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1.
Cell ; 155(5): 997-1007, 2013 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-24267886

RESUMEN

Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to contribute to a common phenotype, we have attempted to identify time periods, brain regions, and cell types in which these genes converge. We have constructed coexpression networks based on the hcASD "seed" genes, leveraging a rich expression data set encompassing multiple human brain regions across human development and into adulthood. By assessing enrichment of an independent set of probable ASD (pASD) genes, derived from the same sequencing studies, we demonstrate a key point of convergence in midfetal layer 5/6 cortical projection neurons. This approach informs when, where, and in what cell types mutations in these specific genes may be productively studied to clarify ASD pathophysiology.


Asunto(s)
Encéfalo/metabolismo , Trastornos Generalizados del Desarrollo Infantil/genética , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Animales , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Trastornos Generalizados del Desarrollo Infantil/patología , Exoma , Femenino , Feto/metabolismo , Feto/patología , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Ratones , Mutación , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Análisis de Secuencia de ADN
2.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731807

RESUMEN

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.


Asunto(s)
Adipocitos , Diferenciación Celular , MicroARNs , Fosfolipasa C beta , ARN Circular , Animales , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/genética , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Fosfolipasa C beta/metabolismo , Fosfolipasa C beta/genética , ARN Circular/genética , ARN Circular/metabolismo , Ovinos , Transducción de Señal
3.
Int J Mol Sci ; 24(19)2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37834341

RESUMEN

Fat deposition involves the continuous differentiation of adipocytes and lipid accumulation. Studies have shown that microRNA miR-136 and 17ß-hydroxysteroid dehydrogenase type 12 (HSD17B12) play important roles in lipid accumulation. However, the regulatory mechanism through which miR-136 targets HSD17B12 during ovine adipogenesis remains unclear. This study aimed to elucidate the role of miR-136 and HSD17B12 in adipogenesis and their relationship in ovine adipose-derived stromal vascular fractions (SVFs). The target relationship between miR-136 and HSD17B12 was predicted and confirmed using bioinformatics and a dual-luciferase reporter assay. The results showed that miR-136 promoted proliferation and inhibited adipogenic differentiation of ovine SVFs. We also found that HSD17B12 inhibited proliferation and promoted adipogenic differentiation of ovine SVFs. Collectively, our results indicate that miR-136 facilitates proliferation and attenuates adipogenic differentiation of ovine SVFs by targeting HSD17B12. These findings provide a theoretical foundation for further elucidation of the regulatory mechanisms of lipid deposition in sheep.


Asunto(s)
Adipogénesis , MicroARNs , Animales , Ovinos/genética , Adipogénesis/genética , MicroARNs/genética , Tejido Adiposo , Proliferación Celular , Lípidos , Diferenciación Celular/genética
4.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36768295

RESUMEN

Adipose tissues represent an important energy storage organ in animals and are the largest endocrine organ. It plays an important regulatory role in the pathogenesis of insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose development is a complex biological process involving multiple key genes, signaling pathways, and non-coding RNAs, including microRNAs and circular RNAs. In this study, we characterized circITGB1 and named its host gene ITGB1, which is differentially expressed in sheep of different months based on sequencing data. We collated and analyzed the sequencing data to select miRNA-23a with strong binding to ARRB1. We found that miRNA-23a regulates the development and differentiation of sheep adipocytes by targeting ARRB1. As a competing endogenous RNA, circITGB1 overexpression effectively alleviated the inhibitory effect of miR-23a on ARRB1. Conclusively, we provide evidence that circITGB1 regulates the proliferation and differentiation of sheep adipocytes via the miR-23a/ARRB1 pathway. This study provides a scientific basis for further studies on adipose tissue development at the circRNA level.


Asunto(s)
Fenómenos Biológicos , MicroARNs , Animales , Ovinos/genética , MicroARNs/metabolismo , Transducción de Señal , Proliferación Celular/genética , Adipocitos/metabolismo
5.
Int J Mol Sci ; 24(4)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36834919

RESUMEN

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular fractions (SVFs). Here, based on previous sequencing data and bioinformatics analysis, a novel circINSR was identified in sheep, which acts as a sponge to promote miR-152 in inhibiting the adipogenic differentiation of ovine SVFs. The interactions between circINSR and miR-152 were examined using bioinformatics, luciferase assays, and RNA immunoprecipitation. Of note, we found that circINSR was involved in adipogenic differentiation via the miR-152/mesenchyme homeobox 2 (MEOX2) pathway. MEOX2 inhibited adipogenic differentiation of ovine SVFs and miR-152 inhibited the expression of MEOX2. In other words, circINSR directly isolates miR-152 in the cytoplasm and inhibits its ability to promote adipogenic differentiation of ovine SVFs. In summary, this study revealed the role of circINSR in the adipogenic differentiation of ovine SVFs and its regulatory mechanisms, providing a reference for further interpretation of the development of ovine fat and its regulatory mechanisms.


Asunto(s)
MicroARNs , Ovinos/genética , Animales , MicroARNs/genética , Fracción Vascular Estromal , Tejido Adiposo/metabolismo , Adipogénesis/genética , Metabolismo de los Lípidos , Diferenciación Celular
6.
BMC Genomics ; 23(1): 323, 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35459093

RESUMEN

BACKGROUND: Tibial dyschondroplasia (TD) is a bone disorder in which dead chondrocytes accumulate as a result of apoptosis and non-vascularization in the tibial bone of broiler chickens. The pathogenicity of TD is under extensive research but is yet not fully understood. Several studies have linked it to apoptosis and non-vascularization in the tibial growth plate (GP). We conceived the idea to find the differentially expressed genes (DEGs) in chicken erythrocytes which vary in expression over time using a likelihood-ratio test (LRT). Thiram was used to induce TD in chickens, and then injected Ex-FABP protein at 0, 20, and 50 µg.kg-1 to evaluate its therapeutic effect on 30 screened immunity and angiogenesis-related genes using quantitative PCR (qPCR). The histopathology was also performed in TD chickens to explore the shape, circularity, arrangements of chondrocytes and blood vessels. RESULTS: Clinical lameness was observed in TD chickens, which decreased with the injection of Ex-FABP. Histopathological findings support Ex-FABP as a therapeutic agent for the morphology and vascularization of affected chondrocytes in TD chickens. qPCR results of 10 immunity (TLR2, TLR3, TLR4, TLR5, TLR7, TLR15, IL-7, MyD88, MHCII, and TRAF6) and 20 angiogenesis-related genes (ITGAV, ITGA2, ITGB2, ITGB3, ITGA5, IL1R1, TBXA2R, RPL17, F13A1, CLU, RAC2, RAP1B, GIT1, FYN, IQGAP2, PTCH1, NCOR2, VAV-like, PTPN11, MAML3) regulated when Ex-FABP is injected to TD chickens. CONCLUSION: Immunity and angiogenesis-related genes can be responsible for apoptosis of chondrocytes and vascularization in tibial GP. Injection of Ex-FABP protein to thiram induced TD chickens decrease the chondrocytes damage and improves vascularization.


Asunto(s)
Osteocondrodisplasias , Enfermedades de las Aves de Corral , Animales , Biomarcadores , Pollos/genética , Pollos/metabolismo , Eritrocitos/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/farmacología , Placa de Crecimiento/metabolismo , Neovascularización Patológica/patología , Osteocondrodisplasias/patología , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/patología , Tiram , Tibia , Transcriptoma
7.
Magn Reson Med ; 87(5): 2194-2208, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34888911

RESUMEN

PURPOSE: To achieve simultaneous T1, w /proton density fat fraction (PDFF)/ R 2 ∗ mapping in abdomen within a single breadth-hold, and validate the accuracy using state-of-art measurement. THEORY AND METHODS: An optimized multiple echo gradient echo (GRE) sequence with dual flip-angle acquisition was used to realize simultaneous water T1 (T1, w )/PDFF/ R 2 ∗ quantification. A new method, referred to as "solving the fat-water ambiguity based on their T1 difference" (SORT), was proposed to address the fat-water separation problem. This method was based on the finding that compared to the true solution, the wrong (or aliased) solution to fat-water separation problem showed extra dependency on the applied flip angle due to the T1 difference between fat and water. The B 1 + measurement sequence was applied to correct the B 1 + inhomogeneity for T1, w relaxometry. The 2D parallel imaging was incorporated to enable the acquisition within a single breath-hold in abdomen. RESULTS: The multi-parametric quantification results of the proposed method were consistent with the results of reference methods in phantom experiments (PDFF quantification: R2  = 0.993, mean error 0.73%; T1, w quantification: R2  = 0.999, mean error 4.3%; R 2 ∗ quantification: R2  = 0.949, mean error 4.07 s-1 ). For volunteer studies, robust fat-water separation was achieved without evident fat-water swaps. Based on the accurate fat-water separation, simultaneous T1, w /PDFF/ R 2 ∗ quantification was realized for whole liver within a single breath-hold. CONCLUSION: The proposed method accurately quantified T1, w /PDFF/ R 2 ∗ for the whole liver within a single breath-hold. This technique serves as a quantitative tool for disease management in patients with hepatic steatosis.


Asunto(s)
Hígado , Imagen por Resonancia Magnética , Abdomen/diagnóstico por imagen , Humanos , Fantasmas de Imagen , Reproducibilidad de los Resultados
8.
Bioorg Med Chem Lett ; 72: 128729, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35413415

RESUMEN

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated encouraging clinical outcomes for patients with EGFR-mutated non-small cell lung cancer, a considerable number of patients will develop drug resistance and eventually undergo disease progression after taking EGFR-TKIs for a period of time. EGFRdel19/T790M/C797S and EGFRL858R/T790M/C797S are two most prevalent tertiary EGFR mutants identified in Osimertinib-resistant tumors and currently there is no therapy approved clinically targeting these mutants. In this study, we designed and synthesized a series of novel 4th generation EGFR inhibitors based on scaffold of Brigatinib. After extensive SAR studies, compound 23, the most promising candidate, exhibited strong biochemical potencies against EGFRdel19/T790M/C797S, EGFRL858R/T790M/C797S and other clinically relevant EGFR mutants while sparing wild type EGFR. In cellular assays, compound 23 potently inhibited proliferation of BaF3EGFR del19/T790M/C797S and PC-9EGFR del19/T790M/C797S. Moreover, compound 23 demonstrated good DMPK profile in mouse PK study.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Resistencia a Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares/patología , Ratones , Mutación , Compuestos Organofosforados , Inhibidores de Proteínas Quinasas/química , Pirimidinas
9.
Environ Res ; 215(Pt 3): 114420, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36167116

RESUMEN

Anaerobic degradation is the major pathway for microbial degradation of benzene, toluene, ethylbenzene, and xylenes (BTEX) under electron acceptor lacking conditions. However, how exogenous electron acceptors modulate BTEX degradation through shaping the microbial community structure remains poorly understood. Here, we investigated the effect of various exogenous electron acceptors on BTEX degradation as well as methane production in anaerobic microbiota, which were enriched from the same contaminated soil. It was found that the BTEX degradation capacities of the anaerobic microbiota gradually increased along with the increasing redox potentials of the exogenous electron acceptors supplemented (WE: Without exogenous electron acceptors < SS: Sulfate supplement < FS: Ferric iron supplement < NS: Nitrate supplement), while the complexity of the co-occurring networks (e.g., avgK and links) of the microbiota gradually decreased, showing that microbiota supplemented with higher redox potential electron acceptors were less dependent on the formation of complex microbial interactions to perform BTEX degradation. Microbiota NS showed the highest degrading capacity and the broadest substrate-spectrum for BTEX, and it could metabolize BTEX through multiple modules which not only contained fewer species but also different key microbial taxa (eg. Petrimonas, Achromobacter and Comamonas). Microbiota WE and FS, with the highest methanogenic capacities, shared common core species such as Sedimentibacter, Acetobacterium, Methanobacterium and Smithella/Syntrophus, which cooperated with Geobacter (microbiota WE) or Desulfoprunum (microbiota FS) to perform BTEX degradation and methane production. This study demonstrates that electron acceptors may alter microbial function by reshaping microbial community structure and regulating microbial interactions and provides guidelines for electron acceptor selection for bioremediation of aromatic pollutant-contaminated anaerobic sites.


Asunto(s)
Contaminantes Ambientales , Microbiota , Anaerobiosis , Benceno/química , Derivados del Benceno , Biodegradación Ambiental , Electrones , Hierro , Metano , Nitratos/química , Oxidantes , Suelo , Sulfatos/química , Tolueno/química , Xilenos
10.
Heredity (Edinb) ; 126(2): 320-334, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32980863

RESUMEN

Genomic best linear-unbiased prediction (GBLUP) assumes equal variance for all marker effects, which is suitable for traits that conform to the infinitesimal model. For traits controlled by major genes, Bayesian methods with shrinkage priors or genome-wide association study (GWAS) methods can be used to identify causal variants effectively. The information from Bayesian/GWAS methods can be used to construct the weighted genomic relationship matrix (G). However, it remains unclear which methods perform best for traits varying in genetic architecture. Therefore, we developed several methods to optimize the performance of weighted GBLUP and compare them with other available methods using simulated and real data sets. First, two types of methods (marker effects with local shrinkage or normal prior) were used to obtain test statistics and estimates for each marker effect. Second, three weighted G matrices were constructed based on the marker information from the first step: (1) the genomic-feature-weighted G, (2) the estimated marker-variance-weighted G, and (3) the absolute value of the estimated marker-effect-weighted G. Following the above process, six different weighted GBLUP methods (local shrinkage/normal-prior GF/EV/AEWGBLUP) were proposed for genomic prediction. Analyses with both simulated and real data demonstrated that these options offer flexibility for optimizing the weighted GBLUP for traits with a broad spectrum of genetic architectures. The advantage of weighting methods over GBLUP in terms of accuracy was trait dependant, ranging from 14.8% to marginal for simulated traits and from 44% to marginal for real traits. Local-shrinkage prior EVWGBLUP is superior for traits mainly controlled by loci of a large effect. Normal-prior AEWGBLUP performs well for traits mainly controlled by loci of moderate effect. For traits controlled by some loci with large effects (explain 25-50% genetic variance) and a range of loci with small effects, GFWGBLUP has advantages. In conclusion, the optimal weighted GBLUP method for genomic selection should take both the genetic architecture and number of QTLs of traits into consideration carefully.


Asunto(s)
Estudio de Asociación del Genoma Completo , Modelos Genéticos , Teorema de Bayes , Genómica , Genotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo
11.
Nanotechnology ; 33(9)2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-34798627

RESUMEN

In the paper, the temperature dependence of magnetic nanoparticle (MNP) paramagnetic chemical shift (paraSHIFT) was studied by magnetic resonance (MR) spectroscopy. Based on it, iron oxide MNPs are considered as MR shifting probes for determining the temperature in liquids. With the increase in measurement temperature of the MNP reagent with MNPs, the decrease of MNP magnetization would make the peak of spectroscopy shift to the higher chemical shift area. The peak shift is related to the magnetic susceptibility of MNPs, which can be determined by MR frequency as a function of temperature and particle size. Experiments on temperature-dependent chemical shifts are performed for MNP samples with different core sizes and the estimated temperature accuracy can achieve 0.1 K. Combined with the contrast effect of magnetic nanoparticles in magnetic resonance imaging at 3 T, this technology can realize temperature imaging.

12.
Sensors (Basel) ; 21(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807200

RESUMEN

Magnetic nanoparticles (MNPs) can work as temperature sensors to realize temperature measurement due to the excellent temperature sensitivity of their magnetization. This paper mainly reports on a performance optimization method of MNPs DC thermometry model. Firstly, by exploring the influencing factors of MNPs magnetization temperature sensitivity, it is found that the optimal excitation of the magnetic field to make the temperature sensitivity of MNPs reach their optimal value is, approximately, inversely proportional to the particle size of MNPs. Then, the temperature sensitivity of MNP magnetization is modulated by adding appropriate DC bias magnetic field in the original triangular wave excitation field, to optimize the original DC thermometry model based on MNP magnetization. The simulation results show that the temperature measurement performance of small-size MNPs can be significantly improved. In short, this paper optimizes the temperature measurement performance of the original DC thermometry model based on MNP magnetization and provides a new application idea for temperature measurement of small-size MNPs.

13.
Environ Geochem Health ; 43(5): 1817-1837, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33125612

RESUMEN

Anhui Province is the most important energy production base for eastern China. Many large pithead coal-fired power plants are being operated in the coal-rich Huainan and Huaibei coalfields in northern Anhui. To assess the environmental risks of local coal-fired power plants, a complete atmospheric emission inventory of F, As, Se, Cd, Sb, Hg, Pb, and U from coal-fired power plants in Anhui was compiled by a simple mass-balance-based method. The results indicated that the atmospheric emissions of F, As, Se, Cd, Sb, Hg, Pb, and U in 2017 from the Anhui coal-fired power plants were 578 t, 2.01 t, 15.3 t, 0.57 t, 0.18 t, 2.80 t, 23.7 t, and 0.099 t, respectively. The emission factor is the major contributor to the uncertainties in this inventory. With increasing energy demand by the more developed eastern China region, the atmospheric emissions of volatile hazardous elements will continue to increase in the near future.


Asunto(s)
Contaminantes Atmosféricos/análisis , Metales/análisis , Centrales Eléctricas , Contaminación del Aire/análisis , China , Carbón Mineral , Monitoreo del Ambiente
14.
Nanotechnology ; 31(34): 345101, 2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32408274

RESUMEN

This paper reports on a highly accurate approach of magnetic resonance (MR) thermometry using iron oxide magnetic nanoparticles (MNPs) as temperature sensors. An empirical model for the description of the temperature dependent R 2 relaxation rate is proposed by taking into account the temperature sensitivity of the MNP magnetization. The temperature sensitivity of the MNP magnetization (η) and the temperature sensitivity of the R 2 relaxation rate (κ) are simulated with the proposed empirical models to investigate their dependence on the magnetic field and the particle size. Simulation results show the existence of optimal magnetic fields Hoη and Hoκ that maximize the temperature sensitivities η and κ. Furthermore, simulations and experiments demonstrate that the optimal magnetic field Hoη (Hoκ ) decreases with increasing the particle size. Experiments on temperature dependent R 2 relaxation rate are performed at different magnetic fields for MNP samples with different iron concentrations. Experimental results show that the proposed MR thermometry using MNPs as temperature sensors allows a temperature estimation accuracy of about 0.05 °C. We believe that the achieved approach of highly accurate MR thermometry is of great interest and significance to biomedicine and biology.

15.
Dig Dis Sci ; 65(4): 1032-1041, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31562612

RESUMEN

BACKGROUND/AIMS: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers with poor prognosis. Metastasis is the leading cause of cancer-related deaths. The growth arrest and DNA damage-inducible 45 gamma (GADD45G) has been reported to correlate with survival, invasion, and metastasis of ESCC. This study was aimed to investigate the role and mechanism of GADD45G in ESCC cell migration and invasion. METHODS: Both the effects of GADD45G and its need for E-cadherin to function on ESCC cell migration and invasion were determined through loss- and gain-of-function approaches via Transwell assays. The interaction between GADD45G and E-cadherin was detected by GST-pull down and IP assays. The expression of E-cadherin upon GADD45G overexpression was evaluated by RT-qPCR and western blot. The level of E-cadherin in cytoplasmic, nuclear, and membrane fractions was examined by western blot following subcellular fractionation. RESULTS: Knockdown of GADD45G increased the migration and invasion abilities of KYSE150 cells, while overexpression of GADD45G showed the opposite effects on YES2 and KYSE30 cells. GADD45G could interact with E-cadherin and enhanced its membrane level. Knockdown of E-cadherin abolished the inhibitory effects of GADD45G on ESCC cell migration and invasion. Intriguingly, dimer-dissociating mutant of GADD45G could not interact with E-cadherin and almost lost its ability to suppress the ESCC cell migration and invasion. CONCLUSIONS: This study reveals a novel role for GADD45G in inhibiting the ESCC cell migration and invasion, which will provide a new insight in understanding the ESCC metastatic mechanism.


Asunto(s)
Biomarcadores de Tumor/deficiencia , Cadherinas/deficiencia , Movimiento Celular/fisiología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Antígenos CD/genética , Biomarcadores de Tumor/genética , Cadherinas/genética , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Técnicas de Silenciamiento del Gen/métodos , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Invasividad Neoplásica/patología , Unión Proteica/fisiología
16.
Biochem Biophys Res Commun ; 516(3): 1013-1018, 2019 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-27003255

RESUMEN

Aberrant expression of ubiquitin Protein ligase E3C (UBE3C) has been documented in breast cancer (BC). MicroRNAs (miRNAs) were shown to play an important role in the regulation of tumor properties in BC. However, whether miRNAs contributes to UBE3C expression in BC cells remains poorly understood. In this study, we report that UBE3C was a direct target of miR-30a-5p. Expression of miR-30a-5p in BC cells reduced UBE3C expression. MCF-7 and MDA-MB-453 cells were transfected miR-30a-5p-overexpression, and found that cell proliferation and migration were inhibited. In contrast, when miR-30a-5p inhibitor were transfected into MCF-7 and MDA-MB-453 cells, cell proliferation and migration were promoted. We study demonstrated that upregulation of miR-30a-5p was significantly suppressed levels of cyclin B1, cyclin D1 and c-myc. Moreover, Correlation analysis indicated that expression of miR-30a-5p was highly negatively correlated with UBE3C, which was upregulated in BC specimens. These data highlight the important role of miR-30a-5p/UBE3C axis in BC development and progression. Therefore, miR-30a-5p activation or UBE3C inhibition may be provide a novel strategy for the treatment of BC.


Asunto(s)
Neoplasias de la Mama/genética , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Ubiquitina-Proteína Ligasas/genética , Regiones no Traducidas 3'/genética , Secuencia de Bases , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Células HEK293 , Humanos , Células MCF-7 , Homología de Secuencia de Ácido Nucleico , Ubiquitina-Proteína Ligasas/metabolismo
17.
Magn Reson Med ; 82(1): 436-448, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30860290

RESUMEN

PURPOSE: To develop a method based on fat-water transition region extraction (TREE) for robust fat-water separation and quantification in challenging scenarios, including low signal-to-noise ratio (SNR), fast changing B0 field, and disjointed anatomies. THEORY AND METHODS: In TREE method, the phasor solutions of each pixel were categorized into fat-dominant and water-dominant groups. The fat-water transition region was then extracted by detecting sudden changes in the phasor maps. The phasor solutions of the pixels in the transition region were solved by choosing the smoothest phasor combinations. For the remaining subregions, the phasor solution was then determined by all the surrounding transition region pixels. The proposed method was validated using various datasets, including some from the International Society for Magnetic Resonance in Medicine (ISMRM) 2012 Challenge. RESULTS: Quantitative score of proposed method (9936.8 of 10,000) is comparable to the winner (9951.9) of ISMRM 2012 Challenge. The total processing time was 179.3 s for 15 datasets. Sagittal spine data with ~400 mm field of view in head-foot direction were used to compare TREE with several representative region-growing methods. Results showed that the proposed method was robust under fast changing B0 field, disjointed anatomies and low SNR area. No apparent fat-water swap was observed in the low SNR (SNR ~ 10) dataset. Accurate proton density fat fraction results were also produced from the proposed method. CONCLUSION: A method based on fat-water transition region extraction was proposed for robust water-fat separation and fat fraction quantification. The method worked well in spatially disjointed objects, fast changing B0 field, and low SNR application.


Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Agua Corporal/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Abdomen/diagnóstico por imagen , Algoritmos , Tobillo/diagnóstico por imagen , Humanos , Relación Señal-Ruido , Columna Vertebral/diagnóstico por imagen
18.
Proteome Sci ; 17: 4, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31673248

RESUMEN

BACKGROUND: In previous study, we performed next-gene sequencing to investigate the differentially expressed transcripts of bovine follicular granulosa cells (GCs) at dominant follicle (DF) and subordinate follicle (SF) stages during first follicular wave. Present study is designed to further identify the key regulatory proteins and signaling pathways associated with follicular development using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multi-omics data analysis approach. METHODS: DF and SF from three cattle were collected by daily ultrasonography. The GCs were isolated from each follicle, total proteins were digested by trypsin, and then proteomic analyzed via LC-MS/MS, respectively. Proteins identified were retrieved from Uniprot-COW fasta database, and differentially expressed proteins were used to functional enrichment and KEGG pathway analysis. Proteome data and transcriptome data obtained from previous studies were integrated. RESULTS: Total 3409 proteins were identified from 30,321 peptides (FDR ≤0.01) obtained from LC-MS/MS analysis and 259 of them were found to be differentially expressed at different stage of follicular development (fold Change > 2, P < 0.05). KEGG pathway analysis of proteome data revealed important signaling pathways associated with follicular development, multi-omics data analysis results showed 13 proteins were identified as being differentially expressed in DF versus SF. CONCLUSIONS: This study represents the first investigation of transcriptome and proteome of bovine follicles and offers essential information for future investigation of DF and SF in cattle. It also will enrich the theory of animal follicular development.

19.
Helicobacter ; 24(2): e12563, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30672082

RESUMEN

BACKGROUND: The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population-based H pylori screen-and-treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). MATERIALS AND METHODS: Decision trees and Markov models were developed to evaluate the cost-effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen-and-treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost-effectiveness ratio. Uncertainty was explored by one-way and probabilistic sensitivity analyses. RESULTS: For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen-and-treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality-adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen-and-treat strategy over the no-screen strategy. The one-way and probabilistic sensitivity analyses confirmed the robustness of our study's results. CONCLUSIONS: Compared with the no-screen strategy, population-based screen-and-treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population.


Asunto(s)
Enfermedades Asintomáticas/terapia , Análisis Costo-Beneficio , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Tamizaje Masivo/economía , Enfermedades Asintomáticas/economía , China , Dispepsia/complicaciones , Dispepsia/prevención & control , Gastritis/complicaciones , Gastritis/diagnóstico , Gastritis/prevención & control , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/economía , Infecciones por Helicobacter/prevención & control , Humanos , Cadenas de Markov , Úlcera Péptica/complicaciones , Úlcera Péptica/prevención & control , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/prevención & control
20.
Helicobacter ; 24(6): e12656, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31571330

RESUMEN

BACKGROUND & AIMS: Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective. METHODS: An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion. RESULTS: A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05). CONCLUSIONS: Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.


Asunto(s)
Infecciones por Helicobacter/psicología , Médicos/psicología , Adulto , Anciano , Antibacterianos/uso terapéutico , Concienciación , China , Países en Desarrollo , Educación Médica , Femenino , Conocimientos, Actitudes y Práctica en Salud , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/fisiología , Humanos , Aprendizaje , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Encuestas y Cuestionarios
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