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1.
J Autism Dev Disord ; 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37326789

RESUMO

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively.

2.
Front Psychiatry ; 13: 895029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935429

RESUMO

Autism spectrum disorder (ASD) is characterized by social communicative abnormalities. Deficits and delays in gestural communication are among the early deficits of ASD and also a major social modality in early caregiver-toddler interaction. Caregiver gestures have an important role in the cognitive and social development of children with ASD. Thus, it is urgent to further explore the role of caregiver gestures in early caregiver-toddler interaction. In this cross-sectional study, we observed the caregivers' gestures and responses of toddlers aged between 18 and 24 months during play (ASD = 44, TD = 29) and dining activities (ASD = 34, TD = 27). By observing the different frequencies and patterns of gestures by the caregiver-child interaction and the different proportions of children's responses to the caregiver's gestures, we found that, compared to caregivers of typically developing toddlers, caregivers of toddlers with ASD had fewer synchronized gestures and more unsynchronized gestures in the play activity and more supplementary gestures in dining activity. Toddlers with ASD produced more social responses to caregivers' synchronized gestures, whereas the use of synchronized gestures by the caregivers in caregiver-toddler interaction had a positive influence on social responses to toddlers with ASD. The findings suggest that effective use of gestures by caregivers during caregiver-toddler activities can improve children's social responses.

3.
J Affect Disord ; 294: 128-136, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284318

RESUMO

BACKGROUND: We aimed to explore the risk profiles attributable to psychosocial and behavioural problems during the coronavirus disease 2019 pandemic. To this end, we created a risk-prediction nomogram model. METHODS: A national multicentre study was conducted through an online questionnaire involving 12,186 children (6-11 years old) and adolescents (12-16 years old). Respondents' psychosocial and behavioural functioning were assessed using the Achenbach Child Behaviour Checklist (CBCL). Data were analysed using STATA software and R-language. RESULTS: The positive detection rate of psychological problems within Wuhan was greater than that outside Wuhan for schizoid (P = 0.005), and depression (P = 0.030) in children, and for somatic complaints (P = 0.048), immaturity (P = 0.023), and delinquent behaviour (P = 0.046) in adolescents. After graded multivariable adjustment, seven factors associated with psychological problems in children and adolescents outside Wuhan were parent-child conflict (odds ratio (OR): 4.94, 95% confidence interval (95% CI): 4.27-5.72), sleep problems (OR: 4.05, 95% CI: 3.77-4.36), online study time (OR: 0.41, 95% CI: 0.37-0.47), physical activity time (OR: 0.510, 95% CI: 0.44-0.59), number of close friends (OR: 0.51, 95% CI: 0.44-0.6), time spent playing videogames (OR: 2.26, 95% CI: 1.90-2.69) and eating disorders (OR: 2.71, 95% CI: 2.35-3.11) (all P < 0.001). Contrastingly, within Wuhan, only the first four factors, namely, parent-child conflict (5.95, 2.82-12.57), sleep problems (4.47, 3.06-6.54), online study time (0.37, 0.22-0.64), and physical activity time (0.42, 0.22-0.80) were identified (all P < 0.01). Accordingly, nomogram models were created with significant attributes and had decent prediction performance with C-indexes over 80%. LIMITATION: A cross-sectional study and self-reported measures. CONCLUSIONS: Besides the four significant risk factors within and outside Wuhan, the three additional factors outside Wuhan deserve special attention. The prediction nomogram models constructed in this study have important clinical and public health implications for psychosocial and behavioural assessment.


Assuntos
COVID-19 , Comportamento Problema , Adolescente , Criança , Estudos Transversais , Humanos , Nomogramas , Pandemias , Fatores de Risco , SARS-CoV-2
4.
Transl Psychiatry ; 11(1): 342, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083509

RESUMO

This study aims to explore the psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools. In this national cross-sectional study, a total of 11072 students from China were naturally divided into two groups based on their schooling status: reopened schools (RS) and home schooling (HS) group. The psychosocial and behavioral functioning were measured by Achenbach Child Behaviour Checklist (CBCL) and compared in these two groups. Multivariable logistic regression analyses were conducted to explore the independent predictors associated with the psychosocial and behavioral problems. Our results showed that the students in the RS group had more adverse behaviors than that of HS group. The RS group had the higher rates of parent-offspring conflict, prolonged homework time, increased sedentary time and sleep problems (all p < 0.001). When separate analyses were conducted in boys and girls, the RS group had the higher scores for (1) overall behavioral problems (p = 0.02 and p = 0.01), internalizing (p = 0.02 and p = 0.02) and externalizing (p = 0.02 and p = 0.004) behaviors in the 6-11 age group; (2) externalizing (p = 0.049 and p = 0.006) behaviors in the 12-16 age group. Multivariable regression showed parent-offspring conflict and increased sedentary time were the most common risk factors, while physical activity and number of close friends were protective factors for behavior problems in RS students (p < 0.01 or 0.05). The present study revealed that students' psychosocial and behavioral problems increased in the early stage of schools reopened unexpectedly. These findings suggest that close attention must be paid and holistic strategies employed in the school reopening process of post-COVID-19 period.


Assuntos
COVID-19 , Comportamento Problema , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Instituições Acadêmicas
5.
Front Psychol ; 12: 604542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584473

RESUMO

Deficits in gestures act as early signs of impairment in social interaction (SI) and communication in children with autism spectrum disorder (ASD). However, the pieces of literature on atypical gesture patterns in ASD children are contradictory. This investigation aimed to explore the atypical gesture pattern of ASD children from the dimensions of quantity, communicative function, and integration ability; and its relationship with social ability and adaptive behavior. We used a semi-structured interactive play to evaluate gestures of 33 ASD children (24-48 months old) and 24 typically developing (TD) children (12-36 months old). And we evaluated the social ability, adaptive behavior, and productive language of ASD and TD children by using the Adaptive Behavior Assessment System version II (ABAS-II) and Chinese Communication Development Inventory (CCDI). No matter the total score of CCDI was corrected or not, the relative frequency of total gestures, behavior regulation (BR) gestures, SI gestures, and joint attention (JA) gestures of ASD children were lower than that of TD children, as well as the proportion of JA gestures. However, there was no significant group difference in the proportion of BR and SI gestures. Before adjusting for the total score of CCDI, the relative frequency of gestures without vocalization/verbalization integration and vocalization/verbalization-integrated gestures in ASD children was lower than that in TD children. However, after matching the total score of CCDI, only the relative frequency of gestures without vocalization/verbalization integration was lower. Regardless of the fact that the total score of CCDI was corrected or not, the relative frequency and the proportion of eye-gaze-integrated gestures in ASD children were lower than that in TD children. And the proportion of gestures without eye-gaze integration in ASD children was higher than that in TD children. For ASD children, the social skills score in ABAS-II was positively correlated with the relative frequency of SI gesture and eye-gaze-integrated gestures; the total score of ABAS-II was positively correlated with the relative frequency of total gestures and eye-gaze-integrated gestures. In conclusion, ASD children produce fewer gestures and have deficits in JA gestures. The deficiency of integrating eye gaze and gesture is the core deficit of ASD children's gesture communication. Relatively, ASD children might be capable of integrating vocalization/verbalization into gestures. SI gestures and the ability to integrate gesture and eye gaze are related to social ability. The quantity of gestures and the ability to integrate gesture with eye gaze are related to adaptive behavior. Clinical Trial Registration: www.ClinicalTrials.gov, identifier ChiCTR1800019679.

6.
J Autism Dev Disord ; 49(4): 1599-1612, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30542942

RESUMO

The Psychoeducational Profile 3rd Edition (PEP-3) is a comprehensive assessment tool designed for children with autism spectrum disorder (ASD). Although its original English version has been validated, few validation studies have been conducted on translated versions including Chinese ones. Based on 554 Chinese children with ASD and 311 typically developing Chinese children as the control group, this study investigated the psychometric properties of a simplified Chinese PEP-3 (sCPEP-3) in China mainland. Psychometric evaluation of the sCPEP-3 showed satisfactory internal consistency, test-retest reliability, inter-rater reliability, convergent validity, construct validity, and factorial validity. The findings have several implications such as utilizing the sCPEP-3 in mainland China for customized educational program planning, early identification, and evaluating the treatment effects for children with ASD.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Avaliação Educacional/normas , Testes Neuropsicológicos/normas , Tradução , Povo Asiático/psicologia , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes
7.
Psychiatry Res ; 267: 277-280, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29945069

RESUMO

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that shown a close association with impaired lipid metabolism. The acyl-carnitine spectrum status in Chinese children with ASD has not been reported. In this study, we assessed the levels of blood acyl-carnitines in Chinese children with ASD and examined the relation between acyl-carnitine profiles and the intelligence levels. Blood levels of acyl-carnitines were determined by tandem mass spectrometry in 60 children with ASD and 30 typically developing children. Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) was used in ASD group. Blood levels of free carnitine, glutaricyl carnitine, octyl carnitine, twenty four carbonyl carnitine and carnosyl carnitine in the ASD group were significantly lower than those in the control group. Glutaryl carnitine and carnosyl carnitine might be potential biomarkers for diagnosis of ASD. The changes in the acyl-carnitine spectrum indicate potential mitochondrial dysfunction and abnormal fatty acid metabolism in preschool ASD children.


Assuntos
Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/diagnóstico , Carnitina/análogos & derivados , Transtorno do Espectro Autista/epidemiologia , Biomarcadores/sangue , Carnitina/sangue , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Inteligência/fisiologia , Masculino , Transtornos do Neurodesenvolvimento/sangue , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia
8.
Obesity (Silver Spring) ; 26(1): 88-93, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29024521

RESUMO

OBJECTIVE: Abnormal fat metabolism is a major disorder in adults who were small for gestational age (SGA). Peroxisome prolferator-activated receptor (PPARγ) participates in adipocyte differentiation and the regulation of lipid metabolism. This study explored the role of PPARγ in the regulation of fat catch-up growth (CUG) and the lipid metabolism of SGA individuals. METHODS: The CUG-SGA rats were treated with pioglitazone. The weight of the visceral adipose tissue, serum lipid levels, and PPARγ expression in the visceral adipose tissue were detected at 4, 8, and 12 weeks of age. RESULTS: The PPARγ expression in the visceral adipose tissue in the CUG-SGA group was lower than that in the appropriate for gestational age (AGA) group at 4, 8, and 12 weeks (P < 0.05). The serum triglycerides in the CUG-SGA group were elevated compared with that in the AGA group at 4 and 12 weeks (P = 0.005; P = 0.037); however, they were significantly decreased after 8 weeks of pioglitazone intervention (P = 0.001). CONCLUSIONS: PPARγ expression in the visceral adipose tissue was lower in SGA rats and may be related to the regulation of adipocyte differentiation. The early increased PPARγ expression by pioglitazone might reduce serum triglycerides and decrease the CUG of the visceral adipose tissue in SGA.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Doenças Metabólicas/genética , PPAR gama/genética , Tiazolidinedionas/uso terapêutico , Adulto , Animais , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Masculino , Doenças Metabólicas/metabolismo , PPAR gama/metabolismo , Pioglitazona , Gravidez , Ratos , Ratos Sprague-Dawley , Tiazolidinedionas/farmacologia
9.
Neurosci Bull ; 33(2): 153-160, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28238115

RESUMO

The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder (ASD) in China's mainland. Children diagnosed with ASD (n = 1064, 228 females) were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). The results showed that girls scored significantly higher in ADI-R socio-emotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors (RRBs). Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys (P < 0.05). Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.


Assuntos
Transtorno do Espectro Autista , Deficiências do Desenvolvimento/etiologia , Caracteres Sexuais , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , China , Comunicação , Feminino , Humanos , Relações Interpessoais , Masculino , Fenótipo , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Estatísticas não Paramétricas , Comportamento Estereotipado/fisiologia
10.
BMC Psychiatry ; 17(1): 51, 2017 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-28166747

RESUMO

BACKGROUND: Researchers from several different countries have found the Social Responsiveness Scale (SRS) to have good psychometric properties. However, to our knowledge, no studies on this subject have been reported in Mainland China. In this study, we investigated the psychometric properties of the Chinese Mandarin version of the SRS when used in Mainland China. METHODS: The reliability and validity of the parent-report SRS in a sample of 749 children of 4- to 14-year-olds: 411 typically developing and 338 clinical participants (202 with autism spectrum disorder (ASD)) were examined. RESULTS: Internal consistency for total scale (0.871-0.922), test-retest reliability (0.81-0.94), and convergent validity with the Autism Behavior Checklist (ABC) (0.302-0.647) were satisfactory. The SRS total score discriminated between the ASD and other developmental disorders. Receiver operating characteristic (ROC) analyses revealed that the SRS was predicted to accurately classify 69.2-97.2% of youth ASD. Exploratory factor analysis (EFA) supported a single-factor solution for the ASD subsample. Confirmatory factor analysis (CFA) did not confirm the theoretical construct of five factors model with inadequate fit in the ASD subsample. CONCLUSIONS: Overall, our findings supported the reliability and validity of the parent-report SRS as one ASD screening instrument. In addition, we also suggest that the use of separate cut-offs for screening purposes (optimizing sensitivity) vs. clinical confirmation (optimizing specificity) should be considered.


Assuntos
Povo Asiático/psicologia , Transtorno do Espectro Autista/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Adolescente , Transtorno do Espectro Autista/psicologia , Estudos de Casos e Controles , Lista de Checagem , Criança , Pré-Escolar , China , Análise Fatorial , Feminino , Humanos , Idioma , Masculino , Psicometria , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Traduções
11.
Mol Med Rep ; 14(1): 888-96, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27222316

RESUMO

Yifuning is a traditional Chinese medicine recipe that has been used for many years in China for its effects on treating climacteric syndrome in women. The present study aimed to demonstrate the effects and underlying molecular mechanism of Yifuning on the ovaries of aging rats. Selected aging rats were administered different doses of Yifuning (1.0 or 2.0 g/kg by lavage), and after 6 weeks the rats were sacrificed. The activit of indicators of oxidative stress in the serum were measured. The expression levels of 8-oxo-2'-deoxyguanosine (8-OHDG) and p53 in the ovaries were examined using immunohistochemistry. The expression levels of the corresponding genes and proteins were detected by reverse transcription­quantitative polymerase chain reaction and western blotting analyses, respectively. The results indicated that Yifuning significantly prevented ovarian failure, as indicated by improvements in estrous cycling, reproductive organ weights and sex hormone serum levels. Yifuning significantly increased the levels of superoxide dismutase, glutathione peroxidase, catalase and reduced malondialdehyde and hydrogen peroxide levels. Yifuning reduced DNA damage in the ovaries by reducing the expression of 8­OHDG and p53. Treatment with Yifuning significantly reduced the age­induced p19, p53, p21 and Rb activity in the ovaries. The present study demonstrates that Yifuning prevents ovarian failure and the mechanism involved is partly associated with antioxidants and suppression of the Rb/p53 signal transduction pathway.


Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Envelhecimento , Animais , Catalase/metabolismo , Dano ao DNA/efeitos dos fármacos , Estradiol/sangue , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Progesterona/sangue , Ratos , Proteína do Retinoblastoma/genética , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética
12.
J Child Neurol ; 31(6): 733-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26690694

RESUMO

Autism spectrum disorder is a group of neurodevelopmental disorders with the higher prevalence in males. Our previous studies have indicated lower progesterone levels in the children with autism spectrum disorder, suggesting involvement of the cytochrome P-450scc gene (CYP11A1) and cytochrome P-45011beta gene (CYP11B1) as candidate genes in autism spectrum disorder. The aim of this study was to investigate the family-based genetic association between single-nucleotide polymorphisms, rs2279357 in the CYP11A1 gene and rs4534 and rs4541 in the CYP11B1 gene and autism spectrum disorder in Chinese children, which were selected according to the location in the coding region and 5' and 3' regions and minor allele frequencies of greater than 0.05 in the Chinese populations. The transmission disequilibrium test and case-control association analyses were performed in 100 Chinese Han autism spectrum disorder family trios. The genotype and allele frequency of the 3 single-nucleotide polymorphisms had no statistical difference between the children with autism spectrum disorder and their parents (P> .05). Transmission disequilibrium test analysis showed transmission disequilibrium of CYP11A1 gene rs2279357 single-nucleotide polymorphisms (χ(2)= 5.038,P< .001). Our findings provide further support for the hypothesis that a susceptibility gene for autism spectrum disorder exists within or near the CYP11A1 gene in the Han Chinese population.


Assuntos
Transtorno Autístico/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Saúde da Família , Polimorfismo de Nucleotídeo Único/genética , Esteroide 11-beta-Hidroxilase/genética , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , China , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Entrevista Psiquiátrica Padronizada
13.
Psychiatry Res ; 230(2): 255-61, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26384573

RESUMO

This study aimed to investigate the validity and reliability of the Chinese parent version of the Autism Spectrum Rating Scale (ASRS, 6-18 years) for a general sample of Chinese children. The study involved assessing 1625 community-based subjects aged 6-12 years from four sites (Shanghai, Guangzhou, Changsha, and Harbin city) in China and 211 clinic-based participants aged 6-18 with a confirmed diagnosis of autism spectrum disorders (ASDs). The internal consistency (Cronbach's alpha) ranged from 0.585 to 0.929, and the test-retest reliability (interclass correlations) ranged from 0.542 to 0.749, indicating no significant difference between the two tests at an interval of 2-4 weeks. The construct validity was relatively excellent, and the concurrent validity with the Social Responsiveness Scale (SRS) (Pearson correlations) was 0.732 between the two total scores. Receiver operating characteristics (ROC) analyses showed excellent and comparable discriminant validity of the ASRS with respect to the SRS, with an area under the curve (AUC) of 0.9507 (95% CI: 0.93-0.97) versus 0.9703 (95% CI: 0.96-0.98), respectively. Our data suggested a cutoff ≥60 for the Chinese version of the ASRS, with good accuracy in screening autism symptoms (sensitivity=94.2%, specificity=77%). The Chinese parent version of the ASRS is therefore a reliable and valid tool for screening autistic symptoms in Chinese children in general.


Assuntos
Povo Asiático/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Pais/psicologia , Inquéritos e Questionários/normas , Adolescente , Transtorno do Espectro Autista/epidemiologia , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes
14.
J Hematol Oncol ; 8: 26, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25886453

RESUMO

BACKGROUND: Aloperine, a natural alkaloid constituent isolated from the herb Sophora alopecuroides displays anti-inflammatory properties in vitro and in vivo. Our group previously demonstrated that aloperine significantly induced apoptosis in colon cancer SW480 and HCT116 cells. However, its specific target(s) remain to be discovered in multiple myeloma (MM) and have not been investigated. METHODS: Human myeloma cell lines (n = 8), primary myeloma cells (n = 12), drug-resistant myeloma cell lines (n = 2), and animal models were tested for their sensitivity to aloperine in terms of proliferation and apoptosis both in vitro and in vivo, respectively. We also examined the functional mechanisms underlying the apoptotic pathways triggered by aloperine. RESULTS: Aloperine induced MM cell death in a dose- and time-dependent manner, even in the presence of the proliferative cytokines interleukin-6 and insulin-like growth factor I. Mechanistic studies revealed that aloperine not only activated caspase-8 and reduced the expression of FADD-like interleukin-1ß-converting enzyme (FLICE)-like inhibitory protein long (FLIPL) and FLICE-inhibitory proteins (FLIPS) but also activated caspase-9 and decreased the expression of phosphorylated (p)-PTEN. Moreover, co-activation of the caspase-8/cellular FLICE-inhibitory protein (cFLIP)- and caspase-9/p-PTEN/p-AKT-dependent apoptotic pathways by aloperine caused irreversible inhibition of clonogenic survival. Aloperine induce more MM apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or borterzomib. A U266 xenograft tumor model and 5T33 MM cells recapitulated the antitumor efficacy of aloperine, and the animals displayed excellent tolerance of the drug and few adverse effects. CONCLUSIONS: Aloperine has multifaceted antitumor effects on MM cells. Our data support the clinical development of aloperine for MM therapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Mieloma Múltiplo/patologia , Piperidinas/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Quinolizidinas , RNA Interferente Pequeno , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Child Neurol ; 30(13): 1794-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25873587

RESUMO

Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental disorders that have strong heritability. To better understand the heritable factors in twins with clinically diagnosed ASD and to discuss the relationship between social impairments and genetic and environmental factors. In last 13 years, over 12,000 cases of ASD were diagnosed in the children's development and behavior center, the authors review 37 pairs of these twins, in each pair, and at least 1 twin had been diagnosed with an ASD, and found that the concordance rate was 80% [95% confidence interval (CI) 51.9-95.7%] for monozygotic twins and 13.6% (95% CI: 2.9-34.9%) for dizygotic twins. The heritability of social impairments for ASD was 60.9% (95% CI: 47.3-74.5%). In addition, the rate of nonshared environmental factors was 39.1% (95% CI: 25.5-52.7%), and there were no shared environmental effects. Genetics and special environmental effect play an important role on ASD social impairments.


Assuntos
Transtorno do Espectro Autista/genética , Criança , Pré-Escolar , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Modelos Genéticos , Caracteres Sexuais , Gêmeos Dizigóticos , Gêmeos Monozigóticos
16.
PLoS One ; 9(6): e100459, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24963636

RESUMO

OBJECTIVE: Insulin resistance has been observed in individuals born small for gestational age (SGA) with catch-up growth (CUG), yet the mechanisms involved remain unclear. This study examined the role of GH and insulin signaling crosstalk in insulin resistance of SGA rats with CUG. DESIGN AND METHODS: SGA rats were developed by dietary restriction in pregnant rats. GH receptor inhibition was performed on four-week old CUG-SGA and AGA rats. Phosphorylation of IRS-1, AKT, and ERK, and expression of SOCS3 in the skeletal muscle were determined via immunoblot analysis at baseline and after insulin stimulation in CUG-SGA, NCUG-SGA and AGA groups. RESULTS: Compared to AGA controls, phosphorylation of IRS-1 and AKT in response to insulin stimulation in CUG-SGA rats was significantly blunted (P<0.05), and phosphorylation of ERK at baseline was dramatically activated (P<0.05). SOCS3 expression was significantly increased in CUG-SGA compared to AGA (P = 0.001) and NCUG-SGA (P = 0.006) rats, and was significantly suppressed following GHR inhibition (P<0.05). Furthermore, phosphorylation of IRS-1 and AKT in response to insulin stimulation increased after GHR inhibition (P<0.05). CONCLUSIONS: Insulin resistance in CUG-SGA rats is associated with impairment of IRS-1-PI3K-AKT signaling, which may result from GH signaling-induced up-regulation of SOCS3.


Assuntos
Peso ao Nascer , Idade Gestacional , Receptor Cross-Talk , Receptor de Insulina/metabolismo , Receptores da Somatotropina/metabolismo , Transdução de Sinais , Animais , Feminino , Regulação da Expressão Gênica , Resistência à Insulina , Masculino , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley
17.
Int J Mol Med ; 33(6): 1613-20, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24682388

RESUMO

Aloperine (ALO) is a quinolizidine alkaloid extracted from the leaves of Sophora alopecuroides (S. alopecuroides) and possesses anti-inflammatory, anti-allergenic, antitumor, and antiviral effects. In this study, when compared with seven other types of alkaloids extracted from S. alopecuroides, ALO treatment produced the most potent effects against HCT116 colon cancer cell types. ALO inhibited proliferation and induced apoptosis in HCT116 cells in a dose- and time-dependent manner as detected by MTT, clonogenic survival, and flow cytometric assays. Results of the western blot analysis and qPCR revealed that ALO increased the protein and mRNA of Bax and decreased Bcl-2 via the mitochondrial death pathway. In addition, ALO induced cell cycle arrest at the G2/M phase with a concomitant increase in p21 and p53 and a decrease in cyclin D1 and B1. ALO also inhibited phosphatidylinositol 3-kinase/Akt and JAK/Stat3. Generally, ALO exerted a significant anti-proliferative effect via apoptotic and cell cycle arrest induction in HCT116 cells. These results suggested that ALO should be investigated further as an agent of chemotherapeutic activity in human colon cancer.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Piperidinas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Divisão Celular/genética , Ciclina B1/genética , Ciclina B1/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fase G2/genética , Células HCT116 , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Quinolizidinas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
18.
Nutr Metab (Lond) ; 9(1): 107, 2012 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-23186039

RESUMO

BACKGROUND AND OBJECTIVE: The study was performed to determine whether catch-up growth is associated with the development of insulin resistance and to explore serum endocrine markers associated with the metabolism of adipose tissue in a Chinese population born small for gestational age(SGA) SUBJECTS AND METHODS: We recruited 56 children born SGA with catch-up growth and 55 born without catch-up growth, who were further grouped into groups I (with BMI catch-up) and II (without BMI catch-up) respectively, as well as 52 children born appropriate for gestational age (AGA) with normal height. Their serum fasting insulin, fasting glucose, insulin-like growth factor-1, adiponectin, IGFBP-1, triglyceride concentrations, and the homeostasis assessment model for insulin resistance (HOMA-IR) were evaluated. RESULTS: (1) The HOMA-IR values in SGA-I with catch-up growth group were significantly higher than those in SGA-II with catch-up growth, SGA-I without catch-up growth and AGA children respectively. (2) The serum adiponectin levels of individuals in the SGA-I without catch-up growth and SGA-II with catch-up growth groups were significantly lower than those from the SGA-II without catch-up growth group. There was no difference in triglyceride or IGFBP-1 levels among the groups. (3) The degree of HOMA-IR was positively correlated with age, current BMI and △height SDS in SGA children. CONCLUSION: The development of insulin resistance and lower levels of adiponectin were closely correlated with higher BMI and the postnatal height catch-up growth in SGA children.

19.
Life Sci ; 91(25-26): 1295-303, 2012 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-23069582

RESUMO

AIMS: To further investigate the anti-colorectal carcinoma (CRC) effect of Sophoridine (SRI) which is a quinolizidine alkaloid extracted from a traditional Chinese medicine (TCM) Sophora alopecuroides L. and detect the mechanism involved, provide some basis for the development of S. alopecuroides L. MAIN METHODS: The anti-proliferation of SRI in human colorectal cells SW480 were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. The potential mechanism of anti-proliferation was also investigated using apoptosis assays. The rate of apoptosis cells was detected also. The apoptosis-related proteins cysteinyl aspartate specific protease (caspase), caspase-3, caspase-7, caspase-9, and poly-ADP-ribose-poly-merase (PARP) were determined by western blotting analysis. In animal studies, nude mice were subcutaneously injected with SW480 cells in the armpit to establish the xenograft tumors and administrated with different drugs (control, 5-Fu, SRI H, and SRI L). The general state of health of the mice and the growth of tumors were observed and the inhibitory rate was calculated. The pathology and ultrastructure of xenograft tumors treated with SRI were observed also. KEY FINDINGS: SRI significantly inhibited the growth of SW480 cells, and the administration of SRI significantly inhibited the growth of xenograft tumors without apparent toxicity. SRI's mechanism of action involved the induction of apoptosis. SIGNIFICANCE: These results suggest that SRI produces obvious anti-tumor effects in vitro and in vivo. It supports the viability of developing SRI as a novel therapeutic prodrug for CRC treatment, as well as providing a method for identifying new anti-tumor drugs in TCM.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Quinolizinas/farmacologia , Sophora/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Western Blotting , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Nus , Poli(ADP-Ribose) Polimerases/metabolismo , Quinolizinas/isolamento & purificação , Ensaios Antitumorais Modelo de Xenoenxerto , Matrinas
20.
Horm Res Paediatr ; 78(3): 180-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23051822

RESUMO

BACKGROUND/AIM: This study was designed to evaluate the effects of a high-protein (HP) diet on insulin resistance and body fat in catch-up growth (CUG) rats born small for gestational age (SGA). METHODS: SGA rats were randomly divided into standard diet and HP diet groups. Perirenal fat weight and blood glucose, serum insulin and insulin-like growth factor-1 levels were measured at 4 and/or 8 weeks. Insulin resistance and ß-cell function were evaluated by homeostatic model assessment for insulin resistance (HOMA-IR) and HOMA%. RESULTS: The values of HOMA-IR in both CUG-SGA groups were significantly higher than those in the appropriate for gestational age (AGA) group (p < 0.01), whereas they were significantly lower in the HP diet CUG-SGA group than in the standard diet CUG-SGA group at week 8 (p < 0.01). At week 8, perirenal fat weight and adipocyte diameters were higher in both CUG-SGA groups than in the AGA group (p < 0.05), but these values were significantly lower in the HP diet CUG-SGA group than in the standard diet CUG-SGA group (p < 0.05). CONCLUSION: The HP diet had positive effects on the prevention of insulin resistance, which may have been caused by the reduction of body fat.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/microbiologia , Proteínas Alimentares/farmacologia , Resistência à Insulina , Adipócitos/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Células Secretoras de Insulina/metabolismo , Masculino , Modelos Biológicos , Ratos , Ratos Sprague-Dawley
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