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1.
Chemosphere ; 250: 126294, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32113092

RESUMO

The adverse effects of lead exposure on children's health have been widely investigated. Physical growth is a central indicator of health in early childhood. However, studies on the associations between lead exposure and the physical growth of young children are still equivocal. This study aimed to investigate the effects of lead exposure on young children's growth. A cross-sectional survey was conducted, and a total of 1678 young children were recruited. Blood lead levels were determined by graphite furnace atomic absorption spectrophotometry and anthropometric measurements were obtained by nurses. The weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI for-age Z-score (BMIZ) of the children were calculated according to World Health Organization standards. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between lead exposure and childhood anthropometric characteristics. Meanwhile, the sex differences in these associations were also examined. The median blood lead levels in total subjects, in boys and in girls were 46.44, 49.00 and 43.27 µg/L, respectively. After adjusting for confounders, a significantly negative association of blood lead levels with WAZ and HAZ was observed. After stratification by sex, the blood lead levels in children were negatively associated with WAZ and HAZ in boys but not in girls. Meanwhile, we further provide evidence that blood lead levels below 50 µg/L may also have adverse effects on young children's HAZ. Our findings suggest that lead exposure may have sex-specific effects on physical growth in young children and that blood lead level in a low levels may also have adverse effects on children's physical growth and development.

2.
Medicine (Baltimore) ; 99(13): e19373, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221064

RESUMO

Mutations in mitochondrial DNA, especially in 12S rRNA gene, are the most important causes for hearing loss. In particular, the A1555G and C1494T mutations have been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. To determine the frequency of C1494T mutation in deaf patients, in the current study, we screened this mutation in 655 patients with non-syndromic hearing loss and 300 control subjects. After PCR amplification of mitochondrial 12S rRNA gene and direct sequence analysis, we found that there were 2 patients carrying the C1494T mutation; however, this mutation was not detected in 300 healthy subjects. Further genetic counseling suggested that only 1 patient had an obvious family history of hearing impairment. Clinical evaluation showed that 3 of 10 matrilineal relatives suffered from hearing loss, with different age at onset of hearing loss. Molecular analysis revealed the presence of homoplasmic 12S rRNA C1494T and ND5 T12338C mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup F2. Interestingly, T12338C mutation resulted in the replacement of the first amino acid, a translation-initiating methionine with a threonine, shortening 2 amino acids of ND5 polypeptide. Moreover, this mutation is located in 2 nucleotides adjacent to the 3' end of the mt-tRNALeu(CUN) gene. Therefore, this mutation may alter ND5 mRNA metabolism and the processing of RNA precursors. Thus, the combination of T12338C and C1494T mutations may contribute to deafness expression in this family. Taken together, our data suggested that the C1494T mutation was the molecular basis for hearing loss, screening for the mitochondrial DNA pathogenic mutations was recommended for early detection, prevention, and diagnosis of mitochondrial deafness.

3.
BMC Bioinformatics ; 21(1): 61, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070280

RESUMO

BACKGROUND: The aberrant expression of microRNAs is closely connected to the occurrence and development of a great deal of human diseases. To study human diseases, numerous effective computational models that are valuable and meaningful have been presented by researchers. RESULTS: Here, we present a computational framework based on graph Laplacian regularized L2, 1-nonnegative matrix factorization (GRL2, 1-NMF) for inferring possible human disease-connected miRNAs. First, manually validated disease-connected microRNAs were integrated, and microRNA functional similarity information along with two kinds of disease semantic similarities were calculated. Next, we measured Gaussian interaction profile (GIP) kernel similarities for both diseases and microRNAs. Then, we adopted a preprocessing step, namely, weighted K nearest known neighbours (WKNKN), to decrease the sparsity of the miRNA-disease association matrix network. Finally, the GRL2,1-NMF framework was used to predict links between microRNAs and diseases. CONCLUSIONS: The new method (GRL2, 1-NMF) achieved AUC values of 0.9280 and 0.9276 in global leave-one-out cross validation (global LOOCV) and five-fold cross validation (5-CV), respectively, showing that GRL2, 1-NMF can powerfully discover potential disease-related miRNAs, even if there is no known associated disease.

4.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019252

RESUMO

Floral bud dormancy release of fruit tree species is greatly influenced by climate change. The lack of chilling accumulation often results in the occurrence of abnormal flower and low yields of sweet cherries (Prunus avium L.) in warm regions. To investigate the regulation of dormancy in sweet cherries, six DAM genes with homology to peach DAM, designated PavDAM1-6, have been identified and characterized. Phylogenetic analysis indicate that these genes are similar to DAMs in peach, apple and pear. The expression patterns of the PavDAMs in the low-chill cultivar 'Royal Lee' were different from that in the high-chill cultivar 'Hongdeng'. 'Royal Lee' exhibits lower transcriptional level of PavDAM1 compared to 'Hongdeng', especially at the stage of chilling accumulation, and transcriptional levels of PavDAM4/5 were high in both cultivars during the endodormancy. Ectopic expression of PavDAM1 and PavDAM5 in Arabidopsis resulted in plants with abnormal flower and seed development, especially the PavDAM5. Higher transcriptional levels of SOC1 were observed in transgenic PavDAM1/5 lines, and ectopic expression of PavSOC1 had the similar floral phenotype. Further, protein interaction analysis demonstrated that PavDAM1/5 could interact with PavSOC1 in vivo and in vitro, which will help clarify the molecular mechanism of the flower development in sweet cherry or other fruit trees.

5.
Plant Physiol Biochem ; 149: 190-200, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078897

RESUMO

Root architecture is very important for plant growth. In this study, we characterized the process of root formation in grapevine (Vitis vinifera L.). Continuous observation of root morphology during development revealed that the establishment of root system could be divided into five stages: initial cultivation (stage I), preliminary development (stage II), even change (stage III), root system formation (stage IV), and root architecture stability (stage V). The level of abscisic acid (ABA) increased from stages II to IV and was stable at stage V. Quantitative expression analysis of 11 genes encoding ABA-related rate-limiting enzymes in different tissues showed that the expression of VvPYL1 was the highest in roots. Spatiotemporal expression analysis showed that VvPYL1 was highly expressed during stages II and III. Furthermore, VvPYL1 was highly expressed in lateral roots of grapevine seedlings in tissue culture. Overexpression of VvPYL1 in Arabidopsis thaliana resulted in longer root hairs compared with wild-type plants. Moreover, the root hair length of transgenic lines was hypersensitive to exogenously applied ABA. Additionally, VvPYL1 overexpressing plants showed greater drought tolerance and longer root hairs than wild-type plants under osmotic stress. These results suggest that VvPYL1 may play a key role in root development and drought resistance.

6.
Plant Cell Environ ; 43(4): 903-919, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31851373

RESUMO

During maize production, drought throughout the flowering stage usually induces seed abortion and yield losses. The influence of postpollination drought stress on seed abortion and its underlying mechanisms are not well characterized. By intervening in the competition for assimilates between kernel siblings under different degrees of postpollination drought stresses accompanied by synchronous pollination (SP) and incomplete pollination (ICP) approaches, the mechanisms of postpollination abortion were investigated at physiological and molecular levels. Upon SP treatment, up to 15% of the fertilized apical kernels were aborted in the drought-exacerbated competition for assimilates. The aborted kernels exhibited weak sucrose hydrolysis and starch synthesis but promoted the synthesis of trehalose-6-phosphate and ethylene. In ICP where basal pollination was prevented, apical kernel growth was restored with reinstated sucrose metabolism and starch synthesis and promoted sucrose and hexose levels under drought stress. In addition, the equilibrium between ethylene and polyamine in response to the drought and pollination treatments was associated with the abortion process. We conclude that competition for assimilates drives postpollination kernel abortion, whereas differences in sugar metabolism and the equilibrium between ethylene and polyamines may be relevant to the "live or die" choice of kernel siblings during this competition.

7.
Environ Int ; 134: 105288, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765862

RESUMO

Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 µg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 µg/L) compared to girls (GM: 25.9 µg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 µg/L) level compared with those aged 36-84 months (GM 27.9 µg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.

8.
Arch Oral Biol ; 109: 104579, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31634727

RESUMO

OBJECTIVES: To investigate the effect and mechanism of calcium on LS8 cell differentiation, especially on phosphatidylinositol 3 kinase (PI3K) /protein kinase B(AKT) pathway. MATERIALS AND METHODS: Ameloblast-like LS8 cell line was used and additional 0-3.5 mmol/L calcium chloride was treated for 24 h, 48 h. Cell viability and morphological changes, cell cycle and associated regulatory proteins were analyzed. RESULTS: No significant effects on morphological changes were observed. Decreased cell viability and increased S phase cells were accompanied by the significant decrease of cyclin A and cyclin B proteins, and significant increase of cyclin D protein in LS8 cells. Additionally, kallikrein-4 and amelotin expressions were significantly increased. Finally, the levels of PI3K, AKT, p-AKT and forkhead box O3 (FOXO3) significantly downregulated after calcium treatment in LS8 cells. CONCLUSIONS: Calcium inhibit proliferation and promotes differentiation in LS8 cells, this is closely related to the downregulation of PI3K/AKT signal in LS8 cells.


Assuntos
Ameloblastos/enzimologia , Cálcio/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ameloblastos/efeitos dos fármacos , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Regulação para Baixo , Camundongos
9.
Mol Cancer ; 18(1): 178, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31810483

RESUMO

Analogous to DNA methylation and histone modification, RNA modification, as another epigenetic layer, plays an important role in many diseases, especially in tumours. As the most common form of RNA modification, m6A methylation has attracted increasing research interest in recent years. m6A is catalysed by RNA methyltransferases METTL3, METTL14 and WTAP (writers), m6A is removed by the demethylases FTO and ALKBH5 (erasers) and interacts with m6A-binding proteins, such as YT521-B homology (YTH) domain-containing proteins. This article reviews recent studies on methylation modification of m6A in gastrointestinal tract cancers.

10.
BMC Plant Biol ; 19(1): 528, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783789

RESUMO

BACKGROUND: Axillary buds allow the production of either vegetative or reproductive shoots, which display a plastic developmental potential of the plant to suit the prevailing environmental changes. Strawberry represents one of many plant species which displays horizontal above-ground growth of shoot development for asexual reproduction. Two distinct runner growth patterns exist in different strawberry species: one is called sympodial type such as Fragaria vesca, and the other one is called monopodial type such as Fragaria pentaphylla. Despite the runner growth morphology of these strawberry species have been well known, the mechanisms that determine the distinct patterns have rarely been reported. RESULTS: In this study, we used Fragaria vesca Hawaii-4 and Fragaria pentaphylla as model species, and captured the initiated dormant bud and non-dormant bud as materials to compare their transcriptome profiles and phytohormone content. Comparisons revealed that relatively higher auxin activity is present in the dormant bud and relatively higher cytokinin activity is in the non-dormant bud. Decapitation and pharmacological experiments on dormant buds showed that the reduction of auxin accumulation triggers the regeneration of vegetative shoots in dormant buds, and exogenous cytokinin application triggers cell fate turnover and generation of reproductive shoots. CONCLUSION: Here, we uncover a mechanism by which auxin and cytokinin coordinate the dormancy and outgrowth of axillary bud in strawberry runner. Our results suggest a contrasting behavior of auxin and cytokinin in control of axillary bud development, facilitating a preliminary understanding of shoot architecture formation in strawberry.

11.
Ageing Res Rev ; 56: 100965, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678652

RESUMO

Dementia represents one of the most common neurodegenerative disorders in older adults. However, it is still unclear whether non-pharmacological therapies (NPTs) are effective or not and which treatment should be preferred. We applied a series of search strategies to identify eligible randomized controlled trials on 1st October, 2018, investigating the effects of NPTs of dementia in the older persons. Pairwise and network meta-analyses were sequentially performed. A total of 31 trials were included, which enrolled 1895 participants and 7 NPTs. Compared with control group, all the NPTs included were statistically beneficial to cognitive function, and our study indicated Comprehensive Therapy(CT) [the surface under the cumulative ranking curve (SUCRA = 92.42%)] might be the best choice for dementia patients. Our study suggests CT might be the optimal NPT for improving the cognitive function of dementia patients. However, the above conclusions need to be further analyzed.

12.
J Synchrotron Radiat ; 26(Pt 6): 2075-2080, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31721753

RESUMO

The upgrade of the laser pump time-resolved X-ray probes, namely time-resolved X-ray absorption spectroscopy (TR-XAS) and X-ray diffraction (TR-XRD), implemented at the Beijing Synchrotron Radiation Facility, is described. The improvements include a superbunch fill, a high-efficiency fluorescence collection, an efficient spatial overlap protocol and a new data-acquisition scheme. After upgrade, the adequate TR-XAS signal is now obtained in a 0.3 mM solution, compared with a 6 mM solution in our previous report. Furthermore, to extend application in photophysics, the TR-XAS probe is applied on SrCoO2.5 thin film. And for the first time, TR-XAS is combined with TR-XRD to simultaneously detect the kinetic trace of structural changes in thin film.

13.
Math Biosci Eng ; 17(1): 910-927, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31731384

RESUMO

Pancreatic ductal adenocarcinoma (PAAD) is one of the most common malignant tumors in digestive system. To find the new therapeutic targets and explore potential mechanisms underlying PAAD, the bioinformatics has been performed in our study. The PAAD gene expression profile GSE28735 was chosen to analyze the differentially expressed genes (DEGs) between PAAD carcinoma tissues and normal adjacent tissues from 45 patients with PAAD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, a protein-protein interaction (PPI) network was also constructed to help us screen the top 20 hub genes in this profile and demonstrated the underlying interactions among them. The Gene Expression Profiling Interactive Analysis (GEPIA) was further performed in order to valid the mRNA levels of top5 up-regulated and top5 down-regualted DEGs, apart from exploring their association with survival rate as well as tumor stage. Finally, Q-PCR was further employed to valid the top5 up-regulated and top5 down-regulated genes in patients with PAAD. In our study, there were a total of 444 DEGs captured (271 up-regulated genes and 173 down-regulated genes). Among these DEGs, the top5 up-regulated genes were CEACAM5, SLC6A14, LAMC2, GALNT5 and TSPAN1 while the top5 down-regulated genes were GP2, CTRC, IAPP, PNLIPRP2 and PNLIPRP1. GO analysis disclosed that the DEGs were predominantly enriched in cell adhesion, lipid metabolism, integrin binding, proteolysis and calcium ion binding. KEGG analysis disclosed that the enriched pathway included pancreatic secretion, protein digestion and absorption, fat digestion and absorption, ECM-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. Survival analysis unveiled that the high expression levels of SLC6A14, GALNT5 and TSPAN1 may correlate with the poor prognosis while high expression levels of IAPP may contribute to a better prognosis in patients with PAAD. Additionally, the levels of CEACAM5, SLC6A14, LAMC2 and GALNT5 were also associated with tumor stage. Furthermore, according to the connectivity degree of these DEGs, we selected the top20 hub genes, namely ALB, FN1, EGF, MMP9, COL1A1, COL3A1, FBN1, CXCL12, POSTIN, BGN, VCAN, THBS2, KRT19, MET, MMP14, COL5A2, GCG, MUC1, MMP1 and CPB1, which were expected to be promising therapeutic targets in PAAD. Collectively, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of PAAD.

14.
BMC Plant Biol ; 19(1): 508, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752685

RESUMO

BACKGROUND: Carbohydrate partitioning and utilization is a key determinant of growth rate and of yield in plants and crops. There are few studies on crops in field conditions. In Arabidopsis, starch accumulation in leaves is a negative indicator of growth rate. RESULTS: Here, we wished to establish if starch accumulation in leaves could potentially be a marker for growth rate and yield in crops such as maize. We characterized daily patterns of non-structural carbohydrate (NSC) at different growth stages over two seasons for maize hybrids in the field. In 27 commercial hybrids, we found a significant negative relationship between residual starch in leaves and plant growth, but not with final yield and biomass. We then focused on three typical hybrids and established a method for calculation of C turnover in photosynthetic leaves that took into account photosynthesis, leaf area and NSC accumulation. The ratios of stored NSC decreased from approximately 15% to less than 4% with ongoing ontogeny changes from V7 to 28 days after pollination. CONCLUSION: The proportion rather than absolute amount of carbon partitioned to starch in leaves at all stages of development related well with yield and biomass accumulation. It is proposed that screening plants at an early vegetative growth stage such as V7 for partitioning into storage may provide a prospective method for maize hybrid selection. Our study provides the basis for further validation as a screening tool for yield.


Assuntos
Carbono/metabolismo , Amido/metabolismo , Zea mays/fisiologia , Ontologias Biológicas , Biomassa , Metabolismo dos Carboidratos , Produtos Agrícolas , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Estações do Ano , Zea mays/crescimento & desenvolvimento
15.
Fish Shellfish Immunol ; 95: 140-150, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629063

RESUMO

To learn more about red swamp crayfish related genes in response to bacterial infections, we investigated immune-related genes induced by lipopolysaccharide (LPS) in the hepatopancreas using high-throughput sequencing method. In present the study, a total of 55,107 unigenes were identified, with an average length of 678 bp. A total of 2215 differentially expressed genes (DEGs) were found, including 669 up-regulated genes and 1546 down-regulated genes. The result of Gene ontology (GO) analysis revealed that 3017 DEGs were enriched in 19 biological process subcategories, 17 cellular component subcategories and 15 molecular function subcategories. The top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that "ribosome" was the most abundant group, which had 34 DEGs. KEGG enrichment analysis identified several immune response pathways. Real-time quantitative reverse transcription-PCR (qRT-PCR) results exhibited that several immune responsive genes were greatly up-regulated following LPS stimulation as observed in the results of high-throughput sequencing. Overall, this study provides new insight into the immune defense mechanisms of P. clarkii against LPS infection.

16.
Materials (Basel) ; 12(20)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614733

RESUMO

Temperature distribution is an important process parameter of steel plates during electromagnetic induction heating treatment. This study uses the digital image correlation method to develop an effective non-contact temperature measurement that allows obtaining valuable information about the temperature value of a high temperature steel plate specimen and analyzing its temperature distribution. A principle of thermal radiation temperature measurement based on the color chagre couled device (CCD) technology was introduced. The image processing system encapsulates the image update module, form mode module, image event module and temperature analysis module. The error analysis and temperature calibration were carried out to make sure the error deviation of the measurement system was within a small range. The temperature distribution of B1500HS at high temperature was analyzed by the designed measurement system which was in good agreement with the result from Raynger 3i Plus temperature gun, indicating that the measurement system based on image processing basically meets the requirements of temperature distribution measurement of a high temperature steel plate, and provides an important reference for a high temperature steel plate in non-contact temperature distribution measurement.

17.
Int J Mol Med ; 44(5): 1789-1800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545402

RESUMO

Keloids are benign skin tumors with a high recurrence rate following surgical excision. Abnormal intracellular signaling is one of the key mechanisms involved in its pathogenesis. Over­activated phosphoinositide 3­kinase/RAC­alpha serine/threonine­protein kinase/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway and overproduction of histone deacetylases 2 (HDAC2) have also been observed in keloid fibroblasts (KFs). The present study aimed to explore the possibility of reversing the KF pathological phenotype using CUDC­907, a dual inhibitor of PI3K/Akt/mTOR pathway and HDACs. KFs and keloid xenografts were treated with CUDC­907 to examine its inhibitory effects on the pathological activities of KFs in vitro and in vivo. CUDC­907 inhibited cell proliferation, migration, invasion and extracellular matrix deposition of in vitro cultured KFs and also suppressed collagen accumulation and disrupted the capillaries of keloid explants ex vivo and in vivo. A mechanistic study of CUDC­907 revealed the initiation of cell cycle arrest at G2/M phase along with the enhanced expression of cyclin­dependent kinase inhibitor 1 and decreased expression of cyclin B in cells treated with CUDC­907. CUDC­907 not only inhibited AKT and mTOR phosphorylation and promoted the acetylation of histone H3, but also significantly inhibited the phosphorylation levels of Smad2/3 and Erk. These preclinical data demonstrating its anti­keloid effects suggest that CUDC­907 may represent a candidate drug for systemic keloid therapy.

18.
Cell Biochem Funct ; 37(7): 525-533, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478234

RESUMO

Increasing evidence has indicated the important roles of long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) in tumourigenesis as a potential oncogene. However, the function of SNHG7 in hepatic carcinoma remains unclear. In the present study, we found that SNHG7 expression was significantly upregulated in hepatic carcinoma tissues, especially in aggressive cases, and it was closely correlated with the poor prognosis. Furthermore, knockdown of SNHG7 inhibited the proliferation, migration, and invasion of hepatic carcinoma cell lines in vitro. Mechanistically, SNHG7 directly interacted with miR-425 as a ceRNA. Moreover, knockdown of SNHG7 significantly inhibited the tumorigenic Wnt/ß-catenin/EMT pathway. SNHG7 regulated Wnt/ß-catenin/EMT pathway through sponging miR-425 and played an oncogenic role in hepatic carcinoma progression. Together, our study elucidated the role of SNHG7 as a ceRNA in hepatic carcinoma, provided new potential diagnosis and therapeutic application in hepatic carcinoma progression. SIGNIFICANCE OF THE STUDY: SNHG7 could promote proliferation and metastasis of hepatic carcinoma cell in vitro and in vivo, suggesting that SNHG7 exerts tumorigenic role in hepatic carcinoma progression. Further mechanism research revealed that SNHG7 exhibited the tumorigenic role through Wnt/ß-catenin/EMT pathway as a miR-425 sponge. These findings provided new cues to understand the molecular signalling network in carcinogenesis of hepatic carcinoma, and it may provide new evidence for therapeutic application in hepatic carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , Animais , Carcinoma Hepatocelular/diagnóstico , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas Experimentais/diagnóstico , Neoplasias Hepáticas Experimentais/metabolismo , Camundongos , Camundongos Nus , RNA Longo não Codificante/genética
19.
Ecotoxicol Environ Saf ; 182: 109388, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299477

RESUMO

Iron in excess can have toxic effects on living organisms. In China, the freshwater crayfish Procambarus clarkii is a source of aquatic food with high-quality protein and has significant commercial value. P. clarkii shows oxidative stress on exposure to heavy metals, and antioxidant enzymes, such as ubiquitination enzymes and proteasomes, play important roles in oxidative stress. To understand the antioxidant defense system of P. clarkii, we analyzed the hepatopancreas transcriptomes of P. clarkii after stimulation with FeCl3. In total, 5199 differentially expressed genes (DEGs) were identified (2747 upregulated and 2452 downregulated). GO analysis revealed that these DEGs belonged to 16 cellular component, 16 molecular function, and 19 biological process subcategories. A total of 1069 DEGs were classified into 25 categories by using COG. Some antioxidant defense pathways, such as "Ubiquitin mediated proteolysis" and "Glutathione metabolism," were identified using KEGG. In addition, quantitative real time-PCR (qRT-PCR) substantiated the up-regulation of a random selection of DEGs including antioxidant and immune defense genes. We obtained information for P. clarkii transcriptome databases and new insights into the responses of P. clarkii hepatopancreas to heavy metals.


Assuntos
Antioxidantes/metabolismo , Astacoidea/efeitos dos fármacos , Compostos Férricos/toxicidade , Hepatopâncreas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Astacoidea/genética , China , Perfilação da Expressão Gênica , Hepatopâncreas/metabolismo , Estresse Oxidativo/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real
20.
Nucleic Acids Res ; 47(17): e98, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31291459

RESUMO

Recent technology has made it possible to measure DNA methylation profiles in a cost-effective and comprehensive genome-wide manner using array-based technology for epigenome-wide association studies. However, identifying differentially methylated regions (DMRs) remains a challenging task because of the complexities in DNA methylation data. Supervised methods typically focus on the regions that contain consecutive highly significantly differentially methylated CpGs in the genome, but may lack power for detecting small but consistent changes when few CpGs pass stringent significance threshold after multiple comparison. Unsupervised methods group CpGs based on genomic annotations first and then test them against phenotype, but may lack specificity because the regional boundaries of methylation are often not well defined. We present coMethDMR, a flexible, powerful, and accurate tool for identifying DMRs. Instead of testing all CpGs within a genomic region, coMethDMR carries out an additional step that selects co-methylated sub-regions first. Next, coMethDMR tests association between methylation levels within the sub-region and phenotype via a random coefficient mixed effects model that models both variations between CpG sites within the region and differential methylation simultaneously. coMethDMR offers well-controlled Type I error rate, improved specificity, focused testing of targeted genomic regions, and is available as an open-source R package.


Assuntos
Ilhas de CpG/genética , Metilação de DNA/genética , Epigênese Genética , Epigenômica/métodos , Software , Humanos , Modelos Biológicos , Fenótipo
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