Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression.

BACKGROUND AND PURPOSE: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1ß, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.

Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer.

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer's disease, and atherosclerosis. Several studies have shown that CHI3L1 can be considered as a marker of disease diagnosis, prognosis, disease activity, and severity. In addition, the proinflammatory action of CHI3L1 may be mediated via responses to various proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interferon-γ. Therefore, CHI3L1 may contribute to a vast array of inflammatory diseases. However, its pathophysiological and pharmacological roles in the development of inflammatory diseases remain unclear. In this article, we review recent findings regarding the roles of CHI3L1 in the development of inflammatory diseases and suggest therapeutic approaches that target CHI3L1.

Effectiveness of Acupotomy Combined with Epidural Steroid Injection for Lumbosacral Radiculopathy: A Randomized Controlled Pragmatic Pilot Study.

Background and Objectives: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine its feasibility for the main study. Materials and Methods: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5-10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits. Results: Mean ODI scores for the experimental and control groups were -9.44 (95% confidence interval [CI]: -12.71, -6.17) and -2.16 (95% CI: -5.01, 0.69) at week 4, and -9.04 (95% CI: -12.09, -5.99) and -4.76 (95% CI: -7.68, -1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (p = 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed. Conclusions: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.

Ultra-soft and highly stretchable tissue-adhesive hydrogel based multifunctional implantable sensor for monitoring of overactive bladder.

A highly stretchable and tissue-adhesive multifunctional sensor based on structurally engineered islets embedded in ultra-soft hydrogel is reported for monitoring of bladder activity in overactive bladder (OAB) induced rat and anesthetized pig. The use of hydrogel yielded a much lower sensor modulus (1 kPa) compared to that of the bladder (300 kPa), while the strong adhesiveness of the hydrogel (adhesive strength: 260.86 N/m) allowed firm attachment onto the bladder. The change in resistance of printed liquid metal particle thin-film lines under strain were used to detect bladder inflation and deflation; due to the high stretchability and reliability of the lines, surface strains of 200% could be measured repeatedly. Au electrodes coated with Platinum black were used to detect electromyography (EMG). These electrodes were placed on structurally engineered rigid islets so that no interfacial fracture occurs under high strains associated with bladder expansion. On the OAB induced rat, stronger signals (change in resistance and EMG root-mean-square) were detected near intra-bladder pressure maxima, thus showing correlation to bladder activity. Moreover, using robot-assisted laparoscopic surgery, the sensor was placed onto the bladder of an anesthetized pig. Under voiding and filling, bladder strain and EMG were once again monitored. These results confirm that our proposed sensor is a highly feasible, clinically relevant implantable device for continuous monitoring OAB for diagnosis and treatment.

[Corrigendum] Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Subsequently to the publication of the above article, the authors have realized that Fig. 3 on p. 6, showing the results of bioluminescence imaging of U87 and U373 cells after applying tumor­treating fields for 72 h, was published containing an erroneous image. Essentially, the data analysis panel for the U87 / U87TTF experiment was inadvertently copied across for the U373 / U373TTF experiment for the '75% Duty' experimental condition. The revised version of Fig. 3, now showing the correct data analysis panel for the '75% Duty' U373 / U373TTF experiment, is shown below. The authors confirm that the error made in the presentation of Fig. 3 did not adversely affect the conclusions reported in this paper, and they are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. All the authors agree to the publication of this Corrigendum; they also apologize to the readership for any inconvenience caused. [International Journal of Oncology 60: 8, 2022; DOI: 10.3892/ijo.2021.5298].

A comparative study of a nerve block therapy with and without a deeply inserted acupotomy applied to hyeopcheok points for lumbosacral radiculopathy: Safety, effectiveness, cost-effectiveness (a randomized controlled, two-arm, parallel study, pilot study, assessor-blind).

INTRODUCTION: The prevalence of lumbosacral radiculopathy is estimated to be approximately 3% to 5% in patient populations. Lumbosacral radiculopathy is largely caused by a complex interaction between biomechanical and biochemical factors. Nerve block therapy (NBT) mainly treats lumbosacral radiculopathy by improving the biochemical factors, whereas acupotomy mainly focuses on improving the biomechanical factors. Therefore, it is thought that synergistic effects may be obtained for the treatment of lumbosacral radiculopathy when both NBT and acupotomy are combined. However, no study in China and Korea, where acupotomy is majorly provided, has reported the effects of such a combination treatment. Therefore, this study aimed to evaluate the safety, effectiveness, and cost-effectiveness of the concurrent use of a deeply inserted acupotomy and NBT for the treatment of lumbosacral radiculopathy. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded, randomized controlled trial, which will include 50 patients with lumbosacral radiculopathy. After patients voluntarily agree to participate in the study, they will be screened, and will undergo necessary examinations and tests according to the protocol. Those who satisfy the selection criteria will be randomly assigned to either the NBT + acupotomy or NBT groups in a 1:1 ratio. Both groups will undergo 2 NBTs once every 2 weeks from 1 week after the screening test. The treatment group will receive additional acupotomy twice a week for 4 weeks. The primary endpoint is the Oswestry Disability Index, whereas the secondary endpoints are the Numeral Rating Scale, European Quality of Life 5-dimension, McGill pain Questionnaire, Roland-Morris Disability Questionnaire, safety assessment, and economic feasibility evaluation. The measurements will be made at 0, 2, 4, and 8 weeks. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS20OISE0085). We intend to submit the results of the trial to a peer-reviewed journal and/or conferences.

Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Tumor­treating fields (TTFields) are emerging cancer therapies based on alternating low­intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.

Sonochemical activation in aqueous medium for solid-state synthesis of BaTiO3 powders.

BaTiO3-based oxide compounds are important ceramic materials for multilayer ceramic capacitors. In this paper, we report a sonochemical activation process of BaCO3 and TiO2 in an aqueous medium for the synthesis of BaTiO3 powders through a solid-state process. Owing to the physical and chemical effects of the ultrasonication in aqueous medium on the raw materials, BaTiO3 powders could be successfully synthesized at relatively low temperatures through a solid-state reaction, which was significantly enhanced as compared to the case in ethanol medium. Detailed investigations on the resulting BaTiO3 powders and ceramics were performed, and a model to understand the role of aqueous medium on the enhancement of the solid-state reaction was proposed in terms of Ba2+ ion leaching and zeta potential of TiO2, which are strongly affected by the pH of the aqueous medium. Our results are not only helpful for cost-effective synthesis of BaTiO3 through the highly reliable solid-state reaction process, but they also provide an understanding of the role of aqueous medium for the sonochemical process using raw materials with partial solubility in water.

Investigation for Thermoelectric Properties of the MoS2 Monolayer-Graphene Heterostructure: Density Functional Theory Calculations and Electrical Transport Measurements.

We investigated the thermoelectric (TE) properties of the MoS2 monolayer-graphene heterostructure which consists of the MoS2 monolayer and graphene. The electronic structures of the MoS2 monolayer-graphene heterostructure are mainly contributed from graphene and the MoS2 monolayer for the valence band maximum and conduction band minimum, respectively. The change in the electronic structures near the Fermi level is responsible for the fact that the calculated Seebeck coefficients S and electrical conductivity σ/τ of MoS2 monolayer-graphene are largely affected from those of graphene and the MoS2 monolayer. Its power factor S 2σ/τ is increased compared to those of graphene and the MoS2 monolayer at an electron concentration of 1011 to 1012 cm-2, which corresponds to a three-dimensional concentration of 3 × 1018 to 3 × 1019 cm-3. We also demonstrated that the MoS2 monolayer shows the p-type TE behavior, while the MoS2 monolayer-graphene heterostructure is given to the n-type TE material. The current study provides a strategy to improve TE properties of the MoS2 monolayer through the formation of the MoS2 monolayer-graphene heterostructure.

Anomalous in-plane lattice thermal conductivity in an atomically thin two-dimensional α-GeTe layer.

Low lattice thermal conductivity is one of the most important physical quantities for phononic device applications. Thus, we investigated the in-plane lattice thermal conductivity of mono- and bi-layer α-GeTe systems. The lattice thermal conductivity of the monolayer system along the zigzag direction was 0.43 (W mK-1) while it was 0.21 (W mK-1) along the armchair direction at 300 K, and the lattice thermal conductivity mostly originated from the out-of-plane acoustic mode. In the bilayer system, it was significantly suppressed to 0.044 (W mK-1) and 0.047 (W mK-1) along the zigzag and armchair directions, respectively, at 300 K. Particularly, the out-of-plane acoustic mode in the bilayer had a tremendous Grüneisen parameter and this led to an ultralow in-plane lattice thermal conductivity in the bilayer, and the optical mode dominated the contribution to the lattice thermal conductivity. Our findings may raise intriguing issues regarding the thermoelectric effect, heat insulators, and phononic device applications, and stimulate further experimental studies to verify our theoretical predictions.

Development of a MEL Cell-Derived Allograft Mouse Model for Cancer Research.

Murine erythroleukemia (MEL) cells are often employed as a model to dissect mechanisms of erythropoiesis and erythroleukemia in vitro. Here, an allograft model using MEL cells resulting in splenomegaly was established to develop a diagnostic model for isolation/quantification of metastatic cells, anti-cancer drug screening, and evaluation of the tumorigenic or metastatic potentials of molecules in vivo. In this animal model, circulating MEL cells from the blood stream were successfully isolated and quantified with an additional in vitro cultivation step. In terms of the molecular-pathological analysis, we were able to successfully evaluate the functional discrimination between methyl-CpG-binding domain 2 (Mbd2) and p66α in erythroid differentiation, and tumorigenic potential in spleen and blood stream of allograft model mice. In addition, we found that the number of circulating MEL cells in anti-cancer drug-treated mice was dose-dependently decreased. Our data demonstrate that the newly established allograft model is useful to dissect erythroleukemia pathologies and non-invasively provides valuable means for isolation of metastatic cells, screening of anti-cancer drugs, and evaluation of the tumorigenic potentials.

Gigantic Phonon-Scattering Cross Section To Enhance Thermoelectric Performance in Bulk Crystals.

In thermoelectric energy conversions, thermal conductivity reduction is essential for enhancing thermoelectric performance while maintaining a high power factor. Herein, we propose an approach based on coated-grain structures to effectively reduce the thermal conductivity to a much greater degree when compared to that done by conventional nanodot nanocomposite. By incorporating CdTe coated layers on the surface of SnTe grains, the thermal conductivity is as low as 1.16 W/m-K at 929 K, resulting in a thermoelectric figure of merit, i.e., zT, of 1.90. According to our developed theory, phonons scatter coherently due to the phase lag between phonons passing through and around the coated grain. Such scattering is induced by the acoustic impedance mismatch between the coated layer and the grain, resulting in a gigantic phonon-scattering cross section. The phonon-scattering cross section of the coated grains is several orders of magnitude larger than that of the nanodots with the same impurity concentration. The power factor was also slightly increased by the energy filtering effect at the coated surface and additional minority carrier blocking by the heterointerfaces. This scheme can be utilized for various bulk crystals, meaning a broad range of materials can be considered for thermoelectric applications.

Phonon-glass electron-crystals in ZnO-multiwalled carbon nanotube nanocomposites.

We propose a strategy for enhancing thermoelectric performance through the realization of a 'phonon-glass electron-crystal' (PGEC) by interface control using multiwalled carbon nanotubes (MWCNTs). By the consolidation of undoped ZnO nanoparticles with MWCNTs (0.5, 1, and 2 wt%) using spark plasma sintering, we fabricated the interface-controlled ZnO-MWCNT nanocomposites, in which ZnO grains were surrounded with a MWCNT network. Both single crystal-like charge transport (electron-crystal) and considerably reduced thermal conductivity (phonon-glass) were achieved simultaneously thanks to the beneficial effects of the MWCNT network, and this led to the enhancement of the thermoelectric figure of merit. We discussed these findings on PGECs in the ZnO-MWCNT nanocomposites from the viewpoint of interface control in detail, and our strategy may provide a promising way to the realization of PGEC in other hybrid thermoelectric materials.

A gigantically increased ratio of electrical to thermal conductivity and synergistically enhanced thermoelectric properties in interface-controlled TiO2-RGO nanocomposites.

We report synergistically enhanced thermoelectric properties through the independently controlled charge and thermal transport properties in a TiO2-reduced graphene oxide (RGO) nanocomposite. By the consolidation of TiO2-RGO hybrid powder using spark plasma sintering, we prepared an interface-controlled TiO2-RGO nanocomposite where its grain boundaries are covered with the RGO network. Both the enhancement in electrical conductivity and the reduction in thermal conductivity were simultaneously achieved thanks to the beneficial effects of the RGO network, and detailed mechanisms are discussed. This led to the gigantic increase in the ratio of electrical to thermal conductivity by six orders of magnitude and also the synergistic enhancement in the thermoelectric figure of merit by two orders. Our results present a strategy for the realization of 'phonon-glass electron-crystals' through interface control using graphene in graphene hybrid thermoelectric materials.

Structurally nanocrystalline-electrically single crystalline ZnO-reduced graphene oxide composites.

ZnO, a wide bandgap semiconductor, has attracted much attention due to its multifunctionality, such as transparent conducting oxide, light-emitting diode, photocatalyst, and so on. To improve its performances in the versatile applications, numerous hybrid strategies of ZnO with graphene have been attempted, and various synergistic effects have been achieved in the ZnO-graphene hybrid nanostructures. Here we report extraordinary charge transport behavior in Al-doped ZnO (AZO)-reduced graphene oxide (RGO) nanocomposites. Although the most challenging issue in semiconductor nanocomposites is their low mobilities, the AZO-RGO nanocomposites exhibit single crystal-like Hall mobility despite the large quantity of nanograin boundaries, which hinder the electron transport by the scattering with trapped charges. Because of the significantly weakened grain boundary barrier and the proper band alignment between the AZO and RGO, freely conducting electrons across the nanograin boundaries can be realized in the nanocomposites. This discovery of the structurally nanocrystalline-electrically single crystalline composite demonstrates a new route for enhancing the electrical properties in nanocomposites based on the hybrid strategy.

Unoxidized graphene/alumina nanocomposite: fracture- and wear-resistance effects of graphene on alumina matrix.

It is of critical importance to improve toughness, strength, and wear-resistance together for the development of advanced structural materials. Herein, we report on the synthesis of unoxidized graphene/alumina composite materials having enhanced toughness, strength, and wear-resistance by a low-cost and environmentally benign pressure-less-sintering process. The wear resistance of the composites was increased by one order of magnitude even under high normal load condition (25 N) as a result of a tribological effect of graphene along with enhanced fracture toughness (KIC) and flexural strength (σf) of the composites by ~75% (5.60 MPa·m(1/2)) and ~25% (430 MPa), respectively, compared with those of pure Al2O3. Furthermore, we found that only a small fraction of ultra-thin graphene (0.25-0.5 vol%, platelet thickness of 2-5 nm) was enough to reinforce the composite. In contrast to unoxidized graphene, graphene oxide (G-O) and reduced graphene oxide (rG-O) showed little or less enhancement of fracture toughness due to the degraded mechanical strength of rG-O and the structural defects of the G-O composites.

Thermal stability of gallium-doped zinc oxide thin film on glass substrates by an RF sputtering process.

The effects of a heat treatment on the structural and electrical properties of GZO thin films grown by RF magnetron sputtering were investigated. The heat treatment involved temperatures in the range from 200 degrees C to 500 degrees C under air. As the temperature was increased, the electrical properties of GZO thin films increased exponentially and the surface morphology was drastically altered. The effect of temperature is discussed based on electrical and structural characterization of the materials.

Interfacial structure and electrical properties of transparent conducting ZnO thin films on polymer substrates.

The effects of polymer substrates on the interfacial structure and the thermal stability of Ga-doped ZnO (GZO) thin films were investigated. The GZO thin films were deposited on polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) substrates by rf-magnetron sputtering at room temperature, and thermal stability tests of the GZO thin films on the polymer substrates were performed at 150°C up to 8 h in air. Electrical and structural characterizations of the GZO thin films on the PET and the PEN substrates were carried out, and the origins of the stable interfacial structure and the improved thermal stability of the GZO thin film on the PEN substrate were discussed.

The cardiovascular effects of midazolam co-induction to propofol for induction in aged patients.

BACKGROUND: The aim of this study was to investigate whether a small dose of midazolam and lessening the propofol dosage could prevent cardiovascular change at tracheal intubation for induction in aged patients. METHODS: Eighty patients over 65 years (ASA physical status 1, 2) scheduled for elective surgery received general anesthesia with remifentanil and propofol or midazolam. Patients in group P (n = 40) were induced with 0.9% NaCl 0.03 ml/kg, propofol 1. 2 mg/kg and remifentanil. Patients in group MP (n = 40) were induced with midazolam 0.03 mg/kg, propofol 0.8 mg/kg and remifentanil. The time taken to reach loss of consciousness (LOC) and the value of bispectral index score (BIS) at LOC were recorded. After LOC, 0.8 mg/kg of rocuronium was given and tracheal intubation was performed. The mean blood pressure (MBP) and heart rate (HR) were recorded before induction as the base value, before intubation, immediately post-intubation and 3 minutes after intubation. RESULTS: Compared with the base values, MBP at before intubation and 3 minutes after intubation was significantly decreased in group P and group MP (P < 0.05). Compared with group P, the decrease of MBP was significantly less at before intubation, immediately after intubation and 3 minutes after intubation in group MP (P < 0.05). The time taken to reach LOC was significantly decreased in group MP compared with that in group P (P < 0.05). There were no significant differences of HR at any time between the two groups. CONCLUSIONS: Co-induction with midazolam and propofol could prevent a marked BP decrease at tracheal intubation for induction in aged patients.

The expression of survivin and its related genes in adipocyte-derived stem cell by demethylation.

BACKGROUND: Survivin is thought to contribute to stem cell maintenance partly by a hypomethylation mechanism. This study attempted to elucidate the signal transduction pathway of adipocyte-derived stem cells (ASCs) by using a demethylating agent, 5-aza-2'-deoxycytidine (ADC), to analyze the survivin, MEK/ERK, c-Myc and p53 gene expression. METHODS: Demethylation in the ASCs was induced by 1 microM ADC treatment. RT-PCR for survivin mRNA was preformed, before and 24, 48 and 72 hours (hr) after ADC treatment. Western blotting analysis was performed for p53, survivin, unphosphorylated and phosphorylated (p)-MEK, and p-ERK. Immunohistochemistry for ERK and survivin was done to evaluate the localization of the proteins. RESULTS: ADC inhibited the population growth of the ASCs and it increased the number of apoptotic cells 24, 48, and 72 hr after treatment. ADC treatment slightly decreased the expression of survivin mRNA after 48 hr and its level was restored after 72 hr of treatment. Otherwise, the level of survivin protein gradually increased up to 48 hr and it was decreased at 72 hr. The levels of p-MEK and p53 were increased time-dependently. c-Myc and p-ERK were elevated after ADC treatment and their highest levels were seen 48 hr after treatment. The ADC treatment increased the nuclear expression of ERK and survivin in the ASCs. CONCLUSIONS: The overexpression of p-MEK/ERK, p53, and c-Myc increased the survivin protein expression of the demethylated ASCs. These results suggest that demethylation could alter the expression of survivin, and p53, c-Myc and the MAPK (MEK/ERK) pathway might play a role in survivin's regulation in ASCs.