Effects of Psychosocial Interventions for Patients with Breast Cancer: A Meta-analysis.

Objective: This study involved a meta-analysis of South Korean studies regarding psychosocial interventions for patients with breast cancer to provide basic data to support the development of an integrated healthcare service model. Methods: Randomized controlled studies with a pretest-posttest design were selected, and those presenting means, standard deviations, and standardized mean differences were included. For quality evaluation and heterogeneity testing, the Jadad scale and the Q-value and I2 were used. To estimate the effect size of each study, Hedge's g was used. Publication bias was analyzed with the Funnel plot and Egger's regression test. Results: Of the 28 studies selected for the, meta-analysis was performed on eight. The total number of datasets included in the meta-analysis was 33. The evaluation based on the Jadad scale revealed no significant inter-rater variation (p = 0.35). The mean number of sessions was 7.93 and the mean intervention time was 13.2 hours. The interventions were mostly administered in a group structure (94%) and, regarding the type, they were categorized as integrated (36.4%), cognitive (30.3%), and meditation (24.2%). The mean effect size was 1.21 against no treatment group. Conclusion: The analyzed studies showed heterogeneity, with a corresponding asymmetry found on the Funnel plot. Despite the heterogeneity and publication bias, the mean effect size was significantly large. Cognitive interventions, meditation, and psychological education programs are expected to assist in reducing negative emotions and enhancing quality of life in patients with breast cancer.

Emetine exerts anticancer effects in U2OS human osteosarcoma cells via activation of p38 and inhibition of ERK, JNK, and ß-catenin signaling pathways.

Osteosarcoma (OS) is a primary bone neoplasm that is highly malignant. As advances in chemotherapy for the treatment of OS have stagnated, discovery of new reagents is required. Emetine is a phytochemical which can be isolated from a medicinal herb Cephaelis ipecacuanha and is traditionally used for amoebicides. Previous studies have demonstrated that emetine can possibly be repositioned for use in anticancer reagents. However, any anticancer effects and underlying mechanisms of emetine on human OS are not yet well understood. In this study, we analyzed the anticancer effects and involved cellular mechanisms after treatment with emetine to U2OS human OS cells. Emetine significantly reduced both the viability and proliferation, and induced apoptosis via activation of caspase-3 and caspase-7 in U2OS cells. Emetine effectively inhibited the migration and invasion of U2OS cells. Gelatinase activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were reduced by emetine. MMP-9 was transcriptionally inhibited, while MMP-2 was posttranscriptionally repressed, via the reduced expression of membrane-type I-matrix metalloproteinase (MT1-MMP). p38, which is closely related with induction of apoptosis, was stimulated by emetine. Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and ß-catenin, which are linked with expression of MMPs, were downregulated. Emetine exerted anticancer effects on MG63 human OS cells as well. Taken together, our study demonstrated the anticancer and antimetastatic potential of emetine in treating human OS for the first time. It is expected that emetine may be a promising drug candidate to be repositioned for chemotherapy of OS.

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid.

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.

Ginsenoside Rg1 Drives Stimulations of Timosaponin AIII-Induced Anticancer Effects in Human Osteosarcoma Cells.

A ginsenoside Rg1 is an active compound extracted from the stem and/or root of ginseng. Rg1 has been known to affect various human organ systems including the immune, cardiovascular, and nervous systems with its pharmacological effects. Timosaponin AIII (TA3) is a type of spirostanol saponins that are the major compounds of Anemarrhena asphodeloides. TA3 exerts anticancer effects in various human cancers, and the effects include attenuations of cancer cell migration and induction of apoptosis. In this study, I report that Rg1 drives the stimulation of TA3-induced cytotoxic effects in MG63 human osteosarcoma cells. Rg1 stimulates TA3-induced apoptosis in MG63 cells via selective intensification of caspase-3 activation. Rg1 and TA3 synergistically induced antimetastatic effects such as attenuation of MG63 cell migration and inhibitions of matrix metalloproteinases (MMP-2 and MMP-9). Rg1 and TA3 synergistically suppressed JNK, p38, ERK, ß-catenin, and CREB signaling, which are key regulators of cancer metastasis. Finally, the synergistic anticancer effects of Rg1 and TA3 were also observed in U2OS human osteosarcoma cells, and this may indicate that the synergy is not limited specifically to MG63 cells. The results presented here suggest that the combinatorial use of Rg1 and TA3 may be a promising way to develop an effective antiosteosarcoma agent.

Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway.

Ursonic acid is a pentacyclic triterpenoid compound that can be extracted from Ziziphus jujuba Mill., a traditional medicine. Matrix metalloproteinases (MMPs) are involved in cancer metastasis and skin aging. Regulation of various MMPs is closely associated with mitogen-activated protein kinases (MAPKs), including ERK, p38, and JNK MAPKs. In this study, we investigated the possibility of ursonic acid as an anti-cancer/anti-skin aging agent targeting MMPs. Cytotoxic effects of ursonic acid were analyzed by cell counting kit-8 (CCK-8) assay. Invasive abilities of ursonic acid-treated A549 and H1299 non-small cell lung cancer (NSCLC) cells were tested with Boyden chamber assay. Effects of ursonic acid on MMPs were analyzed by zymography assays and quantitative real time polymerase chain reaction (qRT-PCR). We also conducted flow cytometry and western blot analysis to elucidate the mechanisms of MMP regulation by ursonic acid. Our results revealed that ursonic acid inhibited transcriptional expression of gelatinases (MMP-2 and MMP-9) via inhibition of ERK and CREB signaling pathways in NSCLC cells. Moreover, ursonic acid reduced mRNA levels of collagenase (MMP-1) via suppression of ERK and c-Fos signaling pathways in HaCaT keratinocytes. These results suggest that ursonic acid could be a potential candidate for development of an effective novel anti-cancer and anti-wrinkle agent.

Maclurin exerts anti-cancer effects on PC3 human prostate cancer cells via activation of p38 and inhibitions of JNK, FAK, AKT, and c-Myc signaling pathways.

Maclurin is a phenolic compound extracted from purple mangosteen and mulberry twigs. Earlier reports indicated that it exerts antioxidant activity. We hypothesized that maclurin exerts antioxidant activity and anti-cancer effects in small cell neuroendocrine carcinomas (SCNCs), a very aggressive type of human prostate cancer. To verify our hypothesis, we selected PC3 cells as a model system and investigated the antioxidant activity and anti-cancer effects of maclurin. In the reactive oxygen species (ROS) detection assay for the verification of antioxidant activity, we observed the unexpected prooxidant activity of maclurin in PC3 cells. For the anti-cancer activities, we investigated the effects of maclurin on induction of apoptosis and inhibition of metastatic characteristics of PC3 cells. In the apoptosis assay, maclurin significantly induced apoptosis of PC3 cells. Maclurin also showed significant anti-metastatic effects. Maclurin inhibited cell migration in a dosage-dependent manner. In addition, the gelatin zymography assay indicated that maclurin inhibited activities of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) that affect cell migration and extracellular matrix (ECM) degradation. Then, we investigated the effects of maclurin on the cancer-related signaling molecules. Maclurin activated p38 signaling and inhibited c-Jun N-terminal kinase (JNK), focal-adhesion kinase (FAK), AKT, and c-Myc signalings in PC3 cells. Finally, we observed prooxidant activity and anti-SCNC effects of maclurin in DU145 cells. This suggests that the effects of maclurin may not be specifically limited to PC3 cells. Our findings suggest that maclurin exerts anti-cancer effects on SCNC cells via activation of p38 and inhibitions of JNK, FAK, AKT and c-Myc signalings.

Effects of Mindfulness-Based Art Therapy on Psychological Symptoms in Patients with Coronary Artery Disease.

BACKGROUND: Mindfulness-based art therapy (MBAT) induces emotional relaxation in coronary artery disease (CAD) patients, and is a treatment known to improve psychological stability. The objective of this study was to evaluate the treatment effects of MBAT for CAD patients. METHODS: A total of 44 CAD patients were selected as participants, 21 patients belonged to a MBAT group, and 23 patients belonged to the control group. The patients in the MBAT group were given 12 sessions of treatments. To measure depression and anxiety, Beck Depression Inventory (BDI) and Trait Anxiety Inventory (TAI) were used. Anger and anger expression were evaluated using the State Trait Anger Expression Inventory (STAXI). The treatment results were analyzed using two-way repeated measures analysis of variance (ANOVA). RESULTS: The results showed that significant effects for groups, time, and interaction in the depression (interaction effect, [F(1,36) = 23.15, P < 0.001]; between groups, [F(1,36) = 5.73, P = 0.022]), trait anxiety (interaction effect, [F(1,36) = 13.23, P < 0.001]; between groups, [F(1,36) = 4.38, P = 0.043]), state anger (interaction effect, [F(1,36) = 5.60, P = 0.023]), trait anger (interaction effect, [F(1,36) = 6.93, P = 0.012]; within group, [F(1,36) = 4.73, P = 0.036]), anger control (interaction effect, [F(1,36) = 8.41, P = 0.006]; within group, [F(1,36) = 9.41, P = 0.004]), anger out (interaction effect, [F(1,36) = 6.88, P = 0.012]; within group, [F(1,36) = 13.17, P < 0.001]; between groups, [F(1,36) = 5.62, P = 0.023]), and anger in (interaction effect, [F(1,36) = 32.66, P < 0.001]; within group, [F(1,36) = 25.90, P < 0.001]; between groups, [F(1,36) = 12.44, P < 0.001]). CONCLUSION: MBAT can be seen as an effective treatment method that improves CAD patients' psychological stability. Evaluation of treatment effects using program development and large-scale research for future clinical application is needed.

Synergistic Effects of Proprioceptive Neuromuscular Facilitation and Manual Lymphatic Drainage in Patients with Mastectomy-Related Lymphedema.

Purpose: Manual lymphatic drainage (MLD) and proprioceptive neuromuscular facilitation (PNF) are potential therapeutic strategies to reduce mastectomy-induced edema. The purpose of this study was to investigate whether the combination of these therapies would induce synergistic effects to treat lymphedema-related complications and to analyze a possible physiological mechanism involved in the observed effects. Methods: A total of 55 patients diagnosed with mastectomy-induced lymphedema were recruited and randomized into three experimental groups: PNF group (n = 17), MLD group (n = 20), and PNF + MLD group (n = 18). They were subjected to designated rehabilitation program three times a week for 16 weeks. ROM (flexion of the shoulder joint), edema size, arterial blood flow velocity, and degree of pain and depression were measured every 4 weeks over experimental period. Results: Lymphedema volume, VAS pain scale, and Beck depression scale were decreased in PNF and MLD groups for 16 weeks in a time-dependent manner. In combination, a greater reduction of these variables was observed over 16 weeks compared to each PNF and MLD. While axillary arterial blood circulation rate in the affected extremity was increased in both PNF and PNF + MLD groups over 16 weeks, this value was not increased in MLD group throughout the experimental period. A greater reduction of scales of VAS pain and Beck Depression Inventory (BDI) was observed in PNF + MLD group after the 16 week-treatment, as compared to each PNF and MLD group. Pearson's coefficients test demonstrated that there are significant correlation of depression against pain (r = 0.616, p < 0.01), ROM (r = -0.478, p < 0.01), and lymphedema size (r = 0.492, p < 0.01). Conclusion: The combination of MLD and PNF induces potent synergistic effects on edema volume, shoulder range of motion (ROM), pain, and depression in patients with lymphedema. In addition, an increased rate of axillary arterial blood flow in PNF-treated patients provide a potential physiological mechanism by which local arterial pulsation in the affected extremity plays a positive role in the treatment of lymphedema. Therefore, it is suggested to incorporate an element of PNF into traditional MLD method to facilitate treatment process for patients with lymphedema.

Melanocyte-protective effect of afzelin is mediated by the Nrf2-ARE signalling pathway via GSK-3ß inactivation.

Vitiligo is an acquired condition characterized by depigmented, cutaneous lesions that result from the death of pigment-producing cells, melanocytes. The occurrence of oxidative stress has been proposed as a pathogenetic mechanism for melanocyte degeneration in vitiligo. Therefore, in this study, we investigated the cytoprotective effects of afzelin against oxidative stress and its mechanism of action in human epidermal melanocytes. We found that afzelin significantly inhibited hydrogen peroxide-induced cell death, cellular reactive oxygen species production and lipid peroxidation in melanocytes. In an antioxidant response element (ARE)-luciferase reporter assay, afzelin increased ARE-luciferase reporter activity in a concentration-dependent manner. Consistently, the expression of antioxidant genes, including NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and catalase, was enhanced by afzelin treatment. Nuclear translocation of Nrf2 also increased in response to afzelin treatment. In addition, the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) was induced by afzelin treatment. The enhancement of HO-1 gene expression by afzelin treatment was reduced by Nrf2-siRNA expression. Furthermore, we found that the expression of Nrf2-siRNA significantly attenuated the cytoprotective effect of afzelin against hydrogen peroxide. These data suggest that the cytoprotective effects of afzelin against hydrogen peroxide may be mediated by Nrf2-ARE signalling via GSK-3ß inactivation. Our data suggest the novel use of afzelin for the prevention of oxidative stress-induced damage in melanocytes and its potential as a therapeutic agent for vitiligo.

Beneficial Effect of Mindfulness-Based Art Therapy in Patients with Breast Cancer-A Randomized Controlled Trial.

BACKGROUND: Mindfulness-based art therapy (MBAT) induces emotional relaxation in cancer patients and is a treatment known to improve psychological stability. The objective of this research was to evaluate the treatment effects of MBAT for breast cancer patients. METHODS: Overall, 24 breast cancer patients were selected as subjects of the study. Two groups, the MBAT group and control group with 12 patients each, were randomly assigned. The patients in the MBAT group were given 12 sessions of treatments. To measure depression and anxiety, low scales of the personality assessment inventory (PAI) was used. Health-related quality of life was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQLQ-C30). The treatment results were analyzed using analysis of covariance (ANCOVA) and two-way repeated measures analysis of variance (ANOVA). RESULTS: The results showed that depression and anxiety decreased significantly and health-related quality of life improved significantly in the MBAT group. In the control group, however, there was no significant change. CONCLUSIONS: MBAT can be seen as an effective treatment method that improves breast cancer patients׳ psychological stability and quality of life. Evaluation of treatment effects using program development and large-scale research for future clinical application is needed.

Effects of Hippotherapy on Psychosocial Aspects in Children With Cerebral Palsy and Their Caregivers: A Pilot Study.

OBJECTIVE: To investigate the effects of hippotherapy on psychosocial and emotional parameters in children with cerebral palsy (CP) and their caregivers. METHODS: Eight children with CP were recruited (three males and five females; mean age, 7.3 years; Gross Motor Function Classification System levels 1-3). Hippotherapy sessions were conducted for 30 minutes once weekly for 10 consecutive weeks in an indoor riding arena. The Gross Motor Function Measure (GMFM), Pediatric Balance Scale (PBS), and the Korean version of the Modified Barthel Index were evaluated. All children were evaluated by the Children's Depression Inventory, Trait Anxiety Inventory for Children, State Anxiety Inventory for Children, Rosenberg Self Esteem Scale, and the Korean-Satisfaction with Life Scale (K-SWLS). Their caregivers were evaluated with the Beck Depression Inventory, the Beck Anxiety Inventory, and the K-SWLS. We assessed children and their caregivers with the same parameters immediately after hippotherapy. RESULTS: Significant improvements on the GMFM, dimension E in the GMFM, and the PBS were observed after hippotherapy compared with the baseline assessment (p<0.05). However, no improvements were detected in the psychosocial or emotional parameters in children with CP or their caregivers. None of the participants showed any adverse effects or accidents during the 10 weeks hippotherapy program. CONCLUSIONS: Hippotherapy was safe and effectively improved gross motor and balance domains in children with CP. However, no improvements were observed in psychosocial or emotional parameters.

AtSRP1, SMALL RUBBER PARTICLE PROTEIN HOMOLOG, functions in pollen growth and development in Arabidopsis.

To identify novel roles of SMALL RUBBER PARTICLE PROTEIN Homolog in the non-rubber-producing plant Arabidopsis (AtSRP1), we isolated a T-DNA-insertion knock-out mutant (FLAG_543A05) and investigated its functional characteristics. AtSRP1 is predominantly expressed in reproductive organs and is localized to lipid droplets and ER. Compared to wild-type (WT) Arabidopsis, atsrp1 plants contain small siliques with a reduced number of heterogeneously shaped seeds. The size of anther and pollen grains in atsrp1 is highly irregular, with a lower grain number than WT. Therefore, AtSRP1 plays a novel role related to pollen growth and development in a non-rubber-producing plant.

AP-1-Targeting Anti-Inflammatory Activity of the Methanolic Extract of Persicaria chinensis.

In traditional Chinese medicine, Persicaria chinensis L. has been prescribed to cure numerous inflammatory disorders. We previously analyzed the bioactivity of the methanol extract of this plant (Pc-ME) against LPS-induced NO and PGE2 in RAW264.7 macrophages and found that it prevented HCl/EtOH-induced gastric ulcers in mice. The purpose of the current study was to explore the molecular mechanism by which Pc-ME inhibits activator protein- (AP-) 1 activation pathway and mediates its hepatoprotective activity. To investigate the putative therapeutic properties of Pc-ME against AP-1-mediated inflammation and hepatotoxicity, lipopolysaccharide- (LPS-) stimulated RAW264.7 and U937 cells, a monocyte-like human cell line, and an LPS/D-galactosamine- (D-GalN-) induced acute hepatitis mouse model were employed. The expression of LPS-induced proinflammatory cytokines including interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor-α (TNF-α) was significantly diminished by Pc-ME. Moreover, Pc-ME reduced AP-1 activation and mitogen-activated protein kinase (MAPK) phosphorylation in both LPS-stimulated RAW264.7 cells and differentiated U937 cells. Additionally, we highlighted the hepatoprotective and curative effects of Pc-ME pretreated orally in a mouse model of LPS/D-GalN-intoxicated acute liver injury by demonstrating the significant reduction in elevated serum AST and ALT levels and histological damage. Therefore, these results strongly suggest that Pc-ME could function as an antihepatitis remedy suppressing MAPK/AP-1-mediated inflammatory events.

Antiproliferative and Apoptosis-Inducing Activities of 4-Isopropyl-2,6-bis(1-phenylethyl)phenol Isolated from Butanol Fraction of Cordyceps bassiana.

The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom.

Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

Anti-inflammatory potential of peat moss extracts in lipopolysaccharide-stimulated RAW 264.7 macrophages.

The aim of the present study was to identify the anti-inflammatory and anti-oxidative effects of peat moss aqueous extract (PME) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. To demonstrate the anti-inflammatory and antioxidant effects of PME, the levels of nitric oxide (NO) and cytokines were measured using Griess reagent and cytokine ELISA kits, respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis were conducted to evaluate the expression of genes and proteins. Immunofluorescence was used to measure the expression and translocation of transcription factors. Pre-treatment with PME inhibited the production of prostaglandin E(2) and NO by suppressing the gene expression of cyclooxygenase-2 and inducible NO synthase, respectively. The LPS-stimulated gene expression and the production of tumor necrosis factor-α and interleukin-1ß were significantly reduced by PME. In the LPS-stimulated RAW 264.7 cells, nuclear factor­κB (NF-κB) translocated from the cytosol to the nucleus, while pre-treatment with PME induced the sequestration of NF-κB in the cytosol through the inhibition of IκBα degradation. In the same manner, PME contributed to the inhibition of the activation of mitogen-activated protein kinases. In addition, the PME-treated RAW 264.7 cells facilitated the activation of nuclear factor-like 2 (Nrf2) , and in turn, enhanced heme oxygenase-1 (HO-1) expression. These results indicate that PME exerts anti-inflammatory and antioxidant effects, and suggest that PME may neutralize inflammation and prevent cellular damage by oxidative stress.

Antibacterial effects of afzelin isolated from Cornus macrophylla on Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals.

The crude ethyl acetate extract of the leaves of Cornus macrophylla showed antibacterial activity against Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals. Bioactivity-guided separation led to the isolation of kaempferol 3-O-α-L-rhamnopyranoside (afzelin). The structure was determined based on evaluation of its spectroscopic (UV, MS, and NMR) data. The minimum inhibitory concentration (MIC) of afzelin against Pseudomonas aeruginosa was found to be 31 µg/mL. In addition, the results indicated that a hydroxyl group at C3 of the C-ring of the flavone skeleton and the rhamnose group may act as a negative factor and an enhancing factor, respectively, in the antibacterial activities of afzelin.

De-novo RNA sequencing and metabolite profiling to identify genes involved in anthocyanin biosynthesis in Korean black raspberry (Rubus coreanus Miquel).

The Korean black raspberry (Rubus coreanus Miquel, KB) on ripening is usually consumed as fresh fruit, whereas the unripe KB has been widely used as a source of traditional herbal medicine. Such a stage specific utilization of KB has been assumed due to the changing metabolite profile during fruit ripening process, but so far molecular and biochemical changes during its fruit maturation are poorly understood. To analyze biochemical changes during fruit ripening process at molecular level, firstly, we have sequenced, assembled, and annotated the transcriptome of KB fruits. Over 4.86 Gb of normalized cDNA prepared from fruits was sequenced using Illumina HiSeq™ 2000, and assembled into 43,723 unigenes. Secondly, we have reported that alterations in anthocyanins and proanthocyanidins are the major factors facilitating variations in these stages of fruits. In addition, up-regulation of F3'H1, DFR4 and LDOX1 resulted in the accumulation of cyanidin derivatives during the ripening process of KB, indicating the positive relationship between the expression of anthocyanin biosynthetic genes and the anthocyanin accumulation. Furthermore, the ability of RcMCHI2 (R. coreanus Miquel chalcone flavanone isomerase 2) gene to complement Arabidopsis transparent testa 5 mutant supported the feasibility of our transcriptome library to provide the gene resources for improving plant nutrition and pigmentation. Taken together, these datasets obtained from transcriptome library and metabolic profiling would be helpful to define the gene-metabolite relationships in this non-model plant.

MED18 interaction with distinct transcription factors regulates multiple plant functions.

Mediator is an evolutionarily conserved transcriptional regulatory complex. Mechanisms of Mediator function are poorly understood. Here we show that Arabidopsis MED18 is a multifunctional protein regulating plant immunity, flowering time and responses to hormones through interactions with distinct transcription factors. MED18 interacts with YIN YANG1 to suppress disease susceptibility genes glutaredoxins GRX480, GRXS13 and thioredoxin TRX-h5. Consequently, yy1 and med18 mutants exhibit deregulated expression of these genes and enhanced susceptibility to fungal infection. In addition, MED18 interacts with ABA INSENSITIVE 4 and SUPPRESSOR OF FRIGIDA4 to regulate abscisic acid responses and flowering time, respectively. MED18 associates with the promoter, coding and terminator regions of target genes suggesting its function in transcription initiation, elongation and termination. Notably, RNA polymerase II occupancy and histone H3 lysine tri-methylation of target genes are affected in the med18 mutant, reinforcing MED18 function in different mechanisms of transcriptional control. Overall, MED18 conveys distinct cues to engender transcription underpinning plant responses.

Overexpression of Arabidopsis YUCCA6 in potato results in high-auxin developmental phenotypes and enhanced resistance to water deficit.

Indole-3-acetic acid (IAA), a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. Step one converts tryptophan to indole-3-pyruvic acid (IPA) by tryptophan aminotransferases followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA proteins. We identified eight putative StYUC (Solanum tuberosum YUCCA) genes whose deduced amino acid sequences share 50%-70% identity with those of Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences: FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences. In addition, five genes were found with ~50% amino acid sequence identity to Arabidopsis tryptophan aminotransferases. Transgenic potato (Solanum tuberosum cv. Jowon) constitutively overexpressing Arabidopsis AtYUC6 displayed high-auxin phenotypes such as narrow downward-curled leaves, increased height, erect stature, and longevity. Transgenic potato plants overexpressing AtYUC6 showed enhanced drought tolerance based on reduced water loss. The phenotype was correlated with reduced levels of reactive oxygen species in leaves. The results suggest a functional YUCCA pathway of auxin biosynthesis in potato that may be exploited to alter plant responses to the environment.