Design, structure-activity relationships, and enzyme kinetic studies of tricyclic and tetracyclic coumarin-based sulfamates as steroid sulfatase inhibitors.

Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin-based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with KI of 0.05 and 0.4 nM, and kinact/KI ratios of 28.6 and 19.1 nM-1min-1 on human placenta STS, respectively.

Emotion regulation and emotional distress: The mediating role of hope on reappraisal and anxiety/depression in newly diagnosed cancer patients.

PURPOSE: A proportion of newly diagnosed cancer patients may experience anxiety and depression. Emotion suppression has been associated with poorer psychoemotional outcomes, whereas reappraisal may be an adaptive emotion regulation strategy. Few studies have examined potential mechanisms linking reappraisal to psychoemotional outcomes in cancer patients. This study aims to replicate findings on reappraisal and suppression and further examines if hope mediates the association between reappraisal and anxiety/depression in patients newly diagnosed with cancer. METHODS: Participants were 144 adult cancer patients (65.3% female, mean age = 48.96 years, SD = 9.23). Patients completed a set of study questionnaires, including the Emotion Regulation Questionnaire, Adult Hope Scale, and the Hospital Anxiety and Depression Scale. Path analysis was used to examine if hope mediated the association between reappraisal and anxiety/depression. RESULTS: Prevalence of anxiety was 39.6% and depression was 25.0%. Reappraisal and hope were correlated with lower anxiety and depression, whereas suppression was correlated with higher anxiety and depression. The hypothesized mediation model provided fit to the data, comparative fit index = 0.95, Tucker-Lewis index = 0.94, root-mean-square-error of approximation = 0.05. There was a significant indirect effect of reappraisal on anxiety and depression via hope, b = -0.95, SE = 0.42, 95% confidence interval = -1.77 to -0.12, whereas the direct effect of reappraisal was nonsignificant. CONCLUSION: The study findings suggest that hope mediated the association between reappraisal and anxiety/depression outcomes. Moreover, the high prevalence of anxiety and depression implies a need for healthcare providers to attend to the psychoemotional needs of newly diagnosed cancer patients.

Effects of horticultural therapy on elderly' health: protocol of a randomized controlled trial.

BACKGROUND: Due to a rapidly ageing population in the world, it is increasingly pertinent to promote successful ageing strategies which are cost-effective, easily accessible, and more likely to be acceptable to the elderly. Past research associates exposure to natural environments and horticultural therapy (HT) with positive psychological, social and physical health benefits. This Randomized Controlled Trial (RCT) is designed to evaluate the efficacy of HT in promoting Asian elderly' mental health, cognitive functioning and physical health. METHODS/DESIGN: 70 elderly participants aged 60 to 85 years old will be randomized to participate in either the active horticultural therapy group or be in the waitlist control. Sessions will be weekly for 12 weeks, and monthly for 3 months. Mental health will be assessed through self-reports of depressive and anxiety symptomatology, life satisfaction, social connectedness and psychological well-being, collaborated with immunological markers. Outcome measures of cognitive functioning and physical health include neuropsychological tests of cognitive function and basic health screening. Outcomes will be assessed at baseline, 3 months and 6 months post-intervention. DISCUSSION: This RCT comprehensively investigates the efficacy of a non-invasive intervention, HT, in enhancing mental health, cognitive functioning and physical health. The results have tremendous potential for supporting future successful ageing programs and applicability to larger populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT02495194 . Trial registration date: July 13, 2015. Retrospectively registered.

A nonpharmacological approach to improve sleep quality in older adults.

OBJECTIVES: Poor sleep quality is highly prevalent among older adults and is associated with poor quality of life, cognitive and physical decline, depression, and increased mortality. Medication options commonly used are not ideal, and alternative treatment strategies are needed. We evaluate a community-based psychosocial intervention program and its effect on sleep quality in older adults. METHOD: Elderly participants aged 60 and above were included. Those with Geriatric Depression Scale and Geriatric Anxiety Inventory scores above 5 and 10, respectively, were excluded. The community program included tai chi exercise, art therapy, mindfulness awareness practice, and music reminiscence therapy. Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Geriatric Anxiety Inventory were administered at baseline and at 1 year. RESULTS: A hundred and eighty-nine subjects (44 men, 145 women; mean age = 69 years, SD = 5.7, range = 60-89) participated. The proportion of participants with good sleep quality had increased from 58.2% to 64.6%. Sleep disturbance was significantly reduced (baseline, 1.04; postintervention, 0.76; mean difference 0.28; P < .01); men experienced greater improvement (P < .001). Improvements were independent of changes in depressive and anxiety symptoms. CONCLUSION: Participation in this community program led to positive effects on sleep disturbances after a year. Psychosocial interventions have potential as a nondrug intervention approach for sleep problems, and further research is needed to understand its mediating mechanisms.

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial.

The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1ß, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) (p = 0.003), CXCL5 (RANTES) (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group (p = 0.01). CONCLUSION: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.