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1.
J Cell Physiol ; 235(2): 1235-1246, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31267540

RESUMO

Prostate cancer (PCa) is the second leading cause of death among American men. Increasing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis of PCa. In this study, we explored the biological functions of small nucleolar RNA host gene 12 (SNHG12) and investigated the interaction between miR-133b and SNHG12 in the progression of PCa. Data was downloaded from The Cancer Genome Atlas and Human Cancer Metastasis Database, and clinicopathological characteristics were analyzed with relapse-free survival rate. We detected SNHG12 expression level in PCa cells and tissues, and then analyzed its clinical significance, which revealed that SNHG12 has the potent to predict prognosis of PCa. Bioinformatic analysis revealed that SNHG12 was closely related to the progression of PCa and could target candidate microRNA (miR-133b). After transfecting SNHG12 silencing plasmid and miR-133b mimic/sponge, biological function assays were conducted and results illustrated that SNHG12 associated with miR-133b exerted biological effects on cancer cell growth, migration, and invasion. Direct interactions between miR-133b and SNHG12 have been found and SNHG12 acts as an oncogene to promote tumorigenesis of PCa by sponging tumor suppressor gene miR-133b.

2.
Chemosphere ; 238: 124594, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445334

RESUMO

Enhancing the biodegradation efficiency of atrazine, a kind of commonly applied herbicide, has been attracted much more concern. Here, Zn2+ which has long been considered essential in adjusting cell physiological status was selected to investigate its role on the biodegradation of atrazine by Arthrobacter sp. DNS10 as well as the transmembrane transport of atrazine during the biodegradation period. The results of gas chromatography showed that the atrazine removal percentages (initial concentration was 100 mg L-1) in 0.05 mM Zn2+ and 1.0 mM Zn2+ treatments were 94.42% and 86.02% respectively at 48 h, while there was also 66.43% of atrazine left in the treatment without exogenous Zn2+ existence. The expression of atrazine chlorohydrolase gene trzN in the strain DNS10 cultured with 0.05 mM and 1.0 mM Zn2+ was 7.30- and 4.67- times respectively compared with that of the non-zinc treatment. In addition, the flow cytometry test suggests that 0.05 mM of Zn2+ could better adjust the membrane permeability of strain DNS10, meanwhile, the amount of atrazine accumulation in the strain DNS10 co-cultured with this level Zn2+ was 2.21 times of that of the strain without Zn2+. This study may facilitate a better understanding of the mechanisms that exogenous Zn2+ enhances the biodegradation of atrazine by Arthrobacter sp. DNS10.

3.
Clin Cancer Res ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796514

RESUMO

PURPOSE: Emerging evidence indicates that castration-resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor (AR) or its V7 splice variant (AR-V7) and commonly becomes resistant to endocrine therapy. The aim of this work is to evaluate the function of a kinesin protein, KIF4A, in regulating AR/AR-V7 in prostate cancer endocrine therapy resistance. EXPERIMENTAL DESIGN: We examined KIF4A expression in clinical prostate cancer specimens by immunohistochemistry. Regulated pathways were investigated by qRT-PCR, immunoblot analysis, immunoprecipitation, and luciferase reporter and chromatin immunoprecipitation (ChIP) assays. A series of functional analyses were conducted in cell lines and xenograft models. RESULTS: Examination of the KIF4A protein and mRNA levels in prostate cancer patients showed that increased expression of KIF4A was positively correlated with AR levels. Patients with lower tumor KIF4A expression had improved overall survival (OS) and disease-free survival (DFS). Mechanistically, KIF4A and AR form an auto-regulatory positive feedback loop in prostate cancer: KIF4A binds AR and AR-V7 and prevents CHIP-mediated AR and AR-V7 degradation; AR binds the promoter region of KIF4A and activates its transcription. KIF4A promotes castration-sensitive and castration-resistant prostate cancer cell growth through AR- and AR-V7-dependent signaling. Furthermore, KIF4A expression is upregulated in enzalutamide (ENZ)-resistant prostate cancer cells, and KIF4A knockdown effectively reverses ENZ resistance and enhances the sensitivity of CRPC cells to endocrine therapy. CONCLUSION: These findings indicate that KIF4A plays an important role in the progression of CRPC and serves as a crucial determinant of the resistance of CRPC to endocrine therapy.

5.
Front Immunol ; 10: 2618, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803180

RESUMO

Adult-onset primary immunodeficiency is characterized by recurrent infections, hypogammaglobulinemia, and poor antibody response to vaccines. In this study, we have analyzed targeted gene panel sequencing results of 270 patients diagnosed with antibody deficiency and identified five disease-associated variants in NFKB1 in five unrelated families. We detected two single base pair deletions and two single base pair insertions, causing severe protein truncations, and one missense mutation. Immunoblotting, lymphocyte stimulation, immunophenotyping, and ectopic expression assays demonstrated the functional relevance of NFKB1 mutations. Besides antibody deficiency, clinical manifestations included infections, autoimmune features, lymphoproliferation, lymphoma, Addison's disease, type 2 diabetes and asthma. Although partial clinical penetrance was observed in almost all pedigrees, all carriers presented a deficiency in certain serum immunoglobulins and the majority showed a lack of memory B cells (CD19+CD27+). Among all tested genes, NFKB1 alterations were the most common monoallelic cause of antibody deficiency in our cohort.

7.
Mikrochim Acta ; 186(12): 771, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31720853

RESUMO

A ratiometric electrochemiluminescent (ECL) assay is described for the determination of the calcium(II) regulator calcitonin (CT). The method is making use of (a) graphite-like carbon nitride (g-C3N4) as the cathodic luminophore, (b) N-(aminobutyl)-N-(ethylisoluminol) (ABEI) as the anodic luminophore, and (c) peroxodisulfate and dissolved oxygen as coreactants. The luminous potential of g-C3N4 and ABEI can be well distinguished because of their different luminescent properties. Energy transfer between g-C3N4 and ABEI is not observed, and the coreactants peroxodisulate and oxygen do not interfere with each other. Au nanoparticles were functionalized with g-C3N4 and placed on the electrode to serve as a matrix for immobilization of primary antibody (Ab1). In the presence of CT, it will bind to the electrode. Then secondary antibody (Ab2) modified with polyaniline (PANI) and ABEI is incubated onto the electrode. With the increase in the concentration of CT, the blue ECL of g-C3N4 is quenched by PANI, while the blue luminescence of ABEI is enhanced. This enables ratiometric detection of calcitonin by ratioing the internsities at 460 and 475 nm. Response is linear in the 0.1~40 pg·mL-1 CT concentration range, and the limit of detection is 23 fg·mL-1. The method breaks the limitation of common ECL ratiometric strategy, namely, two luminophores often share the common coreactant. Graphical abstractSchematic representation of an immunoassay where polyaniline (PANI) in a BSA-Ab2-ABEI-Au@PANI composite quenches the cathodic signal of a graphitic carbon nitride (Au-g-C3N4) modified with gold nanoparticles (Au), while N-(aminobutyl)-N-(ethylisolumino) (ABEI) in the BSA-Ab2-ABEI-Au@PANI composit produces an anodic signal that enables quantitation of calcitonin.

8.
Nanotechnology ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31739294

RESUMO

Hydrophobic particles have been suffering from aggregation in aqueous-media, which limits their applications in oil/water separation. Surfactants have been used to increase the dispersity of the hydrophobic particles in water, but this approach compromises particles' hydrophobicity and oil absorption capabilities. Recently, hierarchical microparticles decorated with nanospikes were found to exhibit long-term anomalous dispersion in liquid medium without adding any surfactants. However, whether this anomalous dispersion phenomenon was applicable to 2D nano-petals decorated microparticles still remains unknown. Here, we developed a ZnO-based flower-like microparticles (FLMPs) whose surfaces were attached with 2D nano-petals, and we examined their anomalous dispersity. Our results showed that both hydrophilic and hydrophobic FLMPs could achieve anomalous dispersity either in water or organic solvents, likely due to reduced interparticle collision by the 2D nano-petals. In addition, the functional hydrophobic FLMPs also possessed a large surface area and superhydrophobic surfaces to efficiently absorb oil spills on water and oil emulsion suspended in water. In contrast, the hydrophobic microbeads (MBs) without nano-petals structure seriously aggregated in water and exhibited reduced oil absorption abilities. Our work demonstrated the new finding of 2D nano-pedal structure-mediated anomalous dispersity, and provided a new method for effective oil/water separation using superhydrophobic particles without surfactants.

9.
Biosens Bioelectron ; : 111872, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31740259

RESUMO

A strong hydroxide (OH-)-dependent ECL emission of carboxyl functionalized-poly (9,9-di-n-octylfluorenyl-2,7-diyl) polymer dots (PFO Pdots) was observed at +1.25 V, which is significantly stronger than the emission at +1.95 V reported in previous work. Moreover, hydrogen peroxide (H2O2) can efficiently quench OH--dependent ECL emission of PFO Pdots. Based on this discovery, a signal "off-on" ECL biosensing platform for microRNA-155 (miRNA-155) was developed. Firstly, PFO Pdots were modified onto the electrode to capture DNA duplex track-locker. In the presence of H2O2 in the test solution, the ECL signal of PFO Pdots was quenched to obtain a signal-off state. Subsequently, the DNA walker produced through the target miRNA-155-triggered catalytic hairpin assembly (CHA) walked along the DNA duplex track-locker to output amounts of G-rich short chain, forming a hemin/G-quadruplex. With the consumption of H2O2 by hemin/G-quadruplex, the ECL signal would be restored to a signal-on state, thus achieving an ultrasensitive detection of miRNA-155. The detection limit was low as 12.2 aM. Furthermore, our proposed biosensor demonstrated a tremendous selectivity and admirable stability, and exhibited a satisfactory performance for determinating intracellular miRNA-155. The integration of excellent ECL performance of PFO Pdots without any exogenous species or dissolved O2 as co-reactant and a highly efficient quenching effect of H2O2 on such an ECL emission will provide an attractive ECL platform for bioanalysis and clinical diagnosis.

11.
ACS Appl Mater Interfaces ; 11(47): 43936-43948, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31696695

RESUMO

One-dimensional nanoneedle-like arrays have emerged as an attractive tool for penetrating the cell membrane to achieve intracellular applications including drug delivery, electrical recording, and biochemical detection. Hollow nanoneedles, also called nanostraws (NSs), combined with nanoelectroporation have been demonstrated as a powerful platform for intracellular drug delivery and extraction of intracellular contents. However, the fabrication technique of nanostraws still requires complicated and expensive atomic layer deposition and etching processes and fails to produce conductive nanostraws. Herein, we developed a commonly accessible and versatile electrodeposition approach to controllably fabricate conductive nanostraw arrays based on various types of metal or conductive polymer materials. Representatively, Pt nanostraws (Pt NSs) with 400 nm diameter were further integrated with a low-voltage nanoelectroporation system to achieve cell detection, intracellular drug delivery, and sensing of intracellular enzymes. Both theoretical simulations and experimental results revealed that the conductive nanostraws in direct contact with cells could induce high-efficiency cell electroporation at relatively low voltage (∼5 V). Efficient delivery of reagents into live cells with spatial control and repeated extraction of intracellular enzymes (e.g., caspase-3) for temporal monitoring from the same set of cells were demonstrated. This work not only pioneers a new avenue for universal production of conductive nanostraws on a large scale but also presents great potential for developing nanodevices to achieve a variety of biomedical applications including cell re-engineering, cell-based therapy, and signaling pathway monitoring.

12.
Small ; : e1902828, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755221

RESUMO

Modern nanotechnologies bring humanity to a new age, and advanced methods for preparing functional nanocrystals are cornerstones. A considerable variety of nanomaterials has been created over the past decades, but few were prepared on the macro scale, even fewer making it to the stage of industrial production. The gap between academic research and engineering production is expected to be filled by flow chemistry technology, which relies on microreactors. Microreaction devices and technologies for synthesizing different kinds of nanocrystals are discussed from an engineering point of view. The advantages of microreactors, the important features of flow chemistry systems, and methods to apply them in the syntheses of salt, oxide, metal, alloy, and quantum dot nanomaterials are summarized. To further exhibit the scaling-up of nanocrystal synthesis, recent reports on using microreactors with gram per hour and larger production rates are highlighted. Finally, an industrial example for preparing 10 tons of CaCO3 nanoparticles per day is introduced, which shows the great potential for flow chemistry processes to transfer lab research to industry.

13.
Anal Chem ; 91(22): 14666-14671, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31697065

RESUMO

Detection of inorganic phosphate is very important in environmental and health care applications. In this work, we found that phenomenon similar to "catalytic hydrogen wave" occurred on a molybdenum phosphide (MoP) modified electrode in the presence of phosphate, that is, a new wave of catalytic hydrogen evolution appeared before the normal hydrogen evolution reaction. The catalytic hydrogen wave arose from a structure similar to phosphomolybdic acid (noted as MoPO), which was formed by the interaction between phosphate and molybdenum oxides on the surface of the MoP modified electrode, resulting in the altered surface structure and adjusted interface catalytic activity. A novel phosphate electrochemical sensor was constructed based on this phenomenon with a linear range from 0.10 to 20.0 mmol·L-1, an actually determined minimum concentration of 0.030 mmol·L-1, and recoveries of 94%-107%, and this sensor was successfully applied to the detection of phosphate in human blood. Furthermore, this work proposes a new sensing method based on catalytic hydrogen waves on the modified electrodes.

14.
Eur J Pharmacol ; : 172778, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31705901

RESUMO

The dysregulation of long non-coding RNA (lncRNA) DLX6-AS1 has been identified to be involved in the development of several cancers, but its functional role and the underlying mechanism of DLX6-AS1 in breast cancer (BC) remains unknown. In the current study, the expression of DLX6-AS1 in the BC tissue samples was evaluated and the correlation between DLX6-AS1 expression and clinicopathological parameters were also analyzed. We found that DLX6-AS1 expression was much higher in tumor tissues than that in adjacent normal tissues and was positively associated with poor prognosis in BC patients. DLX6-AS1 knockdown significantly suppressed BC cell proliferation, invasion, migration, and promoted apoptosis. Moreover, luciferase reporter assay validated that DLX6-AS1 acted as an endogenous sponge to miR-505-3p and negatively regulated its expression. Additionally, miR-505-3p inhibited runt-related transcription factor 2 (RUNX2) expression by directly bind to its 3'- untranslated region (3'-UTR) and overexpression of RUNX2 partially reversed the effect of miR-505-3p mimics on BC cell proliferation and invasion. Furthermore, in BC tissues, miR-505-3p expression level was inversely associated with DLX6-AS1 and RUNX2, respectively. In conclusion, these findings demonstrated that DLX6-AS1 functioned as an oncogenic role that promoted BC proliferation and invasion through miR-505-3p/RUNX2 axis, which might serve as a potential therapeutic target for BC treatment.

15.
Aging (Albany NY) ; 11(21): 9597-9615, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727869

RESUMO

Kidney cancer ranked in the top 10 for both men and women in the estimated numbers of new cancer cases in the United States in 2018. Targeted therapies have recently been administered to patients with clear cell renal cell carcinoma (ccRCC), but the overall survival of patients at the terminal stage of the disease has not been as good as expected. It is therefore necessary to uncover efficient biomarkers for early diagnosis, and to clarify the molecular mechanisms underlying ccRCC progression and metastasis. Increased evidence has shown that long non-coding RNAs (lncRNAs) play important roles during tumor progression. In this study, 10 candidate lncRNAs with diagnostic and prognostic values in ccRCC were identified: IGFL2-AS1, AC023043.1, AP000439.2, AC124854.1, AL355102.4, TMEM246-AS1, AL133467.3, ZNF582-AS1, LINC01510 and PSMG3-AS1. Enrichment analysis revealed metabolic and functional pathways, which may be closely associated with kidney cancer tumorigenesis. Six representative processes were summarized, namely glycolysis, amino acid metabolism, lipid synthesis, reductive carboxylation, nucleotide metabolism, transmembrane transport and signal transduction. In combination, the present results provided prognostic and diagnostic biomarkers for ccRCC and might pave the way for targeted intervention and molecular therapies in the future.

16.
Curr Pharm Des ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31642769

RESUMO

Antibacterial multidrug resistance has been recognized as one of the foremost global health challenge affecting human health. Increasing number of multidrug-resistant pathogens and the emergence of resistant infections have posed a serious challenge, thus collaboration and innovations of different disciplines are required to address these issues. In this review, the development and the mechanisms of bacterial multidrug resistance will be explained at first. With the understanding of resistance mechanisms, a wide range of strategies for combating bacterial multidrug resistance including developing novel antibiotic natural products, combination therapy, development of efflux pump inhibitors and nanotechnology are introduced and discussed subsequently. The rational and effective application of these strategies can guide us to combat bacterial multidrug resistance in the near future.

17.
J Agric Food Chem ; 67(45): 12590-12598, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31639305

RESUMO

Carotenoids play key roles in photosynthesis and photoprotection. Few multicellular plants produce the ketocarotenoid astaxanthin, a strong antioxidant; however, Arabidopsis thaliana lines overexpressing the Chlamydomonas reinhardtii ß-carotene ketolase (CrBKT) accumulated high amounts of astaxanthin in the leaves. In this study, we investigated the changed regulation of key metabolic pathways and the tolerance of the engineered plants to biotic and abiotic stresses resulting from the heterologous expression of CrBKT. Transcriptome analysis identified 1633 and 1722 genes that were differentially expressed in the leaves and siliques, respectively, of CrBKT-overexpressing plants (line CR5) as compared to wild-type Arabidopsis. These genes were enriched in the carotenoid biosynthetic pathways, and plant hormone biosynthesis and signaling pathways. In particular, metabolic profiling showed that, as compared to the wild-type leaves and siliques, overexpression of CrBKT increased the levels of most amino acids, but decreased the contents of sugars and carbohydrates. Furthermore, CR5 plants had lower sensitivity to abscisic acid (ABA) and increased tolerance to oxidative stress. CR5 plants also exhibited enhanced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Our study provides insight into the regulation of carotenoids and the related pathways, which may be involved in plant response to oxidative stress and pathogen infection.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/química , Arabidopsis/microbiologia , Regulação da Expressão Gênica de Plantas , Estresse Oxidativo , Doenças das Plantas/genética , Reguladores de Crescimento de Planta/metabolismo , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/microbiologia , Pseudomonas syringae/fisiologia , Xantofilas/biossíntese
18.
FEBS Open Bio ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515968

RESUMO

Increasing evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in biological processes and are dysregulated in various tumors. The lncRNA DANCR functions as an oncogene in various cancers, but elucidation of its role in pancreatic cancer (PC) requires further investigation. In the current study, we demonstrate that DANCR was increased in PC tissues and cell lines. Knockdown of DANCR significantly suppressed cell proliferation, migration, and invasion, and influenced the levels of epithelial-to-mesenchymal transition-associated proteins, as demonstrated by the observation of enhanced E-cadherin levels and reduced N-cadherin levels in PC cells. In addition, we identified direct binding to the predicted miR-33b binding site on DANCR. We also showed that there is reciprocal repression between DANCR and miR-33b. Furthermore, a miR-33b inhibitor partially abrogated knockdown of DANCR and caused inhibitory effects. We also demonstrated that DANCR functions as a miR-33b sponge to positively regulate MMP16 expression in PC cells. Collectively, the data reveal that DANCR exerts its function by regulating miR-33b/MMP16 expression, implying an important role for a lncRNA-miRNA-mRNA functional network and suggesting a novel potential therapeutic target for PC.

19.
Angew Chem Int Ed Engl ; 58(45): 16210-16216, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31557392

RESUMO

Deterministic methods for tuning polymer dispersity are rare, especially for nonradical polymerizations. Reported here is the first example of photomodulating dispersity in controlled cationic polymerizations of vinyl ethers using carboxy-functionalized dithienylethene initiators. Reversible photoisomerization of these initiators induces changes in their acidities by up to an order of magnitude. Using the more acidic, ring-closed isomers as initiators results in polymers with lower dispersities. The degree of light-induced pKa change in the initiators correlates with the degree of dispersity change in polymers derived from the isomeric initiators. The polymerizations are controlled, and dynamic photoswitching of dispersity during the polymerization reaction was demonstrated. This work provides a framework for photomodulating dispersity in other controlled polymerizations and developing one-pot block copolymerization reactions in which the dispersities of component blocks can be controlled using light.

20.
Future Microbiol ; 14: 1133-1146, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31512521

RESUMO

Aim: This study aimed to evaluate the differences of biosurfactants produced by two Lactobacillus helveticus strains against the biofilm formation of Staphylococcus aureus in vitro and in vivo. Materials & methods: Scanning electron microscopy, Real time-quantitative PCR (RT-qPCR) and cell assay were used to analyze the inhibiting effect of biosurfactants against biofilm formation. Results & conclusion: Results showed that the biosurfactants have anti-adhesive and inhibiting effects on biofilm formation in vivo and in vitro. The biofilm-formative genes and autoinducer-2 signaling regulated these characteristics, and the biosurfactant L. helveticus 27170 is better than that of 27058. Host cell adhesion and invasion results indicated that the biosurfactants L. helveticus prevented the S. aureus invading the host cell, which may be a new strategy to eliminate biofilms.

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