Antiproliferative activity of <i>Curcuma phaeocaulis</i> <i>Valeton</i> extract using ultrasonic assistance and response surface methodology

<p>The objective of the study was to optimize the ultrasonic-assisted extraction of curdione, furanodienone, curcumol, and germacrone from <i>Curcuma phaeocaulis</i> <i>Valeton</i> (Val.) and investigate the antiproliferative activity of the extract. Under the suitable high-performance liquid chromatography condition, the calibration curves for these four tested compounds showed high levels of linearity and the recoveries of these four compounds were between 97.9 and 104.3%. Response surface methodology (RSM) combining central composite design and desirability function (DF) was used to define optimal extraction parameters. The results of RSM and DF revealed that the optimum conditions were obtained as 8 mL g⁻¹ for liquid–solid ratio, 70% ethanol concentration, and 20 min of ultrasonic time. It was found that the surface structures of the sonicated herbal materials were fluffy and irregular. The <i>C. phaeocaulis</i> Val. extract significantly inhibited the proliferation of RKO and HT-29 cells <i>in vitro</i>. The results reveal that the RSM can be effectively used for optimizing the ultrasonic-assisted extraction of bioactive components from <i>C. phaeocaulis</i> Val. for antiproliferative activity.</p

MOESM4 of Optimization and in vitro antiproliferation of Curcuma wenyujin’s active extracts by ultrasonication and response surface methodology

Additional file 4: Figure S3. Bar graph showing individual desirability values (d i ) of various objective responses and the maximum combined desirability of 0.971 for the optimization of ultrasonic extraction conditions for extraction of curdione, furanodienone, curcumol and germacrone from Curcuma wenyujin

Marmoset chair and behavior setup.

<p>A. Marmoset chair with feeding tube, infrared lick detector, and optional head restraint mechanism for single-unit recording. The neck plate slides out to allow a marmoset to enter the chair from below. After securing neck plate, the feeding tube can be adjusted to create a comfortable reach for each monkey. B. Schematic of task setup. Sounds are played from free field speakers while marmosets lick to target sounds for a reward which is delivered by a syringe pump via a feeding tube. Lick responses are recorded when the infrared beam is broken by the animal’s face or tongue. Behavior apparatus are controlled by a personal computer and powered by a custom built power supply and electrical isolation module.</p

Learning curves.

<p>A–E. Learning curves for 5 naive marmosets performing an auditory detection task with broad band noise or pure tone stimuli. Data represent training <i>Phase 2</i> (see <i>Response Shaping</i>). Training is considered complete when 4 of 5 consecutive sessions have been completed with at least 80% hit rate and less than 25% false positives. Average time to train across all animals was 12 sessions with a standard deviation of 6 sessions. F. Average hit rate and false positive rate over all training sessions. Later sessions had fewer data points averaged due to some animals completing training more quickly than others.</p

Single unit recording during behavior.

<p>Example of voltage signal, high pass filtered for spike sorting, from a high impedance microelectrode recording single unit activity in marmoset auditory cortex during task performance. Time is referenced to pre-stimulus delivery interval. The licking behavior can be performed without compromising recording stability (meaning that units can be held reliably) or signal quality. Note that spikes can be easily discerned both before and after a lick is detected.</p

Behavior trial.

<p>After a variable number of background stimuli (or silent periods, for the detection task described here), targets begin alternating with the background stimuli/silent periods. If a lick is registered within the preset number of alternations, a food reward is given. After the animal has finished consuming the reward (as measured via the lick detector), the next inter-target interval begins with background stimuli or silent intervals. A lick outside of a target interval results in a timeout.</p

Bifuctional Amino-Squaramides Catalyzed Asymmetric Spiroannulation Cascades with Aliphatic β,γ-Unsaturated α-Keto Esters: Controlling an Aldehyde Enolate

A quinidine-derived squaramide <b>Ib</b> catalyzed cyclization reaction of β-oxo aldehydes <b>1</b> and aliphatic or aromatic β,γ-unsaturated α-keto ester <b>2</b> is described. Using cyclic aldehyde substrates, this procedure provided a promising approach to a variety of spiro-3,4-dihydropyrans bearing three continuous quaternary and tertiary stereocenters in moderate to good yield with high stereoselectivities. Substituents on the nitrogen atoms of the squaramide moiety of the catalyst proved crucial to the reaction outcome. The stereochemistry of the three newly formed chiral centers (<i>trans</i>-selective) of the major product indicates a Micheal addition/hemiacetalization domino sequence for the present annulations

Performance across testing stages.

<p>Performance of musicians (gray box) and non-musicians (open box) is plotted for each of the four testing stages. The performance is plotted as the RAU value. Each box represents percentiles of the data. The line within the box indicates the median. Error bars represent the minimums and maximum values. Small circles indicate the outliers. The significant difference between musician and non-musicians groups is indicated by the asteroids above the two boxes for each testing stage. (<b><i>A</i></b>) MTS condition in Experiment 1. Musicians’ performance is significantly higher than non-musicians at all four testing stages. (<b><i>B</i></b>) RTS condition in Experiment 1. No significant difference between musicians and non-musicians. (<b><i>C</i></b>) Experiment 2. Musicians’ performance is significantly higher than non-musicians at stages 1, 2, and 3, but not at stage 4. The significant difference was marked as stars.</p

Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation

<div><p>Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as “Wnt signalling pathway” and “endocytosis”. Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA.</p></div

Internalisation of exosomes in hMSCs.

<p>Confocal micrographs of hMSCs incubated for 24h with A) PBS (negative control); B) Exo_P6; C) Exo_D3 and D) Exo_D21. PKH67-stained exosomes are detected mainly in the cytoplasm of some of the cells. The intensity varied between individual cells. No PKH67-stained material was found in the negative control. A1-D1, blue channel; A2-D2, green channel; A3-D3, transmission (TD) channel; A4-D4, merged channels. Blue, DAPI-stained nucleus; Green, PKH67-stained exosomes. Scale bar: 20 μm.</p