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1.
Clin Cardiol ; 47(6): e24301, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38895772

RESUMO

BACKGROUND: Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP). HYPOTHESIS: The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP. METHODS: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%). RESULTS: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (ß = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (ß = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (ß = -0.300, p < 0.001) and intensive statin therapy (ß = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C. CONCLUSIONS: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels.


Assuntos
Biomarcadores , Proteína C-Reativa , Doença da Artéria Coronariana , Ezetimiba , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Humanos , Masculino , Estudos Retrospectivos , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Pessoa de Meia-Idade , Biomarcadores/sangue , Resultado do Tratamento , Intervenção Coronária Percutânea/métodos , Ezetimiba/uso terapêutico , Quimioterapia Combinada , Idoso , Rosuvastatina Cálcica/uso terapêutico , Atorvastatina/uso terapêutico , LDL-Colesterol/sangue , Anticolesterolemiantes/uso terapêutico , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/diagnóstico
2.
Heliyon ; 9(11): e21309, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37885736

RESUMO

Background: Cardiomyocyte ischemia and hypoxia are important causes of oxidative stress damage and cardiomyocyte apoptosis in coronary heart disease (CHD). Epidemiological investigation has shown that eating more plant-based foods, such as vegetables and fruits, may significantly decrease the risk of CHD. As natural antioxidants, botanicals have fewer toxic side effects than chemical drugs and have great potential for development. Procyanidin B2 (PB2) is composed of flavan-3-ol and epicatechin and has been reported to have antioxidant and anti-inflammatory effects. However, whether PB2 exerts protective effects on hypoxic cardiomyocytes has remained unclear. This study aimed to explore the protective effect of PB2 against cardiomyocyte hypoxia and to provide new treatment strategies and ideas for myocardial ischemia and hypoxia in CHD. Methods and results: A hypoxic cardiomyocyte model was constructed, and a CCK-8 assay proved that PB2 had a protective effect on cardiomyocytes in a hypoxic environment. DCFH fluorescence staining, DHE staining, and BODIPY lipid oxidation assessment revealed that PB2 reduced the oxidative stress levels of cardiomyocytes under hypoxic conditions. TUNEL staining, Annexin V/PI fluorescence flow cytometry, and Western blot analysis of the expression of the apoptosis marker protein cleaved caspase-3 confirmed that PB2 reduced cardiomyocyte apoptosis under hypoxic conditions. JC-1 staining indicated that PB2 reduced the mitochondrial membrane potential of cardiomyocytes under hypoxia. In addition, transcriptomic analysis proved that the expression of 158 genes in cardiomyocytes was significantly changed after PB2 was added during hypoxia, of which 53 genes were upregulated and 105 genes were downregulated. GO enrichment analysis demonstrated that the activity of cytokines, extracellular matrix proteins and other molecules was changed significantly in the biological process category. KEGG enrichment analysis showed that the IL-17 signaling pathway and JAK-STAT signaling pathway underwent significant changes. We also performed metabolomic analysis and found that the levels of 51 metabolites were significantly changed after the addition of PB2 to cardiomyocytes during hypoxia. Among them, 39 metabolites exhibited increased levels, while 12 metabolites exhibited decreased levels. KEGG enrichment analysis showed that cysteine and methionine metabolism, arginine and proline metabolism and other metabolic pathways underwent remarkable changes. Conclusion: This study proves that PB2 can reduce the oxidative stress and apoptosis of cardiomyocytes during hypoxia to play a protective role. Transcriptomic and metabolomic analyses preliminarily revealed signaling pathways and metabolic pathways that are related to its protective mechanism. These findings lay a foundation for further research on the role of PB2 in the treatment of CHD and provide new ideas and new perspectives for research on PB2 in the treatment of other diseases.

3.
J Cell Mol Med ; 27(1): 89-100, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36495058

RESUMO

Myocardial infarction (MI) remains a major challenge to cardiovascular health worldwide, with poor healing leaving a direct impact on patients' quality of life and survival. Metabolic abnormalities after MI are receiving increasing attention. Our previous studies showed that enhancing proline catabolism ameliorates hypoxic damage to myocardial cells; therefore, we sought to determine whether reducing the synthesis of endogenous proline also affects MI. We analysed GEO datasets associated with MI and western blot of mouse heart tissue in an MI model to demonstrate pyrroline-5-carboxylate reductase 1 (Pycr1) expression level after MI. We constructed Pycr1 KO mice by CRISPR/Cas9 technology to explore the effect of Pycr1 gene KO after MI using transcriptomic and metabolomic techniques. In this study, we found reduced mRNA and protein expression levels of Pycr1 in the hearts of mice after MI. We observed that Pycr1 gene KO has a protective effect against MI, reducing the area of MI and improving heart function. Using transcriptomics approaches, we found 215 upregulated genes and 247 downregulated genes after KO of the Pycr1 gene, indicating that unsaturated fatty acid metabolism was affected at the transcriptional level. Metabolomics results revealed elevated content for 141 metabolites and decreased content for 90 metabolites, among which the levels of fatty acids, glycerol phospholipids, bile acids, and other metabolites increased significantly. The changes in these metabolites may be related to the protective effect of Pycr1 KO on the heart after MI. Pycr1 gene KO has a protective effect against MI and our research will lay a solid foundation for the development of future Pycr1-related drug targets.


Assuntos
Infarto do Miocárdio , Pirrolina Carboxilato Redutases , Animais , Camundongos , Metabolômica , Infarto do Miocárdio/genética , Prolina , Pirrolina Carboxilato Redutases/genética , Transcriptoma/genética , delta-1-Pirrolina-5-Carboxilato Redutase
4.
Opt Express ; 30(13): 23587-23599, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225035

RESUMO

In the spin-exchange relaxation-free (SERF) magnetometer of a perpendicular pump-probe configuration, the pump and probe beam characteristics significantly affect the performance. In this paper, an efficient evaluation of optical parameters to improve the sensitivity of a miniature magnetometer has been presented. We have determined the pump light's optimal intensity and wavelength through theoretical analysis and the zero-field resonance experiments. Chirp signals are applied to measure the optical rotations at different probe intensities and frequencies. Through theoretical and experimental analysis of noise source characterization under different beam intensities and wavelengths, we demonstrate that dual-beam magnetometer performance is mainly limited by photon shot noise. Based on the optimum pump and probe beam parameters, we demonstrate magnetic field sensitivity of 6.3 fT/Hz in an 87Rb vapor cell filled with nitrogen gas, with an active measurement volume of 3 × 3 × 3 mm3.

5.
Opt Express ; 30(19): 35071-35084, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36242507

RESUMO

The transient dynamics of atomic spins under oscillating and static magnetic fields have been studied in the spin-exchange relaxation-free (SERF) regime with a dual-beam configuration. The spin-relaxation rate can be accurately measured by detecting the transient response signal of the free induction decay (FID) process within several milliseconds. Leveraging this convenient method for measuring a large relaxation rate in a small cell volume, the dependence of the spin-relaxation rate on the probe intensity and ambient magnetic field was studied in the limit of low spin polarization. Moreover, by theoretical analysis of the dynamic evolution of the Rabi oscillation generated by a consecutive oscillating field and a small static magnetic field, we experimentally demonstrate that the amplitude of the Rabi oscillation is affected by the amplitude of the oscillating field in the SERF regime. According to the retrieved frequency of the FID signal and amplitude of relevant Rabi oscillation, the coil constants were 75.55 ± 0.78~nT/mA, 151.5 ± 0.9~nT/mA, and 116.6 ± 0.3~nT/mA along the x-, y-, and z-axes, respectively.

6.
Opt Express ; 30(11): 18300-18309, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36221634

RESUMO

We propose a three-axis closed-loop optically pumped magnetometer with high sensitivity. The closed-loop magnetometer has a three-axis sensitivity of approximately 30 fT/Hz1/2 using two orthogonal laser beams for pumping and probing the alkali metal atoms. In the closed-loop mode, the dynamic range is improved from ±5 nT to ±150 nT. The bandwidth is increased from about 100 Hz to over 2 kHz with 10 kHz modulation fields in x- and y-axes and another 6 kHz modulation field along the z-axis. Compared with single-axis or dual-axis magnetometers, the proposed magnetometer not only provides the direction and magnitude of the magnetic field but also has high robustness in a challenging environment. The magnetometer has applications in biomagnetic measurements, magnetic resonance imaging, and fundamental physics.

7.
Biopreserv Biobank ; 20(6): 567-574, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35294840

RESUMO

Preservation and transportation are essential for the clinical application of chimeric antigen receptor T (CAR-T) cells. This study aimed to optimize a cryopreservation solution for CAR-T cells and evaluate the antitumor efficiency of CAR-T cells using this optimized solution in vitro and in vivo. First, the stability of the cryopreservation solution for CAR-T infusion was detected by the L27 (37) orthogonal experiment. Subsequently, osmolality and pH were analyzed for the preservation reagent. Additionally, apoptosis and CAR expression of CAR-T cells were measured by flow cytometry, and the cytotoxicity was determined by calcein-AM staining. The results showed that cryopreservation solutions used in this study demonstrated high chemical stability, which induced only 2% CAR-T cells apoptosis in optimal solutions, which were slightly lower than other commercial solutions. Moreover, the CAR expression was not significantly affected by preservation with these solutions. There were no significant differences in the cytotoxicity between fresh and thawed CAR-T cells cryopreserved in the cryopreservation solutions in vivo and in vitro. This study developed a new cryopreservation solution for CAR-T cells, and it was safe and also had negligible effects on the CAR-T cells antitumor activity.


Assuntos
Receptores de Antígenos Quiméricos , Imunoterapia Adotiva/métodos , Linfócitos T , Criopreservação/métodos
8.
Opt Express ; 30(1): 336-348, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35201212

RESUMO

We present a theoretical and experimental study of a single-beam spin-exchange relaxation-free magnetometer in 87Rb vapor cells under different nitrogen gas pressures. The spin relaxation rate is a key component to limit the magnetic sensitivity, and the zero-field resonance method was used to measure the spin relaxation rates of different alkali metal cells. Simultaneously, in a single-beam spin-exchange-relaxation-free (SERF) magnetometer, we demonstrated that the fundamental magnetic field sensitivity was also limited by the pumping light intensity. Based on our theoretical analysis and experimental results, we determined the optimal pumping light intensity and optimal gas pressure. We experimentally demonstrated that the magnetic field sensitivity was 8.89 fT/Hz in the single-beam configuration, with an active measurement volume of 3 × 3 × 3~mm3.

9.
Rev Sci Instrum ; 93(1): 013001, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35104997

RESUMO

A single-beam spin-exchange relaxation-free atomic magnetometer is ultra-sensitive in the zero field, which has great potential for the detection of a magnetoencephalogram. The addition of a modulated magnetic field is an important approach to achieve high sensitivity for devices of this kind. In this study, we discovered that the amplitude and frequency of the modulated magnetic field (modulation index 0-3) both influence the light absorption. We defined this effect into a function by combining theoretical analysis and the results of experiments. It is discovered that the transmission intensity decreases with an increase in the modulation index. This effect is weakened under the application of a high modulation index. In addition, the transmission intensity and bias magnetic field no longer follow a strict Lorentz curve, while a high degree of fit can be achieved by applying the numerical solution of the Bloch function. A compact magnetometer with a volume of 10 cm3 and a sensitivity of 20 fT/Hz is developed based on the single beam scheme for the proof of concept. Our study is crucial in two aspects: (1) Obtaining high sensitivity through a short measurement period and (2) alignment of the scale factor of the individual magnetometer in a detection array, which further pave the way for improvement in a magnetometer's performance under a variety of optics platforms.

10.
Herz ; 47(2): 141-149, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33978777

RESUMO

As an essential trace mineral in mammals and the second most abundant metal in the Earth's crust, iron acts as a double-edged sword in humans. Iron plays important beneficial roles in numerous biological processes ranging from deoxyribonucleic acid biosynthesis and protein function to cell cycle progression. However, iron metabolism disruption leads to widespread tissue degeneration and organ dysfunction. An increasing number of studies have focused on iron regulation pathways and have explored the relationship between iron and cardiovascular diseases. Ferroptosis, an iron-dependent form of programmed cell death, was first described in cancer cells and has recently been linked to heart diseases, including cardiac ischemia-reperfusion injury and doxorubicin-induced myocardiopathy. Here, we summarize recent advances in our understanding of iron homeostasis and heart diseases and discuss potential relationships between ferroptosis and cardiac ischemia-reperfusion injury and cardiomyopathy.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Traumatismo por Reperfusão , Animais , Homeostase , Humanos , Ferro , Mamíferos/metabolismo
11.
Opt Express ; 29(10): 15641-15652, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985261

RESUMO

We demonstrate a single-beam atomic magnetometer (AM) capable of measuring a three-axis magnetic field with high-sensitivity, achieved by applying a small DC offset field and a high frequency modulation field. To satisfy the miniaturization demand of AMs, an elliptically polarized light detuned by 50 GHz from the resonance transition center is employed. The circularly polarized component is used to polarize the alkali-metal atoms, while the linearly polarized light is used to detect the dynamics of the polarized spin under a magnetic field. Based on theoretical analysis, parameters that significantly affect the performance are optimized, and a sensitivity of 20 fT/Hz1/2 in x-axis, 25 fT/Hz1/2 in y-axis, 30 fT/Hz1/2 in z-axis is achieved with a miniature 4 × 4 × 4 mm 87Rb vapor cell. Moreover, we also verify that the operation principle of AMs can be used to null background magnetic fields in-situ with isotropic compensation resolution of 6.7 pT, which provides an effectively precise method for zeroing ambient magnetic field. The high-sensitivity operating of an elliptically-polarized-laser-based magnetometer provides prospective futures for constructing a compact, low-cost AM, which is particularly applicable for non-invasive bio-magnetic imaging such as array-based magnetoencephalography (MEG) and magnetocardiography (MCG).

12.
Opt Express ; 29(6): 8333-8343, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820281

RESUMO

In this paper, we experimentally study transient dynamics of spin polarized atoms in the spin-exchange-relaxation-free (SERF) regime with a single-beam configuration. We pumped atoms with a weak detuning pumping beam, along with a sequence of magnetic field pulses orthogonal to the pumping beam were applied. The dynamics of atomic spin, which experiences Larmor precession under the perturbation of magnetic field, is detected by the transmitted pumping beam. Benefited from the long coherence time of atomic spin in the SERF regime, the dependence of precession frequency and decay rate, which is equal to the magnetic resonance linewidth of atomic spin, on magnetic fields is studied with the transient dynamics of atomic spin in the limit of low spin polarization. Moreover, we demonstrate that coil constants can be calibrated by analyzing the precession frequency of the transient dynamics of atomic spin. And the experimental results show that the coil constants are 114.25 ± 0.02 nT/mA and 114.12 ± 0.04 nT/mA in x- and y-axis, respectively. This method is particularly applicable to study the atomic spin dynamics and calibrate the coil constant in situ of a miniature single-beam SERF magnetometer.

13.
Medicine (Baltimore) ; 100(12): e25323, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761735

RESUMO

ABSTRACT: The optimal strategy for lesion preparation in heavily calcified coronary lesions (HCCL) prior to drug-eluting stent (DES) implantation remains debatable. This study sought to compare the performance of rotational atherectomy (RA) and modified balloon (MB)-based strategy in patients with HCCL receiving current-generation DES.This retrospective study comprised 564 consecutive patients who underwent RA (n = 229) or MB (n = 335) for HCCL at our hospital and were treated with DES. Baseline clinical and angiographic data was obtained from our database. Patients were clinically monitored for the occurrence of any adverse events during the hospitalization. One-year follow-up was conducted by either telephone contact or outpatient visits. 1:1 propensity score matching (PSM) was performed to balance the baseline covariates. After PSM, the clinical outcomes between the 2 groups were compared.After PSM, except more target lesion in right coronary artery existing in the RA group (P = .008), no significant statistical differences were shown in regard of the other angiographic and procedural characteristics of the 2 groups. Strategy success rates were all 100% in both groups. In the unadjusted Cox proportional hazard analysis, participants with RA had a significantly lower risk of target lesion revascularization (TLR) (hazard ratio, HR 0.275, 95% confidence intervals, CI 0.119-0.635, P = .003) and major adverse cardiac event (MACE) (HR 0.488, 95% 0.277-0.859, P = .013). After adjusting for potential confounding variables, RA was significantly associated with TLR (HR 0.32, 95% 0.12-0.853, P = .023), but no longer significantly associated with MACE (HR 0.674, 95% 0.329-1.381, P = .282).In patients with HCCL, lesion preparation with RA was safe and could improve strategy success rate. There was lower rate of TLR with RA, however, no significant difference was found in the MACE rate at 1-year follow-up between RA and MB-based strategy.


Assuntos
Angioplastia Coronária com Balão , Aterectomia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Stents Farmacológicos , Calcificação Vascular , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico , Reestenose Coronária/etiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Calcificação Vascular/diagnóstico , Calcificação Vascular/cirurgia
14.
Cardiovasc Drugs Ther ; 35(1): 153-166, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32770521

RESUMO

PURPOSE: To evaluate the potential association between the lowering of low-density lipoprotein cholesterol (LDL-C) with contemporary lipid-lowering medicines and cognitive function. METHODS: Randomized controlled trials (RCTs) in databases including PubMed, Embase, and the Web of Science and all databases in the Cochrane Library and ClinicalTrials.gov were collected from inception to January 1, 2020. The cognitive function of patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, statins and ezetimibe was evaluated using meta-analysis. RESULTS: A total of 2910 studies were obtained from databases and other sources. Thirty-three studies were selected by screening, including 11 studies on alirocumab, 9 studies on evolocumab, 11 studies on statins and 2 studies on ezetimibe. In our study, a total of 128,691 patients with no cognitive impairment were divided into an intervention group (66,330 patients) and a control group (62,361 patients). The data were subjected to a random-effects model or a fixed-effects model for meta-analysis. The contemporary lipid-lowering medicines significantly reduced LDL-C in terms of both percentage (WMD: -45.06%, 95% CI -50.12% to -40.00%, P < 0.001) and absolute value (WMD: -64.01 mg/dL, 95% CI -72.25 to -55.78, P < 0.001). Compared with the control group, patients receiving treatment with contemporary lipid-lowering medicines did not show a significant difference in the rate of neurocognitive disorder (RR: 1.02, 95% CI 0.90 to 1.16, I2 = 0.0%, p = 0.696). Subgroup analysis was performed according to the intervention and LDL-C stratification. The result of this subgroup analysis was consistent with the main findings. Regarding global cognitive performance, no difference in major cognition was found among the pooled data (SMD: 0.02, 95% CI -0.01 to 0.04, P = 0.002), except for psychomotor speed (SMD: 0.09, 95% CI 0.02 to 0.16, P = 0.0024). CONCLUSIONS: Contemporary lipid-lowering medicines were not associated with cognitive impairment in RCTs. A low LDL-C level did not influence the incidence of cognitive disorder or global cognitive performance.


Assuntos
Anticolesterolemiantes/efeitos adversos , LDL-Colesterol/efeitos dos fármacos , Cognição/efeitos dos fármacos , LDL-Colesterol/sangue , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de PCSK9/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Oxid Med Cell Longev ; 2020: 8866946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294127

RESUMO

BACKGROUND: Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is located on the inner mitochondrial membrane and is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study is aimed at investigating whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. METHODS AND RESULTS: First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. CONCLUSIONS: Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.


Assuntos
Hipóxia/complicações , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Prolina/farmacologia , Animais , Apoptose , Hipóxia/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metabolômica/métodos , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Biochem Pharmacol ; 178: 114065, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492448

RESUMO

At present, ischemic heart failure (HF) caused by coronary heart disease (CHD) has a high morbidity and mortality, placing a heavy burden on global human health. L-Proline (Pro), a nonessential amino acid and the foundation of proteins in the human body, was found to be protective against oxidative stress in various diseases. However, the role of Pro in cardiovascular disease (CVD) remains unclear. In vivo, adult mice were subjected to left anterior descending (LAD) artery ligation for 4 weeks with or without Pro treatment. In vitro, H9c2 cardiomyocytes were pretreated with or without Pro, followed by treatment with hydrogen peroxide (H2O2) (200 µM) for 6 and 12 h. Our data showed that Pro metabolism was disturbing after myocardial infarction (MI). Pro treatment improved cardiac remodeling, reduced infarct size, and decreased oxidative stress and apoptosis in mouse hearts after MI. Pro inhibited the H2O2-induced increase in reactive oxygen species (ROS) in H9c2 cells and protected against H2O2-induced apoptosis. Mechanistically, by RNA sequencing (RNA-seq) and pathway analysis, Pro was shown to exert a protective effect through H2O2 catabolic processes and apoptotic processes, especially oxidative phosphorylation (OXPHOS). Taken together, our findings suggested that Pro protects against MI injury at least partially via redox regulation, highlighting the potential of Pro as a novel therapy for ischemic HF caused by CHD.


Assuntos
Apoptose/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Prolina/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/fisiologia , Linhagem Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Prolina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Remodelação Ventricular/fisiologia
17.
Colloids Surf B Biointerfaces ; 183: 110423, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437608

RESUMO

Photothermal therapy (PTT) is a promising method to kill bacteria because of the broad-spectrum of antibacterial activity and the ability of spatiotemporal regulation. In the previously reported systems, light induced high temperature (˜70 °C) was essential for effectively killing of bacteria, which, however, would also damage nearby nontarget cells or tissues. Here we report photothermal nanoparticles (NPs) for more targeting and killing bacteria at a relative low temperature. Polydopamine (PDA) was chosen to prepare NPs because of its excellent capability of photothermal conversion. Magainin I (MagI) which is an antimicrobial peptide was used to modify NPs' surface because it can specifically interact with bacteria. We demonstrate that MagI-PEG@PDA NPs effectively killed E. coli at a low temperature of ˜45 °C upon near-infrared (NIR) light irradiation. In contrast, the native PDA NPs under light irradiation or the MagI-PEG@PDA NPs themselves showed no bacteria killing ability. This work highlights the importance of close interaction between the target bacteria and the photothermal materials and may promote the practical clinical applications of the PTT.


Assuntos
Antibacterianos/efeitos da radiação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Indóis/efeitos da radiação , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/efeitos da radiação , Polímeros/efeitos da radiação , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Escherichia coli/imunologia , Indóis/química , Raios Infravermelhos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos da radiação , Células NIH 3T3 , Nanopartículas/química , Nanopartículas/toxicidade , Polietilenoglicóis/química , Polímeros/química , Temperatura
18.
Ann Transl Med ; 7(22): 664, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31930065

RESUMO

BACKGROUND: Although coronary artery bypass graft (CABG) surgery is the main method to revascularize the occluded coronary vessels in coronary artery diseases, the full benefits of the operation are mitigated by ischemia-reperfusion (IR) injury. Although many studies have been devoted to reducing IR injury in animal models, the translation of this research into the clinical field has been disappointing. Our study aimed to explore the underlying hub genes and mechanisms of IR injury. METHODS: A weighted gene co-expression network analysis (WGCNA) was executed based on the expression profiles in patients undergoing CABG surgery (GSE29396). Functional annotation and protein-protein interaction (PPI) network construction were executed within the modules of interest. Potential hub genes were predicted, combining both intramodular connectivity (IC) and degrees. Meanwhile, potential transcription factors (TFs) and microRNAs (miRNAs) were predicted by corresponding bioinformatics tools. RESULTS: A total of 336 differentially expressed genes (DEGs) were identified. DEGs were mainly enriched in neutrophil activity and immune response. Within the modules of interest, 5 upregulated hub genes (IL-6, CXCL8, IL-1ß, MYC, PTGS-2) and 6 downregulated hub genes (C3, TIMP1, VSIG4, SERPING1, CD163, and HP) were predicted. Predicted miRNAs (hsa-miR-333-5p, hsa-miR-26b-5p, hsa-miR-124-3p, hsa-miR-16-5p, hsa-miR-98-5p, hsa-miR-17-5p, hsa-miR-93-5p) and TF (STAT1) might have regulated gene expression in the most positively related module, while hsa-miR-333-5p and HSF-1 were predicted to regulate the genes within the most negatively related module. CONCLUSIONS: Our study illustrates an overview of gene expression changes in human atrial samples from patients undergoing CABG surgery and might help translate future research into clinical work.

19.
Cytotherapy ; 18(8): 1037-1042, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27288307

RESUMO

BACKGROUND: Experimental studies and clinical trials suggest that endothelial progenitor cell (EPC) transplantation can repair "broken" heart. However, transplantation of autologous EPCs has numerous limitations, including the limited supply of expanded EPCs, the impaired function and activity of the transplanted cells and so on. Therefore, we investigated the feasibility, safety and initial clinical outcome of autologous thymosin ß4 (Tß4) pre-treated EPC transplantation in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: Ten patients with STEMI were included; they were randomized to 2 groups: EPC transplantation group (control group; n = 5) and Tß4-pre-treated EPC transplantation group (experimental group; n = 5). EPCs were pre-treated with Tß4 24 hours before transplantation in experimental group. Cardiac function was evaluated using echocardiography and emission computed tomography, as well as the 6-min walking test before and 6 months after the intervention. RESULTS: After 6 months of follow-up, the average 6-min walking distance was increased by 38.2 m (from 263 ± 42 m to 302 ± 34 m) in the control group and 75.7 m (from 264 ± 42 m to 340 ± 44 m) in the experimental group; the average difference of the 6-min walking distance was 37.5 m (95% confidence interval [CI], 28.7-56.3 m; P < 0.01). In addition, the cardiac function in the experimental group was more significantly improved than that of the control group. There were no severe complications related to the procedure in either group during the follow-up. DISCUSSION: Our pilot study suggested that Tß4-optimized EPC transplantation appeared to be feasible and safe, and might have beneficial effects on exercise capacity and left ventricular function in patients with STEMI.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/transplante , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Transplante de Células-Tronco , Timosina/farmacologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante , Transplante Autólogo/efeitos adversos , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia
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