Ligustilide inhibits Purkinje cell ferritinophagy via the ULK1/NCOA4 pathway to attenuate valproic acid-induced autistic features.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in which social impairment is the core symptom. Presently, there are no definitive medications to cure core symptoms of ASD, and most therapeutic strategies ameliorate ASD symptoms. Treatments with proven efficacy in autism are imminent. Ligustilide (LIG), an herbal monomer extracted from Angelica Sinensis and Chuanxiong, is mainly distributed in the cerebellum and widely used in treating neurological disorders. However, there are no studies on its effect on autistic-like phenotypes and its mechanism of action. PURPOSE: Investigate the efficacy and mechanism of LIG in treating ASD using two Valproic acid(VPA)-exposed and BTBR T + Itpr3tf/J (BTBR) mouse models of autism. METHODS: VPA-exposed mice and BTBR mice were given LIG for treatment, and its effect on autistic-like phenotype was detected by behavioral experiments, which included a three-chamber social test. Subsequently, RNA-Sequence(RNA-Seq) of the cerebellum was performed to observe the biological changes to search target pathways. The autophagy and ferroptosis pathways screened were verified by WB(Western Blot) assay, and the cerebellum was stained by immunofluorescence and examined by electron microscopy. To further explore the therapeutic mechanism, ULK1 agonist BL-918 was used to block the therapeutic effect of LIG to verify its target effect. RESULTS: Our work demonstrates that LIG administration from P12-P14 improved autism-related behaviors and motor dysfunction in VPA-exposed mice. Similarly, BTBR mice showed the same improvement. RNA-Seq data identified ULK1 as the target of LIG in regulating ferritinophagy in the cerebellum of VPA-exposed mice, as evidenced by activated autophagy, increased ferritin degradation, iron overload, and lipid peroxidation. We found that VPA exposure-induced ferritinophagy occurred in the Purkinje cells, with enhanced NCOA4 and Lc3B expressions. Notably, the therapeutic effect of LIG disappeared when ULK1 was activated. CONCLUSION: LIG treatment inhibits ferritinophagy in Purkinje cells via the ULK1/NCOA4-dependent pathway. Our study reveals for the first time that LIG treatment ameliorates autism symptoms in VPA-exposed mice by reducing aberrant Purkinje ferritinophagy. At the same time, our study complements the pathogenic mechanisms of autism and introduces new possibilities for its therapeutic options.

Examining the roles of experiential avoidance and cognitive fusion on the effects from mindfulness to athlete burnout: A longitudinal study.

OBJECTIVES: Athlete burnout is a maladaptive outcome that is potentially detrimental for performance and wellbeing. Cross-sectional evidence suggests that mindfulness might be associated with athlete burnout via experiential avoidance and cognitive fusion. In the current study, we extend knowledge of these hypothesized mediational pathways using a longitudinal design. METHODS: Data was collected at three occasions with a three-month interval. A final sample of 280 elite Chinese athletes aged 15-32 years (Mage = 19.13; SD = 2.92; Female = 130) reported their mindfulness at Time 1, experiential avoidance and cognitive fusion at Time 2, and athlete burnout at Time 3. Structural equation modelling was adopted to examine the mediating roles of experiential avoidance and cognitive fusion on the effects from mindfulness to athlete burnout. RESULTS: We found statistically meaningful directs effects from mindfulness (Time 1) to experiential avoidance and cognitive fusion (Time 2), which in turn influenced athlete burnout (Time 3). However, the direct effect from mindfulness at Time 1 to athlete burnout at Time 3 was non-significant. The indirect effects of experiential avoidance and cognitive fusion on the effects from mindfulness to athlete burnout were significant, providing longitudinal evidence that these two variables contribute meaningfully to the mindfulness-burnout pathway. CONCLUSION: With initial evidence for the mediating effects of experiential avoidance and cognitive fusion, future studies could consider using experimental designs to examine the potential changing mechanisms of mindfulness on reducing athlete burnout.

Mindfulness and Smartphone Addiction before Going to Sleep among College Students: The Mediating Roles of Self-Control and Rumination.

This study aims to examine the effects among college students of mindfulness on smartphone addiction before going to bed at night. We examined the mediating roles of self-control and rumination on the mindfulness-smartphone addiction path. Participants (n = 270, 59.3% females, 18-24 years old) completed self-reporting questionnaires measuring mindfulness, self-control, smartphone addiction, and rumination. In addition to the correlation analysis, we adopted a stepwise regression analysis with bootstrapping to test the mediating effects. It was found that mindfulness was inversely related to smartphone addiction before going to sleep. Most importantly, self-control and rumination significantly mediated the effects of mindfulness on smartphone addiction among college students. The findings of this study indicated that mindfulness training is beneficial to improve the ability of self-control and reduce rumination levels, thereby inhibiting the negative impact of smartphone addiction on college students before they go to sleep, and further promoting their sleep health and mental health.

Acceptance and Commitment Therapy for Health Behavior Change: A Contextually-Driven Approach.

Promoting health behavior change presents an important challenge to theory and research in the field of health psychology. In this paper, we introduce a context-driven approach, the Acceptance and Commitment Therapy (ACT) model which is built on Relational Frame Theory. The ACT-based intervention aims to promote individuals' new health behavior patterns through the improvement of the key construct of psychological flexibility, which is defined as the ability to contact the present moment more fully with acceptance and mindfulness as a conscious human being. Building on the psychological flexibility model, implemented through the six core ACT processes, individuals improve maintenance of long term health behavior change through committed acts in service of chosen values while acknowledging and accepting the existence of contrary thoughts, rules, and emotions as part of themselves but not determinant of their behaviors. Taking advantage of this context-driven approach of health behavior change, we recommend researchers and practitioners to design their health behavior change intervention programs based on ACT.

Assessing acceptance in mindfulness with direct-worded items: The development and initial validation of the Athlete Mindfulness Questionnaire.

PURPOSE: The purpose of the current study was to develop and validate a sport-specific mindfulness measure, the Athlete Mindfulness Questionnaire (AMQ), through 5 related studies using 4 separate samples of Chinese athletes. The AMQ is a 3-factor measure designed to assess mindfulness that reflects present-moment attention, awareness, and acceptance in a sport context. METHODS: In Study 1, an initial pool of items was generated based on previous literature, existing mindfulness scales, as well as interviews with and feedback from the athletes, coaches, and mindfulness experts. Initial support for the 3-factor structure of the AMQ was established via exploratory factor analysis in Study 2, and cross-validated through confirmatory factor analysis in Studies 3 and 4. In Study 5, a modified 3-factor AMQ with direct-worded acceptance items was examined in a fourth independent sample. RESULTS: Convergent and concurrent validities of the acceptance subscale failed to be established in Studies 3 and 4 which may be due to the inattention and confusion of the athletes whilst interpreting the reverse-worded items. A modified 16-item AMQ in Study 5 displayed satisfactory model fit and acceptable internal consistencies. Most importantly, convergent and concurrent validities of the 16-item AMQ were supported. The 3 subscales showed significant positive associations with mindfulness, flow, well-being, and positive affect and significant negative associations with experiential avoidance, burnout, and negative affect. CONCLUSION: The AMQ is a psychometrically sound measure of mindfulness in a sport context. The importance of using direct-worded acceptance items is discussed.

Pollen flow of wheat under natural conditions in the Huanghuai River Wheat Region, China.

The transgenic pollen spread is the main pathway of transgenic plant gene flow. The maximum distance of pollen dispersal (horizontal), the spatial dynamics of pollen movement (vertical), and the patterns of pollen dispersal are important considerations in biosafety assessments of genetically modified crops. To evaluate wheat (Triticum aestivum) pollen dispersal, we measured the pollen suspension velocity and analyzed pollen dispersal patterns under natural conditions in the Huanghuai River wheat-growing region in 2009. The pollen suspension velocity was 0.3-0.4 m/s. The highest pollen densities were detected in the north, northwest, and south of the pollen source. Pollen was dispersed over distances greater than 245 m in the northwest and northeast directions. At the pollen source center, pollen density decreased with increasing vertical height. In the north of the pollen source, the pollen density from 65 m to 225 m showed a wave-mode decrease with increasing height. The horizontal transport of pollen over longer distances fitted polynomial equations. In the north, the pollen density was highest at 45 m from the pollen source, and decreased with increasing distance. In the northwest, the pollen density showed a double-peak trend. In the northeast, pollen density was highest from 45 m to 125 m from the source. Wind speeds greater than the pollen suspension velocity and the duration of continuous gusts were the main factors affecting pollen dispersal. This information will be useful for determining the spatial isolation distances for hybrid seed production and for the commercial production of transgenic wheat.

[The effect of Ginkgo biloba extract on portal hypertension and hepatic microcirculation in rats].

OBJECTIVE: To evaluate the effect of Ginkgo biloba extract (EGb) on hepatic microcirculation and portal hypertension in CCl4 treated rats. METHODS: Twenty-five male Wistar rats were divided into a blank, a CCl4 treated and a CCl4 plus EGb treated group, and all were treated for 10 weeks. The free portal vein pressures were measured through catheterizations. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were studied with transmission electron microscopy. The amounts of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF), nitric oxide (NO), cNOS and iNOS in the liver tissues were determined. RESULTS: The portal vein pressure of the CCl4 plus EGb treated group was (7.4 +/- 0.6) mm Hg while the pressure of the CCl4 treated group was (8.7 +/- 0.8) mm Hg. Aggregation of blood cells or microthrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and spaces of Disse, injury of endothelial cells and capillarization of hepatic sinusoid were significantly milder in the EGb group. The amounts of MDA, ET-1, PAF, NO and iNOS were markedly lower in the CCl4 plus EGb treated group than in the CCl4 treated group. CONCLUSION: The results demonstrated that EGb can decrease the portal vein pressure and improve hepatic microcirculation in CCl4 treated rats. The mechanisms of this effect may involve its inhibition on ET-1, PAF, lipid peroxidation, and down regulation of the hepatic iNOS and NO expressions.

Effects of Ginkgo biloba extract on cell proliferation, cytokines and extracellular matrix of hepatic stellate cells.

BACKGROUND/AIMS: Hepatic fibrosis is the common wound-healing response to chronic liver injury. Ginkgo biloba extract (GbE) has been indicated to reverse hepatic fibrosis and exhibit therapeutic effects both in vitro and in vivo. This study aimed to investigate the underlying mechanism of GbE using HSC-T6 cells, a subline of hepatic stellate cells (HSC) as a model. METHODS: HSC-T6 cells were seeded into six-well plates and allowed to attach overnight. After exposure to different concentrations of GbE761 for 24 or 48 h, cell cycle analysis, semiquantitative RT-PCR, Western blotting analysis and analysis of ECM secretion were performed. RESULTS: It was revealed that GbE (1, 10, 100, 500 mg/l) suppressed HSC proliferation and caused G0/G1 phase arrest in a concentration-dependent manner. RT-PCR and Western blot assays were applied to detect the decline of transforming growth factor beta1(TGF-beta1) and connective tissue growth factor (CTGF) in both mRNA and protein levels after GbE treatment in HSC-T6 cells for 24 or 48 h. Meanwhile, GbE inhibited the synthesis of type I and type III collagens. Secretion of some extracellular matrix (ECM) proteins, such as type III procollagen (PC III), type IV collagen (collagen IV), laminin (LN), hyaluronic acid (HA), were all decreased in supernatant of GbE treated HSC cells. CONCLUSIONS: Our results suggest that GbE confers its anti-fibrosis effects through inhibiting HSC proliferation, reducing TGF-beta1 and CTGF expression and consequently suppressing the collagen production and ECM secretion.

The effect of Ginkgo biloba extract (EGb 761) on hepatic sinusoidal endothelial cells and hepatic microcirculation in CCl4 rats.

It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl4) and EGb groups, and were given normal saline, CCl4 and CCl4 plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl4 group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl4 group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl4. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.