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1.
Plant Cell Physiol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32044993

RESUMO

Spartina alterniflora (Spartina) is the only halophyte in the salt marsh. However, the molecular basis of its high salt tolerance remains elusive. In this study, we used PacBio full-length single molecule long-read sequencing and RNA-seq to elucidate the transcriptome dynamics of high salt tolerance in Spartina by salt-gradient experiments. High quality unigenes, transcription factors, non-coding RNA and Spartina specific transcripts were identified. Co-expression network analysis found that protein kinases-encoding genes (SaOST1, SaCIPK10 and SaLRRs) are hub genes in the salt tolerance regulatory network. High salt stress induced expression of transcription factors but repressed expression of long non-coding RNAs. The Spartina transcriptome is closer to rice than Arabidopsis, and a higher proportion of transporter and transcription factor-encoding transcripts have been found in Spartina. Transcriptome analysis showed that high salt stress induced the expression of carbohydrate metabolism, especially cell wall biosynthesis-related genes in Spartina, while repressed its expression in rice. Compared with rice, high salt stress highly induced the expression of stress response, protein modification and redox-related gene expression, and greatly inhibited translation in Spartina. High salt stress also induced alternative splicing in Spartina, while differentially expressed alternative splicing events associated with photosynthesis were over-represented in Spartina but not in rice. Finally, we built the SAPacBio website for visualizing full-length transcriptome sequences, transcription factors, ncRNAs, salt-tolerant genes, and alternative splicing events in Spartina. Overall, this study suggests that salt tolerance mechanism in Spartina is different from rice from many aspects and is far more complex than expected.

2.
J Colloid Interface Sci ; 565: 205-206, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31972334

RESUMO

A reply to the comment of Kim et al. on "Visible-light-driven, hierarchically heterostructured, and flexible silver/bismuth oxyiodide/titania nanofibrous membranes for highly efficient water disinfection" is presented. We would like to thank Kim et al. for being interested in our recent work [J. Song, J. Yu, G. Sun, Y. Si, and B. Ding, J. Colloid Interface Sci. 555 (2019) 636]. In response to the comment from Kim et al., we studied and discussed the effects of silver ions under both dark and visible light irradiation conditions on the inactivation of E. coli, and verified that Ag ions played quite minor roles in E. coli disinfection for Ag/BiOI/TiO2 under our experimental conditions.

3.
Plant Physiol ; 182(1): 228-242, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31767692

RESUMO

Alternative cleavage and polyadenylation (APA) is increasingly recognized as an important regulatory mechanism in eukaryotic gene expression and is dynamically modulated in a developmental, tissue-specific, or environmentally responsive manner. Given the functional importance of APA and the rapid accumulation of APA sites in plants, a comprehensive and easily accessible APA site database is necessary for improved understanding of APA-mediated gene expression regulation. We present a database called PlantAPAdb that catalogs the most comprehensive APA site data derived from sequences from diverse 3' sequencing protocols and biological samples in plants. Currently, PlantAPAdb contains APA sites in six species, Oryza sativa (japonica and indica), Arabidopsis (Arabidopsis thaliana), Medicago truncatula, Trifolium pratense, Phyllostachys edulis, and Chlamydomonas reinhardtii APA sites in PlantAPAdb are available for bulk download and can be queried in a Google-like manner. PlantAPAdb provides rich information of the whole-genome APA sites, including genomic locations, heterogeneous cleavage sites, expression levels, and sample information. It also provides comprehensive poly(A) signals for APA sites in different genomic regions according to distinct profiles of cis-elements in plants. In addition, PlantAPAdb contains events of 3' untranslated region shortening/lengthening resulting from APA, which helps to understand the mechanisms underlying systematic changes in 3' untranslated region lengths. Additional information about conservation of APA sites in plants is also available, providing insights into the evolutionary polyadenylation configuration across species. As a user-friendly database, PlantAPAdb is a large and extendable resource for elucidating APA mechanisms, APA conservation, and gene expression regulation.

4.
Eur J Pharmacol ; 867: 172797, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31747547

RESUMO

Endothelial dysfunction plays important roles in vascular dysfunction under diabetic conditions. The generation of advanced glycation end products (AGEs), which can induce inflammation and oxidative stress, is pivotal in endothelial dysfunction. Salidroside, a major active compound in Rhodiola rosea, exerts protective effects against vascular diseases. To study the effects and mechanism of salidroside in diabetes-induced vascular endothelial dysfunction, an in vitro model was established with AGEs-induced human umbilical vein endothelial cells (HUVECs). Then, cell viability, cell apoptosis, pro-inflammatory cytokines and oxidative biomarkers were tested to determine the effects of salidroside at 10, 50 and 100 µM doses on AGEs induced HUVECs. Additionally, RNA-Seq and bioinformatics analyses were used to search for the underlying mechanism of salidroside. The results showed that salidroside promoted cell viability and significantly alleviated cell apoptosis in AGEs-induced HUVECs. Furthermore, salidroside remarkably decreased the levels of the pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 and impeded the expression of VCAM-1 and ICAM-1 induced by AGEs. Additionally, salidroside promoted superoxide dismutase (SOD) activity and increased catalase (CAT) and glutathione peroxidase (GSH-Px) levels while inhibiting the intracellular generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in AGEs-induced HUVECs. Importantly, salidroside alleviated endothelial inflammation and oxidative stress by activating AMPK phosphorylation and inhibiting NF-ĸB p65 and NLRP3 inflammasome activation. Therefore, we used compound C, an accepted AMPK inhibitor, to further demonstrate the mechanism. Interestingly, the phenomenon produced by salidroside was abolished. Our findings suggest that salidroside ameliorates AGEs-induced endothelial inflammation and oxidative stress, partially via the AMPK/NF-κB/NLRP3 signaling pathway.

5.
Am J Physiol Renal Physiol ; 318(1): F43-F52, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630547

RESUMO

The offspring of Robo2 mutant mice usually present with variable phenotypes of congenital anomalies of the kidney and urinary tract (CAKUT). An intrauterine low-protein diet can also cause CAKUT in offspring, dominated by the duplicated collecting system phenotype. A single genetic or environment factor can only partially explain the pathogenesis of CAKUT. The present study aimed to establish an intrauterine low-protein diet roundabout 2 (Robo2) mutant mouse model and found that the intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. At the same time, more ectopic and lower located ureteric buds (UBs) were observed in the intrauterine low-protein diet-fed Robo2 mutant mouse model, and the number of UB branches was reduced in the serum-free culture. During UB protrusion, intrauterine low-protein diet reduced the expression of Slit2/Robo2 in Robo2 mutant mice and affected the expression of glial cell-derived neurotrophic factor/Ret, which is a key molecule for metanephric development, with increasing phospho-Akt and phospho-cAMP responsive element-binding protein 3 activity and a reduction of apoptotic cells in embryonic day 11.5 UB tissues. The mechanism by which an intrauterine low-protein diet aggravates CAKUT in Robo2 mutant mice may be related to the disruption of Akt/cAMP responsive element-binding protein 3 signaling and a reduction in apoptosis in UB tissue.

6.
Environ Int ; 135: 105406, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31864033

RESUMO

Arsenic-alkali residue (AAR) from antimony smelting is highly hazardous due to its ready leachability of As, seeking for proper disposal such as stabilization treatment. However, As stabilization in AAR would be challenging due to the high content of coexisting soluble carbonate. This study conducted the stabilization treatments of AAR by ferrous sulfate and lime, respectively, and revealed the significant influence of coexisting carbonate. It was found that ferrous sulfate was more efficient than lime, which required only one-tenth of dosages of lime to reduce the As leaching concentration from 915 mg/L to a level below 2.5 mg/L to meet the Chinese regulatory limit. The combining qualitative and quantitative analyses based on XRD, SEM-EDS, and thermodynamic modeling suggested that the formation of insoluble arsenate minerals, ferrous arsenate or calcium arsenate, was the predominant mechanism for As stabilization in the two treatment systems, and their efficiency difference was primarily attributed to the coexisting carbonate, which had a slight effect on ferrous arsenate but severely obstructed calcium arsenate formation. Moreover, the examination of As leaching concentrations in 1-year-cured samples indicated that the long-term stability of ferrous sulfate treatment was far superior to that of lime treatment. This study provides ferrous salts as a promising and green scheme for stabilization treatment of AAR as well as other similar As-bearing solid wastes with coexisting soluble carbonate.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31454555

RESUMO

BACKGROUND: This research was designed to investigate patient-reported and doctor-reported reasons for the discontinuation of pharmacological treatment in Chinese patients with major depressive disorder (MDD), which was part of the National Survey on Symptomatology of Depression (NSSD) from 2014 to 2015. METHODS: This cross-sectional study included 649 patients who had discontinued antidepressant medications and 711 patients who had remained on them, selected from a group of 3516 candidates who have had at least one depressive episode. Differences in the two groups' sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for drug discontinuation were compared via Student's t-test or chi-square test. Logistic regression analysis was then used to determine the association of all non-subjective dichotomous and ordinal categorical variables, including the additional 63 items of our physician-evaluated symptomatic assessment, with drug compliance. RESULTS: Compared to the spontaneous drug discontinuation (SDD) group, the drug adherence (DA) group had significantly lower rates of the following: family history of mental disease (9.0% vs 13.6%), highest level of education achieved being post-graduate or above (1.6% vs 4.7%), smoking (5.8% vs 9.7%), and other health problems (33.9% vs 42.4%) (p's < 0.05). On the other hand, first-episode depression (48.5% vs 21.9%) and taking of mood stabilizer(s) (8.3% vs 5.6%) were higher in the former group than in the latter (p's < 0.05). Logistic Regression Analysis showed that five symptoms, such as depressed mood, were correlated positively with SDD, while another six symptoms, such as psychomotor retardation, were correlated negatively with it. The receiver operating characteristic (ROC) curve of this model yielded an area under the curve (AUC) of 0.701 (95% CI, 0.673-0.729). Notably, there were three main reasons given by patients in the DA group as to why they discontinued their medication(s): (1) concern about long-term side effects (36.1%), (2) no perceived need for taking said medication(s) long-term (34.2%), and (3) believing oneself to have been cured completely (30.0%). CONCLUSIONS: The aforementioned factors may affect patient compliance and elicit maladaptive thinking even from patients with good educational backgrounds, increasing the risk of drug discontinuation. Compliance of pharmacological treatment might be improved by increasing clarification and elucidation of different symptom clusters to the patient and combating the main reasons for drug discontinuation.

8.
JCI Insight ; 5(3)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31846438

RESUMO

Chronic sympathoexcitation is implicated in ventricular arrhythmogenesis (VAs) following myocardial infarction (MI), but the critical neural pathways involved are not well understood. Cardiac adrenergic function is partly regulated by sympathetic afferent reflexes, transduced by spinal afferent fibers expressing the transient receptor potential cation subfamily V member 1 (TRPV1) channel. The role of chronic TRPV1 afferent signaling in VAs is not known. We hypothesized that persistent TRPV1 afferent neurotransmission promotes VAs after MI. Using epicardial resiniferatoxin (RTX) to deplete cardiac TRPV1-expressing fibers, we dissected the role of this neural circuit in VAs after chronic MI in a porcine model. We examined the underlying mechanisms using molecular approaches, IHC, in vitro and in vivo cardiac electrophysiology, and simultaneous cardioneural mapping. Epicardial RTX depleted cardiac TRPV1 afferent fibers and abolished functional responses to TRPV1 agonists. Ventricular tachycardia/fibrillation (VT/VF) was readily inducible in MI subjects by programmed electrical stimulation or cesium chloride administration; however, TRPV1 afferent depletion prevented VT/VF induced by either method. Mechanistically, TRPV1 afferent depletion did not alter cardiomyocyte action potentials and calcium transients, the expression of ion channels, or calcium handling proteins. However, it attenuated fibrosis and mitigated electrical instability in the scar border zone. In vivo recordings of cardiovascular-related stellate ganglion neurons (SGNs) revealed that MI enhances SGN function and disrupts integrated neural processing. Depleting TRPV1 afferents normalized these processes. Taken together, these data indicate that, after MI, TRPV1 afferent-induced adrenergic dysfunction promotes fibrosis and adverse cardiac remodeling, and it worsens border zone electrical heterogeneity, resulting in electrically unstable ventricular myocardium. We propose targeting TRPV1-expressing afferent to reduce VT/VF following MI.

9.
J Affect Disord ; 264: 1-6, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846806

RESUMO

BACKGROUND: Banana contains many kinds of substances that are beneficial to depressive symptoms. However, there are no epidemiological researches directly to explore the association between banana consumption and depressive symptoms. This study aimed to investigate whether the banana consumption is related to depressive symptoms in a general adult population. METHODS: A cross-sectional study was performed in 24,673 adults in Tianjin. Banana consumption was evaluated via a validated food frequency questionnaire. Depressive symptoms were assessed by using Self-Rating Depression Scale (SDS). The association between banana consumption and depressive symptoms was analyzed by multiple logistic regression analysis. RESULTS: The prevalence of depressive symptoms was 16.1% in males and 18.4% in females (SDS ≥ 45), respectively. In males, comparing to the reference group (almost never), the multivariable adjusted odds ratios (ORs) (95% confidence intervals) of depressive symptoms across banana consumption were 0.86 (0.74, 0.99) for <1 time/week, 0.76 (0.66, 0.88) for 1-3 times/week and 0.97 (0.82, 1.16) for ≥4 times/week. By contrast, the multivariable adjusted ORs (95% confidence intervals) were 1.11 (0.94, 1.32) for <1 time/week, 0.99 (0.85, 1.16) for 1-3 times/week and 1.22 (1.02, 1.46) for ≥4 times/week in females. Similar association was observed when other cut-offs (SDS ≥ 48 and 50) were used to define depressive symptoms. LIMITATION: This is a cross-sectional study, causality remains unknown. CONCLUSION: Findings from this study suggested a negative association between moderate banana consumption and depressive symptoms in males. In females, high banana consumption is positively related to depressive symptoms.

10.
Arterioscler Thromb Vasc Biol ; 40(2): 412-425, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31852219

RESUMO

OBJECTIVE: Atherosclerosis is a leading cause of death in developed countries. MicroRNAs act as fine-tuners of gene expression and have been shown to have important roles in the pathophysiology and progression of atherosclerosis. We, and others, previously demonstrated that microRNA-144 (miR-144) functions to post-transcriptionally regulate ABCA1 (ATP binding cassette transporter A1) and plasma HDL (high-density lipoprotein) cholesterol levels. Here, we explore how miR-144 inhibition may protect against atherosclerosis. Approach and Results: We demonstrate that miR-144 silencing reduced atherosclerosis in male, but not female low-density lipoprotein receptor null (Ldlr-/-) mice. MiR-144 antagonism increased circulating HDL cholesterol levels, remodeled the HDL particle, and enhanced reverse cholesterol transport. Notably, the effects on HDL and reverse cholesterol transport were more pronounced in male mice suggesting sex-specific differences may contribute to the effects of silencing miR-144 on atherosclerosis. As a molecular mechanism, we identify the oxysterol metabolizing enzyme CYP7B1 (cytochrome P450 enzyme 7B1) as a miR-144 regulated gene in male, but not female mice. Consistent with miR-144-dependent changes in CYP7B1 activity, we show decreased levels of 27-hydroxycholesterol, a known proatherogenic sterol and the endogenous substrate for CYP7B1 in male, but not female mice. CONCLUSIONS: Our data demonstrate silencing miR-144 has sex-specific effects and that treatment with antisense oligonucleotides to target miR-144 might result in enhancements in reverse cholesterol transport and oxysterol metabolism in patients with cardiovascular disease.

11.
J Colloid Interface Sci ; 560: 681-689, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706650

RESUMO

TiO2-based fibrous membranes as plasmonic heterojunction photocatalysts would hold great promise in the field of water disinfection, however, it still existed a great challenge to design and construct such materials. Here, we presented the fabrication of continuous, hierarchical, and easy-to-recycle flexible Ag2C2O4/TiO2 heterostructured nanofibrous membranes (NMs) that were composed of thorn-like nanofibers through electrospinning technique followed by successive ionic layer adsorption and reaction (SILAR) process. Ag2C2O4 nanoplates were firmly anchored on the surface of TiO2 and the obtained Ag2C2O4/TiO2 heterojunction photocatalysts underwent a silent-to-active transition of visible-light response under light irradiation due to the surface plasmon resonance (SPR) effect of Ag nanoparticles derived from Ag2C2O4, forming a new plasmonic heterojunction photocatalyst. By virtue of the hierarchical structure, enhanced visible light absorption and efficient charge carriers separation, Ag2C2O4/TiO2 NMs possessed high bactericidal efficiency of >99.999% within 30 min, strong reactive oxygen species (ROS) producing capability (1510 µg g-1 and 659 µg g-1 for superoxide radicals and hydroxyl radicals, respectively), and good reusability. This work may offer new insights into the design of antibacterial materials for pathogenic microorganism-contaminated water purification.

12.
Clin Epigenetics ; 11(1): 183, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801625

RESUMO

BACKGROUND: Smoking leads to the aging of organs. However, no studies have been conducted to quantify the effect of smoking on the aging of respiratory organs and the aging-reversing ability of smoking cessation. RESULTS: We collected genome-wide methylation datasets of buccal cells, airway cells, esophagus tissue, and lung tissue from non-smokers, smokers, and ex-smokers. We used the "epigenetic clock" method to quantify the epigenetic age acceleration in the four organs. The statistical analyses showed the following: (1) Smoking increased the epigenetic age of airway cells by an average of 4.9 years and lung tissue by 4.3 years. (2) After smoking ceased, the epigenetic age acceleration in airway cells (but not in lung tissue) slowed to a level that non-smokers had. (3) The epigenetic age acceleration in airway cells and lung tissue showed no gender difference. CONCLUSIONS: Smoking can accelerate the epigenetic age of human respiratory organs, but the effect varies among organs and can be reversed by smoking cessation. Our study provides a powerful incentive to reduce tobacco consumption autonomously.

13.
Adv Sci (Weinh) ; 6(22): 1901844, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763156

RESUMO

Amyloid beta (Aß) aggregation is generally believed as the crucial and primary cause of Alzheimer's disease (AD). However, current Aß-targeted therapeutic strategies show limited disease-modifying efficacy due to the irreversible damages in the late stage of AD, thus the treatment should be given before the formation of deposition and target primary Aß species rather than advanced plaques. Herein, inspired by heat shock protein, a self-assembly nanochaperone based on mixed-shell polymeric micelle (MSPM) is devised to act as a novel strategy for AD prevention. With unique surface hydrophobic domains, this nanochaperone can selectively capture Aß peptides, effectively suppress Aß aggregation, and remarkably reduce Aß-mediated cytotoxicity. Moreover, the formed nanochaperone-Aß complex after Aß adsorption can be easily phagocytosed by microglia and thereby facilitates Aß clearance. As a result, the nanochaperone reduces Aß burden, attenuates Aß-induced inflammation, and eventually rescues the cognitive deficits of APP/PS1 transgenic AD mice. These results indicate that this biomimetic nanochaperone can successfully prevent the onset of AD symptoms and serve as a promising candidate for prophylactic treatment of AD.

14.
Aging (Albany NY) ; 11(22): 10031-10051, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756171

RESUMO

DNA methylation changes within the genome can be used to predict human age. However, the existing biological age prediction models based on DNA methylation are predominantly adult-oriented. We established a methylation-based age prediction model for children (9-212 months old) using data from 716 blood samples in 11 DNA methylation datasets. Our elastic net model includes 111 CpG sites, mostly in genes associated with development and aging. The model performed well and exhibited high precision, yielding a 98% correlation between the DNA methylation age and the chronological age, with an error of only 6.7 months. When we used the model to assess age acceleration in children based on their methylation data, we observed the following: first, the aging rate appears to be fastest in mid-childhood, and this acceleration is more pronounced in autistic children; second, lead exposure early in life increases the aging rate in boys, but not in girls; third, short-term recombinant human growth hormone treatment has little effect on the aging rate of children. Our child-specific methylation-based age prediction model can effectively detect epigenetic changes and health imbalances early in life. This may thus be a useful model for future studies of epigenetic interventions for age-related diseases.

15.
BMC Infect Dis ; 19(1): 962, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711435

RESUMO

BACKGROUND: High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method. METHODS: We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China). RESULTS: Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9-72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0-75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0-94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002). CONCLUSIONS: Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.

16.
Medicine (Baltimore) ; 98(46): e17921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725643

RESUMO

The aim of the study was to investigate the molecular mechanisms in childhood adrenocortical tumors (ACTs), which is still unclear.A total of 9 girls and 4 boys with ACTs were enrolled. Relevant clinical features were obtained from records. Immunohistochemistry of vimentin, chromogranin A, S100, synaptophysin, cytokeratin (CK), type 2 3ß-hydroxysteroid dehydrogenase (3ßHSD), cytochrome P45017α, p53, p21, p27, cyclin D1, Ki-67, insulin growth facter-2 (IGF-2), and ß-catenin were undertaken for 13 tumors and 3 adjacent normal tissues. TP53 mutations in exon 2-11 were analyzed for 6 tumors and 3 blood samples.Virilization was the most common presentation (8/13, 61.5%). Immunohistochemically, p53 was positive in 8 of 13 ACTs and none in controls while p21 was positive in 12 of 13 ACTs and none in controls (P = .0036). Ki-67 was positive in 10 of 13 ACTs, but not in normal tissues (P = .0089). Although the expression of p27, cyclin D1, IGF-2 and ß-catenin were similar between the ACTs and controls, ß-catenin was noted in nuclear of 3 ACTs but not in controls. The difference of type 2 3ßHSD and P450c17α was not significant (P > .05, respectively). Four variants of TP53 were identified in the 6 tumors. C215G variant was found in 5 of 6 while A701G and G743A variants were found in 1 case, respectively. A novel C680G variant was also noted in 1 case. It was notable that C215G variant was found in the blood mononuclear cell of 3 patients.In conclusion, p53 variant and p21 overexpression, and abnormal ß-catenin distribution may be involved in the etiology and mechanism of childhood ACTs.


Assuntos
Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Virilismo/epidemiologia , 3-Hidroxiesteroide Desidrogenases/biossíntese , Neoplasias do Córtex Suprarrenal/cirurgia , Fatores Etários , Criança , Pré-Escolar , Cromogranina A/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Lactente , Fator de Crescimento Insulin-Like II/biossíntese , Queratinas/biossíntese , Antígeno Ki-67/biossíntese , Masculino , Proteínas de Ligação a Poli-ADP-Ribose/biossíntese , Fatores Sexuais , Sinaptofisina/biossíntese , Vimentina/biossíntese
17.
J Am Chem Soc ; 141(48): 19032-19037, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31729871

RESUMO

Precisely assembled DNA nanostructures are promising candidates for the delivery of biomolecule-based therapeutics. Herein, we introduce a facile strategy for the construction of a branched DNA-based nanoplatform for codelivery of gene editing (sgRNA/Cas9, targeting DNA in the nucleus) and gene silencing (antisense, targeting mRNA in the cytoplasm) components for synergistic tumor therapy in vitro and in vivo. In our design, the branched DNA structure can efficiently load a sgRNA/Cas9/antisense complex targeting a tumor-associated gene, PLK1, through DNA self-assembly. With the incorporation of an active targeting aptamer and an endosomal escape peptide by host-guest interaction, the biocompatible DNA nanoplatform demonstrates efficient inhibition of tumor growth without apparent systemic toxicity. This multifunctional DNA nanocarrier provides a new strategy for the development of gene therapeutics.

18.
Fish Physiol Biochem ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595407

RESUMO

Hypoxia-inducible factors (HIFs) are master transcription factor regulating hypoxic responses in vertebrates. Species of Schizothoracine, a sub-family of cyprinidae, are highly endemic to the hypoxic Qinghai-Tibetan Plateau (QTP). What roles the HIFs play in hypoxic adaptation in the Schizothoracine fish is little known. In this study, the HIF-1α/B gene from Gymnocypris dobula (Gd) was characterized. The predicted protein for Gd-HIF-1α/B contains the main domains (bHLH, PAS, PAC, ODD, N-TAD, and C-TAD). Moreover, a specific mutation that the proline hydroxylation motif (LXXLAP) mutated into PxxLAP was observed in Gd-HIF-1α/B CODD domain, which may lead to changes in the function. To clarify whether HIF-1α/B of G. dobula possesses hypoxic adaptive features, Gd-HIF1α/B and Schizothorax prenanti-HIF1α/B (Sp-HIF1α/B) were cloned into an expression vector and transfected into 293T cells. Cell viability was found to be significantly higher in cells transfected with Gd-HIF-1α/B than those transfected with Sp-HIF-1α/B under hypoxic conditions. In addition, G. dobula HIF-1α/B showed stronger activity in transactivating the expression of nitric oxide (NO)-synthesizing enzyme, NOS2B under hypoxia stresses than the orthologous gene from S. prenanti, which were accompanied with upregulated expressions of NOS2B in heart of G. dobula, which may attribute to elevated NO levels detected in G. dobula than the lower land species. These results indicated that the HIF-1α plays an important role in mediating the iNOS signaling system in the process of evolutionary adaptation of the Schizothoracine to the highland environment.

19.
Bioinformatics ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31557285

RESUMO

MOTIVATION: Alternative polyadenylation (APA) plays a key post-transcriptional regulatory role in mRNA stability and functions in eukaryotes. Single cell RNA-seq (scRNA-seq) is a powerful tool to discover cellular heterogeneity at gene expression level. Given 3' enriched strategy in library construction, the most commonly used scRNA-seq protocol-10× Genomics enables us to improve the study resolution of APA to the single cell level. However, currently there is no computational tool available for investigating APA profiles from scRNA-seq data. RESULTS: Here, we present a package scDAPA for detecting and visualizing dynamic APA from scRNA-seq data. Taking bam/sam files and cell cluster labels as inputs, scDAPA detects APA dynamics using a histogram-based method and the Wilcoxon rank-sum test, and visualizes candidate genes with dynamic APA. Benchmarking results demonstrated that scDAPA can effectively identify genes with dynamic APA among different cell groups from scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: The scDAPA package is implemented in Shell and R, and is freely available at https://scdapa.sourceforge.io. CONTACT: yec@xmu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

20.
PLoS One ; 14(9): e0222288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513613

RESUMO

OBJECTIVE: Systematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis. METHODS: Clinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0. RESULTS: 10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P<0.001, I2 = 74.1%] and boost the mobility speed of patients in Timing 24 Minute Walk Test (T24FW) [SMD = 3,08, 95%CI(1,58, 4.58), P<0.001, I2 = 98.7%]. There are no significant differences of the incidence of adverse events [RR = 1.06, 95%CI (0.99, 1.14), P = 0.928, I2 = 0.0%] and urinary tract infection [RR = 1.21, 95%CI(0.91, 1.60), P = 0.145, I2 = 37.2%] between the DAP test group (Doses≤10 mg) and the placebo control group, and the incidence of adverse events [RR = 1.14, 95%CI(1.02, 1.28), P = 0.793, I2 = 0.0%] and urinary tract infection[RR = 3.05, 95%CI(1.04, 8.99), P = 0.680, I2 = 0.0%] for the DAP test group (Doses>10 mg) is a litter higher than the placebo control group. CONCLUSION: DAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses.

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