The expression of CK19 in primary hepatocellular carcinoma (HCC) is associated with a poor outcome. However, few studies have investigated the expression profile of CK19 in regional lymph nodes (LNs) ...of HCC after hepatic resection. The purpose of this study was to evaluate the expression of CK19 in primary liver tumor and regional LNs of HCC with and without lymph node metastasis (LNM).
The expression of CK19 in patients with (n = 16) and without LNM (n = 26) was examined using immunohistochemical staining. Both the primary tumor and LN specimen were studied for their CK19 expression. Clinico-pathological variables and prognostic significance were analyzed.
Immunopositivity of CK19 in primary liver tumor was significantly correlated with LNM (P = 0.005) and tumor non-encapsulation (P <0.005). Univariate analysis showed that CK19 expression in primary liver tumor, CK19 expression in regional LN, vascular invasion, daughter nodules, positive resection margin and American Joint Committee on Cancer (AJCC) tumor stage significantly decreased overall survival. Multivariate analysis demonstrated that daughter nodules (P = 0.001) and CK19 expression in regional LN (P = 0.002) were independent prognostic factors for overall survival.
This study showed that CK19 expression in regional LN of HCC was associated with LNM and an extremely poor outcome after operation. It is of clinical significance to identify these patients at risk for more aggressive HCC, and multi-modality treatment could be helpful to improve their dismal outcome.
Here, we disclose the complete genomic sequence of a rare rotavirus group A G2P4-I2-R2-C2-M2-A15-N2-T2-E2-H2 strain detected in a fecal specimen from a rotaviral acute gastroenteritis patient who had ...previously received the Rotarix vaccine.
To identify the genetic etiology of recurrent disorders of sex development (DSDs) in a Taiwanese family with 46,XY sex reversal and hypospadias.
Genetic and functional studies.
Academic hospital.
A ...three-generation family consisting of 22 members, with eight cases of 46,XY DSD, of whom four have 46,XY male-to-female sex reversal and four are 46,XY males with hypospadias.
None.
Results of exome sequencing and in vitro protein and RNA analyses.
All patients with DSDs were found to carry heterozygous missense mutations in the doublesex and mab-3-related transcription factor 3 (DMRT3; rs187176004, c.A815C, p.K272T) and 2ʹ,5ʹ-oligoadenylate synthetase 3 (OAS3; rs16942374, c.G2606A, p.R869H) genes. The DMRT3 mutation increased estrogen receptor 1 (ESR1) expression. Upon binding with the OAS3-RNase L complex, wild-type DMRT3 promoted degradation of ESR1 mRNA. However, the DMRT3A815C-OAS3G2606A complex interacted less strongly with ESR1 mRNA and RNase L, ultimately preventing ESR1 mRNA degradation. The interactions between DMRT3, OAS3, and RNase L were confirmed in the patients’ testis.
Our results indicate that DMRT3 and OAS3 are involved in human DSDs by controlling ESR1 expression.
El análisis genético de una familia taiwanesa identifica una interacción DMRT3-OAS3 implicada en la diferenciación sexual humana a través de la regulación de la expresión de ESR1
identificar la etiología genética de trastornos recurrentes del desarrollo sexual (DSDs) en una familia Taiwanesa con sexo 46, XY inverso e hipospadias.
Estudios genéticos y funcionales.
Hospital Universitario.
22 miembros de tres generaciones de una familia con ocho casos de 46, XY, DSD, de los cuales cuatro tienen 46,XY sexo inverso de hombre a mujer y cuatro son 46, XY, hombres con hipospadias.
Ninguna.
Resultados de la secuenciación del exoma y análisis in vitro de proteínas y RNA.
Se encontró que todos los pacientes con DSDs eran portadores heterocigotos de mutaciones missense en los genes del factor de transcripción 3 doublesex y mab-3-related (DMRT3; rs187176004, c.A815C, p.K272T) y 2’5’-oligoadenilato sintetasa 3 (OAS3; rs 16942374, c.G2606A, p.R869H). La mutación DMRT3 aumentaba la expresión del receptor de estrógenos 1 (ESR1). La unión vinculante con el complejo OAS3-RNasa L DMRT3 wild-type promovía la degradación del mRNA del ESR1. Sin embargo, el complejo DMRT3 A815C-OAS3 G2606A interactuaba de manera más débil con mRNA ESR1 y RNAasa L, previniendo en última instancia la degradación del mRNA ESR1. Las interacciones entre DMRT3, OAS3 y RNasa L se confirmaron en el tejido testicular de los pacientes.
Nuestros resultados indican que DMRT3 y OAS3 están implicados en los DSDs en humanos controlando la expresión de ESR1.
Human norovirus (NoV) is the leading cause of acute gastroenteritis and the rapid transmission of NoV renders infection control problematic. Our study aimed to investigate viral shedding in ...gastroenteritis in children caused by variants of emerging norovirus strains infections.We used RNA-dependent RNA polymerase (RdRp) sequencing to measure NoV genome copies in stool to understand the relationship between the clinical manifestations and viral shedding in hospitalized patients. The near full-length NoV genome sequence was amplified via reverse transcription-polymerase chain reaction (RT-PCR) and NoV recombination was analyzed using the Recombination Analysis Tool (RAT).From January 2015 to March 2018, 77 fecal specimens were collected from hospitalized pediatric patients with confirmed NoV gastroenteritis. The NoV genotypes were GII.4 (n = 22), non-GII.4 (n = 14), GII.4 Sydney (n = 21), and GII.P16-GII.2 (n = 20). Viral load increased from days 2 to 9 from the illness onset, resulting in an irregular plateau without peaks. After day 9, the viral load declined gradually and most viral shedding in feces ceased by day 15. The average viral load was highest in GII.4 Sydney followed by GII.P16-GII.2 infections and lowest in non-GII.4 infections. GII.4 unclassified infections showed the longest viral shedding time, followed by GII.4 Sydney infections, GII.P16-GII.2 recombinant infection resulted in the shortest duration. NoVs evolved to form a group of GII.P16-GII.2 variants during the 2017 to 2018 period.The viral load and shedding period and was different in variants of NoV infections in children. High mutation rate of emerging and re-emerging variants was observed to an enhanced epidemic risk rendering continuous surveillance.
Interlaboratory comparison of microarray data, even when using the same platform, imposes several challenges to scientists. RNA quality, RNA labeling efficiency, hybridization procedures and ...data-mining tools can all contribute variations in each laboratory. In Affymetrix GeneChips, about 11-20 different 25-mer oligonucleotides are used to measure the level of each transcript. Here, we report that 'labeling extension values (LEVs)', which are correlation coefficients between probe intensities and probe positions, are highly correlated with the gene expression levels (GEVs) on eukayotic Affymetrix microarray data. By analyzing LEVs and GEVs in the publicly available 2414 cel files of 20 Affymetrix microarray types covering 13 species, we found that correlations between LEVs and GEVs only exist in eukaryotic RNAs, but not in prokaryotic ones. Surprisingly, Affymetrix results of the same specimens that were analyzed in different laboratories could be clearly differentiated only by LEVs, leading to the identification of 'laboratory signatures'. In the examined dataset, GSE10797, filtering out high-LEV genes did not compromise the discovery of biological processes that are constructed by differentially expressed genes. In conclusion, LEVs provide a new filtering parameter for microarray analysis of gene expression and it may improve the inter- and intralaboratory comparability of Affymetrix GeneChips data.
The aim of the present study was to evaluate the microbiota of children with severe or complicated acute viral gastroenteritis (AGE). To that end, next-generation sequencing (NGS) technology was used ...to sequence the 16S ribosomal RNA (16S rRNA) gene in 20 hospitalized pediatric patients with severe or complicated AGE and a further 20 otherwise healthy children; the fecal microbiome was then assessed. Comparative metagenomics data were analyzed by a Wilcoxon rank-sum test and hierarchical clustering analysis of bacterial reads. The statistical analyses showed a significantly decreased Shannon diversity index (entropy score) of the intestinal microbiota in patients with severe AGE compared with normal controls (P = 0.017) and patients with mild-to-moderate AGE (P = 0.011). The intestinal microbiota score of the 5 patients with rotavirus AGE was significantly lower than that of those with norovirus infection (P = 0.048). Greater richness in Campylobacteraceae (P = 0.0003), Neisseriaceae (P = 0.0115), Methylobacteriaceae (P = 0.0004), Sphingomonadaceae (P = 0.0221), and Enterobacteriaceae (P = 0.0451) was found in patients with complicated AGE compared with normal controls. The data suggest a significant reduction in intestinal microbial diversity in patients with severe AGE, particularly those with rotavirus infection.
Objectives/Hypothesis:
We sought to investigate the role of desmoglein 3 in pathogenesis of sinonasal inverted papilloma (IP) and its malignant transformation.
Methods:
Fifteen subjects with ...sinonasal IP and 15 subjects of normal sphenoid sinus mucosa were enrolled. Each specimen was divided into two portions: one for mRNA expression analysis by real‐time polymerase chain reaction, and the other for detection of targeted proteins by immunohistochemistry analysis. In addition, another 10 cases of IP with squamous cell carcinoma (SCC) were added for immunohistochemistry analysis.
Results:
The mRNA expression level of desmoglein 3 was significantly higher in IP tissues than in the normal sinus mucosa (P < .001). In immunohistochemistry study, desmoglein 3 was detected in plasma membrane areas of IP and IP with SCC tissues, but no obvious expression was found in normal sinus mucosa (total score; both P < .001). Positive desmoglein 3 staining was strongly present in nearly all malignant transformation areas of IP with SCC cases (90%), but only in scattered areas of some cases of IP (53%) (total score; P < .001).
Conclusions:
Desmoglein 3 was overexpressed in IP and IP with SCC, and the overexpression was correlated with malignant transformation of IP. It may provide valuable insight into the pathobiology of this disease, and can potentially provide a venue to predict malignant transformation in sinonasal IP. Laryngoscope, 2010
While the gut microbiota is known to be influenced by habitual food intake, this relationship is seldom explored in type 2 diabetes patients. This study aims to investigate the relationship between ...dietary patterns and gut microbial species abundance in 113 type 2 diabetes patients (mean age, 58 years; body mass index, 29.1; glycohemoglobin HbA1c, 8.1%). We analyzed the gut microbiota using 16S amplicon sequencing, and all patients were categorized into either the Bacteroides enterotype (57.5%, n = 65) or the Prevotella enterotype (42.5%, n = 48) using the partitioning around medoids clustering algorithm, based on the most representative genera. Patients with the Bacteroides enterotype showed better glycemic control with a 2.71 odds of HbA1c ≤ 7.0% compared to the Prevotella enterotype (95% confidence interval, 1.02-7.87; P, 0.034). Dietary habits and the nutrient composition of all patients were assessed using a validated food frequency questionnaire. It was observed that the amounts of dietary fiber consumed were suboptimal, with an average intake of 16 g per day. Additionally, we extracted four dietary patterns through factor analysis: eating-out, high-sugar foods, fish-vegetable, and fermented foods patterns. Patients with the Bacteroides enterotype had higher scores for the fish-vegetable pattern compared to the Prevotella enterotype (0.17 ± 0.13 versus -0.23 ± 0.09; P, 0.010). We further investigated the relationship between the microbiota and the four dietary patterns and found that only the fish-vegetable dietary pattern scores were correlated with principal coordinate values. A lower pattern score was associated with the accumulated abundance of the 31 significant microbial features. Among these features, Prevotella copri was identified as the most significant by using a random forest model, with an area under the receiver operating characteristic of 0.93 (95% confidence interval, 0.88-0.98). To validate these results, we conducted a custom quantitative polymerase chain reaction assay. This assay confirmed the presence of P. copri (sensitivity, 0.96; specificity, 0.97) in our cohort, with a prevalence of 47.8%, and a mean relative abundance of 21.0% in subjects harboring P. copri. In summary, type 2 diabetes patients with the Prevotella enterotype demonstrated poorer glycemic control and deviations from a healthy dietary pattern. The abundance of P. copri, as a major contributing microbial feature, was associated with the severity in the deficiency in dietary fish and vegetables. Emphasis should be placed on promoting a healthy dietary pattern and understanding the microbial correlations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ETS1 - an evolutionarily conserved transcription factor involved in the regulation of a number of cellular processes - is overexpressed in several malignancies, including ovarian cancer. Most studies ...on ETS1 expression have been focused on the transcriptional and RNA levels, with post-translational control mechanisms remaining relatively unexplored in the pathogenesis of malignancies. Here, we show that ETS1 forms a complex with glycogen synthase kinase-3β (GSK3β). Specifically, GSK3β-mediated phosphorylation of ETS1 at threonine 265 and serine 269 promoted protein stability, induced the transcriptional activation of matrix metalloproteinase (
)
, and increased cell migration.
experiments revealed that a GSK3β inhibitor was able to suppress both endogenous ETS1 expression and induction of
expression. Upon generation of a specific antibody against phosphorylated ETS1, we demonstrated that phospho-ETS1 immunohistochemical expression in ovarian cancer specimens was correlated with that of MMP-9. Notably, the cumulative overall survival of patients with low phospho-ETS1 histoscores was significantly longer than that of those showing higher scores. We conclude that the GSK3β/ETS1/MMP-9 axis may regulate the biological aggressiveness of ovarian cancer and can serve as a prognostic factor in patients with this malignancy.
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