Acute myeloid leukemia (AML) is a hematological malignancy characterized by a rapid increase in the number of immature myeloid cells in bone marrow. Despite recent advances in the treatment, AML remains an incurable disease. Matrine, a major component extracted from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines. However, the effects of matrine on AML remain largely unknown. Here we investigated its anticancer effects and underlying mechanisms on human AML cells in vitro and in vivo. The results showed that matrine inhibited cell viability and induced cell apoptosis in AML cell lines as well as primary AML cells from patients with AML in a dose- and time-dependent manner. Matrine induced apoptosis by collapsing the mitochondrial membrane potential, inducing cytochrome c release from mitochondria, reducing the ratio of Bcl-2/Bax, increasing activation of caspase-3, and decreasing the levels of p-Akt and p-ERK1/2. The apoptotic effects of matrine on AML cells were partially blocked by a caspase-3 inhibitor Z-DEVD-FMK and a PI3K/Akt activator IGF-1, respectively. Matrine potently inhibited in vivo tumor growth following subcutaneous inoculation of HL-60 cells in SCID mice. These findings indicate that matrine can inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective candidate as chemotherapeutic agent against AML.
Recent work of Dupire and Carr and Lee has highlighted the importance of understanding the Skorokhod embedding originally proposed by Root for the model-independent hedging of variance options. Root's work shows that there exists a barrier from which one may define a stopping time which solves the Skorokhod embedding problem. This construction has the remarkable property, proved by Rost, that it minimizes the variance of the stopping time among all solutions.In this work, we prove a characterization of Root's barrier in terms of the solution to a variational inequality, and we give an alternative proof of the optimality property which has an important consequence for the construction of subhedging strategies in the financial context.
Gas barrier films with water-vapor-permeability have exhibited broad application prospects in gas separation and dehumidification. Herein, multilayer films comprised of layered double hydroxides (LDH) nanosheets and carboxymethyl cellulose sodium (CMC) were fabricated via layer-by-layer assembly. The resulting (LDH/CMC) films show excellent gas barrier properties, which are ascribed to the significantly increased pathway for gas permeation originating from the large aspect ratio and high orientation of two-dimensional LDH nanosheets. Unlike traditional gas barrier films with nonselective blocking effect for various gases (including water vapor), the (LDH/CMC) films exhibit an unusual moisture permselective property. The moisture-permeable property was related to the hygroscopicity of CMC and hydrophilicity of LDH, which can enrich the water molecules from the surroundings and aggrandize the osmotic pressure for water vapor, resulting in an uncommon improvement of water vapor transmission. It is interesting to find that the (LDH/CMC) films exhibit enhanced gas (O, CO, CH, and N) barrier properties upon treatment in a humid environment, due to the formation of hydrogen bonds between the infiltrated water molecules and hydrophilic groups in CMC, thus padding the interstitial space of the CMC molecular chains and increasing the gas transmission path. The reduction of free volume and extension of the gas transmission path further enhance the gas barrier properties of (LDH/CMC) films. Moreover, the (LDH/CMC) films represent the water vapor permselective property in mixed gas (including O, CO, CH, N, and water vapor), while maintaining the barrier for other gases, which can be potentially applied in air dehydration and dehumidification of natural gas.
Background: Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have gained momentum as a treatment for tendinopathy. Multiple studies have demonstrated significant differences in cargo composition between the 2 subtypes of MSC-EVs (ie, exosomes and ectosomes), which may result in different therapeutic effects. However, the effects of the 2 EV subtypes on tendinopathy have not yet been compared. Purpose: To compare the effects of adipose stem cell–derived exosomes (ASC-Exos) and ectosomes (ASC-Ectos) on Achilles tendinopathy. Study Design: Controlled laboratory study. Methods: Rats were administered collagenase injections to generate a model of Achilles tendinopathy. A week later, 36 rats were randomly assigned to 3 groups. In each group, Achilles tendons were injected with equal volumes of ASC-Exos, ASC-Ectos, or saline (12 legs/group). The healing outcomes were evaluated by magnetic resonance imaging, histology, immunohistochemistry, transmission electron microscopy, and biomechanical testing at 3 and 5 weeks after collagenase injection. Results: At 3 and 5 weeks, the ASC-Exo group had better histological scores ( P = .0036 and P = .0276, respectively), a lower fibril density ( P < .0001 and P = .0310, respectively), and a larger collagen diameter ( P = .0052 and P < .0001, respectively) than the ASC-Ecto group. At 5 weeks, the expression of collagen type 1 and CD206 in the ASC-Exo group was significantly higher than that in the ASC-Ecto group ( P = .0025 and P = .0010, respectively). Regarding biomechanical testing, the ASC-Exo group showed higher failure load ( P = .0005), tensile stress ( P < .0001), and elastic modulus ( P < .0001) than the ASC-Ecto group. Conclusion: ASC-Exos had more beneficial effects on tendon repair than ASC-Ectos in a rat model of Achilles tendinopathy. Clinical Relevance: Administration of ASC-EVs may have the potential to treat Achilles tendinopathy, and delivery of ASC-Exos could provide additional benefits. It is necessary to compare the healing responses caused by different EV subtypes to further understand their effects on tendinopathy and to aid clinical decision making.
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