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Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.
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Doenças Cardiovasculares , Sulfeto de Hidrogênio , MicroRNAs , Sulfeto de Hidrogênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Animais , Regulação da Expressão Gênica , Biomarcadores/metabolismoRESUMO
BACKGROUND: Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors. METHODS: The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis. RESULTS: 266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78-0.88) and 0.87 (95%CI, 0.80-0.94). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.
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Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Função Retardada do Enxerto , Nomogramas , Sobrevivência de Enxerto , Rim , Doadores de Tecidos , Biópsia/efeitos adversos , Fatores de RiscoRESUMO
OBJECTIVE: The study aimed at association of family life, resilience and bullying on the use of tobacco in preadolescents. METHODS: A total of 4792 students from 5 junior schools in Baise City were recruited with cluster-sampling method, filled with questionnaire of family life, resilience, parents' Control, bullying, initiation of tobacco and smoking from Feb. to Nov. 2018.The sample comprised of 52.63% male students and 46.66% female students. The average age was(11.8±0.5). There were 56.78% of students lived in city and 43.22% of students lived in county town; The nationality of the sample was as follows: Zhuang nationality 90.00%, Han nationality 7.62%, other minorities(Yao nationality, Miao nationality, Yi nationality, et al)2.05%. The Logistic regression was used to explore the effect. RESULTS: There were 9.75% and 6.97% of the sample reported initiation of tobacco and smoking respectively. The initiation of tobacco and smoking of boys were higher than that of girls(initiation of tobacco: χ~2=57.230, P<0.001; smoking: χ~2=56.013, P<0.001). The multivariate Logistic analysis showed gender was statistically significant factor of initiation of tobacco(OR=0.468, 95%CI 0.377-0.582) and smoking(OR=0.422, 95% CI 0.324-0.551), and age was statistically significant factor of initiation of tobacco(OR=1.609, 95% CI 1.446-1.791) and smoking(OR=2.026, 95%CI 1.776-2.310). Bullying was statistically significant factors of smoking(OR=1.106, 95% CI 1.073-1.140). Three protective factors were associated with a lower likelihood of initiation of tobacco(individual power: OR=0.964, 95% CI 0.951-0.976; family cohesion, OR=0.946, 95% CI 0.892-0.984; family rules, OR=0.949, 95%CI 0.930-0.965) and smoking(individual power: OR=0.962, 95% CI 0.947-0.977; family cohesion, OR=0.937, 95%CI 0.885-0.992; family rules, OR=0.952, 95%CI 0.932-0.973)in the final subscale model. CONCLUSION: Bullying increased the risk of smoking, while Individual power, family cohesion and family rules were associated with a lower likelihood of initiation of tobacco and smoking in preadolescents.
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Bullying , Nicotiana , Criança , Humanos , Instituições Acadêmicas , Fumar , Estudantes , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: The alcohol-hypertension relation has been well documented, but whether women have protective effect or race and type of beverage consumed affect the association remain unclear. To quantify the relation between total or beverage-specific alcohol consumption and incident hypertension by considering the effect of sex and race. METHODS AND RESULTS: Articles were identified in PubMed and Embase databases with no restriction on publication date. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random effects models. Restricted cubic splines were used to model the dose-response association. This study involved 22 articles (31 studies) and included 414,477 participants. The hypertension risk was different among liquor, wine, and beer at 5.1-10 g/d of ethanol consumption (P-across subgroups = 0.002). The hypertension risk differed between men (RR: 1.14, 95% CI: 1.07, 1.20) and women (RR: 0.98, 95% CI: 0.89, 1.06) at 10 g/d (P-across subgroups = 0.005). We found a linear alcohol-hypertension association among white (P-linearity = 0.017), black people (P-linearity = 0.035), and Asians (P-linearity<0.001). With 10 g/d increment of consumption, the RRs for hypertension were 1.06 (95% CI: 1.04, 1.08), 1.14 (95% CI: 1.01, 1.28), and 1.06 (95% CI: 1.01, 1.10) for Asians, black, and white people, respectively. CONCLUSION: Sex modifies the alcohol-hypertension association at low level of alcohol consumption and we did not find evidence of a protective effect of alcohol consumption among women. Black people may have higher hypertension risk than Asians and white people at the same ethanol consumption.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/etnologia , Bebidas Alcoólicas/efeitos adversos , Povo Asiático , População Negra , Pressão Sanguínea , Hipertensão/etnologia , População Branca , Cerveja/efeitos adversos , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Incidência , Masculino , Fatores Raciais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Vinho/efeitos adversosRESUMO
Context: Therapeutic doxorubicin administration is restricted as this anticancer drug may be cardiotoxic. The traditional Chinese medicine qiliqiangxin has been approved for clinical treatment of chronic heart failure.Objective: To explore the protective effects and molecular mechanisms of qiliqiangxin on doxorubicin-induced congestive heart failure (CHF) in rats.Materials and methods: A CHF rat model was established via intraperitoneal DOX injections (2.5 mg/kg/week) for 6 weeks. The rats were randomly assigned to control, CHF, CHF + QL (1.0 g/kg/d), or captopril (3.8 mg/kg/d) treatment groups (n = 10) for 4 weeks. MicroRNA sequencing elucidated the molecular mechanisms of qiliqiangxin on doxorubicin-induced CHF in rats.Results: Unlike in the CHF group, QL significantly reduced Bax:Bcl-2 (2.05 ± 0.23 vs. 0.94 ± 0.09, p < 0.05) and the levels of collagen I (0.19 ± 0.02 vs. 0.15 ± 0.01, p < 0.05), collagen III (0.19 ± 0.02 vs. 0.14 ± 0.02, p < 0.05), TGF-ß1 (5.28 ± 0.89 vs. 2.47 ± 0.51, p < 0.05), Smad3 (1.23 ± 0.12 vs. 0.78 ± 0.09, p < 0.05), MMP-2 (0.89 ± 0.01 vs. 0.53 ± 0.05, p < 0.05), and TIMP-2 (0.24 ± 0.03 vs. 0.44 ± 0.03, p < 0.05). QL also upregulated TGF-ß3 (0.65 ± 0.06 vs. 0.96 ± 0.10, p < 0.05) and Smad7 (0.09 ± 0.01 vs. 0.19 ± 0.023, p < 0.05). Moreover, Smad3 was a target of miR-345-3p.Discussion and Conclusions: The beneficial effects of QL on DOX-induced CHF in rats are mediated by reduction in myocardial fibrosis, promotion of TGF-ß3/Smad7, and inhibition of TGF-ß1/Smad3. QL may also modulate specific miRNAs. These results provide evidence that QL might be an effective treatment for DOX-induced CHF.
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Doxorrubicina/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/patologia , Masculino , Ratos , Ratos Wistar , Remodelação Ventricular/fisiologiaRESUMO
The aim of this study is to improve our understanding of the mechanisms involved in maternal-fetal immune tolerance. We searched the related literatures and overviewed the major antibodies associated with pregnancy and described in details their possible roles in mediating maternal-fetal interactions. Antibodies classified into different types based on their functional or structural characteristics were summarized, including immunoglobulin G, blocking antibody, nonprecipitating asymmetric antibody, antiphospholipid antibody, antitrophoblast antibody and antipaternal antibody. The presence and levels of various circulating antibodies in pregnancy may play a crucial role in the occurrence, development and termination of pregnancy.
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Anticorpos , Feto/imunologia , Troca Materno-Fetal/imunologia , Gravidez/imunologia , Anticorpos/classificação , Feminino , HumanosRESUMO
PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS: Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed. RESULTS: Corneal tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm-1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.
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Comprimento Axial do Olho/fisiopatologia , Córnea/fisiopatologia , Miopia Degenerativa/fisiopatologia , Adulto , Córnea/patologia , Topografia da Córnea , Elasticidade , Feminino , Humanos , Pressão Intraocular , Masculino , Miopia Degenerativa/diagnóstico , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUNDS: Breast cancer screening plays an important role in the early detection, diagnosis and treatment of breast cancer. The aim of this study was to evaluate the screening results and explore the influencing factors of breast cancer detection rate in Guangdong. METHODS: This cross-sectional study was conducted among 2,024,960 women aged 35-64 in Guangdong Province during 2017-2021. The data about breast cancer screening information were collected from the Guangdong maternal and child health information system. Descriptive statistical analysis was used to explain demographic characteristics and results of breast cancer screening. The generalized linear regression model was applied to analyze the related influencing factors of breast cancer detection rate. RESULTS: The estimated detection rate of breast cancer in Guangdong Province is 70.32/105, with an early diagnosis rate of 82.06%. After adjusting covariates, those women with older age (45-55 [OR (95% CI) 2.174 (1.872, 2.526)], 55-65 [OR (95% CI) 2.162 (1.760, 2.657)]), education for high school ([OR (95% CI) 1.491 (1.254, 1.773)]) and older age at first birth ([OR (95% CI) 1.632 (1.445, 1.844)]) were more likely to have higher detection rate of breast cancer. No history of surgery or biopsy ([OR (95% CI) 0.527 (0.387, 0.718)]), no history of breast cancer check ([OR (95% CI) 0.873 (0.774, 0.985)]) and no family history of breast cancer ([OR (95% CI) 0.255 (0.151, 0.432)]) women were more likely to screen negative for breast cancer (P < 0.05). CONCLUSION: The detection rate of breast cancer in screening showed an increasing trend year by year in Guangdong Province. Older age, education for high school and older age at first birth were risk factors for breast cancer detection rate, while no surgery or biopsy history, no family history of breast cancer and no history of breast cancer check were protective factors.
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Neoplasias da Mama , Detecção Precoce de Câncer , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Feminino , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Pessoa de Meia-Idade , Adulto , China/epidemiologia , Estudos Transversais , Mamografia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodosRESUMO
AIMS: Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. METHODS: Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). RESULTS: Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20 mmol/mol]-4.4% [25 mmol/mol]), moderate-stable (range 4.6% [27 mmol/mol]-5.1% [32 mmol/mol]), and elevated-increasing (range 5.0% [31 mmol/mol]-5.6% [38 mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively. CONCLUSIONS: Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy.
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Our aim was to explore the dose-dependent diastolic dysfunction and the mechanisms of heart failure and early death in transgenic (TG) mice modeling human restrictive cardiomyopathy (RCM). The first RCM mouse model (cTnI(193His) mice) carrying cardiac troponin I (cTnI) R193H mutation (mouse cTnI R193H equals to human cTnI R192H) was generated several years ago in our laboratory. The RCM mice manifested a phenotype similar to that observed in RCM patients carrying the same cTnI mutation, i.e. enlarged atria and restricted ventricles. However, the causes of heart failure and early death observed in RCM mice remain unclear. In this study, we have produced RCM TG mice (cTnI(193His)-L, cTnI(193His)-M and cTnI(193His)-H) that express various levels of mutant cTnI in the heart. Histological examination and echocardiography were performed on these mice to monitor the time course of the disease development and heart failure. Our data demonstrate that cTnI mutation-caused diastolic dysfunction is dose-dependent. The key mechanism is myofibril hypersensitivity to Ca(2+) resulting in an impaired relaxation in the mutant cardiac myocytes. Prolonged relaxation time and delay of Ca(2+) decay observed in the mutant cardiac myocytes are correlated with the level of the mutant protein in the heart. Markedly enlarged atria due to the elevated end-diastolic pressure and myocardial ischemia are observed in the heart of the transgenic mice. In the mice with the highest level of the mutant protein, restricted ventricles and systolic dysfunction occur followed immediately by heart failure and early death. Diastolic dysfunction caused by R193H troponin I mutation is specific, showing a dose-dependent pattern. These mouse models are useful tools for the study of diastolic dysfunction. Impaired diastole can cause myocardial ischemia and fibrosis formation, resulting in the development of systolic dysfunction and heart failure with early death in the RCM mice with a high level of the mutant protein in the heart.
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Miócitos Cardíacos/metabolismo , Troponina I/genética , Animais , Western Blotting , Cálcio/metabolismo , Cardiomiopatias/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Ecocardiografia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MutaçãoRESUMO
Hydrogen sulfide (H2S) and sulfur dioxide (SO2), recognized as endogenous sulfur-containing gas signaling molecules, were the third and fourth molecules to be identified subsequent to nitric oxide and carbon monoxide (CO), and exerted diverse biological effects on the cardiovascular system. However, the exact mechanisms underlying the actions of H2S and SO2 have remained elusive until now. Recently, novel post-translational modifications known as S-sulfhydration and S-sulfenylation, induced by H2S and SO2 respectively, have been proposed. These modifications involve the chemical alteration of specific cysteine residues in target proteins through S-sulfhydration and S-sulfenylation, respectively. H2S induced S-sulfhydrylation can have a significant impact on various cellular processes such as cell survival, apoptosis, cell proliferation, metabolism, mitochondrial function, endoplasmic reticulum stress, vasodilation, anti-inflammatory response and oxidative stress in the cardiovascular system. Alternatively, S-sulfenylation caused by SO2 serves primarily to maintain vascular homeostasis. Additional research is warranted to explore the physiological function of proteins with specific cysteine sites, despite the considerable advancements in comprehending the role of H2S-induced S-sulfhydration and SO2-induced S-sulfenylation in the cardiovascular system. The primary objective of this review is to present a comprehensive examination of the function and potential mechanism of S-sulfhydration and S-sulfenylation in the cardiovascular system. Proteins that undergo S-sulfhydration and S-sulfenylation may serve as promising targets for therapeutic intervention and drug development in the cardiovascular system. This could potentially expedite the future development and utilization of drugs related to H2S and SO2.
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DNA cleavage reaction catalyzed by nucleases is essential in many important biological processes and medicinal chemistry. Therefore, it is important to develop reliable and facile methods to assay nuclease activity. With this goal in mind, we report a fluorescent assay for label-free, facile, and real-time monitoring of DNA cleavage by EcoRI endonuclease using SYBR Green I (SGI) as a signal probe. The fluorescence of SGI dramatically increased when the free SGI was mixed with double-stranded DNA (dsDNA) substrate. Upon interacting with EcoRI, which cleaves the dsDNA into small fragments, the weakened interaction between SGI and the shortened DNA fragments caused a decrease in fluorescence of SGI. EcoRI-DNA interaction was real-time studied by monitoring fluorescence change with the prolonging of interaction time. The important kinetic parameters, including Michaelis-Menten constant (K(M)) and maximum initial velocity (V(max)), were accurately calculated, which is consistent with previously reported studies. Site-specific DNA cleavage by EcoRI endonuclease has also been verified by gel electrophoresis analysis, which indicated that this method is a simple and effective approach to assay DNA cleavage reaction. Specificity investigation demonstrated that EcoRI-DNA interactions can be studied with high selectivity. Compared with previously reported methods, this approach is selective, simple, convenient and cost-efficient without any labeling of the probe or of the target.
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Bioensaio/métodos , Clivagem do DNA , Desoxirribonuclease EcoRI/farmacologia , Sequência de Bases , Sítios de Ligação , Clivagem do DNA/efeitos dos fármacos , Fluorescência , Dados de Sequência Molecular , Estrutura Molecular , Coloração e RotulagemRESUMO
The G-rich overhang of human telomere tends to form a G-quadruplex structure, and G-quadruplex formation can effectively inhibit telomerase activity in most cancer cells. Therefore, it is important to identify the formation and properties of the G-quadruplex, with the particular aim of selecting G-quadruplex-binding ligands that could potentially lead to the development of anticancer therapeutic agents. With this goal in mind, we report a fluorescence resonance energy transfer (FRET) assay system for the identification of G-quadruplex ligands using DNA-functionalized gold nanoparticles (DNA-GNPs) as the fluorescence quencher and a carboxyfluorescein (FAM)-tagged human telomeric sequence (F-GDNA) as the recognition probe. A thiolated complementary strand of human telomeric DNA (cDNA), which first adheres to the surface of the GNPs and then hybridizes with F-GDNA, results in the fluorescence quenching of F-GDNA by the GNPs. However, fluorescence is restored when single-stranded F-GDNA folds into a G-quadruplex structure upon the binding of quadruplex ligands, leading to the release of F-GDNA from the surface of the GNPs. Combined data from fluorescence measurements and CD spectroscopy indicated that ligands selected by this FRET method could induce GDNA to form a G-quadruplex. Therefore, this FRET G-quadruplex assay is a simple and effective approach to identify quadruplex-binding ligands, and, as such, it promises to provide a solid foundation for the development of novel anticancer therapeutic agents.
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DNA/química , Quadruplex G , Ouro/química , Ligantes , Nanopartículas Metálicas/química , Dicroísmo Circular , DNA/metabolismo , Transferência Ressonante de Energia de Fluorescência , Humanos , Modelos BiológicosRESUMO
Allergic asthma which is induced by ovalbumin (OVA) is a chronic airway inflammation disease. Isoorientin (Iso) is a natural C-glucosyl flavone with many biological properties. We aimed to evaluate the effectiveness of Iso on OVA-induced allergic asthma. A total of 30 C57BL/6 mice were randomly divided into five groups: control group, OVA group, Dex (dexamethasone, 10 mg/kg) group, low-dose Iso group (Iso-L, 25 mg/kg), and high-dose Iso group (Iso-H, 50 mg/kg). The serum and bronchoalveolar lavage fluid (BALF) were collected for biochemical parameters, the lung tissue was collected for hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), and western blot. The levels of IL-4, IL-5, IL-13, malondialdehyde (MDA), NO, and reactive oxygen species (ROS) in Iso-L and Iso-H groups were significantly lower than that in model group (p < 0.05). Simultaneously, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were higher than that in model group (p < 0.05). Iso significantly ameliorated airway hyperresponsiveness. Meanwhile, H&E staining revealed that mice treated with Iso resulted in the ameliorated inflammatory cell infiltration and a reduction in interstitial thickening. The nuclear factor erythroid 2-like 2 (Nrf2) and HO-1 protein expression in Iso-L and Iso-H groups were enhanced over that in model group, while p-NF-κB-p65 and p-IκB-α protein expression was decreased (p < 0.05). Our research indicated that Iso alleviated the OVA-induced allergic asthma, and this effect can be explained by the modulation of Nrf2/HO-1 and NF-κB signaling pathway; thus, the results providing a therapeutic rationale for the treatment of Iso on allergic asthma.
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Asma , Luteolina , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Citocinas/metabolismo , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Amarelo de Eosina-(YS)/uso terapêutico , Glutationa Peroxidase , Hematoxilina/uso terapêutico , Interleucina-13 , Interleucina-4 , Interleucina-5 , Luteolina/uso terapêutico , Malondialdeído , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Ovalbumina/efeitos adversos , Espécies Reativas de Oxigênio , Superóxido DismutaseRESUMO
The development of a current collector for Li-ion batteries is of great significance for improving the performance of Li-ion batteries. Tensile property and corrosion performance of the positive electrode current collectors are an indispensable prerequisite for the realization of high-performance Li-ion batteries. In our study, the effects of Ag alloying on the microscopic structure, electrical conductivity, tensile property and corrosion resistance of Al-xCu (x = 0.1-0.15%) alloy foils were investigated. Moderate Ag addition on the Al-Cu alloy could reduce the size of second phases and promote the formation of second phases. The tensile strength of the Al-0.1Cu-0.1Ag alloy was higher than that of the Al-0.1Cu alloy at both room and high temperatures. All of the alloy foils demonstrated high electrical conductivity around 58% ICAS. The corrosion potential and corrosion current density of the Al-0.1Cu alloy were demonstrated by Tafel polarization to be -873 mV and 37.12 µA/cm2, respectively. However, the Al-0.1Cu-0.1Ag alloy showed enhanced corrosion resistance after the Ag element was added to the Al-0.1Cu alloy, and the Al-0.1Cu-0.1Ag alloy had a greater positive corrosion potential of -721 mV and a lower corrosion current density of 1.52 µA/cm2, which suggests that the Ag element could significantly improve the corrosion resistance of the Al-Cu alloy.
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In this paper, we have reported a sensitive assay for fluorescence "turn-on" detection of Pb(2+) in aqueous solutions based on FRET between gold nanorods (GNRs) and the FAM-labeled substrate strand of 8-17DNAzyme. The fluorescence of the FAM-labeled substrate strand is quenched when 8-17DNAzyme is adsorbed on GNRs surface through electrostatic interaction. In the presence of lead ions, the fluorescence is restored due to the decrease of FRET efficiency caused by the specific cleavage of the FAM-labeled substrate strand by the enzyme, which weakens the electrostatic interaction between the GNRs and short FAM-labeled DNA fragment. The interference of eleven common metal ions has been tested, indicating that Pb(2+) can be selectively detected. This method exhibits a high sensitivity for Pb(2+) with a detection limit of 61.8 pM and a linear range from 0.1 nM to 100 nM. It is a simple, sensitive, and selective method for Pb(2+) detection. Moreover, this sensing system obtained satisfying results for Pb(2+) detection in tap water samples.
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DNA Catalítico/metabolismo , Transferência Ressonante de Energia de Fluorescência , Ouro/química , Chumbo/análise , Nanotubos/química , Cátions/química , DNA Catalítico/química , Corantes Fluorescentes/química , RNA/metabolismo , Eletricidade Estática , Água/químicaRESUMO
The accurate measurement of heavy metal ions is essential for human health and environmental protection. Here, we report the design of a simple and convenient bimodal strategy for signal-on, label-free lead ion detection in environmental samples based on two-dimensional metal-organic framework (2D-MOF) nanosheets. 2D-MOFs have different affinities toward guanine-rich DNA (ssGDNA) and the G-quadruplex, allowing these structures to be distinguished. The nanosheets were also used as quenchers for fluorescent lead ion detection. Using lead ions to induce G-quadruplex formation from ssGDNA, a simple fluorescence resonance energy transfer (FRET) strategy was developed for lead ion detection; the detection limit was 3.3 nM. Based on changes in the GDNA configuration, the FRET system was converted into an electrochemical sensor for lead ion assays using an electrode modified with the 2D-MOF nanosheets. Electrochemical impedance spectroscopy showed a high sensitivity and a low limit of detection (i.e., 8.7 pM) of the electrode. The adaptability of the bimodal mechanism was verified through the successful detection of lead ions in tap water and fertilizer samples, and the method accuracy was demonstrated through inductively coupled plasma analysis. The developed bimodal device is cost-effective, highly sensitive, and allows for convenient operation, thereby rendering it a promising and reliable system for the detection of lead ions in environmental samples.
RESUMO
Hypoxic pulmonary vascular remodelling (PVR) is the major pathological basis of aging-related chronic obstructive pulmonary disease and obstructive sleep apnea syndrome. The pulmonary artery endothelial cell (PAEC) inflammation, and pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy and collagen remodelling are the important pathophysiological components of PVR. Endogenous sulfur dioxide (SO2) was found to be a novel gasotransmitter in the cardiovascular system with its unique biological properties. The study was aimed to investigate the role of endothelial cell- (EC-) derived SO2 in the progression of PAEC inflammation, PASMC proliferation, hypertrophy and collagen remodelling in PVR and the possible mechanisms. EC-specific aspartic aminotransferase 1 transgenic (EC-AAT1-Tg) mice were constructed in vivo. Pulmonary hypertension was induced by hypoxia. Right heart catheterization and echocardiography were used to detect mouse hemodynamic changes. Pathologic analysis was performed in the pulmonary arteries. High-performance liquid chromatography was employed to detect the SO2 content. Human PAECs (HPAECs) with lentiviruses containing AAT1 cDNA or shRNA and cocultured human PASMCs (HPASMCs) were applied in vitro. SO2 probe and enzyme-linked immunosorbent assay were used to detect the SO2 content and determine p50 activity, respectively. Hypoxia caused a significant reduction in SO2 content in the mouse lung and HPAECs and increases in right ventricular systolic pressure, pulmonary artery wall thickness, muscularization, and the expression of PAEC ICAM-1 and MCP-1 and of PASMC Ki-67, collagen I, and α-SMA (p < 0.05). However, EC-AAT1-Tg with sufficient SO2 content prevented the above increases induced by hypoxia (p < 0.05). Mechanistically, EC-derived SO2 deficiency promoted HPAEC ICAM-1 and MCP-1 and the cocultured HPASMC Ki-67 and collagen I expression, which was abolished by andrographolide, an inhibitor of p50 (p < 0.05). Meanwhile, EC-derived SO2 deficiency increased the expression of cocultured HPASMC α-SMA (p < 0.05). Taken together, these findings revealed that EC-derived SO2 inhibited p50 activation to control PAEC inflammation in an autocrine manner and PASMC proliferation, hypertrophy, and collagen synthesis in a paracrine manner, thereby inhibiting hypoxic PVR.
Assuntos
Colágeno/metabolismo , Células Endoteliais/metabolismo , Inflamação/metabolismo , Artéria Pulmonar/metabolismo , Remodelação Vascular/fisiologia , Animais , Proliferação de Células , Humanos , Camundongos , Camundongos TransgênicosRESUMO
Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA(-/-)) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA(-/-) mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2Hz), is significantly reduced in MsrA(-/-) cardiac myocytes. MsrA(-/-) cardiac myocytes also show a significant decrease in contractility after oxidative stress using H(2)O(2). Corresponding changes in Ca(2+) transients are observed in MsrA(-/-) cardiomyocytes treated with 2Hz stimulation or with H(2)O(2). Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA(-/-) mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA(-/-) mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.