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BACKGROUND: As patients age, the frailty of those with multimorbidity increases, often resulting in adverse health outcomes. The current study investigated the frailty status and the factors which influence it in elderly patients with multimorbidity in Chinese hospitals. The relationship between the frailty of patients with multimorbidity and adverse outcomes was explored. METHODS: The current prospective cohort study investigated inpatients in the internal medicine department of 5 tertiary hospitals in Sichuan Province, China. A total of 3836 elderly patients with multimorbidity were enrolled. Frailty was assessed using the FRAIL scale and adverse outcome events occurring during hospitalization were tracked. Descriptive statistics and logistic regressions were used for data analysis. RESULTS: The prevalence of frailty was 27.2% and of pre-frailty, 58.9%. Logistic regression analysis showed that increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were the main risk factors for frailty in elderly patients with multimorbidity (OR values: 1.020, 1.469, 2.350, 2.836, 1.156 and 1.308, respectively). The incidence of adverse outcomes was 13.9% among the cohort with the most common being deep vein thrombosis (42.4%), followed by pressure injury (38.8%). Regression analysis showed a significant correlation of frailty with adverse outcome (OR: 1.496; p < 0.01). CONCLUSIONS: The prevalence of frailty and pre-frailty in hospitalized elderly patients with multimorbidity was high. Increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were factors which influenced frailty and frailty was an important factor in the occurrence of adverse outcomes. The most common adverse outcome of elderly multimorbidity patients during hospitalization was deep vein thrombosis.
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Fragilidad , Trombosis de la Vena , Anciano , Anciano Frágil , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Multimorbilidad , Estudios ProspectivosRESUMEN
To evaluate the efficacy and safety of topical oxygen therapy (TOT) in diabetic foot ulcers (DFUs), researchers systematically retrieved relevant studies from PubMed, EMBASE, Web of Science, CENTRAL and ClinicalTrials.gov. Relevant studies were searched from database inception to January 2022. Two researchers independently screened the literature, extracted data and assessed the quality of the included studies. Statistical analysis was performed in Stata 16.0. A total of seven RCTs involving 614 participants were included. Compared with the control group, the TOT group had a higher healing rate (RR = 1.63, 95% CI [1.33, 2.00]). According to descriptive analysis, TOT reduced the ulcer area and improved healing durability and quality of life. Furthermore, it had no effect on the occurrence of adverse events. However, it was unclear whether it would be able to reduce the healing time. The existing evidence suggests that TOT is effective and safe for chronic DFUs. Further studies are warranted to validate our findings.
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Diabetes Mellitus , Pie Diabético , Úlcera del Pie , Humanos , Pie Diabético/terapia , Calidad de Vida , Cicatrización de Heridas , Oxígeno/uso terapéuticoRESUMEN
OBJECTIVES: We investigated the safety and feasibility of CT-guided transthoracic pulmonary artery catheterization (TPAC) in a porcine model. METHODS: Procedures were conducted on ten mature Bama miniature pigs. After anesthesia, chest CT was performed in the left lateral decubitus position to determine the puncture route. Under the guidance of multiple CT scans, the introducer sheath was inserted from the right chest wall of the pig into the right pulmonary artery using the Seldinger technique. Then, a catheter connected with a transducer was inserted into the sheath to measure the pulmonary artery pressure. Finally, an active approximator was used to close the puncture site on the pulmonary artery. The pigs were followed up for 8 weeks to evaluate the operation-related complications and survival. RESULTS: Ten of 11 CT-guided TPAC procedures were successfully performed on ten pigs, rendering a technical success rate of 90.9%. One pig had hemoptysis while the needle was being inserted during the first operation, and a second procedure was successfully conducted 17 days later. Other complications, including pulmonary bleeding along the needle track (3 of 11; 27.3%), unclosed pulmonary artery puncture sites (3 of 10; 30%), pneumothorax (1 of 11; 9.1%), and hemopericardium (1 of 11; 9.1%), spontaneously resolved without complication-specific treatment. The mean pulmonary arterial pressure was 32 ± 17.6 mmHg. All animals survived the procedure and reached the end of the follow-up period. CONCLUSIONS: CT-guided TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. KEY POINTS: ⢠TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. ⢠This novel approach allows for faster access to the pulmonary artery, and it might be easier to operate the tip of the catheter to super-select the intent branch of the pulmonary artery. ⢠TPAC can be an alternative pulmonary artery intervention pathway in patients with mechanical right-heart valves, great-vessel transposition, and other obstacles.
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Cateterismo de Swan-Ganz , Prótesis Valvulares Cardíacas , Animales , Humanos , Arteria Pulmonar/diagnóstico por imagen , Punciones , Porcinos , Tomografía Computarizada por Rayos XRESUMEN
Objective: To investigate the effects and its mechanisms of silence information regulator 7(SIRT7)on mouse renal podocytes proliferation and apoptosis under high glucose environment. Methods: Mouse renal podocytes cultured with high glucose and treated with different methods were divided into the following groups:control group(Control),high glucose group(HG),high glucose+transfecting with SIRT7 overexpression vetor(pcDNA3.1-SIRT7) group(SIRT7 OE+HG),high glucose+transfecting with the negative control vetor(pcDNA3.1)group(SIRT7 OE-NC+HG),high glucose+transfecting with small interfering RNA-SIRT7 (siRNA-SIRT7) group (siRNA-SIRT7+HG), high glucose+ transfecting with siRNA-SIRT7 control group (siRNA-SIRT7-NC+ HG). Viability of proliferation was examined by CCK-8 method.Rate of apoptosis was detected by flow cytometry. The level of SIRT7 mRNA expression was measured by qRT-PCR. Western blot was performed to detect the protein expression of Nephrin and key factors of Wnt/ß-catenin signaling pathway. Results: The CCK-8 result showed that,compared with control group, the proliferative activity of mouse renal podocytes in HG group was decreased (Pï¼0.05). After transfected with SIRT7 overexpression vetor or small interfering RNA-SIRT7,compared to HG group,the cell proliferation activity was further decreased in siRNA-SIRT7 group(Pï¼0.05),but it was enhanced in SIRT7 OE+HG group (Pï¼0.05). The results of flow cytometry showed that compared with the control group, the apoptosis rate of cells in the HG group was increased (Pï¼0.05). Compared with the HG group, the apoptosis rate of cells in the siRNA SIRT7+HG group was increased significantly(Pï¼0.05), while that in the SIRT7 OE+HG group was decreased (Pï¼0.05). Compared with control group,the expressions of Nephrin, Wnt5a and ß-catenin were inhibited in HG group (Pï¼0.05). compared to HG group,siRNA-SIRT7 could down-regulate the expression levels of Nephrin, Wnt5a and ß-catenin in siRNA-SIRT7 group (Pï¼0.05), SIRT7 overexpression could up-regulate the expression levels of Nephrin, Wnt5a and ß-catenin in SIRT7 OE+HG group (Pï¼0.05). Conclusion: The findings suggest that high glucose environment is an important factor to inhibit the proliferation and induce apoptosis of mouse renal podocytes.Overexpression of SIRT7 can reverse the effects by activating Wnt/ß-catenin signaling pathway and up-regulating ß-catenin expression.
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Podocitos , beta Catenina , Animales , Ratones , Apoptosis , ARN Interferente Pequeño , Proliferación Celular , GlucosaRESUMEN
Background: Knowledge about the prognostic role of long noncoding RNA (lncRNA) in colorectal cancer (CRC) is limited. Therefore, we constructed a lncRNA-related prognostic model based on data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Materials and Methods: CRC transcriptome and clinical data were downloaded from the GSE20916 dataset and the TCGA database, respectively. R software was used for data processing and analysis. The differential lncRNA expression within the two datasets was first screened, and then intersections were measured. Cox regression and the Kaplan-Meier method were used to evaluate the effects of various factors on prognosis. The area under the curve (AUC) of the receiver operating characteristic curve and a nomogram based on multivariate Cox analysis were used to estimate the prognostic value of the lncRNA-related model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to elucidate the significantly involved biological functions and pathways. Results: A total of 11 lncRNAs were crossed. The univariate Cox analysis screened out two lncRNAs, which were analyzed in the multivariate Cox analysis. A nomogram based on the two lncRNAs and other clinicopathological risk factors was constructed. The AUC of the nomogram was 0.56 at 3 years and 0.71 at 5 years. The 3-year nomogram model was compared with the ideal model, which showed that some indices of the 3-year model were consistent with the ideal model, suggesting that our model was highly accurate. The GO and KEGG enrichment analyses showed that positive regulation of secretion by cells, positive regulation of secretion, positive regulation of exocytosis, endocytosis, and the calcium signaling pathway were differentially enriched in the two-lncRNA-associated phenotype. Conclusions: A two-lncRNA prognostic model of CRC was constructed by bioinformatics analysis. The model had moderate prediction accuracy. LncRNA BBOX1-AS1 and lncRNA FOXP4-AS1 were identified as prognostic biomarkers.
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Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Estimación de Kaplan-Meier , Biología Computacional , Neoplasias Colorrectales/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Factores de Transcripción Forkhead/genéticaRESUMEN
Glaucoma is a neurodegenerative disease that causes progressive, irreversible vision loss. Currently, intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, glaucomatous degeneration may continue despite adequate IOP control. Therefore, there exists a need for treatment that protects the visual system, independent of IOP. This study sought, first, to longitudinally examine the neurobehavioral effects of different magnitudes and durations of IOP elevation using multi-parametric magnetic resonance imaging (MRI), optokinetics and histology; and, second, to evaluate the effects of oral citicoline treatment as a neurotherapeutic in experimental glaucoma. Eighty-two adult Long Evans rats were divided into six groups: acute (mild or severe) IOP elevation, chronic (citicoline-treated or untreated) IOP elevation, and sham (acute or chronic) controls. We found that increasing magnitudes and durations of IOP elevation differentially altered structural and functional brain connectivity and visuomotor behavior, as indicated by decreases in fractional anisotropy in diffusion tensor MRI, magnetization transfer ratios in magnetization transfer MRI, T1-weighted MRI enhancement of anterograde manganese transport, resting-state functional connectivity, visual acuity, and neurofilament and myelin staining along the visual pathway. Furthermore, 3 weeks of oral citicoline treatment in the setting of chronic IOP elevation significantly reduced visual brain integrity loss and visual acuity decline without altering IOP. Such effects sustained after treatment was discontinued for another 3 weeks. These results not only illuminate the close interplay between eye, brain, and behavior in glaucomatous neurodegeneration, but also support a role for citicoline in protecting neural tissues and visual function in glaucoma beyond IOP control.
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Citidina Difosfato Colina/farmacología , Presión Intraocular/efectos de los fármacos , Nootrópicos/farmacología , Nervio Óptico/efectos de los fármacos , Vías Visuales/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Imagen de Difusión Tensora , Medidas del Movimiento Ocular , Femenino , Glaucoma , Imágenes de Resonancia Magnética Multiparamétrica , Vías Nerviosas/efectos de los fármacos , Enfermedades Neurodegenerativas/fisiopatología , Hipertensión Ocular/fisiopatología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Espectroscopía de Protones por Resonancia Magnética , Desempeño Psicomotor/efectos de los fármacos , Ratas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Agudeza Visual/efectos de los fármacos , Vías Visuales/diagnóstico por imagen , Vías Visuales/patologíaRESUMEN
To study the difference in transcriptome level of fatty acid metabolism pathway in Bamei pork and the difference of pork quality caused by the difference. In this study, Bamei pigs breeding in Huzhu farm of QingHai province were selected as the test object, compared with Gansu Black pigs. Four indexes of nutmeg acid (DX1), palmitic acid (DX2), stearic acid (DX3) and linoleic acid (DX4) were set. The expression profiles of fat metabolism related genes between the two groups samples were analysed by GCMS metabolomics and transcriptomics, then coexpression network analysis were conducted to obtain phenotypic related genes. The results showed that the metabolic levels of DX3 and DX4 were significantly higher than those of other fatty acids. Among these differences, the ENSSSCG00000024681 (G1) and ENSSSCG00000036883 (G2) genes play important regulatory roles in fatty acid metabolism, and the upregulated expression of their gene obviously affects the level of fatty acid metabolism, thereby affecting the quality and taste of pork. In addition, we found that there was a good correlation between the same lines, and the genetic traits of the hybrid lines of Bamei pig and Black pig are more inclined to Bamei pig. In the independent fatty acid metabolism, "Mg2+"and flavin adenine dinucleotide are more active, which plays an important role in energy utilization. Therefore, we can be inferred that the metabolism of stearic acid and linoleic acid are important fatty acids for pork quality. It also further confirms that the research method of combined omics is of great significance for the study of species traits and gene functions.
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Ácidos Grasos , Metabolismo de los Lípidos , Metaboloma , Carne de Cerdo , Transcriptoma , Animales , Especificidad de la Especie , PorcinosRESUMEN
Making osteoblast migration manageably target to injury sites has been the key challenging in cell therapy for bone and cartilage regeneration. Superparamagnetic materials, the magnetic guide for cell migration, have been applied to increase cell retention. However, additional targeting modifications are still needed to accelerate the low uptake efficiency and moving speed. Arg-Gly-Asp peptide (RGD)-functionalized magnetic nanoparticles showed cutting-edge competence in cell differentiation control and targeted drug delivery. However, more evidence was required to corroborate its role in osteoblast migration in bone repair. In the present study, RGD-modified γ-Fe2O3 nanoparticles (RGD-Fe2O3 NPs) were prefabricated with the grafting ratio of 33.3-37.4%. The RGD-Fe2O3 NPs unveiled excellent water dispersibility with uniform size distribution at 5-6 nm and negligibly low cytotoxicity. As a result, MC3T3-E1 osteoblasts treated with RGD-Fe2O3 NPs boosted its migration speed in a magnetic field compared with those incubated with unmodified Fe2O3 NPs. Furthermore, osteoblasts treated with RGD-Fe2O3 NPs exhibited more Fe uptake. The results exposed the fact that RGD-mediated specific cellular uptake presented higher efficiency than the non-RGD-mediated one, resulting from a stronger superparamagnetic force between the labeled cells and the magnetic field. These findings indicate that the RGD-functionalized Fe2O3 NPs can promote osteoblast migration in the magnetic field, providing a promising strategy in magnet-guided cell therapy for bone and cartilage regeneration.
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Nanopartículas Magnéticas de Óxido de Hierro , Oligopéptidos/farmacología , Osteoblastos/efectos de los fármacos , Células 3T3 , Animales , Movimiento Celular , RatonesRESUMEN
The incidence of septic acute kidney injury (AKI) is increasing, it has become a major threat to human health because of its acute onset, poor prognosis, and high hospital costs. The most common cause of AKI in critical-care units is sepsis. Septic AKI is a complex and multi-factorial process; its pathogenesis is not fully understood. In sepsis, the destruction of mucosal barriers, intestinal flora disorders, intestinal ischemia/reperfusion injury, use of antibiotics, and lack of intestinal nutrients lead to an inflammatory reactions that in turn affects the metabolism and immunity of the host. Such changes further influence the occurrence and development of AKI. New technology is enabling various detection methods for intestinal flora. Clinical application of these methods in septic renal injury is expected to clarify the relationship among pathogenesis, disease progression mechanism, and intestinal flora.
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Lesión Renal Aguda/microbiología , Animales , Microbioma Gastrointestinal/fisiología , Humanos , Riñón/microbiología , Sepsis/microbiologíaRESUMEN
BACKGROUND: Prediabetes is an intermediate state in which blood glucose is higher than normal but does not meet the diagnostic criteria for diabetes. Diffusion tensor imaging (DTI) is an MRI method that can sensitively detect microscopic lesions in the white matter of the brain, but most previous DTI studies only focused on patients with diabetes, and little is known about prediabetes. PURPOSE: To investigate the changes in the microstructure of brain white matter in prediabetes patients using DTI and trace-based spatial statistics (TBSS). STUDY TYPE: Prospective. POPULATION: Sixty subjects (30 patients with prediabetes and 30 healthy volunteers) were enrolled. FIELD STRENGTH/SEQUENCE: 3.0T/DTI-MRI sequence with single-shot echo-planar imaging sequence (SE-EPI). ASSESSMENT: DTI data were collected and analyzed using the TBSS method in the FMRIB software library. STATISTICAL TESTS: DTI using a two-sample t-test. Pearson correlation analysis was performed on DTI values and neuropsychology scale results (mini-mental state examination [MMSE], Montreal cognitive assessment [MoCA], self-rating anxiety scale [SAS], and self-rating depression scale [SDS]) RESULTS: Compared with the control group, the fractional anisotropy (FA) values in the right part of the corpus callosum body (bCC) (P = 0.035), the right superior longitudinal fasciculus (SLF.R) (P = 0.047), and the left superior longitudinal fasciculus (SLF.L) in the prediabetic group were reduced (P = 0.040). DATA CONCLUSION: DTI as a noninvasive technique can assess early changes in the white matter microarchitecture of patients with prediabetes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1105-1112.
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Imagen de Difusión Tensora , Estado Prediabético/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Anciano , Glucemia/análisis , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios Prospectivos , Programas InformáticosRESUMEN
OBJECTIVE: To investigate the value of joint score of platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI) to predict postoperative recurrence and mortality of patients with hepatocellular carcinoma (HCC) after liver resection. METHODS: Clinical data of HCC patients within Milan criteria who underwent liver resection at our center were retrospectively reviewed (n=269). The preoperative PLR and PNI of all patients were measured, and. the score of PLR+PNI was calculated. The patients with high PLR (≥150) and low PNI <45) were allocated a score of 2; while the patients had one or neither of these elevations were allocated a score of 1 or 0, respectively. Postoperative survival was estimated by Kaplan-Meier method with log-rank test. Multivariate analysis used Cox regression model. RESULTS: Multivariate analysis showed microvascular invasion, high alpha-fetoprotein (AFP) level, multiple tumors and PLR+PNI score were associated with postoperative recurrence. Microvascular invasion, transfusion and PLR+PNI score were independent risks factors for overall survival. The 5-year recurrence-free survival rates for the patient with PLR+PNI score of 0, 1, 2 were 43.4%, 27.8%, and 19.9% respectively (P<0.001). The 5-year overall survival rates were 84.1%, 72.3%, and 17.7% respectively (P<0.001). CONCLUSION: High PLR+PNI score seems related to high incidence of postoperative recurrence and low long-term survival in the patients with HCC after liver resection.
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Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Evaluación Nutricional , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Recuento de Linfocitos , Recurrencia Local de Neoplasia , Recuento de Plaquetas , Pronóstico , Estudios RetrospectivosRESUMEN
Ahead of Print article withdrawn by publisher.
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Although elevated intraocular pressure (IOP) and age are major risk factors for glaucoma, their effects on glaucoma pathogenesis remain unclear. This study examined the onset and progression of glaucomatous changes to ocular anatomy and physiology, structural and physiological brain integrity, and visuomotor behavior in the DBA/2J mice via non-invasive tonometry, multi-parametric magnetic resonance imaging (MRI) and optokinetic assessments from 5 to 12 months of age. Using T2-weighted MRI, diffusion tensor MRI, and manganese-enhanced MRI, increasing IOP elevation at 9 and 12 months old coincided with anterior chamber deepening, altered fractional anisotropy and radial diffusivity of the optic nerve and optic tract, as well as reduced anterograde manganese transport along the visual pathway respectively in the DBA/2J mice. Vitreous body elongation and visuomotor function deterioration were observed until 9 months old, whereas axial diffusivity only decreased at 12 months old in diffusion tensor MRI. Under the same experimental settings, C57BL/6J mice only showed modest age-related changes. Taken together, these results indicate that the anterior and posterior visual pathways of the DBA/2J mice exhibit differential susceptibility to glaucomatous neurodegeneration observable by in vivo multi-modal examinations.
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Envejecimiento , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Ojo/fisiopatología , Glaucoma/fisiopatología , Presión Intraocular , Vías Visuales/fisiopatología , Animales , Femenino , Imagen por Resonancia Magnética/métodos , Masculino , Ratones , Ratones Endogámicos DBA , Nervio Óptico/fisiopatologíaRESUMEN
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in the development of atherosclerosis (AS), and the presence of homocysteine (Hcy) acts as an independent risk factor for AS. However, the underlying mechanisms remain to be elucidated. Phosphatase and tensin homologue on chromosome 10 (PTEN), is endogenously expressed in VSMCs and induces multiple signaling networks involved in cell proliferation, survival and inflammation, however, the specific role of PTEN is still unknown. The present study detected the proliferation ratio of VSMCs following treatment with Hcy and Resveratrol (RSV). In the 100 µM Hcy group, the proliferation ratio increased, and treatment with RSV decreased the proliferation ratio induced by Hcy. Reverse transcriptionquantitative polymerase chain reaction and western blotting were used to analyze PTEN expression, RSV treatment was associated with decreased PTEN expression levels in VSMCs. PTEN levels were decreased in Hcy treated cells, and the proliferation ratio of VSMCs were increased following treated with Hcy. To study the mechanism of regulation of PTEN by Hcy, the present study detected PTEN methylation levels in VSMCs, and PTEN DNA methylation levels were demonstrated to be increased in the 100 µM Hcy group, whereas treatment with RSV decreased the methylation status. DNA methyltransferase 1 is important role in the regulation of PTEN methylation. Overall, Hcy impacts the methylation status of PTEN, which is involved in cell proliferation, and induces the proliferation of VSMCs. This effect is alleviated by treatment with RSV, which exhibits an antagonistic mechanism against Hcy.
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Metilación de ADN/genética , Regulación de la Expresión Génica/efectos de los fármacos , Homocisteína/metabolismo , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/metabolismo , Fosfohidrolasa PTEN/genética , Estilbenos/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Homocisteína/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Fosfohidrolasa PTEN/metabolismo , ResveratrolRESUMEN
A specific, precise and accurate high performance liquid chromatographic (HPLC) analytical method with a fluorescence detector (FLD) was established for the simultaneous determination of nine bisphenols (BPs) in milk samples. Samples were extracted ultrasonically with acetonitrile and cleaned using the QuEChERS technique. Under the optimized conditions, good linearity was obtained for the nine BPs and the correlation coefficients (R2) ranged from 0.9942 to 0.9997. Recovery values for the nine bisphenols in spiked samples were 75.82-93.86% with intra-day and inter-day relative standard deviations (RSDs) from 2.6 to 11.1%. The limits of detection (LODs) and quantification (LOQs) were 1.0-3.1⯵g/kg and 3.5-9.8⯵g/kg, respectively. The results demonstrated clearly that the approach developed provides reliable, simple, rapid and environmentally-friendly quantification and identification of nine bisphenols in a fatty matrix and could be used for monitoring bisphenols in milk.
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Cromatografía Líquida de Alta Presión/métodos , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Leche/química , Fenoles/análisis , Animales , Compuestos de Bencidrilo/análisis , Fluorescencia , Límite de DetecciónRESUMEN
Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner. Knockdown of Cyclin A prominently reduced proliferation of EPCs, while over-expression of Cyclin A significantly promoted the cell proliferation, suggesting that Hcy inhibits EPCs proliferation through downregulation of Cyclin A expression. In addition, epigenetic study also demonstrated that Hcy induces DNA hypomethylation of the Cyclin A promoter in EPCs through downregulated expression of DNMT1. Moreover, we found that Hcy treatment of EPCs leads to increased SAM, SAH and MeCP2, while the ratio of SAM/SAH and MBD expression decrease. In summary, our results indicate that Hcy inhibits Cyclin A expression through hypomethylation of Cyclin A and thereby suppress EPCs proliferation. These findings demonstrate a novel mechanism of DNA methylation mediated by DNMT1 in prevention of Hcy associated cardiovascular disease.
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Proliferación Celular/fisiología , Ciclina A/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN/fisiología , Células Progenitoras Endoteliales/metabolismo , Homocisteína/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo/fisiología , Epigénesis Genética/fisiología , Humanos , Regiones Promotoras Genéticas/fisiología , RatasRESUMEN
Atherosclerosis (AS) is a progressive disease of multifactorial origin, which occurs in response to endothelial injury. Increased homocysteine (Hcy) is considered a major cause of endothelial dysfunction, oxidative stress and DNA methylation; however, the mechanisms remain to be fully elucidated. The aim of the present study was to investigate whether Hcy causes injury to endothelial cells (ECs) by the effect of lectinlike oxidizedlow density lipoprotein receptor1 (LOX1) DNA methylation through tolllike receptor 4(TLR4)/nuclear factor (NF)κB/DNA methyltransferase (DNMT)1. The ECs were treated with different concentrations of Hcy, and it was found that Hcy promoted the expression of TLR4, leading to EC injury. The effect of oxidative stress was analyzed by measuring superoxide dismutase, malondialdehyde and hydrogen peroxide in the ECs. In addition, the association between NFκB and DNMT1 was examined by treatment of the ECs with pyrrolidine dithiocarbamate (PDTC). The results suggested that Hcy induced LOX1 DNA hypomethyaltion to promote the expression levels of LOX1. Taken together, Hcy injured the ECs through the effect of methylation and transsulfuration metabolism of LOX1 through TLR4/NFκB/DNMT1. Following injury to the ECs, lipids, particularly oxLDL, accumulated in the subendothelial layer to promote the formation of AS.
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ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN , Células Endoteliales/metabolismo , Homocisteína/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Receptores Depuradores de Clase E/genética , Receptor Toll-Like 4/metabolismo , Biomarcadores , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Regulación de la Expresión Génica , Homocisteína/farmacología , Humanos , Peróxido de Hidrógeno , Lipoproteínas LDL , Superóxido Dismutasa/metabolismo , Receptor Toll-Like 4/genéticaRESUMEN
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of plateletderived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2). Hypomethylation was observed to occur in the promoter region of PDGF, hypermethylation in p53, PTEN and MFN2, and hypomethylation in two global methylation indicators, aluminium (Alu) and long interspersed nucleotide element1 (Line1). This was accompanied by an increase in the expression of PDGF, and reductions of p53, PTEN and MFN2, both in mRNA and protein levels. An elevation of Sadenosylmethionine (SAM) and a reduction of Sadenosylhomocysteine (SAH) and the SAM/SAH ratio were also identified. In conclusion, Hcy impacted methylation the of ASassociated genes and global methylation status that mediate the cell proliferation, which may be a character of VSMCs treated with Hcy. The data provided evidence for mechanisms of VSMCs proliferation in AS induced by Hcy and may provide a new perspective for AS induced by Hcy.
Asunto(s)
Metilación de ADN/efectos de los fármacos , Epigénesis Genética , Homocisteína/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Regiones Promotoras Genéticas , Elementos Alu , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/patología , Proliferación Celular/efectos de los fármacos , Islas de CpG , Femenino , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Humanos , Elementos de Nucleótido Esparcido Largo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Modelos Biológicos , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Cultivo Primario de Células , S-Adenosilhomocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Venas Umbilicales/citología , Venas Umbilicales/efectos de los fármacos , Venas Umbilicales/metabolismoRESUMEN
A microporous Pb-based metal-organic framework (MOF) [Pb(4,4'-ocppy)2]·7H2O (Pb-MOF) has been constructed from 4-(4-carboxyphenyl)pyridine N-oxide and Pb(NO3)2. Structural analysis reveals that the Pb-MOF possesses three-dimensional framework with a one-dimensional rhombic channel. When tested as a lithium-ion battery anode, a reversible lithium storage capacity of 489 mAh g-1 was maintained after 500 cycles at 100 mA g-1 as well as excellent cycling stability. The superior electrochemical performance may be derived from the sustenance of the Pb-MOF framework and compositional features of the organic moiety.