Effects of Angelica gigas

We investigated the cellular and molecular mechanisms mediating the effects of Angelica gigas Nakai extract (AGNE) through the mitogen-activated protein kinases (MAPKs)/NF-κB pathway using in vitro and in vivo atopic dermatitis (AD) models. We examined the effects of AGNE on the expression of proinflammatory cytokines and chemokines in human mast cell line-1 (HMC-1) cells. Compound 48/80-induced pruritus and 2,4-dinitrochlorobenzene- (DNCB-) induced AD-like skin lesion mouse models were also used to investigate the antiallergic effects of AGNE. AGNE reduced histamine secretion, production of proinflammatory cytokines including interleukin- (IL-) 1β, IL-4, IL-6, IL-8, and IL-10, and expression of cyclooxygenase- (COX-) 2 in HMC-1 cells. Scratching behavior and DNCB-induced AD-like skin lesions were also attenuated by AGNE administration through the reduction of serum IgE, histamine, tumor necrosis factor-α (TNF-α), IL-6 levels, and COX-2 expression in skin tissue from mouse models. Furthermore, these inhibitory effects were mediated by the blockade of the MAPKs and NF-κB pathway. The findings of this study proved that AGNE improves the scratching behavior and atopy symptoms and reduces the activity of various atopy-related mediators in HMC-1 cells and mice model. These results suggest the AGNE has a therapeutic potential in anti-AD

Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model

BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer

Cognitive and behavioral effects of lamotrigine and carbamazepine monotherapy in patients with newly diagnosed or untreated partial epilepsy

AbstractPurposeIn this prospective study, we compared the long-term cognitive and behavioral effects of lamotrigine (LTG) and carbamazepine (CBZ) in patients with newly diagnosed or untreated partial epilepsy.MethodsThis was a multicenter, open-label, randomized study that compared monotherapy with LTG and CBZ in newly diagnosed or untreated patients with partial epilepsy. We employed an 8-week titration period and a 40-week maintenance period. Neuropsychological tests, Symptom Check List-90, and QOLIE-31 were assessed at baseline, 16 weeks, and 48 weeks after drug treatment. A group-by-time interaction was the primary outcome measure and was analyzed by use of the linear mixed model.ResultsA total of 110 patients were eligible and 73 completed the 48-week study (LTG, n=39; CBZ, n=34). Among the cognitive tests, significant group-by-time interaction was identified only in phonemic fluency of Controlled Oral Word Association Task (p=0.0032) and Stroop Color–Word Interference (p=0.0283), with a significant better performance for LTG group. All other neuropsychological tests included did not show significant group-by-time interactions. Among the subscales of Symptom Check List-90, significant group-by-time interactions were identified in Obsessive-Compulsive (p=0.0005), Paranoid Ideation (p=0.0454), Global Severity Index (p=0.0194), and Positive Symptom Total (p=0.0197), with a significant improvement for CBZ group. QOLIE-31 did not show significant group-by-time interactions.ConclusionOur data suggest that epilepsy patients on LTG have better performance on phonemic fluency and the task of Stroop Color–Word Interference than do patients on CBZ, whereas patients on CBZ had more favorable behavioral effects on two subscales and two global scores of Symptom Check List-90 than did patients on LTG

Dual quadratic differentials and entire minimal graphs in Heisenberg space

We define holomorphic quadratic differentials for spacelike surfaces with constant mean curvature in the Lorentzian homogeneous spaces $\mathbb{L}(\kappa,\tau)$ with isometry group of dimension 4, which are dual to the Abresch-Rosenberg differentials in the Riemannian counterparts $\mathbb{E}(\kappa,\tau)$, and obtain some consequences. On the one hand, we give a very short proof of the Bernstein problem in Heisenberg space, and provide a geometric description of the family of entire graphs sharing the same differential in terms of a 2-parameter conformal deformation. On the other hand, we prove that entire minimal graphs in Heisenberg space have negative Gauss curvature.Comment: 19 page

Upper and Lower Limb Muscle Activation during Green Care: An Electromyographic Analysis

Green care activities are associated with lower intensity and a lower risk of injury than agricultural activities aimed at producing agricultural and livestock products; however, the risk of health problems cannot be completely ruled out. To implement green care interventions to improve physical health, it is essential to identify the green care activity levels and biomechanical characteristics of the movements that are appropriate for each subject’s physical functions and goals. Thus, this study was conducted to determine the muscle activation of the upper and lower limbs during 19 green care farming activities. We used electromyography signals, which are biomedical signals that measure the action potentials generated in the muscles and nervous system when the muscles contract, to evaluate the muscle activation. Twenty adults (aged 29.9 ± 9.6 years) participated in this study. Participants performed 19 green care farming activities, including horticultural activity, animal-mediated, and off-farming activities. The participants performed each activity three times. The electromyography data were assessed using surface electromyography during activities to measure muscle activation. As a result, 16 upper and lower limb muscles were activated during the green care farming activities, which showed significantly different muscle activation by care farming activity. As a result of the comparison of muscle activity according to each muscle, many of the muscles of the upper and lower limbs were most activated during organizing a garden plot, transplanting plants, and collecting natural objects. In conclusion, the electromyography data obtained during this study suggest that green care farming interventions may be effective for training specific muscles of the upper and lower limbs

Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway

Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gαq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes Nα-terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their N^α-terminal acetyl group

Nuclear Factor Erythroid-Derived 2-Like 2-Induced Reductive Stress Favors Self-Renewal of Breast Cancer Stem-Like Cells via the FoxO3a-Bmi-1 Axis

Aims: A subpopulation of cancer cells, termed cancer stem cells (CSCs), has stemness properties, such as self-renewal and differentiation, which drive cancer recurrence and tumor resistance. CSCs possess enhanced protection capabilities to maintain reduced intracellular levels of reactive oxygen species (ROS) compared with nonstem-like cancer cells. This study investigated whether reductive stress could regulate self-renewal activity in breast CSCs. Results: We found that manifestation of stemness in breast cancer stem-like cells was associated with an elevated production of reduced glutathione (GSH) maintained by upregulation of glutamate cysteine ligase catalytic subunit (GCLC) and consequently, lowered ROS levels. This was accompanied by upregulation of phospho-AMP-activated protein kinase, FoxO3a, and Bmi-1. Notably, expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) protein was substantially increased in cells undergoing sphere formation. We noticed that expression of Bmi-1 was inhibited after introduction of Nrf2 short interfering RNA into MCF-7 mammosphere cells. Silencing of Nrf2 expression suppressed the xenograft growth of subcutaneously or orthotopically injected human breast cancer cells. Innovation: Association between Nrf2 and self-renewal signaling in CSCs has been reported, but the underlying molecular mechanism remains largely unresolved. This study demonstrates the Nrf2-mediated signaling pathway in maintenance of reductive stress in breast CSCs. Conclusion: Nrf2 overactivation in breast CSCs upregulates GCLC expression and consequently enhances GSH biosynthesis with concurrent reduction in intracellular ROS accumulation, thereby provoking the reductive stress. The consequent upregulation of nuclear FoxO3a and its binding to the promoter of the gene encoding Bmi-1 account for the self-renewal activity of breast cancer stem-like cells and their growth in a xenograft mouse model.