A 21.6 kDa tegumental protein of Clonorchis sinensis induces a Th1/Th2 mixed immune response in mice.

INTRODUCTION: Clonorchis sinensis is a major parasite affecting the Korea population. Despite the high infection rate and pathogenicity, very few studies have been conducted to investigate the immune responses against the proteins of C. sinensis. METHODS: In this study, in vitro immune response induced by a recombinant 21.6 kDa tegumental protein derived from C. sinensis (rCsTegu21.6) was confirmed in murine dendritic cells and T cells. For the in vivo analysis, each mouse was immunized three times. Total serum IgG and T cell cytokine production were determined by ELISA, while T cell proliferation was detected by a WST (Water-Soluble Tetrazolium salt)-1 assay. RESULTS: In vitro tests indicated that rCsTegu21.6 treatment increased the expression of surface molecules, such as CD40 (77%), CD80 (52%) and CD86 (46%), on murine dendritic cells and the secretion of cytokines (TNF-α, IL-6, IL-1ß, IL-10, and IL-12p70). Moreover, co-culturing dendritic cells activated by rCsTegu21.6 with allogenic T cells induced T cell proliferation over time. rCsTegu21.6 also stimulated specific antibody production and cytokine secretion [IL-2, IL-4, and interferon (IFN)-γ)] from T cells following immunization in vivo. Notably, rCsTegu21.6 predominantly induced IgG1 production and secretion of the Th2 cytokine IL-4, regardless of the type of adjuvant used. CONCLUSION: These results serve as a foundation for the development of tegumental protein-based vaccines against C. sinensis.

The effect of cognitive behavior therapy-based "forest therapy" program on blood pressure, salivary cortisol level, and quality of life in elderly hypertensive patients.

OBJECTIVE: This article aimed to develop the "forest therapy" program, which is a cognitive behavior therapy (CBT)-based intervention program using forest environment, and investigate its effects on blood pressure (BP), salivary cortisol, and quality of life (QoL) measures in patients with hypertension. METHODS: A total of 56 men and women were enrolled for this study, being referred from local health centers in Republic of Korea, from April to October 2009. They were conveniently assigned to either "forest" group participating in the forest therapy program or control group doing self-monitoring of BP. Measurements of salivary cortisol level and QoL were done at initial visits and at 8-week final visits. RESULTS: Both groups did not differ significantly in baseline clinical characteristics. The BP change at week 4 and week 8 did not differ between the two groups. Salivary cortisol level reduction was significantly larger and QoL measures improved significantly more in the forest group at week 8 compared with the control group. CONCLUSIONS: The forest therapy program did not induce prolonged systolic blood pressure (SBP) reduction. However, considering the significant decrease in cortisol level and improvement in QoL measures, this may be a useful model of community hypertension management program.

Non-climacteric fruit ripening in pepper: increased transcription of EIL-like genes normally regulated by ethylene.

Only limited information has been published to date on the similarities and differences between climacteric and non-climacteric fruit ripening on transcriptional level. To address this issue, we performed a direct comparative transcriptome analysis between tomato and pepper fruits using heterologous microarray hybridization. Given the significant differences in the morphological, physiological, and biochemical characteristics of pepper and tomato fruits, the existence of extensive common regulons is surprising. This finding suggests the conservation of ripening mechanisms in climacteric and non-climacteric fruits. However, disparate expression profiles were also observed in both fruits. This study revealed that a gene that encodes an enzyme that converts lycopene to downstream carotenoids is induced in pepper but not in tomato. Most of the genes that encode ribosomal proteins are only induced in early fruit-stage pepper fruit and show rapidly diminishing expression in the later developmental stages. The genes involved in ethylene biosynthesis were not induced in pepper fruit. However, the EIL-like genes, ethylene-mediated signaling components, were induced in pepper fruit. Divergent types of transcription factors were expressed in ripening tomato and pepper fruits, suggesting they may be key factors that differentiate these distinct ripening processes.

The effect of cognitive behavior therapy-based psychotherapy applied in a forest environment on physiological changes and remission of major depressive disorder.

OBJECTIVE: Psychotherapeutic intervention combined with pharmacotherapy is helpful for achieving remission of depressive disorder. We developed and tested the effect of cognitive behavior therapy (CBT)-based psychotherapy applied in a forest environment on major depressive disorder. METHODS: We performed 4 sessions during 4 weeks (3 hours/session) in patients with major depressive disorder during pharmacotherapy. For the forest group, sessions were performed in the forest; for the hospital group, sessions were performed in the hospital. The control group was treated with the usual outpatient management. RESULTS: A total of 63 patients completed the study: 23 in the forest group, 19 in the hospital group, and 21 in the control group. Hamilton Rating Scales for Depression (HRSD) scores of the forest group were significantly decreased after 4 sessions compared with controls. Montgomery-Asberg Depression Rating Scales (MADRS) scores of the forest group were significantly decreased compared with both the hospital group and the controls. The remission rate (7 and below in HRSD) of the forest group was 61% (14/23), significantly higher than both the hospital group (21%, 4/19) and the controls (5%, 1/21). In heart rate variability (HRV) analysis, some measurements representing HRV and parasympathetic nerve tone were increased in the forest group after 4 sessions. The salivary cortisol levels of the forest group were significantly decreased. CONCLUSION: CBT-based psychotherapy applied in the forest environment was helpful in the achievement of depression remission, and its effect was superior to that of psychotherapy performed in the hospital and the usual outpatient management. A good environment such as a forest helps improve the effect of psychotherapeutic intervention because it includes various natural instruments and facilitators in the treatment of depression.

Curcumin is an inhibitor of p300 histone acetylatransferase.

Histone acetyltransferases (HATs), and p300/CBP in particular, have been implicated in cancer cell growth and survival, and as such, HATs represent novel, therapeutically relevant molecular targets for drug development. In this study, we demonstrate that the small molecule natural product curcumin, whose medicinal properties have long been recognized in India and Southeast Asia, is a selective HAT inhibitor. Furthermore the data indicate that alpha, beta unsaturated carbonyl groups in the curcumin side chain function as Michael reaction sites and that the Michael reaction acceptor functionality of curcumin is required for its HAT-inhibitory activity. In cells, curcumin promoted proteasome-dependent degradation of p300 and the closely related CBP protein without affecting the HATs PCAF or GCN5. In addition to inducing p300 degradation curcumin inhibited the acetyltransferase activity of purified p300 as assessed using either histone H3 or p53 as substrate. Radiolabeled curcumin formed a covalent association with p300, and tetrahydrocurcumin displayed no p300 inhibitory activity, consistent with a Michael reaction-dependent mechanism. Finally, curcumin was able to effectively block histone hyperacetylation in both PC3-M prostate cancer cells and peripheral blood lymphocytes induced by the histone deacetylase inhibitor MS-275. These data thus identify the medicinal natural product curcumin as a novel lead compound for development of possibly therapeutic, p300/CBP-specific HAT inhibitors.

EST and microarray analyses of pathogen-responsive genes in hot pepper (Capsicum annuum L.) non-host resistance against soybean pustule pathogen (Xanthomonas axonopodis pv. glycines).

Large-scale single-pass sequencing of cDNA libraries and microarray analysis have proven to be useful tools for discovering new genes and studying gene expression. As a first step in elucidating the defense mechanisms in hot pepper plants, a total of 8,525 expressed sequence tags (ESTs) were generated and analyzed in silico. The cDNA microarray analysis identified 613 hot pepper genes that were transcriptionally responsive to the non-host soybean pustule pathogen Xanthomonas axonopodis pv. glycines ( Xag). Several functional types of genes, including those involved in cell wall modification/biosynthesis, transport, signaling pathways and divergent defense reactions, were induced at the early stage of Xag infiltration. In contrast, genes encoding proteins that are involved in photosynthesis, carbohydrate metabolism and the synthesis of chloroplast biogenetic proteins were down-regulated at the late stage of Xag infiltration. These expression profiles share common features with the expression profiles elicited by other stresses, such as fungal challenge, wounding, cold, drought and high salinity. However, we also identified several novel transcription factors that may be specifically involved in the defense reaction of the hot pepper. We also found that the defense reaction of the hot pepper may involve the deactivation of gibberellin. Furthermore, many genes encoding proteins with unknown function were identified. Functional analysis of these genes may broaden our understanding of non-host resistance. This study is the first report of large-scale sequencing and non-host defense transcriptome analysis of the hot pepper plant species. (The sequence data in this paper have been submitted to the dbEST and GenBank database under the codes 10227604-10236595 and BM059564-BM068555, respectively. Additional information is available at http://plant.pdrc.re.kr/ks200201/pepper.html).

Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug.

PURPOSE: Butyrate is a small polar compound able to produce terminal differentiation and apoptosis in a variety of in vitro models at levels above 50-100 microM. Previously our group demonstrated that daily oral administration of the prodrug, tributyrin, is able to briefly achieve levels >100 microM. Given in vitro data that differentiating activity requires continuous butyrate exposure, the short t1/2 of the drug and a desire to mimic the effects of an intravenous infusion, we evaluated a three times daily schedule. PATIENTS AND METHODS: Enrolled in this study were 20 patients with advanced solid tumors for whom no other therapy was available, had life expectancy greater than 12 weeks, and normal organ function. They were treated with tributyrin at doses from 150 to 200 mg/kg three times daily. Blood was sampled for pharmacokinetic analysis prior to dosing and at 15 and 30 min and 1, 1.5, 2, 2.5, 3, 3.5 and 4 h thereafter. RESULTS: The patients entered comprised 15 men and 5 women with a median age of 61 years (range 30-74 years). Prior therapy regimens included: chemotherapy (median two prior regimens, range none to five), radiation therapy (one), no prior therapy (one). There was no dose-limiting toxicity. Escalation was halted at the 200 mg/kg three times daily level due to the number of capsules required. A median butyrate concentration of 52 microM was obtained but there was considerable interpatient variability. No objective responses were seen. There were four patients with prolonged disease stabilization ranging from 3 to 23 months; median progression-free survival was 55 days. Two patients with chemotherapy-refractory non-small-cell lung cancer had survived for >1 year at the time of this report without evidence of progression. CONCLUSION: Tributyrin is well tolerated and levels associated with in vitro activity are achieved with three times daily dosing.