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3.
J Biol Chem ; 295(46): 15588-15596, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32878986

RESUMO

The principal virulence factor of human pathogenic enterohemorrhagic Escherichia coli is Shiga toxin (Stx). Shiga toxin 2a (Stx2a) is the subtype most commonly associated with severe disease outcomes such as hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A1 subunit (Stx2A1) binds to the conserved elongation factor binding C-terminal domain (CTD) of ribosomal P stalk proteins to inhibit translation. Stx2a holotoxin also binds to the CTD of P stalk proteins because the ribosome-binding site is exposed. We show here that Stx2a binds to an 11-mer peptide (P11) mimicking the CTD of P stalk proteins with low micromolar affinity. We cocrystallized Stx2a with P11 and defined their interactions by X-ray crystallography. We found that the last six residues of P11 inserted into a shallow pocket on Stx2A1 and interacted with Arg-172, Arg-176, and Arg-179, which were previously shown to be critical for binding of Stx2A1 to the ribosome. Stx2a formed a distinct P11-binding mode within a different surface pocket relative to ricin toxin A subunit and trichosanthin, suggesting different ribosome recognition mechanisms for each ribosome inactivating protein (RIP). The binding mode of Stx2a to P11 is also conserved among the different Stx subtypes. Furthermore, the P stalk protein CTD is flexible and adopts distinct orientations and interaction modes depending on the structural differences between the RIPs. Structural characterization of the Stx2a-ribosome complex is important for understanding the role of the stalk in toxin recruitment to the sarcin/ricin loop and may provide a new target for inhibitor discovery.

4.
Am J Transl Res ; 12(7): 3926-3939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774746

RESUMO

Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca2+. Aberrant expression has been reported in a number of cancers. However, the biological function of TRPM4 in endometrial carcinoma (EC) is still unknown. We find that decreased TRPM4 expression is significantly correlated with a poor prognosis, overall survival (OS, P<0.001) and recurrence-free survival (P=0.002) through The Cancer Genome Atlas (TCGA) datasets in mRNA level. Multivariate Cox regression analysis suggests that TRPM4 is an independent prognostic factor for OS in EC patients. In vitro assays show that TRPM4-deletion results in significant promotion of proliferation and migration in EC cells. We then conducted a gene set enrichment analysis (GSEA) and according to the results, the expression of TRPM4 is modulated by estrogen, which is inhibited by ER antagonist. Furthermore, the silencing of TRPM4 causes a decreased p53 and hyper-activation of EMT, PI3K/AKT/mTOR signaling pathway in EC, as demonstrated in vitro. Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.

5.
Cancer Biomark ; 29(4): 493-508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831192

RESUMO

Growing evidence has underscored long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic tracking of a lncRNA signature for prognosis prediction in non-small cell lung cancer (NSCLC) has not been accomplished yet. Here, comprehensive analysis with differential gene expression analysis, univariate and multivariate Cox regression analysis based on The Cancer Genome Atlas (TCGA) database was performed to identify the lncRNA signature for prediction of the overall survival of NSCLC patients. A risk-score model based on a 14-lncRNA signature was identified, which could classify patients into high-risk and low-risk groups and show poor and improved outcomes, respectively. The receiver operating characteristic (ROC) curve revealed that the risk-score model has good performance with high AUC value. Multivariate Cox's regression model and stratified analysis indicated that the risk-score was independent of other clinicopathological prognostic factors. Furthermore, the risk-score model was competent for the prediction of metastasis-free survival in NSCLC patients. Moreover, the risk-score model was applicable for prediction of the overall survival in the other 30 caner types of TCGA. Our study highlighted the significant implications of lncRNAs as prognostic predictors in NSCLC. We hope the lncRNA signature could contribute to personalized therapy decisions in the future.

6.
Cancer Manag Res ; 12: 5023-5030, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612389

RESUMO

Purpose: The early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC. Methods: We identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders. Results: A total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P<0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend <0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8-29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5-28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6-17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI<28 kg/m2, grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma. Conclusion: Ionized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(6): 561-566, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32571452

RESUMO

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.


Assuntos
Recém-Nascido de Peso Extremamente Baixo ao Nascer , Antibacterianos , Peso ao Nascer , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Inquéritos e Questionários
8.
ACS Infect Dis ; 6(7): 1894-1905, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32428396

RESUMO

Ricin toxin A subunit (RTA) removes an adenine from the universally conserved sarcin/ricin loop (SRL) on eukaryotic ribosomes, thereby inhibiting protein synthesis. No high affinity and selective small molecule therapeutic antidotes have been reported against ricin toxicity. RTA binds to the ribosomal P stalk to access the SRL. The interaction anchors RTA to the P protein C-termini at a well-defined hydrophobic pocket, which is on the opposite face relative to the active site. The RTA ribosome binding site has not been previously targeted by small molecule inhibitors. We used fragment screening with surface plasmon resonance to identify small molecular weight lead compounds that bind RTA and defined their interactions by crystallography. We identified five fragments, which bound RTA with mid-micromolar affinity. Three chemically distinct binding fragments were cocrystallized with RTA, and crystal structures were solved. Two fragments bound at the P stalk binding site, and the third bound to helix D, a motif distinct from the P stalk binding site. All fragments bound RTA remote from the catalytic site and caused little change in catalytic site geometry. Two fragments uniquely bound at the hydrophobic pocket with affinity sufficient to inhibit the catalytic activity on eukaryotic ribosomes in the low micromolar range. The binding mode of these inhibitors mimicked the interaction of the P stalk peptide, establishing that small molecule inhibitors can inhibit RTA binding to the ribosome with the potential for therapeutic intervention.

9.
Front Med (Lausanne) ; 7: 70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32258043

RESUMO

Introduction: Radiotherapy, combined regimens as platinum-paclitaxel chemotherapy and/or endocrine therapy is an important adjuvant treatment after surgery for endometrial cancer (EC). While, the resistance to them remain unclear. In our study, to separate the characteristics of side population (SP) cells from EC cell lines, study the mechanism of Taxol-resistance, progestin resistance and radioresistanc, and provide the basic for EC. Methods: SP cells from EC cell lines HEC-1A, Ishikawa and RL95-2 were separated by Hoechst 33342 staining and flow cytometry analysis. The expression of breast cancer resistance protein (BCRP) in SP cells and non-SP cells from HEC-1A was examined by immunocytochemistry, and the radiation-resistant and Taxol-resistant characteristics of SP cells and non-SP cells were compared by MTS. Ishikawa, Ishikawa-SP, and Ishikawa-non-SP cells incubated with MPA were selected for cell apoptosis assays by using flow cytometry. The expression of caspase-3 was examined by immunocytochemistry, and autophagy was detected by MDC staining. Results: Small proportions of SP cells, namely, 1.44 ± 0.93%, 2.86 ± 3.09%, and 2.87 ± 1.29%, were detected in HEC-1A, Ishikawa and RL95-2, respectively. There was a stronger clone formation efficiency for the SP cells than for non-SP cells in HEC-1A [(6.02 ± 1.17) vs. (0.53±0.20)%, P = 0.001], and there was a significant difference in the rate of tumourigenicity between the SP cells and non-SP cells in HEC-1A (87.5 vs. 12.5%). There were higher levels of BCRP expression (P = 0.001) and resistance to Taxol and radiation (P < 0.05) in the SP cells than in non-SP cells. After MPA treatment, the apoptosis rates were significantly different among the Ishikawa, Ishikawa-SP and Ishikawa-non-SP groups [(4.64 ± 0.18)%, (4.01 ± 0.43)%, and (9.3 ± 0.67)%; (P = 0.05)], and the expression of Caspase-3 in the Ishikawa group was higher than that in Ishikawa-SP group. The autophagic activity of the Ishikawa-SP cells was the strongest, while the autophagic activity of Ishikawa-non-SP was the weakest. Conclusions: There is a significant enrichment in SP cells among different EC cell lines, and these SP cells be more resistant to Taxol, MPA and radiation therapy. The overexpression of BCRP among SP cells may be the cause of resistance to Taxol, progestin and radiotherapy, which may be related to apoptosis and autophagic activity.

10.
Genes (Basel) ; 11(2)2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024145

RESUMO

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that play an essential role in innate immunity across taxa from invertebrates to vertebrates. The evolution system of AMP system has not been well explained in the literature. In this study, we cloned and sequenced AMP transcriptomes of three frog species, namely Rana dybowskii, Rana amurensis, and Pelophylax nigromaculatus, which are partially sympatric in northeast Asia, but show different habitat preferences. We found that each species contained 7 to 14 families of AMPs and the diversity was higher in species with a large geographic range and greater habitat variation. All AMPs are phylogenetically related but not associated with the speciation process. Most AMP genes were under negative selection. We propose that the diversification and addition of novel functions and improvement of antimicrobial efficiency are facilitated by the expansion of family members and numbers. We also documented significant negative correlation of net charges and numbers of amino acid residues between the propiece and mature peptide segments. This supports the Net Charge Balance Hypothesis. We propose the Cut Point Sliding Hypothesis as a novel diversification mechanism to explain the correlation in lengths of the two segments.


Assuntos
Anti-Infecciosos/classificação , Peptídeos Catiônicos Antimicrobianos/classificação , Peptídeos Catiônicos Antimicrobianos/genética , Anuros/classificação , Evolução Molecular , Mutação , Sequência de Aminoácidos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Anuros/genética , Ásia , Filogenia , Homologia de Sequência , Simpatria/genética , Transcriptoma
11.
J Cell Biochem ; 121(10): 4108-4119, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31898842

RESUMO

This study aimed to identify the association between lnc-LAMC2-1:1 polymorphism rs2147578 and the recurrence of ovary cancer, as well as to study the underlying mechanism of rs2147578 in ovary cancer. Real-time polymerase chain reaction, Western blot analysis, immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Logrank test, and Kaplan-Meier analysis were carried out to explore the role of rs2147578 in ovary cancer. No obvious difference was observed concerning all clinical characteristics among 90 patients genotyped as CC (N = 28), CG (N = 38), and GG (N = 24) in their rs2147578 polymorphism. In addition, the subjects carrying the CC genotype had longer recurrence-free survival time and showed a lower level of malignancy compared with those carrying CG and GG genotypes. Lnc-LAMC2-1:1 and miR-128 were lowly expressed in the CC group, while deleted in colorectal cancer (DCC) was highly expressed in the CC group. Furthermore, DCC was identified as a target gene of miR-128, and miR-128 mimics decreased the luciferase activity of cells cotransfected with wild-type DCC 3'-untranslated region. Lnc-LAMC2:1-1 directly targeted and affected miR-128 expression, and the G allele in lnc-LAMC2-1:1 rs2147578 upregulated miR-128 expression. Transfection with a miR-128 precursor evidently downregulated the expression of lnc-LAMC2-1:1, miR-128, and DCC expression, but did not affect the expression of ABCC5 and body mass index. Finally, miR-128 precursor promoted cell proliferation and inhibited cell apoptosis. Compared with lnc-LAMC2-1:1 rs2147578C allele, the G allele increases the risk of ovarian cancer by reducing the binding between lnc-LAMC2-1:1 and miR-128-3p, which in turn further decreases the expression of DCC and inhibits cell apoptosis.

12.
J Mol Biol ; 432(4): 1109-1125, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31931008

RESUMO

The extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near-perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHHs) previously reported to recognize epitopes in proximity to RTA's active site. Three of the VHHs, V2A11, V8E6, and V2G10, were potent inhibitors of RTA in vitro and protected Vero cells from ricin when expressed as intracellular antibodies ("intrabodies"). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTA's active site and interact with key catalytic residues. V2G10, by contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHHs also penetrated/occluded RTA's active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.toxin, antibody, structure, intracellular.


Assuntos
Anticorpos Neutralizantes/imunologia , Ricina/química , Ricina/imunologia , Anticorpos de Domínio Único/imunologia , Animais , Anticorpos Neutralizantes/metabolismo , Sítios de Ligação de Anticorpos , Domínio Catalítico , Chlorocebus aethiops , Ensaio de Imunoadsorção Enzimática , Reação em Cadeia da Polimerase , Anticorpos de Domínio Único/metabolismo , Ressonância de Plasmônio de Superfície , Células Vero
13.
Math Biosci Eng ; 16(6): 6350-6366, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31698566

RESUMO

Secret image sharing has been widely applied in numerous areas, such as military imaging systems, remote sensing, and so on. One of the problems for image sharing schemes is to efficiently recover original images from their shares preserved by the shareholders. However, most of the existing schemes are based on the assumption that the shares are distortion-free. Moreover, the correspondence between secret images and their shares is definite. To overcome these shortcomings, we propose a novel secret sharing scheme using multiple share images based on the generalized Chinese remainder theorem (CRT) in this paper, where all of the shares are needed to recover the original images. Two categories of distortions are considered. In the first category, some pairs of shares with the same moduli are exchanged, while in the second category, some of pixels in the pairs of shares with the same moduli are exchanged. Based on these two sharing methods, we propose a generalized CRT based recovery method. Compared with the existing CRT based methods as well as combinatorial based methods, the proposed approach is much more efficient and secure. Furthermore, the conditions for successful recovery of two images from the given distorted shares are obtained. Simulations are also presented to show the efficiency of the proposed scheme.

14.
Materials (Basel) ; 12(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752163

RESUMO

The orbital riveting process has been successively adopted in the assembly of wheel hub bearing, due to its special merits of high efficiency, low cost, and so on. The forming process and deformation behavior of the inner ring have significant influence on the axial clamping force and bearing clearance, however, which haven't been addressed yet. In this study, a numerical simulation platform for the assembly of the hub bearing is established by the joint use of the static implicit and dynamic explicit algorithms. Based on the platform, the deformation process and deformation behavior of the inner ring are investigated, along with the interference assembly and riveting assembly on the loading process of the inner ring. Finally, relevant experimental verifications are carried out to consolidate the simulation results. The research findings could be used to guide the design and optimization of the axial clamping force and bearing clearance.

15.
Biosci Rep ; 39(10)2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31548364

RESUMO

Ricin interacts with the ribosomal P stalk to cleave a conserved adenine from the α-sarcin/ricin loop (SRL) of the rRNA. Ricin toxin A chain (RTA) uses Arg235 as the most critical arginine for binding to the P stalk through electrostatic interactions to facilitate depurination. Structural analysis showed that a P2 peptide binds to a hydrophobic pocket on RTA and the last two residues form hydrogen bonds with Arg235. The importance of hydrophobic residues relative to Arg235 in the interaction with the P stalk in vivo and on the toxicity of RTA is not known. Here, we mutated residues in the hydrophobic pocket to analyze their contribution to toxicity and depurination activity in yeast and in mammalian cells. We found that Leu232, Tyr183 and Phe240 contribute cumulatively to toxicity, with Leu232 being the most significant. A quadruple mutant, Y183A/L232A/R235A/F240A, which combined mutations in critical hydrophobic residues with R235A completely abolished the activity of RTA, indicating that Arg235 and hydrophobic residues are required for full biological activity. Y183A and F240A mutants had reduced activity on RNA, but higher activity on ribosomes compared with R235A in vitro, suggesting that they could partially regain activity upon interaction with ribosomes. These results expand the region of interaction between RTA and the P stalk critical for cellular activity to include the hydrophobic pocket and provide the first evidence that interaction of P stalk with the hydrophobic pocket promotes a conformational rearrangement of RTA to correctly position the active site residues for catalytic attack on the SRL.


Assuntos
Ribossomos/química , Ricina/química , Saccharomyces cerevisiae/química , Sítios de Ligação , Interações Hidrofóbicas e Hidrofílicas , Leucina , Ribossomos/genética , Ribossomos/metabolismo , Ricina/genética , Ricina/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
16.
Chin Med J (Engl) ; 132(13): 1550-1562, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31268882

RESUMO

BACKGROUND: Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles. METHODS: A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC. RESULTS: The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. CONCLUSIONS:: Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Adulto , Idoso , Proliferação de Células/genética , Proliferação de Células/fisiologia , Análise por Conglomerados , Feminino , Humanos , Análise em Microsséries , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
17.
Chin Med J (Engl) ; 132(11): 1314-1321, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30888986

RESUMO

BACKGROUND: Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC. METHODS: A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software. RESULTS: New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11-123O10.4-GRIP1, RP11-444D3.1-SOX5, RP11-680G10.1-GSE1, NRIP1-AF127936.7, RP11-96H19.1-RP11-446N19.1, and DPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7 and DPH7-PTP4A3 were found only in stage III patients with EC. DPH7-PTP4A3 was found in grades 2 and 3, and recurrent patients with EC. CONCLUSION: Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7 and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.


Assuntos
Neoplasias do Endométrio/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Distribuição de Qui-Quadrado , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Neoplasias/genética , Proteína 1 de Interação com Receptor Nuclear/genética , Gravidez , Proteínas Tirosina Fosfatases/genética , Análise de Sequência de RNA , Software
18.
Int J Clin Exp Pathol ; 12(6): 2121-2129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934034

RESUMO

Hypertrophic scars are proliferative diseases of dermal fibroblasts that produce abundant amounts of collagen and extracellular matrix in the skin after severe burns, inflammation and trauma. Hypertrophic scars affect the daily life of patients and cause a series of problems. The biological mechanism of hypertrophic scar formation is still unclear and has received much attention in plastic surgery. Therefore, we hypothesized that LPS can activate TLR4 signaling, leading to the overexpression of collagen I and TGF-ß and the induction of hypertrophic scar formation. In the present study, we used LPS to validate the role of the TLR4 signaling pathway in 3T3-L1 cells in vitro and hypertrophic scar mouse models to determine the role of the TLR4 signaling pathway in proliferative scar formation in vivo. The results suggested that LPS leads to the activation of the TLR4 pathway in fibroblasts, and inhibitor experiments confirmed that TLR4 is involved in the expression of collagen I by regulating the NF-κB pathway. The mouse skin wound model experiments demonstrated that TLR4 is involved in wound healing and scar formation. Our experiments demonstrated that the TLR4-IRAK4-NF-κB pathway is involved in the production of hypertrophic scars and wound healing.

19.
Anal Chim Acta ; 1046: 208, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30482301

RESUMO

This article has been retracted at the request of the Editor after the corresponding author pointed the Editor to comments from an anonymous reader. The article reports electron micrographs of different preparations while showing identical images as used in previous publications by the same authors. The particles in Fig. 4C (SEM image of Fe3O4@SiO2) are identical to each other and the corresponding author confirmed that these have been copy-pasted. In addition, these particles have previously been communicated as different substances in Fig. 1B from Pan et al., J. Mater. Chem. A, 2015,3, 23042-23052 (DOI: 10.1039/C5TA05840F) and Fig. 3F from Pan et al., Anal. Methods, 2017,9, 5281-5292 (DOI: 10.1039/C7AY01444A). Furthermore, the curves in Fig. 7, especially the baseline, shows a remarkable similarity to Fig. 8 from Pan et al., J. Mater. Chem. A, 2015,3, 23042-23052 (DOI: 10.1039/C5TA05840F) and Fig. 5F from Pan et al., J. Mater. Chem. A, 2014,2, 15345-15356 (DOI: 10.1039/c4ta02600d). The manipulation of images and data in this way is a serious offense to the integrity of the scientific community and casts doubts on all the data, and accordingly also the conclusions based on that data, in this publication. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

20.
J Virol Methods ; 262: 65-71, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30308216

RESUMO

Covert mortality nodavirus (CMNV), an emerging RNA virus, is the pathogen of viral covert mortality disease (VCMD), which has emerged as a cause of serious losses in shrimp aquaculture in China. To improve VCMD diagnosis, a one-step, real-time TaqMan probe-based reverse transcription quantitative PCR (RT-qPCR) was developed in this study. The TaqMan RT-qPCR was optimized firstly, whereby the best results were obtained with 0.2 µM of each primer, 0.2 µM probe, and 0.5 µL Enzyme Mix II. The optimal reaction program was determined as 15 min at 51ºC for reverse transcription and 5 min at 95 ºC, followed by 40 cycles of denaturation at 94 ºC for 10 s, and annealing and extension at 52.7 ºC for 30 s. The optimized assay detected as little as 9.6 pg total RNA from CMNV-infected shrimp and 5.7 copies of the target plasmid. The RT-qPCR assay for CMNV with a high correlation coefficient (r2 = 0.996) was developed basing on the standard curve generated by plotting the threshold cycle values (y) against the common logarithmic copies (log10nc as x; nc is copy number) of pMD20-CMNV. The diagnostic sensitivity and specificity of this assay versus the previously reported RT-qPCR was 96.2% and 98.0%, respectively. This method is highly specific to CMNV, as it showed no cross-reactivity with other common shrimp viruses. It is anticipated that the newly developed and optimized RT-qPCR assay will be instrumental for the rapid diagnosis and quantitation of CMNV.


Assuntos
Nodaviridae/genética , Penaeidae/virologia , Infecções por Vírus de RNA/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Nodaviridae/isolamento & purificação , Nodaviridae/patogenicidade , Infecções por Vírus de RNA/diagnóstico , RNA Viral/genética , Sensibilidade e Especificidade
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