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OBJECTIVE: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. METHODS: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). RESULTS: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4). CONCLUSION: This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.
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Labio Leporino , Fisura del Paladar , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , Vía de Señalización Wnt/genéticaRESUMEN
OBJECTIVE: In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction. METHODS: We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction. RESULTS: A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios. CONCLUSION: Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.
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Labio Leporino , Fisura del Paladar , Pueblo Asiatico/genética , Labio Leporino/genética , Fisura del Paladar/genética , Estudio de Asociación del Genoma Completo , Humanos , Vía de Señalización Wnt/genéticaRESUMEN
With the rapid developments in compact devices, the multi-function and reconfigurability of nanostructures are highly appreciated, while still very challenging. A majority of devices are usually mono-functional or hard to switch between different functions in one design. In this paper, we proposed graphene-wrapped core-shell nanowires to realize real-time reconfigurable sensors and nanoantenna by tuning the Fermi energies of graphene layers at the surfaces of core and shell, respectively. Owing to the electromagnetic coupling between the two graphene layer, two corresponding Fano resonances of scattering can arise in the Terahertz spectrum, which arises from the interference of bright modes and dark modes. Around the Fano resonances, the scattering can be considerably resonant (as an antenna) or suppressed (as a sensor). Interestingly, the field distributions are distinct at the suppressed scattering states for the two Fano resonances. The presented reconfigurable nanostructures may offer promising potentials for integrated and multi-functional electromagnetic control such as dynamic sensing and emission.
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OBJECTIVE: Little consistent evidence is available for the association between the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction. SUBJECTS AND METHODS: We selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted. RESULTS: We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10-12 ). CONCLUSIONS: Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.
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Betaína-Homocisteína S-Metiltransferasa/genética , Labio Leporino/genética , Fisura del Paladar/genética , Dimetilglicina-Deshidrogenasa/genética , Epistasis Genética , Proteínas Mitocondriales/genética , Pueblo Asiatico/genética , Ácido Fólico/metabolismo , Estudio de Asociación del Genoma Completo , Homocisteína/metabolismo , Humanos , Desequilibrio de Ligamiento , Redes y Vías Metabólicas , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Objective: To evaluate the value of (18)F-FDG PET-CT in predicting the malignant potential of Gastrointestinal Stromal Tumors (GIST). Methods: The clinical and pathological features of 31 patients with GIST confirmed by surgery or biopsy were retrospectively analyzed. The malignant potential of GIST before treatment was assessed by (18)F-FDG PET-CT. The GIST risk classification was graded according to the Standard revised by the National Institutes of Health (NIH) in 2008. The relationship between the maximal standard uptake value (SUVmax) and GIST risk classification, tumor diameter, Ki-67 index, and mitotic count were analyzed respectively. The cut-off level of SUVmax for the diagnosis of malignant GIST was calculated from the Receiver Operating Characteristic (ROC) curve. Results: Among the 31 cases of GIST patients, 14 cases were gastric primary (stomach group) and 17 cases were nongastric primary (outside stomach group). The SUVmax, tumor diameter, Ki-67 index and mitotic count of the 31 patients were 8.21±4.68, (7.82±5.12)cm, (10.03±11.07)% and (12.29±10.55)/50 HPF, respectively. SUVmax was significantly correlated with GIST risk classification (r=0.727, P<0.01), but not with tumor diameter, Ki-67 index and mitotic count (r=0.348, r=0.284, r=0.290, P=0.055, P=0.121, P=0.114). The SUVmax, tumor diameter, Ki-67 index and mitotic count in the stomach group were 4.36±2.36, (6.08±4.31)cm, (3.43±3.03)% and (5.71±2.20)/50 HPF, respectively. SUVmax was significantly correlated with tumor diameter, GIST risk classification and Ki-67 index (r=0.682, r=0.868, r=0.732, P<0.01) but not with mitotic count (r=0.510, P=0.063). The SUVmax of the GIST in the gastric group and the outside gastric group were 4.36±2.36 and 10.68±5.50, respectively. The difference was statistically significant (P=0.001). The SUVmax in the malignant group of GIST (middle or high risk grade) was 8.90±4.89, which was significantly higher than 2.22±0.86 in the benign group (low or very low risk grade). The difference was statistically significant between the two group (P<0.01). ROC curve analysis showed that a SUVmax cut-off of 3.75 was the most sensitive for predicting malignant GIST. When the area under the curve of 0.969, the sensitivity was 84.6% and the specificity was 100%. Conclusions: The SUVmax was strongly correlated with the GIST risk category and also with the tumor diameter and Ki-67 index in the gastric primary GIST, so it can be used as an effective indicator in predicting malignant potential of GIST before treatment.
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Fluorodesoxiglucosa F18 , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Neoplasias Gástricas/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/patología , Humanos , Antígeno Ki-67/análisis , Masculino , Índice Mitótico , Curva ROC , Radiofármacos/farmacocinética , Estudios Retrospectivos , Riesgo , Sensibilidad y Especificidad , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Carga TumoralRESUMEN
Pinelliae rhizoma is the dried tuber of Pinellia ternata (Thunb.) Breit., and has been used for thousands of years as a traditional Chinese medicine. However, its genomic background is little known. With the development of high-throughput genomic sequencing, it is now easy and cheap to obtain genomic information. In this study, 193,032,910 high-quality clean reads were generated using the Illumina Hiseq 2000 platform. A total of 53,544 unigenes were identified from the contigs assembled. Functional annotation analysis annotated 37,318, 27,697, 23,043, 22,869, 23,328, and 27,415 unigenes. KEGG analysis revealed that five pathways (169 genes) were associated with alkaloid synthesis, 201 unigenes were related to fatty acid biosynthesis (ko00061), and 133 unigenes were involved in the biosynthesis of unsaturated fatty acids (ko01040). In addition, 6703 simple sequence repeats were designed based on the unigene sequences for screening germplasm resources in the future. These data are a valuable resource for genomic studies on Pinellia plants.
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Pinellia/genética , Perfilación de la Expresión Génica , Genes de Plantas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN , TranscriptomaRESUMEN
Adipose-derived stem cells (ADSCs) show nearly unlimited potential in medical and animal science. Currently, understanding of the biological mechanisms regulating ADSC growth in vitro remains very limited. Histone acetylation, an epigenetic modification, plays a key role in maintaining stem cell properties. To further study its effect on ADSC growth characteristics in vitro, we treated goat ADSCs with the histone deacetylase inhibitors trichostatin A (TSA) and vorinostat (SAHA). This inhibited SIRT1 expression and increased histone H3K9 acetylation, leading to decreased cell viability, cell cycle arrest, and apoptosis. Quantitative real-time polymerase chain reaction revealed that H3K9 hyperacetylation stimulated transcription of NANOG, OCT4, SOX2, and TERT, but inhibited that of PCNA, P53, and BAX. Western blotting indicated that TSA and SAHA increased protein expression of NANOG, reduced that of SOX2, TERT, PCNA, P53, and BAX, and did not change that of OCT4. These findings provide new experimental evidence contributing to our understanding of the mechanisms underlying ADSC growth characteristics in vitro.
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Tejido Adiposo/citología , Histonas/metabolismo , Células Madre/citología , Células Madre/metabolismo , Acetilación , Animales , Apoptosis/genética , Western Blotting , Ciclo Celular/genética , Proliferación Celular , Supervivencia Celular/genética , Citometría de Flujo , Regulación de la Expresión Génica , Cabras , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
White adipose tissue and brown adipose tissue play critical roles in controlling energy homeostasis and the development of obesity and diabetes. We isolated mouse white adipocytes from inguinal white fat tissues and brown adipocytes from interscapular brown fat tissues, and employed a variety of approaches, including immunofluorescent staining, quantitative real-time PCR, western blotting analysis, and differentiation assay, to characterize those adipocytes. Both white and brown adipocytes stained positively for CD44 and CD29, and lipid droplets were observed after the induction of adipogenesis. The Asc1 expression level in the white adipocytes was 2.5-fold higher than that in the brown adipocytes (P < 0.05), and the expression of Ucp1 in the white adipocytes was approximately 50% of that in the brown adipocytes (P < 0.05). The expression of α-tubulin in the brown adipocytes was approximately 70% of that in the white adipocytes. The brown adipocytes had a higher Cidea mRNA level (P < 0.05) and a lower Pparγ mRNA level (P < 0.05) than the white adipocytes. The results demonstrate that white and brown adipocytes have different gene expression signatures, and may represent two useful cell models to study the mechanisms involved in obesity.
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Adipocitos Marrones/citología , Adipocitos Marrones/metabolismo , Adipocitos Blancos/citología , Adipocitos Blancos/metabolismo , Expresión Génica , Adipogénesis , Tejido Adiposo Pardo/citología , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/citología , Tejido Adiposo Blanco/metabolismo , Animales , Proliferación Celular , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Integrina beta1/genética , Integrina beta1/metabolismo , Masculino , RatonesRESUMEN
Transgene silencing, which is common in transgenic plants and animals, limits the generation and application of genetically modified organisms, and is associated with the exogenous gene copy number, the methylation status of its promoters, and histone modification abnormalities. Here, we analyzed the expression of the exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV) promoter in six healthy transgenic cashmere goats and transgenic nuclear donor cells. The CMV promoter exhibited high methylation levels (74.4-88.2%) in four of the goats, a moderate methylation level (58.7%) in one, and a low methylation level (21.2%) in one, while the methylation level of the transgenic nuclear donor cells was comparatively low (14.3%). DsRed expression was negatively correlated with promoter methylation status. Transgenic cashmere goats carried one to three copies of the CMV promoter fragment and one to six copies of the DsRed fragment, but copy number showed no obvious correlation with DsRed expression. After treatment with the methylation inhibitor 5-azacytidine, DsRed expression in transgenic goat cells significantly increased and CMV promoter methylation significantly decreased; this indicated an inverse correlation between promoter methylation status and DsRed expression. After treatment with the histone deacetylase inhibitor trichostatin A, DsRed expression increased, indicating that an abnormal histone modification in transgenic goats is also involved in exogenous gene silencing. These findings indicate the potential of trichostatin A and 5-azacytidine to rescue the biological activity of silenced exogenous transgenes in adult-derived transgenic cells under culture conditions.
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Azacitidina/farmacología , Cabras/genética , Histonas/genética , Ácidos Hidroxámicos/farmacología , Proteínas Luminiscentes/genética , Regiones Promotoras Genéticas/efectos de los fármacos , Animales , Animales Modificados Genéticamente , Citomegalovirus/genética , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN/efectos de los fármacos , Femenino , Dosificación de Gen , Expresión Génica , Silenciador del Gen/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Histonas/metabolismo , Proteínas Luminiscentes/agonistas , Proteínas Luminiscentes/antagonistas & inhibidores , Proteínas Luminiscentes/metabolismo , Masculino , TransgenesRESUMEN
OBJECTIVE: To explore the association and gene-environment interaction between single nucleotide polymorphisms (SNPs) involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Chinese population. METHODS: A total of 806 NSCL/P trios were drawn by an international consortium, which conducted a genome-wide association study (GWAS) using a case-parent trio design to investigate genes affecting risks to NSCL/P. The transmission disequilibrium test (TDT) was used to explore the association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P. Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children. Four common maternal exposures including maternal smoking, environmental tobacco smoke, alcohol consumption and multivitamin supplementation during pregnancy were included in this study. RESULTS: A total of 226 SNP markers were tested after quality control in this study. Although 23 SNPs in three genes (CTNNB1, CDH1, ACTN1) showed nominal significant association with NSCL/P in the TDT (P<0.05).There were no significant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P>0.000 2). Tests for gene-environment interaction yielded significant results between rs743127 in ACTN1 and environmental tobacco smoke (P=0.000 1) with an estimated OR (case|G and E)=2.00(95%CI: 1.23-3.26) and OR (case|G no E)=0.59 (95%CI: 0.38-0.90). Among the lower P value results in gene-environment tests, there were no significant results between rs1475034, rs370535, rs2273419 in ACTN1, rs106871 in CTNNB1 and environmental tobacco smoke interaction. There were also no significant results between rs7634000, rs2971366, rs2634553, rs1489032, rs7624812 in PVRL3 and multivitamin supplementation during pregnancy in gene-environment tests(P>0.000 2). CONCLUSION: There is no association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P when the genes are considered alone. But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.
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Adhesión Celular/genética , Labio Leporino/genética , Fisura del Paladar/genética , Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Pueblo Asiatico/genética , Niño , Femenino , Ligamiento Genético , Humanos , Modelos Logísticos , Exposición Materna , Polimorfismo de Nucleótido Simple , EmbarazoRESUMEN
Propofol is one of the extensively and commonly used intravenous anesthetic agents. The current study aimed to evaluate the effects of propofol on the behavior of human gastric cancer cells and the molecular mechanisms of this activity. The effects of propofol on SGC7901 and AGS cell proliferation, apoptosis, and invasion were detected by MTT assay, flow cytometric analysis, and matrigel invasion assay. Real-time polymerase chain reaction (PCR) was used to assess microRNA (miR)-221 expression. miR-221 mimics were transfected into SGC7901 and AGS cells to assess the role of miR- 221 in propofol-induced anti-tumor activity. Propofol significantly inhibited cell proliferation and invasion and promoted apoptosis of SGC7901 and AGS cells. Propofol also efficiently reduced miR-221 expression. Moreover, transfection of miR-221 mimics reversed the effects of propofol on the biological behavior of gastric cancer cells. Propofol can effectively inhibit proliferation and invasion and induce apoptosis of gastric cancer cells through, at least partly, downregulation of miR-221 expression.
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Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Propofol/farmacología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/genética , Humanos , MicroARNs/metabolismo , Invasividad NeoplásicaRESUMEN
Propofol is a commonly used intravenous anesthetic. We evaluated its effects on the behavior of human pancreatic cancer cells and the underlying molecular mechanisms. The effects of propofol on Panc-1 cell proliferation, apoptosis, and invasion were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, caspase-3 activity measurement, and Matrigel invasion assay. Quantitative polymerase chain reaction (qPCR) was used to assess microRNA-133a (miR-133a) expression. Anti-miR-133a was transfected into Panc-1 cells to assess the role of miR-133a in propofol-induced antitumor activity. Propofol significantly inhibited Panc-1 cell proliferation and invasion, and promoted apoptosis. Propofol also efficiently elevated miR-133a expression. Moreover, transfection of anti-miR-133a reversed the effects of propofol on the biological behavior of Panc-1 cells. Propofol can effectively inhibit proliferation and invasion, and induce apoptosis of pancreatic cancer cells, at least partly through the upregulation of miR-133a expression.
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MicroARNs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Propofol/farmacología , Regulación hacia Arriba/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/metabolismo , Invasividad Neoplásica , Propofol/químicaRESUMEN
BACKGROUND: Invasion and metastasis are the distinct biologic characteristics of cancer, resulting in an exceptionally low 5-year survival rate in pancreatic ductal adenocarcinoma (PDAC). Understanding in detail the mechanisms underlying PDAC metastasis is critical for prevention and effective interventions. Long non-coding RNAs (lncRNAs) have been documented as having a critical role in cancer development and progression. METHODS: We examined the expression levels of lncRNA ENST00000480739 and osteosarcoma amplified-9 (OS-9) mRNA in a cohort of 35 PDAC patients. Cell proliferation, invasion and migration were examined with and without ENST00000480739 overexpression in PDAC cells. RESULTS: We determined that the ENST00000480739 expression level was remarkably decreased in tumorous tissues compared with their corresponding non-tumorous tissues. The expression of ENST00000480739 was negatively associated with tumour node metastasis stage and lymph node metastasis. In addition, ENST0000048073 was an independent prognostic factor of survival time in PDAC patients following surgery. Besides, enforced expression of ENST00000480739 suppressed PDAC cells' invasion in vitro. Overexpression of ENST00000480739 significantly increased both mRNA and protein levels of OS-9, and the luciferase assays confirmed that ENST00000480739 positively regulates OS-9 by activating the transcription level of the OS-9 promoter. We further found that ENST00000480739 may target hypoxia-inducible factor-1α (HIF-1α) expression by upregulating OS-9. CONCLUSIONS: These findings suggest that the frequently downregulated ENST00000480739 in PDAC contributes to tumour metastasis and progression by regulating HIF-1α. Long non-coding RNA ENST00000480739 may provide not only a therapeutic potential to suppress metastasis but it may also be a novel biomarker for risk prognostication and personal therapy screening of PDAC patients.
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Adenocarcinoma/patología , Carcinoma Ductal Pancreático/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Lectinas/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/fisiología , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Línea Celular Tumoral , Humanos , Metástasis Linfática , Ratones , Invasividad Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidadRESUMEN
The insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the 6 members of the IGFBP family and is involved in the regulation of cell growth, apoptosis, and other IGF-stimulated signaling pathways. To determine the significance of IGFBP-5 in the Inner Mongolia Cashmere goat (Capra hircus), a hair follicle-specific expression vector of IGFBP-5, pCDsRed2-K-IGFBP5 (6.7 kb), was constructed by cloning IGFBP-5 downstream of the keratin-association protein (KAP)6-1 promoter and inserting this fragment into pCDsRed2, which contains a red fluorescent protein (DsRed) expression unit. Inner Mongolia Cashmere goat fetal fibroblast (GFb) cells were transfected with the expression vector by using Lipofectamine(TM) 2000. Cell clones that stably expressed red fluorescence were obtained after selection with Geneticin (G418). The transgene in the cell clones was examined by polymerase chain reaction to verify that exogenous DNA (pKAP6-1 and IGFBP-5) had integrated stably into GFb cells. These data suggest that this method can be used for the construction of a hair follicle-specific expression vector for functional genetic analyses and for obtaining stable transfection donor cells for nuclear transfer.
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Cabras/genética , Folículo Piloso/metabolismo , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/biosíntesis , Transfección , Animales , Animales Modificados Genéticamente , Embrión de Mamíferos/metabolismo , Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Cabras/metabolismo , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genéticaRESUMEN
BACKGROUND: Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal malignant lymphoma and pancreatic tumour. Natural killer/T-cell lymphoma is an aggressive rare form extranodal lymphoma with a predilection for the nasal cavity/nasopharynx, it can arise in other organs such as skin, testicles, spleen, adrenal, or GI tract, but the initial presentation of our patient in the pancreas is unreported. CASE PRESENTATION: We present a case of primary pancreatic natural killer/T-cell nasal type lymphoma in a 62-year-old man. The presenting symptoms were non-specific only for upper abdominal pain and weight loss. Imaging techniques showed the lesion was located in the head of pancreas. Computed tomography (CT) scanning and otorhinolaryngology examination were negative for nasopharyngeal lymphoma. The initial concern was for pancreatic tumor and the patient underwent pancreaticoduodenectomy. The diagnosis of primary pancreatic natural killer/T-cell nasal type lymphoma was established as the combination of NK-lineage antigens (TIA-1, granzyme B, CD56) with EBV-expression. CONCLUSIONS: This is the first case of primary pancreatic natural killer (NK)/T-cell nasal type lymphoma. PPL, although a rare pathologic entity, should be considered in the differential diagnosis for a large homogeneous mass with extrapancreatic extension in the head especially in those of normal serum CA 19-9 level.
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Linfoma Extranodal de Células NK-T/patología , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Dolor Abdominal/etiología , Antígeno CD56/metabolismo , Diagnóstico Diferencial , Granzimas/metabolismo , Humanos , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Nasales/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Proteínas de Unión a Poli(A)/metabolismo , Antígeno Intracelular 1 de las Células T , Tomografía Computarizada por Rayos X , Pérdida de PesoRESUMEN
A kinetic theory is developed to describe the longitudinal decay of two-ion decay (TID): The pump ion-acoustic wave (IAW) decays into two daughter IAWs with a longer wavelength. The instability growth rate and threshold are given by the theory. Both the simulations of full kinetic Vlasov and hybrid Vlasov (kinetic ions and Boltzmann electrons) are employed to verify the theory and have a high quantitative agreement with the theory for 8≤ZT_{e}/T_{i}≤15, where Z is the ion charge number and T_{i}(T_{e}) is the ion (electron) temperature. The kinetic model developed here solves a long-standing problem that the simple fluid theory underestimates growth rate by a factor of 2â¼3. Also, a reasonable explanation is given to the typical characteristics of TID that the dependence curves of subharmonic growth rate γ and wave number k.
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We present a staged hot-electron acceleration mechanism of the two-plasmon decay (TPD) instability in the transverse magnetic field under the parameters relevant to inertial confinement fusion experiments. After being accelerated by the forward electron plasma wave (FEPW) of TPD, the hot-electrons can be anomalously accelerated again by the backward electron plasma wave (BEPW) of TPD and then obtain higher energy. Moreover, the surfatron acceleration mechanism of TPD in the magnetic field is also confirmed, the electrons trapped by the TPD daughter EPWs are accelerated in the direction along the wave front. Interestingly, the velocity of electrons accelerated by surfing from the FEPW is quite easily close to the BEPW phase velocity, which markedly enhances the efficiency of the staged acceleration. The coexistence of these two acceleration mechanisms leads to a significant increase of energetic electrons generated by TPD in the magnetic field. Meanwhile the EPWs are dissipated, TPD instability is effectively suppressed, and the laser transmission increases.
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As a member of a subclass of immunophilins, it is controversial that FKBP38 acts an upstream regulator of mTOR signaling pathway, which control the process of cell-growth, proliferation and differentiation. In order to explore the relationship between FKBP38 and mTOR in the Cashmere goat (Capra hircus) cells, a full-length cDNA was cloned (GenBank accession number JF714970) and expression pattern was analyzed. The cloned FKBP38 gene is 1,248 bp in length, containing an open reading frame (ORF) from nucleotide 13 to 1,248 which encodes 411 amino acids, and 12 nucleotides in front of the initiation codon. The full cDNA sequence shares 98% identity with cattle, 94% with horse and 90% with human. The putative amino acid sequence shows the higher homology which is 98%, 97% and 94%, correspondingly. The bioinformatics analysis showed that FKBP38 contained a FKBP_C domain, two TPR domains and a TM domain. Psite analysis suggested that the ORF encoding protein contained a leucine-zipper pattern and a Prenyl group binding site (CAAX box). Tissue-specific expression analysis was performed by semi-quantitative RT-PCR and showed that the FKBP38 expression was detected in all the tested tissues and the highest level of mRNA accumulation was detected in testis, suggesting that FKBP38 plays an important role in goat cells.
RESUMEN
Insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the six members of IGFBP family, important for cell growth, apoptosis and other IGF-stimulated signaling pathways. In order to explore the significance of IGFBP-5 in cells of the Inner Mongolian Cashmere goat (Capra hircus), IGFBP-5 gene complementary DNA (cDNA) was amplified by reverse transcription polymerase chain reaction (RT-PCR) from the animal's fetal fibroblasts and tissue-specific expression analysis was performed by semi-quantitative RT-PCR. The gene is 816 base pairs (bp) in length and includes the complete open reading frame, encoding 271 amino acids (GenBank accession number JF720883). The full cDNA nucleotide sequence has a 99% identity with sheep, 98% with cattle and 95% with human. The amino acids sequence shares identity with 99%, 99% and 99%, respectively. The bioinformatics analysis showed that IGFBP-5 has an insulin growth factor-binding protein homologues (IB) domain and a thyroglobulin type-1 (TY) domain, four protein kinase C phosphorylation sites, five casein kinase II phosphorylation sites, three prenyl group binding sites (CaaX box). The IGFBP-5 gene was expressed in all the tested tissues including testis, brain, liver, lung, mammary gland, spleen, and kidney, suggesting that IGFBP-5 plays an important role in goat cells.