Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways.

Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

Sleep hygiene education as a treatment of insomnia: a systematic review and meta-analysis.

Background: Sleep hygiene education (SHE) is commonly used as a treatment of insomnia in general practice. Whether SHE or cognitive-behavioural therapy for insomnia (CBT-I), a treatment with stronger evidence base, should be provided first remains unclear. Objective: To review the efficacy of SHE for poor sleep or insomnia. Methods: We systematically searched six key electronic databases up until May 2017. Two researchers independently selected relevant publications, extracted data and evaluated methodological quality according to the Cochrane criteria. Results: Twelve of 15 studies compared SHE with CBT-I, three with mindfulness-based therapy, but none with sham or no treatment. General knowledge about sleep, substance use, regular exercise and bedroom arrangement were commonly covered; sleep-wake regularity and avoidance of daytime naps in seven programs, but stress management in only five programs. Major findings include (i) there were significant pre- to post-treatment improvements following SHE, with small to medium effect size; (ii) SHE was significantly less efficacious than CBT-I, with difference in effect size ranging from medium to large; (iii) pre- to post-treatment improvement and SHE-CBT-I difference averaged at 5% and 8% in sleep-diary-derived sleep efficiency, respectively, and two points in Pittsburgh Sleep Quality Index; (iv) only subjective measures were significant and (v) no data on acceptability, adherence, understanding and cost-effectiveness. Conclusions: Although SHE is less effective than CBT-I, unanswered methodological and implementation issues prevent a firm conclusion to be made on whether SHE has a role in a stepped-care model for insomnia in primary care.

School-Based Sleep Education Programs for Short Sleep Duration in Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: Insufficient sleep among students is a major school health problem. School-based sleep education programs tailored to reach large number of students may be one of the solutions. A systematic review and meta-analysis was conducted to summarize the programs' effectiveness and current status. METHODS: Electronic databases were searched up until May 2015. Randomized controlled trials of school-based sleep intervention among 10- to 19-year-old students with outcome on total sleep duration were included. Methodological quality of the studies was assessed using the Cochrane's risk of bias assessment. RESULTS: Seven studies were included, involving 1876 students receiving sleep education programs and 2483 attending classes-as-usual. Four weekly 50-minute sleep education classes were most commonly provided. Methodological quality was only moderate, with a high or an uncertain risk of bias in several domains. Compared to classes-as-usual, sleep education programs produced significantly longer weekday and weekend total sleep time and better mood among students at immediate post-treatment, but the improvements were not maintained at follow-up. CONCLUSIONS: Limited by the small number of studies and methodological limitations, the preliminary data showed that school-based sleep education programs produced short-term benefits. Future studies should explore integrating sleep education with delayed school start time or other more effective approaches.

Sleep in schizophrenia: A systematic review and meta-analysis of polysomnographic findings in case-control studies.

Polysomnographic studies have been performed to examine the sleep abnormalities in schizophrenia, but the results are inconsistent. An updated systematic review, meta-analysis, and moderator analysis was conducted. Major databases were searched without language restriction from 1968 to January 2014. Data were analyzed using the random-effects model and summarized using the Hedges's g. Thirty-one studies with 574 patients and 515 healthy controls were evaluated. Limited by the number of studies and a lack of patient-level data, moderator analysis was restricted to medication status, duration of medication withdrawal, and illness duration. We showed that patients with schizophrenia have significantly shorter total sleep time, longer sleep onset latency, more wake time after sleep onset, lower sleep efficiency, and decreased stage 4 sleep, slow wave sleep, and duration and latency of rapid eye movement sleep compared to healthy controls. The findings on delta waves and sleep spindles were inconsistent. Moderator analysis could not find any abnormalities in sleep architecture in medication-naïve patients. Patients with antipsychotic withdrawal for longer than eight weeks were shown to have less sleep architectural abnormalities, compared to shorter duration of withdrawal, but the abnormalities in sleep continuity were similar. Slow wave sleep deficit was found in patients with schizophrenia for more than three years, while sleep onset latency was increased in medication-naïve, medication-withdrawn, and medicated patients. Our study showed that polysomnographic abnormalities are present in schizophrenia. Illness duration, medication status, and duration of medication withdrawal are several of the clinical factors that contribute to the heterogeneity between studies.

Correlates and prognostic relevance of sleep irregularity in inter-episode bipolar disorder.

OBJECTIVES: Sleep-wake disturbances, such as sleep irregularity, are common in bipolar disorder. Early studies suggest that sleep irregularity is associated with mood symptoms in bipolar disorder, but little research has been conducted to identify other correlates of sleep irregularity. We investigated the relationship between sleep irregularity and sleep quality, social rhythms, eveningness, sleep-related cognitions and behaviors, and past and future mood episodes in 84 patients with inter-episode bipolar I or II disorder. METHODS: This is a retrospective and prospective, naturalistic follow-up study. The Expanded Consensus Sleep Diary, Pittsburgh Sleep Quality Index (PSQI), Social Rhythm Metric (SRM-II-5), Composite Scale of Morningness (CSM), Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS-16), and Sleep Hygiene Practice Scale (SHPS) were administered. The Square Successive Difference (SSD), derived from a week-long sleep diary, was used as an index of sleep irregularity. Multilevel modeling analysis, which adjusts for biases in parameter estimates, was used to minimize the impact of missing data. Bonferroni correction was performed to account for multiple testing. RESULTS: Higher SSD scores of sleep diary variables were significantly associated with higher PSQI, SRM-II-5, DBAS-16, and SHPS scores. Irregularity in total sleep time was related to more depressive episodes in the past 5years (p=.002), while irregularity in wake after sleep onset predicted the onset of depressive episodes over the next 2years (p=.002). CONCLUSION: Sleep irregularity was associated with poor sleep quality, irregular social rhythms, dysfunctional sleep-related cognitions and behaviors, and greater number of depressive episodes in bipolar disorder.