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1.
Anticancer Drugs ; 31(6): 583-591, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32282367

RESUMO

Colorectal cancer (CRC) is one of most common cancers worldwide. Although miR-203a is reported as a tumor suppressor involved in cell progression in some cancers, the role of miR-203a in CRC is still controversial and the underling mechanism of miR-203a in CRC remains unclear. Here, we demonstrated that low expression of miR-203a had poorer survival in CRC patients. miR-203a was down-regulated in most human colon cancer cells. Overexpression of miR-203a could inhibit colon cancer cell proliferation and arrest cell cycle in G1 phase. Bioinformatics and dual luciferase reporter assay confirmed that RING-finger protein 6 (RNF6) was a target gene of miR-203a. Silencing RNF6 inhibited cell proliferation and arrest cell cycle in G1 phase. RNF6 overexpression reversed the effects of miR-203a overexpression in colon cancer cells. Taken together, our data indicate that miR-203a inhibits colon cancer cell proliferation by targeting RNF6, offer novel insights into the regulatory network of miR-203a-modulated cell cycle and proliferation, and suggest that miR-203a a potential therapeutic target in CRC treatment.

2.
Talanta ; 212: 120799, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113561

RESUMO

A novel amine- and carboxyl-bifunctionalized organic-inorganic hybrid monolithic column (A&C-HMC) was synthesized via one-pot co-condensation of N-(2-aminoethyl)-3-aminopropyltriethoxysilane, carboxyethylsilanetriol sodium salt and tetramethoxysilane with cetyltrimethylammonium bromide and polyethylene glycol 6000 as binary porogens in this work. The introduction of the binary porogens controllably improved the morphology and pore structure of A&C-hybrid monolith (HM) and made the active sites of amine and carboxyl groups more prolific, compared with the monolith prepared with either of porogens. It is found that Cr(VI) and Cr(III) can be selectively adsorbed on A&C-HM under different pH ranges, and eluted by aqueous nitric acid solution completely. The A&C-HMC was used as needle-solid phase microextraction (SPME) matrix for direct separation and enrichment of inorganic chromium species coupled with inductively coupled plasma mass spectrometer without any oxidation/reduction treatment. Various parameters of SPME operation and analytical performance were investigated systematically, and the adsorption mechanism was also discussed and explained in depth. In view of the advantages of facile preparation, low cost, excellent speciation selectivity and high adsorption capacity to Cr(VI) and Cr(III), the A&C-HMC based SPME protocol is a promising alternative for non-disturbed speciation analysis of inorganic chromium in real environmental water samples.

3.
J Neurochem ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052426

RESUMO

Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone throughout life, where they can be activated in response to physiological and pathophysiological stimuli. A recent study indicates metabotropic glutamate receptor 4 (mGluR4) is involved in regulating NSPCs behaviors. Therefore, defining mGluR4 function in NSPCs is necessary for determining novel strategies to enhance the intrinsic potential for brain regeneration after injuries. In this study, mGluR4 was functionally expressed in SVZ-derived NSPCs from male Sprague-Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4-specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5-bromo-2'-deoxyuridine (BrdU)+ and Ki67+ cells, while increased Doublecortin (DCX)/BrdU double-positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU+ cells, G2/M-phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron-specific class III ß-tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA-NCAM-positive cells. However, pharmacological blocking mGluR4 with the antagonist MSOP or knockdown of mGluR4 abolished the effects of VU0155041 on NSPCs proliferation and neuronal differentiation. Further investigation demonstrated that VU0155041 treatment down-regulated AKT phosphorylation and up-regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041-induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO-OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ-derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal.

4.
Cancer Cell Int ; 19: 308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31768130

RESUMO

Background: MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated. Methods: The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene. Results: We found that miR-1269 expression was upregulated in human GC tissues and cell lines. The overexpression of miR-1269 promoted GC cell proliferation and cell cycle G1-S transition and suppressed apoptosis. The inhibition of miR-1269 inhibited cell growth and G1-S transition and induced apoptosis. miR-1269 expression was inversely correlated with RASSF9 expression in GC tissues. RASSF9 was verified to be a direct target of miR-1269 by using a luciferase reporter assay. The overexpression of miR-1269 decreased RASSF9 expression at both the mRNA and protein levels, and the inhibition of miR-1269 increased RASSF9 expression. Importantly, silencing RASSF9 resulted in the same biological effects in GC cells as those induced by overexpression of miR-1269. Overexpression of RASSF9 reversed the effects of miR-1269 overexpression on GC cells. Both miR-1269 overexpression and RASSF9 silencing activated the AKT signaling pathway, which modulated cell cycle regulators (Cyclin D1 and CDK2). In contrast, inhibition of miR-1269 and RASSF9 overexpression inhibited the AKT signaling pathway. Moreover, miR-1269 and RASSF9 also regulated the Bax/Bcl-2 signaling pathway. Conclusions: Our results demonstrate that miR-1269 promotes GC cell proliferation and cell cycle G1-S transition by activating the AKT signaling pathway and inhibiting cell apoptosis via regulation of the Bax/Bcl-2 signaling pathway by targeting RASSF9. Our findings indicate an oncogenic role of miR-1269 in GC pathogenesis and the potential use of miR-1269 in GC therapy.

5.
Toxicol Appl Pharmacol ; 385: 114786, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31655076

RESUMO

The aim of this research was to detect potential serum biomarkers of melamine diet-induced bladder stones in C57BL/6 mice. Magnetic bead-based weak cationexchange chromatography (MB-WCX) and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were employed to detect serum biomarkers in 10 mice fed a melamine diet and 10 control mice. Seventeen peaks (fold change>1.5) with a mass to charge (m/z) value of 1000-10,000 Da were detected in the two groups. Among the significant peaks, five were upregulated and the other 12 were downregulated in the model group. Among the upregulated peaks, 2954.49 and 1710.49 were found to correspond to the peptide regions of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8(Ndufα8) and basigin, respectively, by liquid chromatography with electrospray ionization and tandem triple quadrupole mass spectrometry(LC-ESI-MS/MS). Western blot analysis was used to detect the expression of Ndufα8 and basigin in another 10 model mice and 10 control mice. The western blot results confirmed the LC-ESI-MS/MS data. The expression of serum basigin and Ndufα8 was partly dependent the concentration of melamine, but no time dependence. In conclusion, Ndufα8 and basigin may be potential serum biomarkers for the detection of melamine diet-induced bladder stones in C57BL/6 mice.

6.
Cancer Gene Ther ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31303644

RESUMO

MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1-S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.

7.
Talanta ; 195: 173-180, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625529

RESUMO

Carboxyl-group functionalized mesoporous silica (CFMS) prepared by one-pot co-condensation method was employed for the solid phase extraction (SPE) of chromium species for the first time. A new approach of SPE coupled to inductively coupled plasma mass spectrometry (ICP-MS) was thus established for the speciation of chromium in environmental water samples. The influences of pH, volume of sample, extraction time, amount of adsorbent, elution conditions, co-existing ions and adsorption capacity were investigated on adsorption or elution of chromium species. Cr(VI) was not retained on the CFMS material in the pH range of 1.0-9.0, while Cr(III) was quantitatively adsorbed at pH 5.0-9.0. The captured Cr(III) was enriched by using 1.5 mol L-1 HNO3 as elution solvent and detected by ICP-MS. Under the optimized SPE conditions, the maximum adsorption capacity of the CFMS for Cr(III) was 57.67 mg g-1 and the enrichment factor was 25, with the detection limit (LOD) of 0.02 µg L-1. The proposed protocol has been successfully applied to chromium speciation in rain, lake and river water samples, which exhibited a prospect in field separation and enrichment of chromium species in environmental waters.

8.
Angew Chem Int Ed Engl ; 58(9): 2779-2784, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30648810

RESUMO

A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+ ), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+ , and generated stable membrane potential across lipid bilayers.

9.
ACS Appl Mater Interfaces ; 11(1): 1563-1570, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30499288

RESUMO

Deterministic design of surface patterns has seen a surge of interests because of their wide applications in flexible and stretchable electronics, microfluidics, and optical devices. Recently, instability of bilayer systems has been extensively utilized by which micro-/nano-patterns of a film can be easily achieved through macroscopically deforming the underlying substrate. For a bilayer system with traditional thermostable substrates, the pattern morphology is only determined by initial strain mismatch of the two layers, and the realization of localized patterns appears to be particularly challenging because of the difficulties associated with manipulating inhomogeneous deformations. In this work, we exploit cross-linked polyethylene ( cPE), a shape memory polymer (SMP), as the flexible substrate for building micro-/nano-structures of sputtered gold films. We find that the shape memory effect can offer new dimensions for designing diverse and hierarchical surface structures by harnessing film thickness orheating time and by globally or locally controlling the thermal field. By combining those strategies, we further demonstrate versatile hierarchical, superimposed, and local surface patterns based on this cPE/gold (Au) system. Piezoresistive pressure sensors are assembled with the obtained patterned surface, which have high sensitivity, operational range, and cyclic stability. These results highlight the unique advantages of SMPs for building arbitrary surface patterns.

10.
Talanta ; 192: 339-346, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30348400

RESUMO

A thiol- and amine-bifunctionalized organic-inorganic hybrid monolithic column was prepared for the first time via one-pot co-condensation of 3-mercaptopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropyltriethoxysilane and tetraethylorthosilicate, and utilized for separation and enrichment of inorganic arsenic species. Various parameters of solid phase microextraction (SPME) operation and analytical performance were also investigated systematically. Under the optimum condition, both As(III) and As(V) can be adsorbed over a wide pH range (3.0-8.0) and eluted in turn, in which 3% HNO3 (v/v) was firstly used to selectively release As(V), and then 3% HNO3 with 0.01 mol L-1 KIO3 or 15% mercaptosuccinic acid (MSA) (m/v) to selectively release As(III). Meanwhile, the elution mechanism of As(III) and As(V) was elucidated comprehensively, and notably, the novel eluent, HNO3 + MSA, was recommended for eluting As(III). Therefore, the thiol- and amine-bifunctionalized organic-inorganic hybrid monolithic column as an ideal SPME matrix for the speciation analysis of arsenic in environmental waters has the merits of facile preparation, low cost, high adsorption capacity and selective desorption. In addition, compared with thiol- and amine-bifunctionalized mesoporous silica, the bifunctional hybrid monolith based SPME protocol with less time and reagent consumption is promising to be applied not only to filed sampling but also to on-line analysis.

11.
J Nanosci Nanotechnol ; 19(1): 226-230, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30327027

RESUMO

In this work, three-dimensional (3D) TiO2 nanotubes (NTs) on carbon cloth (CC) (TiO2 NTs/CC) were synthesized by a method involving formation of a ZnO@TiO2 nanorod (NRs) on CC (ZnO@TiO2 NRs/CC) structure and a subsequent chemical etching process for ZnO NRs template. The 3D TiO2 NTs/CC were applied as flexible anodes for sodium ion batteries (SIBs). The TiO2 NTs/CC yielded high specific capacity and good cycling stability, superior to that of some reported TiO2 nanocomposites. The TiO2 NTs/CC delivered a reversible capacity of 260 mA·h·g-1 and 85.1% capacity retention over 150 cycles at current density of 0.25 C (1 C = 335 mA·g-1). It also exhibited high rate capacity of 200 mA·h·g-1 at 0.5 C. Even at a high rate of 1.0 C, the TiO2 NTs/CC can still maintain a high capacity of 100 mA·h·g-1. Moreover, it was observed that the electrochemical performance for the TiO2 NTs/CC was much better than that (150 mA·h·g-1 for up to 150 cycles) of a solid TiO2 NRs/CC counterpart, which also demonstrated the capacity enhancement and good cycling stability.

12.
J Nanosci Nanotechnol ; 19(1): 263-267, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30327034

RESUMO

The new demands for energy storage systems have been placed with demands for flexible wearable electronics. Herein, rugby-like GeO2 nanoparticles (NPs) have been directly grown on carbon cloth (GeO2 NPs/CC) through a one-step hydrolysis process at room temperature, which can be used as a self-supporting flexible anode for lithium ion battery (LIBs). The rugby-like GeO2 NPs/CC showed an improved lithium-storage performance with features of high reversible capacity ~2000 mA·h·g-1 even after 100 cycles and good cycling stability. Besides, its initial coulomb efficiency (79.1%) was also enhanced compared to that of some reported GeO2-based materials.

13.
Cancer Cell Int ; 18: 195, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524203

RESUMO

Background: MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. Methods: The expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene. Results: We demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/ß-catenin signaling pathway. Conclusions: Our study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/ß-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.

14.
Cell Physiol Biochem ; 50(2): 411-425, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308487

RESUMO

BACKGROUND/AIMS: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. METHODS: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. RESULTS: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. CONCLUSION: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC.


Assuntos
Caderinas/metabolismo , Junções Intercelulares/metabolismo , Metaloproteinases da Matriz/metabolismo , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Regiões 3' não Traduzidas , Aciltransferases/antagonistas & inibidores , Aciltransferases/genética , Aciltransferases/metabolismo , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Metilação de DNA , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Neoplasias Gástricas/genética , Proteínas rab de Ligação ao GTP/antagonistas & inibidores , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
15.
Talanta ; 189: 517-526, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30086954

RESUMO

A comprehensively comparative study of thiol-functionalized mesoporous silica and organic-inorganic hybrid monolithic column was reported, aiming at the separation and enrichment of inorganic arsenic. Thiol-functionalized mesoporous silica was synthesized based on the one-step co-condensation method. At the same time, a novel thiol-functionalized organic-inorganic hybrid monolithic column was synthesized using an unconventional ternary weak basic solvent system via one-step sol-gel process. The approach to prepare monolithic column through mild condition remarkably improved delamination phenomenon of thiol-functionalized hybrid monolithic column easily caused by conventional methods. As(III) can be selectively uptaken by the hybrid monolithic column and homemade syringe-based solid phase extraction device containing mesoporous silica through chelation in a wide range of pH, while As(V) cannot, and then the captured As(III) was eluted by 3% HNO3 (v/v) with 0.01 mol L-1 KIO3. Under the optimized conditions, the extraction recoveries were 91-102% and 93-103% for mesoporous silica and monolithic column, respectively. Although both two materials were ideal solid matrices for the removal and speciation analysis of As(III) in environmental waters, the monolith-based solid phase microextration protocol was more fast and reagent-saving than the other, which endued monolithic columns with more application prospects for trace elemental analysis and speciation. Even so, the exploration of mesoporous silica could efficiently pilot the synthesis of monolithic columns.

16.
Oncol Lett ; 16(2): 1931-1936, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30008886

RESUMO

Previous evidence has revealed that long non-coding RNAs serve important functions in numerous types of cancer when dysregulated, including in gastric cancer (GC). In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the expression of small integral membrane protein 10 like 2A (linc00086) in GC tissues and non-cancerous tissues, and the expression of linc00086 in GC cell lines was analyzed. A RT-qPCR assay was used to assess linc00086 expression levels in GC cell lines following treatment with 5-Aza-2'-deoxycytidine (5-aza-dC), which is a DNA methyltransferase inhibitor. Small interfering RNA was used to silence the expression of methyl-CpG binding protein 2 (MeCP2), and then the expression of linc00086 was detected. Linc00086 expression was revealed to be downregulated in GC tissues and GC cell lines. Furthermore, it was revealed that 5-aza-dC induced linc00086 expression in SGC-7901 and MKN45 cells, and analysis of CpG methylation by bisulfite sequencing-polymerase chain reaction demonstrated that DNA methylation may regulate the expression of linc00086. MeCP2 is involved in gene regulation by binding to methylated promoters, and it was revealed that the knockdown of the expression of MeCP2 resulted in a higher expression of linc00086. The present study revealed that DNA methylation regulate the expression of linc00086 in human GC cell lines.

17.
J Am Chem Soc ; 140(26): 8064-8068, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29920089

RESUMO

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SNAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H2.

18.
Proteomics Clin Appl ; 12(5): e1700164, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29754444

RESUMO

PURPOSE: Autism spectrum disorder (ASD) is a neurological and developmental disorder that begins early in childhood and lasts throughout one's life. Early diagnosis is essential for ASD since early treatment can enable children with ASD to make significant gains in language and social skills, but remains challenging since there are currently no specific biomarkers of ASD. This study is aimed to identify serum biomarkers for ASD. EXPERIMENTAL DESIGN: Serum of Han Chinese children with ASD (n = 68) and age-matched healthy controls (n = 80) is analyzed using magnetic bead-based separation combined with mass spectrum. RESULTS: Eight potential ASD serum biomarker peaks (m/z: 3886.69, 7775.12, 2381.71, 6638.63, 3319.17, 894.34, 4968.59, and 5910.53) with higher expression in ASD group are further identified as peptide regions of plasma serine protease inhibitor precursor (SERPINA5), platelet factor 4 (PF4), fatty acid binding protein 1(FABP1), apolipoprotein C-I precursor (APOC1), alpha-fetoprotein precursor (AFP), carboxypeptidase B2 (CPB2), trace amine-associated receptor 6 (TAAR6), and isoform1 of fibrinogen alpha chain precursor (FGA). The expression of identified proteins is validated by enzyme-linked immunosorbent assay (ELISA). CONCLUSIONS AND MEDICAL RELEVANCE: These findings reveal the exceptional disease etiology of ASD from a serum proteomic perspective, and the identified proteins might be potential biomarkers for ASD diagnosis.


Assuntos
Transtorno do Espectro Autista/sangue , Biomarcadores/sangue , Diagnóstico Precoce , Proteoma/genética , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Espectrometria de Massas
19.
Cell Mol Biol (Noisy-le-grand) ; 64(5): 40-45, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29729692

RESUMO

Gastric cancer (GC) is one of the most common malignant cancer around the world, however the mechanisms is still unclear. In the present study, we investigated the function of CREB3 regulatory factor (CREBRF) in human GC and explored its relevant molecular mechanism. We found that CREBRF was highly expressed in primary GC tissues and the expression level was associated with the clinicopathologic characteristics of GC. CREBRF silencing inhibited GC cell proliferation and induced G1/G0 to S phase cell cycle arrest through regulating Cyclin A, Cyclin D1 and CDK2 expressions. Furthermore, the results showed that knockdown of CREBRF suppressed the activation of AKT signaling pathway. We further discovered that activating of AKT rescued the effect of CREBRF silencing on cell growth and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Taken together, our study demonstrated that CREBRF might promote GC cell proliferation and induce G1-S phase transition through activating AKT signaling pathway. These findings suggest that CREBRF acts as a novel oncogene and may be a potential therapeutic target in therapy of GC.


Assuntos
Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Ciclina A/genética , Ciclina A/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismo
20.
Small ; 14(27): e1800819, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29847706

RESUMO

Flexible piezoresistive pressure sensors have been attracting wide attention for applications in health monitoring and human-machine interfaces because of their simple device structure and easy-readout signals. For practical applications, flexible pressure sensors with both high sensitivity and wide linearity range are highly desirable. Herein, a simple and low-cost method for the fabrication of a flexible piezoresistive pressure sensor with a hierarchical structure over large areas is presented. The piezoresistive pressure sensor consists of arrays of microscale papillae with nanoscale roughness produced by replicating the lotus leaf's surface and spray-coating of graphene ink. Finite element analysis (FEA) shows that the hierarchical structure governs the deformation behavior and pressure distribution at the contact interface, leading to a quick and steady increase in contact area with loads. As a result, the piezoresistive pressure sensor demonstrates a high sensitivity of 1.2 kPa-1 and a wide linearity range from 0 to 25 kPa. The flexible pressure sensor is applied for sensitive monitoring of small vibrations, including wrist pulse and acoustic waves. Moreover, a piezoresistive pressure sensor array is fabricated for mapping the spatial distribution of pressure. These results highlight the potential applications of the flexible piezoresistive pressure sensor for health monitoring and electronic skin.

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