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Purpose-To use micro-ribonucleic acid (microRNA) profiles in the vitreous for differential diagnosis of primary vitreoretinal lymphoma and uveitis. Design-A prospective cross-sectional study design Methods-This prospective cross-section study included 17 diffuse large B-cell primary vitreoretinal lymphoma and 12 uveitic patients. The supernatant of ocular fluid was subjected to total RNA extraction, followed by complementary deoxyribonucleic acid (cDNA) synthesis. Selected samples (primarydoi:10.1016/j.ajo.2013.12.014 pmid:24345320 pmcid:PMC3961580 fatcat:quawbr3wbbew5o3e5jh6fcerqu
more »... oretinal lymphoma n=3, uveitis n=3) were arrayed by a real time polymerase chain reaction (RT-PCR)-based microRNA panel that detects 168 human mature microRNAs. The markers promising in distinct levels between uveitis and lymphoma were further tested for all other 23 samples by individual RT-PCR analysis. Results-Of 168 microRNAs in the array, 66.5% were detectable with consistent higher microRNA-484, microRNA-197, and microRNA-132 in the primary vitreoretinal lymphoma vitreous and higher microRNA-155, microRNA-200c, and microRNA-22* in the uveitic ocular fluids. The results were normalized by different combinations of 7 control microRNAs . After optimization, normalization against microRNA-16 was as equally reliable as the average of the 7 control microRNAs. Individual assays of all samples supported the pattern yielded from the array analysis. But only microRNA-155 was significantly higher in the uveitic vitreous compared to that with lymphoma. Conclusions-Mature microRNAs are detectable in ocular fluid samples. Primary vitreoretinal B-cell lymphoma and uveitis might be characterized by distinct microRNA signatures. Quantification of ocular microRNA-155 might be helpful in the differential diagnosis of these two diseases.
With advancing stages of degeneration, denaturation and degradation of proteoglycans in the nucleus pulposus (NP) lead to tissue dehydration and signal intensity loss on T2-weighted MR images. Pfirrmann grading is widely used for grading degeneration of intervertebral discs (IVDs). The criterion to differentiate IVDs of Pfirrmann Grade I from the other grades is NP homogeneity. Pfirrmann grading is qualitative and its assessment may be subjective. Therefore, assessment of quantitative objectivedoi:10.1186/s12891-017-1838-0 pmid:29162082 pmcid:PMC5697099 fatcat:cmgqijvnbjfrpfp6tm3htzx2re
more »... measures correlating with early disc degeneration may complement the grading. This study aimed to evaluate the applicability of the distance between the center weighted by signal intensity (weighted center) and the geometric center as a parameter of NP homogeneity. Other phenomena related to advancing stages of degeneration were also investigated. Methods: MR images of 65 asymptomatic volunteers with a total of 288 lumbar IVDs with clearly identifiable nucleus pulposus boundary (Pfirrmann Grade I, II and III) were included in this study. A custom-written program was developed to determine the IVD longitudinal axis, define the NP boundary, and to locate the coordinates of geometric and weighted NP centers on the mid-sagittal image of each studied IVD. The distances between the weighted and geometric centers on the longitudinal axis and the perpendicular axis of each IVD were calculated. Results: The weighted center located posterior to the geometric center, which indicated the signal intensity was lower at the anterior portion of the NP, in 85.8% of studied IVDs. The distance between the weighted and geometric center on the longitudinal axis was significantly shorter in homogeneous (Pfirrmann Grade I) than in inhomogeneous (Grade II) IVDs. The distance on the perpendicular axis in Grade III IVDs was significantly larger than that in Grade I and Grade II IVDs. Conclusion: The relationship between the weighted and geometric centers can serve as an indicator for NP homogeneity. The distance between both centers through advancing stages of degeneration demonstrated decrease of signal intensity progressing along the longitudinal axis initially and then along the cranio-caudal direction at later stages. These findings could provide insights of initiation and subsequent progression of degenerative changes in IVDs.
Associations between pediatric emergency department (ED) visits and ambient concentrations of particulate matter ≤ 2.5 μm in diameter (PM 2.5 ) have been reported in previous studies, although few were performed in nonmetropolitan areas. oBjective: We estimated associations between daily PM 2.5 concentrations, using a two-stage model that included land use parameters and satellite aerosol optical depth measurements at 1-km resolution, and ED visits for six pediatric conditions in the U.S. statedoi:10.1289/ehp.1509856 pmid:26452298 pmcid:PMC4858390 fatcat:vsjhzy7cvjbg3m7odj6ii2imoa
more »... of Georgia by urbanicity classification. Methods: We obtained pediatric ED visits geocoded to residential ZIP codes for visits with nonmissing PM 2.5 estimates and admission dates during 1 January 2002-30 June 2010 for 2-to 18-year-olds for asthma or wheeze (n = 189,816), and for 0-to 18-year-olds for bronchitis (n = 76,243), chronic sinusitis (n = 15,745), otitis media (n = 237,833), pneumonia (n = 52,946), and upper respiratory infections (n = 414,556). Daily ZIP code-level estimates of 24-hr average PM 2.5 were calculated by averaging concentrations within ZIP code boundaries. We used timestratified case-crossover models stratified on ZIP code, year, and month to estimate odds ratios (ORs) between ED visits and same-day and previous-day PM 2.5 concentrations at the ZIP code level, and we investigated effect modification by county-level urbanicity. results: A 10-μg/m 3 increase in same-day PM 2.5 concentrations was associated with ED visits for asthma or wheeze (OR = 1.013; 95% CI: 1.003, 1.023) and upper respiratory infections (OR = 1.015; 95% CI: 1.008, 1.022); associations with previous-day PM 2.5 concentrations were lower. Differences in the association estimates across levels of urbanicity were not statistically significant. conclusion: Pediatric ED visits for asthma or wheeze and for upper respiratory infections were associated with PM 2.5 concentrations in Georgia. citation: Strickland MJ, Hao H, Hu X, Chang HH, Darrow LA, Liu Y. 2016. Pediatric emergency visits and short-term changes in PM 2.5 concentrations in the U.S. state of Georgia. Environ Health Perspect 124:690-696; http://dx.
MicroRNAs (miRNAs) are the class of small endogenous RNAs that play an important regulatory role in cells by negatively affecting gene expression at transcriptional and post-transcriptional levels. There have been extensive studies aiming to discover miRNAs and to analyze their functions in the cells from a variety of species. However, there are no published studies of miRNA profiles in human testis using next generation sequencing (NGS) technology. Results: We employed Solexa sequencingdoi:10.1371/journal.pone.0066809 pmid:23826142 pmcid:PMC3691314 fatcat:v64ekripxnc67h6x5fsuti6koa
more »... ogy to profile miRNAs in normal human testis. Total 770 known and 5 novel human miRNAs, and 20121 piRNAs were detected, indicating that the human testis has a complex population of small RNAs. The expression of 15 known and 5 novel detected miRNAs was validated by qRT-PCR. We have also predicted the potential target genes of the abundant known and novel miRNAs, and subjected them to GO and pathway analysis, revealing the involvement of miRNAs in many important biological phenomenon including meiosis and p53-related pathways that are implicated in the regulation of spermatogenesis. Conclusions: This study reports the first genome-wide miRNA profiles in human testis using a NGS approach. The presence of large number of miRNAs and the nature of their target genes suggested that miRNAs play important roles in spermatogenesis. Here we provide a useful resource for further elucidation of the regulatory role of miRNAs and piRNAs in the spermatogenesis. It may also facilitate the development of prophylactic strategies for male infertility.
Global Spine Journal
Yang: Research support (SpinalCyte) Jun Zhu: none Ding Chen: none Yejia Zhang: Research support (SpinalCyte) Howard S. ... SpinalCyte) Thomas Cha: Research support (SpinalCyte, North American Spine Society, Gordon and Betty Moore Foundation); Consultant (Bio2, GE Healthcare) Ting-Hsien Kao: Research support (SpinalCyte) Shu-Hua ...doi:10.1055/s-0036-1582391 pmid:27853661 pmcid:PMC5110358 fatcat:n4rcyrr2mfdknowckraj4esf3q
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide and in China. We know miRNAs influence gene expression in tumorigenesis, but it is unclear how miRNAs affect gene expression or influence survival at the genome-wide level in ESCC. We performed miRNA and mRNA expression arrays in 113 ESCC cases with tumor/normal matched tissues to identify dysregulated miRNAs, to correlate miRNA and mRNA expressions, and to relate miRNA and mRNA expression changes to survivaldoi:10.1186/s12885-020-06901-6 pmid:32375686 fatcat:stow4efyj5d4lckde46m4mslxm
more »... and clinical characteristics. Thirty-nine miRNAs were identified whose tumor/normal tissue expression ratios showed dysregulation (28 down- and 11 up-regulated by at least two-fold with P < 1.92E-04), including several not previously reported in ESCC (miR-885-5p, miR-140-3p, miR-708, miR-639, miR-596). Expressions of 16 miRNAs were highly correlated with expressions of 195 genes (P < 8.42E-09; absolute rho values 0.51-0.64). Increased expressions of miRNA in tumor tissue for both miR-30e* and miR-124 were associated with increased survival (P < 0.05). Similarly, nine probes in eight of 818 dysregulated genes had RNA expression levels that were nominally associated with survival, including NF1, ASXL1, HSPA4, TGOLN2, BAIAP2, EZH2, CHAF1A, SUPT7L. Our characterization and integrated analysis of genome-wide miRNA and gene expression in ESCC provides insights into the expression of miRNAs and their relation to regulation of RNA targets in ESCC tumorigenesis, and suggest opportunities for the future development of miRs and mRNAs as biomarkers for early detection, diagnosis, and prognosis in ESCC.
White matter hyperintensity (WMH) has been regarded as one of the major contributor of the vascular hypothesis of late-life depression (LLD) and cognitive decline in the elderly. On the other hand, cognitive reserve (CR) has long been hypothesized to provide resilience and adaptability against age- and disease-related insults. This study examined the role of CR, using proxy of education, in moderating the association between WMH and clinical LLD expression. A total of 54 elderly diagnosed withdoi:10.3389/fpsyt.2020.00249 pmid:32322221 pmcid:PMC7158948 fatcat:gaenjsfd7vht3izi6up5x6q3iq
more »... ajor depressive disorder and 38 matched healthy controls participated in this study. They received MRI scanning and a battery of neuropsychological tests. WMH was quantified by an automated segmentation algorithm. Linear regression analyses were conducted separately in the LLD and control groups to examine the effects of WMH, education and their interaction in depression severity and various cognitive domains. WMH was significantly and negatively associated with executive function only in the healthy controls. In patients with LLD, we observed a significant interactive effect in education on the association between WMH and depression severity and language domain (category fluency task). Specifically, those with high education showed less depressive symptoms and cognitive decline as WMH increased. WMH is associated with lower cognitive function. However, in patients with LLD, high education attenuates the deleterious effect of WMH on mood and cognition. Therefore, CR appears to exert a protective effect on neurocognitive functioning in people with LLD.
Populations in north central China are at high risk for oesophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), and genetic variation in epigenetic machinery genes and pathways may contribute to this risk. Methods: We used the adaptive multilocus joint test to analyse 192 epigenetic genes involved in chromatin remodelling, DNA methylation and microRNA biosynthesis in 1942 ESCC and 1758 GC cases [1126 cardia (GCA) and 632 non-cardia adenocarcinoma (GNCA)] and 2111 controls withdoi:10.1093/ije/dyv050 pmid:25921222 pmcid:PMC4598798 fatcat:34f73rapvje3nbsv736vbu77ki
more »... e ancestry. We examined potential function of risk alleles using in silico and expression quantitative trait loci (eQTLs) analyses. Results: Suggestive pathway-based associations were observed for the overall epigenetic (P-value PATH ¼ 0.034) and chromatin remodelling (P-value PATH ¼ 0.039) pathways with risk of GCA, but not GC, GNCA or ESCC. Overall, 37 different epigenetic machinery genes were associated with risk of one or more upper gastrointestinal (UGI) cancer sites (P-value GENE < 0.05), including 14 chromatin remodelling genes whose products are involved in the regulation of HOX genes. We identified a gastric eQTL (rs12724079; rho ¼ 0.37; P ¼ 0.0006) which regulates mRNA expression of ASH1L. Several suggestive eQTLs were also found in oesophageal (rs10898459 in EED), gastric cardia (rs7157322 in DICER1; rs8179271 in ASH1L), and gastric non-cardia (rs1790733 in PPP1CA) tissues. Conclusions: Results of our analyses provide limited but suggestive evidence for a role of epigenetic gene variation in the aetiology of UGI cancer. • We investigated the relation of genetic variation in genes in the epigenetic pathway and subpathways to risk of upper gastrointestinal (UGI) cancers. • We found suggestive evidence for associations between gastric cardia cancer and the epigenetic pathway as well as the chromatin remodelling subpathway. • The top-ranked epigenetic pathway genes associated with UGI cancer were predominantly from the chromatin remodelling subpathway. • Expression quantitative trait loci (eQTL) analyses found several SNPs whose variants may regulate mRNA levels of important chromatin remodelling and microRNA biosynthesis genes associated with UGI cancer risk. • This analysis, the first comprehensive assessment relating epigenetic pathway gene variation to risk of UGI cancer, provides limited evidence suggesting a role for epigenetic pathway in UGI cancer susceptibility.
Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastricdoi:10.1158/0008-5472.can-15-0338 pmid:26857264 pmcid:PMC4873357 fatcat:l5e34loxdrc6tewra3m4qtpg7y
more »... dia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR. Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. Ó2016 AACR.
Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regionsdoi:10.1186/1471-2164-7-299 pmid:17134496 pmcid:PMC1687196 fatcat:5inlb5efx5holgzd7wtrxk7fz4
more »... re identified by two methods--using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software--and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified. These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.
Objective: To profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy. Methods: We performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62) and gastric noncardia adenocarcinomas (n = 72) and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies.doi:10.1371/journal.pone.0063826 pmid:23717493 pmcid:PMC3661768 fatcat:o7wsfktczrbytayqmotbs5huwi
more »... ion of dysregulated genes was also related to survival of cases. Results: Principal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P,4.7E-07 and at least two-fold difference in magnitude) in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47%) dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%), and about one-fourth in noncardia only (n = 144, 28%). Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers. Conclusions: The dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.
Post-transcriptional regulation of mRNAs plays an essential role in the control of gene expression. mRNAs are regulated in ribonucleoprotein (RNP) complexes by RNA-binding proteins (RBPs) along with associated protein and noncoding RNA (ncRNA) cofactors. A global understanding of post-transcriptional control in any cell type requires identification of the components of all of its RNP complexes. We have previously shown that these complexes can be purified by immunoprecipitation using anti-RBPdoi:10.1261/rna.055186.115 pmid:26847261 pmcid:PMC4793217 fatcat:npbmi56hifgfvlnr7q3othxge4
more »... nthetic antibodies produced by phage display. To develop the large number of synthetic antibodies required for a global analysis of RNP complex composition, we have established a pipeline that combines (i) a computationally aided strategy for design of antigens located outside of annotated domains, (ii) high-throughput antigen expression and purification in Escherichia coli, and (iii) high-throughput antibody selection and screening. Using this pipeline, we have produced 279 antibodies against 61 different protein components of Drosophila melanogaster RNPs. Together with those produced in our low-throughput efforts, we have a panel of 311 antibodies for 67 RNP complex proteins. Tests of a subset of our antibodies demonstrated that 89% immunoprecipitate their endogenous target from embryo lysate. This panel of antibodies will serve as a resource for global studies of RNP complexes in Drosophila. Furthermore, our high-throughput pipeline permits efficient production of synthetic antibodies against any large set of proteins.
Cancer stem cells (CSCs) possess characteristics associated with normal stem cells, specifically the abilities to renew themselves and to give rise to all cell types (differentiation). It is assumed that induction of differentiation in CSCs would reduce their ability to form tumors. What triggers CSC differentiation and the role of "differentiation" in tumorigenesis remain elusive. Methods: Glioma stem cell (GSC) lines and subcutaneous as well as orthotopic xenografts established from freshdoi:10.1186/s13287-015-0174-2 pmid:26472041 pmcid:PMC4606508 fatcat:yc3mnoredrbizgnnzrtpchxhxq
more »... ical specimens of glioblastoma multiforme were used. Results: Exposure of GSCs to serum activates mitochondrial respiration and causes an increase in mitochondrial reactive oxygen species (ROS) as well as oxidative stress responses, leading to the appearance of differentiation morphology and a deceased expression of CSC markers. Chemical perturbation of the mitochondrial electron transport chain causes ROS increase and further downregulation of stem cell markers, while antioxidant N-acetylcysteine reduces ROS and suppresses the differentiation of GSCs. Surprisingly, the serum-induced differentiated GSCs exhibit greater ability to form tumor in both orthotopic and subcutaneous xenograft models, which can be suppressed by N-acetyl-cysteine. Mitochondrial ROS from the serum-stimulated cells triggered the activation of nuclear factor-kappa-B (NFκB) pathway, which is a potential mechanism for the promotion of tumorigenesis. Conclusion: This study suggests that ROS generated from active mitochondrial respiration in the presence of serum is critical in CSCs activation, which promotes tumor development in vivo.
While this paper was being prepared, Yang et al. 37 published a brief report on an ESCC pathway analysis (based on missense SNPs and SNPs located to gene coding regions) which used Gene Ontology (GO) ... In agreement with our current results, Yang et al. 37 reported that CASP8 rs376982 and not rs13016963 was the more likely causal ESCC SNP, but the authors did not describe the regulatory mechanism linking ...doi:10.1093/ije/dyv294 pmid:26635288 pmcid:PMC4881832 fatcat:nhd42anierhvva52rkivaanrmy
Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors. In the current study we focus on biallelic loss and its relation to expression of mRNA and miRNA in ESCC using results from 500K SNP, mRNA, and miRNA arrays in 30 cases from a high-risk region of China. Results: (i) Biallelic loss was uncommon but when itdoi:10.1186/s12864-015-1919-0 pmid:26409826 pmcid:PMC4584010 fatcat:drvwmfjy2zbklhwm336tu4y5ei
more »... d it exhibited a consistent pattern: only 77 genes (<0.5 %) showed biallelic loss in at least 10 % of ESCC samples, but nearly all of these genes were concentrated on just four chromosomal arms (ie, 42 genes on 3p, 14 genes on 9p, 10 genes on 5q, and seven genes on 4p). (ii) Biallelic loss was associated with lower mRNA expression: 52 of the 77 genes also had RNA expression data, and 41 (79 %) showed lower expression levels in cases with biallelic loss compared to those without. (iii) The relation of biallelic loss to miRNA expression was less clear but appeared to favor higher miRNA levels: of 60 miRNA-target gene pairs, 34 pairs (57 %) had higher miRNA expression with biallelic loss than without, while 26 pairs (43 %) had lower miRNA expression. (iv) Finally, the effect of biallelic loss on the relation between miRNA and mRNA expression was complex. Biallelic loss was most commonly associated with a pattern of elevated miRNA and reduced mRNA (43 %), but a pattern of both reduced miRNA and mRNA was also common (35 %). Conclusion: Our results indicate that biallelic loss in ESCC is uncommon, but when it occurs it is localized to a few specific chromosome regions and is associated with reduced mRNA expression of affected genes. The effect of biallelic loss on miRNA expression and on the relation between miRNA and mRNA expressions was complex.
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