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1.
Sci China Life Sci ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33009993

RESUMO

As a potential cancer immunotherapeutic agent, chlorogenic acid (CHA) has entered phase II clinical trials in China as a lyophilized powder formulation for treating glioma. However, the in vivo instability of CHA necessitates daily intramuscular injections, resulting in patient noncompliance. In this study, CHA-phospholipid complex (PC)-containing PEGylated liposomes (CHA-PC PEG-Lipo, named as CPPL), with CHA-PC as the drug intermediate, were prepared to lower the administration frequency. CPPL demonstrated excellent physicochemical properties, enhanced tumor accumulation, and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes (CHA-PC Lipo, labeled as CPL), both of which only demonstrated antitumor efficacy with once-daily administration. Further evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL, such as stimulating both CD4+ and CD8+ T cell infiltration, inhibiting myeloid-derived suppressor cell expression, reducing the expression of Th2 related factors, and notably, increasing the memory T cells in tumor tissues. This CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via T cells, especially memory T cell regulation.

2.
Liver Int ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025657

RESUMO

Liver plays a critical role in metabolism, nutrient storage and detoxification. Emergency signals or appropriate immune response lead to pathological inflammation and break the steady state when liver dysfunction appears, which makes body more susceptible to chronic liver infection, autoimmune diseases and tumor. Compelling proof has illustrated the nonredundant importance of C-C chemokine receptor type 2 (CCR2), one of G-protein-coupled receptors, in different diseases. Selectively expressed on the surface of cells, CCR2 is involved in various signaling pathways and regulates the migration of cells. Especially, a peculiar role of CCR2 has been identified within decades in the onset and progression of hepatic diseases, which led to particular focusing on CCR2 as a new therapeutic and diagnostic target for nonalcoholic fatty liver disease and hepatocellular carcinoma. In this review, we discuss the effect of CCR2 in monocytes/macrophages on liver diseases. The application and translation of the decades of discoveries into therapies promise novel approaches in the treatment of liver disease.

3.
J Gen Intern Med ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021715

RESUMO

BACKGROUND: Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow. OBJECTIVE: To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients. DESIGN: Randomized community intervention trial. PARTICIPANTS: The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China. MAIN MEASURES: Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention. KEY RESULTS: BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P < 0.001). Along with the duration of the follow-up period, systolic and diastolic BP decreased rapidly in the early stages and then gradually after 6 months in the intervention group (P < 0.001). In the intervention group, drug therapy adherence was increased by 39.5% (from 48.1% at 1 month to 87.6% at 1 year) (P < 0.001), more in women (45.6%) than in men (31.2%; P < 0.001). The net effect of the lifestyle intervention improved the rate of BP control by 56.1% (70.8% for men and 44.7% for women). For all physiological and biochemical factors, such as body mass index, waist circumference, lipid metabolism, and glucose control, improvements were more significant in the behavioral intervention group than those in the control group (all P < 0.001). CONCLUSION: The addition of lifestyle intervention by physicians or nurses helps control BP effectively and lowers BP better than usual care with antihypertensive drug therapy alone.

4.
Virology ; 551: 36-45, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33011521

RESUMO

Children with HFMD due to EV71 infection are more likely to suffer from neurogenic complications, leading to higher morbidity and mortality. ILCs play crucial roles in the initiation of host immunity. However, the contribution of ILCs to the occurrence and development of HFMD due to EV71 infection remains to be explored. The results of our study showed that the levels of peripheral ILC1s and Th1 cells were increased in children with severe HFMD compared to healthy children, as were ILC1- and Th1-related cytokines and transcription factors. Furthermore, HFMD children with a higher frequency of circulating ILC1s exhibited a 2.9-fold greater risk of severity when HFMD was accompanied by VEM. Our study is the first to show that ILC1 abnormalities contribute to the pathogenesis of the severity of HFMD, in which ILC1s are aberrant increased and affect the cellular and humoral immunity. ILC1s could be used in the diagnosis of HFMD.

5.
Plant Biotechnol J ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047500

RESUMO

Sugar will eventually be exported transporter (SWEET) is a family of sugar transporters that plays a critical role during host and pathogen interaction (Bezrutczyk et al., 2018). In rice, SWEET11/Xa13, SWEET13/Xa25, and SWEET14 were identified as targets of Xanthomonas oryzae pv. oryzae effectors (Antony et al., 2010; Hutin et al., 2015; Yang et al., 2006). However, the role of SWEET genes in rice and Rhizoctonia solani, the causative agent of sheath blight disease (ShB), is largely unknown. Our previous transcriptome data showed that SWEET14 expression is sensitive to R. solani infection (De Peng Yuan, 2020). qPCR results verified that R. solani infection dramatically induces SWEET14 expression along with a pathogen-related protein PBZ1 (Figure 1a).

6.
J Hypertens ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031176

RESUMO

OBJECTIVE: We aimed to comprehensively determine the effects of hypertension on left ventricular (LV) structure, microcirculation, tissue characteristics, and deformation in type 2 diabetes mellitus (T2DM) using multiparametric cardiac magnetic resonance (CMR) imaging. METHODS: We prospectively enrolled 138 asymptomatic patients with T2DM (80 normotensive and 58 hypertensive individuals) and 42 normal glucose-tolerant and normotensive controls and performed multiparametric CMR examination to assess cardiac geometry, microvascular perfusion, extracellular volume (ECV), and strain. Univariable and multivariable linear analysis was performed to analyze the effect of hypertension on LV deformation in patients with T2DM. RESULTS: Compared with controls, patients with T2DM exhibited decreased strain, decreased microvascular perfusion, increased LV remodeling index, and increased ECV. Hypertension lead to greater deterioration of LV strain (peak strain-radial, P = 0.002; peak strain-longitudinal, P = 0.006) and LV remodeling index (P = 0.005) in patients with T2DM after adjustment for covariates; however, it did not affect microvascular perfusion (perfusion index, P = 0.469) and ECV (P = 0.375). In multivariable analysis, hypertension and diabetes were independent predictors of reduced LV strain, whereas hypertension is associated with greater impairment of diastolic function (P = 0.009) but not systolic function (P = 0.125) in the context of diabetes, independent of clinical factors and myocardial disorder. CONCLUSION: Hypertension in the context of diabetes is significantly associated with LV diastolic function and concentric remodeling; however, it has little effect on systolic function, myocardial microcirculation, or fibrosis independent of covariates, which provide clinical evidence for understanding the pathogenesis of comorbidities and explaining the development of distinct heart failure phenotypes.

7.
J Matern Fetal Neonatal Med ; : 1-8, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33032479

RESUMO

BACKGROUND AND OBJECTIVE: Lung ultrasound (LUS) has been widely used in the diagnosis and differential diagnosis of neonatal lung diseases (NLDs), but whether it can replace the routine use of chest X-ray (CXR) in neonatal intensive care units (NICUs) remains controversial. This paper summarizes the clinical practice of our neonatal intensive care unit (NICU) during the past three years to explore the feasibility and necessity of using LUS instead of CXR to diagnose NLDs in the NICU setting. METHODS: The clinical data and LUS examination results from 1,381 newborn infants with respiratory difficulty who were hospitalized in our NICU from March 2017 to February 2020 were retrospectively collected to analyze the types of lung diseases diagnosed and the reliability of LUS for diagnosing NLDs. RESULTS: (1) During this period, 1381 newborn infants with dyspnea were admitted to our NICU, accounting for 41.2% of all hospitalized children. (2) Among the 1381 infants, 17 patients with respiratory distress were confirmed as having severe heart disease by echocardiography, while the remaining 1364 patients had different kinds of lung diseases: pneumonia (697 patients, 51.1%), respiratory distress syndrome (251 patients, 17.4%), transient tachypnea of the newborn (197 patients, 13.3%), atelectasis (89 patients, 5.6%), pneumothorax (46 patients, 3.2%), pulmonary hemorrhage (69 patients, 4.5%), severe pleural effusion (18 patients, 1.32%), congenital pulmonary sequestration (3 patients, 0.22%), bullae of the lung (2 patients, 0.15%), and congenital cystic adenomatoid malformation (2 patients). (5) Among the 1381 infants, 217 received CXR examination before admission, which resulted in misdiagnosis in 45 patients (20.7%) and missed diagnosis in 12 patients (5.5%); the missed diagnosis and misdiagnosis rate was 26.3%. CONCLUSION: Our 3-year clinical practice experience indicated that LUS could completely replace chest X-ray for the diagnosis and differential diagnosis of NLDs in the NICU. Compared with X-ray, LUS had higher accuracy and reliability in diagnosing NLDs.

8.
Anal Bioanal Chem ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33029671

RESUMO

In this study, a novel fluorescent labeling reagent 2-(9-acridone)-ethyl chloroformate (AEC-Cl) was designed, synthesized and applied for the determination of free amino acids by high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The free amino acids were rapidly and efficiently labeled by AEC-Cl in the presence of basic catalyst (pH 9.0) within 5 min at room temperature (25 °C). The derivatives exhibited excellent stability and fluorescence properties, with maximum excitation and emission wavelengths at 268 nm and 438 nm, respectively. Derivatives of 22 kinds of natural amino acids were completely separated by gradient elution on a Hypersil ODS C18 column. Under the optimal conditions, the calibration curves exhibited excellent linear responses, with correlation coefficients of R2 > 0.9994. The detection and quantification limits were in the range of 0.61-2.67 µg kg-1 and 2.07-8.35 µg kg-1, respectively. Therefore, AEC-Cl was successfully applied for the detection of trace levels of free amino acids in honey samples. Graphical abstract A novel fluorescent labeling reagent was applied for the determination of free amino acids in honey by high-performance liquid chromatography with a fluorescence detector.

9.
Nat Commun ; 11(1): 5033, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024092

RESUMO

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , Máquina de Vetores de Suporte
10.
PLoS One ; 15(10): e0240596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064752

RESUMO

To explore the underlying mechanism of dietary restriction (DR) induced lifespan extension in fruit flies at protein level, we performed proteome sequencing in Drosophila at day 7 (young) and day 42 (old) under DR and ad libitum (AL) conditions. A total of 18629 unique peptides were identified in Uniprot, corresponding to 3,662 proteins. Among them, 383 and 409 differentially expressed proteins (DEPs) were identified from comparison between DR vs AL at day 7 and 42, respectively. Bioinformatics analysis revealed that membrane-related processes, post-transcriptional processes, spliceosome and reproduction related processes, were highlighted significantly. In addition, expression of proteins involved in pathways such as spliceosomes, oxidative phosphorylation, lysosomes, ubiquitination, and riboflavin metabolism was relatively higher during DR. A relatively large number of DEPs were found to participate in longevity and age-related disease pathways. We identified 20 proteins that were consistently regulated during DR and some of which are known to be involved in ageing, such as mTORC1, antioxidant, DNA damage repair and autophagy. In the integration analysis, we found 15 genes that were stably regulated by DR at both transcriptional as well as translational levels. Our results provided a useful dataset for further investigations on the mechanism of DR and aging.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32914230

RESUMO

OBJECTIVES: The associations of PM with the risk and prognosis of breast cancer have not been determined. This systematic review aimed to provide an updated understanding of the relationship between PM exposure level and breast cancer incidence and mortality. METHODS: Articles from Web of Science and PubMed databases were methodically inspected until March 8, 2020. In final, 15 studies were kept for analysis, which provided necessary information to estimate the impact of PM on breast cancer risk and prognosis. These studies were combined for quantitative analyses to evaluate the effect of per 10 µg /m3 increment exposure of PM2.5 (< 2.5 µm in aerodynamic diameter) and PM10 (< 10 µm in aerodynamic diameter) using random-effects model. RESULTS: PM2.5 exposure was associated with increased breast cancer mortality (relative risk [RR] = 1.09; 95% confidence interval [CI]: 1.02, 1.16; PQ-test = 0.158). No association of PM2.5 (1.02; 0.97, 1.18; 0.308) and PM10 (1.03; 0.98, 1.09; 0.009) with the increase incidence of breast cancer was observed. Stratified analysis suggested that PM2.5 was associated with the increase mortality of breast cancer (1.10; 1.03, 1.17; 0.529) in subgroup of developed country. PM10 was associated with breast cancer incidence based on studies published after 2017 (1.08; 1.00, 1.15; 0.157) and European studies (1.15; 1.06, 1.25; 0.502). CONCLUSIONS: Our study indicated that PM2.5 exposure was related to breast cancer mortality. Further researches in this field are needed to validate the conclusion.

12.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3726-3739, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893565

RESUMO

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/classificação , Cromatografia Líquida , Metabolômica , Ratos , Espectrometria de Massas em Tandem
13.
Phytother Res ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965773

RESUMO

Pancreatic cancer is a disease with a high mortality rate. Although survival rates for different types of cancers have improved in recent years, the five-year survival rate of pancreatic cancer stands at 8%. Moreover, the current first-line therapy, gemcitabine, results in low remission rates and is associated with drug resistance problems. Alternative treatments for pancreatic cancer such as surgery, chemotherapy and radiation therapy provide marginal remission and survival rates. This calls for the search of more effective drugs or treatments. Traditional Chinese medicine contains numerous bioactive ingredients some of which show activity against pancreatic cancer. In this review, we summarize the mechanisms of five types of traditional Chinese medicine monomers. In so-doing, we provide new potential drug candidates for the treatment of pancreatic cancer.

14.
Orphanet J Rare Dis ; 15(1): 240, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907608

RESUMO

BACKGROUND: Desbuquois dysplasia (DBQD) was a rare autosomal recessive skeletal dysplasia. Calcium activated nucleotidase 1 (CANT1) mutation was identified as a common pathogenic change for DBQD type 1 and Kim variant but not for DBQD type 2. To our knowledge, all patients with DBQD type 1 currently found could be explained by mutations in the CANT1 gene, but mutations in the CANT1 gene might not be directly diagnosed as DBQD type 1. RESULTS: We have identified two novel CANT1 mutations (mut1: c.594G > A [p.Trp198*], mut2: c.734C > T [p.Pro245Leu]) in three children from a family of Chinese origin for the first time. Two of the three children could be diagnosed as typical DBQD type 1 and one child could not be diagnosed as DBQD type 1 based on the clinical data we had. To further clarify the effect of the two mutations of the CANT1 gene, we studied the CANT1 gene expression and detected the protein secretion and nucleotide enzyme activity through cDNA cloning and expression vectors construction for wild and mutant types. The mut1 was a nonsense mutation which could lead to premature termination and produced the truncated bodies; The CANT1 dimer of mut2 was significantly reduced and even undetectable. The extracellular secretion of mut1 was extremely high while mut2 was significantly reduced compared with the wild type. And mut1 and mut2 also could result in a significant reduction in the activity of CANT1 nucleotidease. From the results we could deduce that the two mutations of the CANT1 gene were the causes of the two cases in this study. CONCLUSIONS: Regarding the particularity of the cases reported in this study, the pathogenesis of CANT1 might be more complicated. The genetic and phenotype of three children with the same genetic background need to be further studied. Larger cohort of patients was needed to establish genotype-phenotype correlations in DBQD.

15.
Medicine (Baltimore) ; 99(33): e21623, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872020

RESUMO

BACKGROUND: Prediabetes is an abnormal metabolic state that develops prior to the onset of diabetes with proven to common comorbid states of coronary artery disease. However, whether prediabetes worsens prognosis after percutaneous coronary intervention remains controversial. The aim of this study is to summarize previous cohort studies and to specify the impact of prediabetes on the long-term outcomes after percutaneous coronary intervention. METHODS: This meta-analysis will be performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines for conducting and reporting meta-analysis data. Pubmed, Embase and Google scholar will be systematically searched, and supplemented with manual searches of the included reference lists to identify cohort studies. Pooled effects on the discontinuous variables will be expressed by adjusted hazard ratios with 95% confidence intervals. All analyses will be performed with Stata 15.0 (StataCorp LP, College Station, TX). RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide new information and help enhance clinical decision-making on management of these patients. REGISTRATION NUMBER: INPLASY202060079.


Assuntos
Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estado Pré-Diabético/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Humanos , Estado Pré-Diabético/mortalidade , Prognóstico , Projetos de Pesquisa , Fatores de Risco
16.
Brain Res ; 1748: 147081, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882231

RESUMO

The growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis plays an important role in normal brain development, and GH deficiency inevitably affects the growth of the cerebral cortex. This study was designed to analyze morphological differences in gray matter volume, cortical surface area, and gray matter thickness between children with isolated growth hormone deficiency (IGHD) and children with idiopathic short stature (ISS). Twenty-four children with IGHD (mean age 9.42 years, peak GH < 5 µg/l) and 24 controls with ISS (mean age 9.21 years, peak GH > 10 µg/l) were included. High-resolution three-dimensional T1-weighted MRIs were acquired at participants' first visit. Measurements of gray matter volume, cortical surface area and gray matter thickness were obtained using FreeSurfer. The total and regional differences between groups were statistically analyzed. Correlations between the FreeSurfer results and GH and IGF-I levels were also obtained. The gray matter volume, cortical surface area and gray matter thickness of the total brain and of the bilateral hemispheres of children with IGHD were significantly smaller than those of children with ISS (all P values < 0.05). All the measurements had similar cortical distributions between groups but varied across regions. Cortical regions with significant differences in the mean gray matter volume and surface area were mainly distributed around the bilateral central sulci and the lateral and basal parts of the temporal lobes (all P values < 0.05). There were negative correlations between gray matter volume, cortical surface area and GH levels, and the right hemispheric and total cortical surface area correlated significantly with GH levels (all P values < 0.05) in children with IGHD. There were significant positive correlations between gray matter volume, cortical surface area and IGF-I levels (all P values < 0.05) in both groups, except for in left hemispheric gray matter volume in children with ISS. Children with IGHD have significant morphological changes in the cerebral cortex, which were partially influenced by GH and IGF-I levels. These cortical changes may be related to deficits in their relatively slower development in intelligence, motor performance, and other functions.

17.
J Agric Food Chem ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32869636

RESUMO

In this study, protein was extracted from extruded lupin and submitted to gastroduodenal digests to obtain lupin peptides, which were characterized using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After this, IQDKEGIPPDQQR (IQD), the lupine peptide monomer characterized after UPLC-MS/MS, was screened out by macrophage inflammatory cytokine production assay. RNA-sequencing analysis was performed to explore the mechanisms underlying the anti-inflammatory activity associated with this peptide. The results indicated that lupin peptides effectively inhibited the lipopolysaccharide-induced overproduction of proinflammatory mediators. IQD inhibited the production of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and monocyte chemoattractant protein-1 by 51.20, 38.52, 44.70, and 40.43%, respectively. RNA-sequencing results showed that IQD inhibited the inflammatory response by regulating the gene expression of the p38 mitogen-activated protein kinase pathway and inhibiting downstream inflammatory cytokines. These bioactive peptides may be used to develop new ingredients for anti-inflammatory nutritional supplements.

18.
J Int Med Res ; 48(9): 300060520934659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32940102

RESUMO

OBJECTIVE: Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and the fifth most common cancer in women. Circular RNAs (circRNAs) have been shown to play vital functions in cancers, but few studies have focused on the functions and mechanism of dysregulated circRNAs in PTC. METHODS: Quantitative reverse transcription PCR was used to measure circ-NCOR2 levels in PTC tissues and cell lines. The functions of circ-NCOR2 in PTC were examined by analysis using the cell counting kit-8, clone forming, flow cytometry, and Transwell experiments. Bioinformatic analysis and dual luciferase reporter gene testing were used to identify the mechanisms of circ-NCOR2. RESULTS: Circ-NCOR2 overexpression was observed in PTC tissues and cells. Silenced or overexpressed expression of circ-NCOR2 strikingly attenuated or facilitated, respectively, the growth, migration, and invasion of PTC cells. Mechanistically, miR-615a-5p was identified as the target of circ-NCOR2. Moreover, circ-NCOR2 enhanced the expression of metastasis-associated protein 2 (MTA2) by sponging miR-615a-5p, thereby facilitating PTC cell progression. CONCLUSIONS: Taken together, our findings reveal a novel circ-NCOR2/miR-615a-5p/MTA2 axis in PTC, which could become a potential therapeutic target for this disease.

19.
Environ Int ; 145: 106140, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32966951

RESUMO

Belgian coastal sediment serves as an important sink for trace elements, yet a systematic study covering a wide range of elements including redox-sensitive metals (Fe, Mn, and Co), cationic trace metals (Cd, Pb, Ni, Cu, and Zn), oxyanions (P, V, As, and Mo), and sulfide has not been performed and the mechanisms controlling their mobilization were not investigated. Here, a passive sampling technique, Diffusive Gradients in Thin-films (DGT), was used in situ to obtain high resolution concentration profiles of these elements in the sediment porewater. Our results revealed two mobilization mechanisms of cationic trace metals and oxyanions in Belgian coastal sediments, both strongly linked to the cycling of Fe. Mobilization of Co, Pb, Ni, and Cu is controlled by electrogenic sulfur oxidation, acidification of the porewater and dissolution of FeS, while that of oxyanions (P, V, and As) is controlled by reductive dissolution of Fe oxyhydroxides. Constant cationic trace metal to Fe molar ratios were established in FeS, while the oxyanion to Fe ratios in Fe oxyhydroxides differ significantly between sampling stations, which is primarily caused by competing effects. We found no evidence that cationic trace metal mobilization was related to Fe oxyhydroxides, or oxyanion mobilization to FeS. This suggests that particulate organic matter forms the major pathway for cationic trace metal input in coastal sediments and that oxyanions will not be incorporated in FeS but form their own oxyanion-sulfide compound. These findings will contribute to a better understanding of the mobilization mechanisms of cationic trace metals and oxyanions in coastal sediments, and of their biogeochemical cycling in coastal ecosystems.

20.
Sci Rep ; 10(1): 13924, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811880

RESUMO

Leaf flattening influences plant photosynthesis, thereby affecting product yield and quality. Here, we obtained a stably inherited leaf crinkled mutant (lcm), derived from the Chinese cabbage doubled haploid (DH) 'FT' line using EMS mutagenesis combined with isolated microspore culture. The crinkled phenotype was controlled by a single recessive nuclear gene, namely Bralcm, which was preliminarily mapped to chromosome A01 by bulked segregant analysis RNA-seq, and further between markers SSRS-1 and IndelD-20 using 1,575 recessive homozygous individuals in F2 population by a map-based cloning method. The target region physical distance was 126.69 kb, containing 23 genes; the marker SSRMG-4 co-segregated with the crinkled trait. Further, we found SSRMG-4 to be located on BraA01g007510.3C, a homolog of AHA2, which encodes H+-ATPase2, an essential enzyme in plant growth and development. Sequence analysis indicated a C to T transition in exon 7 of BraA01g007510.3C, resulting in a Thr (ACT) to Ile (ATT) amino acid change. Genotyping revealed that the leaf crinkled phenotype fully co-segregated with this SNP within the recombinants. qRT-PCR demonstrated that BraA01g007510.3C expression in lcm mutant leaves was dramatically higher than that in wild-type 'FT'. Thus, BraA01g007510.3C is a strong candidate gene for Bralcm, and AHA2 is possibly associated with leaf flattening in Chinese cabbage.

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