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Inflammation caused by the excessive secretion of inflammatory mediators in abnormally activated macrophages promotes many diseases along with oxidative stress. Loganin, a major iridoid glycoside isolated from Cornus officinalis, has recently been reported to exhibit anti-inflammatory and antioxidant effects, whereas the underlying mechanism has not yet been fully clarified. Therefore, the aim of the present study is to investigate the effect of loganin on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results indicated that loganin treatment markedly attenuated the LPS-mediated phagocytic activity and release of nitric oxide (NO) and prostaglandin E2, which was associated with decreased the expression of inducible NO synthase and cyclooxygenase-2. In addition, loganin suppressed the expression and their extracellular secretion of LPS-induced pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Furthermore, loganin abolished reactive oxygen species (ROS) generation, and promoted the activation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated macrophages. However, zinc protoporphyrin, a selective HO-1 inhibitor, reversed the loganin-mediated suppression of pro-inflammatory cytokines in LPS-treated macrophages. In conclusion, our findings suggest that the upregulation of the Nrf2/HO-1 signaling pathway is concerned at least in the protective effect of loganin against LPS-mediated inflammatory and oxidative stress, and that loganin can be a potential functional agent to prevent inflammatory and oxidative damage.

Indole-6-carboxaldehyde (I6CA), an indole derivative isolated from the marine brown algae Sargassum thunbergii, is known to have several beneficial effects, but no studies on immune regulation have been conducted. In this study, the immunomodulatory properties of I6CA on murine RAW 264.7 monocyte/macrophage cells were evaluated. As the concentration of I6CA increased, the morphology of RAW 264.7 cells changed to a typical active macrophage shape, and the phagocytic activity increased significantly. I6CA effectively enhanced the production and secretion of immunomodulatory mediators and cytokines due to increased expression of their respective genes. Additionally, I6CA markedly stimulated the expression of Toll-like receptor 4 (TLR4) and its adapter molecule, myeloid differentiation factor 88 (Myd88), and increased TLR4 complexed with Myd88. Furthermore, I6CA promoted the nuclear translocation of nuclear factor-kappa B (NF-κB) by increasing the degradation of the inhibitor of NF-κB-α. Meanwhile, similar trends were also found in lipopolysaccharide-treated cells as a positive control. Furthermore, molecular docking simulation showed that I6CA interacted with TLR4-myeloid differentiation 2 complex. Taken together, the results support the concept that I6CA may increase the activity of the TLR4/NF-κB signaling pathway in order to enhance the immunomodulatory activity of RAW 264.7 cells.

Honokiol is one of the main active components of Magnolia officinalis, and has been demonstrated to have multiple pharmacological activities against a variety of diseases. Recently, this phenolic compound is known to have antioxidant activity, but its mechanism of action remains unclear. The purpose of the current study was to evaluate the preventive effects of honokiol against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. The present study found that honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation. The inhibitory effect of honokiol on H2O2-induced apoptosis was associated with the up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, these results demonstrate that honokiol defends C2C12 myoblasts against H2O2-induced DNA damage and apoptosis, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS.

Mori Ramulus, the dried twigs of Morus alba L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H2O2) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H2O2-induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H2O2-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H2O2-triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome c release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H2O2. Furthermore, AEMR diminished H2O2-induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H2O2-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H2O2-induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy.

Because cable-driven parallel robots (CDPRs) have lightweight moving parts, CDPRs have been used in various industrial applications requiring high speeds and accelerations. Especially, CDPRs with polymer cables can achieve higher accelerations and speeds compared to those with steel cables. However, they also have some disadvantages, such as a nonlinear creep, a hysteresis, and a short- and long-term recovery. Because these nonlinear characteristics, the accuracy of CDPRs gets worse and worse. In this study, we proposed a hybrid recurrent neural network (H-RNN) to predict nonlinear characteristics of the cable elongation and to solve the problems associated with CDPRs and apply the real-time control. In the algorithm, the long short-term memory (LSTM) algorithm was used to learn the characteristics of the low-frequency data, and the basic RNN learned the features of the high-frequency data. We also confirmed that the cut-off frequency was determined based on the non-operating frequency related to rest time. Also, it yielded more accurate results because the LSTM has a wider effective frequency range. Finally, the learning process was completed by combining these two algorithms. These results made it possible to predict position errors of CDPRs with high accuracy, in which error varies under both while operating and no operation conditions. The H-RNN had a lower root mean square error than both the optimal RNN and the optimal LSTM, so it was effective for controlling systems that have errors across a range of frequencies.

Gamma irradiation is a useful technology to change the physical and biological properties of natural molecules. In this study, we investigated whether gamma irradiation improve properties of chrysin as an anti-inflammatory candidates. Chrysin was converted into two compounds (CM1 and CM2) by gamma irradiation. We determined the therapeutic potential of these compounds in bone marrow-derived macrophages and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in Balb/c mice. The structural changes to chrysin led to the reduction of cytotoxicity without loss of anti-inflammatory properties in BMDMs. Purified CM2 inhibited lipopolysaccharide (LPS)-induced overexpression of nitric oxide, tumor necrosis factor-α, interleukin (IL)-6, and surface molecules without cytotoxicity in BMDMs, while CM1 revealed strong cytotoxicity. Furthermore, treatment with CM2 significantly alleviated AD-like skin symptoms and clinical signs in DNCB-induced AD mice model. The suppression of AD mediated by CM2 treatment was accompanied by decrease inflammatory T cell cytokines (IFN-γ, IL-5, IL-4, and IL-17). The chemical structure of CM2 and structural transformation mechanism were determined by nuclear magnetic resonance and mass spectrometry. Our study findings provide evidence that CM2 produced by gamma irradiation of chrysin can be an attractive therapeutic agent for AD.

The polymer cable is a widely used material in the cable-driven parallel robot (CDPR) system because of its many advantages such as high sensitivity, large workspace and so on. However, the accurate control of CDPR is not easy because of complicated response of the cable. In our previous study, the integrated cable model was derived. Based on the model, parametric studies were progressed in this paper. While operating CDPR, various parameters such as length, applied tension, and tensile rate can be changed and dominantly affect the dynamics of CDPR. For this reason, parametric study was based on these parameters. In this investigation, dynamic creep, hardening factor and short-term recovery were saturated as processing cyclic load. Each saturation rate was dominantly influenced by cable length and applied tension. As the tensile rate was increased, the dynamic creep was decreased. The hysteresis was the characteristic combining all of dynamics. So, the hysteresis also had saturation trends. When the exerted tension was decreased, the length of cable could be reduced or elongated because the creep and recovery occur at the same time.

Background: Trans-cinnamaldehyde (tCA), a bioactive component found in Cinnamomum cassia, has been reported to exhibit anti-inflammatory and antioxidant effects, but its efficacy in muscle cells has yet to be found. In this study, we investigated the inhibitory effect of tCA on inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in C2C12 mouse skeletal myoblasts. Methods: To investigate the anti-inflammatory and antioxidant effects of tCA in LPS-treated C2C12 cells, we measured the levels of pro-inflammatory mediator, cytokines, and reactive oxygen species (ROS). To elucidate the mechanism underlying the effect of tCA, the expression of genes involved in the expression of inflammatory and oxidative regulators was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of tCA against LPS in the zebrafish model. Results: tCA significantly inhibited the LPS-induced release of pro-inflammatory mediators and cytokines, which was associated with decreased expression of their regulatory genes. tCA also suppressed the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor, and attenuated the nuclear translocation of nuclear factor-kappa B (NF-κB) and the binding of LPS to TLR4 on the cell surface in LPS-treated C2C12 cells. Furthermore, tCA abolished LPS-induced generation of ROS and expression levels of ROS producing enzymes, NADPH oxidase 1 (NOX1) and NOX2. However, tCA enhanced the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated C2C12 myoblasts. In addition, tCA showed strong protective effects against NO and ROS production in LPS-injected zebrafish larvae. Conclusions: Our findings suggest that tCA exerts its inhibitory ability against LPS-induced inflammatory and antioxidant stress in C2C12 myoblasts by targeting the TLR4/NF-κB, which might be mediated by the NOXs and Nrf2/HO-1 pathways.

Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of the central nervous system and are currently being tested in clinical trials for neurological disorders. However, no studies have examined the various roles of embryonic stem cell derived (ES)-MSCs in eliciting therapeutic effects for Alzheimer's disease (AD). In the present study, we investigated the neuroprotective effect of ES-MSCs in cellular and animal models of AD, as well as the safety of the intra-arterial administration of ES-MSCs in an AD animal model. ES-MSCs displayed higher cell viability than that of bone marrow (BM)-MSCs in amyloid-β (Aβ)-induced cellular models. Moreover, the efficacy of autophagy induction in ES-MSCs was comparable to that of BM-MSCs; however, intracellular Aβ levels were more significantly reduced in ES-MSCs than in BM-MSCs. In a rat model of AD, ES-MSCs significantly inhibited Aβ-induced cell death in the hippocampus and promoted autophagolysosomal clearance of Aβ, which was concomitantly followed by decreased levels of Aβ in the hippocampus. Furthermore, ES-MSC treatment in Aβ-treated rats featured a higher memory performance than that of rats injected solely with Aβ. Finally, intra-arterial administration of an appropriate cell density of ES-MSCs was safe and free from in situ occlusion or cerebral ischemia. These data support the therapeutic potential of ES-MSCs and clinical applications of the intra-arterial route of ES-MSC administration in AD.

There has been a rapid increase in the number of classical swine fever (CSF) sero-positive wild boars captured near the demilitarized zone (DMZ), located the border with North Korea. In 2015&ndash, 2016, few CSFV-positive antibody boars were detected, however, the number has increased steeply since 2017. Most occurred in the northern region of Gyeonggi before spreading slowly to Gangwon (west to east) in 2018&ndash, 2019. Multi-distance spatial cluster analysis provided an indirect estimate of the time taken for CSFV to spread among wild boars: 46.7, 2.6, and 2.49 days/km. The average CSF serum neutralization antibody titer was 4&ndash, 10 (log 2), and CSFV Ab B-ELISA PI values ranged from 65.5 to 111.5, regardless of the age and sex of wild boars. Full genome analysis revealed that 16 CSFV strains isolated from wild boars between 2017 and 2019 were identical to the YC16CS strain (sub-genotype 2.1d) isolated from an outbreak in breeding pigs near the border with North Korea in 2016. The rapid increase in CSF in wild boars may be due to a continuously circulating infection within hub area and increased population density. The distribution pattern of CSFV in Korean wild boars moves from west to southeast, affected by external factors, including small-scale hunting, geographical features and highways.

Isorhamnetin, which is a flavonoid predominantly found in fruits and leaves of various plants, including Hippophae rhamnoides L. and Oenanthe javanica (Blume) DC, is known to possess various pharmacological effects. However, the anti‑inflammatory potential of isorhamnetin remains poorly studied. Therefore, the present study aimed to investigate the inhibitory potential of isorhamnetin against inflammatory responses in lipopolysaccharide (LPS)‑stimulated BV2 microglia. To measure the effects of isorhamnetin on inflammatory mediators and cytokines, and reactive oxygen species (ROS) generation, the following methods were used: cell viability assay, griess assay, ELISA, reverse transcriptase‑polymerase chain reaction, flow cytometry, western blotting and immunofluorescence staining. The results revealed that isorhamnetin significantly suppressed LPS‑induced secretion of pro‑inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, without exhibiting significant cytotoxicity. Consistent with these results, isorhamnetin inhibited LPS‑stimulated expression of regulatory enzymes, including inducible NO synthase and cyclooxygenase‑2 in BV2 cells. Isorhamnetin also downregulated LPS‑induced production and expression of pro‑inflammatory cytokines, such as tumor necrosis factor‑α and interleukin‑1β. The mechanism underlying the anti‑inflammatory effects of isorhamnetin was subsequently evaluated; this flavonoid inhibited the nuclear factor (NF)‑κB signaling pathway by disrupting degradation and phosphorylation of inhibitor κB‑α in the cytoplasm and blocking translocation of NF‑κB p65 into the nucleus. In addition, isorhamnetin effectively suppressed LPS‑induced expression of Toll‑like receptor 4 (TLR4) and myeloid differentiation factor 88. It also suppressed the binding of LPS with TLR4 in BV2 cells. Furthermore, isorhamnetin markedly reduced LPS‑induced generation of ROS in BV2 cells, thus indicating a strong antioxidative effect. Collectively, these results suggested that isorhamnetin may suppress LPS‑mediated inflammatory action in BV2 microglia through inactivating the NF‑κB signaling pathway, antagonizing TLR4 and eliminating ROS accumulation. Further studies are required to fully understand the anti‑inflammatory effects associated with the antioxidant capacity of isorhamnetin; however, the findings of the present study suggested that isorhamnetin may have potential benefits in inhibiting the onset and treatment of neuroinflammatory diseases.

Cable-driven parallel robots (CDPRs) have been widely used in various industrial applications requiring high sensitivity. These CDPRs mainly use high strength polymer ropes with light weight and low inertia. However, the polymer cable used in CDPR has the complicated dynamic characteristics such as nonlinear elongation, hysteresis, creep and short and long-term recovery. As CDPR cables are loaded and unloaded under various forces and velocities, dynamic creep and recovery due to loading and unloading strain rate occurs in real time. We proposed the integrated nonlinear dynamic model of polymer cable for the low tensile rate. All of dynamic behaviors were described with only integrated nonlinear dynamic model based on the visco-elastic model. Since the total time when the tension is applied to the system is an important factor in the dynamic creep characteristics, we calculated the loading and unloading time using the concept of equivalent force and the Newton–Raphson method. The constructed model was verified by comparing with experimental results for the hardening effect, dynamic creep, hysteresis and short- and long-term recovery. The proposed model had a good agreement with experimental result.

Automobile tires consist of more than ten layers, including tread, belt, carcass, sidewall, etc. The outermost layer, known as the tread, plays an important role during driving as it comes in direct contact with the road. This tread has grooves with complicated shapes, which are formed by a mold during the shaping process. When the tread rubber does not fill the mold properly, tire quality deteriorates crucially. As such, it is important to observe the flow of the tread rubber during the shaping process. To determine the flow of tread rubber in the mold, we conducted an experiment and computer simulation with white rubber strips inserted into specific areas of the tread. The white rubber strips showed detailed flow behavior of the tread rubber visually in the mold during the shaping process. No significant flows were observed for rubber in the central area of each block of the mold, but more changes were found near the edges of each block. The strips of rubber below the grooves exhibited more significant changes as they were pressed down by the protruding area of the mold. Moreover, there was no flow of rubber between blocks in the mold. This implies the profile design of the extruded tread should match the mold profile and the volume of each block. The experiment and simulation had similar results, and the observations of rubber flow in the mold using simulation proved to be highly useful.

The leaves of Aster yomena (Kitam.) Honda have long been used as a traditional herb for treating disorders including coughs, asthma, and insect bites. According to recent studies, A. yomena leaf extracts have several pharmacological properties, including anti-inflammatory, antioxidant, and anti-asthmatic activities. However, little information is available regarding their anti-obesity effect. In this study, we investigated the inhibitory effect of the ethanol extracts of A. yomena leaves (EEAY) on adipocyte differentiation and adipogenesis using 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were treated with various concentrations of EEAY (ranging from non-toxic), the number of lipid droplets, lipid content, and triglyceride production, the typical characteristics of adipocytes, were suppressed in a concentration-dependent manner. During this process, EEAY significantly reduced the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α and β, and sterol regulatory element-binding protein-1c. In addition, EEAY was also found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein and leptin. In particular, EEAY treatment effectively enhanced the activation of the AMP-activated protein kinase (AMPK) signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EEAY-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EEAY may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the leaf extract of A. yomena may be a potential anti-obesity agent.

Esculetin, a coumarin derivative isolated from a variety of medicinal herbs, has been reported to possess multiple therapeutic and pharmacological actions. Although several studies have demonstrated the antioxidant activity of esculetin, its mechanisms of action have not been clearly established. The aim of this study was to evaluate the effects of esculetin against hydrogen peroxide (H2O2)‑induced oxidative stress in C2C12 myoblasts and to investigate the mechanisms involved in this process. Our data indicated that esculetin preconditioning significantly attenuated H2O2‑induced growth inhibition and DNA damage and the apoptosis of C2C12 cells by suppressing intracellular reactive oxygen species (ROS) accumulation. Treatment with esculetin effectively increased the phosphorylation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1). Esculetin treatment also activated extracellular signal‑regulated kinase (ERK), and pre‑treatment with PD98059, an ERK‑specific inhibitor, blocked esculetin-mediated phosphorylation of Nrf2 and the induction of NQO1 expression. In addition, the protective effects of esculetin against H2O2‑induced ROS accumulation, apoptosis and growth inhibition were abrogated in the C2C12 cells pre‑treated with PD98059. Thus, the present study demonstrates that esculetin protects C2C12 cells against oxidative stress-induced injury, possibly through the activation of the Nrf2/NQO1 pathway.

We examined the anti-cancer effect of genistein, a soy-derived isoflavone, in human bladder transitional cell carcinoma T24 cells. According to our data, genistein induced G2/M phase arrest of the cell cycle and apoptosis. Genistein down-regulated the levels of cyclin A and cyclin B1, but up-regulated the levels of p21WAF1/CIP1, cyclin-dependent kinase (Cdk) inhibitor, that was complexed with Cdc2 and Cdk2. Furthermore, genistein induced the activation of caspases (caspase-3, -8 and -9), and cleavage of poly (ADP-ribose) polymerase cleavage. However, genistein-induced apoptosis was significantly inhibited by a pan-caspase inhibitor, indicating that the induction of apoptosis by genestein was caspase-dependent. In addition, genistein increased the cytosolic release of cytochrome c by increasing the Bax/Bcl-2 ratio and destroying mitochondria integrity. Moreover, genistein inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of genistein. Genistein further increased the accumulation of reactive oxygen species (ROS), which was significantly suppressed by N-acetyl cysteine (NAC), a ROS scavenger, and in particular, NAC prevented genistein-mediated inactivation of PI3K/Akt signaling, G2/M arrest and apoptosis. Therefore, the present results indicated that genistein promoted apoptosis induction in human bladder cancer T24 cells, which was associated with G2/M phase cell cycle arrest via regulation of ROS-dependent PI3K/Akt signaling pathway.

Excessive bone resorption by osteoclasts causes bone loss-related diseases and reactive oxygen species (ROS) act as second messengers in intercellular signaling pathways during osteoclast differentiation. In this study, we explored the protective effects of fermented oyster extract (FO) against receptor activator of nuclear factor-&kappa, B (NF-&kappa, B) ligand (RANKL)-induced osteoclast differentiation in murine monocyte/macrophage RAW 264.7 cells. Our results showed that FO markedly inhibited RANKL-induced activation of tartrate-resistant acid phosphatase and formation of F-actin ring structure. Mechanistically, FO has been shown to down-regulate RANKL-induced expression of osteoclast-specific markers by blocking the nuclear translocation of NF-&kappa, B and the transcriptional activation of nuclear factor of activated T cells c1 (NFATc1) and c-Fos. Furthermore, FO markedly diminished ROS production by RANKL stimulation, which was associated with blocking the expression of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) and its regulatory subunit Rac-1. However, a small interfering RNA (siRNA) targeting NOX1 suppressed RANKL-induced expression of osteoclast-specific markers and production of ROS and attenuated osteoclast differentiation as in the FO treatment group. Collectively, our findings suggest that FO has anti-osteoclastogenic potential by inactivating the NF-&kappa, B-mediated NFATc1 and c-Fos signaling pathways and inhibiting ROS generation, followed by suppression of osteoclast-specific genes. Although further studies are needed to demonstrate efficacy in in vivo animal models, FO may be used as an effective alternative agent for the prevention and treatment of osteoclastogenic bone diseases.

Recent accumulating studies have reported that hypoxic preconditioning during ex vivo expansion enhanced the self-renewal or differentiation of various stem cells and provide an important strategy for the adequate modulation of oxygen in culture conditions, which might increase the functional bioactivity of these cells for cardiac regeneration. In this study, we proposed a novel priming protocol to increase the functional bioactivity of cardiac progenitor cells (CPCs) for the treatment of cardiac regeneration. Firstly, patient-derived c-kit(+) CPCs isolated from the atrium of human hearts by enzymatic digestion and secondly, pivotal target molecules identifi ed their differentiation into specific cell lineages. We observed that hCPCs, in response to hypoxia, strongly activated ERK phosphorylation in ex vivo culture conditioning. Interestingly, pre-treatment with an ERK inhibitor, U0126, significantly enhanced cellular proliferation and tubular formation capacities of CPCs. Furthermore, we observed that hCPCs efficiently maintained the expression of the c-kit, a typical stem cell marker of CPCs, under both hypoxic conditioning and ERK inhibition. We also show that hCPCs, after preconditioning of both hypoxic and ERK inhibition, are capable of differentiating into smooth muscle cells (SMCs) and cardiomyocytes (CMs), but not endothelial cells (ECs), as demonstrated by the strong expression of α-SMA, Nkx2.5, and cTnT, respectively. From our results, we conclude that the functional bioactivity of patient-derived hCPCs and their ability to differentiate into SMCs and CMs can be effi ciently increased under specifically defined culture conditions such as shortterm hypoxic preconditioning and ERK inhibition.

Cable robots can generate high velocities and accelerations due to the very small inertia of the end-effector. Therefore, CDPRs have been used widely in special industrial applications requiring high dynamics. However, the high acceleration generated affects the wrench-feasible workspace of a CDPR system significantly. In addition, as a pulley rotates, the frictional force at the pulley bearing disturbs the motion, changes the cable tensions. Thus, pulley bearing friction cannot be neglected in ultra-high acceleration systems where high tensions are imposed. A workspace analysis was carried out for a wrench-feasible condition in a 6-DOF CDPR system considering the pulley bearing friction connected in series. Then, the pulley bearing friction was modeled with the Coulomb friction model including the variation of wrapping angle of pulley and a loss factor. The simulated tension profiles considering pulley bearing friction were in good agreement with data measured with a load cell. And a wrench-feasible workspace analysis under various accelerations was carried out. In conclusion, as the external acceleration was increased, the whole tension was increased and workspaces to exceed available tension occurred in case of 100 m/s2. And the pulley bearing force increased or decreased the cable tension because of the direction of the signum function. As a result, the wrench-feasible workspace was changed in the presence of pulley bearing force effects.

Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

3) Abstract: Seven outbreaks of foot-and-mouth disease (FMD) have occurred in South Korea during the period January 2000-September 2015. The Korean government changed national goal to FMD-free country with vaccination after the November 2010 outbreak when approximately 3.5 million cattle and pigs were culled. With regard to vaccination, Korean pig producers have claimed that the occurrence of injection site reaction (inflammatory or non-inflammatory granuloma) is potentially associated with intensive vaccination campaign since 2011. The present study was undertaken to assess the incidence of injection site lesions in slaughtered pigs caused by FMD vaccination and the corresponding economic losses. Data obtained from two meat packers were classified into 3 vaccination periods: non-vaccination (July-November, 2010, n=96,959); one injection (July-November, 2014, n=162,089); and two injections (March-July, 2015, n=161,928). A total of 420,976 carcasses from 6,526 farms were analyzed. The incidence of the lesions was 18.6% for non-vaccination, 46.5% for one injection, and 73.7% for two injections. Economic loss per head slaughtered due to removal of the lesions was estimated to 1,302 won (US$ 1.1) for non-vaccination, 8,286 won (US$ 7.2) for one injection, and 17,378 won (US$ 15.1) for two injections (converted using 2015 exchange rate where Korean won 1,150 = 1 US$). It was estimated that the national annual losses excluding costs of an FMD vaccine and its application is US$ 115 million for one injection and US$ 241 million for two injections. The adoption of measures that cause minimal tissue damages and economic losses would appear to be of high priority.

Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumu-lation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was as-sociated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT in-duces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26-2.83, P = .002) and 3.526 (95% CI: 2.12-5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42-5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.

Cable driven parallel robots (CDPRs) have been widely used in precision Industries. However, an error occurs in repetitive motion of the CDPR because of the elongation and recovery of cable. Also, it is difficult to apply the numerical cable model because of its complexity. In this paper, we use the frequency based H-RNN method for accurate kinematics. H-RNN predicted more accurately compared with LSTM and RNN algorithms.

This paper addresses the problem of target detection in adaptive arrays in situations where only a small number of training samples is available. Within the framework of two-stage adaptive detection paradigm, we propose a new two-stage (TS) joint loaded persymmetric- Toeplitz adaptive matched filter (JLPT -AMF) detector. This new detector combines, using a joint detection strategy, individual scalar CFAR decisions from two rapidly adaptive detectors: a TS TAMF detector and a TS LPAMF detector. The former is based on a TMI filter, which is an adaptive array filter employing a Toeplitz covariance matrix estimator introduced in [1]. The latter is based on an adaptive LPMI filter that uses diagonally loaded persymmetric covariance matrix (CM) estimate inversion. The TS JLPT -AMF detector ensures the constant false alarm rate (CFAR) property independently of the antenna array dimension M, the interference CM, and the number of training samples NCME to be used for estimating this CM. This new detector exhibits highly reliable detection performance, which is robust to the angular separation between the sources, even when NCME is about m/2 ~ m, m is the number of interference sources. The robustness of the proposed adaptive detector to the angular separation is analytically proven and verified with statistical simulation.

Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.

Considering the steady increase in life expectancy slowing or reversing the deleterious effects of aging has garnered considerable interest. Accordingly, functional cosmetics based on stem cell technology (Stem cell cosmetics), which combine the anti-aging concept with high technology, is an emerging trend in the cosmetics industry. Stem cells possess self-renewal properties and the potency to differentiate. Therefore, stem cells are the most important cells in the skin, as they are the source for continuous regeneration of the epidermis. Stem cell cosmetics are developed based on stem cell technology, which involves using extracts or culture media of stem cells. However, cosmetics containing stem cells or their extracts have not been released into the market due to legal, ethical, and safety concerns. Meanwhile, plant stem cells, which circumvent these problems, are highly regarded in the cosmetics industry for improving culture technology. The European Union prohibits the use of cells, tissues, or products of human origin in cosmetics, whereas the Korea Food and Drug Association has allowed the use of sources originating from stem cell media in cosmetics since 2009. The global cosmetics market is worth more than 242 billion dollars; however, cosmetic companies across the world that are developing and launching stem cell cosmetics based on stem cell activators, culture extracts, and culture media are much more focused on the Korean cosmetic market.

Classical swine fever (CSF) is a highly contagious systemic hemorrhagic viral disease of pigs. Wild boar plays a crucial role in the epidemiology of CSF. Between 2010 and 2014, samples were collected nationwide from 6,654 wild boars hunted in South Korea. Anti-CSF antibodies were identified in 0.59% (39 of 6,654) of the wild boar samples using a virus neutralization test and were primarily detected in wild boars living close to the demilitarized zone and the area of the Taebaek Mountains surroundings. The CSF virus (subgroup 2.1b) was isolated from two wild boars captured in a nearby border area. The criteria used to define high-risk areas for targeted CSF surveillance in South Korea should be further expanded to include other regions nationwide.

The efficacy of cell therapy using endothelial colony-forming cells (ECFCs) in the treatment of ischemia is limited by the replicative senescence of isolated ECFCs in vitro. Such senescence must therefore be overcome in order for such cell therapies to be clinically applicable. This study aimed to investigate the potential of sulfated polysaccharide fucoidan to rescue ECFCs from cellular senescence and to improve in vivo vascular repair by ECFCs. Fucoidan-preconditioning of senescent ECFCs was shown by flow cytometry to restore the expression of functional ECFC surface markers (CD34, c-Kit, VEGFR2, and CXCR4) and stimulate the in vitro tube formation capacity of ECFCs. Fucoidan also promoted the expression of cell cycle-associated proteins (cyclin E, Cdk2, cyclin D1, and Cdk4) in senescent ECFCs, significantly reversed cellular senescence, and increased the proliferation of ECFCs via the FAK, Akt, and ERK signaling pathways. Fucoidan was found to enhance the survival, proliferation, incorporation, and endothelial differentiation of senescent ECFCs transplanted in ischemic tissues in a murine hind limb ischemia model. Moreover, ECFC-induced functional recovery and limb salvage were markedly improved by fucoidan pretreatment of ECFCs. To our knowledge, the findings of our study are the first to demonstrate that fucoidan enhances the neovasculogenic potential of ECFCs by rescuing them from replicative cellular senescence. Pretreatment of ECFCs with fucoidan may thus provide a novel strategy for the application of senescent stem cells to therapeutic neovascularization. Stem Cells 2015;33:1939–1951

Since cable driven parallel robots (CDPRs) have many advantages, they have been used in many industrial fields. Fully constrained CDPRs mainly use Dyneema polyethylene because it has advantage of the lower weight than steel wire. However, the polyethylene cable has complex elastic characteristics (e.g. permanent stretch and hysteresis). In this paper, the advanced numerical modeling of nonlinear elastic cable with permanent stretch using cable driven parallel robot was derived and simulated for various cable condition. Based on the advanced numerical nonlinear cable model, the simulation was carried out under the various cable lengths and tensions. Compared to the experimental results, the simulation results are good agreement with the experimental data.

Cable driven parallel robots (CDPRs) have many advantages such as low inertia and large workspace. These advantages lead to the industrial applications. CDPRs mainly use Dyneema polymer cable for more high sensitivity because it has advantage of the lower weight than steel wire. However, the polymer cable is continuously deformed when actuating the CDPR because of the elasto-plastic cable characteristics such as recovery. In this paper, numerical cable recovery was proposed using the modified burger model. Finally, the models were simulated and compared with the experimental profiles. As the result, the simulations are good agreement with the experimental profiles.