Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Effects of brief mindfulness meditation training on attention and dispositional mindfulness in young adult males.

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.

Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder.

BACKGROUND: Abundant evidence suggests that inflammatory cytokines contribute to the symptoms of major depressive disorder (MDD) by altering neurotransmission, neuroplasticity, and neuroendocrine processes. Given the unsatisfactory response and remission of monoaminergic antidepressants, anti-inflammatory therapy is proposed as a feasible way to augment the antidepressant effect. Recently, there have been emerging studies investigating the efficiency and efficacy of anti-inflammatory agents in the treatment of MDD and depressive symptoms comorbid with somatic diseases. METHODS: In this narrative review, prospective clinical trials focusing on anti-inflammatory treatment for depression have been comprehensively searched and screened. Based on the included studies, we summarize the rationale for the anti-inflammatory therapy of depression and discuss the utilities and confusions regarding the anti-inflammatory strategy for MDD. RESULTS: This review included over 45 eligible trials. For ease of discussion, we have grouped them into six categories based on their mechanism of action, and added some other anti-inflammatory modalities, including Chinese herbal medicine and non-drug therapy. Pooled results suggest that anti-inflammatory therapy is effective in improving depressive symptoms, whether used as monotherapy or add-on therapy. However, there remain confusions in the application of anti-inflammatory therapy for MDD. CONCLUSION: Based on current clinical evidence, anti-inflammatory therapy is a promisingly effective treatment for depression. This study proposes a novel strategy for clinical diagnosis, disease classification, personalized treatment, and prognostic prediction of depression. Inflammatory biomarkers are recommended to be assessed at the first admission of MDD patients, and anti-inflammatory therapy are recommended to be included in the clinical practice guidelines for diagnosis and treatment. Those patients with high levels of baseline inflammation (e.g., CRP > 3 mg/L) may benefit from adjunctive anti-inflammatory therapy.

Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation.

BACKGROUND: Abundant evidence suggests that the prevalence and risk of depression in people with diabetes is high. However, the pathogenesis of diabetes-related depression remains unclear. Since neuroinflammation is associated with the pathophysiology of diabetic complications and depression, this study aims to elucidate the neuroimmune mechanism of diabetes-related depression. METHODS: Male C57BL/6 mice were injected with streptozotocin to establish a diabetes model. After screening, diabetic mice were treated with the NLRP3 inhibitor MCC950. Then, metabolic indicators and depression-like behaviors were evaluated in these mice, as well as their central and peripheral inflammation. To explore the mechanism of high glucose-induced microglial NLRP3 inflammasome activation, we performed in vitro studies focusing on its canonical upstream signal I (TLR4/MyD88/NF-κB) and signal II (ROS/PKR/P2X7R/TXNIP). RESULTS: Diabetic mice exhibited depression-like behaviors and activation of NLRP3 inflammasome in hippocampus. In vitro high-glucose (50 mM) environment primed microglial NLRP3 inflammasome by promoting NF-κB phosphorylation in a TLR4/MyD88-independent manner. Subsequently, high glucose activated the NLRP3 inflammasome via enhancing intracellular ROS accumulation, upregulating P2X7R, as well as promoting PKR phosphorylation and TXNIP expression, thereby facilitating the production and secretion of IL-1ß. Inhibition of NLRP3 with MCC950 significantly restored hyperglycemia-induced depression-like behavior and reversed the increase in IL-1ß levels in the hippocampus and serum. CONCLUSION: The activation of NLRP3 inflammasome, probably mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Association between Sleep and Suicidal Ideation in Chinese Undergraduate Students.

Suicide is an important global public health issue, which deserves more attention. This study aims to examine the relative independent relationship between suicide ideation and subjective sleep quality, sleep hygiene, and insomnia symptoms in undergraduate students in China. This population-based study included 2379 undergraduate students aged 18-26, randomly recruited from three public universities in Shanghai. The participants completed four questionnaires: the Pittsburgh Sleep Quality Index; Sleep Hygiene Practice Scale; Insomnia Severity Index; and the Symptom Checklist 90 (specifically the depression and anxiety dimensions and Q15-suicide ideation). The results of Spearman's correlation analysis indicate that poor sleep quality, short sleep duration, poor sleep hygiene, and insomnia symptoms were all associated with suicidal ideation in undergraduate students. However, according to the results of the hierarchical linear regression, no experience of sharing a bedroom at home, poor relationship with roommates, short sleep duration, sleep medicine use, and good daytime function were related to suicidal ideation, after controlling for the symptoms of depression and anxiety, which may be important in the identification of suicidal ideation. Sleep problems are highly discoverable and modifiable, and have a low sense of shame, therefore, sleep interventions for individuals with suicidal ideation and poor sleep quality may be an efficient and effective approach to suicide prevention.

Childhood Trauma and Suicide: The Mediating Effect of Stress and Sleep.

This study aimed to investigate the relationship between suicide risk, perceived stress, and sleep quality through a structural equation modeling approach. This study used convenience sampling to survey 780 undergraduate and graduate students aged 18-30 years. Students were invited to participate in the online questionnaires, which included the Beck Scale for Suicide Ideation, the Suicidal Behaviors Questionnaire-Revised, the Perceived Stress Scale, the Childhood Trauma Questionnaire-Short Form, and the Pittsburgh Sleep Quality Index. The results showed that suicide ideation and suicidal behavior were positively correlated with childhood trauma, stress, and sleep. A well-fitted structural equation model (χ2 = 1.52, df = 1, χ2/df = 1.52, RMSEA = 0.03, CFI = 1.00, NFI = 1.00) was constructed in this study. The hierarchical regression test showed significance in all the path coefficients of the model. The total effect of emotional abuse on suicide behaviors was 49.5%. The mediating effects accounted for 73.7% of the total effects of emotional abuse on suicidal behaviors. The results demonstrate efforts targeting stress and poor sleep might mitigate the risk of suicidal behaviors among individuals with early emotional abuse experiences.

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus.

Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microglia-related inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment.

Psychological responses of medical staff during COVID-19 and the adjustment effect of brief mindfulness meditation.

BACKGROUND: COVID-19 has posed an unprecedented threat to public health and remains a critical challenge for medical staff, especially those who have been fighting against the virus in Wuhan, China. Limited data have been reported regarding the psychological status of these medical staff members. Therefore, we conducted this study to explore the mental health status of medical staff and the efficacy of brief mindfulness meditation (BMM) in improving their mental health. METHODS: A survey was conducted between April 18 and May 3, 2020. Upon completing the pre-test, participants in the treatment group received a 15-min BMM intervention every day at 8 p.m. Post-test questionnaires were completed after 16 days of therapy. The questionnaire comprised demographic data and psychological measurement scales. The levels of pre and post-test depression, anxiety, stress, and insomnia were assessed using the 9-item Patient Health Questionnaire, 7-item Generalized Anxiety Disorder Scale, Perceived Stress Scale, and Athens Insomnia Scale, respectively. RESULTS: A total of 134 completed questionnaires were received. Of the medical staff, 6.7%, 1.5%, and 26.7% reported symptoms of depression, anxiety, and insomnia, respectively. Public officials from military hospitals reported experiencing greater pressure than private officials (t = 2.39, p = 0.018, d = 0.50). Additionally, BMM treatment appeared to effectively alleviate insomnia (t = 2.27, p = 0.027, d = 0.28). CONCLUSIONS: The medical staff suffered negative psychological effects during the COVID-19 pandemic. BMM interventions are advantageous in supporting the mental health of medical staff.

Biological Diagnosis of Depression: A Biomarker Panel from Several Nonspecial Indicators Instead of the Specific Biomarker(s).

It is a consensus that the diagnosis efficiency of depression is rather low in clinic. The traditional way of diagnosing depression by symptomatology is flawed. Recent years, a growing body of evidence has underlined the importance of physiological indicators in the diagnosis of depression. However, the diagnosis of depression is difficult to be like some common clinical diseases, which have clear physiological indicators. A single physiological index provides limited information to clinicians and is of little help in the diagnosis of depression. Thus, it is more rational and practical to diagnose depression with a biomarker panel, which covers a few non-specific indicators, such as hormones, cytokines, and neurotrophins. This open review suggested that biomarker panel had a bright future in creating a new model of depression diagnosis or at least providing a reference to the existing depression criteria. The viewpoint is also the future of other psychiatric diagnosis.

Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation.

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Life in the flame: Inflammation sounds the alarm for suicide risk.

As suicide became a critical issue in mental healthcare, the World Health Organization (WHO) presented a Mental Health Action Plan in 2013. Particularly, the plan set an explicit goal for suicide prevention, which called for 10% reduction in the suicide rate in member countries by 2020. Now the tough year of 2020 has passed by, many valuable breakthroughs on suicide research have emerged during these recent years. To some extent, a multi-stage system for the prediction and prevention of suicide is taking shape. Inflammatory biomarkers may have a promising future within this field.

A Large Sample Survey of Suicide Risk among University Students in China.

BACKGROUND: This study aimed to examine suicide ideation, suicide attempts, and suicide risk by examining a large sample of Chinese university students and identify the predictive factors, including depressive and anxiety symptoms, for suicide attempt and suicide risk. METHODS: We recruited 6,836 students (aged 18-30) based on all students enrolled in 2016 from one university using cluster sampling. They completed four questionnaires: the Beck Scale for Suicide Ideation and the Suicidal Behaviors Questionnaire-Revised were used to measure suicide risk, and students' depressive/anxiety symptoms were estimated using Patient Health Questionnaire and Generalized Anxiety Disorder Scale. RESULTS: Four major findings emerged. First, 18% of the students showed high suicide ideation, 14.5% showed suicide risk, 18.8% had suicide plans, and 1% had attempted suicide. Second, a weak sense of life's value was common among university students, as 61.4% of students considered suicide as a way to end or evade problems. Third, the results of the binary logistic regression showed that education, suicide ideation, including the wish to die, attitude toward suicide, specificity/planning of suicide, and deception or concealment of contemplated suicide were predictive factors of suicide attempt and suicide risk. The variable "deterrents to active attempt" was also a predictive factor of suicide risk. Fourth, depressive and anxiety symptoms did not significantly predict suicide attempts or suicide risk. Only 10.8% and 5.6% of the students had self-reported scores above the clinical cut-off points for depression and anxiety, respectively. CONCLUSIONS: This study highlighted the prevalence of suicide risk among Chinese university students. The high risk of suicide may not only be due to affective disorders, but also a weak sense of life's value or other reasons. Suicide ideation that significantly predicts suicide risk can be used for suicide risk assessment. Universities should provide appropriate life education and suicide prevention and intervention such as teaching instructors gate-keeper skills.

COVID-19 pandemic related long-term chronic stress on the prevalence of depression and anxiety in the general population.

BACKGROUND: The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it. METHODS: A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis. RESULTS: In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic. CONCLUSION: COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.

Chronic stress induces fur color change from dark to brown by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice.

Increasing evidence suggests that stress may induce changes in hair color, with the underlying mechanism incompletely understood. In this study, female C57BL/6 mice subjected to electric foot shock combined with restraint stress were used to build chronic stress mouse model. The melanin contents and tyrosinase activity were measured in mouse skin and B16F10 melanoma cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor α (TNF-α), interleukin- 1ß (IL-1ß) and interleukin-6 (IL-6) in the mouse skin. The content of nuclear factor κB (NFκB)/p65 subunit in mouse skins was valued by immunofluorescence staining. The results demonstrated that under chronic stress, the fur color turned from dark to brown in C57BL/6 mice due to the decrease of follicle melanocytes and tyrosinase activity in C57BL/6 mouse skin. Simultaneously, inflammatory responses in skins were detected as shown by increased NFκB activity and TNF-α expression in stressed mouse skin. In cultured B16F10 melanoma cells, TNF-α reduced the melanogenesis and tyrosinase activity in a dose-dependent manner. These findings indicate that chronic stress induces fur color change by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice, and TNF-α may play an important role in stress-induced hair color change.

Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial.

BACKGROUND: Recently, abundant evidence indicated proinflammatory cytokines might play a crucial role in pathophysiology and treatment of depression. According to our preclinical research, we propose glycyrrhizic acid (GZA) for an adjunctive treatment owing to its safety, economical and anti-inflammatory profile. METHODS: Eligible participants were recruited and randomly allocated into independent treatment groups of SSRI+GZA (n = 30) and SSRI+PBO (placebo, n = 26). Depressive symptoms and specific serum biomarkers were detected during the 4-week treatment course. Afterward, the relationships between biomarkers and clinical effects were explored. RESULTS: Depressive symptoms relieved more in SSRI+GZA than SSRI+PBO, both at week 2 (P = 0.003) and week 4 (P = 0.016). Meanwhile, at week 4, both response rate (P = 0.035) and remission rate (P = 0.031) acutely became higher in SSRI+GZA compared with SSRI+PBO. Mediation analysis further demonstrated that TNF-α reduction mediated the association between GZA treatment and clinical improvement, the indirect effect lay between 0.124 and 3.514 (95% CI). The exploratory analysis also suggested that the symptomatic improvement existed in patients with high-inflammation (baseline CRP > 3 mg/L) rather than those with low-inflammation (baseline CRP ≤ 3 mg/L). LIMITATIONS: The sample size in this study was not large enough and the follow-up duration was relatively short. CONCLUSIONS: This study offers a novel strategy for the diagnosis, categorization, individualization and prognosis regarding upgrading traditional antidepressant therapy, which is from biomarkers to diagnostic indicator and therapeutic target. Patients are necessary to be classified according to the inflammatory state, those with high levels of baseline inflammation should receive combined treatment with anti-inflammatory agents like GZA.

Brief Mindfulness Meditation Improves Emotion Processing.

Mindfulness-based interventions have previously been shown to have positive effects on psychological well-being. However, the time commitment, teacher shortage, and high cost of classic mindfulness interventions may have hindered efforts to spread the associated benefits to individuals in developing countries. Brief mindfulness meditation (BMM) has recently received attention as a way to disseminate the benefits of mindfulness-based interventions. Most existing BMM methods are adaptations of the classic approach. Few studies have investigated the mechanisms underlying the beneficial effects of BMM. We developed a 15-min BMM named JW2016, which is based on the core concepts of mindfulness, Anapanasati (breath meditation of Buddhist Vipassana), our practical experience, and the results of scientific reports on meditation. We investigated the effects of this BMM on mood and emotion processing in an effort to create an effective, convenient, safe, and standardized BMM method that could benefit individuals with limited time or money to devote to meditation. Forty-six healthy participants (aged 18-25 years) were randomly allocated to the BMM group (n = 23) or the emotional regulation education (ERE) control group (n = 23). Forty-two of the study participants cooperated fully in all measurements and interventions (one time daily for seven consecutive days). Mood was measured with the Centre for Epidemiological Studies-Depression scale (CES-D) and the State Anxiety Inventory (SAI). Emotion processing was evaluated by assessing performance on an emotion intensity task, an emotional memory task, and an emotional dot-probe task. After intervention, the BMM group, but not the ERE group, showed a significant decreases in emotional intensity in response to positive as well as negative emotional stimuli, response time for emotional memory, and duration of attention bias toward negative emotional stimuli. Negative effects on mood state were found in the ERE group but not in the BMM group. This study demonstrated that BMM may improve aspects of emotion processing such as emotion intensity, emotional memory, and emotional attention bias. JW2016 BMM may be an effective, convenient, safe and standardized way to help practitioners remain focused and peaceful without any negative effect on emotion.

FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice.

Forkhead box O1 (FoxO1) is involved in lipid metabolisms. However, its role in chronic stress-related nonalcoholic fatty liver disease (NAFLD) is unclear. The scientific premise of our study was based on the finding that FoxO1 expression is increased in the liver of mice after chronic stress. It is important to understand the mechanisms involved in the activation of FoxO1 and how its function affects the liver lipid deposition. We employed a murine chronic stress model, in which mice were treated by plantar electrical stimulation and restraint for 6 weeks, and a cellular model, in which Hepa1-6 cells were treated with corticosterone. We also used a pharmacologic approach as1842856, a highly specific FoxO1 inhibitor. Lipid metabolism related genes levels were measured by qRT-PCR and the lipid levels by biochemical detection. We show that the level of FoxO1 is significantly elevated in the liver of chronic stress mice. Transcription factor FoxO1 regulates a lipid synthesis phenotype of hepatocyte that is involved in the development and progression of NAFLD. We have shown that inhibition of FoxO1 induced phenotypic conversion of hepatocytes and down-regulates lipid synthesis genes expression by hepatocytes, which contribute to lipid deposition in NAFLD. At the cellular level, the inhibitor of FoxO1 as1842856 can also attenuate the lipid deposition of Hepa1-6 cells induced by corticosterone. Targeting FoxO1 is a novel therapeutic target for chronic stress-related NAFLD.