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1.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783706

RESUMO

RNA Polymerase II (Pol II) transcriptional elongation pausing is an integral part of the dynamic regulation of gene transcription in the genome of metazoans. It plays a pivotal role in many vital biological processes and disease progression. However, experimentally measuring genome-wide Pol II pausing is technically challenging and the precise governing mechanism underlying this process is not fully understood. Here, we develop RP3 (RNA Polymerase II Pausing Prediction), a network regularized logistic regression machine learning method, to predict Pol II pausing events by integrating genome sequence, histone modification, gene expression, chromatin accessibility, and protein-protein interaction data. RP3 can accurately predict Pol II pausing in diverse cellular contexts and unveil the transcription factors that are associated with the Pol II pausing machinery. Furthermore, we utilize a forward feature selection framework to systematically identify the combination of histone modification signals associated with Pol II pausing. RP3 is freely available at https://github.com/AMSSwanglab/RP3.


Assuntos
Código das Histonas , RNA Polimerase II , RNA Polimerase II/metabolismo , Humanos , Elongação da Transcrição Genética , Cromatina/metabolismo , Cromatina/genética , Histonas/metabolismo , Aprendizado de Máquina , Animais
2.
Am Heart J ; 273: 90-101, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38575049

RESUMO

BACKGROUND: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multifaceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. MATERIALS AND METHODS: The CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. Forty-one primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1,600 patients aged 35 to 80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants' characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12 months. DISCUSSION: The CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, NCT05605418.


Assuntos
Hipertensão , Atenção Primária à Saúde , Humanos , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Adulto , Idoso , Sistemas de Apoio a Decisões Clínicas , Telemedicina , Smartphone , Idoso de 80 Anos ou mais , Monitorização Ambulatorial da Pressão Arterial/métodos , Sistemas de Alerta
3.
Fam Process ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749926

RESUMO

Due to the rapid sociocultural changes in China, Chinese parents' childrearing beliefs and practices have undergone dramatic transformations. Against this context, this study examined whether Chinese parents' endorsement of progressive and traditional childrearing beliefs would predict children's academic achievement, as well as whether parenting practices would mediate this association. This study utilized a longitudinal design and followed 206 Chinese families for 2 years from the end of preschool to Grade 2. Parents showed greater endorsement of progressive than traditional childrearing beliefs, as well as higher use of authoritative than authoritarian parenting practices. Parents' childrearing beliefs in preschool predicted children's math achievement in Grade 2 via authoritative parenting. However, parenting beliefs were unrelated to authoritarian parenting, and authoritarian parenting did not predict any of the child academic outcomes in Grade 2. The findings suggest Chinese parents' orientations toward progressive parenting beliefs and authoritative parenting practices. They also highlight the utility of parenting beliefs in explaining disparities in early academic achievement. The nonsignificant findings pertinent to authoritarian parenting call for re-examination of the cultural meaning and effects of authoritarian parenting in Chinese society.

4.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33048117

RESUMO

The DNA methyltransferases (DNMTs) (DNMT3A, DNMT3B and DNMT3L) are primarily responsible for the establishment of genomic locus-specific DNA methylation patterns, which play an important role in gene regulation and animal development. However, this important protein family's binding mechanism, i.e. how and where the DNMTs bind to genome, is still missing in most tissues and cell lines. This motivates us to explore DNMTs and TF's cooperation and develop a network regularized logistic regression model, GuidingNet, to predict DNMTs' genome-wide binding by integrating gene expression, chromatin accessibility, sequence and protein-protein interaction data. GuidingNet accurately predicted methylation experimental data validated DNMTs' binding, outperformed single data source based and sparsity regularized methods and performed well in within and across tissue prediction for several DNMTs in human and mouse. Importantly, GuidingNet can reveal transcription cofactors assisting DNMTs for methylation establishment. This provides biological understanding in the DNMTs' binding specificity in different tissues and demonstrate the advantage of network regularization. In addition to DNMTs, GuidingNet achieves good performance for other chromatin regulators' binding. GuidingNet is freely available at https://github.com/AMSSwanglab/GuidingNet.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Metilação de DNA/genética , Regulação Enzimológica da Expressão Gênica , Genoma Humano , Modelos Biológicos , Mapas de Interação de Proteínas , Fatores de Transcrição , Animais , Cromatina/genética , Cromatina/metabolismo , DNA (Citosina-5-)-Metiltransferases/biossíntese , DNA (Citosina-5-)-Metiltransferases/genética , Bases de Dados Genéticas , Humanos , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Mol Phylogenet Evol ; 181: 107704, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36657625

RESUMO

The present study aimed to apply bioinformatic methods to analyze the structure of the S protein of human respiratory coronaviruses, including severe respiratory disease syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus HKU1 (HCoV-HKU1), and severe respiratory disease syndrome coronavirus type 2 (SARS-CoV-2). We predicted and analyzed the physicochemical properties, hydrophilicity and hydrophobicity, transmembrane regions, signal peptides, phosphorylation and glycosylation sites, epitopes, functional domains, and motifs of the S proteins of human respiratory coronaviruses. All four S proteins contain a transmembrane region, which enables them to bind to host cell surface receptors. All four S proteins contain a signal peptide, phosphorylation sites, glycosylation sites, and epitopes. The predicted phosphorylation sites might mediate S protein activation, the glycosylation sites might affect the cellular orientation of the virus, and the predicted epitopes might have implications for the design of antiviral inhibitors. The S proteins of all four viruses have two structural domains, S1 (C-terminal and N-terminal domains) and S2 (homology region 1 and 2). Our bioinformatic analysis of the structural and functional domains of human respiratory coronavirus S proteins provides a basis for future research to develop broad-spectrum antiviral drugs, vaccines, and antibodies.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , SARS-CoV-2 , Filogenia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Biologia Computacional
6.
Anim Biotechnol ; 34(4): 1305-1313, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34985384

RESUMO

This study aimed to explore the genetic basis of muscle development in goats. The transcriptome dataset for differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) of goat muscle at different developmental stages were obtained using RNA-Seq. A total of 447,806,481 and 587,559,465 clean reads in the longissimus dorsi muscle of Dazu black goats between 75d embryonic stage and 1d after birth were generated through Illumina paired-end sequencing, and their mapping rates were 89.82 and 90.99%, respectively. Moreover, 4517 DEGs and 648 DELs were identified, and 4784 lncRNA-mRNA targeting relationships were predicted. Gene function annotation results showed that 4101 DEGs were significantly enriched to 1098 GO terms, and 2014 DEGs were significantly enriched to 40 KEGG pathways, including many GO terms and pathways related to muscle development, such as cell differentiation and Wnt signaling pathway. Then, 10 DELs and 20 DEGs were randomly selected for RT-qPCR verification, and the agreement rate between the verification and RNA-Seq results was 90%, indicating the high reliability of the RNA-Seq data analysis. In conclusion, this study obtained several mRNAs and lncRNAs related to the muscle development of Dazu black goats and identified several targeted regulatory pairs of lncRNA-mRNA. This study may serve as a reference to understand the genetic basis and molecular mechanism of muscle development in goats.


Assuntos
RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica/veterinária , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Cabras/genética , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Análise de Sequência de RNA/veterinária , Desenvolvimento Muscular/genética
7.
Int J Psychol ; 58(3): 227-236, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36754862

RESUMO

China has experienced dramatic transformations over recent decades, which has significant implications for childrearing. This study examined whether Chinese parents' perceived social change would mediate the association between family socioeconomic status (SES) and children's involvement in various learning activities in the home, community and extracurricular contexts. The study included 312 urban Chinese parents with preschool-aged children. Parents completed measures on perceived social change, their involvement in children's home literacy, numeracy and play activities, as well as children's participation in community-based activities and commercially provided extracurricular activities (EAs). The results indicated that higher-SES parents perceived more opportunities and prospects and less work-related risk and adversity as a function of social change. Parents who perceived more opportunities and prospects were more involved in almost all types of children's learning activities except EAs. Parents who perceived more work-related risk and adversity only showed decreased involvement in home literacy activities. Parents who endorsed new values more strongly were more likely to enrol their children in EAs and demonstrate greater involvement in children's home literacy activities. The findings revealed substantial within-group variations in parents' subjective experiences with social change and how parents' perceived social change might shape their ways of organising children's learning environment.


Assuntos
Aprendizagem , Mudança Social , Pré-Escolar , Humanos , População do Leste Asiático , Alfabetização , Pais
8.
Cancer Cell Int ; 21(1): 323, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183010

RESUMO

BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. RESULTS: MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. CONCLUSION: These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

9.
Child Dev ; 92(3): 1028-1047, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32840884

RESUMO

Organized extracurricular activities (EAs) are prevalent among Chinese preschoolers, yet their role in children's development is poorly understood. This study investigated the relations between EA participation and Chinese preschoolers' school readiness (N = 343; Mage  = 55.14 months) among a predominantly middle-class sample. EA breadth had positive linear relations with children's early math and social skills, while attendance intensity demonstrated nonlinear associations, partially supporting the overscheduling hypothesis. EA breadth had stronger associations with early reading and math skills among lower socioeconomic status children, as well as greater benefits for math skills in children with less exposure to home learning activities, indicating a compensatory role of EAs. The findings highlight the interplay between EA and family contexts in relation to child development.


Assuntos
Desenvolvimento Infantil , Leitura , Criança , Pré-Escolar , China , Humanos , Matemática , Instituições Acadêmicas
10.
Fam Process ; 60(1): 216-234, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32294798

RESUMO

Family socioeconomic status (SES) has been frequently linked to children's early development. Treating SES as an aggregated variable has many issues, as different components of SES may relate to child outcomes through divergent mechanisms. The purpose of the study was to examine whether parents' engagement in home learning activities and children's participation in extracurricular activities (EAs) would function as pathways through which individual SES components related to children's school readiness. A total of 588 families with preschool-aged children were recruited from Guangdong province in China. Children's receptive vocabulary, Chinese reading, and early math skills were individually assessed at three time points, and children's social skills were rated by parents. Parents reported their engagement in home learning activities with children and their children's participation in EAs. The results showed that all three components of family SES were related to multiple aspects of children's school readiness, but through different pathways. Parental income was related to children's school readiness through EA participation only; parental education and occupational status were associated with school readiness via both parental engagement and child EA participation. The findings suggest that considering SES components separately will produce a more nuanced understanding of the divergent pathways through which family SES may relate to children's school readiness. Chinese government may provide parent education programs focused on cognitive stimulation for low-SES families to promote children's school readiness. Furthermore, the government needs to ensure children's equal access to EAs to prevent increasing the developmental gap among children from discrepant socioeconomic backgrounds.


El nivel socioeconómico familiar se ha asociado frecuentemente con el desarrollo de la primera infancia. Tratar el nivel socioeconómico familiar como una variable agregada tiene muchos problemas, ya que los diferentes componentes del nivel socioeconómico familiar pueden relacionarse con los resultados de los niños mediante diferentes mecanismos. El propósito del estudio fue analizar si la participación de los padres en actividades de aprendizaje en el hogar y la participación de los niños en actividades extracurriculares funcionan como vías por las cuales los componentes individuales del nivel socioeconómico se relacionan con la madurez de los niños para la escolaridad. Se convocó a un total de 588 familias con niños en edad preescolar de la provincia de Cantón en China. Se evaluaron individualmente el vocabulario receptivo de los niños, la lectura en chino y las habilidades matemáticas iniciales en tres intervalos de tiempo, y los padres calificaron las habilidades sociales de los niños. Los padres informaron su participación en actividades de aprendizaje en el hogar con los niños y la participación de sus hijos en actividades extracurriculares. Los resultados demostraron que los tres componentes del nivel socioeconómico familiar estuvieron relacionados con varios aspectos de la madurez de los niños para la escolaridad, pero mediante diferentes vías. Los ingresos de los padres estuvieron relacionados con la madurez de los niños para la escolaridad mediante la participación en actividades extracurriculares solamente; la educación de los padres y la situación ocupacional estuvieron asociadas con la madurez para la escolaridad mediante la participación de los padres y la participación de los niños en actividades extracurriculares. Los resultados sugieren que tener en cuenta los componentes del nivel socioeconómico por separado producirá una comprensión más sutil de las diversas vías mediante las cuales el nivel socioeconómico de la familia puede relacionarse con la madurez de los niños para la escolaridad. El gobierno chino puede proporcionar programas de capacitación para padres centrados en la estimulación cognitiva para familias de bajo nivel socioeconómico a fin de promover la madurez de los niños para la escolaridad. Además, el gobierno necesita garantizar el acceso equitativo de los niños a las actividades extracurriculares para evitar el aumento de la brecha en el desarrollo entre niños de diferentes orígenes socioeconómicos.


Assuntos
Pais , Classe Social , Criança , Pré-Escolar , China , Humanos , Relações Pais-Filho , Instituições Acadêmicas
11.
New Dir Child Adolesc Dev ; 2019(163): 9-37, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30615267

RESUMO

This chapter addresses how child-, family-, and school-level characteristics are associated with Chinese children's academic skill development during their preschool years. Academic skills are defined in terms of young children's emergent competencies in academic domains including literacy, mathematics, and science. First, we review the relations of young Chinese children's cognition (language, visuospatial, and executive functioning), behavior (social behavior and behavioral regulation), and affect (interest and attitude) to their performance in these academic domains. Second, we review the roles of familial variables, including family socioeconomic status and broad and specific aspects of parenting practices and parental involvement. Third, we review school- and classroom-level factors, with a special emphasis on preschool and classroom quality that is particularly relevant to young Chinese children's academic skills. We discuss the educational implications of these study findings and identify methodological limitations that may threaten their internal and external validity. Our aim is to bring attention to the growing body of research on young Chinese children's academic skill development and to highlight several areas that need further research.


Assuntos
Povo Asiático/psicologia , Função Executiva , Aprendizagem , Relações Pais-Filho/etnologia , Criança , Desenvolvimento Infantil , Pré-Escolar , China , Cognição , Escolaridade , Feminino , Humanos , Masculino , Poder Familiar , Instituições Acadêmicas , Meio Social , Fatores Socioeconômicos
12.
Appl Environ Microbiol ; 84(8)2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29427423

RESUMO

Streptococcus suis, a global zoonosis of pigs, shows regional differences in the prevalence of human-associated disease for Asian and non-Asian countries. The isolation rates and diversities of S. suis on tonsils of healthy slaughter pigs in China and the United Kingdom were studied for effects of geography, temperature, pig age, and farm type. Isolates underwent analysis of molecular serotype and multilocus sequence type and virulence-associated genotyping. Although we found no significant difference in positive isolation rates between Chinese and UK farms, the prevalences of serotypes previously associated with human disease were significantly greater in the Chinese collection (P = 0.003). A significant effect of temperature was found on the positive isolation rate of the Chinese samples and the prevalence of human disease-associated serotypes in the UK S. suis population (China, P = 0.004; United Kingdom, P = 0.024) and on the prevalence of isolates carrying key virulence genes in China (P = 0.044). Finally, we found marked diversity among S. suis isolates, with statistically significant temperature effects on detection of multiple strain types within individual pigs. This study highlighted the high carriage prevalence and diversity of S. suis among clinically healthy pig herds of China and the United Kingdom. The significant effect of temperature on prevalence of isolation, human disease-associated serotypes, and diversity carried by individual pigs may shed new light on geographic variations in human S. suis-associated disease.IMPORTANCEStreptococcus suis is a global zoonotic pathogen and also a normal colonizer mainly carried on the tonsil of pigs. Thus, it is important to study the effect of environmental and management-associated factors on the S. suis populations in clinically healthy pigs. In this research, we investigated the similarities and differences between the S. suis populations obtained from different pig ages, seasons, and farm management systems and discovered the relationship between high climatic temperature and the prevalence of S. suis.


Assuntos
Criação de Animais Domésticos/métodos , Variação Genética , Infecções Estreptocócicas/veterinária , Streptococcus suis/fisiologia , Doenças dos Suínos/epidemiologia , Fatores Etários , Animais , China/epidemiologia , Genoma Bacteriano , Estudos Longitudinais , Prevalência , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Suínos , Doenças dos Suínos/microbiologia , Temperatura , Reino Unido/epidemiologia
13.
Lipids Health Dis ; 15(1): 127, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27514378

RESUMO

BACKGROUND: Beta defensins are secreted from ovine oviduct epithelial cells (OOECs) in response to microbial infection, and are potential alternatives to antibiotic agents in the treatment of microorganism infection, particularly given the abuse of antibiotic agents and the increasing number of drug-resistant bacteria. The aberrant expression of defensins may result in disorders involving organ and oviduct inflammation, such as salpingitis. METHODS: In the present study, we investigated the effects of LPS on the mRNA expression levels of sheep ß-defensin-1 (SBD-1) in ovine oviduct epithelial cells. The OOECs in vitro culturing system were established and treated with different concentrations of LPS for indicated time. In addition, MAPK inhibitors and TLR4 antibodies were pretreated to investigate the potential mechanism which involves in LPS regulating SBD-1 expression. RESULTS: LPS markedly upregulated SBD-1 expression in a concentration- and time-dependent manner. Treatment with 100 ng/mL LPS resulted in the phosphorylation of JNK, ERK and P38 MAPK. Interestingly, the LPS stimulated SBD-1 expression was attenuated by pretreatment with the P38 MAPK inhibitors SB203580 and SB202190 but not the JNK inhibitor SP600125, while the ERK inhibitor PD98059 had a minor effect. Furthermore, treatment with a Toll-like receptor 4 (TLR4) neutralizing antibody significantly decreased P38 MAPK phosphorylation and LPS induced SBD-1 expression. CONCLUSIONS: Together, these findings suggest that SBD-1 is upregulated by LPS via the TLR4 receptor, mainly through the P38 MAPK signaling pathway in ovine oviduct epithelial cells to protect the ovine oviduct epithelium from pathogen invasion.


Assuntos
Tubas Uterinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ovinos , beta-Defensinas/genética , Animais , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , Fosforilação , RNA Mensageiro/análise , Receptor 4 Toll-Like/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
14.
BMC Cancer ; 14: 308, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24885368

RESUMO

BACKGROUND: Androgen deprivation therapy is the primary strategy for the treatment of advanced prostate cancer; however, after an initial regression, most patients will inevitably develop a fatal androgen-independent tumor. Therefore, understanding the mechanisms of the transition to androgen independence prostate cancer is critical to identify new ways to treat older patients who are ineligible for conventional chemotherapy. METHODS: The effects of 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the viability and the apoptosis of the androgen-dependent (LNCaP) and androgen-independent (PC3) cell lines were examined by MTS assay and western blot analysis for the activation of caspase-3. The subcutaneous LNCaP xenografts were established in a nude mice model. MiR-146a and DNMTs expressions were analyzed by qRT-PCR and DNA methylation rates of LINE-1 were measured by COBRA-IRS to determine the global DNA methylation levels. The methylation levels of miR-146a promoter region in the different groups were quantified by the bisulfite sequencing PCR (BSP) assay. RESULTS: We validated that 5-Aza-CdR induced cell death and increased miR-146a expression in both LNCaP and PC3 cells. Notably, the expression of miR-146a in LNCaP cells was much higher than in PC3 cells. MiR-146a inhibitor was shown to suppress apoptosis in 5-Aza-CdR-treated cells. In a castrate mouse LNCaP xenograft model, 5-Aza-CdR significantly suppressed the tumors growth and also inhibited prostate cancer progression. Meanwhile, miR-146a expression was significantly enhanced in the tumor xenografts of 5-Aza-CdR-treated mice and the androgen-dependent but not the androgen-independent stage of castrated mice. In particular, the expression of miR-146a was significantly augmented in both stages of the combined treatment (castration and 5-Aza-CdR). Additionally, the methylation percentage of the two CpG sites (-444 bp and -433 bp), which were around the NF-κB binding site at miR-146a promoter, showed the lowest methylation levels among all CpG sites in the combined treatment tumors of both stages. CONCLUSION: Up-regulating miR-146a expression via the hypomethylation of the miR-146a promoter by 5-Aza-CdR was correlated with delayed progression of castration-resistant prostate cancers. Moreover, site-specific DNA methylation may play an important role in miR-146a expression in androgen-dependent prostate cancer progression to androgen-independent prostate cancer and therefore provides a potentially useful biomarker for assessing drug efficacy in prostate cancer.


Assuntos
Azacitidina/análogos & derivados , Metilação de DNA/genética , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Animais , Apoptose/efeitos dos fármacos , Azacitidina/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Decitabina , Progressão da Doença , Humanos , Masculino , Metiltransferases/genética , Camundongos , Regiões Promotoras Genéticas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Comput Biol Med ; 171: 108182, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422958

RESUMO

Cell-type-Specific Chromatin Loops (CSCLs) are crucial for gene regulation and cell fate determination. However, the mechanisms governing their establishment remain elusive. Here, we present SpecLoop, a network regularization-based machine learning framework, to investigate the role of transcription factors (TFs) cooperation in CSCL formation. SpecLoop integrates multi-omics data, including gene expression, chromatin accessibility, sequence, protein-protein interaction, and TF binding motif data, to predict CSCLs and identify TF cooperations. Using high resolution Hi-C data as the gold standard, SpecLoop accurately predicts CSCL in GM12878, IMR90, HeLa-S3, K562, HUVEC, HMEC, and NHEK seven cell types, with the AUROC values ranging from 0.8645 to 0.9852 and AUPR values ranging from 0.8654 to 0.9734. Notably SpecLoop demonstrates improved accuracy in predicting long-distance CSCLs and identifies TF complexes with strong predictive ability. Our study systematically explores the TFs and TF pairs associated with CSCL through effective integration of diverse omics data. SpecLoop is freely available at https://github.com/AMSSwanglab/SpecLoop.


Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sítios de Ligação/genética , Cromatina/genética , Ligação Proteica
16.
J Fam Psychol ; 38(4): 606-617, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38252086

RESUMO

Grandparental involvement in childrearing has been associated with children's social-emotional development, yet findings are mixed. Grandparental involvement is a multidimensional concept that includes both quantity (i.e., the degree of grandparental involvement) and quality aspects (i.e., the quality of parent-grandparent coparenting and the quality of grandparenting practices). This study included both quantity and quality aspects to identify heterogeneous patterns of grandparental involvement and examined the associations between distinct patterns of grandparental involvement and children's social-emotional outcomes. Participants were 428 families with Chinese preschoolers (Mage = 53.75 months, SD = 10.32; 51.4% boys). Primary parental and grandparental caregivers completed the questionnaires. Four patterns of grandparental involvement emerged: the low-involvement mediocre-quality, the median, the high-involvement uneven-quality, and the high-involvement high-quality groups. Heterogeneous patterns of grandparental involvement exist and are differentially associated with children's social-emotional development. Children with grandparents in the high-involvement high-quality group demonstrated higher levels of social skills than those in the low-involvement mediocre-quality group and the high-involvement uneven-quality group. They also showed the lowest level of problem behaviors. This study highlights variations in grandparental involvement and helps to clarify previous inconsistent findings regarding the role of grandparental involvement in child development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Desenvolvimento Infantil , Educação Infantil , Avós , Humanos , Masculino , Feminino , Avós/psicologia , Pré-Escolar , Desenvolvimento Infantil/fisiologia , Educação Infantil/psicologia , Educação Infantil/etnologia , Poder Familiar/psicologia , China , Relação entre Gerações , Emoções/fisiologia , Adulto , População do Leste Asiático
17.
J Sch Psychol ; 101: 101250, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37951663

RESUMO

Participation in organized extracurricular activities (EAs) has become increasingly common among preschool-aged children. Prior studies have shown inconsistent findings on the association between young children's involvement in EAs and their subsequent developmental outcomes. Moving beyond examining the main effects of EA participation, this study focused on whether children's behavioral regulation and approaches to learning-two important domain-general skills closely linked to learning-would moderate the association between EA participation and academic readiness. Participants included 317 Chinese preschoolers residing in Shanghai. The breadth of EA participation positively predicted children's early math skills, but only for those demonstrating relatively lower behavioral regulation or less positive approaches to learning. The findings provide support for the compensatory hypothesis that participation in EAs is more beneficial for children at greater developmental risk. Unexpectedly, the intensity of EA participation negatively predicted receptive vocabulary beyond certain thresholds among children with relatively poor behavioral regulation or approaches to learning (B = -2.272, p = .032, effect size (ES) = 0.423), but this relationship was not significant for children with better learning behaviors (B = 0.111, p = .712, ES = 0.021). According to the findings, children with worse behavioral regulation and approaches to learning were actually more vulnerable to the negative effects of intensive participation in EAs (B = -15.698, p = .022, ES = 1.797). EA participation did not predict children's Chinese word reading (ps > 0.05). The findings revealed a complex pattern of relationships between preschoolers' EA participation and academic readiness and have highlighted the importance of considering child characteristics when examining the developmental effects of EA involvement.


Assuntos
Aprendizagem , Relações Pais-Filho , Criança , Pré-Escolar , Humanos , China
18.
Epigenetics Chromatin ; 16(1): 9, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36890610

RESUMO

Polycomb group RING finger protein 6 (PCGF6) plays an important role as a regulator of transcription in a variety of cellular processes, including tumorigenesis. However, the function and expression of PCGF6 in papillary RCC (pRCC) remain unclear. In the present study, we found that PCGF6 expression was significantly elevated in pRCC tissues, and high expression of PCGF6 was associated with poor survival of patients with pRCC. The overexpression of PCGF6 promoted while depletion of PCGF6 depressed the proliferation of pRCC cells in vitro. Interestingly, myc-related zinc finger protein (MAZ), a downstream molecular of PCGF6, was upregulated in pRCC with hypomethylation promoter. Mechanically, PCGF6 promoted MAZ expression by interacting with MAX and KDM5D to form a complex, and MAX recruited PCGF6 and KDM5D to the CpG island of the MAZ promoter and facilitated H3K4 histone demethylation. Furthermore, CDK4 was a downstream molecule of MAZ that participated in PCGF6/MAZ-regulated progression of pRCC. These results indicated that the upregulation of PCGF6 facilitated MAZ/CDK4 axis expression and pRCC progression by hypomethylation of the MAZ promoter. The PCGF6/MAZ/CDK4 regulatory axis may be a potential target for the treatment of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA , Complexo Repressor Polycomb 1/metabolismo , Antígenos de Histocompatibilidade Menor , Histona Desmetilases , Quinase 4 Dependente de Ciclina/genética
19.
Viruses ; 15(4)2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37112936

RESUMO

Various coronaviruses have emerged as a result of cross-species transmission among humans and domestic animals. Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea, vomiting, dehydration, and high mortality in neonatal piglets. Porcine small intestinal epithelial cells (IPEC-J2 cells) can be used as target cells for PEDV infection. However, the origin of PEDV in pigs, the host range, and cross-species infection of PEDV remain unclear. To determine whether PEDV has the ability to infect human cells in vitro, human small intestinal epithelial cells (FHs 74 Int cells) were inoculated with PEDV LJX and PEDV CV777 strains. The results indicated that PEDV LJX, but not PEDV CV777, could infect FHs 74 Int cells. Furthermore, we observed M gene mRNA transcripts and N protein expression in infected FHs 74 Int cells. A one-step growth curve showed that the highest viral titer of PEDV occurred at 12 h post infection. Viral particles in vacuoles were observed in FHs 74 Int cells at 24 h post infection. The results proved that human small intestinal epithelial cells are susceptible to PEDV infection, suggesting the possibility of cross-species transmission of PEDV.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Humanos , Animais , Suínos , Linhagem Celular , Vírus da Diarreia Epidêmica Suína/genética , Intestinos , Células Epiteliais , Infecções por Coronavirus/veterinária , Diarreia
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 14(11): 859-62, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23146736

RESUMO

OBJECTIVE: To study the significance and safety of flexible bronchoscopy and balloon dilatation in the diagnosis and treatment of respiratory diseases in children. METHODS: A total of 438 children (236 males and 202 females) with respiratory diseases who were aged from 17 days to 15 years, were examined and/or treated by bronchoscopy (including bronchoscopic intervention) under local anesthesia. RESULTS: Of the 438 children, 311 were diagnosed with pulmonary infection, 68 with atelectasis, 36 with recurrent cough and asthma, 6 with hemoptysis of unknown origin, 6 with bronchial foreign body, 5 with congenital bronchopulmonary dysplasia, 2 with bronchiectasis, 1 with ciliary dyskinesia syndrome, 1 with lung tumor, and 2 with congenital immunodeficiency disease. After bronchoscopic examination, local flushing or bronchoalveolar lavage, and foreign body extraction, marked response was seen in 379 cases and response was seen in 46 cases. High-pressure balloon dilatation under bronchoscopy was performed in 5 cases with inflammatory stricture and achieved satisfying clinical effect. No severe complications were found in bronchoscopy. CONCLUSIONS: Bronchoscopy and balloon dilatation under local anesthesia is safe and effective for the diagnosis and treatment of respiratory diseases in children.


Assuntos
Anestesia Local , Broncoscopia/métodos , Dilatação/métodos , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/terapia , Adolescente , Broncoscopia/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
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