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The ecological environment is closely related to the growth and quality of authentic medicinal materials. Ginseng is very strict with its natural environment and grows mostly in the damp valleys of forests, and the appearance and chemical composition of ginseng under different growth environments are very different. This article reviews the effects of different ecological factors(including light, temperature, altitude, moisture, soil factors, etc.)on the appearance and chemical composition(mainly ginsenosides) of ginseng. Through systematic review, it is found that soil physical factors are the most important ecological factors that affect the appea-rance of ginseng, and soil bulk density plays a key role; temperature affects ginsenosides in ginseng medicinal materials The dominant ecological factors for the accumulation of chemical ingredents; strong light, high altitude, high soil moisture, low soil nutrient and strong acid soil can influence the accumulation of secondary metabolites in ginseng. Environmental stress can also stimulate the formation and accumulation of secondary metabolites in medicinal plants. Appropriate low temperature stress, high or low water stress, acid or alkali stress can also promote the accumulation of ginsenosides. This article systematically reviews the ecological factors that affect the appearance and chemical composition of ginseng, and clarifies the dominant ecological factors and limiting factors for the formation of ginseng's appearance and quality, as well as beneficial environmental stress factors, in order to provide a theoretical basis for ginseng ecological planting and ginseng quality improvement.
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Ginsenósidos , Panax , Plantas Medicinales , Bosques , SueloRESUMEN
Arterial media calcification is related to mitochondrial dysfunction. Protective mitophagy delays the progression of vascular calcification. We previously reported that lactate accelerates osteoblastic phenotype transition of VSMC through BNIP3-mediated mitophagy suppression. In this study, we investigated the specific links between lactate, mitochondrial homeostasis, and vascular calcification. Ex vivo, alizarin S red and von Kossa staining in addition to measurement of calcium content, RUNX2, and BMP-2 protein levels revealed that lactate accelerated arterial media calcification. We demonstrated that lactate induced mitochondrial fission and apoptosis in aortas, whereas mitophagy was suppressed. In VSMCs, lactate increased NR4A1 expression, leading to activation of DNA-PKcs and p53. Lactate induced Drp1 migration to the mitochondria and enhanced mitochondrial fission through NR4A1. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection showed that NR4A1 knockdown was involved in enhanced autophagy flux. Furthermore, NR4A1 inhibited BNIP3-related mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, and LC3-II co-localization with TOMM20. The excessive fission and deficient mitophagy damaged mitochondrial structure and impaired respiratory function, determined by mPTP opening rate, mitochondrial membrane potential, mitochondrial morphology under TEM, ATP production, and OCR, which was reversed by NR4A1 silencing. Mechanistically, lactate enhanced fission but halted mitophagy via activation of the NR4A1/DNA-PKcs/p53 pathway, evoking apoptosis, finally accelerating osteoblastic phenotype transition of VSMC and calcium deposition. This study suggests that the NR4A1/DNA-PKcs/p53 pathway is involved in the mechanism by which lactate accelerates vascular calcification, partly through excessive Drp-mediated mitochondrial fission and BNIP3-related mitophagy deficiency.
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Diabetes Mellitus Experimental/genética , Ácido Láctico/farmacología , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Calcificación Vascular/genética , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Proteína Morfogenética Ósea 2/genética , Proteína Morfogenética Ósea 2/metabolismo , Colecalciferol/farmacología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Dieta Alta en Grasa/efectos adversos , Dinaminas/genética , Dinaminas/metabolismo , Regulación de la Expresión Génica , Masculino , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Proteínas Mitocondriales/metabolismo , Mitofagia/efectos de los fármacos , Mitofagia/genética , Nicotina/farmacología , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/antagonistas & inhibidores , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Técnicas de Cultivo de Órganos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Wistar , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Estreptozocina/administración & dosificación , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Calcificación Vascular/metabolismo , Calcificación Vascular/patologíaRESUMEN
The cluster brand is the embodiment of the core competitiveness of an industry. Developing and cultivating cluster brand of ecological agriculture of Dao-di herbs not only helps to optimize the value chain of the Chinese medicinal materials(CMMs) industry cluster, realize the value-added of the CMMs industry cluster, but also enhance the visibility and influence of the industrial cluster, enhance the core competitiveness of the industrial cluster. This has important practical significance for promoting the "orderly" "safe" and "effective" development of the Dao-di herbs. Based on the industry development status of CMMs, this article introduces several concepts related to cluster brands and their relationships, and focuses on the cultivation models and strategies of cluster brand in the CMMs industry. Based on the current status of the development of the CMMs industry, this article introduces several concepts related to cluster brands and their interrelationships. It discusses the cultivation models and strategies of cluster brands in the CMMs industry, industry associations, Chinese medicine companies and individual growers as the support, insists on the ecological cultivation of authentic medicinal materials and the cultivation of cluster brands. Finally, it points out the direction for the high-quality development of the ecological agriculture of CMMs.
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Medicamentos Herbarios Chinos , Plantas Medicinales , Agricultura , Desarrollo Industrial , Medicina Tradicional ChinaRESUMEN
BACKGROUND: Single nucleotide polymorphisms (SNPs) located in the vascular endothelial growth factor (VEGF) gene may be correlated with the susceptibility to coronary artery disease (CAD) - although results have been controversial. The aim of this meta-analysis is to clarify the effects of VEGF -2578A/C (rs699947), -1154G/A (rs1570360), +405C/G (rs2010963), and + 936C/T (rs3025039) polymorphisms on CAD risk. METHODS: Pooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the strength of the association between VEGF gene polymorphisms and CAD risk. Fixed- or random-effects model was used depending on the heterogeneity between studies. RESULTS: In total, 13 eligible articles containing 29 studies were analysed. The pooled analysis indicated that the VEGF gene polymorphisms of rs699947, rs2010963, and rs3025039 were associated with an increased risk of CAD, whereas no significant associations were observed with the rs1570360 polymorphism. A subgroup analysis stratified by ethnicity revealed that the rs699947 and rs3025039 polymorphisms were associated with CAD risk in Asian populations. In addition, stratification by control source indicated an increased risk of CAD susceptibility with the rs699947 polymorphism for population-based studies of reduced heterogeneity. CONCLUSIONS: In summary, we concluded that the VEGF gene polymorphisms rs699947, rs2010963, and rs3025039 are correlated with an elevated CAD risk.
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Enfermedad de la Arteria Coronaria/genética , Polimorfismo de Nucleótido Simple/genética , Factor A de Crecimiento Endotelial Vascular/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , HumanosRESUMEN
It needs on-line monitoring of ammonia concentration on dairy feedlot to disclose ammonia emissions characteristics accurately for reducing ammonia emissions and improving the ecological environment. The on-line monitoring system for ammonia concentration has been designed based on Tunable Diode Laser Absorption Spectroscopy (TDLAS) technology combining with long open-path technology, then the study has been carried out with inverse dispersion technique and the system. The ammonia concentration in-situ has been detected and ammonia emission rules have been analyzed on a dairy feedlot in Baoding in autumn and winter of 2013. The monitoring indicated that the peak of ammonia concentration was 6.11 x 10(-6) in autumn, and that was 6.56 x 10(-6) in winter. The concentration results show that the variation of ammonia concentration had an obvious diurnal periodicity, and the general characteristic of diurnal variation was that the concentration was low in the daytime and was high at night. The ammonia emissions characteristic was obtained with inverse dispersion model that the peak of ammonia emissions velocity appeared at noon. The emission velocity was from 1.48 kg/head/hr to 130.6 kg/head/hr in autumn, and it was from 0.004 5 kg/head/hr to 43.32 kg/head/hr in winter which was lower than that in autumn. The results demonstrated ammonia emissions had certain seasonal differences in dairy feedlot scale. In conclusion, the ammonia concentration was detected with optical technology, and the ammonia emissions results were acquired by inverse dispersion model analysis with large range, high sensitivity, quick response without gas sampling. Thus, it's an effective method for ammonia emissions monitoring in dairy feedlot that provides technical support for scientific breeding.
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Contaminantes Atmosféricos/análisis , Amoníaco/análisis , Industria Lechera , Análisis Espectral , Rayos Láser , Modelos Teóricos , Estaciones del AñoRESUMEN
Autophagy is a lysosomal degradative process that is closely related to the pathogenesis of vascular calcification. Recent evidence suggests that periostin (POSTN) is a unique extracellular matrix protein that is associated with diabetic vascular complications. The aim of current study is to investigate the role of POSTN in diabetic vascular calcification and the underlying mechanisms. Results showed that POSTN was highly upregulated in both calcified arteries of diabetic rats and AGEs-BSA mediated vascular smooth muscle cell (VSMC) calcification. POSTN blocked autophagic flux during the diabetic calcification process, as evidenced by increased protein expression of Beclin1, LC3-II, and P62, as well as the co-localization of LC3-II and LAMP1. Inhibition of POSTN alleviated AGEs-BSA-induced autophagic flux blockade, thereby attenuating AGEs-BSA-induced VSMC calcification. Mechanistically, the upregulation of POSTN impaired the fusion of autophagosomes and lysosome and resulted in the autophagic flux blockade in AGEs-BSA-treated VSMC. Furthermore, this autophagic blockade was intracellular ROS-dependent. In summary, this study uncovered a novel mechanism of POSTN in autophagy regulation of diabetic vascular calcification.
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Autofagia , Moléculas de Adhesión Celular/metabolismo , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/metabolismo , Animales , Moléculas de Adhesión Celular/genética , Complicaciones de la Diabetes/genética , Diabetes Mellitus Experimental/genética , Ratas , Ratas Sprague-Dawley , Calcificación Vascular/etiología , Calcificación Vascular/genéticaRESUMEN
Ferroptosis is a form of regulated cell death that involves metabolic dysfunction resulting from iron-dependent excessive lipid peroxidation. Elevated plasma levels of free fatty acids are tightly associated with cardiometabolic risk factors in patients with obesity, diabetes mellitus, and metabolic syndrome. Metformin (Met) is an antidiabetic drug with beneficial cardiovascular disease effects. The aim of this study was to determine the effects of Met on ferroptosis induced by lipid overload and the effects of these changes on vascular smooth muscle cells (VSMCs) calcification. We developed a hyperlipidaemia-related vascular calcification in vivo model with rats fed a high-fat diet combined with vitamin D3 plus nicotine, and palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma, was used to induce lipid overload and develop an oxidative stress-related calcification model in vitro. The results showed that Met inhibits hyperlipidaemia-associated calcium deposition in the rat aortic tissue. In vitro, treatment of VSMCs with PA stimulates ferroptosis concomitant with increased calcium deposition in VSMCs, while pretreatment with Met attenuates these effects. Furthermore, PA also promotes the protein expression of the extracellular matrix protein periostin (POSTN) and its secretion into the extracellular environment. More importantly, upregulation of POSTN increased the sensitivity of cells to ferroptosis. Mechanistically, upregulation of POSTN suppresses SLC7A11 expression through the inhibition of p53 in VSMCs, which contributes to a decrease in glutathione synthesis and therefore triggers ferroptosis. Interestingly, overexpression of p53 attenuates the inhibitory effect of POSTN on SLC7A11 expression, accompanied by increased Gpx4 expression. Furthermore, p53 knockdown suppresses Met-mediated anti-ferroptosis effects in PA-treated VSMCs, which may be related to the downregulation of SLC7A11 expression. In addition, supplementation of VSMCs with Met enhances the antioxidative capacity of VSMCs through Nrf2 signalling activation. Collectively, targeting POSTN in VSMCs may provide a new strategy for vascular calcification prevention or treatment.
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Hiperlipidemias , Metformina , Calcificación Vascular , Animales , Humanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología , Metformina/farmacología , Músculo Liso Vascular , Miocitos del Músculo Liso , Ratas , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/etiologíaRESUMEN
In this study, we examined the effects of four phosphorus treatments on crop yields, and analyzed crop phosphorus uptake and phosphorus utilization efficiency, as well as changes in soil phosphorus deficit in maize-wheat rotation system, based on a 7-year field experiment in Baoding City, Hebei Province. The results showed that long-term phosphorus application significantly increased the yield and phosphorus uptake of maize and wheat. The yield and phosphorus uptake of maize and wheat showed a parabolic trend that first increased and then decreased with the increases of phosphorus application. The utilization efficiency of phosphorus fertilizer in the corn season was higher than that in the wheat season under various phosphorus application treatments. The cumulative utilization efficiency of phosphorus fertilizer in the wheat season showed a downward trend. The decline rate showed that optimized phosphorus application > 70% optimized phosphorus application >130% optimized phosphorus application. The cumulative utilization efficiency of phosphorus fertili-zer in the corn season showed an upward trend. For the rising rate, the optimized phosphorus application > 70% optimized phosphorus application > 130% optimized phosphorus application. Both the apparent phosphorus surplus and the accumulated phosphorus surplus of the soil without phosphorus application were under phosphorus deficiency. Under the treatment of phosphorus application, soil phosphorus showed a status of phosphorus surplus. The higher the phosphorus application rate, the longer the accumulation period, the higher the soil phosphorus surplus. Under the straw returning condition, phosphorus application rate for wheat of 105-150 kg·hm-2 and the phosphorus application rate for maize of 63-90 kg·hm-2 in Hebei fluvo-aquic soil could ensure the high crop yield, keep the phosphorus utilization efficiency at a high level, and reduce soil phosphorus accumulation and environmental risks.
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Fósforo Dietético , Suelo , Agricultura , China , Fertilizantes , Nitrógeno/análisis , Fósforo , Rotación , Triticum , Zea maysRESUMEN
Taking the main production area of yam in North China Plain as the research area, we analyzed the status of soil fertility and fertilizer application in yam production through field investigation and tracking monitoring, examined soil nutrient balance using the input-output model of nutrients in agricultural system, and assessed the environmental risks in the yam planting system. The results showed that: 1) the contents of soil organic matter and total N were extremely low, and the contents of available P and available Zn were both low; both nitrate and available Cu contents were at the middle level, the contents of soil slowly available K, available S, and exchangeable Ca and Mg were all extremely high, the contents of available K, available Fe, and available Mn were all at high level; 2) The nitrogen (N), phosphorus (P2O5), and potassium (K2O) inputs were 575-943 kg·hm-2, 341-981 kg·hm-2, and 655-1219 kg·hm-2 during the whole growth period of yam, with chemical fertilizer accounting for 83.0%, 88.6%, and 91.3%, respectively; The input imbalance between organic and inorganic fertilizer, as well as the excessive nutrients input were prominent; 3) The surplus rate of soil nitrogen, phosphorus and potassium reached 271.14 kg·hm-2, 466.34 kg·hm-2, and 739.97 kg·hm-2, with corresponding surplus ratio of 48.7%, 258.1%, and 324.5%, respectively, which all exceeded the environmental safety threshold and were classified as moderate risk, severe risk, and severe risk, respectively. The overall environmental risk caused by chemical fertilizer application in yam production had reached severe risk level.
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Dioscorea , Suelo , China , Nutrientes , Medición de RiesgoRESUMEN
Bile acids (BAs) are classically known to play a vital role in the metabolism of lipids and in absorption. It is now well established that BAs act as signaling molecules, activating different receptors (such as farnesoid X receptor, vitamin D receptor, Takeda G-protein-coupled receptor 5, sphingosine-1-phosphate, muscarinic receptors, and big potassium channels) and participating in the regulation of energy homeostasis and lipid and glucose metabolism. In addition, increased BAs can impair cardiovascular function in liver cirrhosis. Approximately 50% of patients with cirrhosis develop cirrhotic cardiomyopathy. Exposure to high concentrations of hydrophobic BAs has been shown to be related to adverse effects with respect to vascular tension, endothelial function, arrhythmias, coronary atherosclerotic heart disease, and heart failure. The BAs in the serum BA pool have relevant through their hydrophobicity, and the lipophilic BAs are more harmful to the heart. Interestingly, ursodeoxycholic acid is a hydrophilic BA, and it is used as a therapeutic drug to reverse and protect the harmful cardiac effects caused by hydrophobic elevated BAs. In order to elucidate the mechanism of BAs and cardiovascular function, abundant experiments have been conducted in vitro and in vivo. The aim of this review was to explore the mechanism of BAs in the cardiovascular system.
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Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy regulation. Previous studies suggested that PDK4 is increased in the calcified vessels of patients with atherosclerosis and is closely associated with mitochondrial function, but the precise regulatory mechanisms remain largely unknown. This study aims to investigate the role of PDK4 in vascular calcification and the molecular mechanisms involved. Using a variety of complementary techniques, we found impaired autophagic activity in the process of vascular smooth muscle cells (VSMCs) calcification, whereas knocking down PDK4 had the opposite effect. PDK4 drives the metabolic reprogramming of VSMCs towards a Warburg effect, and the inhibition of PDK4 abrogates VSMCs calcification. Mechanistically, PDK4 disturbs the integrity of the mitochondria-associated endoplasmic reticulum membrane, concomitantly impairing mitochondrial respiratory capacity, which contributes to a decrease in lysosomal degradation by inhibiting the V-ATPase and lactate dehydrogenase B interaction. PDK4 also inhibits the nuclear translocation of the transcription factor EB, thus inhibiting lysosomal function. These changes result in the interruption of autophagic flux, which accelerates calcium deposition in VSMCs. In addition, glycolysis serves as a metabolic adaptation to improve VSMCs oxidative stress resistance, whereas inhibition of glycolysis by 2-deoxy-D-glucose induces the apoptosis of VSMCs and increases the calcium deposition in VSMCs. Our results suggest that PDK4 plays a key role in vascular calcification through autophagy inhibition and metabolic reprogramming.
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Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Calcificación Vascular/metabolismo , Animales , Autofagia/fisiología , Señalización del Calcio , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Calcificación Vascular/patologíaRESUMEN
A field experiment was conducted to investigate the effects of three types of humic acid, i.e. oxidized humic acid (OHA), aminated humic acid (AHA) and microbial-humic acid (MHA), on physico-chemical properties of saline-alkali soil and maize growth. Results showed that the application of all humic acid materials had no significant effect on soil pH in the current season. However, the soil electrical conductivity (EC), the contents of water-soluble Na+ and K+, and sodium adsorption ratio (SAR) decreased under all three treatments of humic acid application measured in up to 40 cm soil depth. OHA had the strongest effect in reducing soil EC, while no significant differences were detected among the three tested materials in reducing contents of water-solu-ble Na+ and K+ and SAR. In addition, humic acid reduced soil NO3--N content and increased soil NH4+-N content, soluble organic nitrogen (SON) content and total soluble nitrogen (TSN) content, with higher effects of AHA and MHA than OHA. Moreover, the application of humic acid materials increased the content of soil available phosphorus, which was most significant in MHA. Humic acid addition could significantly enhance the yield and function leaf SPAD value of maize, which did not vary among the tested humic acid materials. The rank of effect size on apparent utilization efficiency of N and P fertilizer was in the order of AHA>MHA>OHA. While OHA treatment had the highest agronomic efficiency of N and P, AHA treatment achieved the highest partial factor productivity of applied N and P.
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Fertilizantes , Sustancias Húmicas , Suelo/química , Álcalis , NitrógenoRESUMEN
Arterial media calcification is one of the major complications of diabetes mellitus, which is related to oxidative stress and apoptosis. Mitophagy is a special regulation of mitochondrial homeostasis and takes control of intracellular ROS generation and apoptotic pathways. High circulating levels of lactate usually accompanies diabetes. The potential link between lactate, mitophagy and vascular calcification is investigated in this study. Lactate treatment accelerated VSMC calcification, evaluated by measuring the calcium content, ALP activity, RUNX2, BMP-2 protein levels, and Alizarin red S staining. Lactate exposure caused excessive intracellular ROS generation and VSMC apoptosis. Lactate also impaired mitochondrial function, determined by mPTP opening rate, mitochondrial membrane potential and mitochondrial biogenesis markers. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection for autophagy flux revealed that lactate blocked autophagy flux. LC3-II co-staining with LAMP-1 and autophagosome quantification revealed lactate inhibited autophagy. Furthermore, lactate inhibited mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, LC3-II colocalization with BNIP3 and TEM assays. In addition, BNIP3-mediated mitophagy played a protective role against VSMC calcification in the presence of lactate. This study suggests that lactate accelerates osteoblastic phenotype transition of VSMC and calcium deposition partly through the BNIP3-mediated mitophagy deficiency induced oxidative stress and apoptosis.
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Ácido Láctico/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Mitofagia , Músculo Liso Vascular/metabolismo , Calcificación Vascular/metabolismo , Animales , Células Cultivadas , Potencial de la Membrana Mitocondrial , Estrés Oxidativo , Ratas Sprague-DawleyRESUMEN
Mitochondrial abnormalities have long been observed in the development of vascular calcification. Metformin, a member of the biguanide class of antidiabetic drugs, has recently received attention owing to new findings regarding its protective role in cardiovascular disease. Since the precise control of mitochondrial quantity and quality is critical for the survival and function of vascular smooth muscle cells (VSMCs), maintaining mitochondrial homeostasis may be a potential protective factor for VSMCs against osteoblast-like phenotypic transition. However, limited studies have been reported in this area. Here, we investigated the role of metformin in the phenotypic transformation of VSMCs, as well as its intracellular signal transduction pathways. We demonstrated that supplementation with metformin restored the ß-glycerophosphate (ß-GP)-mediated impairment of mitochondrial biogenesis in VSMCs, as evidenced by an increased mitochondrial DNA copy number, a restored mitochondrial membrane potential (MMP), and upregulated mitochondrial biogenesis-related gene expression, whereas the AMP-activated protein kinase (AMPK) inhibitor compound C suppressed these effects. We also observed that overexpression of pyruvate dehydrogenase kinase 4 (PDK4), an important mitochondrial matrix enzyme in cellular energy metabolism, exacerbated ß-GP-induced oxidative stress and subsequent apoptosis in VSMCs but that these effects were suppressed by dichloroacetate, a widely reported PDK4 inhibitor. More importantly, enhanced mitochondrial biogenesis attenuated the ß-GP-induced phenotypic transformation of VSMCs into an osteogenic phenotype through inhibition of the PDK4/oxidative stress-mediated apoptosis pathway, whereas disruption of mitochondrial biogenesis by zidovudine aggravated ß-GP-induced apoptosis in VSMCs. In addition, inhibition of autophagy by small interfering RNA targeting Atg5 reduced mitochondrial biogenesis in VSMCs. In summary, we uncovered a novel mechanism by which metformin attenuates the phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of the PDK4/oxidative stress-mediated apoptosis pathway, and mitochondrial homeostasis is involved in this process.
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Apoptosis/efectos de los fármacos , Glicerofosfatos/farmacología , Metformina/farmacología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Biogénesis de Organelos , Osteogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteínas Quinasas/metabolismo , Adenilato Quinasa/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Masculino , Mitofagia/efectos de los fármacos , Modelos Biológicos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/ultraestructura , Fenotipo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Although cigarette smoking is an independent risk factor for cardiovascular disease, inconsistent results have been published in the literature on its impacts on the cardiovascular health of patients after coronary revascularization with a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). We performed a comprehensive electronic database search through July 2018. Studies reporting the risk estimates of all-cause mortality and cardiovascular outcomes in patients after coronary revascularization with PCI or CABG on the basis of smoking status were selected. Multivariate-adjusted relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random-effects models with inverse variance weighting. Data from 37 records including 126 901 participants were finally collected. Overall, the pooled RR (95% CI) associated with cigarette smoking was 1.26 (95% CI: 1.09-1.47) for all-cause mortality, 1.08 (95% CI: 0.92-1.28) for major adverse cardiovascular events, 0.96 (95% CI: 0.69-1.35) for cardiovascular mortality and 1.15 (95% CI: 0.81-1.64) for myocardial infarction. The increased risk of all-cause mortality was also observed in former smokers compared with those who had never smoked (RR: 1.19; 95% CI: 1.03-1.38). Furthermore, the negative effects of cigarette smoking on all-cause mortality were also observed in most subgroups. Cigarette smoking has been shown to increase the likelihood of all-cause mortality in patients after coronary revascularization with PCI or CABG. Smoking cessation is essential for PCI or CABG patients to manage their coronary artery disease.
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Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea/mortalidad , Fumadores , Fumar/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease.
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Background: The osteogenic differentiation of vascular smooth muscle cell (VSMCs) is important for the development of vascular calcification (VC), particularly in diabetes. Exosomes derived from Mesenchymal Stromal Cells (MSCs) are effective against cardiovascular diseases, yet their role in VC remains unclear. Advanced glycation end products (AGEs) inhibit bone marrow stromal cell osteogenesis by targeting osteogenesis-associated genes. Thus, we investigated the role of exosomes derived from MSCs pretreated with AGEs-BSA in VC and its potential mechanisms. Methods: Primary VSMCs and MSCs were isolated from the aorta and bone marrow of Sprague-Dawley rats, respectively. VSMCs were cultured with AGEs-BSA to induce osteogenic differentiation. Exosomes were harvested from MSCs by ultracentrifugation. MSCs and VSMCs were cocultured in Transwells, and exosomes were added to VSMC culture medium to assess their effects on osteogenic differentiation. Double luciferase reporter assay was applied to confirm that miR-146a directly targets the 3' UTR of the thioredoxin-interacting protein (TXNIP) gene. Results: Pretreatment of VSMCs with AGEs-BSA increased the expression of thioredoxin-interacting protein (TXNIP) by inhibiting that of miR-146a, resulting in enhanced ROS production and VSMC calcification. By contrast, the expression of miR-146a in MSCs was increased by AGEs-BSA treatment. Thus, miR-146a was transferred from AGEs-BSA-pretreated or miR-146a-transfected MSCs to VSMCs via exosomes. After coculture with miR-146a-containing exosomes, the AGEs-BSA-mediated increase in VSMC calcification was diminished, accompanied by decreased TXNIP expression and ROS production. Furthermore, TXNIP overexpression counteracted the anti-calcification effects of MSC-derived miR-146a-containing exosomes. In addition, TXNIP was identified as a target gene of miR-146a, and the results of double luciferase reporter assay confirmed that TXNIP was the direct target gene of miR-146a. Conclusions: Exosomes secreted by MSCs pretreated with AGEs-BSA contained a high level of miR-146a, which was transferred to VSMCs and inhibited AGEs-BSA-induced calcification in a TXNIP-dependent manner. Thus, miR-146a-containing exosomes may be a potential therapeutic target for VC.
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Lipoprotein lipase (LPL) is widely linked to lipid and lipoprotein metabolism, but its effects on coronary artery disease (CAD) are not clearly elucidated. The aim of this study was to clarify the association between LPL gene polymorphisms and CAD susceptibility. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the relationship between LPL gene polymorphisms and CAD risk. Comprehensive electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library, were systematically searched. A total of 45 records containing 80 eligible studies were analyzed. The results indicated an increased risk between the LPL D9N polymorphism and susceptibility to CAD in the dominant genetic model (AA + GA vs. GG: OR = 1.46, 95% CI = 1.14-1.87), whereas the LPL HindIII polymorphism showed a protective effect against CAD under all tested models (GG+GT vs. TT: OR = 0.85, 95% CI = 0.75-0.97; GG vs. TT + TG: OR = 0.62, 95% CI = 0.47-0.83; G vs. T: OR = 0.81, 95% CI = 0.71-0.92). No significant association was identified for the LPL N291S and PvuII polymorphisms. Stratification analysis by ethnicity suggested a significant correlation between the LPL S447X polymorphism and CAD susceptibility in Caucasians under the dominant and allele genetic models. In summary, our meta-analysis indicated that the LPL D9N polymorphism was associated with an increased risk of CAD, whereas the S447X and HindIII polymorphisms showed protective effects. There was no association observed between the N291S and PvuII polymorphisms and CAD risk.
RESUMEN
Arterial media calcification is associated with diabetes mellitus. Previous studies have shown that advanced glycation end products (AGEs) are responsible for vascular smooth muscle cell (VSMC) calcification, but the underlying mechanisms remain unclear. Hypoxia-inducible factor-1α (HIF-1α), one of the major factors during hypoxia, and pyruvate dehydrogenase kinase 4 (PDK4), an important mitochondrial matrix enzyme in cellular metabolism shift, have been reported in VSMC calcification. The potential link among HIF-1α, PDK4, and AGEs-induced vascular calcification was investigated in this study. We observed that AGEs elevated HIF-1α and PDK4 expression levels in a dose-dependent manner and that maximal stimulation was attained at 24 h. Two important HIF-1α-regulated genes, vascular endothelial growth factor A (VEGFA) and glucose transporter 1 (GLUT-1), were significantly increased after AGEs exposure. Stabilization or nuclear translocation of HIF-1α increased PDK4 expression. PDK4 inhibition attenuated AGEs-induced VSMC calcification, which was evaluated by measuring the calcium content, alkaline phosphatase (ALP) activity and runt-related transcription factor 2 (RUNX2) expression levels and by Alizarin red S staining. In addition, the glucose consumption, lactate production, key enzymes of glucose metabolism and oxygen consumption rate (OCR) were decreased during AGEs-induced VSMC calcification. In conclusion, this study suggests that AGEs accelerate vascular calcification partly through the HIF-1α/PDK4 pathway and suppress glucose metabolism.
Asunto(s)
Glucosa/metabolismo , Productos Finales de Glicación Avanzada/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas Quinasas/genética , Calcificación Vascular/genética , Animales , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Regulación de la Expresión Génica , Transportador de Glucosa de Tipo 1/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ácido Láctico/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Consumo de Oxígeno/genética , Proteínas Quinasas/metabolismo , Ratas , Túnica Media/metabolismo , Túnica Media/patología , Calcificación Vascular/patología , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Winter wheat and summer maize were the main crops in the North China Plain. While intensive farming system could generally achieve high yield, the perennial large amounts of nitrogen (N) fertilization application cause environmental problems including NO3--N accumulation and leaching at deep soil layer. Here, the effects of different N application rates on soil NO3--N accumulation and leaching in winter wheat-summer maize cropping system were investigated from 2010 to 2016 at Qingyuan County, Hebei Province, China. There were five treatments with N application rates at 0 (N0), 100 (N100), 180 (N180), 255 (N255) and 330 (N330) kg·hm-2. Results showed that crop yield and soil N status significantly varied among treatments for both wheat and maize after each harvest, respectively. Soil NO3--N were accumulated during winter wheat growing season and leached to deeper soil during summer maize growing season. Moreover, the soil NO3--N accumulation amount in the 90 to 180 cm soil profile decreased with the decreases of N inputs (N330 > N255 > N180 > N100 > N0). Soil NO3--N could be leached to 990 cm soil depth. There were six NO3--N accumulation peaks in the soil profile, with the peaks presenting at deeper soil profile with higher N fertilization rate. The deepest peak appeared at 840 cm soil depth with the N application rate of 330 kg·hm-2. From the distribution of NO3--N accumulation in the soil profile, only around 10% of total NO3--N was accumulated between 0-90 cm soil depth, while the rest accumulated below 90 cm, which could not be largely absorbed by plants. Therefore, NO3--N leaching during summer maize growing season was serious and it was greater with higher N fertilization rate which might lead to increased risk of underground water contamination. In terms of balanced crop yield and soil NO3--N accumulation, the rate of 180 kg·hm-2 would be the optimum one in areas with similar cultivation and environmental conditions to the present study.