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The synthesis of graphene quantum dots-like enriched with specific oxygenated groups (o-GQDs) exhibiting great catalytic performance offers a promising tool for diagnosis and biomedicine, but introducing specific oxygen groups remains a challenge. Here, we propose a mild synthetic protocol for producing regulated fluorescence emission (from blue to yellow) carbonyl functionalized GQDs with double catalytic function through Fe3O4-catalyzed hydroxyl radical (·OH) oxidation the precursors like graphene oxide, polyaniline (PANI) and polydopamine (PDA). The method can be carried out at room temperature than the traditional high-temperature oxidation in concentrated acid. Interestingly, o-GQDs exhibit excellent peroxidase (POD)- and ascorbate oxidase-like activity. XPS characterization showed a significant increase in carbonyl content in o-GQDs compared to the precursor, even a 14-fold increase in blue-emitting iron-doped GQDs (b-Fe-GQDs). The introduction of Fe3O4 during the synthesis process results in a minor degree of Fe doping, which enhances the catalytic activity of b-Fe-GQDs through coordination with N. Based on this feature, highly sensitive single-signal and ultra-selective dual-signal methods for alkaline phosphatase detection were developed. This low cost and safe synthesis strategy paves the way for practical usage of o-GQDs.
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Grafito , Radical Hidroxilo , Puntos Cuánticos , Puntos Cuánticos/química , Grafito/química , Radical Hidroxilo/análisis , Radical Hidroxilo/química , Fluorescencia , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/química , Fosfatasa Alcalina/análisis , Indoles/química , Indoles/síntesis química , Catálisis , Materiales Biomiméticos/química , Materiales Biomiméticos/síntesis química , Espectrometría de Fluorescencia , Oxidación-ReducciónRESUMEN
A dual-mode sensor was developed for detecting acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) via bifunctional BSA-CeO2 nanoclusters (NCs) with oxidase-mimetic activity and fluorescence property. The dual-mode sensor has the characteristics of self-calibration and self-verification, meeting the needs of different detection conditions and provide more accurate results. The colorimetric sensor and fluorescence sensor have been successfully used for detecting AChE with limit of detection (LOD) of 0.081 mU/mL and 0.056 mU/mL, respectively, while the LOD for OPs were 0.9 ng/mL and 0.78 ng/mL, respectively. The recovery of AChE was 93.9-107.2% and of OPs was 95.8-105.0% in actual samples. A novel strategy was developed to monitor pesticide residues and detect AChE level, which will motivate future work to explore the potential applications of multifunctional nanozymes.
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Acetilcolinesterasa , Técnicas de Química Analítica , Plaguicidas , Teléfono Inteligente , Acetilcolinesterasa/análisis , Hidrogeles , Compuestos Organofosforados , Plaguicidas/efectos adversos , Técnicas de Química Analítica/métodosRESUMEN
BACKGROUND: To explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors. METHODS: Retrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA). RESULTS: DR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group. CONCLUSIONS: A relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Retinopatía Diabética , Edema Macular , Humanos , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Retinopatía Diabética/diagnóstico , Nefropatías Diabéticas/complicaciones , Estudios Retrospectivos , Edema Macular/diagnóstico , Edema Macular/etiología , Diabetes Mellitus Tipo 2/complicaciones , LDL-Colesterol , RetinaRESUMEN
The prevalence of cardiovascular disease (CVD) has been rising due to sedentary lifestyles and unhealthy dietary patterns. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor regulating multiple biological processes, such as lipid metabolism and inflammatory response critical to cardiovascular homeostasis. Healthy endothelial cells (ECs) lining the lumen of blood vessels maintains vascular homeostasis, where endothelial dysfunction associated with increased oxidative stress and inflammation triggers the pathogenesis of CVD. PPARα activation decreases endothelial inflammation and senescence, contributing to improved vascular function and reduced risk of atherosclerosis. Phenotypic switch and inflammation of vascular smooth muscle cells (VSMCs) exacerbate vascular dysfunction and atherogenesis, in which PPARα activation improves VSMC homeostasis. Different immune cells participate in the progression of vascular inflammation and atherosclerosis. PPARα in immune cells plays a critical role in immunological events, such as monocyte/macrophage adhesion and infiltration, macrophage polarization, dendritic cell (DC) embedment, T cell activation, and B cell differentiation. Cardiomyocyte dysfunction, a major risk factor for heart failure, can also be alleviated by PPARα activation through maintaining cardiac mitochondrial stability and inhibiting cardiac lipid accumulation, oxidative stress, inflammation, and fibrosis. This review discusses the current understanding and future perspectives on the role of PPARα in the regulation of the cardiovascular system as well as the clinical application of PPARα ligands.
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Aterosclerosis , Enfermedades Cardiovasculares , Sistema Cardiovascular , Humanos , PPAR alfa/agonistas , PPAR alfa/metabolismo , Células Endoteliales/metabolismo , Aterosclerosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Enfermedades Cardiovasculares/tratamiento farmacológicoRESUMEN
AIMS: Diabetic cardiomyopathy (DCM) is an ill-defined entity. This study aims to explore the clinical characteristics and prognosis of diabetic patients that disparately develop heart failure (HF) with preserved ejection fraction (HFpEF) other than HF with reduced ejection fraction (HFrEF). PATIENTS AND METHODS: A total of 911 patients diagnosed with diabetes mellitus were identified in the ChiHFpEF cohort (NCT05278026). DCM was defined as diabetic patients diagnosed with HF, absent from flow obstructive coronary artery disease (CAD), uncontrolled refractory hypertension and hemodynamics significant heart valvular diseases, arrhythmia and congenital heart diseases. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. RESULTS: As compared to DCM-HFrEF patients, DCM-HFpEF patients had a longer duration of diabetes, were older and more noticeable in hypertension and non-obstructive CAD. After a median follow-up of 45.5 months, survival analysis showed that DCM-HFpEF patients had a better composite endpoint. Cox regression implicated that non-obstructive CAD was a negative (HR 0.101, 95% CI 0.028-0.373, p = 0.001) predictor for the composite endpoint of DCM-HFrEF patients. Age was a positive predictor for the composite endpoint of DCM-HFpEF patients (HR 1.044, 95% CI 1.007-1.082, p = 0.018). CONCLUSION: DCM-HFpEF is a disparate entity from DCM-HFrEF. Additional phenomic studies are needed to explore the molecular mechanisms and develop targeted therapies.
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Background: Coronary artery disease (CAD) is a complex disease and the leading cause of death worldwide. It is caused by genetic and environmental factors or their interactions. Candidate gene association studies are an important genetic strategy for the study of complex diseases, and multiple variants of inflammatory cytokines have been found to be associated with CAD using this method. Interleukin-5 (IL-5) is an important inflammatory immune response factor that plays a role in a various inflammatory disease. Clinical tests and animal experiments indicated that IL-5 is involved in CAD development, but the exact mechanisms are unclear. This study investigated the genetic relationship between the single nucleotide polymorphisms (SNPs) in IL5 and CAD. Materials and Methods: Based on the Chinese Han population, we collected 1,824 patients with CAD and 1,920 control subjects and performed a two-stage case-control association analysis for three SNPs in IL5 (rs2057687, rs78546665, and rs2069812) using the high resolution melt (HRM) technology. Logistic regression analyses were applied to adjust for traditional risk factors for CAD and to perform haplotype and gene interaction analyses. Multiple linear regression analyses were used to study relationships between the selected SNPs and serum lipid levels. Results: In this study, two-stage case-control association analysis revealed that the allele and genotype frequency distributions of the three IL5 SNPs were not statistically significant between the case and control groups. In addition, none of the IL5 haplotypes were associated with CAD. Further stratified analyses were conducted by sex, age, hypertension, and disease status, respectively, and the results revealed that the rs2057687 and rs2069812 of IL5 were associated with CAD in the male group (p adj = 0.025, OR, 0.77 (95% CI, 0.62-0.97); p adj = 0.016, OR, 0.82 (95% CI, 0.70-0.97), respectively); the rs2057687 and rs78546665 of IL5 were associated with late-onset CAD (p adj = 0.039, OR, 0.78 (95% CI, 0.62-0.99); p adj = 0.036, OR, 1.46 (95% CI, 1.02-1.53), respectively); the rs2069812 of IL5 was associated with CAD in the hypertension group (p adj = 0.036, OR, 0.84 (95% CI, 0.71-0.99)); and none of the SNPs in IL5 were associated with different CAD states (anatomical CAD and clinical CAD). In addition, the association between SNPs and the serum lipid levels indicated that rs78546665 was positively correlated with triglyceride levels (p = 0.012). Finally, SNP-SNP interaction analyses revealed that interactions of rs2057687 and rs2069812 were associated with CAD (p adj = 0.046, OR, 0.77 (95% CI, 0.13-4.68)). Conclusion: This study suggested that the common variants of IL5 might play a role in CAD by affecting the risk factors for CAD and through SNP-SNP interactions, which provides a new target for specific treatment of CAD patients and a theoretical basis for personalized medicine.
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Enfermedad de la Arteria Coronaria , Hipertensión , Humanos , Masculino , Enfermedad de la Arteria Coronaria/genética , Interleucina-5 , Predisposición Genética a la Enfermedad , Pueblos del Este de Asia , Frecuencia de los Genes , Genotipo , Factores de Riesgo , Polimorfismo de Nucleótido Simple/genética , Hipertensión/complicaciones , Lípidos , Estudios de Casos y Controles , ChinaRESUMEN
AIMS: Studies have confirmed that the IL-23R/IL-17A axis plays an important role in the development of autoimmune and inflammatory diseases. However, its role in coronary artery disease (CAD) remains unclear. Here, we conducted a large sample case-control study to investigate the association between the IL23R/IL17A axis and CAD in the Chinese Han population. METHODS: Two SNPs, rs2275913: G>A (IL17A) and rs6682925: T>C (IL23R), were genotyped in 3042 CAD cases and 3216 controls using the high-resolution melt technology (HRM). Logistic regression analyses were used to adjust the traditional risk factors for CAD and perform the gene interaction analyses. Multiple linear regression analyses were used to study the relationships between the selected SNPs and the levels of serum lipids. In addition, meta-analysis also was performed for the association between rs6682925 and rs2275913 with CAD in different popolations. RESULTS: Our case-control and meta-analysis for single SNPs demonstrated that the frequencies of the alleles and the distribution of the genotypes had no significant differences in CAD cases compared with controls. In the stratified analysis, we observed that the frequency of the IL17A rs2275913-A allele was more epidemic in early-onset CAD than in the controls (Padjâ¯=â¯0.005, ORâ¯=â¯1.209, 95% CI: 1.059-1.382), and the minor allele C of rs6682925 was associated with a decreased level of serum total cholesterol under a recessive model (Padjâ¯=â¯0.011). We demonstrated a significant interaction between rs6682925 and rs2275913 and CAD in the Chinese Han population. Four genotypes (CTGG, CCAA, CCAG, CCGG) were significantly associated with CAD (Padjâ¯=â¯2.94â¯×â¯10-4, ORâ¯=â¯0.619, 95% CI: 0.478-0.803; Padjâ¯=â¯0.01, ORâ¯=â¯1.808, 95% CI: 1.152-1.869; Padjâ¯=â¯6â¯×â¯10-6, ORâ¯=â¯2.179, 95% CI: 1.558-3.049; Padjâ¯=â¯0.001, ORâ¯=â¯1.883, 95% CI: 1.282-2.762, respectively). CONCLUSION: Our study found no single SNP of rs2275913 in IL17A and rs6682925 in IL23R was associated with CAD in the Chinese population, but the interaction of them were significantly associated with CAD susceptibility, highlighting the key role of the IL-23R/IL-17A axis in the development of CAD. In addition, we also found rs2275913 was associated with early-onset CAD and rs6682925 was associated with total cholesterol levels, which will contribute to the clinical stratified management of this common disease.
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Enfermedad de la Arteria Coronaria , Interleucina-17 , Humanos , Interleucina-17/genética , Enfermedad de la Arteria Coronaria/genética , Estudios de Casos y Controles , Polimorfismo de Nucleótido Simple/genética , Colesterol , Predisposición Genética a la Enfermedad , Receptores de Interleucina/genéticaRESUMEN
AIM: To explore the efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of central retinal vein occlusion (CRVO) through optical coherence tomography angiography (OCTA). METHODS: Patients with prior treatment of a minimum of three consecutive intravitreal injections of either bevacizumab or ranibizumab, followed by injection of conbercept, were recruited. The minimal follow-up period after switching was 12mo. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), the interval of injections was reviewed. Perfusion density (PD) and vascular length density (VLD) of superficial and deep capillary plexus were acquired from OCTA images before and after switching. RESULTS: Twenty-four eyes were included. CRT significantly decreased from 460.71±153.23 µm (before switching) to 283.92±38.27 µm at the end of follow-up (P<0.001). However, BCVA gained to some extent (from 0.98±0.33 to 0.76±0.42 logMAR) but the difference was not significant (P=0.070). After switching to conbercept the injection interval extended from 5.2±2.3wk to 8.3±3.9wk (P=0.012). At the end of follow-up, PD of deep retinal layer decreased significantly compared with before switching (from 34.62%±5.27% to 33.26%±5.82%, P=0.016), similar result was found in VLD of deep retinal layer but not in PD or VLD in superficial layer. CONCLUSION: In cases of refractory macular edema secondary to CRVO, switching to conbercept improves macular thickness and extends interval of injection. Retinal microvasculature cannot improve with treatment of conbercept.
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OBJECTIVES: To investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for ≥10 years. DESIGN: A retrospective study. PARTICIPANTS: Patients aged ≥50 with a diagnosis of T2DM no less than 10 years were included. METHODS: Variables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic retinopathy (DR) were diagnosed by funduscopy, optical coherence tomography and/or fluorescein angiography. The subgroup analysis was performed in early and late AMD. The protective effect of metformin was evaluated in duration-response and dose-response patterns. RESULTS: A total of 324 patients (115 metformin non-users and 209 users) were included in the final analysis. AMD was observed in 15.8% of metformin users and 45.2% of metformin non-users (p<0.0001). The ORs for any AMD, early AMD and late AMD present in patients with DR were 0.06 (0.02-0.20), 0.03 (0.00-0.20) and 0.17 (0.04-0.75). The serum high-density lipoprotein level was positively associated with the late AMD risk (p=0.0054). When analysed by the tertiles of cumulative duration, a similarly reduced risk was observed for the second (5-9 years) (OR: 0.24, 95% CI: 0.08 to 0.75) and third tertiles (≥10 years) (OR: 0.22, 95% CI: 0.09 to 0.52) compared with the first tertile (≤4 years). CONCLUSION: Among patients with T2DM for ≥10 years, metformin users were less likely to develop any AMD and early AMD than non-users; however, the late AMD was not significantly associated with the use of metformin. Also, AMD was less prevalent in patients with DR. The prolonged metformin treatment with a high cumulative dose enhanced the protective effect against AMD. Metformin significantly reduces the AMD risk when the cumulative duration is >5 years.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Degeneración Macular , Metformina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Degeneración Macular/complicaciones , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Metformina/uso terapéutico , Estudios RetrospectivosRESUMEN
OBJECTIVE: Branched-chain amino acids (BCAAs) are popular dietary supplements for exercise. However, increased BCAA levels positively correlate with obesity and diabetes. The metabolic impact of BCAA supplementation on insulin sensitivity during exercise is less understood. METHODS: Male C57BL/6 mice were fed for 12 weeks with a high-fat diet, normal chow diet, or BCAA-restricted high-fat diet. They were subjected to running exercise with or without BCAA treatment for another 12 weeks. RESULTS: Exercise reduced body weight, improved insulin sensitivity, lowered BCAAs in plasma, and inhibited the upregulation of BCAAs and metabolites caused by BCAA supplementation in the subcutaneous white adipose tissue (sWAT) of obese mice. BCAA supplementation reversed insulin sensitivity ameliorated by exercise. The phosphorylation of protein kinase B (Ser473 and Ser474) was decreased by BCAAs in the sWAT of obese mice. However, BCAA supplementation had no such effects in lean mice. BCAAs also increased the expression of fatty acid synthase and other lipogenesis genes in the sWAT of exercised obese mice. BCAA restriction had no effect on body weight and insulin sensitivity in obese mice. CONCLUSIONS: BCAA supplementation impaired the beneficial effect of exercise on glycolipid metabolism in obese but not lean mice. Caution should be taken regarding the use of BCAAs for individuals with obesity who exercise.
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Resistencia a la Insulina , Aminoácidos de Cadena Ramificada , Animales , Peso Corporal , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Lipogénesis , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/metabolismoRESUMEN
AIMS: Heart failure (HF) is a chronic heart disease with a high incidence and mortality. Due to the regulatory complexity of gene coexpression networks, the underlying hub genes regulation in HF remain incompletely appreciated. We aimed to explore potential key modules and genes for HF using weighted gene coexpression network analysis (WGCNA). METHODS AND RESULTS: The expression profiles by high throughput sequencing of heart tissues samples from HF and non-HF samples were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF samples were firstly identified. Then, a coexpression network was constructed to identify key modules and potential hub genes. The biological functions of potential hub genes were analysed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, a protein-protein interaction (PPI) network was constructed using the STRING online tool. A total of 135 DEGs (133 up-regulated and 2 down-regulated DEGs) between HF and non-HF samples were identified in the GSE135055 and GSE123976 datasets. Moreover, a total of 38 modules were screened based on WGCNA in the GSE135055 dataset, and six potential hub genes (UCK2, ASB1, CCNI, CUX1, IRX6, and STX16) were screened from the key module by setting the gene significance over 0.2 and the module membership over 0.8. Furthermore, 78 potential hub genes were obtained by taking the intersection of the 135 DEGs and all genes in the key module, and enrichment analysis revealed that they were mainly involved in the MAPK and PI3K-AKT signalling pathways. Finally, in a PPI network constructed with the 78 potential hub genes, CUX1 and ASB1 were identified as hub genes in HF because they were also identified as potential hub genes in the WGCNA. CONCLUSIONS: To the best of our knowledge, our study is the first to employ WGCNA to identify the key module and hub genes for HF. Our study identified a module and two genes that might play important roles in HF, which may provide potential biomarkers for the diagnosis of HF and improve our knowledge of the molecular mechanisms underlying HF.
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Insuficiencia Cardíaca , Fosfatidilinositol 3-Quinasas , Biomarcadores/metabolismo , Ciclina I , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Insuficiencia Cardíaca/genética , Proteínas de Homeodominio , Humanos , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: In diet-induced arterial atherosclerosis, increased KCa3.1 channel was associated with atherosclerotic plaque progression and instability. Macrophages are involved in the formation of atherosclerotic plaques, and the release of inflammatory cytokines and oxygen free radicals promotes plaque progression. However, whether the macrophage KCa3.1 channel facilitates diabetes-accelerated atherosclerosis is still unclear. This study investigated atherosclerotic plaque in ApoE-/- mice regulated by the KCa3.1 channel. METHODS AND RESULTS: In vivo, blocking KCa3.1channel inhibit the development of the atherosclerotic lesion in diabetic ApoE-/- mice fed with a high-fat diet. In vitro, upregulation of KCa3.1 channel level occurred in RAW264.7 cells treated with HG plus ox-LDL in a time-dependent manner. Blocking KCa3.1 significantly reduced the uptake of ox-LDL in mice peritoneal macrophages. Further studies indicated the KCa3.1 siRNA and TRAM-34 (KCa3.1 inhibitor) attenuated the scavenger receptor CD36 expression via inhibiting STAT3 phosphorylation. CONCLUSION: Blockade of macrophage KCa3.1 channel inhibit cellular oxidized low-density lipoprotein accumulation and decrease proinflammation factors expression via STAT3/CD36 axis. This study provided a novel therapeutic target to reduce the risk of atherosclerosis development in diabetic patients.
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Aterosclerosis , Diabetes Mellitus , Placa Aterosclerótica , Animales , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Antígenos CD36/genética , Antígenos CD36/metabolismo , Humanos , Lipoproteínas LDL , Ratones , Ratones Noqueados , Placa Aterosclerótica/etiología , Factor de Transcripción STAT3/metabolismoRESUMEN
Interleukin-9 (IL-9) plays important role in coronary artery disease (CAD). However, the exact relationship between them is not explored yet. Here, four tag SNPs covering IL9 (rs31563, rs2069868, rs2069870 and rs31564) were selected to conduct case-control association analyses in a total of 3704 individuals from Chinese Han population (1863 CAD vs 1841 control). Results showed that: first, rs2069868 was associated with CAD combined with hypertension (Padjâ¯=â¯0.027); second, IL9 haplotype (CGAT) was associated with CAD (Padjâ¯=â¯0.035), and the combination genotype of "rs31563_CC/rs31564_TT" would remarkably decrease the risk of CAD (Padjâ¯=â¯0.001); third, significant associations were found between rs2069870 and decreased LDL-c levels and decreased total cholesterol levels, and between rs31563 and increased HDL-c levels (Padjâ¯<â¯0.05). Therefore, we conclude that IL9 might play a causal role in CAD by interacted with CAD traditional risk factors, which might confer a new way to improve the prevention and treatment of CAD.
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Enfermedad de la Arteria Coronaria , Interleucina-9 , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Enfermedad de la Arteria Coronaria/genética , Etnicidad , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
AIMS: In addition to its involvement of inflammatory responses, limited information is available on the phenotype and behaviour of vascular macrophages during hypertensive vascular remodelling. Here, we aim at studying the contribution of BMAL1 to the pro-fibrotic macrophage phenotype in the vasculature during hypertension, which leads to enhanced vascular remodelling and promoted blood pressure increase. METHODS AND RESULTS: Wild type Bmal1f/f and myeloid cell selective Bmal1 knockout Bmal1f/f; LysMCre/+ mice were infused with AngII for 4 weeks to induce hypertension. AngII-induced blood pressure increase, vascular media thickness and vascular dysfunction were enhanced in Bmal1f/f; LysMCre/+ mice, accompanied with a pro-fibrotic M2 phenotype of the vascular macrophages. Bmal1f/f; LysMCre/+ mice also have more up-regulations of MMP9 and MMP13 expression in the vascular wall, accompanied by enhanced collagen deposition after AngII infusion. Loss of Bmal1 in bone marrow-derived macrophages enhanced STAT6 activation induced by IL4, and the subsequent MMP13 up-regulation and activity. In macrophages, loss of Bmal1 enhanced the phosphorylation and nuclear translocation of STAT6 triggered by IL4, through possibly a direct interaction between BMAL1 and STAT6. To further determine whether IL4-induced signalling in macrophage contributes to enhanced vascular remodelling in hypertensive mice, we showed that deletion of myeloid IL4Rα in Il4raf/f; LysMCre/+ mice attenuated blood pressure increase and hypertensive vascular remodelling after AngII infusion. CONCLUSIONS: Our results suggested a tonic effect of BMAL1 deletion on hypertensive vascular remodelling. BMAL1 might inhibit IL4-STAT6 signalling in macrophages through the interaction with STAT6 to reduce STAT6 activation and target gene transcription, especially MMP9 and MMP13, contributing to vascular remodelling.
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Factores de Transcripción ARNTL , Hipertensión , Factor de Transcripción STAT6 , Remodelación Vascular , Animales , Ratones , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Hipertensión/metabolismo , Interleucina-4/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Transcripción STAT6/genética , Factor de Transcripción STAT6/metabolismoRESUMEN
With the rapid aging of the population, coronary artery disease (CAD) has become one of the most fatal chronic diseases. However, the genetic mechanism of CAD is still unclear. The purpose of this study is to construct the lncRNA-miRNA-mRNA regulatory network for CAD diseases and systematically identify differentially expressed genes in patients with coronary heart disease. In this study, two lncRNA datasets (GSE69587 and GSE113079) and a microRNA dataset (GSE105449) which contained 393 and 38 CAD samples were selected. In addition, two mRNA datasets which named GSE113079 (98 CAD samples) and GSE9820 (8 CAD samples) were selected to search the differentially expressed genes (DEGs). By comparing the expression data between CAD and control samples, a total of 1111 lncRNAs, 2595 mRNAs and 22 miRNAs were identified. Based on the DEGs, a lncRNA-miRNA-mRNA ceRNA network was constructed to explore the hub nodes in CAD. In the ceRNA network, the lncRNAs KCNQ1OT1 and H19 showed high connectivity with the nine miRNAs. GO and KEGG results showed that genes in ceRNA networks were mainly involved in nitrogen compound metabolic process, PI3K-Akt signaling pathway and retrograde endocannabinoid signaling. These findings will improve the understanding of the occurrence and development mechanism of CAD.
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Enfermedad de la Arteria Coronaria/genética , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Transducción de Señal , Biomarcadores/metabolismo , Sistema Cardiovascular , Biología Computacional , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Macrófagos/metabolismo , MicroARNs/metabolismo , Permeabilidad , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
OBJECTIVE: Presently, the prone position is necessary for popliteal vein puncture access, but it makes the patients uncomfortable and does not allow traditional femoral or jugular access. To address these deficiencies, this study introduces two new methods, anterior and medial access carried out in the supine position. METHODS: Venous interventions with punctures in the popliteal vein of 120 limbs in 97 patients were performed during the period from February 2017 to April 2019. After puncture, venographic guidance was achieved by dorsal vein injection of contrast medium. Interventional therapy was performed after puncture and insertion of the introducer sheath. RESULTS: In all, 120 limbs were punctured in the popliteal vein, with technical success in 118 (98.3% in total) cases: 100%, 96.1%, and 100% successful punctures in, respectively, 32 anterior, 49 medial, and 37 posterior access cases. A comparison of the three groups revealed that the fluoroscopy time and duration of puncture were longer in the medial and anterior access groups than in the posterior access group. The rate of intra-operative and post-operative complications was 7.5% (9/120), with no statistically significant difference between the three access groups. Compared with the pre-operative median score of 2.5, the post-operative SVS (Society of Vascular Surgery) score of the popliteal vein was reduced to 1.5 in the anterior and 0.5 in the medial groups. CONCLUSION: Medial and anterior puncture of the popliteal vein in the supine position can be used as a safe alternative in venous endovascular therapy. The two new methods can mitigate frailty or respiratory problems resulting from the prone position and facilitate traditional femoral and jugular access.
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Cateterismo Periférico , Posicionamiento del Paciente , Flebografía , Vena Poplítea/diagnóstico por imagen , Radiografía Intervencional , Posición Supina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Periférico/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Punciones , Estudios Retrospectivos , Adulto JovenRESUMEN
[Figure: see text].
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Circulación Sanguínea , Proteínas Morfogenéticas Óseas/metabolismo , Endotelio Vascular/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteínas Smad/metabolismo , Calcificación Vascular/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Aorta/metabolismo , Aorta/patología , Endotelio Vascular/patología , Transición Epitelial-Mesenquimal , Femenino , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Transducción de Señal , Calcificación Vascular/fisiopatologíaRESUMEN
BACKGROUND: Fibrinogen, lipoprotein, and high-density lipoprotein levels were associated with vascular calcification, but their predictive capacity for a vascular calcification was not reported. AIMS: The purpose of this study was to evaluate the predictive efficacy of fibrinogen, lipoprotein, and high-density lipoprotein by retrospective analysis of fibrinogen, lipoprotein, and high-density lipoprotein levels in patients with vascular calcification, to explore the effective predictive indexes of vascular calcification, to predict the occurrence and development of vascular calcification, and to provide a simple and effective method for the diagnosis and prevention of vascular calcification.Hypothesis: Fibrinogen is a good prediction of vascular calcification. METHODS: Univariate and multivariate analyses were used to assess the effects of fibrinogen, lipoprotein, and high-density lipoprotein on the CV, and the ROC curve of the predictive model was used to assess its predictive effectiveness. We collected the relevant indicators of 462 patients admitted to the Department of Vascular Surgery of the First Hospital of Hebei Medical University from August 2018 to July 2020, including 189 patients with vascular calcification (40.9%) and 273 patients without vascular calcification (59.1%); 75% of the collected data is used for modeling (modeling group) and 25% for verification (verification group). RESULTS: Results from the multivariate analysis showed fibrinogen, lipoprotein, and high-density lipoprotein to be independent predictors of vascular calcification. Next, the three-factor models are developed respectively. The area below the ROC curve in the fibrinogen, lipoprotein, and high-density lipoprotein forecast model was 0.8018, 0.7348, and 0.7019, respectively. CONCLUSIONS: Fibrinogen is more predictive than high-density lipoprotein and lipoprotein in patients with arteriosclerosis.
Asunto(s)
Aterosclerosis/sangre , Fibrinógeno/análisis , Calcificación Vascular/sangre , Anciano , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Biomarcadores/sangre , China/epidemiología , Femenino , Humanos , Lipoproteínas/sangre , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Calcificación Vascular/diagnóstico , Calcificación Vascular/epidemiologíaRESUMEN
Despite the widely explored biomaterial scaffolds in vascular tissue engineering applications lately, no ideal platform has been provided for small diameter synthetic vascular grafts mainly due to the thrombosis issue. Endothelium is the only known completely non-thrombogenic material; so, functional endothelialization onto vascular biomaterials is critical in maintaining the patency of vascular networks. Bacterial cellulose (BC) is a natural biomaterial with superior biocompatibility and appropriate hydrophilicity as potential vascular grafts. In previous studies, surface modification of active peptides such as Arg-Gly-Asp (RGD) sequences onto biomaterials has been proven to achieve accelerated and selective endothelial cell (EC) adhesion. In our study, we demonstrated a new strategy to remotely regulate the adhesion of endothelial cells based on an oscillating magnetic field and achieve successful endothelialization on the modified BC membranes. In details, we synthesized bacterial cellulose (BC), magnetic BC (MBC), and RGD peptide-grafted magnetic BC (RMBC), modified with the HOOC-PEG-COOH-coated iron oxide nanoparticles (PEG-IONs). The endothelial cells were cultured on the three materials under different frequencies of an oscillating magnetic field, including "stationary" (0 Hz), "slow" (0.1 Hz), and "fast" (2 Hz) groups. Compared to BC and MBC membranes, the cells on RMBC membranes generally show better adhesion and proliferation. Meanwhile, the "slow" frequency of a magnetic field promotes this phenomenon on RMBC and achieves endothelialization after culture for 4 days, whereas "fast" inhibits the cellular attachment. Overall, we demonstrate a non-invasive and convenient method to regulate the endothelialization process, with promising applications in vascular tissue engineering.