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1.
J Cell Physiol ; 235(1): 394-407, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31225658

RESUMO

As the most commonly diagnosed malignant tumor in female population, the prognosis of breast cancer is affected by complex gene interaction networks. In this research weighted gene co-expression network analysis (WGCNA) would be utilized to build a gene co-expression network to identify potential biomarkers for prediction the prognosis of patients with breast cancer. We downloaded GSE25065 from Gene Expression Omnibus database as the test set. GSE25055 and GSE42568 were utilized to validate findings in the research. Seven modules were established in the GSE25065 by utilizing average link hierarchical clustering. Three hub genes, RSAD2, HERC5, and CCL8 were screened out from the significant module (R 2 = 0.44), which were considerably interrelated to worse prognosis. Within test dataset GSE25065, RSAD2, and CCL8 were correlated with tumor stage, grade, and lymph node metastases, whereas HERC5 was correlated with lymph node metastases and tumor grade. In the validation dataset GSE25055 and RSAD2 expression was correlated with tumor grade, stage, and size, whereas HERC5 was related to tumor stage and tumor grade, and CCL8 was associated with tumor size and tumor grade. Multivariable survival analysis demonstrated that RSAD2, HERC5, and CCL8 were independent risk factors. In conclusion, the WGCNA analysis conducted in this study screened out novel prognostic biomarkers of breast cancer. Meanwhile, further in vivo and in vitro studies are required to make the clear molecular mechanisms.

2.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692061

RESUMO

Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.

3.
Plant Cell ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666295

RESUMO

Gene functional studies often rely on the expression of a gene of interest as transcriptional and translational fusions with specialized tags. Ideally, this is done in the native chromosomal contexts to avoid potential misexpression artifacts. Although recent improvements in genome editing make it possible to directly modify the target genes in their native chromosomal location, classical transgenesis is still the preferred experimental approach chosen in most gene tagging studies because of its time efficiency and accessibility. We have developed a recombineering-based tagging system that brings together the convenience of the classical transgenic approaches and the high degree of confidence in the obtained results provided by the direct chromosomal tagging achievable by genome editing strategies. These simple, scalable and customizable recombineering toolsets and protocols allow for the generation of a variety of genetic modifications. In addition, a highly efficient recombinase-mediated cassette exchange system has been developed to facilitate the transfer of the desired sequences from a BAC clone to a transformation-compatible binary vector, expanding the use of the recombineering approaches beyond Arabidopsis. The utility of this system is demonstrated by the generation of over 250 whole-gene translational fusions and 123 Arabidopsis transgenic lines corresponding to 62 auxin-related genes, and the characterization of the translational reporter expression patterns for 14 auxin biosynthesis genes.

4.
J Cell Physiol ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31663114

RESUMO

Long noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight-lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)-positive breast cancer receiving endocrine therapy. Patients were separated into a low-risk group and a high-risk group based on this signature. Patients in high-risk group have worse survival compared to those in low-risk group using Kaplan-Meier curve analysis with log-rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight-lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse-free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight-lncRNA-based signature. To sum up, our results indicated that the eight-lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER-positive breast cancer receiving endocrine therapy.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 298-304, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631593

RESUMO

Objective: To determine the effect of Huntingtin-associated protein 1 ( Hap1) on fibroblast proliferation. Methods: Hap1 knockout ( Hap1 -/-) primary fibroblasts were isolated and cultured in vitro. The proliferation of Hap1 -/- fibroblasts was detected by EdU proliferation assay and cell flow assay. Transcriptome sequencing of the wild-type and Hap1 -/- fibroblasts was screened for proliferation-related genes. Real-time quantitative PCR (qPCR) was performed to verify changes in expressions of related genes. Skin repair was examined in Hap1 knockdown mice with skin wounds. The proliferation of fibroblasts during wound repair was detected by PCNA immunohistochemical staining. Results: Hap1 -/- fibroblasts were successfully cultured. Compared with WT, EdU-positive fibroblasts decreased in Hap1 -/-,with less cells entering the S phase. Transcriptome sequencing of primary fibroblasts identified genes of Cdc25C, E2f7, E2f8 and Ccl5. qPCR confirmed that Hap1 knockout increased E2f7 expression. Hap1 +/- mice had larger skin lesions, slower healing and lower positive density of fibroblast proliferation than those of wild type mice. Conclusion: Hap1 may positively regulate fibroblast proliferation by inhibiting the expression of cell cycle negative regulator E2f7.Its deletion inhibits fibroblasts entering the S phase, thereby reducing cell proliferation and affecting wound repair.

6.
Waste Manag ; 100: 287-295, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568977

RESUMO

The objective of this study was to investigate the feasibility of removing Pb2+ by pilot-scale fluidized bed biochar, and then to put forward an industrial-scale fluidized bed pyrolysis progress of cogeneration of biochar and high-temperature gas. Corn stalk biochars (CSBs) were prepared at 400-600 °C, in which the maximum Pb2+adsorption capacity (Qm) of CSB450 is 49.70 mg⋅g-1 at the optimal condition. Adsorption isotherms, kinetics, and thermodynamics were determined, and Pb2+-loaded biochar was analyzed by fourier transform infrared spectroscopy (FTIR), x-ray photoelectron spectroscopy (XPS), x-ray diffraction (XRD) and scanning electron microscope with energy dispersive spectrometer (SEM-EDS). Ion exchange, complexation and mineral precipitation together contributed to Pb2+ adsorption on CSBs. For high-temperature CSBs with fewer oxygen functional groups (OFGs) and stronger aromatization, Pb2+ adsorption by ion exchange and functional group complexation was reduced. The mineral precipitationwas formed during the adsorption process. Using the pilot-scale fluidized bed in this study, the carbon yield per year would achieve 31.79 t, and about 1.58 t of Pb2+ would be adsorbed according to the adsorption capacity at the pyrolytic temperature of 450 °C.The results are beneficial to screen for effective biochar as a cost-effective industrial adsorbent to remove Pb2+ in contaminated water.


Assuntos
Chumbo , Pirólise , Adsorção , Carvão Vegetal , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117509, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31606660

RESUMO

The low-frequency vibrational properties of D-, L- and DL-pyroglutamic acid (PGA) have been investigated with the terahertz time-domain spectroscopy (THz-TDS) from 0.5 to 4.5 THz. The enantiomers (D- and L-PGA) present similar absorption spectra, while the spectrum of racemate (DL-PGA) is obviously different. The temperature-dependent THz spectra of different PGA were recorded in the range of 293-83 K. The spectral changes during the cooling process suggest that D- and L-PGA undergo a structural phase transition, and no phase change of DL-PGA was found. The results indicate that THz spectroscopy is highly sensitive to the crystal structure of molecules. The density functional theory (DFT) calculations based on the crystal structures were performed to simulate the sample's THz spectra. It was demonstrated that the characteristic resonant absorption peaks of the enantiomeric and racemic PGA in the low-frequency THz region originate from the different vibrations, which corresponding to the specific structures and intermolecular interactions. The conformational diversity and fluctuation may help to understand the properties of PGA in biochemistry and functional material.

8.
PLoS One ; 14(9): e0221957, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532792

RESUMO

BACKGROUND: Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease. METHODS: AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation. RESULTS: Baseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1-2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10-7) in those with 1-2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10-7) in those with 0 risk alleles. CONCLUSIONS: Hypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required.

9.
J Invest Surg ; : 1-8, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533488

RESUMO

Background: To investigate the perioperative peripheral blood levels of CD4+CD25+ regulatory T cells, programed cell death 1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in patients with advanced Siewert type II adenocarcinoma of esophagogastric junction (AEG). Methods: Patients (n = 102) with advanced Siewert type II AEG underwent open total gastrectomy/proximal gastrectomy with a transhiatal resection of the distal esophagus and lymphadenectomy of the lower mediastinum and the abdominal D2 compartment. Flow cytometry was used to detect CD4+CD25+ T cells, PD-1 and LAG-3 expression on both CD4+ and CD8+ T cells in the peripheral blood of the Siewert type II AEG patients prior to surgery and on postoperative day (POD) 1, 3, 7, and 9. Results: The proportion of CD4+CD25+ T cells rapidly decreased on POD 1, then gradually increased and peaked at POD 7. The proportion of CD4+PD-1+ T cells significantly increased after surgery, reaching a maximum on POD 1, and remained significantly elevated on POD 3 compared to the preoperative day. The proportion of CD8+ PD-1+ and CD4+LAG-3+ T cells gradually increased after surgery and reached a peak at POD 7. The change in proportion of CD8+LAG-3+ T cells in the peripheral venous blood lymphocytes after surgery was not statistically significant. Conclusion: The change in the CD4+PD-1+ T lymphocyte ratio may likely reflect the cellular immunity status of the perioperative period.

10.
Int J Biol Macromol ; 139: 377-386, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377294

RESUMO

Cancer chemotherapy and the patient's life will be more convenient if oral administration of anti-cancer drugs can be achieved. The feasibility of folate-targeted Pluronic F127/polylactic acid (FA-F127-PLA) polymersomes as the oral delivery carriers of paclitaxel (PTX) has been explored in this study. PTX loaded in FA-F127-PLA and PLA-F127-PLA polymersomes showed biphasic release behaviors in simulated gastric and intestinal fluids. PTX loaded in FA-F127-PLA polymersomes exhibited higher cytotoxicity and cellular uptake than PTX loaded in PLA-F127-PLA polymersomes. In vivo pharmacokinetic studies in rats showed that oral PTX loaded in FA-F127-PLA polymersomes had a higher bioavailability than oral PTX loaded in PLA-F127-PLA polymersomes. D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was also added to the FA-F127-PLA polymersomes as an optimization agent. Compared with PTX-loaded FA-F127-PLA polymersome, PTX-loaded FA-F127-PLA/TPGS mixed polymersomes showed even better cytotoxic ability, more cellular uptake and higher bioavailability. The above results indicate that FA-F127-PLA and FA-F127-PLA/TPGS mixed polymersomes could be good candidates for the oral delivery carrier of anti-cancer drugs.

11.
Curr Eye Res ; : 1-9, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31425668

RESUMO

Purpose: This study is aimed to investigate the effects of periocular steroids induction on intraocular pressure (IOP), retinal ganglion cells (RGCs) and trabecular meshwork (TM) ultrastructure in glucocorticoid-induced ocular hypertension mice model. Materials and Methods: Dexamethasone-21-acetate (Dex-Ace) was administered through periocular conjunctival fornix injection every 3 days in C57BL/6J mice. Intraocular pressure was measured weekly by rebound tonometry. RGCs were examined with immunofluorescent staining of BRN3a at week 1, 4, and 8. TM morphology was visualized with electron microscopy. Autophagy was evaluated with immunoblotting in TM tissues. Results: Dex-Ace rapidly and significantly induced IOP, which peaked at week 4. The absolute increase in IOP in the Dex-Ace-treated mice was 8.1 ± 1.4 mmHg, a 60% induction (p < .0001) compared with that in the vehicle-treated mice. The IOP sustained a higher level in the Dex-Ace group from week 4 to week 8. Dex-Ace treatment decreased the number of RGCs in a time-dependent manner, suggesting that high IOP resulted in optic neuropathy. In addition, Dex-Ace thickened trabecular beams and decreased intertrabecular spaces, with marked accumulation of fibrillar and amorphous granular extracellular material. Moreover, Dex-Ace induced swollen and elongated mitochondria in TM cells. The average mitochondria area was 0.090 ± 0.044 µm2 in the vehicle-treated mice, and increased to 0.161 ± 0.094 µm2 (p < .0001), 0.121 ± 0.029 µm2 (p = .0223) and 0.171 ± 0.076 µm2 (p < .0001) in the Dex-Ace-treated mice at weeks 1, 4 and 8, respectively. Autophagy was also increased by Dex-Ace treatment, indicating by the upregulation of LC3-I, LC3-II and beclin-1, and downregulation of p62. Conclusion: Dex-Ace administration decreased RGCs and changed TM ultrastructure, mimicking hallmarks of human glucocorticoid-induced glaucoma (GIG). In addition, mitochondria and autophagy dysfunction suggested abnormal energy metabolism in TM cells, which warranted further study to fully elucidate the pathogenesis of GIG.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31403360

RESUMO

Background: Hypertension is a major modifiable risk factor for coronary artery disease (CAD), the main cause of death in women. While association between the two is frequent, limited data exist regarding the feasibility of blood pressure (BP) management and outcomes in women across the spectrum of CAD. Accordingly, we analyzed patient characteristics, BP control rates, and outcomes among hypertensive women with CAD, enrolled in The INternational VErapamil SR-trandolapril STudy (INVEST). Methods: The 11,770 hypertensive women with CAD in INVEST were studied based on presence (n = 3,879) or absence (n = 7,891) of history of myocardial infarction (MI) or coronary revascularization, to evaluate outcomes across risk groups based on severity of CAD. Results: Women with prior MI or revascularization were older (4 years, p < 0.0001), were predominantly white (62% vs. 29%), and had more associated comorbidities than women without these events. At 24 months, JNC VI (sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) BP control rates were lower in women with prior MI or revascularization (57% vs. 64%, p < 0.0001), despite more intensive antihypertensive therapy. The primary outcome (first occurrence of all-cause death, nonfatal MI, or nonfatal stroke) was also more frequent in women with prior MI or revascularization (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.34-1.74), who were 42% more likely to die (adjusted HR 1.42; 95% CI 1.22-1.64), twice as likely to have a nonfatal MI (adjusted HR 2.4, 95% CI 1.64-3.51), and 56% more likely to have a nonfatal stroke (adjusted HR 1.56, 95% CI 1.1-2.21). Conclusions: In a prospective, multinational cohort of hypertensive women with CAD, those with prior MI or revascularization comprised a group at higher risk for death, nonfatal MI, and nonfatal stroke, and were less likely to have their BP controlled, despite more aggressive therapy. The feasibility and benefit of reducing BP to <130/80 mmHg in women, particularly with more severe CAD, warrant further investigation.

13.
J Mater Chem B ; 7(34): 5182-5189, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31460558

RESUMO

A chromophore is essential to a classic molecular probe, but its intrinsic optical properties can trigger a spectral background, which is considered to produce a negative influence on detection sensitivity. Hence, developing spectral sensing assays with chromophores generated in situ by probes and analytes could realize detection. Herein, we elaborated a novel proposal based on the in situ condensation reaction between 4-diethylaminobenzaldehyde (DEASA) and hydrazine readily promoted by CTAB micelles, resulting in new chromophores with intramolecular hydrogen bonds generated in situ acting as indicators for hydrazine. A background-free detection pattern was, therefore, formulated, along with a relatively low detection limit of 0.42 nM. This avoided tedious preparation and the use of organic solvents during the experiments. In addition, extensive studies, including actual water/serum samples, living cells, and even mouse imaging, revealed that the DEASA probe and the well-designed in situ sensing scheme exhibited good performance regarding future applications in terms of sensitivity, anti-interference capability, and imaging stability.

14.
J Am Heart Assoc ; 8(16): e013115, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31423876

RESUMO

BackgroundThere exists a wide interindividual variability in blood pressure (BP) response to ß1-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants influencing ß1-blocker BP response.Methods and ResultsGenome-wide association analysis for systolic BP and diastolic BP response to ß1-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P<10-4 were tested for replication in 2 independent randomized clinical trials of ß1-blocker-treated patients of European ancestry (n=1552). Regions harboring the replicated SNPs were validated in a ß1-blocker-treated black cohort from 2 randomized clinical trials (n=315). A missense SNP rs28404156 in BST1 was associated with systolic BP response to ß1-blockers in the discovery meta-analysis (P=9.33×10-5, ß=-3.21 mm Hg) and replicated at Bonferroni significance (P=1.85×10-4, ß=-4.86 mm Hg) in the replication meta-analysis with combined meta-analysis approaching genome-wide significance (P=2.18×10-7). This SNP in BST1 is in linkage disequilibrium with several SNPs with putative regulatory functions in nearby genes, including CD38, FBXL5, and FGFBP1, all of which have been implicated in BP regulation. SNPs in this genetic region were also associated with BP response in the black cohort.ConclusionsData from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with ß1-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.

15.
Biotechnol Adv ; : 107442, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31470046

RESUMO

Immunoassay has been routinely used in hospitals and central labs. Nowadays, to further meet the requirement of widespread applications of immunoassays, it is urgently needed to produce a simplified, rapid and low-cost immunoassay to perform tests on site. To this end, paper-based point-of-care (POC) immunoassays have attracted intensive interests in recent years. In this paper, we present a comprehensive review of the recent advances and emerging trends of paper-based POC immunoassays, including the fundamental components and work principles, various detection mechanisms and applications, and existing commercialized devices/products. At last, we envision three promising development directions for paper-based POC immunoassays.

16.
J Cell Mol Med ; 23(10): 6775-6784, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429520

RESUMO

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death among females. Multiple molecular alterations are observed in breast cancer. LncRNA transcripts were proved to play important roles in the biology of tumorigenesis. In this study, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival. We developed a 10-lncRNA signature-based risk score which was used to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better survival than those in the high-risk group. Receiver operating characteristic analysis indicated that this signature exhibited excellent diagnostic efficiency for 1-, 3- and 5-year disease-relapse events. Moreover, multivariate Cox regression analysis demonstrated that this 10-lncRNA signature was an independent risk factor when adjusting for several clinical signatures such as age, tumour size and lymph node status. The prognostic value of risk scores was validated in the validation set. In addition, a nomogram was established and the calibration plots analysis indicated the good performance and clinical utility of the nomogram. In conclusion, our results demonstrated that this 10-lncRNA signature effectively grouped patients at low and high risk of disease recurrence.

17.
J Cancer Res Clin Oncol ; 145(9): 2383-2396, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280346

RESUMO

PURPOSE: Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. Weighted gene co-expression network analysis was used to construct free-scale gene co-expression networks and to identify potential biomarkers for breast cancer progression. METHODS: The gene expression profiles of GSE42568 were downloaded from the Gene Expression Omnibus database. RNA-sequencing data and clinical information of breast cancer from TCGA were used for validation. RESULTS: A total of ten modules were established by the average linkage hierarchical clustering. We identified 58 network hub genes in the significant module (R2 = 0.44) and 6 hub genes (AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK), which were significantly correlated with prognosis. Receiver-operating characteristic curve validated that the mRNA levels of these six genes exhibited excellent diagnostic efficiency in the test data set of GSE42568. RNA-sequencing data from TCGA showed that the expression levels of these six genes were higher in triple-negative tumors. One-way ANOVA suggested that these six genes were upregulated at more advanced stages. The results of independent sample t test indicated that MCM10 and TTK were associated with tumor size, and that AGO2, CDC20, CDCA5, MCM10, and MYBL2 were overexpressed in lymph-node positive breast cancer. CONCLUSIONS: AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK were identified as candidate biomarkers for further basic and clinical research on breast cancer based on co-expression analysis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Redes Reguladoras de Genes , Transcriptoma , Biomarcadores Tumorais/análise , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise por Conglomerados , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Ensaios de Triagem em Larga Escala , Humanos , Análise em Microsséries , Prognóstico
18.
J Periodontal Res ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292966

RESUMO

OBJECTIVE: The purpose of this study was to investigate involvement of the P2X7 receptor in the rare condition, localized aggressive periodontitis. MATERIAL AND METHODS: Peripheral blood from 220 African Americans (103 with localized aggressive periodontitis and 117 healthy unrelated controls) was stimulated with lipopolysaccharide from E coli and Porphyromonas gingivalis. P2RX7 single nucleotide polymorphisms rs208294 (H155Y), rs1718119 (T348A), rs2230911 (T357S) and rs3751143 (E496A) were genotyped in 103 localized aggressive periodontitis patients and 117 healthy unrelated subjects. We examined genetic association between four P2RX7 single nucleotide polymorphisms and localized aggressive periodontitis, and tested for correlations between the single nucleotide polymorphisms and inflammatory response to lipopolysaccharide in blood samples from these patients. RESULTS: A significant association with localized aggressive periodontitis was observed with rs1718119 A (Thr) allele (P = 0.0063, odds ratio = 1.904) and with a haplotype containing this allele (P = 0.0075). Additionally, significant correlations with these data were found: the rs1718119 G allele correlated with greater production of IL-6, IL-2 and GM-CSF; the C (His) allele of rs208294 correlated with lower levels of IL-12p40; and the C (Thr) allele of rs2230911 correlated with greater levels of G-CSF. CONCLUSIONS: The data from these analyses support a possible biological relationship between P2RX7 genetic variants and inflammatory response in localized aggressive periodontitis patients.

19.
J Acquir Immune Defic Syndr ; 82(4): 421-425, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335591

RESUMO

BACKGROUND: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. METHODS: HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined. RESULTS: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA. CONCLUSIONS: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.

20.
J Colloid Interface Sci ; 553: 409-417, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228755

RESUMO

Efficient multifunctional Titania/Lignocellulosic Biomass (TiO2-OP) composite photocatalysts were fabricated via ultrasonic-assisted sol-gel for the photoreduction of Cr(VI) under UV and visible light. Materials were fully characterized using FTIR, XPS, BET, SEM-EDS, UV-DRS, XRD, photo-current and contact angle measurements. It was deduced that the produced TiOC bonding bridge between TiO2 clusters and olive pits lignocellulosic surface exhibits a significant role for the visible light response and band gap narrowing, wherein, Eg values were between 3.02 and 2.63 eV as a function of TiO2/OP ratio. TiO2-OP composites showed an astonishing photocatalytic efficiency, i.e., a complete reduction of Cr(VI) at 10 ppm was found within 30 min with TiO2-OP(50%), against 90 min for TiO2 under UV light. Nevertheless, in terms of TiO2-OP(50%), a total reduction was obtained within 50 min under visible light, while no photoactivity was observed with bare-TiO2. Several plausible mechanistic pathways behind the photocatalytic efficiency of TiO2-OP composites were discussed.

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