Publications by authors named "Jian-Ping He"

71 Publications

Headache and mental disorders in a nationally representative sample of American youth.

Eur Child Adolesc Psychiatry 2021 Mar 15. Epub 2021 Mar 15.

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, 35 Convent Drive, MSC 3720, Bldg 35A, Room 2E420-F, Bethesda, MD, 20892, USA.

The objective of this study is to examine the association between headache and mental disorders in a nationally representative sample of American youth. We used the National Comorbidity Survey-Adolescent Supplement to assess sex-specific prevalence of lifetime migraine and non-migraine headache using modified International Headache Society criteria and examine associations between headache subtypes and DSM-IV mental disorders. Adolescent report (n = 10,123) was used to identify headache subtypes and anxiety, mood, eating, and substance use disorders. ADHD and behavior disorder were based on parent report (n = 6483). Multivariate logistic regression analyses controlling for key demographic characteristics were used to examine associations between headache and mental disorders. Headache was endorsed by 26.9% (SE = 0.7) of the total sample and was more prevalent among females. Youth with headache were more than twice as likely (OR 2.74, 95% CI 1.94-3.83) to meet criteria for a DSM-IV disorder. Migraine, particularly with aura, was associated with depression and anxiety (adjusted OR 1.90-2.90) and with multiple classes of disorders. Adolescent headache, particularly migraine, is associated with anxiety, mood, and behavior disorders in a nationally representative sample of US youth. Headache is highly prevalent among youth with mental disorders, and youth with headache should be assessed for comorbid depression and anxiety that may influence treatment, severity, and course of both headache and mental disorders.
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http://dx.doi.org/10.1007/s00787-020-01599-0DOI Listing
March 2021

Headache and mental disorders in a nationally representative sample of American youth.

Eur Child Adolesc Psychiatry 2021 Mar 15. Epub 2021 Mar 15.

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, 35 Convent Drive, MSC 3720, Bldg 35A, Room 2E420-F, Bethesda, MD, 20892, USA.

The objective of this study is to examine the association between headache and mental disorders in a nationally representative sample of American youth. We used the National Comorbidity Survey-Adolescent Supplement to assess sex-specific prevalence of lifetime migraine and non-migraine headache using modified International Headache Society criteria and examine associations between headache subtypes and DSM-IV mental disorders. Adolescent report (n = 10,123) was used to identify headache subtypes and anxiety, mood, eating, and substance use disorders. ADHD and behavior disorder were based on parent report (n = 6483). Multivariate logistic regression analyses controlling for key demographic characteristics were used to examine associations between headache and mental disorders. Headache was endorsed by 26.9% (SE = 0.7) of the total sample and was more prevalent among females. Youth with headache were more than twice as likely (OR 2.74, 95% CI 1.94-3.83) to meet criteria for a DSM-IV disorder. Migraine, particularly with aura, was associated with depression and anxiety (adjusted OR 1.90-2.90) and with multiple classes of disorders. Adolescent headache, particularly migraine, is associated with anxiety, mood, and behavior disorders in a nationally representative sample of US youth. Headache is highly prevalent among youth with mental disorders, and youth with headache should be assessed for comorbid depression and anxiety that may influence treatment, severity, and course of both headache and mental disorders.
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http://dx.doi.org/10.1007/s00787-020-01599-0DOI Listing
March 2021

Prenatal diagnosis of Cri-du-Chat syndrome with concomitant distal trisomy 10q syndrome in one fetus with ultrasound anomalies.

Taiwan J Obstet Gynecol 2021 Mar;60(2):318-323

Medical Genetics and Prenatal Diagnosis, Kunming Maternal and Child Care Hospital, Yunnan, China. Electronic address:

Objective: The aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening.

Materials And Methods: A 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18 weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis.

Results: CNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent.

Conclusion: This is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.
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http://dx.doi.org/10.1016/j.tjog.2021.01.010DOI Listing
March 2021

Associations of Social Capital with Mental Disorder Prevalence, Severity, and Comorbidity among U.S. Adolescents.

J Clin Child Adolesc Psychol 2021 Mar 3:1-12. Epub 2021 Mar 3.

Intramural Research Program, National Institute of Mental Health.

: To examine cross-sectional associations between social capital constructs and 1) adolescent lifetime mental disorders, 2) severity of functional impairment, and 3) psychiatric comorbidity.: Data were from the National Comorbidity Survey Adolescent Supplement, a nationally representative mental health survey of 6,483 U.S. adolescents aged 13-18 years. Information from fully-structured diagnostic interviews, including adolescent and caregiver reports, was used to measure seven social capital constructs and lifetime DSM-IV mental disorders (mood, anxiety, behavior, substance use and eating disorder classes). Disorder severity was divided into severe vs. mild/moderate. Comorbidity was measured as the number of different classes of lifetime mental disorders.: Adjusted for socio-demographics and caregivers' mental health, the most consistent associations with adolescent mental disorder were for supportive friendships (any disorder OR = 0.95, 95%CI = 0.91-0.99), family cohesion (OR = 0.81, 95%CI = 0.75-0.86), school bonding (OR = 0.76, 95%CI = 0.71-0.81), and extracurricular participation (OR = 0.90, 95%CI = 0.86-0.95), although results differed by disorder class. Caregiver-reported neighborhood trust and reciprocity and caregiver community involvement were less consistently associated with mental disorder. Medium levels of adolescent-reported affiliation with neighbors was associated with lower odds of mood (OR = 0.81, 95%CI = 0.66-0.98) and anxiety (OR = 0.78, 95%CI = 0.64-0.96) disorder, while high levels were associated with higher odds of behavior disorder (OR = 1.47, 95%CI = 1.16-1.87). Several associations were stronger for severe vs. mild/moderate disorder and with increasing comorbidity.: Although we cannot infer causality, our findings support the notion that improving actual and/or perceived social capital, especially regarding friendships, family, and school, (e.g., through multimodal interventions) could aid in the prevention and treatment of both individual adolescent mental disorders and psychiatric comorbidity.
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http://dx.doi.org/10.1080/15374416.2021.1875326DOI Listing
March 2021

Psychological, physical, and sleep comorbidities and functional impairment in irritable bowel syndrome: Results from a national survey of U.S. adults.

PLoS One 2021 14;16(1):e0245323. Epub 2021 Jan 14.

Genetic epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America.

Background/aims: Patients with irritable bowel syndrome (IBS) in referral practice commonly report mental disorders and functional impairment. Our aim was to determine the prevalence of mental, physical and sleep-related comorbidities in a nationally representative sample of IBS patients and their impact on functional impairment.

Methods: IBS was defined by modified Rome Criteria based on responses to the chronic conditions section of the National Comorbidity Survey-Replication. Associations between IBS and mental, physical and sleep disorders and 30-day functional impairment were examined using logistic regression models.

Results: Of 5,650 eligible responders, 186 met criteria for IBS {weighted prevalence 2.5% (SE = 0.3)}. Age >60 years was associated with decreased odds (OR = 0.3; 95% CI:.1-.6); low family income (OR = 2.4; 95% CI:1.2-4.9) and unemployed status (OR = 2.3; 95% CI:1.2-4.2) were associated with increased odds of IBS. IBS was significantly associated with anxiety, behavior, mood disorders (ORs 1.8-2.4), but not eating or substance use disorders. Among physical conditions, IBS was associated with increased odds of headache, chronic pain, diabetes mellitus and both insomnia and hypersomnolence related symptoms (ORs 1.9-4.0). While the association between IBS and patients' role impairment persisted after adjusting for mental disorders (OR = 2.4, 95% CI 1.5-3.7), associations with impairment in self-care, cognition, and social interaction in unadjusted models (ORs 2.5-4.2) were no longer significant after adjustment for mental disorders.

Conclusion: IBS is associated with socioeconomic disadvantage, comorbidity with mood, anxiety and sleep disorders, and role impairment. Other aspects of functional impairment appear to be moderated by presence of comorbid mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245323PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808669PMC
January 2021

Psychological, physical, and sleep comorbidities and functional impairment in irritable bowel syndrome: Results from a national survey of U.S. adults.

PLoS One 2021 14;16(1):e0245323. Epub 2021 Jan 14.

Genetic epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, United States of America.

Background/aims: Patients with irritable bowel syndrome (IBS) in referral practice commonly report mental disorders and functional impairment. Our aim was to determine the prevalence of mental, physical and sleep-related comorbidities in a nationally representative sample of IBS patients and their impact on functional impairment.

Methods: IBS was defined by modified Rome Criteria based on responses to the chronic conditions section of the National Comorbidity Survey-Replication. Associations between IBS and mental, physical and sleep disorders and 30-day functional impairment were examined using logistic regression models.

Results: Of 5,650 eligible responders, 186 met criteria for IBS {weighted prevalence 2.5% (SE = 0.3)}. Age >60 years was associated with decreased odds (OR = 0.3; 95% CI:.1-.6); low family income (OR = 2.4; 95% CI:1.2-4.9) and unemployed status (OR = 2.3; 95% CI:1.2-4.2) were associated with increased odds of IBS. IBS was significantly associated with anxiety, behavior, mood disorders (ORs 1.8-2.4), but not eating or substance use disorders. Among physical conditions, IBS was associated with increased odds of headache, chronic pain, diabetes mellitus and both insomnia and hypersomnolence related symptoms (ORs 1.9-4.0). While the association between IBS and patients' role impairment persisted after adjusting for mental disorders (OR = 2.4, 95% CI 1.5-3.7), associations with impairment in self-care, cognition, and social interaction in unadjusted models (ORs 2.5-4.2) were no longer significant after adjustment for mental disorders.

Conclusion: IBS is associated with socioeconomic disadvantage, comorbidity with mood, anxiety and sleep disorders, and role impairment. Other aspects of functional impairment appear to be moderated by presence of comorbid mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245323PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808669PMC
January 2021

Direct synthesis of 2,3,5-trisubstituted pyrroles copper-mediated one-pot multicomponent reaction.

Org Biomol Chem 2020 Dec;18(48):9831-9835

State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, China.

We have developed a copper-mediated one-pot synthesis of 2,3,5-trisubstituted pyrroles from 1,3-dicarbonyl compounds and acrylates using ammonium acetate as a nitrogen source. The reaction achieves C-C and C-N bond formation and provides an efficient approach to access highly functionalized pyrroles without further raw material preparation. This method is operationally simple, compatible with a wide range of functional groups, and provides the target products in moderate to good yields.
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http://dx.doi.org/10.1039/d0ob01952fDOI Listing
December 2020

Meta-analysis of protein intake on the effect of Crohn's disease and ulcerative colitis.

Rev Esp Enferm Dig 2021 Mar;113(3):164-169

Anorectal, ZhuJiang Hospital of Southern Medical University, China.

Background And Purpose: published studies have assessed the effect of protein intake on Crohn's disease (CD) and ulcerative colitis (UC). However, the results were inconsistent. To provide a more precise estimation, a meta-analysis was performed to evaluate the association of protein intake in Crohn's disease and ulcerative colitis.

Methods: the PubMed, Chinese National Knowledge Infrastructure databases (CNKI), and Wanfang databases were searched to identify relevant studies. The summarized results of the relative risk (RR) with the corresponding 95 % confidence intervals (CI) were calculated using a random effects model.

Results: the final analysis included a total of nine articles. Nine studies reported on protein intake for the risk of UC and five studies reported on protein intake for the risk of CD. Overall, based on current studies, no significant association was found between protein intake and the risk of UC (RR = 1.13, 95 % CI = 0.82-1.55) or CD (RR = 1.18, 95 % CI = 0.51-2.74). A significant change was not found in the stratified analysis by study design and geographic location.

Conclusions: in conclusion, the present meta-analysis suggested that dietary protein intake did not show a significant effect on the risk of UC or CD.
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http://dx.doi.org/10.17235/reed.2020.6851/2019DOI Listing
March 2021

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Proc Natl Acad Sci U S A 2020 11 21;117(44):27412-27422. Epub 2020 Oct 21.

State Key Laboratory of Cellular Stress Biology, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, 361005 Xiamen, Fujian Province, China

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of and to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.
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http://dx.doi.org/10.1073/pnas.2002997117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959534PMC
November 2020

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Proc Natl Acad Sci U S A 2020 11 21;117(44):27412-27422. Epub 2020 Oct 21.

State Key Laboratory of Cellular Stress Biology, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, 361005 Xiamen, Fujian Province, China

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of and to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.
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http://dx.doi.org/10.1073/pnas.2002997117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959534PMC
November 2020

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Proc Natl Acad Sci U S A 2020 11 21;117(44):27412-27422. Epub 2020 Oct 21.

State Key Laboratory of Cellular Stress Biology, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, 361005 Xiamen, Fujian Province, China

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of and to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.
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http://dx.doi.org/10.1073/pnas.2002997117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959534PMC
November 2020

Excessive sleepiness and associated symptoms in the U.S. adult population: prevalence, correlates, and comorbidity.

Sleep Health 2020 02 2;6(1):79-87. Epub 2019 Nov 2.

National Institute of Mental Health Intramural Research Program, Genetic Epidemiology Research Branch, Bethesda, MD.

Objective: This study examined the prevalence, sociodemographic features, patterns of comorbidity, and impact on functional impairment of excessive sleepiness (Ex.S) and associated symptoms in a nationally representative sample of adults using the National Comorbidity Survey Replication (NCS-R) dataset.

Methods: Participants ≥18 years (n = 5,962) were queried about their sleep using the Composite International Diagnostic Interview (CIDI). Specifically, respondents were questioned about feeling sleepy during the day and falling asleep in permissive situations, feelings of insufficient sleep despite adequate time in bed, and/or difficulty waking up. Those endorsing daytime sleepiness and at least one additional symptom were considered to have Ex.S plus associated symptoms. Associations between Ex.S plus associated symptoms and sociodemographics, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) mental disorders, chronic physical conditions, and functional impairment were examined.

Results: The prevalence of Ex.S plus associated symptoms in U.S. adults was 23.34% (standard error [SE] = 0.88) and significantly co-occurred with insomnia-related symptoms after adjusting for confounders (Odds ratio [OR] = 5.65; 95% confidence interval [CI] = 4.55-7.02). The presence of Ex.S and associated symptoms was more common in women, particularly younger women, those with lower family income, and the unemployed (all P<.001). After controlling for demographic characteristics and other confounders, Ex.S plus associated symptoms was associated with having a DSM-IV mental disorder (OR = 4.25; 95% CI = 3.53-5.10), a chronic physical condition (OR = 2.57; 95% CI = 1.94-3.42) and greater disability (P<.001).

Conclusion: Ex. S with associated symptoms was common, frequently co-occurred with other mental and physical conditions, and was associated with substantial disability. Dissipation of some associations after controlling for insomnia-related symptoms indicated that physical-mental comorbidity and disability were greater among individuals with more pervasive sleep disturbances.
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http://dx.doi.org/10.1016/j.sleh.2019.09.004DOI Listing
February 2020

Prevalence and Correlates of Hypersomnolence Symptoms in US Teens.

J Am Acad Child Adolesc Psychiatry 2019 07 30;58(7):712-720. Epub 2018 Oct 30.

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD.

Objective: Recent attention to pervasive sleep deficits in US adolescents has focused on sleep patterns and insomnia, but there are limited data on the prevalence and correlates of hypersomnolence symptoms.

Method: The sample included 6,483 adolescents 13 to 18 years of age who were interviewed directly and had parent reports in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a nationally representative sample of US youth. Information on sleep patterns/symptoms that were collected in the interview was used to determine the population prevalence of DSM-5 criterion A-defined hypersomnolence and component symptoms. Logistic regression analyses were used to examine associations between sleepiness and sub-symptoms of hypersomnolence with weekday/weekend bedtime, sleep duration, mental disorders, and psychotropic medication use.

Results: Of the sample, 41.5% reported feeling sleepy during the daytime and 11.7% met criteria for hypersomnolence. The prevalence of hypersomnolence varied depending on age (p < .001) and was more common in adolescent girls (odds ratio [OR] 1.40, 95% CI 1.09-1.78). Excessive sleepiness and hypersomnolence symptoms were associated with shorter sleep duration and delayed bedtimes on weekdays and weekends Hypersomnolence was significantly associated with insomnia (OR 2.45, 95% CI 1.87-3.21) and mental disorders (OR 1.99, 95% CI 1.42-2.77). After accounting for insomnia, hypersomnolence was no longer associated with use of psychotropic medication (OR 1.61, 95% CI 0.97-2.66).

Conclusion: Of adolescents with adequate sleep duration, 11.7% still reported symptoms of hypersomnolence. The strong association between hypersomnolence and insomnia suggests that sleep disorders in adolescents can fluctuate between over- and under-sleeping. Potential mechanisms underpinning the strong associations between sleep disturbances and mental disorders should be further pursued and could provide insight into prevention efforts.
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http://dx.doi.org/10.1016/j.jaac.2018.09.435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491259PMC
July 2019

Physical-Mental Comorbidity of Pediatric Migraine in the Philadelphia Neurodevelopmental Cohort.

J Pediatr 2019 02 29;205:210-217. Epub 2018 Oct 29.

Genetic Epidemiology Branch, National Institute of Mental Health, Bethesda, MD. Electronic address:

Objective: To examine the associations between headaches and migraine with physical and mental disorders in a large pediatric registry.

Study Design: In total, 9329 youth aged 8-21 years from the Philadelphia Neurodevelopmental Cohort were included. Physical conditions, including headache, were ascertained from electronic medical records and in-person interviews. Modified International Classification of Headache Disorders (ICHD-II) criteria were used to classify migraine symptoms. Forty-two other physical conditions were classified into 14 classes of medical disorders. Mental disorders were assessed using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia.

Results: Lifetime prevalence of any headache was 45.5%, and of migraine was 22.6%. Any headache was associated with a broad range of physical disorders, attention-deficit/hyperactivity disorder (OR 1.2 [95% CI 1.1-1.4]), and behavior disorders (1.3 [1.1-1.5]). Youth with migraine had greater odds of specific physical conditions and mental disorders, including respiratory, neurologic/central nervous system, developmental, anxiety, behavior, and mood disorders than those with nonmigraine headache (OR ranged from 1.3 to 1.9).

Conclusions: Comorbidity between headaches with a range of physical conditions that have been associated with adult migraine demonstrates that multimorbidity occurs early in development. Comorbidity may be an important index of heterogeneity of migraine that can guide clinical management, genetic investigation, and future research on shared pathophysiology with other disorders.
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http://dx.doi.org/10.1016/j.jpeds.2018.09.033DOI Listing
February 2019

Physical Activity and Mental Disorder Among Adolescents in the United States.

J Adolesc Health 2018 11 29;63(5):628-635. Epub 2018 Aug 29.

Genetic Epidemiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland. Electronic address:

Objective: To estimate associations between physical activity (PA) and a broad range of lifetime mental disorders among adolescents, and to evaluate whether the context of sports participation impacts these associations.

Methods: The sample included 6,483 13-18 year-olds from the National Comorbidity Survey Adolescent Supplement. Adolescents completed face-to-face psychiatric interviews and a parent provided diagnostic and other family-level information on the participating adolescent by completing a self-administered questionnaire. PA was measured by adolescent self-report and dichotomized to indicate vigorous exercise several times a week. Nineteen psychiatric disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders criteria. Multiple logistic regression analyses were used to estimate associations of PA with mental disorders, suicidality, and psychological distress.

Results: Two thirds of adolescents reported being physically active. Active adolescents had significantly lower odds of mood disorder (Odds ratio[OR] = .74, 95% confidence interval [CI]=.58-.94), bipolar II disorder (OR = .54, 95% CI=.30-.99), and general psychological distress (OR = .71, 95% CI=.52-.96) than less/inactive adolescents. In contrast, adolescents who engaged in PA were more likely to have lifetime alcohol use disorder (OR = 1.78, 95% CI = 1.11-2.85), bulimia (OR = 5.84, 95% CI = 2.48-13.79), generalized anxiety disorder (OR = 2.04, 95% CI = 1.16-3.58), and posttraumatic stress disorder (OR = 1.65, 95% CI = 1.07-2.55). The direct associations between PA and alcohol use disorder and bulimia appeared to be specific to adolescents who participated in organized sports.

Discussion: Associations between PA and lifetime mental disorder among adolescents may differ according to both disorder type and the context in which PA occurs. Longitudinal studies that assess the context of PA may be able to explain apparent discrepant associations between PA and mental disorder.
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http://dx.doi.org/10.1016/j.jadohealth.2018.05.030DOI Listing
November 2018

Flightless-I Blocks p62-Mediated Recognition of LC3 to Impede Selective Autophagy and Promote Breast Cancer Progression.

Cancer Res 2018 09 13;78(17):4853-4864. Epub 2018 Jun 13.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, P.R. China.

p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here, we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded the development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlated with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer. Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer..
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http://dx.doi.org/10.1158/0008-5472.CAN-17-3835DOI Listing
September 2018

Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation.

Mol Cell 2018 02 27;69(3):480-492.e7. Epub 2018 Jan 27.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, China. Electronic address:

Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPβ, a rate-limiting enzyme in FAO. Although TPβ activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPβ association results in Nur77 self-sacrifice to protect TPβ from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPβ interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.
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http://dx.doi.org/10.1016/j.molcel.2018.01.001DOI Listing
February 2018

Parenting style and mental disorders in a nationally representative sample of US adolescents.

Soc Psychiatry Psychiatr Epidemiol 2018 01 6;53(1):11-20. Epub 2017 Nov 6.

Genetic Epidemiology Branch, Intramural Research Program, National Institute of Mental Health, Building 35, Room 2E480, 35 Convent Drive, MSC #3720, Bethesda, MD, 20892, USA.

Purpose: We examined associations between parenting style and past-year mental disorders in a nationally representative cross-sectional survey of US adolescents and whether the associations differed by adolescent demographic characteristics.

Methods: The sample included 6483 adolescents aged 13-18 years who were interviewed for a full range of DSM-IV mental disorders. Parenting style was assessed by adolescent-reported maternal and paternal care and control using items from the Parental Bonding Instrument. We controlled for socio-demographics, parental history of mental disorders, stressful life events, sexual violence, inter-parental conflict, and household composition. We also tested for two-way interactions between parental care and control and adolescent age, sex, and race/ethnicity.

Results: In adjusted models, high maternal care was associated with lower odds of depressive, eating, and behavioral disorders, and high maternal control was associated with greater odds of depressive, anxiety, eating, and behavioral disorders. High paternal care was associated with lower odds of social phobia and alcohol abuse/dependence. High paternal control was associated with greater odds of agoraphobia and alcohol abuse/dependence but with lower odds of attention-deficit/hyperactivity disorder. Associations of maternal and paternal control with anxiety disorders and substance abuse/dependence differed by sex. High paternal care was associated with lower odds of anxiety disorders only among Hispanics and non-Hispanic blacks.

Conclusions: Perceived parental care and control were associated with adolescent mental disorders after controlling for multiple potential confounders. Differential patterns of association were found according to adolescent sex and race/ethnicity. Findings have implications for prevention and intervention programs that incorporate familial contextual factors.
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http://dx.doi.org/10.1007/s00127-017-1435-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823599PMC
January 2018

Generalizability of Clinical Trial Results for Adolescent Major Depressive Disorder.

Pediatrics 2017 Dec 2;140(6). Epub 2017 Nov 2.

Genetic Epidemiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

Background: Although there have been a number of clinical trials evaluating treatments for adolescents with major depressive disorder (MDD), the generalizability of those trials to samples of depressed adolescents who present for routine clinical care is unknown. Examining the generalizability of clinical trials of pharmacological and psychotherapy interventions for adolescent depression can help administrators and frontline practitioners determine the relevance of these studies for their patients and may also guide eligibility criteria for future clinical trials in this clinical population.

Methods: Data on nationally representative adolescents were derived from the National Comorbidity Survey: Adolescent Supplement. To assess the generalizability of adolescent clinical trials for MDD, we applied a standard set of eligibility criteria representative of clinical trials to all adolescents in the National Comorbidity Survey: Adolescent Supplement with a diagnosis of MDD ( = 592).

Results: From the overall MDD sample, 61.9% would have been excluded from a typical pharmacological trial, whereas 42.2% would have been excluded from a psychotherapy trial. Among those who sought treatment ( = 412), the corresponding exclusion rates were 72.7% for a pharmacological trial and 52.2% for a psychotherapy trial. The criterion leading to the largest number of exclusions was "significant risk of suicide" in both pharmacological and psychotherapy trials.

Conclusions: Pharmacological and, to a lesser extent, psychotherapy clinical trials likely exclude most adolescents with MDD. Careful consideration should be given to balancing eligibility criteria and internal validity with applicability in routine clinical care while ensuring patient safety.
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http://dx.doi.org/10.1542/peds.2016-1701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703774PMC
December 2017

Percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue for advanced pancreatic carcinoma: Case Report.

Medicine (Baltimore) 2017 Sep;96(37):e8018

Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy Department of Psychiatry Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Rationale: The aim of this study was to determine the effectiveness of intratumoral injection of chemotherapeutics in improving the quality of life and survival of patients with pancreatic carcinoma.

Patient Concerns: We present a case series of 5 patients with unresectable pancreatic adenocarcinoma.

Diagnoses: Patients diagnosed with unresectable poorly differentiated pancreatic ductal adenocarcinoma by intraoperative frozen biopsyor percutaneous biopsy.

Interventions: Five patients with unresectable pancreatic adenocarcinoma received a computed tomography-guided percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue.

Outcomes: Mean overall survival was 16.2 ± 3.7 months. Local control rates were 100% and 80% at postoperative 3 and 6 months, respectively. Mean Visual Analogue Scale pain score decreased from 7.2 ± .84 preoperatively to 2 ± 1.22 at postoperative 4 weeks. There were no complications associated with the procedure.

Lessons: Percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue for advanced pancreatic may be safe and effective.
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http://dx.doi.org/10.1097/MD.0000000000008018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604654PMC
September 2017

Differential responsiveness in VEGF receptor subtypes to hypoxic stress in various tissues of plateau animals.

Physiol Res 2017 05 16;66(2):357-362. Epub 2016 Dec 16.

College of Life Science, Shaanxi Normal University, Xi'an, China.

With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress. ELISA and Western blot analysis were employed to determine HIF-1alpha and the protein expression of VEGFRs in control animals and plateau pikas. We further blocked HIF-1alpha signal to determine if HIF-1alpha regulates alternations in VEGFRs in those tissues. We hypothesized that responsiveness of VEGFRs in the major end organs of plateau animals is differential with insult of hypoxic stress and is modulated by low oxygen sensitive HIF-1alpha. Our results show that hypoxic stress induced by exposure of lower O(2) for 6 h significantly increased the levels of VEGFR-2 in skeletal muscle, heart and lung and the increases were amplified in plateau pikas. Our results also demonstrate that hypoxic stress enhanced VEGFR-3 in lungs of plateau animals. Nonetheless, no significant alternations in VEGFR-1 were observed in those tissues with hypoxic stress. Moreover, we observed decreases of VEGFR-2 in skeletal muscle, heart and lung; and decreases of VEGFR-3 in lung following HIF-1alpha inhibition. Overall, our findings suggest that in plateau animals 1) responsiveness of VEGFRs is different under hypoxic environment; 2) amplified VEGFR-2 response appears in skeletal muscle, heart and lung, and enhanced VEGFR-3 response is mainly observed in lung; 3) HIF-1alpha plays a regulatory role in the levels of VEGFRs. Our results provide the underlying cellular and molecular mechanisms responsible for hypoxic environment in plateau animals, having an impact on research of physiological and ecological adaptive responses to acute or chronic hypoxic stress in humans who living at high attitude and who live at a normal sea level but suffer from hypoxic disorders.
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http://dx.doi.org/10.33549/physiolres.933408DOI Listing
May 2017

Correlates of Overweight and Obesity Among Adolescents With Bipolar Disorder in the National Comorbidity Survey-Adolescent Supplement (NCS-A).

J Am Acad Child Adolesc Psychiatry 2016 12 28;55(12):1020-1026. Epub 2016 Sep 28.

Genetic Epidemiology Research Branch and the Developmental Trajectories of Mental Disorders Branch, National Institute of Mental Health.

Objective: Despite substantial evidence on the prevalence and correlates of overweight and obesity (OW/OB) in adults with bipolar disorder (BD), little is known about this topic in adolescents with BD.

Method: The method consisted of the National Comorbidity Survey-Adolescent Supplement, a face-to-face survey of mental disorders from 2001 through 2004, using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview. Participants were adolescents 13 to 17 years of age, with bipolar disorder I or II (n = 295), major depressive disorder (n = 1,112), or controls with neither mood disorder (n = 8,716). Analyses examined for group differences in the prevalence of OW/OB and for correlates of OW/OB in the group with BD.

Results: There were no significant differences in weight categories across groups. OW and OB in adolescents with BD were associated with significantly higher lifetime rates of suicide attempt (odds ratio 3.02, 95% CI 1.11-8.24), physical or sexual abuse (2.82, 1.20-6.60), binge eating or bulimia (2.66, 1.13-6.26), and conduct disorder (2.60, 1.10-6.13) in covariate-adjusted analyses. OW and OB also were significantly associated with seeing a professional for depression, being hospitalized overnight for depression, and receiving general medical treatment.

Conclusion: The similar prevalence of OW/OB in adolescents with and without BD suggests that this potent association in adults likely comprises a consequence of BD or its correlates. In contrast, the strong association of OW/OB with proxies for depression severity, including suicide attempts and hospitalization, is already evident even in this young, nonclinical sample. Studies are warranted to determine whether early intervention of OW/OB in BD might optimize physical and mental health.
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http://dx.doi.org/10.1016/j.jaac.2016.08.010DOI Listing
December 2016

Medical Comorbidity of Attention-Deficit/Hyperactivity Disorder in US Adolescents.

J Child Neurol 2016 10 22;31(11):1282-9. Epub 2016 Jun 22.

National Institute of Mental Health, Bethesda, MD, USA

Understanding patterns of medical comorbidity in attention-deficit/hyperactivity disorder (ADHD) may lead to better treatment of affected individuals as well as aid in etiologic study of disease. This article provides the first systematic evaluation on the medical comorbidity of ADHD in a nationally representative sample (National Comorbidity Replication Survey-Adolescent Supplement; N = 6483) using formal diagnostic criteria. Survey-weighted odds ratios adjusted for demographics, additional medical, and mental disorders were calculated for associations between ADHD and medical conditions. Models adjusted for demographics revealed significantly increased odds of allergy, asthma, enuresis, headache/migraine, and serious stomach or bowel problems. After adjusting for comorbidity, across the medical conditions, enuresis and serious stomach problems were the strongest correlates of ADHD. These findings confirm the pervasive medical comorbidity of ADHD reported in previous clinical and community-based studies. The intriguing salience of enuresis and serious stomach or bowel conditions may also provide an important clue to multisystem involvement in ADHD.
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http://dx.doi.org/10.1177/0883073816653782DOI Listing
October 2016

Ag nanoclusters could efficiently quench the photoresponse of CdS quantum dots for novel energy transfer-based photoelectrochemical bioanalysis.

Biosens Bioelectron 2016 Nov 8;85:930-934. Epub 2016 Jun 8.

State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Herein the influence of ultrasmall Ag nanoclusters (Ag NCs) against CdS quantum dots (QDs) in a photoelectrochemical (PEC) nanosystem was exploited for the first time, based on which a novel PEC bioanalysis was successfully developed via the efficient quenching effect of Ag NCs against the CdS QDs. In a model system, DNA assay was achieved by using molecular beacon (MB) probes anchored on a CdS QDs modified electrode, and the MB probes contain two segments that can hybridize with both target DNA sequence and the label of DNA encapsulated Ag NCs. After the MB probe was unfolded by the target DNA sequence, the labels of oligonucleotide encapsulated Ag NCs would be brought in close proximity to the CdS QDs electrode surface, and efficient photocurrent quenching of QDs could be resulted from an energy transfer process that originated from NCs. Thus, by monitoring the attenuation in the photocurrent signal, an elegant and sensitive PEC DNA bioanalysis could be accomplished. The developed biosensor displayed a linear range from 1.0pM to 10nM and the detection limit was experimentally found to be of 0.3pM. This work presents a feasible signaling principle that could act as a common basis for general PEC bioanalysis development.
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http://dx.doi.org/10.1016/j.bios.2016.06.018DOI Listing
November 2016

Association of Lifetime Mental Disorders and Subsequent Alcohol and Illicit Drug Use: Results From the National Comorbidity Survey-Adolescent Supplement.

J Am Acad Child Adolesc Psychiatry 2016 Apr 2;55(4):280-8. Epub 2016 Feb 2.

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health (NIMH), Bethesda, MD. Electronic address:

Objective: To estimate the association of prior lifetime mental disorders with transitions across stages of substance use in a cross-sectional, nationally representative sample of US adolescents.

Method: The sample includes 10,123 adolescents aged 13 to 18 years who participated in the National Comorbidity Survey-Adolescent Supplement (NCS-A), and who were directly interviewed with the Composite International Diagnostic Interview (CIDI) Version 3.0 that generates criteria for DSM-IV disorders.

Results: Adolescents with prior lifetime mental disorders had high rates of both alcohol (10.3%) and illicit drug (14.9%) abuse, with or without dependence. Alcohol and drug abuse were highest among adolescents with prior anxiety disorders (17.3% and 20%, respectively) and behavior disorders (15.6% and 24%, respectively). Any prior disorder significantly increased the risk of transition from nonuse to first use, and from use to problematic use of either alcohol or illicit drugs. Multivariate models attenuated the magnitude of the risk of transition associated with each disorder, although prior weekly smoking and illicit drug use demonstrated significant risks of transitions across the 3 stages of alcohol or drug use, as did behavior disorders.

Conclusion: The findings provide the first evidence from a nationally representative sample that prior mental disorders represent risk factors for the transition from nonuse to use, and the progression to drug- and alcohol-related problems. Treatment of primary mental disorders is likely to be an important target for the prevention of secondary substance use disorders in youth.
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http://dx.doi.org/10.1016/j.jaac.2016.01.006DOI Listing
April 2016

Neoadjuvant chemotherapy with cetuximab for locally advanced penile cancer.

J Cancer Res Ther 2015 Oct-Dec;11(4):1041

Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, Chengdu, China.

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http://dx.doi.org/10.4103/0973-1482.151945DOI Listing
November 2016

Disruptive Mood Dysregulation Disorder at Ages 13-18: Results from the National Comorbidity Survey-Adolescent Supplement.

J Child Adolesc Psychopharmacol 2016 Mar 15;26(2):107-13. Epub 2016 Jan 15.

2 Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health , Bethesda, Maryland.

Objective: "Disruptive mood dysregulation disorder" (DMDD) has been introduced into the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. but the utility of this new label and the clinical correlates of the children it describes are yet to be determined.

Methods: A proxy for the DMDD diagnosis was extracted from the National Comorbidity Survey - Adolescent Supplement (NCS-A) data on 6483 adolescents (51.4% female) including Composite International Diagnostic Interview (CIDI) diagnoses and measures of impaired functioning from the Sheehan Disability Scale. Cross tabulations and logistic regression were used to assess for prevalence and comorbidity.

Results: A total of 310 (5.26%) adolescents met the criteria for DMDD when diagnostic hierarchy and frequency of outbursts were not considered. At the low end of prevalence estimation, only nine adolescents (0.12%) met the most stringent proxy diagnosis, and they also met criteria for a number of comorbid disorders and functional impairment. The rates of comorbidity and functional impairment in adolescents with bipolar disorder were the same, irrespective of their meeting criteria for DMDD.

Conclusions: The DMDD diagnosis captures a small group of adolescents with multiple other psychiatric and neurologic conditions. The specificity of this diagnostic label, therefore, at least in adolescents, remains an open question.
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http://dx.doi.org/10.1089/cap.2015.0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800387PMC
March 2016

Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.

Chem Biol 2015 Aug 30;22(8):1040-51. Epub 2015 Jul 30.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, P.R. China. Electronic address:

Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death.
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http://dx.doi.org/10.1016/j.chembiol.2015.06.023DOI Listing
August 2015

School Start Time and Adolescent Sleep Patterns: Results From the U.S. National Comorbidity Survey--Adolescent Supplement.

Am J Public Health 2015 Jul 14;105(7):1351-7. Epub 2015 May 14.

Diana Paksarian, Jian-Ping He, and Kathleen R. Merikangas are with the Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD. Kara E. Rudolph is with the School of Public Health, University of California, Berkeley, and Center for Health and Community, University of California, San Francisco.

Objectives: We estimated associations between school start time and adolescent weeknight bedtime, weeknight sleep duration, and weekend compensatory sleep and assessed whether associations differ by age, sex, or urbanicity.

Methods: We used a subsample of a nationally representative, cross-sectional survey of 7308 students aged 13 to 18 years attending 245 schools to estimate associations of school start time, reported by school principals, with weeknight bedtime and sleep duration and weekend compensatory sleep, reported during adolescent face-to-face interviews.

Results: Start time was positively associated with weeknight bedtime. Associations between start time and weeknight sleep duration were nonlinear and were strongest for start times of 8:00 am and earlier. Associations differed by sex and urbanicity, with the strongest association among boys in major metropolitan counties. Start time was negatively associated with sleep duration among boys in nonurban counties. Start time was not associated with weekend compensatory sleep.

Conclusions: Positive overall associations between school start time and adolescent sleep duration at the national level support recent policy recommendations for delaying school start times. However, the impact of start time delays may differ by sex and urbanicity.
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http://dx.doi.org/10.2105/AJPH.2015.302619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463387PMC
July 2015

Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation.

Nat Chem Biol 2015 May 30;11(5):339-46. Epub 2015 Mar 30.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China.

Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the κB element. However, this function of Nur77 is countered by the LPS-activated p38α phosphorylation of Nur77. Dampening the interaction between Nur77 and p38α would favor Nur77 suppression of the hyperinflammatory response. A compound, n-pentyl 2-[3,5-dihydroxy-2-(1-nonanoyl) phenyl]acetate, screened from a Nur77-biased library, blocked the Nur77-p38α interaction by targeting the ligand-binding domain of Nur77 and restored the suppression of the hyperinflammatory response through Nur77 inhibition of NF-κB. This study associates the nuclear receptor with immune homeostasis and implicates a new therapeutic strategy to treat hyperinflammatory responses by targeting a p38α substrate to modulate p38α-regulated functions.
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http://dx.doi.org/10.1038/nchembio.1788DOI Listing
May 2015