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AIM: We explored the performance of demographic characteristics, physiological state, cognitive function, sensory function, and biomarkers when used as predictors of frailty for patients with schizophrenia. DESIGN: A cross-sectional study design was adopted. METHODS: Demographic data and data on physiological state, cognitive function, sensory function, biochemical indices, and frailty status of patients with schizophrenia were collected. The data were analysed using descriptive statistics, a chi-square test, one-factor analysis of variance, and logistic regression. RESULTS: The results revealed that frailty was prevalent among patients with lower educational attainment, longer hospital stay, higher skeletal muscle mass, higher basal metabolic rate, lower cognitive function, the use of tranquillisers and sleeping pills, and the use of assistive equipment as well as having fallen in the past year. In addition, cognitive function (p < 0.05), use of a wheelchair (p < 0.05), and use of an assistive walker (p < 0.001) were used as predictors of frailty condition of patients with schizophrenia. PATIENT CONTRIBUTION: Patients with schizophrenia have higher risk of having complications than patients with other chronic illnesses. Therefore, medical staff should regularly assess the levels of frailty risk to help patients with schizophrenia.
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Fragilidad , Esquizofrenia , Anciano , Humanos , Fragilidad/psicología , Anciano Frágil/psicología , Estudios Transversales , Cognición , Biomarcadores , SensaciónRESUMEN
AIMS: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder of neurodevelopment in children. The diagnosis of ADHD mainly relies on the symptoms and some may be misdiagnosed due to age-based variation in behaviours. This study aimed to explore biomarkers that are greatly needed for the accurate diagnosis of ADHD. METHODS: Seven hundred and forty-two samples were retrospectively investigated in three independent cohorts, screening, training, and validation, for circulation microRNA measurement using microarray, Taqman polymerase chain reaction, and regression analysis. RESULTS: A panel of five miRNAs (miR-4516, miR-6090, miR-4763-3p, miR-4281, and miR-4466) were identified as ADHD independent risk factors that provided a high diagnostic accuracy and specificity of ADHD (AUC = 0.940 and 0.927 in the training and validation datasets, respectively). This panel of miRNAs differentiated ADHD well from control groups. After clinical improvement by treatment, the panel of miRNAs in patients and AUC changed significantly and were close to those in healthy controls. Importantly, the targets of the miRNAs identified were commonly enriched in receptor signalling pathways, ion channels, and synapse structures. CONCLUSION: Our study identified a useful panel of miRNAs that have considerable clinical value in evaluating ADHD and provide important evidence for aberrant epigenetic regulation in ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , MicroARNs , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/genética , Biomarcadores , Biomarcadores de Tumor , Niño , Epigénesis Genética , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , Estudios RetrospectivosRESUMEN
Management of frequent epileptic seizures in febrile infection-related epilepsy (FIRES) is often challenging. FIRES is an uncommon disease condition. Children with FIRES develop refractory epilepsy with severe cognitive deficits that affect the function of the temporal and frontal lobes. However, better seizure control during the acute stage of FIRES could protect against injury to the nervous system. Ketogenic diet (KD) can effectively resolve super-refractory status epilepticus (SRSE) in the acute phase and improve the prognosis of FIRES. We present the case of a previously healthy 3-year-old male with new-onset status epilepticus (SE) admitted to the paediatric intensive care unit for 55 days. Despite treatment with multiple anti-epileptic agents in addition to IV anaesthetics, the patient remained in SRSE and continued to have generalised epileptic activity on electroencephalography (EEG). KD therapy was initiated on the 14th day of the onset, and the patient achieved complete neurological recovery following the KD. Throughout the remainder of admission, the patient was successfully weaned off the ventilator, tolerated oral meals, and worked with occupational and physical therapists to return to his baseline functional status. The convulsions were well controlled after discharge. We discuss the treatment strategies for FIRES and highlight the role of KD therapy in the acute phase to control disease progression and improve the prognosis, and early diagnosis of FIRES and early initiation of KD therapy combined with anti-epileptic drugs (AEDs) could improve the prognosis.
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OBJECTIVE: To study the association of microRNA expression before and after drug therapy with clinical symptoms in children with attention deficit hyperactivity disorder (ADHD). METHODS: A total of 80 previously untreated children with ADHD who were diagnosed from May 2017 to October 2018 were enrolled. The children who were willing to receive drug therapy were randomly divided into concerta-treated group with 31 children and strattera-treated group with 33 children. The children who were unwilling to receive treatment were enrolled as the untreated group with 16 children. A total of 60 children who underwent physical examination during the same period of time were enrolled as the healthy control group. SNAP-V score was determined at initial diagnosis and 3 and 6 months of follow-up. Serum samples were collected from the children with ADHD and the healthy control group. Quantitative real-time PCR was used to measure the relative expression of miR-4566-3p and miR-7641. RESULTS: The repeated measures analysis of variance showed that the SNAP-V score of attention deficit symptoms were different among the two treatment groups and the untreated group at the first visit and 3 months and 6 months after treatment (P<0.05). There were significant differences in the relative expression of the two miRNAs among the two treatment groups and the healthy control group at the first visit and 3 months and 6 months after treatment (P<0.05). The SNAP-V score of attention deficit symptoms and the relative expression of the two miRNAs were different in different time points in the subjects (P<0.05). There were interactions between grouping and time factors in the SNAP-V score of attention deficit symptoms and the relative expression of the two miRNAs (P<0.05). The SNAP-V score of hyperactive impulsive symptoms was different in different time points in the two treatment groups and the untreated group (P<0.05), but the significant difference in the score was not observed between two treatment groups and the untreated group (P>0.05), and there was no interaction between the time factor and the grouping factor (P>0.05). The SNAP-V score of attention deficit symptoms was negatively correlated with the relative expression of miRNA-4655-3p and miRNA-7641 (r=-0.314, -0.495 respectively; P<0.05) in ADHD children after drug treatment. CONCLUSIONS: Drug therapy can significantly improve the clinical symptoms of children with ADHD. The expression of miR-4655-3p and miR-7641 in serum can be used as biomarkers for the diagnosis and outcome evaluation of ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , MicroARNs/genética , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/genética , Niño , HumanosRESUMEN
Attention deficit hyperactivity disorder (ADHD) is a child developmental and behavioral disorder which seriously hinders their education and development. To investigate the key regulators in the prefrontal cortex (PFC), the major affected areas of ADHD, microRNA (miR)-138,138*, 34c*, 296, and 494, were noted for their significant downregulation in ADHD model rats spontaneously hypertensive rats (SHRs) compared to Wistar Kyoto (WKY) rat control. Based on promoter sequence analysis and activity assay, glucocorticoid receptor (Nr3c1) was identified for the inhibition of the promoter activity of miR-138-1, 34c*, 296, and 494 genes and their transcription. In the PFC of ADHD model rats SHR, Nr3c1 expression was abnormally elevated and reversely correlated with the levels of miR-138-1, 34c, 296, and 494 expression. Luciferase report assays indicated that all miR-138, 138*, 34c*, 296, and 494 targeted the 3' untranslated region of transcription factor Bhlhb2 (Bhlhe40) messenger RNA (mRNA) in common and ectopic expression of miR-138,138*, 34c*, 296, and 494 further suppressed the expression of Bhlhb2 gene. Consistently, Bhlhb2 expression was significantly higher in PFC of ADHD model SHR than control. Overexpressed Bhlhb2 in vitro significantly suppressed PC12 cell differentiation, and silence of Bhlhb2 enhanced the growth of neurite axon and dendrite. To observe the roles of Bhlhb2 further in vivo, Bhlhb2 was silenced in the PFC of nine SHR rats. Interestingly, knockdown of Bhlhb2 significantly improved the hyperactivity behaviors in SHRs compared to control. These findings show that Nr3c1-Bhlhb2 axis dysregulation was involved in the development of attention deficit and hyperactivity.
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Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteínas de Homeodominio/genética , Receptores de Glucocorticoides/genética , Animales , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/biosíntesis , Redes Reguladoras de Genes/fisiología , Células HEK293 , Proteínas de Homeodominio/biosíntesis , Humanos , Masculino , Células PC12 , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Glucocorticoides/biosíntesisRESUMEN
Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment. The profile analysis of sialylated proteins showed that a protein band at 55KD was greatly enhanced especially in PC12L cells after CycloManN pro treatment. After enrichment with lectin MAL II, the proteins in this band were analyzed by mass spectrometry. The results showed that 23 proteins were in the band, but the score of vimentin was the highest among them. To investigate further the role of vimentin in the process of neurite differentiation, vimentin construct was transfected into PC12 cells. We interestingly observed that ectopic expression of vimentin significantly enhanced the neurite outgrowth induced by CycloManN pro. However, after three potential glycosylation sites (Ser-7, Thr-33, Ser-34:) of vimentin were mutated to alanine, overexpression of the mutated vimentin completely lost the enhancement activity for the neural differentiation even in the presence of CycloManN pro. Taken together, our study demonstrated that vimentin was important in the induction of neural differentiation by CycloManN pro.
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Neuritas/metabolismo , Proyección Neuronal , Procesamiento Proteico-Postraduccional , Ácidos Siálicos/metabolismo , Vimentina/metabolismo , Animales , Lectinas/metabolismo , Mutación , Células PC12 , Ratas , Vimentina/genéticaRESUMEN
Up to date, there has been no molecular signature available in the clinical practice for attention-deficit/hyperactivity disorder (ADHD). To investigate circulating miRNA let-7d significance in ADHD, we investigated serum miRNA let-7d in 35 newly diagnosed ADHD subjects who were randomly selected from 406 patients out of 7450 children, paired with gender- and age-matched control through case-control study. We observed that circulating miRNA let-7d was significantly higher in ADHD subjects than in control (p < 0.05). Higher circulation level of miRNA let-7d was significantly associated with ADHD (odds ratio 16.7; 95% confidence, p < 0.05). Meanwhile, serum galectin-3 level was down-regulated in ADHD subjects and the subjects with low galectin-3 expression accounted for 66% in ADHD. The difference of the serum galectin-3 levels between ADHD and non-ADHD groups reached significance (p < 0.05). In 1-year follow-up, a significantly higher rate of clinical improvement was noted in subjects with low level of circulating miRNA let-7d (p < 0.05) than those with high level of circulating miRNA let-7d. Our data demonstrated that miRNA let-7d was elevated in the serum of ADHD subjects, which might be a novel, useful molecule signature for ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/sangre , Galectina 3/sangre , MicroARNs/sangre , Adolescente , Animales , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Modelos Animales de Enfermedad , Femenino , Galectina 3/genética , Galectina 3/metabolismo , Humanos , Masculino , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Muestreo , Resultado del TratamientoRESUMEN
A mature miRNA generally suppresses hundreds of mRNA targets. To evaluate the selective effect of synthetic oligonucleotide decoys on hsa-miR-223 activity, reporters containing 3' untranslated regions (UTR) of IGF1R, FOXO1, POLR3G, FOXO3, CDC27, FBXW7 and PAXIP1 mRNAs were constructed for the luciferase assay. The oligonucleotide decoys were designed and synthesized according to mature miR-223 sequence and its target mRNA sequence. Quantitative RT-PCR & western analysis were used to measure miR-223-targeted mRNA expression, Interestingly, apart from the antisense oligonucleotide, decoy nucleotides which were complementary to the 5', central or 3' region of mature miR-223 suppressed miR-223 targeting the 3'UTR of IGF1R, FOXO1, FOXO3, CDC27, POLR3G, and FBXW7 mRNAs and rescued the expression of these genes to varying degrees from miR-223 suppression at both mRNA and protein levels. All decoys had no effect on PAXIP1 which was not targeted by miR-223. The decoy 1 that was based on the sequence of IGF1R 3'UTR rescued the expression of IGF1R more significantly than other decoy nucleotides except the antisense decoy 4. Decoy 1 also rescued the expression of FOXO3 and POLR3G of which their 3'UTRs have similar binding sites for miR-223 with IGF1R 3'UTR. However decoy 1 failed to recover Sp1, CDC27 and FBXW7 expression. These data support that the sequence-specific decoy oligonucleotides might represent exogenous competing RNA which selectively inhibits microRNA targeting.
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MicroARNs/metabolismo , Oligonucleótidos/farmacología , Receptor IGF Tipo 1/metabolismo , Regiones no Traducidas 3'/genética , Apoptosis/efectos de los fármacos , Secuencia de Bases , Proliferación Celular/efectos de los fármacos , Células HEK293 , Células HeLa , Humanos , Luciferasas/metabolismo , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Integrin is important in migration and metastasis of tumor cells. Changes of integrin expression and distribution will cause an alteration of cellular adhesion and migration behaviors. In this study, we investigated sulfatide regulation of the integrin αV subunit expression in hepatoma cells and observed that either exogenous or endogenous sulfatide elicited a robust upregulation of integrin αV subunit mRNA and protein expression in hepatoma cells. This regulatory effect occurred with a corresponding phosphorylation (T739) of the transcription factor Sp1. Based on the electrophoretic mobility shift assay, sulfatide enhanced the integrin αV promoter activity and strengthened the Sp1 complex super-shift. The results of chromatin immunoprecipitation analysis also indicated that sulfatide enhanced Sp1 binding to the integrin αV promoter in vivo. Silence of Sp1 diminished the stimulation of integrin αV expression by sulfatide. In the early stage of sulfatide stimulation, phosphorylation of Erk as well as c-Src was noted, and inhibition of Erk activation with either U0126 or PD98059 significantly suppressed Sp1 phosphorylation and integrin αV expression. We demonstrated that sulfatide regulated integrin αV expression and cell adhesion, which was associated with Erk activation.
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Integrina alfaV/metabolismo , Sulfoglicoesfingolípidos/farmacología , Butadienos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Cerebrósidos/metabolismo , Inmunoprecipitación de Cromatina , Flavonoides/farmacología , Humanos , Nitrilos/farmacología , Fosforilación/efectos de los fármacos , Factor de Transcripción Sp1/metabolismoAsunto(s)
Doxorrubicina/análogos & derivados , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Ácido Valproico/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Ácido Valproico/administración & dosificaciónRESUMEN
The synthesis of the first family of fully substituted cucurbit[n]uril is discussed, and the structural features of precursor glycolurils are highlighted in their importance to achieving higher homologues. The members of the family, where n = 5-7, have been fully characterized, and increased binding affinities have been identified for dioxane in CyP(6)Q[6] and adamantyl NH(3)(+) in CyP(7)Q[7]. A higher homologue is indicated but not conclusively identified.
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SMMC-7721 hepatocellular carcinoma cells (HCC) were incubated with fucosylated glycoproteins that had been isolated from retinoic acid-treated cells by affinity chromatography. HCC migration was significantly inhibited by AAL- and LCA-glycoproteins. Glycopeptides, obtained by digestion of the glycoproteins with trypsin and papain, were found to have a similar inhibitory effect on HCC migration as the corresponding glycoproteins. The inhibitory actions of the glycoproteins were almost abolished after digestion with alpha-L-1,3/4- or alpha-L-1,2-fucosidase. Induction of HCC migration with chemokines including interleukin-8 (IL-8), lymphotactin, monocyte chemoattractant protein-1, and stroma cell-derived factor-1 was examined and IL-8 was found to be the most potent. Interestingly, the isolated glycoproteins significantly inhibited HCC migration and F-actin aggregation induced by IL-8, whereas the glycans themselves did not induce F-actin assembly. From receptor binding analysis AAL-glycan was found to bind IL-8 receptors especially CXCR2 directly and such binding could be blocked by 3'- or 2'-fucosyllactose. After CXCR2 silence by target RNAi, the cells almost lost the response to AAL-glycan inhibition. Our findings suggest that fucosylation plays an important role in the interaction between IL-8 and its receptors inducing HCC migration.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular/efectos de los fármacos , Fucosa/farmacología , Glicoproteínas/farmacología , Neoplasias Hepáticas/metabolismo , Receptores de Quimiocina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Fucosa/metabolismo , Glicopéptidos/farmacología , Glicoproteínas/metabolismo , Humanos , Neoplasias Hepáticas/patología , Unión Proteica , Relación Estructura-Actividad , Tretinoina/farmacologíaRESUMEN
BACKGROUND: 3'-Sulfo-Le(a) is known to be the potent ligand of E-selectin which is important in cell adhesion and migration. Yet the significance of serum 3'-sulfo-Le(a) has not been explored and reported. METHODS: Serum 3'-sulfo-Le(a) was analyzed by enzyme-linked immunosorbent assay. SPSS software was used for statistics analysis. Cell adhesion to HUVEC and sL-selectin, and cell migration were performed in gastric cancer cells SCG7901 with 3'-sulfo-Le(a) silence by Gal3ST-2 RNAi. RESULTS: Through analysis, the mean levels of serum 3'-sulfo-Le(a) antigen were found significantly higher in 108 patients with gastric cancer than that in 74 healthy volunteers. Depth of tumor invasion, lymph node metastasis, and differentiation were noted to be significantly correlated with the expression of this antigen in gastric carcinoma. After treatment with 5-FU (5-fluorouracil) and ATRP (N-all-trans-retinoyl-L-proline), the expression of 3'-sulfo-Le(a) antigen was markedly down regulated in SCG7901 gastric cancer cells. After transfection of Gal3ST-2 RNAi, the expression of 3'-sulfo-Le(a) was silenced and the cell adhesion to HUVEC or sL-selectin, and cell migration were suppressed. CONCLUSION: Serum 3'-sulfo-Le(a) antigen can provide important information in patients with primary gastric cancer, which might be useful as a predictive marker especially for the detection of tumor metastasis.
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Biomarcadores de Tumor/sangre , Oligosacáridos/sangre , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fluorouracilo/farmacología , Humanos , Antígenos del Grupo Sanguíneo de Lewis , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Péptidos/química , Péptidos/farmacologíaRESUMEN
OBJECTIVE: To investigate the effect of adenovirus-mediated endostatin gene transfer on transplanted lung cancer in mice and its mechanism of action. METHODS: Transplant tumor model was induced by subcutaneous inoculation of 2 x 10(6) Lewis lung cancer (LLC) cells into the back of C57BL/6 mice. The mice were treated by intratumoral injection of 2 x 10(9) pfu Ad-mEndostatin. The expression of endostatin in situ and its maintaining time were detected by immunohistochemistry and Western Blot, respectively. The endostatin level in serum was determined by ELISA . The inhibition of tumor growth and changes of survival were recorded and the microvessel density (MVD) was determined by histochemical stainingwith CD31 and CD105 antibodies. The tumor apoptosis was observed by electron microscopy. RESULTS: In comparison with controls, intratumoral injection of Ad-mEndostatin significantly inhibited the tumor growth and metastasis, and prolonged the survival rate of mice (P < 0.05). Strong positive expression of mEndostatin was seen in the tumor tissue after injection of Ad-mEndostatin, immunhistochemically ostained by mouse endostatin monoclonal antibody, while the control groups showed only very low expression or absence. Serum endostatin concentration was 1540 +/- 560 ng/ml at the second week of administration, the expression of endostatin diminished a month later. The microvessel density (MVD)) decreased from 42.4 +/- 4.8 to 10.5 +/- 3.2 per x 200 magnificetion microscopic field by CD10 staining and from 68.5 +/- 4.5 to 37.5 +/- 4.6 by CD31 staining, respectively (P < 0.05). More apoptotic tumor cells were seen under the transmission electron microscope. CONCLUSION: Endostatin gene therapy mediated by adenoviral vector efficiently induces expression of endostatin in vivo, and inhibits the growth and metastasis of tumor. It is concluded that its action is targeted to tumor neovasculature and the mechanism is inhibition of tumor angiogenesis.
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Adenoviridae/genética , Inhibidores de la Angiogénesis , Carcinoma Pulmonar de Lewis/terapia , Endostatinas , Terapia Genética , Inhibidores de la Angiogénesis/genética , Inhibidores de la Angiogénesis/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Endostatinas/genética , Endostatinas/metabolismo , Endostatinas/uso terapéutico , Vectores Genéticos , Masculino , Ratones , Ratones Endogámicos C57BL , Microvasos/patología , Trasplante de Neoplasias , Neovascularización Patológica/patología , Distribución Aleatoria , Transfección , Carga TumoralRESUMEN
AIM: The aim of the present study was to understand the role of retinoic acid (RA) in the development of isolated patent ductus arteriosus and the features of arterial duct-derived vascular smooth muscle cells (VSMC). METHODS: The VSMC were isolated, and the biological characteristics and the response to RA were investigated in the arterial duct, aorta, and pulmonary artery VSMC from 6 human embryonic samples. Western blotting, immunostaining, and cell-based ELISA were employed to analyze the proliferation regulation of VSMC. RESULTS: The VSMC from the arterial duct expressed proliferating cell nuclear antigen (PCNA) at a significantly lower rate than those from the aorta and pulmonary artery, but expressed a higher level of Bax and Bcl-2. The expression level of PCNA or Bcl-2 was associated with the embryonic age. The effects of RA on the VSMC from the arterial duct were quite different from those from the aorta and pulmonary artery. In arterial duct VSMC, RA stimulated PCNA expression, but such stimulation could be suppressed by CD2366, an antagonist of nuclear retinoid receptor activation. In aorta or pulmonary artery VSMC, the expression response of PCNA to RA was insignificant. The ratio of Bax/Bcl-2 decreased in arterial duct VSMC after RA treatment due to the significant inhibition of Bax expression. CONCLUSION: The VSMC from the arterial duct possessed distinct biological behaviors. RA might be important in the development of ductus arteriosus VSMC.