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1.
Artigo em Inglês | MEDLINE | ID: mdl-32459310

RESUMO

CONTEXT: The contribution of blood extracellular vesicular (EV) programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) in papillary thyroid cancer (PTC) is uncertain. OBJECTIVE: We sought to determine the relationship of EV PD-L1/PD-1 with the clinical features of pediatric PTC and the role of EV PD-L1 in immunosuppression. MAIN OUTCOME MEASURES: Plasma levels of EV and soluble PD-L1 and PD-1 and levels of plasma cytokines in PTC children and controls were determined by ELISA. Levels of tumor PD-L1 and the tumor-infiltrating lymphocyte (TIL) score were determined by immunohistochemistry. Correlations of the plasma PD-L1/PD-1 level with clinicopathological characteristics, levels of plasma cytokines, tumor PD-L1 expression and TIL score were analyzed. T cell suppression by EVs from PTC patients was determined by incubation of PD-L1high or PD-L1low EVs with activated CD8+ T cells. Changes in CD69 and PD-1 expression and changes in TNFa and IFNγ secretion were measured by flow cytometry. RESULTS: The levels of plasma PD-L1/PD-1 were significantly higher in PTC children than in controls. The levels of plasma EV PD-L1 significantly correlated with tumor T stage, tumor PD-L1 expression, TIL score, and plasma cytokine content. Levels of plasma soluble PD-1 significantly correlated with patient age, plasma EV PD-L1 and IFNα concentration. PD-L1high EVs significantly inhibited the activation of CD8+ T cells. CONCLUSIONS: Plasma levels of EV PD-L1, but not soluble PD-L1, were associated with tumor T stage in PTC children. Plasma EV PD-L1 emerges as a useful metric for assessing tumor T stage and T cell suppression in PTC.

2.
Orphanet J Rare Dis ; 15(1): 108, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349771

RESUMO

BACKGROUND: Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body. Mutations in the AGPAT2, BSCL2, CAV1 and PTRF genes define I-IV subtype of BSLC respectively and clinical data indicate that new causative genes remain to be discovered. Here, we retrieved 341 cases from 60 BSCL-related studies worldwide and aimed to explore genotype-phenotype correlations based on mutations of AGPAT2 and BSCL2 genes from 251 cases. We also inferred new candidate genes for BSCL through protein-protein interaction and phenotype-similarity. RESULTS: Analysis results show that BSCL type II with earlier age of onset of diabetes mellitus, higher risk to suffer from premature death and mental retardation, is a more severe disorder than BSCL type I, but BSCL type I patients are more likely to have bone cysts. In BSCL type I, females are at higher risk of developing diabetes mellitus and acanthosis nigricans than males, while in BSCL type II, males suffer from diabetes mellitus earlier than females. In addition, some significant correlations among BSCL-related phenotypes were identified. New candidate genes prediction through protein-protein interaction and phenotype-similarity was conducted and we found that CAV3, EBP, SNAP29, HK1, CHRM3, OBSL1 and DNAJC13 genes could be the pathogenic factors for BSCL. Particularly, CAV3 and EBP could be high-priority candidate genes contributing to pathogenesis of BSCL. CONCLUSIONS: Our study largely enhances the current knowledge of phenotypic and genotypic heterogeneity of BSCL and promotes the more comprehensive understanding of pathogenic mechanisms for BSCL.

3.
Plant Dis ; : PDIS12192736RE, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396054

RESUMO

Wheat stem rust, caused by Puccinia graminis f. sp. tritici, is one of the most serious fungal diseases in wheat production, seriously threatening the global supply of wheat and endangering food security. The present study was conducted to evaluate wheat monogenic lines with known Sr genes to the most prevalent P. graminis f. sp. tritici races in China. In addition, wheat lines introduced from the International Maize and Wheat improvement Center (CIMMYT) with resistance to the Ug99 race group were also evaluated with the prevalent Chinese P. graminis f. sp. tritici races. The monogenic lines containing Sr9e, Sr21, Sr26, Sr31, Sr33, Sr35, Sr37, Sr38, Sr47, and SrTt3 were effective against races 21C3CTTTM, 34C0MRGSM, and 34C3MTGQM at both seedling and adult-plant stages. In contrast, monogenic lines containing Sr6, Sr7b, Sr8a, Sr9a, Sr9b, Sr9d, Sr9f, Sr9g, Sr13, Sr16, Sr18, Sr19, Sr20, Sr24, Sr28, Sr29, and Sr34 were highly susceptible to these races at both seedling and adult-plant stages. Lines with Sr5, Sr10, Sr13, Sr14, Sr15, Sr17, Sr21, Sr22, Sr23, Sr25, Sr27, Sr29, Sr30, Sr32, Sr36, and Sr39 were resistant to one or more of the tested races. Among the 123 CIMMYT lines, 38 (30.9%) showed varying levels of susceptibility to Chinese P. graminis f. sp. tritici races. The results should be useful for breeding wheat cultivars with resistance to stem rust.

4.
Int J Pediatr Otorhinolaryngol ; 134: 110074, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32416530

RESUMO

OBJECTIVE: Retropharyngeal lymphatic malformations (LMs) are uncommon congenital anomalies. Open surgery, sclerotherapy and various pharmaceutical agents have been described to manage these lesions. However, when such lesions involve the retropharyngeal space with evidence of airway compromise, none of the above aforementioned modalities has shown superior result without repeated imaging and procedures. We describe the use of radiofrequency ablation (Coblation) in an endoscopic-assisted, transoral approach as a one-off treatment for pediatric retropharyngeal lymphatic malformations. METHODS: Six patients with retropharyngeal lymphatic malformations, presented with airway compromise, were treated with endoscopic-assisted, transoral submucosal coblation in our unit between April 2015 to August 2018. We retrospectively reviewed their medical records, imaging and endoscopic findings. RESULTS: Five out of our six patients had LMs involving only the retropharyngeal space, who received the coblation as their sole treatment. One patient with extensive LMs involving multiple neck compartments received coblation to the retropharyngeal part as an adjunct procedure. The average operation time was 62.8 min, and the average intraoperative blood loss was 3.8 ml. All patients were safely extubated immediately after the surgery. None required admission to pediatric intensive care unit (PICU), nor prolonged dysphagia reported. They were observed for 2-5 days post operatively. The average follow up was 28 months (1-5 years) and none required re-operation to date. CONCLUSIONS: We presented our approach and outcome of 6 children with endoscopic-assisted, transoral submucosal coblation to retropharyngeal lymphatic malformation. We believe it is a safe and effective primary treatment to these patients, and a possible adjunct to complex vascular malformation involving multiple sites.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32330344

RESUMO

Porous materials, especially the metal-organic frameworks, covalent organic frameworks and supramolecular organic frameworks are widely used in the fields of heterogeneous catalysis, adsorption, and ion exchange. Cucurbit[ n ]urils (Q[ n ]s) are expected to become basic building units because they possess neutral electrostatic potential cavities, negative electrostatic potential portal carbonyls and positive electrostatic potential outer surfaces, which may result in the formation of Q[ n ]-based supramolecular frameworks (QSFs) assembled through the inclusion of Q[ n ]s with guests, the coordination of Q[ n ]s with metal ions and the outer surface interaction of Q[ n ]s (OSIQ). This review summarizes the various QSFs assembled via OSIQs, and the QSFs can be classified as being assembled by i) self-induced OSIQ; ii) anion-induced OSIQ and iii) aromatic-induced OSIQ. The design and construction of QSFs through OSIQs with novel structures and specific functional properties may establish a new research direction in Q[ n ] chemistry.

6.
J Pediatr Urol ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32334969

RESUMO

INTRODUCTION: Laparoscopic pyeloplasty (LP) has been widely used in the treatment of pediatric ureteropelvic junction obstruction (UPJO). However, no prior reports with a large pediatric series have focused on the analysis of complications and impact factors of the outcomes. We hypothesized there were risk factors of higher Clavien grade postoperative complications. OBJECTIVE: To analyze the characteristics of complications and risk factors of high Clavien grade postoperative complications. PATIENTS AND METHODS: All children with UPJO treated with primary transperitoneal LP between July 2016 and July 2018 were retrospectively reviewed. The Clavien complication grades in groups with different weight, intraoperative complication (drainage methods), anteroposterior pelvic diameters (APPD), side, gender, title of surgeon, preoperative presentation and obstruction reason were compared. RESULTS: Of the 279 children, intraoperative complications in which the placement of double-J stents was not accomplished and conversion to open surgery (Satava grade II) occurred in 17 (6.09%) and 2 (0.72%) patients, respectively. A total of 270 patients (277 kidneys) were included in the analysis of postoperative complications. Postoperative complications occurred in 51 (18.89%) patients. The most frequent postoperative incident was febrile UTI in 27 patients. Of the 13 patients who required reoperations, 6 patients had kidney restenosis and were considered as failure of surgery. All complications with an exact onset time occurred within 10 months after surgery. In the univariate and multivariate analysis, weight <10 kg and having intraoperative complication with nephrostomy tube were risk factors of higher Clavien postoperative complication grade (P<0.05). DISCUSSION: Patients who were <10 kg in weight and having intraoperative complication with nephrostomy tube had a greater risk of a higher Clavien grade postoperative complication. To reduce high Clavien grade postoperative complications, asymptomatic patients under 10 kg in weight and having intraoperative complication with nephrostomy tube need close monitoring. In the 26 patients who had an exact time of the postoperative complications, the longest time we found was 10 months. Thus, we recommend the follow-up time required to observe postoperative complications in patients should be at least 10 months after surgery. CONCLUSIONS: LP has been proven to be safe and effective in children with a low rate of complications. Weight <10 kg and having intraoperative complications with nephrostomy tube were risk factors of higher Clavien grade postoperative complications. Children with low weight and intraoperative complications need more attention in terms of the occurrence of complications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32343611

RESUMO

Preterm birth is one of the most common complications during human pregnancy, and associated with a dramatic switch within the uterus from quiescence to contractility. However, the mechanisms underlying uterine remodeling are largely unknown. Protein kinases and phosphatases play critical roles in regulating the phosphorylation of proteins involved in the smooth muscle cell functions. In the present study, we found that src-homology phosphatase type-1 (SHP-1, PTPN6) was significantly decreased in human myometrium in labor compared with that not in labor. Timed-pregnant mice injected intraperitoneally with the specific SHP-1 inhibitor, PTPI-1, manifested significantly preterm labor, with enriched plasmalemmal dense plaques between myometrial cells and increased phosphorylation at Tyr397 and Tyr576/577 sites of focal adhesion kinase (FAK) in myometrial cells, which remained to the time of labor, whereas the phosphorylation levels of ERK1/2 and PI3K showed a rapid increase upon PTPI-1 injection, but fell back to normal at the time of labor. The Tyr576/577 in FAK played an important role in the interaction between FAK and SHP-1. Knockdown of SHP-1 dramatically increased the spontaneous contraction of HUSMCs, which was reversed by co-infection of a FAK-knockdown lentivirus. PGF2a downregulated SHP-1 via PLCß-PKC-NF-kB or PI3K-NF-kB pathways, suggesting the regenerative downregulation of SHP-1 enhances the uterine remodeling and plasticity by activating FAK and subsequent focal adhesion pathway, which eventually facilitates myometrium contraction and leads to labor. The study examined mechanisms that underlie the initiation of labor, and interventions for modulation of SHP-1 may provide a potential strategy for preventing preterm birth.

8.
Sheng Li Xue Bao ; 72(2): 148-156, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328608

RESUMO

The adrenal gland is an important endocrine organ of human body. CYP11B1 gene was specifically expressed in the zona fasciculata in adrenal cortex. In order to better study the function of genes specifically expressed in the zona fasciculata in adrenal cortex, the mice with Cre recombinase specifically expressed in the zona fasciculata in adrenal cortex were constructed. It was then confirmed that CYP11B1 was specifically expressed in adrenal glands. Then, using CRISPR/Cas9 technique, CYP11B1-2A-GfpCre recombinant vector was constructed and subsequently injected into the fertilized eggs of mice. It was confirmed that the Cre gene was mainly expressed in the zona fasciculata in adrenal cortex of CYP11B1Cre mice by using mTmG and LacZ staining. The CYP11B1Cre mice were then mated with cystathionine γ-lyase (CTH)f/f mice, thereby generating CTHf/f/CYP11B1Cre mice. It was also confirmed that CTH gene in the zona fasciculata in adrenal cortex was specifically knocked out in these mice. These results suggest that transgenic mice with specific Cre recombinase expression in the zona fasciculata in adrenal cortex were constructed successfully. This animal model can be a powerful tool for the study of the function of genes expressed in the zona fasciculata in adrenal cortex.

9.
Mol Genet Genomic Med ; 8(5): e1217, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32168437

RESUMO

BACKGROUND: The objective of this study was to investigate the genetic causes of two probands diagnosed as Waardenburg syndrome (WS type I and IV) from two unrelated Chinese families. METHODS: PAX3 and SOX10 were the main pathogenic genes for WS type I (WS I) and IV (WS IV), respectively; all coding exons of these genes were sequenced on the two probands and their family members. Luciferase reporter assay and co-immunoprecipitation (CO-IP) were conducted to verify potential functional outcomes of the novel mutations. RESULTS: The first proband is a 9 years old girl diagnosed with WS I. A novel PAX3 heterozygous mutation of c.372-373delGA (p.N125fs) was identified, which results in a frameshift and truncation of PAX3 protein. In family II, a 2 years old girl was diagnosed with WS IV, and Sanger sequencing revealed a de novo SOX10 mutation of c.1114insTGGGGCCCCCACACTACACCGAC (p.Q372fs), a frameshift mutation that extends the amino acid chain of SOX10 protein. Functional studies indicated that the novel mutation of SOX10 had no effects on the interaction of SOX10 and PAX3, but reduced transactivate capacity of melanocyte inducing transcription factor (MITF) promoter. Both PAX3 and SOX10 mutation-induced defects of MITF transcription might contribute to the WS pathogenesis. CONCLUSION: We revealed a novel mutation in PAX3 and a de novo mutation in SOX10, which might account for the underlying pathogenesis of WS. This study expands the database of both PAX10 and PAX3 mutations and improves our understanding of the causes of WS.

10.
J Otolaryngol Head Neck Surg ; 49(1): 11, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131901

RESUMO

BACKGROUND: The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting. METHODS: Children between 2 and 15 years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ≥ 1 were defined as OSAS. RESULTS: A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ≥ 3 months, male gender, preterm birth, breastfeeding, obesity, neck circumference ≥ 30 cm, waist/hip ratio ≥ 0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn't. Multivariate analysis showed that snoring for ≥ 3 months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS. CONCLUSION: The independent risk factors for OSAS in children included snoring ≥ 3 months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is "Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children" and the URL is https://clinicaltrials.gov/.

11.
Sleep Med ; 67: 110-119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918116

RESUMO

BACKGROUND: The peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility. METHODS: This systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS). RESULTS: In sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15-1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23-52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19-61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87-2.18); (Recessive model, OR = 1.42; 95% CI = 0.83-2.42); (Allele model, OR = 1.07; 95% CI = 0.96-1.18). CONCLUSIONS: This systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.

12.
Environ Res ; 182: 109013, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918310

RESUMO

Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P < 0.01 for interaction in all thyroid cancers. In the common homozygote groups, no association with cell phone use was observed. In the variant group (heterozygotes and rare homozygotes), cell phone use was associated with an increased risk for rs11070256 (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.30-4.30), rs1695147 (OR: 2.52, 95% CI: 1.30-4.90), rs6732673 (OR: 1.59, 95% CI: 1.01-2.49), rs396746 (OR: 2.53, 95% CI: 1.13-5.65), rs12204529 (OR: 2.62, 95% CI: 1.33-5.17), and rs3800537 (OR: 2.64, 95% CI: 1.30-5.36) with thyroid cancers. In small tumors, increased risk was observed for 5 SNPs (rs1063639, rs1695147, rs11070256, rs12204529 and rs3800537), In large tumors, increased risk was observed for 3 SNPs (rs11070256, rs1695147, and rs396746). Our result suggests that genetic susceptibilities modify the associations between cell phone use and risk of thyroid cancer. The findings provide more evidence for RFR carcinogenic group classification.

13.
Chem Commun (Camb) ; 56(15): 2304-2307, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31989126

RESUMO

A Schiff-base macrocyclic host (MH) showing ESIPT and AIEE is reported for the first time; the fluorescent macrocycle exhibited good pH tolerance and could serve as a probe for Cu2+ and Fe3+ ion sensing and removal. In addition, a series of size-tunable nanoparticles was fabricated by the self-assembly of free MH and its coordination complex with Fe3+ in THF/water solution.

14.
Laryngoscope ; 130(1): 269-273, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30953386

RESUMO

OBJECTIVES/HYPOTHESIS: The definition of large-volume pathologic N1 metastases has been changed in the 2017 version 2 of the National Comprehensive Cancer Network guidelines, leading to a controversy over the optimal surgical approach selection for patients with biopsy-proven papillary thyroid carcinoma (PTC). The aim of this study was to investigate the therapeutic efficacy of total thyroidectomy (TT) and thyroid lobectomy (TL) for these patients. STUDY DESIGN: Retrospective population-based database analysis. METHODS: A total of 906 consecutive PTC patients with pathologic N1 metastases (>5 involved nodes with metastases ≤5 mm in the largest dimension) were retrieved from the Surveillance, Epidemiology, and End Results database, and divided into two groups (≤2 mm, >2-5 mm) based on the size of the extent of disease. Overall survival (OS) was then compared between patients treated with TT and TL, followed by Cox proportional hazards regression analysis to explore multiple prognostic factors. RESULTS: OS favored TT compared with TL in patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension (P < .05). Cox analysis showed that the TL was not an independent factor associated with poorer OS than TT in these patients (P > .05). CONCLUSIONS: TT showed better survival than TL for patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension. For patients with more than five involved nodes and metastases ≤2 mm in the largest dimension, either TT or TL can be recommended because there was no difference in survival. LEVEL OF EVIDENCE: NA Laryngoscope, 130:269-273, 2020.

15.
J Hazard Mater ; 384: 121474, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635819

RESUMO

A water-soluble terpyridine-based cationic fluorescent probe (SP-TPy) was synthesized, which emerged with pH-dependent amphiphilicity, resulting in self-assembly and disassembly in aqueous media with the aggregation-induced emission (AIE) property. In neutral water (pH 7.4), a moderate sensing response to Hg2+ ions was given by the self-assembly of SP-TPy. However, in acidic aqueous media, the monomer of SP-TPy not only appeared to be highly selective and sensitive for Hg2+ ions, but also displayed highly efficient removal of Hg2+ ions from solution by rapid precipitation, which was attributed to the coordination-triggered reassembly of SP-TPy. The removal efficiency of SP-TPy for Hg2+ was found to be over 99%. Further study indicated that the precipitates were composed of various polyhedral porous frameworks, a property that was further used to adsorb H2S gas to form HgS complexes with higher uptake capacities. In addition, SP-TPy can be efficiently regenerated and recycled using a simple treatment with acidic water after adsorption of the H2S gas.

16.
Nucleic Acids Res ; 48(D1): D856-D862, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31598709

RESUMO

Aberrant DNA methylation plays an important role in cancer progression. However, no resource has been available that comprehensively provides DNA methylation-based diagnostic and prognostic models, expression-methylation quantitative trait loci (emQTL), pathway activity-methylation quantitative trait loci (pathway-meQTL), differentially variable and differentially methylated CpGs, and survival analysis, as well as functional epigenetic modules for different cancers. These provide valuable information for researchers to explore DNA methylation profiles from different aspects in cancer. To this end, we constructed a user-friendly database named DNA Methylation Interactive Visualization Database (DNMIVD), which comprehensively provides the following important resources: (i) diagnostic and prognostic models based on DNA methylation for multiple cancer types of The Cancer Genome Atlas (TCGA); (ii) meQTL, emQTL and pathway-meQTL for diverse cancers; (iii) Functional Epigenetic Modules (FEM) constructed from Protein-Protein Interactions (PPI) and Co-Occurrence and Mutual Exclusive (COME) network by integrating DNA methylation and gene expression data of TCGA cancers; (iv) differentially variable and differentially methylated CpGs and differentially methylated genes as well as related enhancer information; (v) correlations between methylation of gene promoter and corresponding gene expression and (vi) patient survival-associated CpGs and genes with different endpoints. DNMIVD is freely available at http://www.unimd.org/dnmivd/. We believe that DNMIVD can facilitate research of diverse cancers.

17.
Cancer Epidemiol Biomarkers Prev ; 29(2): 500-508, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31826911

RESUMO

BACKGROUND: Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. METHODS: We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. RESULTS: An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 µg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 µg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 µg/day compared with <40 µg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 µg/day compared with <760 µg/day) was associated with moderate genistein intake among women. CONCLUSIONS: Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. IMPACT: The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer.

18.
Cell Prolif ; 53(1): e12723, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31828845

RESUMO

OBJECTIVE: The long non-coding RNA zinc finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1-AS1 in colon adenocarcinoma (COAD). METHODS: QRT-PCR was used to detect the expression of ZEB1-AS1, miR-455-3p and p21-activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1-AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull-down assay were used to demonstrate the mechanism of ZEB1-AS1. We further explore the role of ZEB1-AS1 in vivo though xenograft tumour assay. RESULTS: We found that ZEB1-AS1 expression was significantly up-regulated in COAD tissues, and high ZEB1-AS1 level was correlated with the poor prognosis of COAD patients. MiR-455-3p plays an anti-cancer role in COAD by targeting PAK2. We confirmed that ZEB1-AS1 promotes PAK2 expression by sponging miR-455-3p, thus facilitating COAD cell growth and metastasis. CONCLUSIONS: To sum up, this result illustrates the novel molecular mechanism of ZEB1-AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Transdução de Sinais , Quinases Ativadas por p21/metabolismo , Adenocarcinoma/patologia , Animais , Neoplasias do Colo/patologia , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Metástase Neoplásica , Regulação para Cima
19.
Int J Pediatr Otorhinolaryngol ; 130: 109811, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31837561

RESUMO

OBJECTIVE: To evaluate and compare the microbiological features in ACPs groups and control subjects in pediatric group, further to explore the potential role of microbial in the etiology of ACPs. METHODS: A total of 32 patients with ACPs, and 10 control subjects were enrolled in this study. Demographic datas were collected. The TaqMan low-density array assays were used to detect the microbial of swab specimens and nasal tissue samples from ACPs patients. RESULTS: A total of 15 species were identified in all groups. Of all the species, Mycoplasma pneumoniae was the most common species in ACP patients, but was negative in control group. Of all the viruses detected, Adenovirus positivity was significantly higher in control group than that in ACPs middle meatus on unaffected side, ACPs middle meatus on affected side, and ACPs polypous surface group (P < 0.05). Cytomegalovirus positivity was significantly higher in control group than that in ACP polypous group (P < 0.05). Human herpesvirus 6 (HHV-6) was absent in control goup, and positive in ACP middle meatus on affected side was significantly higher than that in ACP polypous surface and ACP polyp group (P < 0.05). The expression of other microbial differed not significantly in unaffected side, affected side of ACPs, ACPs polypous surface, and ACPs polyp. CONCLUSIONS: Mycoplasma pneumoniae was the most common species in ACP patients. Streptococcus pneumonia and Moraxella catarrhalis were the only bacteria detected at certain frequency in nasal polyps and control subjects. Human herpesvirus 6 andMycoplasma pneumoniae may have potential role in the development of ACPs. The isolates rate of microbial differed in middle meatus on unaffected and affected side of ACPs, ACPs polypous surface, ACPs polyp, and their role in the etiology of ACPs need to be further studied.

20.
Exp Cell Res ; 387(1): 111779, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846625

RESUMO

Renal fibrosis is a key pathological feature in chronic kidney diseases (CKDs). Dysregulation of hydrogen sulfide (H2S) homeostasis is implicated in the pathogenesis of CKDs. Here, C57/BL6 mice were allocated to Sham and unilateral ureteral obstruction (UUO) groups, which were treated with NaHS or NLRP3 inflammasome inhibitor 16673-34-0 for 3-14 days. UUO mice displayed downregulation of H2S production and increased macrophage infiltration in obstructed kidneys. H2S donor NaHS treatment attenuated renal damage and fibrosis and inhibited M1 and M2 macrophage infiltration. NLPR3 inflammasome was activated and levels of phosphorylated nuclear factor κB (NF-κB) p65 subunit, phosphorylated signal transducer and activator of transcription 6 (STAT6) and interleukin (IL)-4 protein were increased in the kidneys after UUO. NLRP3 inhibitor inactivated NF-κB and IL-4/STAT6 signaling, suppressed M1 and M2 macrophage infiltration and attenuated renal damage and fibrosis in UUO mice. NaHS treatment also suppressed NLRP3, NF-κB and IL-4/STAT6 activation in the obstructed kidneys. In conclusion, the therapeutic effects of H2S on UUO-induced renal injury and fibrosis are at least in part by inhibition of M1 and M2 macrophage infiltration. H2S suppresses NLRP3 activation and subsequently inactivates NF-κB and IL-4/STAT6 signaling, which may contribute to the anti-inflammatory and anti-fibrotic effects of H2S.

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