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1.
DNA Cell Biol ; 39(2): 289-298, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916853

RESUMO

TBX3 reprograms cardiac myocytes into cells that possess sinoatrial node phenotype, but no specific funny current (If) was detected. We explore whether overexpression of TBX3 alone or combined with HCN2 can reprogram human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) into pacemaker-like cells. HiPSC-CMs were transfected with TBX3 and/or HCN2 in this study. Expression analysis showed that overexpression of TBX3 induces a reduced reduction expression profile of working cardiomyocytes into that of pacemaker cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and electrophysiological analyses showed a reduced expression of connexins subunits (CX40, CX43), the sodium current (SCN5A, INa), the inward rectified potassium channels (Kir2.1, IK1), and an increased expression of connexins subunits (CX30.2, CX45). No If was detected. The reduction of IK1 resulted in a more depolarized maximum diastolic potential together with an expression of If (generated by HCN2), which they work in synergy to generate spontaneous diastolic depolarization that was the most typical characteristic of pacemaker cells. In conclusion, overexpression of TBX3 and HCN2 could reprogram hiPSC-CMs into pacemaker-like cells. The ability to enable diastolic depolarization formation provides a new strategy for the construction of a biological pacemaker.


Assuntos
Diferenciação Celular/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Canais de Potássio/genética , Proteínas com Domínio T/genética , Potenciais de Ação/fisiologia , Relógios Biológicos/genética , Humanos , Miócitos Cardíacos/metabolismo
2.
Huan Jing Ke Xue ; 40(6): 2565-2571, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854647

RESUMO

Based on the annual average concentration values, the health effects and health benefits as well as 95% confidence intervals of PM10 and PM2.5 pollution control from 2014 to 2016 in Zhengzhou were evaluated by applying the Poisson regression relative risk model. Results showed that the health benefits of PM10 pollution control were 18.18 billion RMB (15.04, 21.12), 24.25 billion RMB (20.25, 27.94), and 20.62 billion RMB (17.33, 23.92), which accounted for 2.7%, 3.3%, and 2.5% of the GDP of Zhengzhou, respectively, in 2014-2016. The health benefits of PM2.5 pollution control were 17.88 billion RMB (14.37, 21.16), 21.65 billion RMB (17.46, 25.53), and 17.25 billion RMB (13.78, 20.55), which accounted for 2.6%, 3.0%, and 2.1% of the GDP of Zhengzhou, respectively, in 2014-2016. After the PM10 and PM2.5 pollution was controlled, the number of urban beneficiaries was higher than that of rural areas, and acute bronchitis beneficiaries were higher than the beneficiaries of other health end-points. For chronic bronchitis, adults benefited more than children, while the opposite occurred for asthma. In this study, chronic bronchitis had the highest health benefit, followed by asthma, and outpatient and inpatient setting had the lower health benefits.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/prevenção & controle , Material Particulado/efeitos adversos , Adulto , Asma/prevenção & controle , Bronquite Crônica/prevenção & controle , Criança , China , Humanos , Análise de Regressão
3.
Huan Jing Ke Xue ; 40(11): 4847-4855, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854550

RESUMO

The three typical carbon enterprises in Zhengzhou were selected as research targets, and the emission characteristics of volatile organic compounds (VOCs) and their ozone formation potential (OFP) in different functional areas were studied. The US Environmental Protection Agency (EPA) health risk assessment model was used to evaluate the health risks of VOCs emitted by the carbon industry. The results showed that the concentration of VOCs in the production areas of the three research enterprises was between 89.77-964.60 µg·m-3, and the management area was between 51.46-121.59 µg·m-3. Naphthalene and carbon disulfide were at the highest concentrations in the carbon plants. The ozone formation potential of VOCs in the production area was between 75.42-1416.73 µg·m-3, and in the management area was between 65.32-202.42 µg·m-3, mainly from the contribution of aromatic hydrocarbons and olefins. The carcinogenic health risk (Risk) of VOCs in the production area was 3.5×10-5-2.8×10-3, and in the management area was 2.0×10-5-9.4×10-5, which was higher than the maximum acceptable level recommended by the EPA (10-6). The non-carcinogenic health risk index (HI) of the VOCs in the production area was 3.2-1.4×102, and in the management area was 4.3×10-1-3.8, except for the management area of the first enterprise, which was greater than 1, which may expose the workers. These health factors cause cancer and non-carcinogenic hazards.


Assuntos
Poluentes Atmosféricos , Saúde Ambiental , Medição de Risco , Compostos Orgânicos Voláteis , Carbono , Monitoramento Ambiental , Humanos
4.
Huan Jing Ke Xue ; 40(7): 2977-2984, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854694

RESUMO

In order to explore the pollution characteristics of water-soluble ions in PM2.5 in Zhengzhou, high time resolution and continuous observation of water-soluble inorganic ions in PM2.5 was conducted from December 1, 2017, to November 30, 2018, in Zhengzhou. The results showed that during the observation period, the average concentration of total water-soluble ions in Zhengzhou was 42.7 µg·m-3. The order of mass concentration of each ion, from large to small, was as follows:NO3-(17.7 µg·m-3), SO42-(10.2 µg·m-3), NH4+(9.0 µg·m-3), Cl-(2.3 µg·m-3), K+(1.3 µg·m-3), Na+(1.3 µg·m-3), Ca2+(0.8 µg·m-3), and Mg2+(0.1 µg·m-3). The mass concentration of total water-soluble ions was the highest in winter, slightly higher in autumn than in spring, and lowest in summer. The diurnal variation in single peak distribution was observed across the whole year in spring, summer, and autumn, while there was no significant diurnal variation in winter. The mass concentration of secondary inorganic ions (SO42-, NO3-, and NH4+) accounted for 43.8% of PM2.5, mainly in the form of (NH4)2SO4 and NH4NO3. There was a large degree of secondary transformation throughout the observation period; relative humidity had a significant influence on the sulfur oxidation rate, and temperature had a significant influence on the nitrogen oxidation rate. During the observation period, there was a good correlation between secondary ions, and K+ showed a good correlation with Mg2+ and Cl-. The main source of the secondary ions was the secondary conversion of gaseous pollutants. Mg2+ and Ca2+ were derived from soil dust and construction dust. K+ was one of the main biomarkers of biomass combustion. Na+ was mainly derived from sea salt and soil dust, and Cl- was derived not only from sea salt but also biomass and fossil fuel combustion. The results of principal component analysis showed that the water-soluble ions in PM2.5 in Zhengzhou were mainly affected by secondary transformation, combustion sources, and dust emission from soil or building construction.

5.
DNA Cell Biol ; 38(12): 1470-1479, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31633376

RESUMO

Vascular smooth muscle cells (VSMCs) of ascending aorta and TBX18+ sinus node both originated from the second heart field. The study explored whether ascending aortic smooth muscle cells in vitro could be reprogrammed into pacemaker-like cells with human TBX18. In the study, VSMCs were infected with TBX18, and then cocultured with neonatal rat ventricular cardiomyocytes (NRVMs) in vitro. By overexpressing TBX18, the transfected VSMCs expressed high levels of hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), insulin gene enhancer binding protein 1, and human dwarf homeobox gene SHOX2, cardiac troponin I, and low level of connexin 43. In addition, funny current (If) was recorded by patch clamp appeared the time and voltage dependence in TBX18 group, which the amplitude of If density was from -5.164 ± 0.662 pA/pF to -0.765 ± 0.358 pA/pF (n = 14). Furthermore, TBX18-transfected VSMCs coupled with NRVMs showed typical action potential of pacemaker-like cells and the beating rate was faster (178.00 ± 7.55 bpm, p < 0.05) compared with other groups. In conclusion, our study indicated that transcription factor TBX18 could reprogram VSMCs into pacemaker-like cells in vitro.


Assuntos
Aorta/citologia , Reprogramação Celular , Músculo Liso Vascular/citologia , Miócitos Cardíacos/citologia , Marca-Passo Artificial , Proteínas com Domínio T/metabolismo , Animais , Animais Recém-Nascidos , Aorta/metabolismo , Diferenciação Celular , Células Cultivadas , Masculino , Músculo Liso Vascular/metabolismo , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley
6.
Int J Mol Med ; 44(6): 2103-2112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638180

RESUMO

Recent studies have suggested that calcium­activated potassium channel (KCa) agonists increase the proportion of mouse embryonic stem cell­derived cardiomyocytes and promote the differentiation of pacemaker cells. In the present study, it was hypothesized that adipose­derived stem cells (ADSCs) can differentiate into pacemaker­like cells via overexpression of the SK4 gene. ADSCs were transduced with a recombinant adenovirus vector carrying the mouse SK4 gene, whereas the control group was transduced with GFP vector. ADSCs transduced with SK4 vector were implanted into the rat left ventricular free wall. Complete atrioventricular block (AVB) was established in isolated perfused rat hearts after 2 weeks. SK4 was successfully and stably expressed in ADSCs following transduction. The mRNA levels of the pluripotent markers Oct­4 and Sox­2 declined and that of the transcription factor Shox2 was upregulated following SK4 transduction. The expression of α­actinin and hyperpolarization­activated cyclic nucleotide­gated potassium channel 4 (HCN4) increased in the SK4 group. The hyperpolarizing activated pacemaker current If (8/20 cells) was detected in ADSCs transduced with SK4, but not in the GFP group. Furthermore, SK4 transduction induced the expression of p­ERK1/2 and p­p38 MAPK. In the ex vivo experiments, the heart rate of the SK4 group following AVB establishment was significantly higher compared with that in the GFP group. Immunofluorescence revealed that the transduced ADSCs were successfully implanted and expressed HCN4 in the SK4 group. In conclusion, SK4 induced ADSCs to differentiate into cardiomyocyte­like and pacemaker­like cells via activation of the extracellular signal­regulated kinase 1/2 and p38 mitogen­activated protein kinase pathways. Therefore, ADSCs transduced with SK4 may be used to generate biological pacemakers in ex vivo rat hearts.

7.
Cardiology ; 144(3-4): 112-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600748

RESUMO

Cardiac arrhythmias occur frequently in patients with acute stroke, with atrial fibrillation (AF) being the most common. Newly detected AF may lead to increased risk of ischemic stroke, which in turn generates stroke recurrence and adverse outcomes. Currently, most studies are focusing on the role of AF in ischemic stroke and attributing cryptogenic ischemic stroke to previously undetected AF. However, in these studies, subjects used to have neither symptoms of palpitation nor evidence of AF. A better understanding of this association will contribute to the management and therapy for patients after clinical decisions regarding stroke patients. Currently, the definition of newly detected AF has not come to an agreement, and the pathophysiology remains incompletely understood, possibly involving complex alterations in both the autonomic network and humoral regulation. Therefore, this review aims to introduce the definition and epidemiology of newly detected AF after stroke with updated information and elucidate the potential pathophysi-ology, such as autonomic imbalance, catecholamine surge, poststroke systematic inflammation, and microvesicles and microRNAs.

8.
Life Sci ; 237: 116949, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605712

RESUMO

AIMS: New-onset atrial fibrillation (AF) is frequently observed following acute stroke. The aim of this study was to investigate the effects of the brain-stellate ganglion-atrium network on AF vulnerability in a canine model with acute middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: Twenty-six dogs were randomly divided into the sham-operated group (n = 6), acute stroke (AS) group (n = 7), stellate ganglion ablation (SGA) group (n = 6) and clodronate liposome (CL) group (n = 7). In the sham-operated group, dogs received craniotomy without MCAO. Cerebral ischemic model was established in AS dogs by right MCAO. Right MCAO along with SGA and CL injection into the atrium was performed in SGA and CL dogs, respectively. After 3 days, atrial electrophysiology, neural activity, and the phenotype and function of macrophages in the atrium were studied in all the dogs. KEY FINDINGS: Higher AF inducibility (24.4 ±â€¯4.4% versus 4.4 ±â€¯2.2%, P < 0.05) and AF duration (15.7 ±â€¯3.8 s versus 2.6 ±â€¯1.1 s, P < 0.05) were observed in the AS group compared with the sham-operated group, and were associated with increased left stellate ganglion activity, higher macrophage infiltration and higher levels of inflammatory cytokines in the atrium. SGA or CL injection sharply suppressed AF inducibility (5.5 ±â€¯2.7% versus 24.4 ±â€¯4.4%; 5.3 ±â€¯3.2% versus 24.4 ±â€¯4.4%, both P < 0.05) and AF duration (2.9 ±â€¯1.2 s versus 15.7 ±â€¯3.8 s; 3.6 ±â€¯1.0 s versus 15.7 ±â€¯3.8 s, both P < 0.05) in canines with acute stroke. SIGNIFICANCE: A brain-stellate ganglion-atrium network may increase AF vulnerability through macrophage activation after acute stroke.


Assuntos
Fibrilação Atrial/patologia , Modelos Animais de Doenças , Átrios do Coração/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Macrófagos/patologia , Gânglio Estrelado/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Fibrilação Atrial/etiologia , Cães
9.
DNA Cell Biol ; 38(11): 1313-1322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545082

RESUMO

This study investigated whether overexpression of paired-related homeobox 1 (prrx1) can successfully induce differentiation of brown adipose-derived stem cells (BADSCs) into sinus node-like cells. The experiments were performed in two groups: adenovirus-green fluorescent protein (Ad-GFP) group and Ad-prrx1 group. After 5-7 days of adenoviral transfection, the expression levels of sinus node cell-associated pacing protein (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 [HCN4]) and ion channel (calcium channel, voltage-dependent, T type, alpha 1G subunit [Cacna1g]), as well as transcription factors (T-box 18 [TBX18], insulin gene enhancer binding protein 1 [ISL-1], paired-like homeodomain transcription factor 2 [pitx2], short stature homeobox 2 [shox2]), were detected by western blot and reverse transcription-quantitative polymerase chain reaction. Immunofluorescence assay was carried out to detect whether prrx1 was coexpressed with HCN4, TBX18, and ISL-1. Finally, whole-cell patch-clamp technique was used to record pacing current hyperpolarization-activated inward current (If). The isolated cells were CD90+, CD29+, and CD45-, indicating that pure BADSCs were successfully isolated. After 5-7 days of Ad transfection into cells, the mRNA levels and protein levels of pacing-related factors (TBX18, ISL-1, HCN4, shox2, and Cacna1g) in Ad-prrx1 group were significantly higher than those in Ad-GFP group. However, the expression level of pitx2 was decreased. Immunofluorescence analysis showed that prrx1 was coexpressed with TBX18, ISL-1, and HCN4 in the Ad-prrx1 group, which did not appear in the Ad-GFP group. Whole-cell patch clamps were able to record the If current in the experimental group rather than in the Ad-GFP group. Overexpression of prrx1 can successfully induce sinus node-like cells.


Assuntos
Tecido Adiposo Marrom/fisiologia , Células-Tronco Adultas/fisiologia , Diferenciação Celular/genética , Proteínas de Homeodomínio/fisiologia , Nó Sinoatrial/fisiologia , Tecido Adiposo Marrom/citologia , Células-Tronco Adultas/citologia , Animais , Transdiferenciação Celular/genética , Células Cultivadas , Masculino , Ratos , Ratos Sprague-Dawley , Nó Sinoatrial/citologia , Transfecção
10.
Mol Med Rep ; 20(4): 3406-3414, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432175

RESUMO

Ion channels serve important roles in the excitation­contraction coupling of cardiac myocytes. Previous studies have shown that the overexpression or activation of intermediate­conductance calcium­activated potassium channel (SK4, encoded by KCNN4) in embryonic stem cell­derived cardiomyocytes can significantly increase their automaticity. The mechanism underlying this effect is hypothesized to be associated with the activation of hyperpolarization­activated cyclic nucleotide­gated channel 2 (HCN2). The aim of the present study was to explore whether a biological pacemaker could be constructed by overexpressing SK4 alone or in combination with HCN2 in a rat model. Ad­green fluorescent protein (GFP), Ad­KCNN4 and Ad­HCN2 recombinant adenoviruses were injected into the left ventricle of Sprague­Dawley rat hearts. The rats were divided into a GFP group (n=10), an SK4 group (n=10), a HCN2 group (n=10) and an SK4 + HCN2 (SK4/HCN2) group (n=10). The isolated hearts were perfused at 5­7 days following injection, and a complete heart block model was established. Compared with the GFP group, overexpressing SK4 alone did not significantly increase the heart rate after establishment of a complete heart block model [98.1±8.9 vs. 96.7±7.6 beats per min (BPM)], The heart rates in the SK4/HCN2 (139.9±21.9 BPM) and HCN2 groups (111.7±5.5 BPM) were significantly increased compared with the GFP and SK4 groups, and the heart rates in the SK4/HCN2 group were significantly increased compared with the SK4 or HCN2 groups. In the HCN2 (n=8) and the SK4/HCN2 (n=7) groups, the shape of the spontaneous ventricular rhythm was the same as the pacing­induced ectopic rhythm in the transgenically altered site. By contrast, these rhythms were different in the SK4 (n=10) and GFP (n=10) groups. There were no significant differences in action potential duration alternans or ventricular arrhythmia inducibility between the four groups (all P>0.05). Western blotting, reverse transcription­quantitative PCR and immunohistochemistry analyses showed that the expression levels of SK4 and HCN2 were significantly increased at the transgene site. Biological pacemaker activity could be successfully generated by co­overexpression of SK4 and HCN2 without increasing the risk of ventricular arrhythmias. The overexpression of SK4 alone is insufficient to generate biological pacemaker activity. The present study provided evidence that SK4 and HCN2 combined could construct an ectopic pacemaker, laying the groundwork for the development of improved biological pacing mechanisms in the future.

11.
Huan Jing Ke Xue ; 40(5): 2052-2061, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087840

RESUMO

Samples of particulate matter from flue gas emissions of typical brick, cement, and firebrick industrial kilns in Zhengzhou City were collected by dilution channel systems. Cr, Mn, Fe, Co, Na, Mg, Al, Si, P, S, Cl, K, Ca, Ti, V, Ni, Cu, Zn, Ga, As, Se, Sr, Cd, Sb, Sn, Ba, and Pb were analyzed. The emission factors (EFs) and emissions of inorganic elements of PM2.5 from kilns flue gases of three industries in Zhengzhou City during 2016 were calculated. A grid list of 1 km×1 km was also established. The results show that the highest concentration of total inorganic elements was in the firebrick industry, corresponding to(609.97±490.97) µg·m-3. The concentration of inorganic elements in the three industries accounted for 34%-54%, 27%-42%, and 23%-53% of PM2.5. The inorganic elements emitted from industrial kilns in brick and cement industries were mainly crust elements, and the highest concentration elements were Cl and Al. The inorganic elements emitted by industrial furnaces in the firebrick industry were mainly heavy metals, and the highest concentration element was Pb. The coefficient of divergence (CD) of inorganic elements in brick and cement industry was 0.389, that is slightly different. The CD between cement and refractory industry was 0.732, which represents a significant difference between inorganic element emissions. In 2016, the emissions of Pb, S, Zn, Cl, K, As, Fe, Si, Cr, Al, Na, and Ca in PM2.5 from major industrial furnaces in Zhengzhou City were 919.0, 793.1, 124.7, 378.6, 82.6, 12.2, 60.4, 145.4, 7.4, 86.6, 15.8, and 111.4 kg·a-1, respectively. Heavy metal emission in the Xinmi area was the highest, representing a high health risk.

12.
J Cardiol ; 74(5): 460-465, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31101572

RESUMO

BACKGROUND: The sympathetic nerve plays an important role in atrial fibrillation (AF) vulnerability. Norepinephrine (NE) has a relationship with AF and nerve growth factor (NGF) injection can induce sympathetic innervation. However, the mechanisms of NE and NGF on AF vulnerability remain unclear. METHODS: Four groups of rabbits were studied: the control group, the NGF group, the NE group, and the NGF+valsartan+metoprolol group. After receiving drugs for 15 days, induced AF was observed, and left atrium (LA) tissues were obtained. Immunocytochemical staining of cardiac nerves and ionic remodeling were performed using anti-growth-associated protein 43 (GAP43), anti-tyrosine hydroxylase (TH) antibodies, and patch clamp. RESULTS: The incidence of AF was significantly higher (p<0.01) in the NGF group and the NE group than in the control group and the NGF+valsartan+metoprolol group. The nerve densities for TH and GAP43-positive at the LA were significantly higher (p<0.01) after NGF, but the nerve densities decreased after NE. ICa,L was increased while instant outward K+ channel current (Ito) was decreased in the LA of rabbits after treatment with NGF and NE. Metoprolol and valsartan can reverse the ICa,L and Ito remodeling and the vulnerability to AF. However, these drugs did not inhibit the effect of NGF on sympathetic sprouting. CONCLUSIONS: The effects of NE and NGF on AF vulnerability have a relationship with the ionic remodeling, while the sympathetic hyperinnervation did not have a strong association with the induction of AF.

13.
J Cardiovasc Electrophysiol ; 30(6): 910-917, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30907035

RESUMO

OBJECTIVE: Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during follow-up. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice. METHODS AND RESULTS: Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5/40 [12.5%] vs 15/45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-α, IL-6, CRP, TGF-ß1, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008). CONCLUSION: Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors.

14.
Mol Med ; 25(1): 7, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894138

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been shown to be associated with liver fibrosis. Nevertheless, the role of PVT1 in atrial fibrosis remains undefined. This study aims to elucidate the pathophysiological role of lncRNA PVT1 in the regulation of atrial fibrosis and to explore the underlying mechanism. METHODS: Expression of PVT1, miR-128-sp, and Sp1 were examined in human atrial muscle tissues and angiotensin-II (Ang-II)-induced human atrial fibroblasts. Furthermore, the role of PVT1 in regulating atrial fibrosis in Ang-II-treated human atrial fibroblasts and Ang-II-induced atrial fibrosis in mice was investigated. Moreover, the interaction among PVT1, miR-128-3p, and Sp1 were examined using bioinformatics, expression correlation analysis, gain- or loss-of-function assays, RIP assays, and luciferase reporter assays. The involvement of transforming growth factor beta 1 (TGF-ß1)/Smad pathway in this process was also explored. RESULTS: PVT1 was increased in atrial muscle tissues from AF patients and positively with collagen I and collagen III. In vitro assay revealed that PVT1 overexpression facilitated the Ang-II-induced atrial fibroblasts proliferation, collagen production, and TGF-ß1/Smad signaling activation, whereas PVT1 knockdown caused the opposite effect. In vivo assay further confirmed that PVT1 knockdown attenuated the Ang-II-induced mouse atrial fibrosis. Mechanically, PVT1 acted as a sponge for miR-128-3p to facilitate Sp1 expression, thereby activating the TGF-ß1/Smad signaling pathway. CONCLUSION: LncRNA PVT1 promotes atrial fibrosis via miR-128-3p-SP1-TGF-ß1-Smad axis in atrial fibrillation.


Assuntos
Fibrilação Atrial , Átrios do Coração/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Smad/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Angiotensina II/farmacologia , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Feminino , Fibroblastos/metabolismo , Fibrose , Átrios do Coração/metabolismo , Átrios do Coração/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade
15.
Sci Total Environ ; 660: 47-56, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30639718

RESUMO

Episodic haze is frequently observed in Zhengzhou, China. Such haze typically contains secondary inorganic aerosols. In this paper, we explore the formation mechanisms of sulfate, nitrate, and ammonium (SNA) in Zhengzhou from January 3 to 25, 2018 based on the results of a series of online instruments and a size-segregated filter sampler. Our results document the remarkable contributions of SNA to winter haze episodes in Zhengzhou, where they account for about 50% of PM2.5 mass concentration. SNA were mainly concentrated in droplet-mode particles, which increased remarkably with the aggravation of the haze episode. In addition, KNO3 and NaNO3 were formed in droplet-mode particles and coarse-mode particles respectively with increasing PM2.5 concentration. The atmosphere during the observation period was ammonia-rich, and the aerosol was acidic under high PM2.5 concentration. Homogeneous reactions dominated the formation of nitrate. HONO photolysis played a more important role in the origin of OH radicals when O3 decreased during haze episode. Under high relative humidity (RH), nitrate formation was influenced by heterogeneous hydrolysis reactions of N2O5. Sulfates were mainly formed through aqueous-phase reactions, especially when the RH was higher than 60%. Under these conditions, there were amounts of liquid water content existed in aerosols. Finally, we observed enhanced conversion of SO2 and NO2 during snowfall periods. This effect may be attributable to the higher RH and O3 levels despite the unfavorable effects of wet deposition and low concentrations of gaseous precursors.

16.
Int J Mol Med ; 43(2): 879-889, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30483766

RESUMO

Hybrid approaches combining gene­ and cell­based therapies to make biological pacemakers are a promising therapeutic avenue for bradyarrhythmia. The present study aimed to direct adipose tissue­derived stem cells (ADSCs) to differentiate specifically into cardiac pacemaker cells by overexpressing a single transcription factor, insulin gene enhancer binding protein 1 (ISL­1). In the present study, the ADSCs were transfected with ISL­1 or mCherry fluorescent protein lentiviral vectors and co­cultured with neonatal rat ventricular cardiomyocytes (NRVMs) in vitro for 5­7 days. The feasibility of regulating the differentiation of ADSCs into pacemaker­like cells by overexpressing ISL­1 was evaluated by observation of cell morphology and beating rate, reverse transcription­quantitative polymerase chain reaction analysis, western blotting, immunofluorescence and analysis of electrophysiological activity. In conclusion, these data indicated that the overexpression of ISL­1 in ADSCs may enhance the pacemaker phenotype and automaticity in vitro, features which were significantly increased following co­culture induction.


Assuntos
Tecido Adiposo/citologia , Sistema de Condução Cardíaco/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Biomarcadores , Células Cultivadas , Técnicas de Cocultura , Fenômenos Eletrofisiológicos , Imunofluorescência , Expressão Gênica , Imunofenotipagem , Masculino , Ratos , Transfecção
17.
Europace ; 20(4): 712-718, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28379329

RESUMO

Aims: Studies have shown that stellate ganglion nerve activity has association with atrial electrical remodelling and atrial fibrillation (AF) inducibility, while median nerve stimulation (MNS) decreases cardiac sympathetic drive. In this study, we tested the hypothesis that MNS suppresses atrial electrical remodelling and AF vulnerability. Methods and results: The atrial effective refractory period (AERP) and AF inducibility at baseline and after 3 h of rapid atrial pacing were determined in dogs undergoing MNS (n = 7), MNS+ application of methyllycaconitine (n = 7) or sham procedure (n = 6). Then, the levels of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and acetylcholine (Ach) in the plasma and atrial tissues were measured. The control dogs (n = 4) were assigned to measure atrial inflammation cytokines. Short-term rapid atrial pacing induced shortening of the AERP, an increase in AERP dispersion, and an increase AF vulnerability in the sham dogs, which were all suppressed by MNS. Levels of TNF-a and IL-6 were higher, and Ach levels were lower in the left and the right atrium in the sham dogs than in the MNS dogs. Methyllycaconitine blunted the effects of MNS on the AERP, AERP dispersion, the AF vulnerability, and TNF-a and IL-6 levels in the atrium, but had no impact on the levels of Ach. Conclusions: The effects of MNS on atrial electrical remodelling and AF inducibility might be associated with the cholinergic anti-inflammatory pathway.


Assuntos
Fibrilação Atrial/terapia , Remodelamento Atrial , Sistema Nervoso Autônomo/fisiopatologia , Estimulação Cardíaca Artificial , Terapia por Estimulação Elétrica/métodos , Átrios do Coração/inervação , Frequência Cardíaca , Mediadores da Inflamação/sangue , Nervo Mediano , Acetilcolina/sangue , Potenciais de Ação , Animais , Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Sistema Nervoso Autônomo/metabolismo , Modelos Animais de Doenças , Cães , Interleucina-6/sangue , Período Refratário Eletrofisiológico , Fator de Necrose Tumoral alfa/sangue
18.
Huan Jing Ke Xue ; 39(11): 4866-4875, 2018 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628207

RESUMO

To study the compositional characteristics of atmospheric particulates with different particle sizes in the central city of Zhengzhou, China, a Tisch graded impact sampler was used to sample atmospheric particulates in summer and autumn. The mass concentrations of water-soluble inorganic ions, including anions (Cl-, F-, NO3-, and SO42-) and cations (Na+, Ca2+, NH4+, K+, and Mg2+) were measured by ion chromatography, and the online ion chromatography-based analyzer MARGA monitored the real-time concentration of particulate nitrate. The results showed that the average concentration of water-soluble ions in Zhengzhou City was (70.9±52.1) µg·m-3 during the sampling period, and the order of water-soluble ion mass concentrations was NO3- > SO42- > NH4+ > Ca2+ > Na+ > Cl- > Mg2+ > K+ > F-; NO3-, SO42-, and NH4+ accounted for 79.9% of total water-soluble ions. The NO3- concentration was mainly concentrated in the 0.65-3.3 µm particle size segment, despite the SO42- concentration being concentrated in the ≤ 1.1 µm particle size segment in autumn or summer. Both NO3- and SO42- had a bimodal distribution in summer and autumn and were mainly distributed as fine particles. NH4+ showed seasonal variation with a bimodal distribution in summer and a unimodal distribution in autumn. Zhengzhou City had serious ozone pollution in summer, and O3 and NO3- showed the "staggered peak" phenomenon, indicating photochemical reactions in the atmosphere. In autumn, water-soluble inorganic ion concentration in particulate matter was high, and the ratio of[NO3-]/[SO42-] was higher than 0.5. The mobile source is an important source of particles. NOR and SOR peaks were on the 1.1-2.1 µm particle size segment in summer, whereas those in the 0.65-1.1 µm particle size segment occurred in autumn. The sulfur gas-to-grain conversion in summer was larger than that of nitrogen, contrary to the result in autumn.

19.
Exp Ther Med ; 14(6): 5429-5437, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29285072

RESUMO

The present study examined changes in the transcranial electrical motor-evoked potentials (TceMEP) waveform to predict neurological deficits and histopathological changes during the early and reversible stage of different levels of permanent spinal cord ischemic injury in a rabbit animal model. A total of 24 New Zealand rabbits were randomly divided into four groups of 6 rabbits each. Group 1 underwent a ligation of the lumbar artery at three levels (L1-L3), group 2 underwent a ligation of the lumbar artery at four levels (L1-L4) and group 3 underwent a ligation of the lumbar artery at five levels (L1-L5). The sham group contained 6 rabbits and did not receive ligation. TceMEP was recorded within 5 min of ligation and, 2 days later, motor function was assessed and the spinal cords were removed for histological examination. Following spinal cord injury, the relationship between variations in the TceMEP waveform and motor function and pathological damage was analyzed. It was observed that the amplitude of TceMEP began to decrease within 1 min of lumbar artery ligation and that the amplitude stabilized within 5 min. These amplitude changes that occurred within 5 min of different levels of permanent spinal cord ischemic injury were positively related to changes in motor function following recovery from anesthesia and 2 days after ligation. The Pearson correlation coefficient was 0.980 and 0.923 for these two time points, respectively (P<0.001). In addition, the amplitude changes were positively related to pathological damage, with a Pearson correlation coefficient of 0.945 (P<0.001). The results of the present study suggested that amplitude changes in TceMEP are particularly sensitive to ischemia. Ischemia may be detected within 1 min and the amplitude changes begin to stabilize within 5 min following ligation of the lumbar artery. The use of intraoperative monitoring of TceMEP allows for the detection of spinal cord ischemic injury with no time delay, which may allow for protective measures to be taken to prevent the occurrence of irreversible spinal cord injury.

20.
J Cardiovasc Electrophysiol ; 28(7): 819-827, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28422349

RESUMO

OBJECTIVE: To investigate the effect of the mutual regulation of the extrinsic cardiac nerves on atrial electrophysiology and atrial fibrillation (AF) vulnerability. METHODS AND RESULTS: Fourteen dogs were randomly divided into two groups: spinal cord stimulation (SCS) group (n = 7) and spinal cord block (SCB) group (n = 7). SCS was performed with 90% of the threshold voltage stimulating the T1 -T2 spinal level, while SCB was performed by injecting 2% lidocaine into the epidural space at the T2-3 level. The effective refractory period (ERP), ERP dispersion, and AF inducibility were measured during atrial pacing combined with different extrinsic cardiac nerve stimulation. ERPs were decreased in the atrium and pulmonary veins and ERP dispersion was increased from baseline during left cervical vagus nerve stimulation (VNS) or left stellate ganglion stimulation (SGS) in the two groups. When combined with SCS, VNS resulted in diminished ERPs at all recording sites, longer ERP dispersion and more episodes of AF than were observed during VNS, whereas ERPs were greater and correspondingly fewer episodes of AF occurred during SCS combined with SGS than SGS. In the SCB group, ERPs were shortened, ERP dispersion was lengthened, and episodes of AF were increased during SGS after SCB. SCS enhanced the activity of the left vagus nerve but attenuated the left stellate ganglion and superior left ganglionated plexus. CONCLUSION: SCS modulates extrinsic and intrinsic cardiac nerve activity among the vagus nerve, stellate ganglion, and ganglionated plexus. SCS facilitates the effect of VNS and attenuates the effect of SGS on atrial electrophysiology.


Assuntos
Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo/fisiologia , Coração/inervação , Coração/fisiologia , Estimulação da Medula Espinal/métodos , Medula Espinal/fisiologia , Animais , Fibrilação Atrial/etiologia , Cães , Distribuição Aleatória , Estimulação da Medula Espinal/efeitos adversos
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