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1.
Biomed Pharmacother ; 125: 109944, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32062386

RESUMEN

Cardiac fibrosis is a common pathological condition that contributes to the progression of many cardiac diseases. Circular RNAs (circRNAs) are emerging as new regulators of cardiac fibrosis. However, the expression and function of circRNAs in cardiac fibrosis remain largely unknown. The present study aims to investigate the circRNA expression profile and identify the roles of circRNAs in cardiac fibrosis. Transforming growth factor-ß1 (TGF-ß1) was used to establish an in vitro model of cardiac fibrosis in cardiac fibroblasts. CircRNA sequencing revealed that a total of 283 circRNAs were aberrantly expressed in fibrotic cardiac fibroblasts, with 79 upregulated and 204 downregulated. The expression changes of randomly selected circRNAs were validated by real-time PCR. A circRNA-based competing endogenous RNA network 1755 nodes and 30394 edges was established, and module analysis was conducted using the plug-in MCODE. KEGG pathway enrichment analysis was performed for mRNAs involved in the top three enriched modules. The results showed that these mRNAs were enriched in cardiac fibrosis-related signalling pathways, including the 'TGF-beta signaling pathway', 'MAPK signaling pathway', 'AMPK signaling pathway', and 'PI3K-Akt signaling pathway'. The predicted ceRNAs and bioinformatics analysis revealed the potential role of circRNAs in cardiac fibrosis, which would provide useful information for understanding the mechanism and finding effective prevention and treatment targets for cardiac fibrosis.


Asunto(s)
Fibroblastos/patología , ARN Circular/genética , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Biología Computacional , Regulación hacia Abajo , Fibrosis/patología , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Regulación hacia Arriba
2.
Yi Chuan ; 38(12): 1056-1068, 2016 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-28034838

RESUMEN

Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. They play important roles in development, disease initiation and progression such as tumorigenesis. Compared to typical enhancers (TEs), most key oncogenes in tumor cells are driven by SEs, and common diseases such as Alzheimer's disease related variations are enriched in SEs. SEs hold great promising in key oncogenes identification and diseases-associated variants discovery. In this review, we first summarize how to identify enhancers on a genome-wide scale, and then introduce the concept of SEs and the methodology for SEs identification. Lastly, we describe SEs' main structural and functional properties and discuss its application in the future research.


Asunto(s)
Secuencias Reguladoras de Ácidos Nucleicos/fisiología , Transcripción Genética/genética , Animales , Humanos , Secuencias Reguladoras de Ácidos Nucleicos/genética
3.
Exp Diabetes Res ; 2012: 128694, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22899900

RESUMEN

The skin, the body's largest organ, plays an important role in the biotransformation/detoxification and elimination of xenobiotics and endogenous toxic substances, but its role in oxidative stress and insulin resistance is unclear. We investigated the relationship between skin detoxification and oxidative stress/insulin resistance by examining burn-induced changes in nicotinamide degradation. Rats were divided into four groups: sham-operated, sham-nicotinamide, burn, and burn-nicotinamide. Rats received an intraperitoneal glucose injection (2 g/kg) with (sham-nicotinamide and burn-nicotinamide groups) or without (sham-operated and burn groups) coadministration of nicotinamide (100 mg/kg). The results showed that the mRNA of all detoxification-related enzymes tested was detected in sham-operated skin but not in burned skin. The clearance of nicotinamide and N(1)-methylnicotinamide in burned rats was significantly decreased compared with that in sham-operated rats. After glucose loading, burn group showed significantly higher plasma insulin levels with a lower muscle glycogen level than that of sham-operated and sham-nicotinamide groups, although there were no significant differences in blood glucose levels over time between groups. More profound changes in plasma H(2)O(2) and insulin levels were observed in burn-nicotinamide group. It may be concluded that decreased skin detoxification may increase the risk for oxidative stress and insulin resistance.


Asunto(s)
Quemaduras/metabolismo , Resistencia a la Insulina , Estrés Oxidativo , Piel/metabolismo , Animales , Antioxidantes/química , Glucemia/metabolismo , Glucógeno/química , Peróxido de Hidrógeno/química , Insulina/metabolismo , Masculino , Niacinamida/análogos & derivados , Niacinamida/farmacología , Ratas , Ratas Sprague-Dawley , Xenobióticos/química
4.
Theor Appl Genet ; 123(6): 943-58, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21735236

RESUMEN

Changes in water potential, growth elongation, photosynthesis of three-leaf-old seedlings of maize inbred line YQ7-96 under water deficit (WD) for 0.5, 1 and 2 h and re-watering (RW) for 24 h were characterized. Gene expression was analyzed using cDNA microarray covering 11,855 maize unigenes. As for whole maize plant, the expression of WD-regulated genes was characterized by up-regulation. The expression of WD-regulated genes was categorized into eight different patterns, respectively, in leaves and roots. Newly found and WD-affected cellular processes were metabolic process, amino acid and derivative metabolic process and cell death. A great number of the analyzed genes were found to be regulated specifically by RW and commonly by both WD and RW, respectively, in leaves. It is therefore concluded that (1) whole maize plant tolerance to WD, as well as growth recovery from WD, depends at least in part on transcriptional coordination between leaves and roots; (2) WD exerts effects on the maize, especially on basal metabolism; (3) WD could probably affect CO(2) uptake and partitioning, and transport of fixed carbons; (4) WD could likely influence nuclear activity and genome stability; and (5) maize growth recovery from WD is likely involved in some specific signaling pathways related to RW-specific responsive genes.


Asunto(s)
Sequías , Genes de Plantas , Agua , Zea mays/crecimiento & desarrollo , Zea mays/genética , Dióxido de Carbono/metabolismo , Elementos Transponibles de ADN , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Análisis de Secuencia por Matrices de Oligonucleótidos , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plantones/genética , Plantones/metabolismo , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Estrés Fisiológico , Zea mays/metabolismo
5.
Plant Mol Biol ; 74(6): 573-90, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20957510

RESUMEN

A cDNA library was constructed from the root tissues of cassava variety Huanan 124 at the root bulking stage. A total of 9,600 cDNA clones from the library were sequenced with single-pass from the 5'-terminus to establish a catalogue of expressed sequence tags (ESTs). Assembly of the resulting EST sequences resulted in 2,878 putative unigenes. Blastn analysis showed that 62.6% of the unigenes matched with known cassava ESTs and the rest had no 'hits' against the cassava database in the integrative PlantGDB database. Blastx analysis showed that 1,715 (59.59%) of the unigenes matched with one or more GenBank protein entries and 1,163 (40.41%) had no 'hits'. A cDNA microarray with 2,878 unigenes was developed and used to analyze gene expression profiling of Huanan 124 at key growth stages including seedling, formation of root system, root bulking, and starch maturity. Array data analysis revealed that (1) the higher ratio of up-regulated ribosome-related genes was accompanied by a high ratio of up-regulated ubiquitin, proteasome-related and protease genes in cassava roots; (2) starch formation and degradation simultaneously occur at the early stages of root development but starch degradation is declined partially due to decrease in UDP-glucose dehydrogenase activity with root maturity; (3) starch may also be synthesized in situ in roots; (4) starch synthesis, translocation, and accumulation are also associated probably with signaling pathways that parallel Wnt, LAM, TCS and ErbB signaling pathways in animals; (5) constitutive expression of stress-responsive genes may be due to the adaptation of cassava to harsh environments during long-term evolution.


Asunto(s)
Etiquetas de Secuencia Expresada , Biblioteca de Genes , Manihot/genética , Perfilación de la Expresión Génica , Manihot/crecimiento & desarrollo , Manihot/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Transducción de Señal , Almidón/biosíntesis , Almidón/genética
6.
World J Gastroenterol ; 15(45): 5674-84, 2009 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-19960564

RESUMEN

AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance. CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Niacinamida/análogos & derivados , Niacinamida/efectos adversos , Adulto , Anciano , Aldehído Oxidasa/antagonistas & inhibidores , Aldehído Oxidasa/metabolismo , Animales , Glucemia/metabolismo , Eritrocitos/metabolismo , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Insulina/metabolismo , Masculino , Persona de Mediana Edad , NAD/metabolismo , Niacinamida/administración & dosificación , Niacinamida/metabolismo , Oxidantes/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Sudor/química , Adulto Joven
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