Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

Salvianolic acid B alleviates neurological injury by upregulating stanniocalcin 1 expression.

Background: Salvianolic acid B (Sal B) is a representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which promotes angiogenesis in myocardial infarction and diabetic cardiomyopathy. However, whether Sal B has a neuroprotective function in ischemic stroke by promoting angiogenesis is still unclear. Methods: In the present study, ischemic stroke models were induced in rats by middle cerebral artery occlusion (MCAO), and Sal B (10 or 20 mg/kg/d) was intraperitoneally injected according to a previous study. Neurological deficits were evaluated by the modified Longa five-point scale, modified Bederson scores and cerebral infarction sizes by triphenyltetrazolium chloride (TTC) staining. Apoptotic cells were tested by cleaved-caspase3 immunofluorescence staining and an in situ cell death (TUNEL) detection kit. Human umbilical vein endothelial cells (HUVECs) exposed to hypoxia were used to investigate the effects of Sal B on angiogenesis and tube formation in vitro. Results: Sal B ameliorated the neurological deficits, decreased the cerebral infarction volumes in rats with ischemic stroke, significantly increased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and VEGFA and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B increased stanniocalcin 1 (STC1) expression, induced the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) activity, enhanced cell migration, and activated VEGFR2/VEGFA signaling in endothelial cells. Conclusions: This study showed that Sal B promoted angiogenesis and alleviated neurological apoptosis in rats with ischemic stroke by promoting STC1.

Sleep disordered breathing symptoms are associated with depressive symptoms: A longitudinal study of Chinese adolescents.

BACKGROUND: Little is known about the prospective association between sleep disordered breathing (SDB) and depressive symptoms in Chinese adolescents. This study examined the independent predictive role of SDB symptoms in depressive symptoms in a large sample of adolescents. METHODS: A total of 11831 adolescents who participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort and 7072 adolescents who were resurveyed 1 year later were included for the analyses. Adolescents completed a self-administered questionnaire about demographics, mental health, sleep problems, and family environment. SDB symptoms were assessed by 3 items about loud snoring, breathing pauses, and snorting/gasping. The Chinese Youth Self-Report anxious/depressed subscale was used to assess depressive symptoms. RESULTS: In the cross-sectional analyses, 11.8% adolescents had depressive symptoms, and elevated frequency of SDB symptoms were significantly associated with depressive symptoms. In the longitudinal study, 4.5% of adolescents had persistent depressive symptoms, the incidence rate of depressive symptoms at 1-year follow-up was 6.5%, and elevated frequency of any SDB symptoms (often: OR=2.23, 95%CI:1.50-3.32) at baseline was significantly associated with incident depressive symptoms after adjusting for potential confounders. The associations between SDB symptoms and depressive symptoms were similar for boys and girls. LIMITATION: SDB symptoms and depressive symptoms were measured by self-report. CONCLUSION: SDB symptoms are an independent and significant predictor of depressive symptoms in adolescents. Further research is needed to understand the biological mechanisms between SDB and mood dysregulation in adolescents.

Depressive symptoms are associated with short and long sleep duration: A longitudinal study of Chinese adolescents.

AIMS: Sleep loss and irregular sleep patterns in adolescents are major public health concerns in the modern society. This study aimed to explore the associations between short and long sleep duration and depressive symptoms among Chinese adolescents. METHODS: A total of 7311 adolescents who participated in the baseline survey and were followed up 1 year or 2 years later were included in the analyses. Participants completed a self-administered questionnaire at baseline and follow-up surveys. The Center for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms. Generalized estimating equation (GEE) and restrictive cubic spline models were used to estimate the association between sleep duration and depressive symptoms. RESULTS: After adjusting for adolescent and family covariates, sleep duration <8 h and >=9 h on weekdays and sleep duration <8 h and >=12 h on weekends were significantly associated with depressive symptoms compared with sleep 8 h. Weekend-weekday sleep difference >=3 h or <-1 h (ie. sleeping >1 h on weekdays than weekends) was also associated with depressive symptoms. There were U-shaped relationships between sleep duration on weekdays, weekends, or weekday-weekend sleep difference and depressive symptoms. LIMITATIONS: Sleep duration and depression were measured by self-report. CONCLUSIONS: Our findings highlight the risk of short and long sleep duration, and weekday-weekend sleep imbalance for depression in adolescents.

Nightmares Are Associated With Future Suicide Attempt and Non-Suicidal Self-Injury in Adolescents.

OBJECTIVE: To determine which sleep variables, including sleep duration, sleep quality, insomnia symptoms, and nightmares, were significantly and independently associated with subsequent adolescent suicidal behavior and non-suicidal self-injury (NSSI). METHODS: A prospective longitudinal study was conducted in Shandong, China. Participants were 7,072 adolescents initially assessed in November and December in 2015 and reassessed 1 year later in 2016. Self-administered structured questionnaires were used to assess suicidal behavior, NSSI, night sleep duration, insomnia symptoms, sleep quality, nightmares, impulsivity, depression, and family demographics. Logistic regression analyses were performed to examine the associations between sleep variables and suicidal behavior and NSSI. RESULTS: At 1-year follow-up, 190 participants (2.7%) attempted suicide and 621 (8.8%) engaged in NSSI. Insomnia symptoms and frequent nightmares (several times a month) at baseline were significantly associated with subsequent suicide attempt and NSSI 1 year later. After adjustment for covariates including adolescent and family demographics, depression, impulsiveness, and prior suicide attempt/NSSI, frequent nightmares in the past year remained significant for suicide attempt (OR = 1.96; 95% CI, 1.15-3.33) and NSSI (OR = 1.52; 95% CI, 1.10-2.08). With further adjustment for insomnia symptoms, sleep quality, and sleep duration, the associations between frequent nightmares and subsequent suicide attempt and NSSI had almost no change. Insomnia, short sleep duration, and poor sleep quality were not independently associated with subsequent suicide attempt and NSSI. CONCLUSIONS: Frequent nightmares were independently associated with subsequent suicide attempt and NSSI among adolescents. Assessing and intervening for nightmares may have important implications for early identification of adolescents at risk and prevention of adolescent self-harm and suicide.

Stressful life events, insomnia and suicidality in a large sample of Chinese adolescents.

AIMS: This study aimed to examine the associations between stressful life events, insomnia, and suicidality including suicidal ideation (SI), suicide plan (SP) and suicide attempt (SA) in a large sample of Chinese adolescents. METHODS: A total of 11,831 adolescents who participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort were included for the analysis. Participants were sampled from 8 middle/high schools in 3 counties of Shandong, China. Participants completed a structured behavior and health questionnaire, including suicidality, demographics, depression/anxiety, stressful life events (SLEs), and insomnia in November-December 2015. A series of logistic regression models and mediation analyses were performed to examine the associations between SLEs, insomnia and suicidality. RESULTS: The prevalence rates of overall suicidality, SI, SP and SA in the last year were 13.1%, 12.5%, 3.3%, and 1.5%, respectively. SLEs were significantly associated with overall suicidality, SI, and SP. Insomnia was an independent risk factor of suicidality and a mediator of the association between SLEs and suicidality. The total effect of SLEs on overall suicidality was 0.597 (95%CI: 0.534-0.661), including 0.457 (95%CI: 0.391-0.523) for direct effect and 0.158 (95%CI: 0.138-0.178) for indirect effect. Insomnia also mediated the associations of SLEs with SI, SP and SA, respectively. LIMITATIONS: Causal relationship could not be concluded because this study is cross-sectional. CONCLUSIONS: Stressful life events and insomnia are directly associated with suicidality in adolescents. The association between SLEs and suicidality is partially mediated by insomnia.

Age at menarche, menstrual problems, and daytime sleepiness in Chinese adolescent girls.

STUDY OBJECTIVES: Menstrual problems and daytime sleepiness are prevalent in adolescent girls. Little is known about the associations between age at menarche, menstrual problems, and daytime sleepiness. This study aimed to examine the associations of age at menarche and menstrual problems with daytime sleepiness among Chinese adolescent girls. METHODS: Of 11,831 adolescents who participated in the baseline survey of Shandong Adolescent Behavior & Health Cohort (SABHC), 5,813 were girls and included for the analysis. A structured self-administered questionnaire was used to collect information about menstrual problems, sleep, mental health, and demographics. Daytime sleepiness was measured by the Chinese Adolescent Daytime Sleepiness Scale (CADSS). RESULTS: The mean age of the girls was 15.02 (SD = 1.44) years. The prevalence rates of mild, moderate, and severe daytime sleepiness were 20.5%, 16.7%, and 5.5%, respectively. After adjusting for adolescent and family covariates (age, body mass index, physical health, physical exercise, sleep duration, sleep problems, anxious/depressive symptoms, and family social economic status), sometimes irregular (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.01 to 1.52), often irregular menstruation (OR = 1.58, 95% CI = 1.17 to 2.12), moderate (OR=1.39, 95% CI = 1.12 to 1.72), and severe (OR = 1.46, 95% CI = 1.04 to 2.04) menstrual pain were significantly associated with increased risk of daytime sleepiness. CONCLUSIONS: Our findings suggest that menstrual irregularity and menstrual pain are associated with increased risk of daytime sleepiness. These findings emphasize the importance of evaluating and intervening menstrual problems for preventing daytime sleepiness in adolescent girls.

Daytime sleepiness predicts future suicidal behavior: a longitudinal study of adolescents.

Study Objectives: Daytime sleepiness is associated with poor daytime functioning and adverse cognitive and emotional consequences, such as impaired decision-making and increased impulsivity. Little is known about the association between daytime sleepiness and suicidal behaviors. This study examined the prospective relationship between daytime sleepiness and suicidal behaviors, including suicidal thought (ST), suicide plan (SP), and suicide attempt (SA), in a large sample of adolescents. Methods: A prospective longitudinal study of 7072 adolescents (mean age = 14.6 years) was conducted in Shandong province, China. Participants completed a self-administered questionnaire to assess suicidal behaviors, daytime sleepiness, nighttime sleep duration, insomnia, snoring, hopelessness, impulsivity, anxiety/depression, and family demographics. Participants were first surveyed in November-December 2015 and resurveyed 1 year later. Of the 7072 participants, 77.1% (n = 5451) who did not report suicidal behaviors at baseline were included for primary analysis. Results: The incidence rates of ST, SP, and SA at 1 year follow-up were 6.0%, 2.1%, and 1.6%, respectively. The incidence rates of ST and SP significantly increased with elevated daytime sleepiness score at baseline. After adjusting for adolescent and family covariates including sleep-related variables (i.e. insomnia, nighttime sleep duration, and snoring), a daytime sleepiness score ≥ median at baseline was significantly associated with increased risk of ST (OR = 1.55, 95%CI = 1.02-2.35) and SP (OR = 2.60, 95%CI = 1.22-5.53). Conclusions: Daytime sleepiness appears to be a significant predictor of subsequent suicidal behaviors in adolescents. These findings emphasize the importance of assessing and intervening daytime sleepiness for preventing suicide in adolescents.

Suicidal behaviours among Chinese adolescents exposed to suicide attempt or death.

AIMS: Suicidal behaviours in adolescents are prevalent and multifactorial. This study was conducted to examine the associations between exposure to suicide attempt (ESA) or suicide death (ESD) and suicidal behaviours in a large sample of Chinese adolescents. METHODS: Participants included for the analysis were 11 831 adolescent students who participated in the baseline survey of the Shandong Adolescent Behavior and Health Cohort (SABHC). Participants were sampled from five middle and three high schools in three counties of Shandong province, China. A self-administered structured questionnaire was used to collect data on demographics, behavioural and emotional problems, family environment, suicidal behaviours (suicidal thought, plan and attempt), and history of ESA or death of a family member, relative, friend or close acquaintance. Based on the sources of exposure, the participants were divided into four groups: non-exposure, exposure from relatives only, exposure from friends/close acquaintances only (EFO) and exposure from both relatives and friends (ERF). Logistic regressions were used to examine the associations between ESA or ESD and suicidal behaviours. RESULTS: Mean age of the participants was 14.97 ± 1.46 years and 50.9% were boys. Of the participants, 9.4% reported having ESA, and 6.6% reported having ESD. The prevalence rates of suicidal behaviours were significantly higher in adolescents who had been exposed to suicide attempt or death than those who had not. Multivariate logistic regressions showed that ESA and ESD were both significantly associated with increased risks of suicidal thought (ESA: OR = 1.96, 95% CI = 1.66-2.31; ESD: OR = 1.59, 95% CI = 1.31-1.94), plan (ESA: OR = 2.37, 95% CI = 1.84-3.05; ESD: OR = 1.62, 95% CI = 1.18-2.23) and attempt (ESA: OR = 2.73, 95% CI = 1.92-3.89; ESD: OR = 1.82, 95% CI = 1.18-2.82), respectively. When participants were exposed to suicide attempt, ERF and EFO groups had significantly higher risks of suicidal thought (ERF: OR = 2.61, 95% CI = 1.28-1.64; EFO: OR = 1.96, 95% CI = 1.64-2.36), plan (ERF: OR = 3.72, 95% CI = 2.04-6.78; EFO: OR = 2.31, 95% CI = 1.74-3.01) and attempt (ERF: OR = 4.83, 95% CI = 2.30-10.17; EFO: OR = 2.57, 95% CI = 1.73-3.81), respectively. CONCLUSIONS: ESA or ESD was associated with increased risks of suicidal behaviours in adolescents. Exposure to suicidal behaviours of relatives and friends/close acquaintances appeared to have different influence on adolescent suicidal behaviours. Further research is warranted to examine the biological and psychosocial mechanisms between suicidal exposure and subsequent suicidal behaviours in adolescents.