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1.
Zhongguo Zhen Jiu ; 43(11): 1239-1245, 2023 Sep 01.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-37986247

RESUMEN

OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.


Asunto(s)
Electroacupuntura , Corteza Motora , Humanos , Corteza Motora/fisiología , Estimulación Magnética Transcraneal/métodos , Extremidad Superior , Ejercicio Físico , Músculo Esquelético/fisiología
2.
Materials (Basel) ; 16(9)2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37176422

RESUMEN

This study presents a simple and innovative approach for producing one-dimensional Mn5Si3 nanorods through a casting-extraction process. In this technique, the Mn5Si3 nanorods were synthesized by reacting Mn and Si during brass solidification and extracted by electrochemical etching of the brass matrix. The effect of the cooling rate during casting on the nanorods' dimension, morphology, and magnetic properties was investigated. The results demonstrate that the prepared high-purity Mn5Si3 nanorods had a single-crystal D88 structure and exhibited ferromagnetism at room temperature. The morphology of the nanorods was an elongated hexagonal prism, and their preferred growth was along the [0001] crystal direction. Increasing the cooling rate from 5 K/s to 50 K/s lead to a decrease in the dimension of the nanorods but an increase in their ferromagnetism. At the optimal cooling rate of 50 K/s, the nanorods had a diameter and length range of approximately 560 nm and 2~11 µm, respectively, with a highest saturation magnetization of 7.5 emu/g, and a maximum coercivity of 120 Oe. These properties make the fabricated Mn5Si3 nanorods potentially useful for magnetic storage applications, and this study also provides a new perspective on the preparation of one-dimensional nanomaterials.

3.
J Biopharm Stat ; 33(5): 555-574, 2023 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-36852969

RESUMEN

The main purpose of this paper is to survey the statistical inference for covariate-specific time-dependent receiver operating characteristic (ROC) curves with nonignorable missing continuous biomarker values. To construct time-dependent ROC curves, we consider a joint model which assumes that the failure time depends on the continuous biomarker and the covariates through a Cox proportional hazards model and that the continuous biomarker depends on the covariates through a semiparametric location model. Assuming a purely parametric model on the propensity score, we utilize instrumental variables to deal with the identifiable issue and estimate the unknown parameters of the propensity score by a simple and efficient method. In addition, when the propensity score is estimated, we develop HT and AIPW approaches to estimate our interested quantities. In the presence of nonignorable missing biomarker, our AIPW estimators of the interested quantities are still doubly robust when the true propensity score is a special parametric logistic model. At last, simulation studies are conducted to assess the performance of our proposed approaches, and a real data analysis is also carried out to illustrate its application.


Asunto(s)
Modelos Estadísticos , Humanos , Curva ROC , Simulación por Computador , Puntaje de Propensión , Modelos Logísticos , Biomarcadores
4.
Mediators Inflamm ; 2022: 2298865, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36248187

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to inflammatory damage in multiple target organs, and lupus nephritis (LN) is one of the most life-threatening organ manifestations. CCAAT/enhancer-binding protein ß (CEBPB) regulates the NLRP3 inflammasome and is involved in the pathogenesis of SLE. However, the role and mechanism of CEBPB in LN remains unclear. MRL/lpr mice and lipopolysaccharides (LPS) combined with adenosine triphosphate- (ATP-) treated glomerular podocytes were used as models of LN in vivo and in vitro, respectively. In vivo, we investigated the expressions of CEBPB during the development of MRL/lpr mice. Then we assessed the effect of CEBPB inhibition on renal structure and function through injecting shCEBPB lentivirus into MRL/lpr mice. In vitro, glomerular podocytes were treated with Pim-1-OE and siCEBPB to explore the relation between CEBPB and Pim-1. The progression of LN in mice was associated with the increased level of CEBPB, and the inhibition of CEBPB ameliorated renal structure impairments and improved renal function damage associated with LN. Knockdown of CEBPB could suppress the activation of NLRP3 inflammasome and the secretion of IL-1ß and IL-6. Furthermore, the knockdown of CEBPB could inhibit NLRP3 inflammasome activation and pyroptosis via binding to Pim-1 promoter to downregulate its expression, and the overexpression of Pim-1 reversed the effects of CEBPB deficiency. The regulation of CEBPB on Pim-1 facilitated pyroptosis by activating NLRP3 inflammasome, thereby promoting the development of LN.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/genética , Lupus Eritematoso Sistémico , Nefritis Lúpica , Adenosina Trifosfato , Animales , Inflamasomas/metabolismo , Interleucina-6 , Lipopolisacáridos/farmacología , Nefritis Lúpica/metabolismo , Ratones , Ratones Endogámicos MRL lpr , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo
5.
Materials (Basel) ; 15(3)2022 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-35161149

RESUMEN

The paper presents the microstructure and mechanical property of pure aluminum (Al) fabricated by multi-pass caliber rolling at room temperature. The finite element modeling (FEM) simulation was performed to explore the changes in rolling force, effective stress and strain, and temperature under various rolling passes. As the number of rolling passes increased, the overall temperature, effective stress, and strain gradually increased, while the maximum rolling force decreased. In addition, due to the dynamic recrystallization (DRX), the average grain size reduced from 1 mm to 14 µm with the increase in rolling passes. The dislocation density increased and it gradually evolved into the high-angle grain boundaries (HAGBs). Moreover, the initial cubic texture rotated to the brass component and finally changed to a mixture of Cube and Brass types. The highest tensile yield strength (TYS), ultimate tensile strength (UTS) and elongation (El.) of caliber rolled pure Al (116 MPa, 135 MPa, and 17%, respectively) can be achieved after 13 rolling passes, which mainly attributed to grain refinement.

6.
Iran J Kidney Dis ; 15(3): 169-176, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33994376

RESUMEN

INTRODUCTION: LN is an important complication affecting the prognosis of SLE. We retrospectively analysed the influence of thrombotic microangiopathy (TMA) on LN, identified risk factors of TMA in LN and renal failure in LN-TMA, and evaluated the availability of plasmapheresis. METHODS: After balancing epidemiological characteristics and pathological types between groups, 127 patients (LN-TMA:42, LN:85) were included. After consulting medical records and followup data, we used the corresponding statistical methods, such as chi-squared test and Student's t-test, to compare differences in various aspects and explore the correlation among factors. RESULTS: LN-TMA patients had significantly higher blood urea nitrogen (13.2 mmol/L vs. 7.5 mmol/L, P < .001), systolic and diastolic blood pressures (both P < .01), serum creatinine (157.75 µmol/L vs. 79.00 µmol/L, P < .001), lactic dehydrogenase (P < .05), renal activity index (8.00 vs. 2.00; P < .001), SLE disease activity index score (13.8 ± 3.4 vs. 10.88 ± 6.0; P < .01), and pleurisy (P < .01) and lower haemoglobin (84.4 ± 20.14 vs. 99.38 ± 23.45 g/L, P < .05), platelets (87 vs. 155 ×109/L, P < .001), estimated glomerular filtration rate (39.24 vs. 97.40 mL/min/ 1.73m2, P < .05), and 3- and 5-year renal survival rates (P < .001 and P < .01, respectively) than non- TMA patients. Infection and TMA (P < 0.01) were independent risk factors for LN-TMA and renal failure, respectively. There was no obvious effect of plasmapheresis. CONCLUSION: TMA is an independent risk factor for renal failure in LN. As TMA affects the severity and prognosis of LN, identifying specific diagnostic indicators and effective treatment for LN is necessary.


Asunto(s)
Nefritis Lúpica , Microangiopatías Trombóticas , Humanos , Riñón , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/terapia , Pronóstico , Estudios Retrospectivos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/etiología
7.
Materials (Basel) ; 13(3)2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-32033276

RESUMEN

An exceptionally high-strength rare-earth-free Mg-8Al-3Bi (AB83) alloy was successfully fabricated via extrusion and caliber rolling. After three-pass caliber rolling, the homogenous microstructure of the as-extruded AB83 alloy was changed to a necklace-like bimodal structure consisting of ultra-fine dynamic recrystallized (DRXed) grains and microscale deformed grains. Additionally, both Mg17Al12 and Mg3Bi2 nanoprecipitates, undissolved microscale Mg17Al12, and Mg3Bi2 particles were dispersed in the matrix of caliber-rolled (CRed) AB83 alloy. The CRed AB83 sample demonstrated a slightly weakened basal texture, compared with that of the as-extruded sample. Consequently, CRed AB83 showed a tensile yield strength of 398 MPa, an ultimate tensile strength of 429 MPa, and an elongation of 11.8%. The superior mechanical properties of the caliber-rolled alloy were mainly originated from the combined effects of the necklace-like bimodal microstructure containing ultra-fine DRXed grains, the homogeneously distributed nanoprecipitates and microscale particles, as well as the slightly modified basal texture.

8.
Biom J ; 62(4): 1038-1059, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31957095

RESUMEN

This paper considers statistical inference for the receiver operating characteristic (ROC) curve in the presence of missing biomarker values by utilizing estimating equations (EEs) together with smoothed empirical likelihood (SEL). Three approaches are developed to estimate ROC curve and construct its SEL-based confidence intervals based on the kernel-assisted EE imputation, multiple imputation, and hybrid imputation combining the inverse probability weighted imputation and multiple imputation. Under some regularity conditions, we show asymptotic properties of the proposed maximum SEL estimators for ROC curve. Simulation studies are conducted to investigate the performance of the proposed SEL approaches. An example is illustrated by the proposed methodologies. Empirical results show that the hybrid imputation method behaves better than the kernel-assisted and multiple imputation methods, and the proposed three SEL methods outperform existing nonparametric method.


Asunto(s)
Biometría/métodos , Funciones de Verosimilitud , Modelos Estadísticos , Curva ROC , Estadísticas no Paramétricas
9.
Mol Med Rep ; 20(4): 3840-3848, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31485654

RESUMEN

Myocardial infarction (MI) is a leading cause of mortality in adults worldwide. Over the last two decades, gene therapy has been a hot topic in cardiology, and there has been a focus on cell cycle inhibitors and their protective effects on the myocardium post­MI. In our previous study, the haploinsufficiency of p27kip1 (p27) was demonstrated to improve cardiac function in mice post­MI by promoting angiogenesis and myocardium protection through the secretion of growth factors. Autophagy is an adaptive response of cells to environmental changes, such as nutrient deprivation, ischemia and hypoxia. The appropriate regulation of autophagy may improve myocardial function by preventing apoptosis of cardiomyocytes. In this study, we used immunoassays, transmission electron microscopy and cardiac ultrasound to confirm that p27 haploinsufficiency prevents myocardial apoptosis by restoring autophagy protein 5­mediated autophagy flux in the early stages of MI. The present study provides a novel method for studying MI or ischemic heart disease therapy.


Asunto(s)
Proteína 5 Relacionada con la Autofagia/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Haploinsuficiencia , Infarto del Miocardio/genética , Miocardio/metabolismo , Animales , Apoptosis , Autofagia , Células Cultivadas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Masculino , Ratones Endogámicos C57BL , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Ratas
10.
Materials (Basel) ; 11(8)2018 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-30103418

RESUMEN

In this study, precompression deformation with a strain level of 5.38% along the transverse direction (TD) at room temperature was conducted on a AZ31 magnesium alloy thin sheet with thickness of 1mm. Then subsequent annealing treatment was carried out at various temperatures (200, 300, 400, and 500 °C) to induce static recrystallization (SRX) and grain growth. The stretch formability was also investigated using the hemispherical test. The results showed that the twinning texture induced by the precompression process was nearly inherited by recrystallized grains after annealing process. Grains grew up and the size increased with the increase of annealing temperature. The largest grain size was obtained when annealing at 400 °C. The mechanical properties including strength and ductility decreased due to the development of coarse grains, however, the stretch formability was enhanced significantly. Indeed, the IE-value increased from 2.83 mm in the as-received Mg alloy sheet to 5.78 mm in the precompressed and 400 °C annealed specimens, leading to an improvement of 104%. This was ascribed to the rotated grain orientation and higher activity of (10⁻12) twins in coarse grains.

11.
Materials (Basel) ; 11(7)2018 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-29986456

RESUMEN

A low-alloyed Mg⁻Sn⁻Al⁻Zn system was developed and successfully fabricated through the extrusion process. The dependence of tensile properties and corrosion behavior on microstructural characteristics of the studied alloy has been investigated. After extrusion, the alloy consists of fine dynamically recrystallized (DRXed) grains of ~2.65 μm and strongly textured coarse unDRXed grains. As a consequence, the extruded alloy showed a high-tensile yield strength (YS) of 259 MPa, ultimate tensile strength (UTS) of 297 MPa and elongation (EL) of 19.0%. The strengthening response was discussed in terms of grain size, texture and solutes. The as-extruded alloy presented severe pitting corrosion and the dependence of corrosion properties on the crystallographic orientation and the formation of corrosion products was analyzed.

12.
Materials (Basel) ; 11(1)2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29342951

RESUMEN

Mg-9Al-1Si-1SiC composites with various initial microstructures prior to equal channel angular pressing (ECAP) were obtained by different pre-treatments (without and with homogenization treatment), and the resultant grain size, second phase and tensile properties of ECAPed composites were reported. The ECAPed composite with homogenization treatment (HT) exhibited finer grain size, higher fraction of dynamically recrystallized (DRXed) grains, weaker texture intensity, as well as the presence of dynamic precipitated Mg17Al12 phase compared to that without HT. Besides, the morphology of pre-existing Mg2Si changed from massive-like to needle-like in the ECAPed composite with HT. Room-temperature tensile test results showed that ultimate tensile strength (UTS), yield strength (YS), and elongation (El) of ECAPed composites with HT were 16.1%, 23%, and 27.3% larger than that without HT, respectively.

13.
Open Life Sci ; 13: 374-378, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33817105

RESUMEN

We report the case of a thirty-eight-year-old woman admitted to our hospital due to palpitation and chest distress. ST-T segment change was found in her ECG. She was then diagnosed with hypertrophic cardiomyopathy by two-dimensional echocardiography. Physical examination showed no obvious abnormal signs and all laboratory examinations were within the normal range. Myocardial fibrosis was detected by cardiac magnetic resonance imaging (MRI). A novel heterozygous mutation (c.235C>T/p.Arg79Cys) in TNNI3 for cardiac troponin I was identified in her. Subsequently, her families were investigated. No one died suddenly in her family. Her father, one of her siblings and one of her daughters had the same genetic mutation but with different clinical manifestations while the others were healthy. Her father and brother were also diagnosed with hypertrophic cardiomyopathy with different clinical manifestation. However, the echocardiography of her daughter was absolutely normal. We hypothesized that the Arg79Cys mutation in TNNI3 leads to a slow development of cardiac hypertrophy and the phenotype of this gene mutation is diverse.

14.
Biochem Biophys Res Commun ; 493(3): 1296-1303, 2017 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-28965948

RESUMEN

OBJECTIVE: To investigate the effect of tacrolimus (FK506) on myocardial infarction, and to further explore its function mechanism. MATERIAL AND METHODS: C57BL/6J mice were randomly divided into three groups: the sham group, the control group and the FK506 group. Anterior descending branch ligation was conducted in the control and the FK506 groups, while sham operation was conducted in the sham group. Mice in the sham and the control groups were intragastrical administration with saline, while the FK506 group were with FK506. Heart function were detected by echocardiogram at 3rd day or 21st day after MI. Hearts were harvested at 3rd day or 21st day after MI for the detection of apoptosis, autophagy, mTOR and NF-κB pathway. RESULTS: FK506 treatment increased survival rate and cardiac function in mice after MI. It decreased infarction area, inflammation reaction and apoptosis. To further study the mechanism of FK506 protection effect, we discovered it could increase autophagy via inhibit mTOR pathway. CONCLUSION: FK506 protect heart function after MI as it improved myocardial cells autophagy process via inhibiting mTOR pathway.


Asunto(s)
Autofagia/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Tacrolimus/farmacología , Animales , Apoptosis/efectos de los fármacos , Cardiotónicos/farmacología , Electrocardiografía , Corazón/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Infarto del Miocardio/metabolismo , Infarto del Miocardio/mortalidad , Infarto del Miocardio/patología , Miocardio/patología , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo
15.
Materials (Basel) ; 10(7)2017 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-28773072

RESUMEN

An I-phase containing Mg-8Sn-6Zn-2Al (wt %; TZA862) alloy was fabricated and subjected to different number of passes of equal channel angular pressing (ECAP) processing at 300 °C. The results showed that the alloys exhibited a bimodal microstructure, which consisted of fine dynamically recrystallized (DRX) grains and coarse non-DRX grains. When increasing the number of ECAP passes from 2 to 6, the fraction of DRX grains and the dispersed second phase particles subsequently increase. However, the fraction and particles then decrease once the number of ECAP passes increases to 8. After 6 ECAP passes, remarkable grain refinement was achieved and increasing the number of passes to 8 cannot further refine the microstructure. Furthermore, the alloys having undergone ECAP exhibited a strong ED-tilted texture, the intensity of which increased with an increase in the number of ECAP passes. The ultimate tensile strength (UTS; 338 MPa) and elongation (El.; 14.2%) of the alloy processed with 6 ECAP passes were considerably higher compared to those of the other materials that had undergone ECAP. These significant enhancements were attributed to extensive grain boundary strengthening, precipitation strengthening and a higher work-hardening capacity.

16.
Materials (Basel) ; 10(7)2017 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-28773180

RESUMEN

In this study, Mg-8Sn-2Zn-2Al (TZA822) alloys with varying Mg2Sn contents prior to extrusion were obtained by different pre-treatments (without and with T4), and the strengthening response related to micro and nano-size Mg2Sn precipitates in the extruded TZA822 alloys was reported. The results showed that the morphology of nano-size Mg2Sn precipitates exhibits a significant change in basal plane from rod-like to spherical, owing to the decrement in the fraction of micro-size particles before extrusion. Meanwhile, the spherical Mg2Sn precipitates provided a much stronger strengthening effect than did the rod-like ones, which was ascribed to uniform dispersion and refinement of spherical precipitates to effectively hinder basal dislocation slip. As a consequence, the extruded TZA822 alloy with T4 showed a higher tensile yield strength (TYS) of 245 MPa, ultimate tensile strength (UTS) of 320 MPa and elongation (EL) of 26.5%, as well as a lower degree of yield asymmetry than their counterpart without T4. Detailed reasons for the strengthening effect were given and analyzed.

17.
Cell Physiol Biochem ; 40(5): 847-860, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27941320

RESUMEN

BACKGROUND/AIMS: The discovery of c-kit+ cardiac stem cells (CSCs) provided us with new therapeutic targets to repair the damaged heart. However, the precise mechanisms regulating CSC proliferation and differentiation in the aged heart remained elusive. Necroptosis, a type of regulated cell death, has recently been shown to occur following myocardial infarction (MI); however, its effect on c-kit+ CSCs remains unknown. We investigated the effects of hepatocyte growth factor (HGF) and necroptosis on the proliferation and differentiation of endogenous c-kit+ CSCs in aged rat hearts following MI. METHODS: The c-kit+ CSCs and HGF/p-Met expression levels in neonatal, adult and aged rats were compared using immunofluorescence and Western blotting. Immediately after MI, adenovirus carrying the HGF gene (Ad-HGF) was injected into the left ventricular wall surrounding the infarct areas of the aged rat heart. The proliferation and differentiation of the endogenous c-kit+ CSCs were studied using immunofluorescence. The signalling pathways were analysed via Western blotting and ELISA. RESULTS: HGF/p-Met expression levels and c-kit+ CSC abundance gradually decreased with age. Ad-HGF promoted c-kit+ CSC differentiation into precursor cells of cardiomyocyte, endothelial and smooth muscle cell lineages and enhanced cardiomyocyte proliferation and angiogenesis in aged rats; these effects were reversed by the inhibition of necroptosis. Ad-HGF administration induced necroptosis by increasing the expression of receptor interacting protein kinase (RIP) 1 and receptor interacting protein kinase (RIP) 3 proteins in the infarcted heart. Moreover, Ad-HGF-induced necroptosis increased high-mobility group box 1 protein (HMGB1) levels and enhanced the abundance of c-kit+ cells in the bone marrow, which may partly account for the beneficial effect of necroptosis on the c-kit+ CSCs. CONCLUSION: Ad-HGF-induced necroptosis facilitated aged heart repair after MI by promoting c-kit+ CSC proliferation and differentiation. These findings may lead to the development of new methods for the treatment of ischaemic heart disease in aged populations.


Asunto(s)
Apoptosis , Factor de Crecimiento de Hepatocito/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Miocitos Cardíacos/patología , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-kit/metabolismo , Células Madre/citología , Adenoviridae/metabolismo , Envejecimiento , Animales , Médula Ósea/patología , Recuento de Células , Proliferación Celular , Proteína HMGB1/metabolismo , Masculino , Infarto del Miocardio/metabolismo , Necrosis , Fosforilación , Proteínas Proto-Oncogénicas c-met/metabolismo , Ratas Sprague-Dawley , Regeneración
18.
Am J Transl Res ; 8(10): 4425-4433, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27830026

RESUMEN

Transforming growth factor-ß1 (TGF-ß1) and inflammation play important roles in the cardiac fibrosis development associated with myocardial infarction (MI). Puerarin is wildly used for treatment of diabetes, cardiovascular disease and cerebrovascular disease in China, and recently some studies have shown its anti-cardiac fibrotic effect on myocardial hypertrophy. The purpose of our study was to determine whether puerarin has an anti-cardiac fibrotic effect after MI and find the potential mechanism. A mouse model of MI was established by standard LAD coronary artery ligation, and cardiac fibrosis was confirmed by Masson's staining and the expression of collagen I, III and α-SMA. The expression level of F4/80 (macrophage/monocyte marker in mouse), monocyte chemoattractant protein (MCP)-1 and TGF-ß1 in cardiac tissue treated with or without puerarin was evaluated by immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). The downstream protein phospho-Smad (small mother against decapentaplegic) 2/3 was evaluated by westernblot. The results displayed that puerarin could inhibit the recruitment and activation of monocytes/macrophages, decrease the expression of TGF-ß1 in the cardiac tissues, and consequently significantly attenuated cardiac fibrosis after MI. Our results also displayed a strong positive correlation between MCP-1 and TGF-ß1 expression in MI. Thus, this study revealed the mechanism by which prevented cardiac fibrosis after MI through a decrease in MCP-1 expression and an inhibition TGF-ß1 pathway, and indicated puerarin could be a potential agent in attenuating MI-induced cardiac fibrosis.

19.
Cell Physiol Biochem ; 38(6): 2401-13, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27299574

RESUMEN

BACKGROUND: Hepatocyte growth factor (HGF) is widely known as a protective factor in ischemic myocardium, however HGF sensitive cellular mechanism remained ill-defined. Autophagy at early stage of hypoxia has been demonstrated to play a role in protecting myocardium both in vivo and vitro. We performed this study to investigate the association between the protective effect of HGF and autophagy. METHODS: Ventricular myocytes were isolated from neonatal rat heart (NRVMs). We evaluated cardiomyocytes apoptosis by Hoechst staining and flow cytometry. Autophagy was assessed by transmission electron microscope and mRFP-GFP-LC3 adenovirus infection. Mitochondrial membrane potential was estimated by JC-1 staining. Western blotting and ELISA assay were used to quantify protein concentrations. RESULTS: We found that autophagy in NRVMs increased at early stage after hypoxia and HGF release was consistent with the change of autophagy. Exogenous HGF enhanced autophagy and decreased apoptosis, while neutralizing HGF yielded opposite effects. Besides, inhibition of autophagy increased apoptosis of myocytes. Furthermore, exogenous HGF induced Parkin, the marker of mitochondrial autophagy, indicating increased clearance of injured mitochondria. CONCLUSIONS: Our results revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. Upregulation of Parkin through administration of exogenous HGF may be a potential therapeutic strategy ptotecting myocytes during ischemia.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/farmacología , Factor de Crecimiento de Hepatocito/farmacología , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Animales , Hipoxia de la Célula/efectos de los fármacos , Células Cultivadas , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Miocitos Cardíacos/patología , Ratas Sprague-Dawley
20.
Biochem Biophys Res Commun ; 463(4): 1108-14, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-26079885

RESUMEN

It is well recognized that the incidence of heart failure and the risk of death is high in diabetic patients after myocardial infarction (MI). Accumulating evidence showed that puerarin (PUE) has protecting function on both cardiovascular disease and diabetes. The aim of this study is to explore whether puerarin could improve cardiac function in diabetic mice after MI and the underlying mechanism. The left anterior of Streptozotocin (STZ)-Nicotinamide (NA) induced diabetic mice were ligated permanently except for the Shame group. Then the operated mice were randomly treated with PUE or saline. Cardiac function was evaluated by echocardiograph before and at 1, 2, 4 weeks after MI. GLUT4/CD36/p-Akt/PPAR α of the heart was examined after treatment for 4 weeks. The results indicated that PUE significantly increased survival rate, improved cardiac function compared with MI group. Moreover, PUE increased expression and translocation of GLUT4 while attenuated expression and translocation of CD36. Western blot analysis showed that PUE enhanced phosphorylation of Akt and decreased PPAR α. This study demonstrated that PUE improved cardiac function after MI in diabetic mice through regulation of energy metabolism, the possible mechanism responsible for the effect of PUE was increasing the expression and translocation of GLUT4 while attenuating the expression and translocation of CD36.


Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Metabolismo Energético/efectos de los fármacos , Corazón/efectos de los fármacos , Isoflavonas/farmacología , Infarto del Miocardio/fisiopatología , Niacinamida/administración & dosificación , Estreptozocina/administración & dosificación , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Corazón/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo
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