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PURPOSE: Circadian disruption has been a common issue due to modern lifestyles. Ventricular remodeling (VR) is a pivotal progressive pathologic change after acute myocardial infarction (AMI) and circadian disruption may have a negative influence on VR according to the latest research. Whether or not Guanxin V (GXV) has a positive effect on VR after AMI with circadian disruption drew our interest. METHODS: Rats were randomly divided into a sham group, an AMI group, an AMI with circadian disruption group, and an AMI with circadian disruption treated with the GXV group according to a random number table. RNA sequencing (RNA-Seq) was utilized to confirm the different expressed genes regulated by circadian disruption. Cardiac function, inflammation factors, pathological evaluation, and mitochondrial dynamics after the intervention were conducted to reveal the mechanism by which GXV regulated VR after AMI with circadian disruption. RESULTS: RNA-Seq demonstrated that NF-κB was up-regulated by circadian disruption in rats with AMI. Functional and pathological evaluation indicated that compared with the AMI group, circadian disruption was associcataed with deteriorated cardiac function, expanded infarcted size, and exacerbated fibrosis and cardiomyocyte apoptosis. Further investigation demonstrated that mitochondrial dynamics imbalance was induced by circadian disruption. GXV intervention reversed the inflammatory status including down-regulation of NF-κB. Reserved cardiac function, limited infarct size, and ameliorated fibrosis and apoptosis were also observed in the GXV treated group. GXV maintained mitochondrial fission/fusion imbalance through suppressed expression of mitochondrial fission-associated proteins. CONCLUSION: The study findings suggest that identified mitochondrial dysfunctions may underlie the link between circadian disruption and VR. GXV may exert cardioprotection after AMI with circadian disruption through regulating mitochondrial dynamics.
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Dinâmica Mitocondrial , Infarto do Miocárdio , Remodelação Ventricular , Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Ratos , Dinâmica Mitocondrial/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Medicamentos de Ervas Chinesas/farmacologia , Transtornos Cronobiológicos/tratamento farmacológico , Transtornos Cronobiológicos/fisiopatologia , Transtornos Cronobiológicos/genética , Modelos Animais de DoençasRESUMO
The aim of the study was to develop a model of coronary microembolization (CME) in rats at a lower cost. We developed a novel rat model without thoracotomy and ventilation under the guidance of echocardiography. Rats were sacrificed at 3 h, 24 h and 1 month postoperatively in both the Echo-CME and Open-chest CME groups for the comparison of the modeling accuracy, mortality, cardiopulmonary circulation, pleural adhesion and ventilation-induced lung injury (VILI). Results showed that the coronary microthrombus formed at 3 h and reached its peak at 24 h postoperatively, which included platelet aggregation and fibrin web. The Echo-group increases success rates, decreased mortality, postoperative complications including pleural adhesion, cardiopulmonary dysfunction and VILI postoperatively than the Open-chest group at 1month postoperatively. The ejection fraction of the CME group decreased to 50% and obvious cardiac fibrosis formed at 3 months postoperatively. Our unique surgical method provided a platform to study molecular mechanisms and potential new pathways for CME treatment.
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Vasos Coronários/patologia , Ecocardiografia , Embolia/patologia , Trombose/patologia , Animais , Vasos Coronários/diagnóstico por imagem , Modelos Animais de Doenças , Embolia/diagnóstico por imagem , Masculino , Ratos Sprague-Dawley , Trombose/diagnóstico por imagemRESUMO
An attractive field of plasmon-mediated chemical reactions (PMCRs) is developing rapidly, but there is still incomplete understanding of how to control the kinetics of such a reaction related to hot carriers. Here, we chose 8-bromoadenine (8BrAd) as a probe molecule of hot electrons to investigate the influence of the electrode potential, laser wavelength, and power on the PMCR kinetics on silver nanoparticle-modified silver electrodes. Plasmonic hot electron-mediated cleavage of the C-Br bond in 8BrAd has been investigated by combining in situ electrochemical surface-enhanced Raman spectroscopy and density functional theory calculations. The experimental and theoretical results reveal that the energy position of plasmon relaxation-generated hot electrons can be modulated conveniently by applied potentials and laser light. This allows the proposal of a mechanism of modulating the matching energy of the hot electron of plasmon relaxation to promote the efficiency of PMCRs in electrochemical interfaces. Our work will be helpful to design surface plasmon resonance photoelectrochemical reactions on metal electrode surfaces of nanostructures with higher efficiency.
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Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs have attracted increasing interest in recent years. However, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial ischemia, is rarely reported. In the present study, we examined a circular RNA, hsa_circ_0007623, which is highly expressed in hypoxia-induced human umbilical vein endothelial cells (HUVECs) and can act as a sponge for miR-297, which is involved in cardiac repair after acute myocardial ischemia. In hypoxia-stimulated HUVECs, the inhibition of hsa_circ_0007623 expression was found to reduce cell proliferation, migration, and angiogenesis. Further in vivo experiments confirmed the cardioprotective effect of hsa_circ_0007623 expression in isoproterenol-induced acute ischemia mice. Bioinformatics analysis predicted hsa_circ_0007623, sponge miR-297 and miR-297 directly target VEGFA, which was validated by dual-luciferase assay. Subsequently, functional experiments revealed hsa_circ_0007623 silencing could up-regulate miR-297 and down-regulate VEGFA expression, and reduce cell proliferation, migration, and angiogenesis. We concluded that hsa_circ_0007623 can bind to miR-297, promote cardiac repair after acute myocardial ischemia, and protect cardiac function.
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MicroRNAs/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , RNA Circular/metabolismo , Regeneração , Animais , Sequência de Bases , Cardiomiopatias/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Isoproterenol , Masculino , Camundongos Endogâmicos BALB C , Isquemia Miocárdica/genética , Isquemia Miocárdica/patologia , Neovascularização Fisiológica/genética , RNA Circular/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty-one migraine patients without aura and 21 age- and gender-matched healthy controls participated in our study. Voxel-based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting-state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients showed significantly decreased gray matter volume in five brain regions: the left medial prefrontal cortex (MPFC), dorsal anterior cingulate cortex (dACC), right occipital lobe, cerebellum and brainstem. The gray matter volume of the dACC was correlated with the duration of disease in migraine patients, and thus we chose this region as the seeding area for resting-state analysis. We found that migraine patients showed increased functional connectivity between several regions and the left dACC, i.e. the bilateral middle temporal lobe, orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (DLPFC). Furthermore, the functional connectivity between the dACC and two regions (i.e. DLPFC and OFC) was correlated with the duration of disease in migraine patients. We suggest that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex, and these changes may explain the functional impairments in migraine patients.
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Encéfalo/patologia , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Enxaqueca sem Aura/patologia , Enxaqueca sem Aura/fisiopatologia , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Adulto , Idoso , Mapeamento Encefálico/métodos , Conectoma/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Crude oil is the most important energy source in the world, and fluctuations in oil prices can significantly influence investors, companies, and governments. However, crude oil prices have numerous characteristics, including randomness, sudden structural changes, intrinsic nonlinearity, volatility, and chaotic nature. This makes the accurate forecasting of crude oil prices a difficult and challenging task. In this paper, a hybrid prediction model for crude oil futures prices is proposed, the accuracy and robustness of which are demonstrated via controlled experiments and sensitivity analysis. This study uses a new data denoising method for data processing to improve the accuracy and stability of the predictions of crude oil prices. Furthermore, the chaotic time-series prediction method, shallow neural networks, linear model prediction methods, and deep learning methods are adopted as submodels. The results of interval forecasts with narrow widths and high prediction accuracies are derived by introducing a confidence interval adjustment coefficient. The results of the simulation experiments indicate that the proposed hybrid prediction model exhibits higher accuracy and efficiency, as well as better robustness of the forecasting than the control models. In summary, the proposed forecasting framework can derive accurate point and interval forecasts and provide a valuable reference for the price forecasting of crude oil futures.
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The high distribution of water resources among provinces in China considerably impacts the development of society and economy in each region. Thus, it is of great practical significance to examine the water resources carrying capacity (WRCC) of each Chinese province. This paper constructs a comprehensive evaluation index system for the WRCC from two aspects: pressure and support. First, it analyzes dynamic changes in the WRCC of 31 Chinese provinces in China by using the decoupling model (DM). Second, it analyzes the key factors that hinder the improvement of WRCC by using the obstacle degree model (ODM). The study found that there are significant inter-provincial differences in China's WRCC. Provinces with greater natural water resources have a higher WRCC. Under the condition of similar natural water resources, WRCC in economically developed provinces is higher. From 2008 to 2015, China's overall WRCC has been increasing. Moreover, three-fifth of China's provinces can be classified as Upward-type (Upward I, Upward II, and Upward III) provinces and their WRCC is in a good state by considering the decoupling type and trend of WRCC in two periods together. The main obstacle factors hindering the improvement of the WRCC are total water resources ([Formula: see text]), water supply per capita ([Formula: see text]), total water supply ([Formula: see text]), forest cover rate ([Formula: see text]), soil erosion control area ([Formula: see text]), water consumption saving ([Formula: see text]), and water usage penetration rate ([Formula: see text]). This study can provide a scientific basis for understanding change trend of WRCC in Chinese provinces and improve their WRCC.
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Conservação dos Recursos Naturais , Recursos Hídricos , China , Água , Abastecimento de ÁguaRESUMO
Ferroptosis is associated with the pathology of myocardial ischemia/reperfusion (MI/R) injury following myocardial infarction, which is a leading cause of death worldwide. Although long noncoding RNAs (lncRNAs) are known to regulate gene expression, their roles in MI/R-induced ferroptosis remain unclear. In this study, we explored the lncRNA expression profiles in a rat model of MI/R injury and found that the novel lncRNA, lncAABR07025387.1, was highly expressed in MI/R-injured myocardial tissues and hypoxia/reoxygenation (H/R)-challenged myocardial cells. Silencing lncAABR07025387.1 improved MI/R injury in vivo and inhibited myocardial cell ferroptosis under H/R conditions. Bioinformatics analyses and luciferase, pull-down, and RNA-binding immunoprecipitation assays further revealed that lncAABR07025387.1 interacted with miR-205, which directly targeted ACSL4, a known contributor to ferroptosis. Furthermore, downregulating miR-205 reversed the ACSL4 inhibition induced by silencing lncAABR07025387.1. These findings suggest that, mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. In conclusion, this study demonstrates that lncAABR07025387.1 acts as a competing endogenous RNA during MI/R injury and highlights the therapeutic potential of lncRNAs for treating myocardial injury.
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At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE-/- mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE-/- mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.
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Aterosclerose , Medicamentos de Ervas Chinesas , PPAR gama , Animais , Camundongos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Colesterol/metabolismo , Células Endoteliais/metabolismo , Células Espumosas , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Receptores X do Fígado/metabolismo , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , PPAR gama/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Knockout para ApoERESUMO
BACKGROUND: The inflammatory state of diabetes promotes high platelet response and endothelial adhesion, which are the main risk factors for cardiovascular events. Tetramethylpyrazine (TMP) is an amide alkaloid isolated from the traditional Chinese medicine Rhizoma Ligustici Chuanxiong, which has been widely used in the clinical treatment of ischemic cardiovascular disease. PURPOSE: This study aimed to investigate whether TMP could alleviate diabetes-induced high platelet response and endothelial adhesion and the underlying mechanisms. METHODS: Type 2 diabetes mellitus (T2DM) rat model was established by high-fat feeding combined with low dose of streptozotocin. Rats in the TMP treatment group were administered with TMP (100 or 200 mg/kg) for 21 days. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with glucose (5.5 mM) to induce endothelial activation. The NOD-like receptor protein 3 (NLRP3) over- and low-expressing cell models were established via transfection of NLRP3 lentivirus plasmid into HUVECs. INF39 (25 mg/kg), a chemical inhibitor of NLRP3 inflammasome, was used to explore the role of NLRP3 in T2DM associated high platelet response and endothelial adhesion. RESULTS: TMP effectively improved the prothrombotic phenotypes and inhibited the expression of vascular inflammatory factors and adhesion molecules in T2DM rats. TMP inhibited NLRP3 inflammasome and reduced the adhesion of HUVECs to platelets and monocytes in vitro. Over-expression of NLRP3 blocked the effect of TMP on HUVECs activation and adhesion, while TMP had no effect on NLRP3 low-expressing HUVECs. The NLRP3 inhibitor INF39 produced similar effects of TMP on diabetes-induced high platelet response, endothelial adhesion and vascular inflammation. CONCLUSION: TMP ameliorates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation in T2DM rats, which provide a new basis for the clinical prevention and treatment of diabetes-associated cardiovascular events.
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Diabetes Mellitus Tipo 2 , Inflamassomos , Animais , Plaquetas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas NLR , Pirazinas , RatosRESUMO
Myocardial ischemia and reperfusion injury (MIRI), induced by coronary heart disease (CHD), causes damage to the cardiomyocytes. Furthermore, evidence suggests that thrombolytic therapy or primary percutaneous coronary intervention (PPCI) does not prevent reperfusion injury. There is still no ideal animal model for MIRI. This study aims to improve the MIRI model in rats to make surgery easier and more feasible. A unique method for establishing MIRI is developed by using a soft tube during a key step of the ischemic period. To explore this method, thirty rats were randomly divided into three groups: sham group (n = 10); experimental model group (n = 10); and existing model group (n = 10). Findings of triphenyltetrazolium chloride staining, electrocardiography, and percent survival are compared to determine the accuracies and survival rates of the operations. Based on the study results, it has been concluded that the improved surgery method is associated with a higher survival rate, elevated ST-T segment, and larger infarct size, which is expected to mimic the pathology of MIRI better.
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Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Animais , Miócitos Cardíacos , Ratos , Ratos Sprague-Dawley , RoedoresRESUMO
Objective: Propofol-based sedation has been widely used for gastroscopy, but the risk of respiratory suppression in elderly patients should not be overlooked. Intravenous (IV) lidocaine during surgery can reduce the demand for propofol and the incidence of cardiopulmonary complications. We examined whether IV lidocaine reduces the dose of propofol and the occurrence of adverse events during gastroscopy in elderly patients. Methods: We conducted a prospective, single-center, double-blind randomized controlled trial in elderly patients aged ≥65 years with ASA I-II. Subjects were randomly assigned to the lidocaine group (Group L, n=70), who received IV 1.5 mg kg-1 lidocaine followed by a continuous infusion of 4 mg kg-1 h-1 lidocaine, or the normal saline group (Group N, n=70), who received an equal volume of saline in the same way. Results: IV lidocaine reduced the total and maintenance propofol dose in Group L (p<0.001), with no significant effect on the induction dose. The incidence of intraoperative hypoxia (p=0.035), emergency airway management events (p=0.005), duration of gastroscopy (p<0.05), consciousness recovery time (p<0.001), and postoperative pain (p=0.009) were all reduced in Group L. Patient (p=0.025) and gastroscopist (p=0.031) satisfaction was higher in Group L. Intraoperative hemodynamic parameters, the respiratory rate, the incidence of sedation-related events and anesthesiologist satisfaction were similar between the two groups. Conclusion: IV lidocaine can significantly reduce the amount of propofol, the incidence of hypoxia and postoperative pain during gastroscopy in elderly patients, with a higher patient and gastroscopist satisfaction.
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Lidocaína , Propofol , Idoso , Anestésicos Intravenosos/efeitos adversos , Anestésicos Locais , Método Duplo-Cego , Gastroscopia , Humanos , Hipóxia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Propofol/efeitos adversos , Estudos ProspectivosRESUMO
Focusing on the heart rate control mode of acceleration sensor based rate responsive pacemakers, this paper implemented the design of activity--heart rate prediction system. Bluetooth module was used as communication means in activity--heart rate prediction system, and the slave computer was used to complete the acceleration signal acquisition and processing, map from acceleration signal to the pacing rate signal, and achieve real-time transmission of acceleration signal and heart rate signal. The master computer fulfilled real-time display and recording of acceleration signal and heart rate signal, moreover, it achieved control function to the slave computer algorithm through classification of 6 parameters. The results of verification experiment showed that there was a significant relation between mapping heart rate and actual heart rate using linear mapping algorithm (R2 = 0.787, P < 0.001).
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Estimulação Cardíaca Artificial/métodos , Processamento de Sinais Assistido por Computador , Algoritmos , Frequência Cardíaca/fisiologia , Humanos , Atividade Motora , Marca-Passo ArtificialRESUMO
Background: The coronary microvascular dysfunction has attracted more and more attention in recent years, but there is still a lack of effective treatment. Shexiang Baoxin Pill is one of the commonly used drugs for the treatment of coronary artery disease in China. More recently, some studies found that it has the effect of improving coronary microvascular function. Objective: To evaluate the effects of Shexiang Baoxin Pill for coronary microvascular function. Methods: Databases including MEDLINE, Web of Science, CNKI, Wanfang, The Cochrane Library, EMbase, VIP and CBM were searched from inception to June 2021 to screen out relevant clinical studies. The 2019 version 2 of the Cochrane risk of bias tool (RoB2) were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. Results: Eleven studies meeting the criteria were included, with a total of 1,075 patients. The results of meta-analysis showed that compared with conventional treatment alone, combination of Shexiang Baoxin Pill and conventional treatment can further increase the coronary flow reserve (CFR) [mean difference (MD) = 0.43, 95%CI (0.28, 0.58), p < 0.000 01], decrease the index of microvascular resistance (IMR) [MD = -4.23, 95%CI (-5.49, -2.97), p < 0.000 01], increase serum nitric oxide (NO) [MD = 11.96, 95%CI (2.74, 21.18), p = 0.001] and decrease serum hypersensitive C-reactive protein (hs-CRP) [MD = -2.49, 95%CI (-3.08, -1.90), p < 0.000 01], but did not increase the time of duration on the exercise testing (TET) [MD = 3.64, 95%CI (-1.17, 8.45), p = 0.14]. In terms of safety, a total of 10 patients developed adverse reactions in the intervention group and 17 patients developed adverse reactions in the control group. Conclusion: Current evidence suggests that Shexiang Baoxin Pill may be effective in the improvement of coronary microvascular function when used in combination with conventional treatment. However, due to the low quality of the included studies, lack of placebo control and high heterogeneity among different studies, we should take a cautious attitude towards this conclusion. Moreover, the safety of Shexiang Baoxin Pill remains uncertain, more high-quality clinical studies are needed to verify the efficacy and safety of this drug in the future. Systematic Review Registration: [website], identifier [registration number: CRD42021265113].
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Ferroptosis is a form of cell death induced by excess iron and accumulation of reactive oxygen species in cells. Recently, ferroptosis has been reported to be associated with cancer and ischemia/reperfusion (I/R) injury in multiple organs. However, the regulatory effects and underlying mechanisms of myocardial I/R injury are not well-understood. The role of miR-135b-3p as an oncogene that accelerates tumor development has been confirmed; however, its role in myocardial I/R is not fully understood. In this study, we established an in vivo myocardial I/R rat model and an in vitro hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocyte injury model and observed that ferroptosis occurred in tissues and cells during I/R myocardial injury. We used database analysis to find miR-135b-3p and validated its inhibitory effect on the ferroptosis-related gene glutathione peroxidase 4 (Gpx4), using a luciferase reporter assay. Furthermore, miR-135b-3p was found to promote the myocardial I/R injury by downregulating GPX4 expression. The results of this study elucidate a novel function of miR-135b-3p in exacerbating cardiomyocyte ferroptosis, providing a new therapeutic target for improving I/R injury.
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Background: The number of heart failure with preserved ejection fraction (HFpEF) patients is increasing year by year, yet all western medicines currently used for heart failure have been shown to be ineffective for HFpEF. Qishen Yiqi Dripping Pill is one of the commonly drugs for the treatment of heart failure in China. In recent years, some clinical studies found that it has curative effect on HFpEF. Objective: To evaluate the efficacy and safety of Qishen Yiqi Dripping Pill in treatment of HFpEF. Methods: Databases including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, The Cochrane Library and EMbase were searched from their inception to May 2020 to screen relevant randomized controlled trials. The "risk of bias" evaluation tool in the Cochrane Handbook was used to evaluate the quality of the included studies. RevMan 5.3 software was used for meta-analysis. Results: Eight studies meeting the criteria were included, with a total of 895 patients. The results of meta-analysis showed that compared with western medicine alone, combination of western medicine and Qishen Yiqi Dripping Pill can further increase the quotient of early diastolic mitral inflow velocity and late diastolic mitral inflow velocity (E/A) in patients with HFpEF [mean difference (MD) = 0.20, 95% CI (0.14, 0.26), p < 0.000 01], decrease the quotient of early diastolic mitral inflow velocity and mitral annular tissue velocity (E/e') [MD = -2.50, 95% CI (-3.18, -1.82), p < 0.000 01], decrease brain natriuretic peptide (BNP) [MD = -151.83, 95% CI (-245.78, -57.89), p = 0.002], increase cardiac function improvement rate [relative risk (RR) = 1.30, 95% CI (1.11, 1.52), p = 0.001], and increase six-minutes walking distance (6-MWD) [MD = 64.75, 95% CI (22.65, 106.85), p = 0.003]. Four studies reported the occurrence of adverse reactions, among which three studies reported no adverse reactions and one study reported three patients with mild adverse reactions in the intervention group. Conclusion: Current evidence suggests that Qishen Yiqi Dripping Pill may be effective in the treatment of HFpEF. However, due to the low quality of the included studies, lack of placebo control, large heterogeneity among different studies, and great possibility of publication bias, the results of our review should be evaluated with more prudence, more high-quality clinical studies are needed to verify the conclusion in the future. In addition, the safety of Qishen Yiqi Dripping Pill remains uncertain, further assessment is required in the future.
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Effect of simvastatin on the expression of caspase-3 in myocardial ischemia reperfusion injury in rats was observed to explore the protective effect of caspase-3 through anti-apoptosis mechanism. A total of 48 healthy male SD rats weighing 160-240 g were selected and divided into 4 groups randomly, namely, the blank group, the sham operation group, the ischemia-reperfusion group and the simvastatin group, with 12 rats in each group. The model of SD rats was made by ligation. The loosen ligature made the reperfusion animal model, the occurrence of arrhythmia in the electrocardiogram of lead II in the experimental animal model was observed, and the area of myocardial infarction in the experimental animal models was detected. The number of apoptotic cells was detected by immunohistochemistry, and the expression of caspase-3 was detected by western blotting. The infarct area in the simvastatin group was significantly lower than the ischemia reperfusion group (P<0.05). The positive rate of the expression of caspase-3 and the positive rate of the expression of apoptotic cells in the ischemic reperfusion and simvastatin groups were significantly higher than that of the blank and sham operation groups, and the positive rate of the expression of caspase-3 and apoptotic cells in the simvastatin group was significantly lower than that of the ischemia-reperfusion group (P<0.05). The arrhythmia score of the simvastatin group was significantly lower than that of the ischemia-reperfusion group (P<0.05). Compared with the blank and sham operation groups, the expression of caspase-3 protein in the ischemia-reperfusion and simvastatin groups was significantly increased, and the expression of caspase-3 protein in the simvastatin group was significantly lower than that of the ischemia reperfusion group (P<0.05). Simvastatin has a protective effect on myocardial ischemia-reperfusion injury, which may be related to the reduction of caspase-3 expression and inhibition of apoptosis.
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AIMS AND METHODS: Acute myocardial infarction (AMI) is a common cardiovascular disease with high mortality. Astragaloside IV (AS-IV) was reported to have cardioprotective effect after AMI. We hypothesize that the cardioprotective role of AS-IV is exerted by enhancing angiogenesis via regulating PTEN/PI3K/Akt signaling pathway. To valid our hypothesis, AMI rats and human umbilical vein endothelial cells (HUVECs) were employed in our study. KEY FINDINGS: After treatment, cardiac function, survival rate, infarct size, pathological changes and fibrosis, cell apoptosis, ultrastructural changes, angiogenesis and expression of PTEN/PI3K/Akt signaling pathway were evaluated, respectively. In vitro study we detected proliferation, tube formation and signaling pathway activation of HUVECs treated with AS-IV, lentivirus overexpressed PTEN was employed to elucidate the potential mechanism. The results indicated that AS-IV administration significantly improved cardiac function and survival rate, limited infarct size, ameliorated pathological changes and fibrosis deposition, inhibited apoptosis, relieved ultrastructure injury and enhanced angiogenesis, PTEN/PI3K/Akt signaling pathway was activated simultaneously compared to the model group. In vitro study suggested that AS-IV treatment promoted cell proliferation and tube formation, and induced PTEN/PI3K/Akt signaling pathway activation. Importantly, overexpression of PTEN by lentivirus abolished AS-IV-induced angiogenesis. SIGNIFICANCE: Our study indicated that AS-IV could promote angiogenesis and cardioprotection after myocardial infarction. The mechanisms involve activation of PTEN/PI3K/Akt signaling pathway.
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Infarto do Miocárdio/tratamento farmacológico , Saponinas/farmacologia , Triterpenos/farmacologia , Indutores da Angiogênese , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Infarto do Miocárdio/metabolismo , Neovascularização Patológica/metabolismo , PTEN Fosfo-Hidrolase/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
In order to explore a novel method for the treatment of drug abuse, we evaluated the effect of chronic deep brain stimulation (DBS) of the rat nucleus accumbens (NAc) on morphine reinforcement, using a DBS apparatus and an implant method we developed. Thirty-two adult rats weighing 240-260 g were divided into three groups, which included a DBS group (n = 10, administration of surgery, morphine and DBS), a sham DBS group (n = 12, administration of surgery and morphine) and a control group (n = 10, administration of physiological saline). The DBS electrode was stereotaxically implanted into the core of unilateral NAc and connected to an implantable pulse generator. Then, they were fixed to the rat skull. One week later, the rats in each group were intraperitoneally injected with morphine at an increasing dose (10-60 mg/kg) once daily. The rats in the DBS group were administered a 130-Hz high-frequency stimulation (HFS) once daily. A 900-second conditioned place preference (CPP) paradigm was used for determining the effect of electrical stimulation on morphine reinforcement in rats. The data showed that 7-10 days later, the preference score of the DBS group was significantly lower than that of the sham DBS group. The results suggest that chronic HFS of the rat NAc can block CPP induced by morphine and attenuate morphine reinforcement.
Assuntos
Estimulação Encefálica Profunda/instrumentação , Dependência de Morfina/fisiopatologia , Morfina/administração & dosagem , Motivação , Núcleo Accumbens/fisiopatologia , Animais , Comportamento de Escolha/fisiologia , Condicionamento Clássico/fisiologia , Dopamina/fisiologia , Relação Dose-Resposta a Droga , Desenho de Equipamento , Injeções Intraperitoneais , Sistema Límbico/fisiopatologia , Mesencéfalo/fisiopatologia , Morfina/toxicidade , Vias Neurais/fisiopatologia , Ratos , Ratos Sprague-Dawley , Meio Social , Síndrome de Abstinência a Substâncias/fisiopatologiaRESUMO
Clogging of the leachate collection system (LCS) has been a common operation problem in municipal solid waste (MSW) landfills in China, which can result in high water levels that threaten the safety of landfill operations. To determine the cause of failure in an LCS, raw leachate from a municipal solid waste transfer station was collected and the high content of particulate matter was characterized. Based on the parameters obtained in a filtration test, a numerical simulation was performed to estimate the influence of particle deposition on drainage system clogging. The results showed that LCSs were confronted with the risk of clogging due to the deposition of particulate matter resulting from the higher concentration of total suspended solids (TSS level > 2200 mg L-1) and larger particle size (>30% TSS particles > 15 µm) in the leachate. On one hand, the non-woven geotextile, as the upper layer of the LCS, retained most particulate matter of large diameters, reducing its hydraulic conductivity to approximately 10-8 to 10-9 m s-1 after 1-2 years of operation and perching significant leachate above it (0.6-0.7 m). On the other hand, the geotextile prevented the gravel layer from physically clogging and minimized the leachate head above the bottom liner. Therefore, the role of geotextile should be balanced to optimize the LCS in MSW landfills in China.