RESUMEN

Despite extensive research, the prognosis of high-grade glioblastoma multiforme (GBM) has improved only slightly because of the limited response to standard treatments. Recent advances (discoveries of molecular biomarkers) provide new opportunities for the treatment of GBM. The aim of the present study was to identify diagnostic biomarkers of high-grade GBM. First, we combined 3 microarray expression datasets to screen them for genes differentially expressed in patients with high-grade GBM relative to healthy subjects. Next, the target network was constructed via the empirical Bayesian coexpression approach, and centrality analysis and a molecular complex detection (MCODE) algorithm were performed to explore hub genes and functional modules. Finally, a validation test was conducted to verify the bioinformatic results. A total of 277 differentially expressed genes were identified according to the criteria P < 0.05 and |log2(fold change)| ≥ 1.5. These genes were most significantly enriched in the cell cycle pathway. Centrality analysis uncovered 9 hub genes; among them, TFDP1 showed the highest degree of connectivity (43) and is a known participant in the cell cycle pathway; this finding pointed to the important role of TFDP1 in the progression of high-grade GBM. Experimental validation mostly supported the bioinformatic results. According to our study results, the gene TFDP1 and the cell cycle pathway are strongly associated with high-grade GBM; this result may provide new insights into the pathogenesis of GBM.

Asunto(s)

Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/genética , Factor de Transcripción DP1/biosíntesis , Adulto , Algoritmos , Biología Computacional , Femenino , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/genética , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Transducción de Señal/genética , Factor de Transcripción DP1/genética

RESUMEN

The polymerase chain reaction-single-strand conformation polymorphism technique was employed to measure mononucleotide diversity in the coding region of the leptin and leptin receptor genes in the Arctic fox. The relationships between specific genetic mutations and reproductive performance in Arctic foxes were determined to im-prove breeding strategies. We found that a leptin gene polymorphism was significantly associated with body weight (P < 0.01), abdominal circumference (P < 0.01), and fur length (P < 0.01). Furthermore, a polymorphism in the leptin receptor gene was associated with carcass weight and guard hair length (P < 0.01). Leptin and leptin receptor gene combinatorial genotypes were significantly associated with abdominal circumference, fur length (P < 0.01), and body weight (P < 0.05). The leptin gene is thus a key gene affecting body weight, abdominal circumference, and fur length in Arctic foxes, whereas variations in the leptin receptor mainly affect carcass weight and guard hair. The marker loci identified in this study can be used to assist in the selection of Arctic foxes for breeding to raise the production performance of this species.

Asunto(s)

Peso Corporal/genética , Cabello , Leptina/genética , Receptores de Leptina/genética , Animales , Cruzamiento , Zorros/genética , Genotipo , Polimorfismo de Nucleótido Simple

RESUMEN

The large-scale loach, Paramisgurnus dabryanus, is a small freshwater fish of major economic importance in many Asian countries, particularly China and South Korea. Fifteen polymorphic microsatellite (simple sequence repeat) markers were obtained through cross-species amplification between this loach and a related species, Misgurnus anguillicaudatus (GenBank accession numbers: KC117456 to KC117470). The number of alleles per locus ranged from 5 to 12 among 40 individuals, and the average observed and expected heterozygosities were 0.344 and 0.828, respectively. Three loci showed significant deviations from Hardy-Weinberg equilibrium. These polymorphic loci could provide a valuable tool for investigations of the population genetics, phylogeography, and conservation genetics of P. dabryanus.

Asunto(s)

Cipriniformes/genética , Genética de Población , Repeticiones de Microsatélite/genética , Polimorfismo Genético , Alelos , Animales , China , Heterocigoto

RESUMEN

Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.

Asunto(s)

Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Hipoglucemiantes/farmacología , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales , Quinasas Asociadas a rho/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcio/metabolismo , Caspasa 9/genética , Caspasa 9/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Dinaminas/genética , Dinaminas/metabolismo , GTP Fosfohidrolasas , Hipoglucemiantes/uso terapéutico , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Ratas , Ratas Sprague-Dawley

RESUMEN

Birth defects are structural and/or functional malformations present at birth that cause physical or mental disability and are important public health problems. Our study was aimed at genetic analysis and prenatal diagnosis of congenital anomalies to understand the cause of certain birth defects. Karyotypes and array-comparative genomic hybridization (aCGH) were performed on a pregnant woman, surrounding amniotic fluid, and her husband. A short-stature panel genetic test was conducted in accordance with the phenotype of the fetus. Following examination, it was determined that the karyotype and aCGH results were normal. The RECQL4 gene in the fetus showed compound heterozygous mutations, and each parent was found to be a carrier of one of the mutations. The two heterozygous mutations (c.2059-1G>C and c.2141_2142delAG) were detected in the RECQL4 (NM_004260) gene in the fetus; therefore, the fetus was predicted to have Baller-Gerold syndrome. These two mutations have not previously been reported. In addition, these results identified a 25% risk of the parents having a sec-ond conceptus with this congenital disease. Therefore, prenatal genetic diagnosis was highly recommended for future pregnancies.

Asunto(s)

Craneosinostosis/diagnóstico , Heterocigoto , Mutación , Radio (Anatomía)/anomalías , RecQ Helicasas/genética , Adulto , Hibridación Genómica Comparativa , Craneosinostosis/genética , Femenino , Humanos , Cariotipificación , Masculino , Embarazo , Diagnóstico Prenatal

RESUMEN

In this study, a survey was conducted through questionnaire distribution and physical examinations were performed in 10,150 residents that were over 40 years old in Luzhou city. Respondents were selected by the multi-stage sampling method. The mean body mass index (BMI) of the sample population was 23.9 ± 3.3 kg/m(2). Among men, BMI showed a negative relationship with increasing age (P < 0.05), whereas among women, it showed a positive relationship (P < 0.001). The rates of overweight and obesity increased with age and reached a peak between 60 to 70 years of age (P < 0.001). The rates of overweight and obesity varied with different working conditions, training situations, educational levels, marital status, and other factors (P < 0.05). Age, educational level, daily sitting time, and family history of diabetes were factors that influenced the prevalence of overweight and obesity through multivariate logistic regression analysis (P < 0.05). The incidences of overweight and obesity among the middle-aged population were found to be significantly high. Therefore, prevention and control measures should be adopted as soon as possible.

Asunto(s)

Obesidad/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Aumento de Peso

RESUMEN

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Asunto(s)

Humanos , Antineoplásicos/farmacología , Movimiento Celular/genética , Proliferación Celular/genética , /genética , Proteína del Grupo de Complementación F de la Anemia de Fanconi/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Interferencia de ARN , ARN Interferente Pequeño

RESUMEN

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Asunto(s)

Antineoplásicos/farmacología , Movimiento Celular/genética , Proliferación Celular/genética , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación F de la Anemia de Fanconi/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Interferencia de ARN , ARN Interferente Pequeño

RESUMEN

Sequence-related amplified polymorphism (SRAP) is a recently developed molecular marker technique that is stable, simple, reliable, and achieves moderate to high numbers of codominant markers. This study is the first to apply SRAP markers in a mammal, namely the Arctic fox. In order to investigate the genetic diversity of the Arctic fox and to provide a reference for use of its germplasm, we analyzed 7 populations of Arctic fox by SRAP. The genetic similarity coefficient, genetic distance, proportion of polymorphic loci, total genetic diversity (Ht), genetic diversity within populations (Hs), and genetic differentiation (Gst) were calculated using the Popgene software package. The results indicated abundant genetic diversity among the different populations of Arctic fox studied in China. The genetic similarity coefficient ranged from 0.1694 to 0.0417, genetic distance ranged from 0.8442 to 0.9592, and the proportion of polymorphic loci was smallest in the TS group. Genetic diversity ranged from 0.2535 to 0.3791, Ht was 0.3770, Hs was 0.3158, Gst was 0.1624, and gene flow (Nm) was estimated at 2.5790. Thus, a high level of genetic diversity and many genetic relationships were found in the populations of Arctic fox evaluated in this study.

Asunto(s)

Zorros/genética , Polimorfismo Genético , Animales , Femenino , Sitios Genéticos , Marcadores Genéticos , Masculino , Técnicas de Amplificación de Ácido Nucleico

RESUMEN

With the development of molecular marker technology, crop breeding has been accelerated by marker-assisted selection for the improvement of quantitative traits. However, due to the traits' polygenic nature, traditional marker-assisted selection methods are ill-suited for identification of quantitative trait loci. Genomic selection (GS) was introduced into crop breeding to achieve more accurate predictions by considering all genes or markers simultaneously. We used dozens of sequence-characterized amplified region (SCAR) markers for genotyping soybean varieties, and we identified markers associated with hundred-seed weight. The best linear unbiased predictor and Bayesian liner regression methods were used to construct GS models to predict the hundred-seed weight trait based upon genotype information for trait selection. Both GS models showed good prediction performance in soybean, as the correlation coefficient between genomic estimated breeding values and true breeding values was as high as 0.904. This indicated that GS was performed effectively based on dozens of SCAR markers in soybean; these markers were of low density but easily detectable. Therefore, the combination of GS modeling and highly effective molecular marker technology involving SCAR markers can facilitate genetic breeding in soybean. This approach may also be suitable for genetic selection in other crops, such as wheat, maize, and rice.

Asunto(s)

Genoma de Planta , Glycine max/genética , Semillas/genética , Selección Genética , Marcadores Genéticos , Modelos Genéticos , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Semillas/anatomía & histología , Glycine max/anatomía & histología

RESUMEN

There are many kinds of dicotyledonous C(3) plants, which often release CO(2) fixed by photosynthesis and consume energy in photorespiration. In Escherichia coli, glycolate can be metabolized by an oxidation pathway that has some of the same compounds as dicotyledonous photorespiration. With the bacterial glycolate metabolism pathway, photorespiration of dicotyledonous plants is genetically modified for less CO(2) release and more biomass. In this study, two plasmids involved in this modification were constructed for targeting two enzymes of the glycolate oxidizing pathway, glyoxylate carboligase and tartronic semialdehyde reductase, and glycolate dehydrogenase in Arabidopsis thaliana mitochondria in this pathway. All three enzymes are located in chloroplast by transit peptide derived from Pisum sativum small unit of Rubisco. So far, some crops have been transformed by the two plasmids. Through transformation of the two plasmids, photosynthesis of dicotyledonous plants may be promoted more easily and release less CO(2) into the atmosphere.

Asunto(s)

Oxidorreductasas de Alcohol/genética , Arabidopsis/genética , Carboxiliasas/genética , Glicolatos/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Secuencia de Aminoácidos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/genética , Escherichia coli/genética , Pisum sativum/genética , Fotosíntesis/genética , Plantas Modificadas Genéticamente , Plásmidos/genética , Ribulosa-Bifosfato Carboxilasa/genética