Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.

Evaluation of Food Effect on the Pharmacokinetics of Velufenacin, a New Muscarinic Receptor Antagonist, in Healthy Subjects.

Velufenacin (DA-8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open-label, single-dose, 4-sequence, 4-treatment, 4-period crossover study was conducted. Subjects received a single oral dose of velufenacin 2.5 or 5 mg in a fasted or fed (high-fat meal) state in each period with a 7-day washout. PK parameters including maximum plasma concentration (Cmax ) and area under the concentration-time curve from time 0 to the last measurable point were compared between the fed and fasted states. Twenty-seven subjects completed the study. The mean area under the concentration-time curve from time 0 to the last measurable point of the velufenacin 2.5 and 5 mg doses under the fed condition showed a 1.5- and 1.3-fold increase, respectively, compared to the fasted condition. The corresponding values for Cmax were a 2.3- and 2.0-fold increase, respectively. The time to reach Cmax was comparable regardless of the dose or food intake, showing median values of 4.5-5.0 hours. These results suggest a modest increase of velufenacin absorption by food intake. Velufenacin was generally safe and well tolerated at the 2.5 and 5 mg doses regardless of food.

Phenylalkyl Glycosides from the Flowers of Brugmansia arborea L. and Their Radical Scavenging Effect and Protective Effect on Pancreatic Islets Damaged by Alloxan in Zebrafish (Danio rerio) Larvae.

The study aimed to investigate the antioxidant and antidiabetic activity of Brugmansia arborea L. flower extracts, solvent fractions, and isolated compounds. B. arborea L flowers were extracted with aqueous methanol, and concentrated extract was successively partitioned into EtOAc, n-BuOH, and H2O fractions. Repeated silica gel and octadecyl silica gel column chromatographies for EtOAc and n-BuOH fractions led to the isolation of a new phenylalkyl glycoside (6), along with five known ones. Several spectroscopic data led to the structure determination of one new phenylalky glycoside as brugmansioside C (named) (6) and five known ones as benzyl-O-ß-D-glucopyranoside (1), benzyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (2), 2-phenylethyl-O-ß-D-glucopyranoside (3), 2-phenylethyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (4), and 3-phenylpropyl-O-ß-D-glucopyranoside (5). The five known ones (1-5) were isolated from B. arborea flowers for the first time in this study. The extract, solvent fractions, and all isolated compounds showed radical scavenging activities using ABTS radical, and EtOAc fraction showed the highest scavenging capacity, whereas compounds 2, 4, and 6 did not display the capacity to use the DPPH radical. The extract, solvent fractions, and all isolated compounds showed a protective effect on pancreatic islets damaged by alloxan treatment in zebrafish larvae. The pancreatic islet size treated with EtOAc, n-BuOH fractions, and all compounds significantly increased by 64.0%, 69.4%, 82.0%, 89.8%, 80.0%, 97.8%, 103.1%, and 99.6%, respectively, compared to the alloxan-induced group. These results indicate that B. arborea flowers and their isolated compounds are useful as potential antioxidant and antidiabetic agents.

Anti-Neuroinflammatory Effect of the Ethanolic Extract of Black Ginseng through TLR4-MyD88-Regulated Inhibition of NF-κB and MAPK Signaling Pathways in LPS-Induced BV2 Microglial Cells.

Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the ethanolic extract of black ginseng (BGE) in lipopolysaccharide (LPS)-induced BV2 microglial cells. Pre-treatment with BGE inhibited the overproduction of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 cells. In addition, BGE reduced the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) MAPK signaling pathways induced by LPS. These anti-neuroinflammatory effects were mediated through the negative regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) signaling pathway. Among the four ginsenosides contained in BGE, ginsenosides Rd and Rg3 inhibited the production of inflammatory mediators. Taken together, this investigation suggests that BGE represents potential anti-neuroinflammatory candidates for the prevention and treatment of neurodegenerative diseases.

Synergistic Effect, Improved Cell Selectivity, and Elucidating the Action Mechanism of Antimicrobial Peptide YS12.

Antimicrobial peptides (AMPs) have attracted considerable attention as potential substitutes for traditional antibiotics. In our previous research, a novel antimicrobial peptide YS12 derived from the Bacillus velezensis strain showed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. In this study, the fractional inhibitory concentration index (FICI) indicated that combining YS12 with commercial antibiotics produced a synergistic effect. Following these findings, the combination of YS12 with an antibiotic resulted in a faster killing effect against bacterial strains compared to the treatment with the peptide YS12 or antibiotic alone. The peptide YS12 maintained its antimicrobial activity under different physiological salts (Na+, Mg2+, and Fe3+). Most importantly, YS12 exhibited no cytotoxicity towards Raw 264.7 cells and showed low hemolytic activity, whereas positive control melittin indicated extremely high toxicity. In terms of mode of action, we found that peptide YS12 was able to bind with LPS through electrostatic interaction. The results from fluorescent measurement revealed that peptide YS12 damaged the integrity of the bacterial membrane. Confocal laser microscopy further confirmed that the localization of peptide YS12 was almost in the cytoplasm of the cells. Peptide YS12 also exhibited anti-inflammatory activity by reducing the release of LPS-induced pro-inflammatory mediators such as TNF-α, IL-1ß, and NO. Collectively, these properties strongly suggest that the antimicrobial peptide YS12 may be a promising candidate for treating microbial infections and inflammation.

Pharmacokinetics of the novel 5-HT4 receptor agonist, DA-6886, in dogs.

The pharmacokinetics of a new 5-hydroxytryptamine receptor 4 agonist, DA-6886, intended for the treatment of constipation-predominant irritable bowel syndrome, were evaluated in beagle dogs following both intravenous and oral administration of DA-6886 (1-10 mg/kg). The study also examined the effects of gender and food on the pharmacokinetics of DA-6886 in dogs.DA-6886 demonstrated dose-proportional area under the plasma concentration-time curve (AUC) values and dose-independent clearance (21.0-24.6 mL/min/kg) after administration via both routes. The steady-state volume of distribution (Vss) for DA-6886 was dose-independent and relatively large (6.76-8.57 L/kg), aligning with its observed high distribution in rat tissues.No significant differences were observed in the pharmacokinetics of DA-6886 between male and female dogs. Post oral administration, extent of absolute oral bioavailability (BA) was relatively high (48.2-96.1%) in contrast to the rates observed in rats (18.9-55.0%).Dogs that were fed exhibited a significantly lower Cmax and a delayed Tmax in comparison to those that were fasted. However, the AUC values were similar between the two groups. The extended stomach transit time in the fed state may account for this delayed absorption of DA-6886 without substantial changes in AUC.

Grasping through dynamic weaving with entangled closed loops.

Pick-and-place is essential in diverse robotic applications for industries including manufacturing, and assembly. Soft grippers offer a cost-effective, and low-maintenance alternative for secure object grasping without complex sensing and control systems. However, their inherent softness normally limits payload capabilities and robustness to external disturbances, constraining their applications and hindering reliable performance. In this study, we propose a weaving-inspired grasping mechanism that substantially increases payload capacity while maintaining the use of soft and flexible materials. Drawing from weaving principles, we designed a flexible continuum structure featuring multiple closed-loop strips and employing a kirigami-inspired approach to enable the instantaneous and reversible creation of a woven configuration. The mechanical stability of the woven configuration offers exceptional loading capacity, while the softness of the gripper material ensures safe and adaptive interactions with objects. Experimental results show that the 130 g·f gripper can support up to 100 kg·f. Outperforming competitors in similar weight and softness domains, this breakthrough, enabled by the weaving principle, will broaden the scope of gripper applications to previously inaccessible or barely accessible fields, such as agriculture and logistics.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Boar fertility is controlled through systematic changes of mitochondrial protein expression during sperm capacitation.

Vigorous activation of mitochondria in spermatozoa during capacitation induces the biological and morphological changes of spermatozoa to acquire fertilizing ability. To in-depth understand the dynamic roles of mitochondrial and male fertility, this study was to identify how the mitochondrial proteins are changed during sperm capacitation and regulate male fertility using boar spermatozoa. The mitochondrial proteins were differentially changed during sperm capacitation according to fertility status, i.e., superior litter size (SL) and normal litter size (NL). Following sperm capacitation, ubiquitin-cytochrome c reductase core protein (UQCRC1) and ATP synthase F1 (ATP5F1) increased in NL, while cytochrome c oxidase subunit 5B (COX5B), and cytochrome c1 (CYC1) proteins decreased. In contrast, only and ubiquinone oxidoreductase core subunit 8 (NDUFS8) protein was increased in SL following capacitation. The protein expression difference value of CYC1, COX5B, and NDUFS8 following sperm capacitation was lower in NL than SL boars. Based on these complicated changes during sperm capacitation, the accuracy for predicting male fertility of NDUFS8 was increased to 87 %. Overall, considering the systematic orchestration of mitochondrial protein expression according to sperm capacitation status, it will be possible to better understand male fertility.

Anti-Neuroinflammatory and Neuroprotective Effect of Intermedin B Isolated from the Curcuma longa L. via NF-κB and ROS Inhibition in BV2 Microglia and HT22 Hippocampal Cells.

Compounds derived from Curcuma longa L. (C. longa) have been extensively studied and reported to be effective and safe for the prevention and treatment of various diseases, but most research has been focused on curcuminoids derived from C. longa. As neurodegenerative diseases are associated with oxidation and inflammation, the present study aimed to isolate and identify active compounds other than curcuminoids from C. longa to develop substances to treat these diseases. Seventeen known compounds, including curcuminoids, were chromatographically isolated from the methanol extracts of C. longa, and their chemical structures were identified using 1D and 2D NMR spectroscopy. Among the isolated compounds, intermedin B exhibited the best antioxidant effect in the hippocampus and anti-inflammatory effect in microglia. Furthermore, intermedin B was confirmed to inhibit the nuclear translocation of NF-κB p-65 and IκBα, exerting anti-inflammatory effects and inhibiting the generation of reactive oxygen species, exerting neuroprotective effects. These results highlight the research value of active components other than curcuminoids in C. longa-derived compounds and suggest that intermedin B may be a promising candidate for the prevention of neurodegenerative diseases.

Safety, tolerability, and pharmacokinetics of single and multiple ascending Oral doses of DA-8010 in healthy subjects: First-in-human phase I study.

This study assessed the safety, tolerability, and pharmacokinetics of single and multiple oral doses of DA-8010, a muscarinic M3 receptor antagonist, in healthy subjects. This was a randomized, double-blind, placebo-controlled, ascending single (Part A: 1, 2.5, 5, 20, and 40 mg QD fasted and 10 mg QD fasted and fed) and multiple doses (Part B: 5, 10, and 20 mg QD from Days 1 to 7 fasted), sequential-group study. Safety data were analyzed descriptively, time to maximum plasma concentration (tmax ) nonparametrically, and pharmacokinetic parameters using power and mixed models and ANOVA. Of 109 subjects randomized (Part A = 69 and Part B = 40; each part consisted a female group), 31 (44.9%) in Part A and 29 (72.5%) in Part B experienced treatment-emergent adverse events (TEAEs) in a dose-related manner. Common drug-related TEAEs in Part A and B were dizziness (8.7% and 15.0%), headache (5.8% and 12.5%) and blurred vision (8.7% and 20%). One male (20 mg) and one female (10 mg) from Part B discontinued the study due to a confusional state, and nausea and vomiting. Irrespective of sex, DA-8010 was steadily absorbed following single and multiple doses in the fasted state with increased systemic exposure in a dose-proportional manner with maximum plasma concentration occurring at a median tmax between 4.0 and 6.0 h. A high-fat meal increased systemic exposure. DA-8010 was safe, well tolerated, and well absorbed at lower doses and moderately tolerated at higher doses without any notable effects of food and sex.

Synthesis of Alpha-Linked Glucosides from Soybean Isoflavone Aglycones Using Amylosucrase from Deinococcus geothermalis.

Soybean isoflavone aglycones (SIAs) have many biological activities but are poorly water-soluble in the human body. Glycosylation provides structural diversity to SIAs and can alter their physicochemical properties, including water solubility. An alpha-linked glucosylation of SIA was achieved using amylosucrase from Deinococcus geothermalis. A total of 13 alpha-linked glucosyl SIAs were obtained, and their colors in solution were confirmed. The structures of the isolated compounds were identified by mass spectrometry and multidimensional nuclear magnetic resonance spectroscopy. The amylosucrase transglycosylation formed new isoflavone glycosides with alpha glycosidic bonds at C-7 and/or C-4' of SIAs, followed by the production of isoflavone glycosides with alpha (1 → 6) glycosidic bonds. The products with a glucosyl moiety attached to the C-4' of SIAs were found to be more water-soluble than their counterparts attached to the C-7 and/or beta-linkages. This study suggests a strategy for the synthesis of bioactive compounds with enhanced water solubility through alpha-linked glucosylation.

Antioxidant-Based Preventive Effect of Phytochemicals on Anticancer Drug-Induced Hepatotoxicity.

Significance: Drug-induced liver injury (DILI) or hepatotoxicity has been a hot issue to overcome on the safety and physiological function of the liver, since it is known to have biochemical, cellular, immunological, and molecular alterations in the liver mainly induced by alcohol, chemicals, drugs, heavy metals, and genetic factors. Recently efficient therapeutic and preventive strategies by some phytochemicals are of interest, targeting oxidative stress-mediated hepatotoxicity alone or in combination with anticancer drugs. Recent Advances: To assess DILI, the variety of in vitro and in vivo animal models has been developed mainly by using carbon tetrachloride, d-galactosamine, acetaminophen, and lipopolysaccharide. Also, the mechanisms on hepatotoxicity by several drugs and herbs have been explored in detail. Recent studies reveal that antioxidants including vitamins and some phytochemicals were reported to prevent against DILI. Critical Issues: Antioxidant therapy with some phytochemicals is noteworthy, since oxidative stress is critically involved in DILI via production of chemically reactive oxygen species or metabolites, impairment of mitochondrial respiratory chain, and induction of redox cycling. Future Directions: For efficient antioxidant therapy, DILI susceptibility, Human Leukocyte Antigen genetic factors, biomarkers, and pathogenesis implicated in hepatotoxicity should be further explored in association with oxidative stress-mediated signaling, while more randomized preclinical and clinical trials are required with optimal safe doses of drugs and/or phytochemicals alone or in combination for efficient clinical practice along with the development of advanced DILI diagnostic tools. Antioxid. Redox Signal. 38, 1101-1121.

SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.

The ethanolic extract of Curcuma longa grown in Korea exhibits anti-neuroinflammatory effects by activating of nuclear transcription factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

BACKGROUND: Curcuma longa has been used as spices, food preservative, coloring material, and traditional medicine. This plant also has long been used for a variety of diseases including dyslipidemia, stomach disorders, arthritis, and hepatic diseases. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the 50% ethanolic extract of C. longa in lipopolysaccharide (LPS)-induced BV2 microglial cells. METHODS: Griess reaction was employed to measure the production of nitric oxide (NO), and the levels of prostaglandin E2 (PGE2) and pro-inflammatory cytokines such as interleukin 1-beta (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) were determined by using profit ELISA kits. Western blotting was used to determine the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), mitogen activated protein kinases (MAPKs), heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2). RESULTS: Pre-treatment with CLE inhibited the overproduction and overexpression of pro-inflammatory mediators including NO, PGE2, iNOS, COX-2, and pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in LPS-induced BV2 cells. In addition, CLE suppressed the activation of the NF-κB and three MAPK signaling pathways. Treatment with CLE induced HO-1 protein expression by activating Nrf2 pathway, and inhibiting the HO-1 expression reversed the anti-inflammatory effect of CLE. CONCLUSION: CLE showed anti-neuroinflammatory effects against LPS-induced microglial cells activation through the inhibition of production and expression of pro-inflammatory mediators by negative regulation of the NF-κB and MAPK signaling pathways. These anti-neuroinflammatory effects of CLE were mediated by HO-1/Nrf2 signaling pathway. Taken together, the present study suggests a potent effect of CLE to prevent neuroinflammatory diseases. It is necessary to perform additional efficacy evaluation through in vivo experiments.

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice.

The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification.

A Wearable Textile-Embedded Dielectric Elastomer Actuator Haptic Display.

With advances in mobile computing and virtual/augmented reality technologies, communicating through touch using wearable haptic devices is poised to enrich and augment current information delivery channels that typically rely on sight and hearing. To realize a wearable haptic device capable of effective data communication, both ergonomics and haptic performance (i.e., array size, bandwidth, and perception accuracy) are essential considerations. However, these goals often involve challenging and conflicting requirements. We present an integrated approach to address these conflicts, which includes incorporating multilayered dielectric elastomer actuators, a lumped-parameter model of the skin, and a wearable frame in the design loop. An antagonistic arrangement-consisting of an actuator deforming the skin-was used to achieve effective force transmission while maintaining a low profile, and the effect of the wearable frame and structure was investigated through lumped-model analysis and human perception studies.

Validation of a Quantification Method for Curcumin Derivatives and Their Hepatoprotective Effects on Nonalcoholic Fatty Liver Disease.

Curcumin (CM), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are major curcumin derivatives found in the rhizome of turmeric (Curcuma longa L.), and have yielded impressive properties to halt various diseases. In the present study, we carried out a method validation for curcumin derivatives and analyzed the contents simultaneously using HPLC with UV detection. For validation, HPLC was used to estimate linearity, range, specificity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ). Results showed a high linearity of the calibration curve, with a coefficient of correlation (R2) for CM, DMC, and BDMC of 0.9999, 0.9999, and 0.9997, respectively. The LOD values for CM, DMC, and BDMC were 1.16, 1.03, and 2.53 ng/µL and LOQ values were 3.50, 3.11, and 7.67 ng/µL, respectively. Moreover, to evaluate the ability of curcumin derivatives to reduce liver lipogenesis and compare curcumin derivatives' therapeutic effects, a HepG2 cell model was established to analyze their hepatoprotective properties. Regarding the in vivo study, we investigated the effect of DMC, CM, and BDMC on nonalcoholic fatty liver disease (NAFLD) caused by a methionine choline deficient (MCD)-diet in the C57BL/6J mice model. From the in vitro and in vivo results, curcumin derivatives alleviated MCD-diet-induced lipid accumulation as well as high triglyceride (TG) and total cholesterol (TC) levels, and the protein and gene expression of the transcription factors related to liver adipogenesis were suppressed. Furthermore, in MCD-diet mice, curcumin derivatives suppressed the upregulation of toll-like receptors (TLRs) and the production of pro-inflammatory cytokines. In conclusion, our findings indicated that all of the three curcuminoids exerted a hepatoprotective effect in the HepG2 cell model and the MCD-diet-induced NAFLD model, suggesting a potential for curcuminoids derived from turmeric as novel therapeutic agents for NAFLD.

Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo.

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

Antitumor mechanism of combination of Angelica gigas and Torilis japonica in LNCaP prostate cancer cells via G1 arrest and inhibition of Wnt/ß-catenin and androgen receptor signaling.

The goal of the current study is to assess the antitumor mechanism by the combination (7:3) of Angelica gigas and Torilis japonica (AT) that was found most effective through screening against prostate-specific antigen (PSA) in LNCaP prostate cancer cells. Here, AT reduced the viability and the number of colonies in androgen-dependent LNCaP cells more than in androgen independent PC3 and DU145 cells. Also, AT induced G1 phase arrest, cleaved PARP and caspase 3, activated p27 and decreased the expression of Cyclin D1, Cyclin E, cdk2 in LNCaP cells. Furthermore, AT decreased the expression of PSA and androgen receptor (AR) at mRNA and protein levels in LNCaP cells. Interestingly, AT attenuated the expression of AR, PSA and Wnt-3a and the stability of AR and PSA in LNCaP cells. Furthermore, AT reversed dihydrotestosterone (DHT)-induced upregulation of AR and PSA in LnCaP cells. Notably, AT disrupted the protein-protein interaction, nuclear translocation and fluorescent expression of ß-catenin and AR in LNCaP cells. Consistently, ß-catenin depletion enhanced the decreased expression of AR in AT treated LNCaP cells. Taken together, our findings highlight evidence that AT suppresses the proliferation of LNCaP cells via G1 arrest and inhibition of ß-catenin and AR as a potential anticancer agent.