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1.
iScience ; 27(6): 110130, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38952687

RESUMO

The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model's effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.

2.
Small Methods ; 6(12): e2201114, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36336652

RESUMO

Safety of lithium metal batteries (LMBs) has been improved by using the solid-state polymer electrolytes, but the performance of LMBs is still troubled by the poor interface of solid electrolytes/electrodes, leading to insufficient interfacial Li+ transport. Here, a novel ultrathin, robust-flexible polymeric electrolyte is achieved by in situ polymerization of 1,3-dioxolane in soft nanofibrous skeleton at room temperature without any extra initiator or plasticizer, leading to the electrolyte with rapid interfacial ion transport. This facilitated Li+ transportation is demonstrated by molecular dynamics simulation. Consequently, the as-prepared electrolyte exhibits excellent cycling performance. The results indicate that the electrolyte works well in the LiFePO4 //Li cell at elevated temperature up to 90 °C, and further matches with the high-voltage LiNi0.8 Mn0.1 Co0.1 O2 cathode. This study provides an effective approach to constructing a practical polymeric electrolyte for fabrication of safe, high performance LMBs.

3.
Cell Death Dis ; 13(10): 886, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36270980

RESUMO

Erythroblast enucleation is a precisely regulated but not clearly understood process. Polycythemia shows pathological erythroblast enucleation, and we discovered a low miR-125b-5p level in terminal erythroblasts of patients with polycythemia vera (PV) compared to those of healthy controls. Exogenous upregulation of miR-125b-5p levels restored the enucleation rate to normal levels. Direct downregulation of miR-125b-5p in mouse erythroblasts simulated the enucleation issue found in patients with PV, and miR-125b-5p accumulation was found in enucleating erythroblasts, collectively suggesting the importance of miR-125b-5p accumulation for erythroblast enucleation. To elucidate the role of miR-125b-5p in enucleation, gain- and loss-of-function studies were performed. Overexpression of miR-125b-5p improved the enucleation of erythroleukemia cells and primary erythroblasts. Infused erythroblasts with higher levels of miR-125b-5p also exhibited accelerated enucleation. In contrast, miR-125b-5p inhibitors significantly suppressed erythrocyte enucleation. Intracellular imaging revealed that in addition to cytoskeletal assembly and nuclear condensation, miR-125b-5p overexpression resulted in mitochondrial reduction and depolarization. Real-time PCR, western blot analysis, luciferase reporter assays, small molecule inhibitor supplementation and gene rescue assays revealed that Bcl-2, as a direct target of miR-125b-5p, was one of the key mediators of miR-125b-5p during enucleation. Following suppression of Bcl-2, the activation of caspase-3 and subsequent activation of ROCK-1 resulted in cytoskeletal rearrangement and enucleation. In conclusion, this study is the first to reveal the pivotal role of miR-125b-5p in erythroblast enucleation.


Assuntos
MicroRNAs , Camundongos , Animais , MicroRNAs/genética , Caspase 3/genética , Eritroblastos , Regulação para Baixo/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética
4.
Small ; 18(38): e2203693, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36007148

RESUMO

Lithium-sulfur batteries (LSBs) have attracted extensive attention owing to their high energy density and abundant sulfur resources. However, LSBs are still restricted by the unsatisfactory electrochemical performance resulting from the shuttle effect of lithium polysulfide (LiPSs), and the potential fire hazard caused by inflammable ether electrolytes and polyolefin separators. Herein, a facile immobilization strategy for hexachlorocyclotriphosphazene (HCCP) is creatively applied to address the above issues simultaneously. Insoluble HCCP cross-linked microspheres (H-CMP) are firstly obtained at ambient temperature using tannic acid (TA) as a cross-linking agent and then a multifunctional separator coating is constructed based on H-CMP. The released phosphorus-related radicals from H-CMP in wide temperatures effectively prevent the combustion of electrolytes and separators, and hence improve the fire safety of the Li-S pouch cell. Furthermore, H-CMP availably chemisorbs LiPSs to interdict the shuttle effect, thereby dramatically improving the electrochemical performance of LSBs. The effectiveness of this strategy is also verified in high sulfur loading (6.38 mg cm-2 ), high temperature (50 °C), and Li-S pouch cells. More importantly, H-CMP exhibits sufficient stability for Li metal and suppression of Li dendrites. This facile immobilization strategy for multifunctional phosphazenes provides a competitive option for the large-scale fabrication of high-safety and high-performance LSBs.


Assuntos
Lítio , Enxofre , Éteres , Íons , Fósforo
5.
J Phys Chem B ; 126(24): 4531-4542, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35695471

RESUMO

The association of ions describes the formation of ion species in electrolyte solutions and is strongly related to the salt concentration. However, the discussion of ion species and their transport is ambiguous in some studies on electrolyte materials due to the assumption of ideal solutions. Accordingly, in this work, molecular dynamics simulations are used to study ion association and transport properties of poly(ethylene)oxide (PEO)-lithium bis(trifluoromethanesulfonyl)imide electrolytes over a range of salt concentrations (r = [Li]/[EO]) from 0.01 to 0.20. Based on the analysis of the solvation environment and ion species, it is revealed that the distinct ion-ion correlations exist in two different characteristic areas, with a salt concentration of 0.10 as the limit. Below the critical concentration, the dynamic equilibrium between free ions and ion pairs is the most important process affecting the transport properties of electrolytes, but the process may have a minor influence on the applicability of the Nernst-Einstein relation. In concentrated solutions, a large number of ion pairs, triplets, and so forth appear in the electrolytes. The high-order ion clusters, with an average size of 3.95 at r = 0.20, are the main stable structures for transporting Li+, but the trapped free ions are the most abundant ion species. Meanwhile, the effect of salt concentrations on the average transport of ion clusters is to increase their average lifetime, but their transport rates remain unchanged. In addition, the coupling dynamics between ions and polymers is also discussed in order to gain a complete insight into the importance of salt concentrations.

7.
Adv Sci (Weinh) ; 9(4): e2103663, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894106

RESUMO

Lithium metal battery (LMB) possessing a high theoretical capacity is a promising candidate of advanced energy storage devices. However, its safety and stability are challenged by lithium dendrites and the leakage of liquid electrolyte. Here, a self-enhancing gel polymer electrolyte (GPE) is created by in situ polymerizing 1,3-dioxolane (DOL) in the nanofibrous skeleton for enabling safe LMB. The nanofiber membrane possesses a better affinity with poly-DOL (PDOL) than commercial separator for constructing homogeneous GPE with enhanced ion conductivity. Furthermore, polydopamine is introduced on nanofiber membrane to form hydrogen bonding with PDOL and bis((trifluoromethyl)sulfonyl)imide anion, dramatically improving the mechanical strength, ionic conductivity, and transference number of GPE. Besides, molecular dynamic simulation is used to reveal the intrinsic factors of high ionic conductivity and reinforcing effect in the meantime. Consequently, the LiFePO4 //Li batteries using self-enhancing GPE show extraordinary cyclic stability over 800 cycles under high current density of 2 C, with a capacity decay of 0.021% per cycle, effectively suppressing the growth of lithium dendrites. This ingenious strategy is expected to manufacture advanced performance and high safety LMBs and compatible with the current battery production.

8.
BMC Ophthalmol ; 21(1): 235, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044792

RESUMO

PURPOSE AND BACKGROUND: Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis. MATERIALS AND METHODS: Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR). RESULTS: A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05). CONCLUSION: The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.


Assuntos
Doenças do Nervo Abducente , Esotropia , Diferenciação Celular , Esotropia/cirurgia , Proteínas de Homeodomínio , Humanos , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Estudos Retrospectivos
9.
Drug Des Devel Ther ; 15: 927-936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688167

RESUMO

PURPOSE: To assess the cellular and molecular effects of lidocaine on muscles/myoblasts. METHODS: Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine. RESULTS: Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥0.08%, producing a dramatic reduction in cell viability. These ≥0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1. CONCLUSION: This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.


Assuntos
Lidocaína/farmacologia , Mioblastos/efeitos dos fármacos , Receptores Notch/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Receptores Notch/genética , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
10.
Mikrochim Acta ; 188(4): 125, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723966

RESUMO

An electrochemiluminescence (ECL) DNA biosensor based on ExoIII exonuclease assistance and hybridization chain reaction (HCR) amplification technology has been constructed. ExoIII exonuclease and triple-helix DNA molecular switch are used in detecting a target in circulation. By combining HCR with AuNPs@DNA, a novel signal probe is built, which enables multiple signal amplification and the high-sensitive detection of transgenic rice BT63 DNA. The Fe3O4@Au solution is added to a magneto-controlled glassy carbon electrode, and sulfhydryl-modified capture DNA (CP) is immobilized on Fe3O4@Au through the Au-S bond. Mercaptoethanol is added to close sites and prevent the nonspecific adsorption of CP on the magnetron glassy carbon electrode. A target DNA is added to a constructed triple-helix DNA molecular centrifuge tube for reaction. Owing to base complementation and the reversible switching of the triple-helix DNA molecular state, the target DNA turns on the triple-helix DNA molecular switch and hybridizes with a long-strand recognition probe (RP) to form a double-stranded DNA (dsDNA). Exonuclease ExoIII is added to specifically recognize and cut the dsDNA and to release the target DNA. The target DNA strand then circulates back completely to open the multiple triple-helix DNA molecular switch, releasing a large number of signal transduction probes (STP). To hybridize with CP, a large amount of STP is added to the electrode. Finally, a AuNPs@DNA signal probe is added to hybridize with STP. H1 and H2 probes are added for the hybridization chain reaction and the indefinite extension of the primer strand on the probe. Then, tris-(bipyridyl)ruthenium(II) is added for ECL signal detection with PBS-tri-n-propylamine as the base solution. In the concentration range 1.0 × 10-16 to 1.0 × 10-8 mol/L of the target DNA, good linear relationship was achieved with the corresponding ECL signal. The detection limit is 3.6 × 10-17 mol/L. The spiked recovery of the rice samples range from 97.2 to 101.5%. The sensor is highly sensitive and has good selectivity, stability, and reproducibility. A novel electrochemiluminescence biosensor with extremely higher sensitivity was prepared for the determination of ultra-trace amount transgenic rice BT63 DNA. The sensitivity was significantly improved by multiple signal enhancements. Firstly, a large number of signal transduction probes are released when the triple-helix DNA molecular switch unlock after recycles assisted by ExoIII exonuclease under target BT63 DNA; and then the signal transduction probes hybridize with the signal probes of AuNPs@(DNA-HCR) produced through hybridization chain reaction. Finally, the signal probes which were embedded with a large amount of electrochemiluminescence reagent produce high luminescence intensity. The detection limit was 3.6 × 10-17 mol/L, which is almost the most sensitive methods reported.


Assuntos
Técnicas Biossensoriais/métodos , DNA Bacteriano/análise , Exodesoxirribonucleases/química , Substâncias Luminescentes/química , Nanopartículas de Magnetita/química , Toxinas de Bacillus thuringiensis/genética , Técnicas Biossensoriais/instrumentação , Sondas de DNA/química , Sondas de DNA/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Endotoxinas/genética , Ouro/química , Proteínas Hemolisinas/genética , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/genética , Limite de Detecção , Medições Luminescentes/métodos , Hibridização de Ácido Nucleico , Compostos Organometálicos/química , Oryza/química , Plantas Geneticamente Modificadas/química , Reprodutibilidade dos Testes
11.
Ophthalmic Res ; 64(2): 337-344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32344402

RESUMO

INTRODUCTION: Paralytic strabismus involves a functional loss of extraocular muscles resulting from muscular or neuronal disorders. Currently, only a limited number of drugs are available for functional repair of extraocular muscles. Here, we investigated the effects of a novel drug, flavonoids sophoranone, on the differentiation of extraocular muscles as assessed in bothin vivo and in vitro models. MATERIALS AND METHODS: The effect of flavonoids sophoranone on C2C12 cells was examinedin vitro as evaluated with use of apoptosis, reactive oxygen species (ROS), and cell viability assays. Then, both in vivo and in vitro effects of this drug were examined on the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits. For these latter experiments, RT-PCR and Western blot assays were used to determine expression levels of markers for myogenic differentiation. RESULTS: With use of flavonoids sophoranone concentrations ranging from 0 to 10 µM, no effects were observed upon cell apoptosis, ROS, and cell cycle in C2C12 cells. Based on MTT assay results, flavonoids sophoranone was shown to increase C2C12 cell proliferation. Moreover, flavonoids sophoranone promoted the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits, which were verified as based on cell morphology and expression levels of mRNA and protein markers of myogenic differentiation. Finally, flavonoids sophoranone treatment also increased gene expressions of Myh3, Myog, and MCK. CONCLUSION: The capacity for flavonoids sophoranone to upgrade the differentiation of both C2C12 and satellite cells within extraocular muscles in rabbits at concentrations producing no adverse effects suggest that this drug may provide a safe and effective means to promote repair of damaged extraocular muscles.


Assuntos
Apoptose , Flavonoides/farmacologia , Desenvolvimento Muscular/genética , Mioblastos/efeitos dos fármacos , Músculos Oculomotores/citologia , Animais , Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais , Mioblastos/citologia , Mioblastos/metabolismo , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/metabolismo , Coelhos , Espécies Reativas de Oxigênio/metabolismo
12.
Medicine (Baltimore) ; 98(47): e17837, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764779

RESUMO

INTRODUCTION: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare differential diagnosis for patients presenting with abdominal pain. Due to limited cases reported, surgical management strategies are poorly defined. PATIENT CONCERNS: A 54-year-old man presented to our emergency department with a 4-day history of epigastric pain combined with nausea and vomiting. The pain was dull, constant, and unbearable. It was accompanied by abdominal distention, but there was no radiating pain, chills, fever, or hematochezia. The patient did not have a history of abdominal surgeries, or tobacco or illicit drug use. DIAGNOSIS: A contrast-enhanced computerized tomography (CT) scan demonstrated an isolated and spontaneous superior mesenteric artery dissection with aneurysmal evolution of the false lumen, involving multiple side branches. The middle-lower jejunum and the whole ileum were extensively dilated, and the middle jejunum was ischemic with edema. INTERVENTIONS: Exploratory laparotomy and autologous small bowel transplantation. OUTCOMES: The patient was successfully treated using exploratory laparotomy and intestinal autotransplantation (IATx) without bowel resection and had a stable recovery without complications. CONCLUSION: For patients with severe mesenteric ischemia or those who fail to respond to initial conservative treatment, IATx may be a reasonable treatment strategy.


Assuntos
Dissecção Aórtica/cirurgia , Intestino Delgado/transplante , Artéria Mesentérica Superior/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Procedimentos Cirúrgicos Vasculares/métodos
13.
Mikrochim Acta ; 186(9): 628, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418084

RESUMO

An electrochemiluminescent (ECL) biosensor is described for the determination of the breast cancer biomarker microRNA. The method is based on the amplification via target cyclic regeneration through a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe quantum dots (QDs) and gold nanoparticles. The assay is performed by exploiting the luminescence properties of CdTe-QDs and K2S2O8 as a co-reactive agent to increase the ECL signal. It was successfully applied to ECL-based detection of a 20-mer microRNA. The sensor has a linear response in the 0.1 fM to 0.2 pM microRNA concentration range and a detection limit as low as 33 aM. The assay has been applied to the determination of microRNA spiked in serum samples, and recoveries ranged from 94.4 to 100.5%. Graphical abstract A novel electroluminescence biosensor based on the amplification of target cyclic regeneration is described. It is achieved by using a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe QDs and Au NPs, and was successfully applied to microRNA detection.


Assuntos
Biomarcadores Tumorais/análise , Técnicas Biossensoriais , Neoplasias da Mama/diagnóstico por imagem , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs/análise , Compostos de Cádmio/química , DNA Polimerase Dirigida por DNA/química , DNA Polimerase Dirigida por DNA/metabolismo , Feminino , Ouro/química , Humanos , Nanopartículas de Magnetita/química , Tamanho da Partícula , Pontos Quânticos/química , Propriedades de Superfície , Telúrio/química
14.
Anal Chim Acta ; 1078: 24-31, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358225

RESUMO

A novel electrochemical DNA biosensor was developed and MON89788 of soybean transgenic gene sequence was detected based on a strategy of rolling circle amplification (RCA) and gold nanoparticle cube (AuNPC)-labeled multiple probes. First, the mercapto-modified capture DNA was immobilized on the surface of the Fe3O4@Au magnetic nanoparticles via an Au-S bond, and the capture DNA was opened and complementarily hybridized with the target DNA to form a double-stranded DNA. In the 10 × reaction buffer, Exonuclease III (ExoIII) specifically recognized and sheared the double-stranded DNA to release the target DNA, which led to the next round of reaction. Afterward, AuNP cube-loaded ssDNA (AuNPC/DNA) was added with the rolling circle reaction with the help of Phi29 DNA polymerase and T4 ligase. Finally, [Ru(NH3)6]3+ was attracted directly by the anionic phosphate of ssDNA via electrostatic interaction. The determination was carried out by using chronocoulometry (CC), and the CC signal was recorded. The mass amount of DNA strands extended infinitely on the AuNPs cube and numerous [Ru(NH3)6]3+ were absorbed, thus the detected signal was highly amplified. The corresponding CC signal showed a good linear relationship with the logarithm of the target DNA concentration in the range of 1 × 10-16 to 1 × 10-7 mol L-1, with a detection limit of 4.5 × 10-17 mol L-1. Specific gene sequence of MON89788 in soybean samples was determined, and the recoveries ranged from 97.3% to 102.0%. This sensor is one of the most sensitive sensors for genetic sequence assessment at present. Moreover, it demonstrates good selectivity, stability, and reproducibility.


Assuntos
Técnicas Biossensoriais/métodos , DNA de Plantas/análise , Técnicas Eletroquímicas/métodos , Glycine max/genética , Plantas Geneticamente Modificadas/genética , Sequência de Bases , Calibragem , Sondas de DNA/química , Sondas de DNA/genética , DNA de Plantas/química , DNA de Plantas/genética , Exodesoxirribonucleases/química , Ouro/química , Limite de Detecção , Nanopartículas de Magnetita/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/genética , Reprodutibilidade dos Testes , Compostos de Rutênio/química
15.
Mol Med Rep ; 19(5): 4468-4474, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942442

RESUMO

Increasing evidence has suggested that long non­coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has critical roles in multiple biological processes; however, few studies have reported on its function in heart disease. The present study indicated that NEAT1 expression is markedly downregulated in cardiomyocytes following ischemia/reperfusion injury in vivo and hydrogen peroxide treatment in vitro. Further experiments suggested that ectopic overexpression of NEAT1 suppresses cardiomyocyte apoptosis induced by hydrogen peroxide, as assessed by TUNEL assay and flow cytometry. In addition, using a dual­luciferase reporter assay, NEAT1 was demonstrated to directly interact with microRNA (miR)­125a­5p and overexpression of miR­125a­5p efficiently reversed the stimulatory effect of NEAT1 on B­cell lymphoma­2­like 12 (BCL2L12) expression. Furthermore, the results indicated that NEAT1 inhibits cardiomyocyte apoptosis via regulating the expression of BCL2L12, which appeared to be mediated via miR­125a­5p. In conclusion, the present study suggested that NEAT1 functions as a miR sponge to inhibit cardiomyocyte apoptosis and may be a novel therapeutic target for cardiomyocyte apoptosis­associated heart diseases.


Assuntos
Apoptose , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Longo não Codificante/química , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley
16.
Anal Bioanal Chem ; 411(1): 139-146, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30374725

RESUMO

A novel electrochemical luminescence (ECL) aptamer biosensor via polymerase amplification is constructed for label-free detection of leukemia marker mRNA (miR-16). In order to achieve the ultrasensitive detection of the target mRNA, the cyclic target chain displacement polymerization of leukemia marker mRNA assisted with Klenow fragment of DNA polymerase is employed. The determination is carried out by recording the ECL emission of pyridine ruthenium (Ru(bpy)32+) complexes embedded into the assistance DNA (ADNA) loaded on the nanogold surface, after the hybridization reaction between the probe DNA (PDNA) and the remaining sequence of the CP's stem part, and the formation of a core-shell sun-like structure. The mercapto-modified capture DNA (CP) is immobilized on the surface of a magneto-controlled glassy carbon electrode by Au-S bond. The CP is opened and hybridized with the target mRNA to form double-stranded DNA. In the presence of polymerase, primer DNA, and bases (dNTPs), the primer chain gets access to its complementary sequence of the stem part and then triggers a polymerization of the DNA strand, leading to the release of mRNA and starting the next polymerization cycle. Finally, the composite of PDNA-covered and ADNA-covered (embedded with Ru(bpy)32+) gold nanoparticles (hereafter called AuNPs@(PDNA+ADNA-Ru(bpy)32+) is added, and the ECL intensity is recorded. Because of the polymerization cycle and the aggregation of the illuminator of Ru(bpy)32+, the detected signal is amplified significantly. The results showed that the corresponding ECL signal has a good linear relationship with a logarithm of target mRNA concentration in the range of 1 × 10-16 to 1 × 10-7 mol/L, with a detection limit of 4.3 × 10-17 mol/L. The mRNA spiked in the human serum sample is determined, and the recoveries are from 97.2 to 102.0%. This sensor demonstrates good selectivity, stability, and reproducibility. Graphical abstract ᅟ.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/métodos , DNA Polimerase Dirigida por DNA/metabolismo , Técnicas Eletroquímicas/métodos , Leucemia/sangue , MicroRNAs/sangue , RNA Mensageiro/sangue , Calibragem , Sondas de DNA , Técnicas Eletroquímicas/normas , Eletrodos , Óxido Ferroso-Férrico/química , Ouro/química , Humanos , Limite de Detecção , Luminescência , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes
17.
Ultrasound Med Biol ; 45(2): 385-394, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30509784

RESUMO

The study described here aimed to evaluate left ventricular (LV) systolic mechanical synchronization during permanent selective His bundle pacing (SHBP) using 3-D speckle-tracking echocardiography post-operatively and 6 mo after pacemaker implantation in 62 patients randomly assigned to SHBP (n = 32) or right ventricular apical pacing (RVAP, n = 30). A standard apex four-chamber view was exposed and was transformed into full-volume mode under 3-D echocardiography. Three-dimensional speckle-tracking echocardiography was analyzed offline. The primary endpoint was LV mechanical synchronization post-operatively and during the 6-mo follow-up. Significant LV dyssynchrony was detected while evaluating the maximum time difference and standard deviation of 16-segment systolic time to peak 3-D strain at 1 wk and 6 mo. The pacing thresholds were significantly higher in the SHBP than in the RVAP group throughout follow-up. The R-wave amplitude was significantly lower in the SHBP group than with RVAP. The pacing parameters during SHBP were as stable as during conventional RVAP during the mid-term follow-up. In conclusion, 3-D speckle-tracking echocardiography is feasible and provides a more convenient method for evaluating LV synchrony.


Assuntos
Fascículo Atrioventricular/diagnóstico por imagem , Fascículo Atrioventricular/fisiologia , Estimulação Cardíaca Artificial/métodos , Ecocardiografia Tridimensional/métodos , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Clin Cardiol ; 41(3): 354-359, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29577347

RESUMO

BACKGROUND: Electrocardiographic (ECG) characteristics of true right ventricular outflow tract (RVOT) septal pacing have not been clearly demonstrated. HYPOTHESIS: We hypothesized that ECG parameters would help operators differentiate true RVOT septum from non-septal septum. METHODS: We analyzed 151 patients who underwent pacemaker implantation with a ventricular lead in the RVOT. Transthoracic echocardiographic (TTE) determination of pacing sites was applied in all patients after implantation. A 12-lead ECG was recorded during forced ventricular pacing. RESULTS: According to TTE orientation, pacing at the RVOT septum was achieved in 94 patients (62.3%). Compared with nonseptal pacing, septal pacing had significantly shorter QRS duration (139.2 ± 18.5 ms vs 155.5 ± 14.7 ms; P < 0.001). More frequent negative or isoelectric QRS vector in lead I (76% vs 32%; P < 0.001), lead II/III R-wave amplitude ratio < 1 (52% vs 25%; P = 0.001), and aVR/aVL QS-wave amplitude ratio < 1 (59% vs 32%; P = 0.001) were observed in septal pacing. Transitional zone (TZ) score (3.8 ± 0.96 vs 4.2 ± 0.90; P = 0.004) and TZ index (0.3 ± 0.5 vs 0.6 ± 0.7; P = 0.008) were significantly lower in septal pacing than in nonseptal pacing, respectively. In multivariate analysis, paced QRS duration and negative or isoelectric QRS vector in lead I independently predicted RVOT septal pacing (P < 0.001). At ROC curve analysis, paced QRS duration ≤145 ms identified RVOT septal pacing with 85.1% sensitivity and 78.9% specificity. CONCLUSIONS: This study reveals the heterogeneity of lead placement within the RVOT. Narrower paced QRS duration and negative or isoelectric QRS vector in lead I independently predict RVOT septal pacing.


Assuntos
Fibrilação Atrial/terapia , Estimulação Cardíaca Artificial/métodos , Ecocardiografia/métodos , Eletrocardiografia , Função Ventricular Direita/fisiologia , Septo Interventricular/diagnóstico por imagem , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
19.
Zhongguo Zhen Jiu ; 37(9): 971-6, 2017 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-29354919

RESUMO

OBJECTIVE: To observe effects of electroacupuncture (EA) at "Weizhong" (BL 40) on morphology and expression of creatine kinase (CK) and interleukin-17 (IL-17) in rats with bupivacaine-induced multifidus muscle injury. METHODS: A total of 32 male SD rats were randomly divided into a control group, a model group, a Weizhong group and a Shenshu group, 8 rats in each one. The rats in the model group, Weizhong group and Shenshu group were treated with intramuscular injection of 0.5% bupivacaine to establish the model of multifidus muscle injury; the rats in the control group were injected with 0.9% sodium chloride solution. The rats in the Weizhong group and Shenshu group were treated with EA (2 Hz/10 Hz in frequency, 1~2 mA in intensity) at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20 min per treatment. No treatment was given in the control group and model group. After 14-day treatment of EA, the inflammatory cell count, scar tissues area and muscle fiber cross sectional area of multifidus muscle were observed with HE and Masson staining method. The activity of CK and serum content of IL-17 were test with enzyme-linked immunosorbent assay (ELISA) method; the expression of IL-17 in multifidus muscle was measured with immunohistochcmical method. RESULTS: After intervention, the inflammatory cell count and scar tissues area in the model group, Weizhong group and Shenshu group were higher than those in the control group (all P<0.01), but the muscle fiber cross sectional area was significantly reduced (all P<0.01); the inflammatory cell count and scar tissues area in the Weizhong group and Shenshu group were lower than those in the model group (all P<0.01), and the muscle fiber cross sectional area was significantly increased (P<0.01, P<0.05). After intervention, the expression of IL-17 in multifidus muscle, serum content of IL-7 and activity of CK in the model group, Weizhong group and Shenshu group were higher than those in the control group (all P<0.01); the expression of IL-17 in multifidus muscle, serum content of IL-7 and activity of CK in the Weizhong group and Shenshu group were lower than those in the model group (P<0.01, P<0.05); compared with the Shenshu group, the down-regulation of IL-17 was more obvisous in the Weizhong group (P<0.01). CONCLUSION: EA at "Weizhong" (BL 40) can down-regulate the overexpression of serum CK and IL-17, alleviate inflammation reaction and improve the repair of multifidus muscle.


Assuntos
Pontos de Acupuntura , Creatina Quinase/metabolismo , Eletroacupuntura/métodos , Interleucina-17/metabolismo , Doenças Musculares/metabolismo , Doenças Musculares/terapia , Músculos Paraespinais , Anestésicos Locais , Animais , Bupivacaína , Masculino , Doenças Musculares/induzido quimicamente , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
20.
Biosci Trends ; 10(3): 188-96, 2016 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-27237219

RESUMO

Chronic hyperlipemia increases the incidence of vascular endothelial dysfunction and can even induce cardiovascular disease. Sea buckthorn contains a host of bioactives such as flavonoids and polyphenols that can prevent the development of cardiovascular disease. The current study isolated active ingredients, polyphenols, from sea buckthorn berries (SVP) and orally administered SVP at a dose of 7-28 mg/kg. This treatment significantly reduced serum lipids, it enhanced the activity of antioxidant enzymes, and it decreased the level of serum TNF-α and IL-6. SVP also alleviate vascular impairment by decreasing the expression of eNOS, ICAM-1, and LOX-1 mRNA and proteins in aortas of rats with hyperlipidemia. Based on these findings, SVP has antioxidant action and it protects endothelium.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Flavonoides/uso terapêutico , Hippophae/química , Hiperlipidemias/tratamento farmacológico , Polifenóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antioxidantes/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Flavonoides/administração & dosagem , Flavonoides/química , Flavonoides/isolamento & purificação , Frutas/química , Interleucina-6/sangue , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Extratos Vegetais/química , Polifenóis/administração & dosagem , Polifenóis/química , Polifenóis/isolamento & purificação , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
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