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Teff ( Eragrostis tef ), a gluten-free cereal crop cultivated originally in Northeast Africa, is increasingly utilized due to its nutritional and health benefits. The aim of the present study was to investigate the effects of ethanol extract obtained from raw and thermally treated teff, referred to as RTE and TTE, respectively, on uncontrolled growth and activated metastasis using human cancer cell lines. Both RTE and TTE contained flavones, such as orientin (luteolin 8-C-glucoside) and vitexin (apigenin 8-C-glucoside), and phenolic acids, such as protocatechuic acid and p -coumaric acid. TTE showed higher total phenol, protocatechuic acid, and p -coumaric acid contents, but lower orientin content compared to RTE. RTE and TTE significantly suppressed cell growth of H1299 human lung cancer cells, with TTE exhibiting more pronounced effects than RTE, while both extracts had only minimal effects on the growth of non-malignant human umbilical vein endothelial cells. The growth-inhibitory activities of RTE and TTE in H1299 cells were associated with apoptosis induction and cell cycle arrest at the G2/M phase. TTE produced an additional effect on inducing cell cycle arrest at the S phase in H1299 cells, potentially contributing to its stronger growth-inhibitory effects. Moreover, both RTE and TTE effectively inhibited key events in metastasis, such as invasion, migration, and adhesion, in H1299 cells under non-cytotoxic conditions, with TTE showing stronger effects. In HCT116 human colon cancer cells, a similar pattern of inhibition was demonstrated against the metastatic events, accompanied by reduced levels of matrix metalloproteinase-2 and -9. Our results indicate that teff extracts exhibit in vitro anti-growth and anti-metastatic activities, which are enhanced by thermal treatment of teff.

Olive flounder (Paralichthys olivaceus), a popular aquaculture species, is plagued by the disease scuticociliatosis caused by Miamiensis avidus, which has a high mortality rate and is typically treated with chemicals such as formalin and hydrogen peroxide. However, Carpesii fructus extract has shown potential as a natural therapeutic agent by reducing the motility of M. avidus. However, despite its potential importance, the effect of the extract on fish metabolism remains unknown. In this study, the effect of Carpesii fructus extract and formalin on fish metabolism was analysed by whole transcriptome analysis in the liver of P. olivaceus. A total of 37,796 transcripts were generated and differential expression genes (DEGs) were identified in the liver of P. olivaceus treated with Carpesii fructus extract or formalin. In addition, functional analysis of DEGs between treatment groups was presented using Gene Ontology. These results will be crucial for the study of scuticociliatosis in various fish species, including P. olivaceus, and for the development of therapeutic agents for other diseases.

Real-time quantitative PCR (RT-qPCR) is a widely used method for accurate quantitative gene expression analysis. For accurate quantitative verification of RT-qPCR, it is essential to select a reference gene with high expression stability depending on the experimental environment or the different tissues. In this study, we evaluated the stability of nine candidate reference genes, labeled elongation factor 1-alpha (EF1A), ERBB receptor feedback inhibitor 1-like isoform x2 (ERRFI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), integrin beta2 like (ITGB2), phosphatidylinositol-binding clathrin assembly protein-like isoform x3 (PICALM), 60 s ribosomal protein L5 (RPL5), 60 s ribosomal protein L7 (RPL7), tubulin beta chain (TUBB), and ubiquitin-conjugating enzyme E2A (UBE2A), in the brain (including pituitary gland) gonads and caudal fins of silvertip tetra ( Hasemania nana ) males and females. The stability evaluation of the reference gene was analyzed using a program based on the geNorm, NormFinder, BestKeeper, and RankAggreg algorithms. As a result, RPL5 (brain, caudal fin), EF1A (gonad), and PICALM (three tissue types) genes were evaluated as the most stable genes in silvertip tetra females. In males, TUBB (brain, caudal fin) and ITGB2 (gonads, three tissue types) genes were the most stable, and in both sexes, TUBB (brain), ITGB2 (caudal fin), RPL5 (gonads), and PICALM (three tissue types) genes are considered appropriate as reference genes for qRT-PCR analysis. However, the GAPDH gene was judged to be inappropriate for use as a reference gene because gene stability in the brain, caudal fin, and gonads was evaluated to be low in all males and females. As an introductory study on silvertip tetra, a new research model fish, the results of this study are expected to provide helpful information regarding sex differentiation and determination in fish., (© 2024 The Authors.)

The study aimed to investigate antioxidant activities of two different thermally treated sesame ( Sesamum indicum L.) leaf ethanol extract, steamed sesame leaf extract (SSLE) and roasted sesame leaf extract (RSLE), and their inhibitory effects on uncontrolled growth and increased metastatic properties in human colon cancer cell lines. Both SSLE and RSLE contained pedaliin as the major polyphenol and its aglycon, pedalitin, as a minor component and exhibited radical scavenging activities and ferric reducing antioxidant power. SSLE and RSLE decreased growth of HT29 and HCT116 colon cancer cells, which was attributed to the induction of apoptosis and cell cycle arrest at either G2/M (by SSLE in HCT116) or S phase (by RSLE in HCT116). Furthermore, SSLE and RSLE inhibited migration and adhesion in both cell lines. These results indicate that thermally treated sesame leaves retained pedaliin content and exhibited antioxidant activities and inhibitory activities against the growth and metastatic properties of colon cancer cells., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interests., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Hovenia dulcis Thunb. fruit (HDF) is traditionally used for treating liver diseases and alcohol poisoning. The purpose of this study was to explore the effects of HDF on hyperproliferation, levels of inflammatory cytokines, and signaling mechanisms in human psoriatic keratinocyte HaCaT cells. HDF showed a preventive effect on tumor necrosis factor- α (TNF- α )-induced abnormal proliferation of psoriatic keratinocytes. Furthermore, real-time reverse transcription-PCR analysis showed that HDF suppressed the expressions of inflammatory cytokines; interleukin (IL)-1 α and IL-1 β and chemokines; CCL-20 and CXCL-8 in TNF- α -induced HaCaT cells. Western blotting revealed that HDF suppressed the levels of phosphorylated I κ B and STAT3 together with a decline in the levels of phosphorylated mitogen-activated protein kinases (MAPKs). These outcomes indicate that HDF prevents the abnormal proliferation of keratinocytes and modulates inflammatory responses by suppressing nuclear factor- κ B (NF- κ B) and STAT3 activation through downregulation of the MAPK signaling pathway in TNF- α -induced psoriatic keratinocytes. Our study demonstrates that HDF is prospective and beneficial for psoriatic skin inflammation.

The fundic gland type (GA-FG) of gastric adenocarcinoma is a rare variant of gastric cancer recently included in the 5th edition of the World Health Organization's classification of digestive system tumors. Five patients with GA-FG underwent an endoscopic resection at our institution. None of the patients had a Helicobacter pylori infection. Four lesions were located in the upper third of the stomach, and one was in the lower third. Three lesions had a IIa shape, while two resembled a subepithelial tumor. An endoscopic submucosal dissection was performed in four patients and endoscopic mucosal resection in one. Tumor cells were composed of well-differentiated columnar cells mimicking fundic gland cells, and the median tumor size was 10 mm. Three lesions exhibited submucosal invasion. No lymphatic or venous invasion was observed. Tumor cells were positive for MUC6 in all five cases; one case was focally positive for MUC5AC. No recurrence was observed during a median follow-up period of 13 months. An endoscopic resection can be a safe treatment modality for GA-FG, considering its small size and low risk of recurrence or metastasis.

Biological invasions are known to cause local extinctions on islands. Dok-do, a small, remote volcanic island in the East Sea of Korea in the western Pacific, has recently been invaded by rats, posing ecological problems. To infer their origin and invasion pathway, we collected rats from Dok-do and from the potential introduction source locations, Ulleung-do in the Pacific Ocean, and four east coastal ports. First, we identified that the brown rat ( Rattus norvegicus ) was the only rat species occurring at collecting sites based on the key morphological characteristics. To determine the population-level genetic diversity pattern, we applied the 3-RADseq approach. After a series of filtrations (minor allele frequency < 0.05, Hardy-Weinberg equilibrium p < 1 × 10 -7 ), 4042 SNPs were retained for the final dataset from the 25,439 SNPs initially isolated. The spatial structure and genetic diversity pattern of brown rats suggested that the rat population on Dok-do was likely introduced from Ulleung-do. Our work provides practical information that will assist in the management of invasive brown rats in vulnerable island ecosystems.

Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of A. princeps ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) ( 1 ), 4-epi-seco-tanapartholide A ( 2 ), 11,13-dehydrodesacetylmatricarin ( 3 ) and desacetylmatricarin ( 4 ). Compounds 1  -  3 dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1β and tumour necrosis factor-α) in LPS-stimulated RAW 264.7 macrophages. Moreover, compound 3 effectively enhanced the expression of heme oxygenase-1 (HO-1) in macrophages in the presence or absence of LPS. Additionally, the exocyclic methylene of α-methylene-γ-lactone moiety of compound 3 was found to be essential for the activation of the NF erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Here, we firstly report the isolation of compounds 3 and 4 from A. princeps and the anti-inflammatory activity of compound 3 by up-regulation of Nrf2/HO-1 pathway.

Transient receptor potential vanilloid 4 (TRPV4) is an osmosensory cation channel that respond to an increase in cell volume and participates in various physiological functions. Among organisms in aquatic environments, euryhaline teleost is are suitable experimental models to study ion channel proteins related to physiological functions involving osmosensing. Among the studies of various regulatory molecules that mediate osmotic regulation in fish, however, information is lacking, particularly on the TRP family. This study investigated the structural characteristics of theTRPV4 gene of chum salmon (Oncorhynchus keta) and their responses to changes in salinity and temperature. Interestingly, TRPV4 generates transcript variants of the intron-retention form through alternative splicing, resulting in a frameshift leading to the generation of transcripts of different structures. In particular, TRPV4 x1 and TRPV x2 mRNAs were predominant in the gill and skin including at the lateral line. The expression levels of chum salmon TRPV4 x1 were significantly increased with increase in salinity and temperature, whereas TRPV4 x2 mainly responded to temperature decrease. Overall, these results demonstrate for the first time the effects of salinity and temperature on the expression of two salmonid TRPV4 transcript variants, suggesting their contribution to the regulation of hydromineral balance., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sesame ( Sesamum indicum L.) leaves (SLs) are used as vegetables and traditional medicines in Asian and African countries. We investigated in vitro antioxidant and anti-colon cancer efficacy of ethanol extract of SL (SLE) and its major bioactive component. SLE contained appreciable amount of major classes of antioxidant phytochemicals, such as total polyphenols, total flavonoids, and carotenoids, and correspondingly exhibited antioxidant activities, such as radical scavenging activity and ferric reducing antioxidant power (FRAP). A cell viability assay showed that SLE time- and dose-dependently attenuated the growth of human colon cancer cells, HT29 and HCT116. Flow cytometry analysis showed that SLE increased sub-G1 (in HT29 and HCT116) and G2/M (in HCT116) cell populations, suggesting that the growth inhibition by SLE was due to induction of apoptosis and G2/M cell cycle arrest. Trans-well and wound-healing assays showed that SLE alleviated invasion and migration of HT29 and HCT116 cells in non-cytotoxic conditions. High-performance liquid chromatography analysis revealed that pedaliin (6-hydroxylueolin 7-methyl ether 6-glucoside; pedalitin-6- O -glucoside) was a major constituent of SLE. Moreover, FRAP, growth-inhibitory, anti-invasive, and anti-migratory activities of pedaliin were found. These results demonstrated that SLE possesses in vitro antioxidant and anti-colon cancer activities and that pedaliin is a major component contributing to such activities.

We developed two distinct forest therapy programs (FTPs) and compared their effects on dementia prevention and related health problems for older adults. One was focused on Qigong practice in the forest (QP) and the other involved active walking in the forest (WP). Both FTPs consisted of twelve 2-h sessions over six weeks and were conducted in an urban forest. We obtained data from 25, 18, and 26 participants aged 65 years or above for the QP, WP, and control groups, respectively. Neuropsychological scores via cognition (MoCA), geriatric depression (GDS) and quality of life (EQ-5D), and electrophysiological variables (electroencephalography, bioimpedance, and heart rate variability) were measured. We analyzed the intervention effects with a generalized linear model. Compared to the control group, the WP group showed benefits in terms of neurocognition (increases in the MoCA score, and alpha and beta band power values in the electroencephalogram), sympathetic nervous activity, and bioimpedance in the lower body. On the other hand, the QP group showed alleviated depression and an increased bioimpedance phase angle in the upper body. In conclusion, both active walking and Qigong in the forest were shown to have distinctive neuropsychological and electrophysiological benefits, and both had beneficial effects in terms of preventing dementia and relieving related health problems for elderly individuals.

Ionizing radiation induces biological/physiological changes and affects commensal microbes, but few studies have examined the relationship between the physiological changes induced by irradiation and commensal microbes. This study investigated the role of commensal microbes in the γ-ray irradiation-induced physiological changes in Drosophila melanogaster . The bacterial load was increased in 5 Gy irradiated flies, but irradiation decreased the number of operational taxonomic units. The mean lifespan of conventional flies showed no significant change by irradiation, whereas that of axenic flies was negatively correlated with the radiation dose. γ-Ray irradiation did not change the average number of eggs in both conventional and axenic flies. Locomotion of conventional flies was decreased after 5 Gy radiation exposure, whereas no significant change in locomotion activity was detected in axenic flies after irradiation. γ-Ray irradiation increased the generation of reactive oxygen species in both conventional and axenic flies, but the increase was higher in axenic flies. Similarly, the amounts of mitochondria were increased in irradiated axenic flies but not in conventional flies. These results suggest that axenic flies are more sensitive in their mitochondrial responses to radiation than conventional flies, and increased sensitivity leads to a reduced lifespan and other physiological changes in axenic flies.

Herein, the effects of various alcohols on lecithin/CaCl 2 organogels are investigated. Mixtures of lecithin and CaCl 2 form reverse cylindrical micelles, resulting in optically transparent organogels. The addition of various alcohols to a mixture of lecithin and CaCl 2 induces a decrease in viscosity through which reverse cylindrical micelles are transformed into spherical micelles (or short cylindrical micelles). Long-hydrocarbon-chain alcohols decrease the viscosity of lecithin/CaCl 2 mixtures more efficiently. Hydrogen bonding and hydrocarbon chain interactions between lecithin and alcohol play important roles in the morphological transition. More importantly, isothermal titration calorimetry was conducted to obtain thermodynamic variables such as the enthalpy, equilibrium constant, Gibbs free energy, entropy, and stoichiometry of the associated molecules observed in the transition. It was found that the transition is an entropically driven process, in which the endothermic and exothermic behaviors were observed depending on the hydrocarbon chain length in the alcohol. In addition, the enthalpy for the association of the alcohol with lecithin showed a linear relationship depending on the hydrocarbon chain length, in which the magnitude of hydrogen bonding and hydrocarbon chain interactions was obtained quantitatively. To the best of our knowledge, this is the first study reporting the thermodynamic properties of the morphological transition observed in a reverse self-assembly process.

Polymer composite membranes containing aniline were prepared for CO 2 /N 2 separation. Aniline was selected for high separation performance as an additive containing both the benzene ring to interfere with gas transport and an amino group that could induce the accelerated transport of CO 2 molecules. As a result, when aniline having both a benzene ring and an amino group was incorporated into polymer membranes, the selectivity was largely enhanced by the role of both gas barriers and CO 2 carriers. Selective layers coated on the polysulfone were identified by scanning electron microscopy (SEM) images and the interaction with aniline in the polymer matrix was confirmed by FT-IR spectroscopy. The binding energy of oxygen in the polymer matrix was investigated by XPS, and the thermal stability of the composite membrane was confirmed by TGA.

Background: In cervical open-door laminoplasty for cervical myelopathy, a high-speed rotatory drill and rongeurs are used to make unicortical troughs and bicortical openings in the laminae. The lamina is reflected at the trough to enlarge the spinal canal, followed by bone healing on the hinge side to stabilize laminoplasty. The ultrasonic bone scalpel (UBS) has been used due to theoretical advantages including a better hinge union rate, less soft tissue trauma, less neurological injury, and shorter operative time., Objective: To assess the superiority of UBS for hinge union compared to the drill through randomized controlled trial., Methods: In 190 randomly allocated cervical myelopathy patients, the trough and opening at the lamina were made using either the drill (n = 95) or UBS (n = 95) during 2015 to 2018. The primary outcome was the hinge union rate on 6-mo postoperative computed tomography. Secondary outcomes included the hinge union rate at 12 mo, the operative time, intraoperative/postoperative bleeding, neurological injury, complications, and clinical outcomes over a 24-mo follow-up., Results: Hinge union in all laminae was achieved in 60.0% (drill) and 43.9% (UBS) of patients at 6 mo (intention-to-treat analysis; P = .02; odds ratio, 2.1) and in 91.9% (drill) and 86.5% (UBS) at 12 mo. Dural injury only occurred in the drill group (2.1%), and the UBS group showed significantly less intraoperative bleeding (P < .01). The other secondary outcomes did not differ between groups., Conclusion: The hinge union rate was inferior in the UBS group at 6 mo postoperatively, but UBS was efficacious in reducing dural injuries and bleeding., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Salmonid fishes, chum salmon (Oncorhynchus keta) have the developed adaptive strategy to withstand wide salinity changes from the early life stage. This study investigated gene expression patterns of cell membrane proteins in the gill of chum salmon fry on the transcriptome level by tracking the salinity acclimation of the fish in changing environments ranging from freshwater (0 ppt) to brackish water (17.5 ppt) to seawater (35 ppt). Using GO analysis of DEGs, the known osmoregulatory genes and their functional groups such as ion transport, transmembrane transporter activity and metal ion binding were identified. The expression patterns of membrane protein genes, including pump-mediated protein (NKA, CFTR), carrier-mediated protein (NKCC, NHE3) and channel-mediated protein (AQP) were similar to those of other salmonid fishes in the smolt or adult stages. Based on the protein-protein interaction analysis between transmembrane proteins and other related genes, we identified osmotic-related genes expressed with salinity changes and analyzed their expression patterns. The findings of this study may facilitate the disentangling of the genetic basis of chum salmon and better able an understanding of the osmophysiology of the species.

Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed β-catenin response transcriptional activity, intracellular β-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. To clarify the regulatory mechanism of decreased β-catenin levels, we examined the effect of Z-ajoene on β-catenin phosphorylation, which is involved in β-catenin degradation. Z-Ajoene promoted the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner, which is an essential step in β-catenin degradation in the cytosol. These findings indicate that Z-ajoene from garlic may be a potential chemotherapeutic agent by modulating CK1α activity and the Wnt/β-catenin signaling pathway.

In this study, we determined the complete mitochondrial genome (mt genome) of Semisulcospira gottschei for the first time and then compared it with the mt genome of species belonging to Cerithioidea. The mt genome consists of 13 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and non-coding region with a total length of 16,101 bp. The type of constitutive genes and the direction of the coding strand which appeared in the mt genome were the same as the ones observed in Cerithioidea except for the tRNA-Q and tRNA-R positions. The S. gottschei mt genome had a non-coding region with an AT-rich loop between tRNA-F and tRNA-C regions. In regard to molecular phylogeny, two types of analysis were performed to confirm the introgressive hybridization of S. gottschei and to identify the phylogenetic location among the species in Caenogastropoda. As a result, S. gottschei used in this study belonged to the same clade as other non-introgressed S. gottschei. As for the molecular phylogenic analysis of species belonging to Caenogastropoda, S. gottschei was found to be the closest to S. coreana taxonomically and to be included in Cerithioidea., (Copyright © 2019. Published by Elsevier B.V.)

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala ; 1 , 2-[(2 E )-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2 , 1-acetoxy-tetradeca-6 E ,12 E -diene-8, 10-diyne-3-ol; 3 , 1,3-diacetoxy-tetradeca-6 E , 12 E -diene-8, 10-diyne. Compounds 1 - 3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1 - 3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1 - 3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1 , could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1 - 3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases.

We aimed to evaluate whether the longitudinal interaction between APOA5-1131C variants and overweight could accelerate age-related increases in arterial stiffness and circulating triglycerides in healthy subjects. This 3-year prospective cohort study included 503 healthy subjects. Brachial-ankle pulse wave velocity (baPWV), triglycerides, APOA5 -1131T > C, apolipoprotein (apo) A-V level, and low-density lipoprotein (LDL) particle size were measured at baseline and within a mean follow-up period of 3 years. At the 3-year follow-up, in the overweight group, subjects with the C allele showed increases in triglycerides and baPWV relative to baseline. Additionally, in the overweight group, there was a genotype effect on changes in triglycerides: subjects with the C allele had greater increases in triglyceride concentrations than subjects with the TT genotype. Furthermore, overweight subjects with the C allele had greater increases in triglyceride concentrations than normal-weight subjects with the C allele (P-interaction = 0.013). Overweight subjects with the C allele had greater increases in baPWV than normal-weight subjects with the C allele (P-interaction = 0.047). Changes in baPWV were affected by age, baseline baPWV, and changes in systolic blood pressure (BP) and triglycerides. Changes in triglycerides were affected by APOA5 -1131T > C genotype, age, baseline triglyceride level, and changes in BMI and apo A-V. In the overweight group, changes in baPWV were affected by changes in systolic BP, LDL particle size, and triglycerides. This prospective study shows that the interactive effect between APOA5 -1131C variants and overweight can accelerate age-related increase in arterial stiffness via the regulation of circulating triglycerides in healthy subjects.

Objectives: Individuals delivered from preeclamptic pregnancies exhibit a long-term increased risk of developing cardiovascular and metabolic diseases, likely caused by aberrant fetal cell reprogramming incurred in utero. The present study investigated the functional impairment and epigenetic changes exhibited by endothelial progenitor cells derived from offspring born to preeclamptic pregnancies., Study Design: The capacity of CD133 + /C-kit + /Lin - (CKL - ) human umbilical cord blood endothelial progenitor cells (EPCs) derived from gestationally matched normal and preeclamptic (n = 10 each) pregnancies to differentiate to form outgrowth endothelial cells (OECs) was assessed by observing both their morphology, and the number and size of generated OECs colonies. Likewise, OECs angiogenic function was evaluated via migration, adhesion, and tube-formation assays. EPCs from preeclampsia were cultured in normal-, and preeclampsia-derived serum-conditioned media to assess the effects of environmental factors on EPC differentiation potency and OEC angiogenic function, and finally, EPCs H3K4, H3K9, and H3K27 trimethylation levels were assayed., Results: The preeclampsia-derived CKL - EPCs exhibited decreased H3K4 and H3K9 trimethylation levels, significantly delayed differentiation times, and a significant reduction in both their number of generated OECs colonies, and exhibited reduced OECs migration, adhesion, and tube formation activities compared to those achieved by the normal-derived EPCs. Interestingly, the reduced differentiation potency of the preeclampsia-derived EPCs was not rescued via exposure to normal serum., Conclusions: Exposure to preeclampsia significantly and irreversibly reduced CKL - EPC differentiation potency and OEC angiogenic function, likely reflecting incurred irreversible epigenetic changes., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Problem: The lymphatic vasculature controls leukocytes trafficking and limits the adaptive immune response. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophysiology. Especially, the dysfunction of regulatory T cells (Treg) at the maternal-fetal interface may be one of the causes of severe PE. In particular, activation of Tregs to obtain immune tolerance requires adequate antigen presentation through the lymphatic system. We hypothesized that impaired lymphangiogenesis and imbalanced Tregs at the maternal-fetal interface are associated with the pathophysiology of severe PE. However, the current research addressing this hypothesis is limited. Therefore, to compare differences in lymphangiogenesis in severe PE and normal conditions, we aimed to examine the location of lymphatics at the maternal-fetal interface and to investigate the association between lymphangiogenesis and Tregs in severe PE., Method of Study: We obtained entire uterus from normal pregnant mice. Placental and fetal membranes, including decidua, were obtained from 10 pregnant women with severe PE and 10 gestational age-matched controls. Immunohistochemistry for LYVE1 was used to localize the distribution of lymphatic vessels and CD4, CD25, and FOXP3 for Treg., Results: LYVE1-positive vessels were present in the uterine wall of mice. LYVE1-positive lymphatic vessels were localized on the human decidua. Tubular lymphatics were abundant in the control decidua, but significantly reduced in severe PE. Furthermore, lymphatic vessel density correlated with the number of decidual Tregs., Conclusion: Abnormal decidual lymphangiogenesis is associated with reduced numbers of decidual Tregs in severe PE., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Qigong, Tai-chi and dancing have all been proven effective for Parkinson's disease (PD); however, no study has yet assessed the efficacy of Turo, a hybrid qigong dancing program developed to relieve symptoms in PD patients., Objective: To determine whether Turo may provide benefit in addressing the symptoms of PD patients., Design: Randomized, assessor blind, waiting-list control, partial crossover study., Setting: Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea., Participants: A total of 32 PD patients (mean age 65.7 ± 6.8)., Intervention: Participants were assigned to the Turo group or the waiting-list control group. The Turo group participated in an 8-week Turo training program (60-minute sessions twice a week). The waiting-list control group received no additional treatment during the same period; then underwent the same 8-week Turo training., Outcome Measures: The primary outcome was a score on the Unified Parkinson's Disease Rating Scale (UPDRS), and the secondary outcomes included the perceived health status assessed using the Parkinson's disease Quality of Life questionnaire (PDQL), balance function as assessed by the Berg Balance Scale (BBS) and the results of the Beck Depression Inventory (BDI)., Results: The Turo group showed statistically significant improvements in the UPDRS (P < 0.01) and PDQL (P < 0.05) as compared to the control group. The changes in BBS scores displayed a tendency toward improvement, but was not statistically significant (P = 0.051)., Conclusion: These findings suggest that Turo PD training might improve the symptoms of PD patients., (Copyright © 2018. Published by Elsevier Inc.)

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols ( 1 - 7 ) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols ( 2 - 4 and 6 ) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC 50 values of less than 6 µM. The compounds 2 - 4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor κB (NF-κB) activity by inhibiting the degradation of inhibitory-κB-α (I-κB-α) and the translocation of NF-κB into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases., Competing Interests: The authors declare no conflict of interest.

To understand the dietary ecology of the leopard cat (Prionailurus bengalensis), DNA analysis was performed to identify prey species using DNA isolated from teeth harvested from the faeces of this feline species. From 70 DNA samples, a total of 52 mitochondrial DNA (mtDNA) cytochrome b (cytb) gene sequences of mammals were identified. The results of a sequence identity test indicated that those sequences were derived from four rodent species (Apodemus agrarius, Apodemus peninsulae, Eothenomys regulus and Tamias sibiricus) and two shrew species (Crocidura lasiura and Crocidura shantungensis). The sequences contained nine unique cytb sequences from site 1 and 13 from site 2. These results indicate that the leopard cat hunts rodents and shrews, and at least nine animals at site 1 and 13 animals at site 2 were eaten. These findings suggest that the animal molecular signatures that remain undigested in the faeces may provide useful ecological information about food items and may contribute to a better understanding of the leopard cat's feeding ecology.

Generalization of learned fear has been considered to be critical for our survival. Patients with anxiety problems show overgeneralization of learned fear, as reflected by defensive physiological responses to harmless stimuli. Together with these physiological responses, conscious feeling of fear is a seminal part of emotional process that is directly related to the suffering of anxiety patients. However, the effect of anxiety on the generalization of conscious feeling remains unclear. We thus focused on the question whether the generalization of conscious feeling of fear depends on individual anxiety level in nonpatient participants. To address this question, we developed a fear generalization paradigm using natural scene images. We found that subjective feeling of fear was generalized to similar stimuli with the conditioned stimuli (CS), and that this generalization of conscious fear was positively correlated with the level of individual anxiety. Anxiety and depression frequently co-occur, but the individual depression level was not correlated with the fear generalization. These suggest that individual anxiety level mainly affects the generalization of conscious fear.

The overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by microglia may cause neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone ( 1 ), bavachromene ( 2 ), and kanzonol B ( 3 ). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE₂ production in lipopolysaccharide (LPS)-activated microglia. Western blotting and RT-PCR analysis demonstrated that these prenylchalcones reduced the expression of protein and mRNA of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-activated microglia. Furthermore, three prenylated chalcones blocked the inhibitory-κBα (I-κBα) degradation and down-regulated nuclear factor κB (NF-κB) level of nucleus in LPS-stimulated BV-2 microglia. Therefore, these prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating iNOS and COX-2 expressions in activated microglial cells., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate soft- and hard-tissue changes in the mandibular angle area after the administration of botulinum toxin type A (BoNT-A) injection to patients with masseteric hypertrophy by using three-dimensional cone-beam computed tomography (3D-CBCT)., Methods: Twenty volunteers were randomly divided into two groups of 10 patients. Patients in group I received a single BoNT-A injection in both masseter muscles, while those in group II received two BoNT-A injections in each masseter muscle, with the second injection being administered 4 months after the first one. In both groups, 3D-CBCT was performed before the first injection and 6 months after the first injection., Results: Masseter muscle thicknesses and cross-sectional areas were significantly reduced in both groups, but the reductions were significantly more substantial in group II than in group I. The intergonial width of the mandibular angle area did not change significantly in either group. However, the bone volume of the mandibular gonial angle area was more significantly reduced in group II than in group I., Conclusions: The repeated administration of BoNT-A injections may induce bone volume changes in the mandibular angle area., Competing Interests: The authors report no commercial, proprietary, or financial interest in the products or companies described in this article.

Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

Motor imagery (MI) has attracted increased interest for motor rehabilitation as many studies have shown that MI shares the same neural networks as motor execution (ME). Nevertheless, MI in terms of facial movement has not been studied extensively; thus, in the present study, we investigated shared neural networks between facial motor imagery (FMI) and facial motor execution (FME). In addition, FMI somatotopy within-face was investigated between the forehead and the mouth. Functional MRI was used to examine 34 healthy individuals with ME and MI paradigms for the forehead and the mouth. The general linear model and a paired t-test were performed to define the facial area in the primary motor cortex (M1) and this area has been used to investigate somatotopy between the forehead and mouth FMI. FMI recruited similar brain motor areas as FME, but showed less neural activity in all activated regions. The facial areas in M1 were distinguishable from other body movements such as finger movement. Further investigation of this area showed that forehead and mouth imagery tended to lack a somatotopic representation for position on M1, and yet had distinct characteristics in terms of neural activity level. FMI showed different characteristics from general MI as the former exclusively activated facial processing areas. In addition, FME and FMI showed different characteristics in terms of BOLD signal level, while sharing the same neural areas. The results imply a potential usefulness of MI training for rehabilitation of facial motor disease considering that forehead and mouth somatotopy showed no clear position difference, and yet showed a significant BOLD signal intensity variation.

Pancreatic cancer is aggressive and therefore difficult to treat; however, continued efforts have been made with the aim of developing an effective therapy against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved in the proliferation and survival of pancreatic cancer cells. The transcription factor glioma-associated oncogene (Gli) is a key component of the Hh signaling pathway and the primary effector of pancreatic cancer development. Inhibiting Gli is a proven therapeutic strategy for this disease. The present study examined the regulation of Gli and the expression of its target genes to identify an inhibitor of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was isolated from Siegesbeckia glabrescens as an inhibitor of Gli-mediated transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone from S. glabrescens may therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer.

Oxidative stress promotes several diseases, including liver disease. We have isolated several stilbenoids from Rheum undulatum to investigate their hepatoprotective activities and mechanism. Stilbenoids from R. undulatum protects hepatocytes against arachidonic acid + iron (AA + Fe) induced oxidative stress. Pterostilbene (compound 5) shows stronger activity than the others. Trimethoxystilbenoid (compound 6) shows best activity on protection of HepG2 cells from AA + Fe-induced oxidative stress, and trans-stilbenoid (compound 7) shows weak activity. These stilbenoids suppress ROS generation in AA + Fe-treated HepG2 cells and also suppress AA + Fe-induced MMP disruption. Their protective effects on AA + Fe-induced MMP disruption were abrogated by treatment of AMP-activated protein kinase (AMPK) inhibitor, compound C or transfection of dominant negative form of AMPK. Taken together, stilbenoids from R. undulatum protect hepatocytes against AA + Fe-induced oxidative stress through AMPK activation. And the methoxy groups in the aryl groups are important for their cytoprotective activity., (Copyright © 2015 John Wiley & Sons, Ltd.)

Abnormal activation of β-catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β-catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti-colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β-catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of β-catenin in SW-480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW-480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti-colorectal cancer activities through inhibiting Wnt/β-catenin pathway., (Copyright © 2015 John Wiley & Sons, Ltd.)

Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF-7, AsPC-1, SW480, HCT 116, HepG2, HeLa). Compounds 1-4 showed differential cytotoxic effects on the target cancer cells with IC50 values in the range of 0.9-33.3 μM.

Wnt/β-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated β-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of β-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed β-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3β. AC down-regulated the nuclear level of β-catenin through the suppression of galectin-3 mediated nuclear translocation of β-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

We have isolated four sesquiterpenoids from Tussilago farfara, a traditional herbal medicine in Korea and China, and investigated the protective effects on LPS-induced neuronal cell death. Four sesquiterpenoids inhibited the production of nitric oxide, prostaglandin E2 and tumor necrosis factor-α in LPS-treated BV-2 cells through the inhibition of NF-κB pathway. These sesquiterpenoids also inhibited reactive oxygen species (ROS) generation in LPS-treated BV-2 cells. Furthermore, they inhibited LPS-induced neuronal cell death in co-culture system through the inhibition of NF-κB pathway and scavenging of ROS. These results indicated that sesquiterpenoids from Tussilago farfara may have beneficial therapeutic potential for the treatment of neurodegenerative diseases through inhibition of microglial activation.

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones (1-7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine (1), xanthoangelol E (2), xanthokeismin A (4), and xanthoangelol B (5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory-κBα (I-κBα) and the translocation of nuclear factor κB (NF-κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones (1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I-κBα and nuclear translocation of NF-κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents.

Abnormal activation of the Wnt/β-catenin signaling pathway frequently induces colon cancer progression. In the present study, we identified tussilagone (TSL), a compound isolated from the flower buds of Tussilago farfara, as an inhibitor on β-catenin dependent Wnt pathway. TSL suppressed β-catenin/T-cell factor transcriptional activity and down-regulated β-catenin level both in cytoplasm and nuclei of HEK293 reporter cells when they were stimulated by Wnt3a or activated by an inhibitor of glycogen synthase kinase-3β. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of β-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the β-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/β-catenin signaling pathway, and consequently inhibited the proliferation of colon cancer cells. Taken together, TSL might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Microglial activation has been associated with neurodegenerative diseases by inducing the neuroinflammatory mediators such as nitric oxide (NO), TNF-α and IL-1β. (-)-Nyasol, a norlignan isolated from a medicinal plant Anemarrhena asphodeloides, showed anti-inflammatory potential in lipopolysaccharide (LPS)-activated BV-2 microglial cells. (-)-Nyasol inhibited the production of NO and prostaglandin E2 (PGE2) and also the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are responsible for the respective production of NO and PGE2. It also suppressed the mRNA levels of TNF-α and IL-1β in activated microglial cells. These effects of (-)-nyasol were correlated with the inactivation of p38 MAPK and the suppression of LPS-induced I-κBα degradation. Taken together, these results suggest that (-)-nyasol can be a modulator in neuroinflammatory conditions induced by microglial activation.

A series of 2-aminodihydroquinoline analogs were synthesized and their in vitro cytotoxicities against metastatic breast adenocarcinoma cell line MDA-MB-231 were tested. Five out of 16 compounds exhibited promising activity and structure-activity relationship revealed major role of dialkylaminoethyl substituents on dihydroquinoline ring for the activity. Two compounds, 5f and 5h, presented cytotoxicity with IC50 values of about 2 μM when the compounds were treated to the cells without serum. The cell proliferation was inhibited mildly when the cells cultured with serum. Flow cytometry analyses showed that those compounds arrested the cells at G2/M checkpoint when the cell cycle is active while they induce apoptosis when the cell growth is restricted due to the absence of growth factors. These results suggest the two novel compounds may have anticancer activity through cell cycle arrest and pro apoptosis mechanism., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: ETHONOPHARMACOLOGICAL RELEVANCE: Thuja orientalis (L) ENDL (Cupressaceae) is an evergreen arbor that is distributed throughout Northeast Asia. This plant has been used as a traditional medicine for the treatment of various inflammatory diseases such as dermatitis, gout and chronic tracheitis., Aim of the Study: To isolate the active principles responsible for the anti-inflammatory activities of Thuja orientalis and to disclose their mechanism of action in lipopolysaccharide (LPS)-stimulated macrophages., Materials and Methods: The methanolic leaves and stem extracts of the Thuja orientalis were successively fractionated into EtOAc, n-BuOH and the remaining aqueous fractions. The EtOAc soluble fraction, which exhibited significant inhibitory activity on LPS-induced nitric oxide (NO) production, was followed by successive activity-guided chromatography to yield seven diterpenoids. The anti-inflammatory properties of active constituents were evaluated by RT-PCR, Western blotting and reporter gene assay in cell culture system., Results: A new labdane diterpene, 15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid (1), and six known diterpenoids (2-7) were isolated from the EtOAc extracts of Thuja orientalis. The isolated compounds 1-7 were evaluated for the inhibitory activity of LPS-induced NO production in RAW264.7 macrophage cells. Compound 1 was the most potent among the isolated compounds for the inhibition of LPS-induced NO production (IC501: 3.56μM). Compound 1 reduced the production of pro-inflammatory mediators and suppressed the expression of the inflammatory enzymes of iNOS and COX-2. In addition, compound 1 attenuated the LPS-induced transcriptional activity of NF-κB by the inhibition of inhibitory-κBα degradation, and suppressed the activity of extracellular signal regulated kinase (ERK)., Conclusions: This study demonstrates that a new labdane diterpene from Thuja orientalis inhibits the inflammatory responses by the suppression of NF-κB activity and ERK phosphorylation. This compound might be a valuable candidate for the development of anti-inflammatory drugs., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives. Strong aversions to acupuncture have been an obstacle to understanding its intrinsic action of acupuncture. Thus, it is necessary to evaluate the nature and extent of fear of acupuncture treatment. Our study aims to develop and validate an instrument that evaluates a patient's fear of acupuncture treatment. Methods. We have developed an acupuncture fear scale, a 16-item instrument which assesses the acupuncture fear score and uses it to survey 275 participants in South Korea, thus testing the reliability and validity of the instrument. Results. Internal consistency was high (Cronbach's alpha = 0.935). Test-retest reliability (Spearman's rank correlation coefficient) among 33 participants out of 275 ranged from 0.565 to 0.797 (P < 0.001). Principal component analysis revealed two factors accounting for 68% of the variance, which are painful sensation and possible adverse events, respectively. The acupuncture fear scale was positively correlated with the total of fear of pain questionnaire-III (r = 0.423, P < 0.001). Conclusions. The acupuncture fear scale can be a valid and reliable instrument that can measure fear of acupuncture treatment. These results strongly suggest that it would be a clinically useful tool to assess fear of acupuncture in the acupuncture clinic setting and an important instrument to understand the complex social-behavioral component of acupuncture modality.

We identified four anti-inflammatory sulfur-containing compounds from garlic, and their chemical structures were identified as Z- and E-ajoene and oxidized sulfonyl derivatives of ajoene. The sulfur compounds inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide (LPS)-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these sulfur compounds attenuated the LPS-induced expression of the inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA. Moreover, these sulfur-containing compounds suppressed the nuclear factor-κB (NF-κB) transcriptional activity and the degradation of inhibitory-κBα in LPS-activated macrophages. Furthermore, we observed that they markedly inhibited the LPS-induced phosphorylations of p38 mitogen-activated protein kinases and extracellular signal-regulated kinases (ERK) at 20 μM. These data demonstrate that the sulfur compounds from garlic, (Z, E)-ajoene and their sulfonyl analogs, can suppress the LPS-induced production of NO/PGE(2) and the expression of iNOS/COX-2 genes by inhibiting the NF-κB activation and the phosphorylations of p38 and ERK. Taken together, these data show that Z- and E-ajoene and their sulfonyl analogs from garlic might have anti-inflammatory therapeutic potential.

We demonstrated that ectopic expression of metabotropic glutamate receptor 1 (mGluR1/Grm1) in mouse melanocytes was sufficient to induce melanoma development in vivo with 100% penetrance. We also showed that about 60% of human melanoma biopsies and cell lines, but not benign nevi or normal human melanocytes expressed mGluR1, suggesting that GRM1 may be involved in melanomagenesis. mGluR1 is expressed primarily in neurons. In various non-neuronal cells, mGluR1 expression is regulated via binding of Neuron-Restrictive-Silencer-Factor (NRSF) to a Neuron-Restrictive-Silencer-Element (NRSE). Here, we report on the possibility that aberrant mGluR1 expression in melanoma is due to alterations in NRSF and/or NRSE. We show that in human melanocytes, binding of NRSF to NRSE in the GRM1 promoter region is necessary for the suppression of mGluR1 expression. We also show that inhibiting the expression of the transcription factor Sp1 or interference with its ability to bind DNA can result in increased mGluR1 expression perhaps via its function as a negative regulator. In addition, we also provide evidence that demethylation within the promoter region of GRM1 may also be a mechanism for the derepression of mGluR1 expression in melanocytes that progress to cell transformation and tumor formation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to compare the success rates of the manual and motor-driven mini-screw insertion methods according to age, gender, length of mini-screws, and insertion sites., Methods: We retrospectively reviewed 429 orthodontic mini-screw placements in 286 patients (102 in men and 327 in women) between 2005 and 2010 at private practice. Age, gender, mini-screw length, and insertion site were cross-tabulated against the insertion methods. The Cochran-Mantel-Haenszel test was performed to compare the success rates of the 2 insertion methods., Results: The motor-driven method was used for 228 mini-screws and the manual method for the remaining 201 mini-screws. The success rates were similar in both men and women irrespective of the insertion method used. With respect to mini-screw length, no difference in success rates was found between motor and hand drivers for the 6-mm-long mini-screws (68.1% and 69.5% with the engine driver and hand driver, respectively). However, the 8-mm-long mini-screws exhibited significantly higher success rates (90.4%, p < 0.01) than did the 6-mm-long mini-screws when placed with the engine driver. The overall success rate was also significantly higher in the maxilla (p < 0.05) when the engine driver was used. Success rates were similar among all age groups regardless of the insertion method used., Conclusions: Taken together, the motor-driven insertion method can be helpful to get a higher success rate of orthodontic mini-screw placement.

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (i-NOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of i-NOS, thus, may be useful candidates for the treatment of inflammatory diseases that accompany the overproduction of NO. Two phenolic glycosides, salicortin (1) and salicortin-6'-benzoate (2), were purified as active principles from the extracts of Populus davidiana by activity-guided purification procedures. They showed dose dependent inhibition of NO production in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The IC50 values of salicortin (1) and salicortin-6'-benzoate (2) was 15 microM and over 50 microM, respectively. In immunoblot analysis, salicortin inhibited the expression of i-NOS. These new inhibitors of overproduction of NO may have potentials for the treatment of inflammation.

Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compounds is also reported. Among these compounds, compound 12b was the most potent with 6.5 μM of IC(50). They inhibited NO production through the suppression of iNOS protein and mRNA expression and nuclear translocation of p65., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Tumor necrosis factor-alpha (TNF-α) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear., Objective: To explore the lipogenic effect by TNF-α and possible molecular mechanisms in sebocyte., Methods: Using SZ95 human sebocytes, lipid formation by TNF-α was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N-terminal kinase (JNK) and Akt in TNF-α-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors., Results: TNF-α treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-α-induced expression of FAS and SREBP-1. TNF-α could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA., Conclusions: TNF-α induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: Melanoma is a heterogeneous disease where monotherapies are likely to fail due to variations in genomic signatures. B-RAF inhibitors have been clinically inadequate but response might be augmented with combination therapies targeting multiple signaling pathways. We investigate the preclinical efficacy of combining the multikinase inhibitor sorafenib or the mutated B-RAF inhibitor PLX4720 with riluzole, an inhibitor of glutamate release that antagonizes metabotropic glutamate receptor 1 (GRM1) signaling in melanoma cells., Experimental Design: Melanoma cell lines that express GRM1 and either wild-type B-RAF or mutated B-RAF were treated with riluzole, sorafenib, PLX4720, or the combination of riluzole either with sorafenib or with PLX4720. Extracellular glutamate levels were determined by glutamate release assays. MTT assays and cell-cycle analysis show effects of the compounds on proliferation, viability, and cell-cycle profiles. Western immunoblotting and immunohistochemical staining showed apoptotic markers. Consequences on mitogen-activated protein kinase pathway were assessed by Western immunoblotting. Xenograft tumor models were used to determine the efficacy of the compounds in vivo., Results: The combination of riluzole with sorafenib exhibited enhanced antitumor activities in GRM1-expressing melanoma cells harboring either wild-type or mutated B-RAF. The combination of riluzole with PLX4720 showed lessened efficacy compared with the combination of riluzole and sorafenib in suppressing the growth of GRM1-expressing cells harboring the B-RAF(V600E) mutation., Conclusions: The combination of riluzole with sorafenib seems potent in suppressing tumor proliferation in vitro and in vivo in GRM1-expressing melanoma cells regardless of B-RAF genotype and may be a viable therapeutic clinical combination.

A new sesquiterpene lactone was isolated from Siegesbeckia glabrescens as an inhibitor of nitric oxide and prostaglandin E2 synthesis in the LPS-activated RAW264.7 macrophage cell line. It dose-dependently decreased the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Reporter gene assay revealed that the compound attenuated the LPS-induced DNA transcriptional activity of nuclear factor-kappa B (NF-κB). In addition, it inhibited the nuclear translocation of the p65 subunit of NF-κB by blocking the inhibitory kappa B-α degradation. This compound from Siegesbeckia glabrescens might be beneficial for the treatment of inflammation-related diseases., (Copyright © 2011 John Wiley & Sons, Ltd.)