suggest that a combination of biotic and abiotic factors is responsible for the inhibitory effect of the suppressive soil.     

The Effect of Salicylic Acid on the Growth of Lemna gibba

Salicylic acid added as the iron chelate causes extension ofthe pedicels and distortion in the growth of daughter frondsof Lemna gibba, when included in a nutrient salt medium whichcontains the ammonium ion. The effect is abolished if iron orcopper is omitted from the nutrient solution or if the mediumcontains only nitrate nitrogen. The effect is specific for salicylicacid or acetyl salicylic acid; substituted or analogous compoundsare without effect.     

The hyperalgesic effects of prostacyclin and prostaglandin E2

Hyperalgesia induced in rat paws or dog knee joints by prostacyclin (PGI₂) and prostaglandin E₂ was measured by a modification of the Randall-Selitto method (1) of by the degree of incapacitation (2). In both species PGI₂ induced an immediate hyperalgesic effect but the effect of PGE₂ had a longer latency. Low doses of PGI₂ caused a short lasting effect but PGE₂, large doses of PGI₂ or successive administration of small doses of PGI₂ caused a long lasting effect.It is suggested that prostacyclin mediates rat paw hyperalgesia induced by carrageenin. The long lasting hyperalgesic effect of PGE₂ and high doses of PGI₂ is possibly an indirect effect caused by stimulation of a sensory nerve sensitising mechanism.     

Effet de la caféine sur le developpement des tumeurs melaniques chez la drosophile

Caffeine, added to the nutrient medium of strain cl tu^48a larvae which can develop spontaneous melanotic tumours, produces a double effect: a toxic effect and an inhibitory effect on tumorigenesis.The toxic effect manifests itself especially if young larvae are treated, and is observed as an increase in their mortality.The effect of caffeine on tumorigenesis is only seen if it is administered during the 2nd and 3rd day of the larval life. Outside of this period, or if caffeine is only applied during a part of the period, it exerts no influence or tumorigenesis. The effect on tumorigenesis consists of a decrease in the frequency of tumourous individuals. In individuals who have developed at least one tumour,caffeine does not modify the probability of the development of other tumours. Its action thus, is at the individual scale and not at that of the tumour.The time during which larvae are sensitive to caffeine indicates that the effect must intervene before the appearance of the first tumour cells.     

The presence of heterospecific males causes an Allee effect

The Allee effect is a positive causal relationship between any component of fitness and population density or size. Allee effects strongly affect the persistence of small or sparse populations. Predicting Allee effects remains a challenge, possibly because not all causal mechanisms are known. We hypothesized that reproductive interference (an interspecific reproductive interaction that reduces the fitness of the species involved) can generate an Allee effect. If the density of the interfering species is constant, an increase in the population of the species receiving interference may dilute the per capita effect of reproductive interference and may generate an Allee effect. To test this hypothesis, we examined the effect of heterospecific males on the relationship between per capita fecundity and conspecific density in Callosobruchus chinensis and C. maculatus. Of the two species, only C. maculatus females suffer reproductive interference from heterospecific males. Only C. maculatus, the species susceptible to reproductive interference, demonstrated an Allee effect, and only when heterospecific males were present. In contrast, C. chinensis, the species not susceptible to reproductive interference, demonstrated no Allee effect regardless of the presence of heterospecific males. Our results show that reproductive interference in fact generated an Allee effect, suggesting the potential importance of interspecific sexual interactions especially in small or sparse populations, even in the absence of a shared resource. It may be possible to predict Allee effects produced by this mechanism a priori by testing reproductive interference between closely related species.     

Number of conspecifics and reproduction in the invasive plant Eschscholzia californica (Papaveraceae): is there a pollinator‐mediated Allee effect?

The component Allee effect has been defined as ‘a positive relationship between any measure of individual fitness and the number or density of conspecifics’. Larger plant populations or large patches have shown a higher pollinator visitation rate, which may give rise to an Allee effect in reproduction of the plants. We experimentally tested the effect of number of conspecifics on reproduction and pollinator visitation in Eschscholzia californica Cham., an invasive plant in Chile. We then built patches with two, eight and 16 flowering individuals of E. californica (11 replicates per treatment) in an area characterised by dominance of the study species. We found that E. californica exhibits a component Allee effect, as the number of individuals of this species has a positive effect on individual seed set. However, individual fruit production was not affected by the number of plants examined. Pollinator visitation rate was also independent of the number of plants, so this factor would not explain the Allee effect. This rate was positively correlated with the total number of flowers in the patches. We also found that the number of plants did not affect the seed mass or proportion of germinated seeds in the patches. Higher pollen availability in patches with 16 plants and pollination by wind could explain the Allee effect. The component Allee effect identified could lead to a weak demographic Allee effect that might reduce the rate of spread of E. californica. Knowledge of this would be useful for management of this invasive plant in Chile.     

Stimulation of lettuce seed germination by ethylene

Ethylene increased the germination of freshly imbibed lettuce (Lactuca sativa L. var. Grand Rapids) seeds. Seeds receiving either red or far-red light or darkness all showed a positive response to the gas. However, ethylene was apparently without effect on dormant seeds, those which failed to germinate after an initial red or far-red treatment. Carbon dioxide, which often acts as a competitive inhibitor of ethylene, failed to clearly reverse ethylene-enhanced seed germination. While light doubled ethylene production from the lettuce seeds, its effect was not mediated by the phytochrome system since both red and far-red light had a similar effect.     

Presynaptic Regulation by ACh of the NE Mediated Responses in the Rat Vas Deferens

Abstract

In the isolated electrically stimulated vas deferens preparation the effect of exogenous acetylcholine (ACh) was studied. It was possible to differentiate two separate sites for the action of ACh. A postsynaptic effect (M₁) which is revealed as a sudden decrease in the basal tension of the muscular twitch, antagonized competitively by atropine (pA₂ = 8.44 ± 0.79), potentiated at a ratio of 10.24 by neostigmine, and not altered by hexamethonium, yohimbine, clonidine, theophylline or prazosin. Treatment with reserpine or 6-OH-DA induced a supersensitivity of this effect. The second action is a presycaptic effect (M₂), which is manifested by a rapid increase in the muscular twitch, is dose-dependent to Ach, and is potentiated significantly by reserpine, neostigmine and clonidine. This latter effect was not modified by atropine, hexamethonium, yohimbine, prazosin or theophylline. The normal efficacy of ACh is 185 times greater in presynaptic over postsynaptic receptors. The increase in the twitch is not considered to be by the release of endogenous ACh or ATP. The evidence presented here indicates that the presynaptic effect of ACh (M₂) is due to participation of α₂ - adrenoceptors in enhancement of the release of norepinephrine (NE) from the nerve terminals.