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1.
Colloids Surf B Biointerfaces ; 223: 113141, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36682296

RESUMO

Dopamine is a small molecule inspired by the dopamine motif of mussel foot proteins, and PDA is formed by the self-polymerization of dopamine. Under the UV-irradiation,PDA would be oxidized by reactive oxygen species (ROS) which were produced by photocatalytic reactions on TiO2 surfaces,thus regulating the adhesion behavior of endothelial cells (ECs) TiO2 inhibited platelet (Plt) adhesion after UV exposure. Polydopamine (PDA)-TiO2 micropatterns (P-PDA-TiO2) were prepared by magnetron sputtering and photolithography. This micropatterns successfully achieves selective adhesion of Plt and ECs. The selective adhesion of ECs disappears after vacuum reduction. In contrast to conventional cell patterning strategies, P-PDA-TiO2 can easily achieve pattern separation of ECs and Plts and provide a new concept for building complex blood-contacting devices.

2.
Biomed Pharmacother ; 159: 114285, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36706630

RESUMO

Tea consumption has been linked to a decreased risk of cardiovascular disease (CVD) mortality, which imposes a heavy burden on the healthcare system; however, which components in tea cause this beneficial effect is not fully understood. Here we uncovered a cystatin (namely CsCPI1), which is a cysteine proteinase inhibitor (CPI) of the tea plant (Camellia sinensis) that promotes antithrombotic activity. Since thrombosis is a common pathogenesis of fatal CVDs, we investigated the effects of CsCPI1, which showed good therapeutic effects in mouse models of thrombotic disease and ischemic stroke. CsCPI1 significantly increases endothelial cell production of nitric oxide (NO) and inhibits platelet aggregation. Notably, CsCPI1 exhibited no cytotoxicity or resistance to pH and temperature changes, which indicates that CsCPI1 might be a potent antithrombotic agent that contributes to the therapeutic effects of tea consumption against CVD. Specifically, the antithrombotic effects of CsCPI1 are distinct from the classical function of plant cystatins against herbivorous insects. Therefore, our study proposes a new potential role of cystatins in CVD prevention and treatment, which requires further study.

3.
Org Biomol Chem ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655625

RESUMO

We report herein a cationic iridium-catalysed thioether-directed alkyne-azide cycloaddition reaction. Diverse 2-alkynyl phenyl sulfides can undergo cycloaddition with different azides in a regioselective fashion. The reaction features high efficiency, a short reaction time, and a broad substrate scope, providing modular access to complex S-containing triazoles.

4.
J Biomater Appl ; : 8853282231151230, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633217

RESUMO

Dopamine has been widely used for surface modification of cardiovascular medical devices as it forms films on most substrates that provide functional groups for surface chemical modification. However, under oxidative stress, the phenolic hydroxyl group on dopamine can undergo reversible transformation into phenol-semiquinone-quinone, which can cause cytotoxicity and immunotoxicity. In this study, we measured the effects of semiquinone on the behavior of vascular wall cells and inflammatory cells under oxidative stress via ultraviolet irradiation with a hydrogen peroxide diluent. Na2S2O3 was used as a stabilizer to obtain a semiquinone-rich poly-dopamine film, then phenol-semiquinone-quinone ratio on its surface was evaluated at three irradiation-oxidation time points. We found that the poly-dopamine film with ultraviolet irradiation in hydrogen peroxide solution for 15 min had the highest semiquinone occupancy of 19.18%. In the experimental group irradiated for 15 min, endothelial cells were cultured statically for 3 days and the number of surface adherent endothelial cells in the group with added semiquinone stabilizer was reduced to 73% of that in the group without stabilizer, indicating that semiquinone rich surface inhibits adhesion and proliferation of endothelial cells; Smooth muscle cells were cultured statically for 3 days, and the number of adherent smooth muscle on surfaces without stabilizer was reduced to 75% of that on surfaces with stabilizer added, indicating that semiquinone rich surfaces promote smooth muscle proliferation. These results demonstrate that semiquinone can adversely affect the repair effect after implantation of cardiovascular materials. Therefore, our study provides a reference for the application and optimization of dopamine in cardiovascular implant materials.

5.
Int J Mol Med ; 51(3)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36704846

RESUMO

Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)­specific FLNA­deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia­induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)­PAK­1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p­PAK­1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH.

6.
Eur J Hosp Pharm ; 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564159

RESUMO

Hydrocortisone is widely used for the anti-inflammatory and immunosuppressive effects and physiological substitute of endogenous glucocorticoid. Allergic reaction to hydrocortisone is infrequent, but once it occurs, it can affect the disease profile or survival of patients. The present study reported a case of hydrocortisone-induced blood pressure reduction in a patient with anterior pituitary hypofunction due to allergic reaction. The patient was admitted with burns. Anterior pituitary hypofunction was diagnosed during hospitalisation owing to persistent hyponatremia. During hydrocortisone intravenous administration, blood pressure was decreased to 70/40 mmHg, accompanied with flushed face and vasodilation. According to World Health Organization Uppsala Monitoring Centre (WHO-UMC) causality assessment and Naranjo scale, there was a probable relationship of reduced blood pressure with hydrocortisone. To the best of our knowledge, we have presented the first case of an anaphylaxis reaction of blood pressure reduction following hydrocortisone administration in the anterior pituitary hypofunction patient.

7.
J Pediatr Nurs ; 69: 1-5, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36584591

RESUMO

OBJECTIVE: To translate the English version Child Food Neophobia Scale (CFNS) into the Chinese version and test its reliability and validity in preschool children. METHODS: To create the Chinese version of the CFNS, it was translated, back-translated, and cross-culturally adapted. The use of the Chinese version of CFNS by 575 parents of preschool children in two kindergartens in Yangzhou City was investigated using cluster sampling to assess the reliability and validity of the scale. RESULTS: The Chinese version of CFNS has nine items in total. The scale-level average content validity index (S-CVI/Ave) is 0.983. Exploratory factor analysis (EFA) extracted 2 common factors, and the cumulative variance contribution rate was 49.437%. Confirmatory factor analysis (CFA) showed that the 2-factor model was well fitted. The Cronbach'α coefficient of the scale was 0.759, the Cronbach'α coefficients of the two factors were 0.735 and 0.713, the split-half reliability was 0.788, and the test-retest reliability was 0.756. CONCLUSION: The Chinese version of the Child Food Neophobia Scale has good reliability and validity in preschool children and can be used as an assessment tool for food neophobia in preschool children in China. PRACTICE IMPLICATIONS: This study has gone through a rigorous translation process, and the CFNS may support future exploration of food neophobia in preschool children. Food allergy factors in the results may be the next step in the research, and several studies are still needed to understand the relationship between food allergy and food neophobia.

8.
Eur J Cancer Prev ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36484275

RESUMO

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade (P = 0.013), infiltration depth (P = 0.033), and clinicopathological stage (P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression (P = 0.037), tumor differentiation (P = 0.010), lymph node metastasis (P < 0.001), and clinicopathological stage (P = 0.037). Tumor differentiation (P = 0.033) and lymph node metastasis (P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

9.
Hortic Res ; 9: uhac223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479585

RESUMO

Globally, medicinal plant natural products (PNPs) are a major source of substances used in traditional and modern medicine. As we human race face the tremendous public health challenge posed by emerging infectious diseases, antibiotic resistance and surging drug prices etc., harnessing the healing power of medicinal plants gifted from mother nature is more urgent than ever in helping us survive future challenge in a sustainable way. PNP research efforts in the pre-genomic era focus on discovering bioactive molecules with pharmaceutical activities, and identifying individual genes responsible for biosynthesis. Critically, systemic biological, multi- and inter-disciplinary approaches integrating and interrogating all accessible data from genomics, metabolomics, structural biology, and chemical informatics are necessary to accelerate the full characterization of biosynthetic and regulatory circuitry for producing PNPs in medicinal plants. In this review, we attempt to provide a brief update on the current research of PNPs in medicinal plants by focusing on how different state-of-the-art biotechnologies facilitate their discovery, the molecular basis of their biosynthesis, as well as synthetic biology. Finally, we humbly provide a foresight of the research trend for understanding the biology of medicinal plants in the coming decades.

10.
Chem Sci ; 13(44): 13141-13146, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36425480

RESUMO

The reactivity of diazoalkanes most commonly proceeds through the formation of carbene intermediates or dipolar cycloaddition reactions. The reaction of diazoalkanes with intermediates with unpaired electrons, however, is much less elaborated. Herein, we report on the photochemical reaction of acceptor-only diazoalkanes with azodicarboxylates. Photoexcitation of the latter results in the formation of a triplet species, which undergoes an addition reaction with diazoalkanes and formation of an azomethine ylide followed by dipolar cycloaddition reaction with organic nitriles to give a 1,2,4-triazole. The application of this transformation was elaborated in a broad and general substrate scope (48 examples), including scale-up via flow chemistry and downstream transformations. Experimental and computational studies were performed to elucidate the reaction mechanism and to rationalize the reaction outcome.

11.
Org Biomol Chem ; 20(46): 9184-9191, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36350091

RESUMO

Recently, multifunctional fluorescent probes have received more and more attention with the rapid development of fluorescence imaging technology. In this article, a multifunctional fluorescent probe NAP-OH was designed and synthesized. NAP-OH exhibited outstanding polarity-sensing performance and was used to detect trace water in different organic solvents by means of fluorescence emission intensity. The fluorescence spectroscopy results indicated that NAP-OH was highly responsive to trace water in acetone (LOD = 28 ppm). The co-localization experiment and cell starvation imaging showed that the probe NAP-OH could be used to distinguish lysosomes from lipid droplets, showing bright red fluorescence in lipid droplets and weak red fluorescence in lysosomes. The oleic acid stimulation experiment shows that the probe can detect the dynamic changes of lipid droplets while observing lysosomes. In addition, NAP-OH showed great photostability and low cytotoxicity and was successfully used in zebrafish imaging. Therefore, these results indicated that NAP-OH, as a multifunctional fluorescent probe, would be used in trace water detection and biological imaging.


Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Animais , Humanos , Corantes Fluorescentes/química , Água , Peixe-Zebra , Lisossomos , Células HeLa
12.
Diabetol Metab Syndr ; 14(1): 165, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345040

RESUMO

BACKGROUND: Rheumatoid arthritis, metabolic syndrome (MS) and cardiovascular disease (CVD) are mutually connected. We aim to investigate the association between rheumatoid factor (RF) and MS in general population, explore the potential value of RF for assessment of metabolic status, and further provide a reference to the establishment of CVD primary prevention for this population. METHODS: We assessed the health check-up subjects, accordance with the inclusive criteria, from 1 January 2015 to 31 October 2021 in a large refereed general hospital, in this retrospective study. Subjects were categorized into four groups according to their levels of RF. Multivariate logistic regression models along with the Odds ratio (OR) and Confidence interval (CI) values were used to measure the association between RF and MS. RESULTS: A total of 13,690 subjects were analyzed. Prevalence of MS increased with RF level (P for trend < 0.001). Logistic regression analysis showed that, after adjusting for multiple covariates, RF level was significantly associated with MS prevalence (highest RF quartile: OR, 1.420; 95% CI 1.275,1.581, according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria; OR, 2.355; 95% CI 2.085,2.660, according to the International Diabetes Federation criteria) (both P for trends < 0.001). Among the MS components, there were evidence of increasing trends for overweight/obesity (highest RF quartile: OR, 3.165; 95% CI 2.827,3.543) and hypertension (highest RF quartile: OR, 1.722; 95% CI 1.549,1.914) (both P for trends < 0.001), but decreasing trend for low high-density lipoprotein-cholesterol (highest RF quartile: OR, 0.245; 95% CI 0.214,0.281) (P for trend < 0.001), with increasing RF quartiles. CONCLUSIONS: RF level is associated with MS prevalence in general population. RF might be a valuable biomarker for assessment of metabolic status in this population. We should be aware of the cardiovascular risk for the higher-RF subjects.

13.
Anal Methods ; 14(47): 4931-4937, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36441178

RESUMO

Chlorogenic acid and caffeic acid often coexist in traditional Chinese medicines (TCMs) and play roles as antioxidation, antiviral, antitumor and anti-inflammatory agents. Due to their low content and the presence of structural analogues, they cannot be effectively separated by conventional extraction methods. Molecularly imprinted polymers, as synthesized receptors with antibody-like binding properties, have significant advantages in separating structural analogues. However, the harsh imprinting conditions easily induced the degradation of chlorogenic acid. Therefore, caffeic acid was used as an epitope template to replace chlorogenic acid for imprinting. Boronic acid-functionalized magnetic nanoparticles (MNPs) were selected as substrates, which could not only facilitate the immobilization and removal of the templates by pH regulation, but also achieve rapid separation under an external magnetic field. Tetraethyl orthosilicate was selected as an imprinting monomer which allowed for precise control of the thickness of the imprinting layer by adjusting the imprinting time. The prepared epitope-imprinted MNPs showed excellent specificity, in combination with high performance liquid chromatography, have been successfully applied to the selective separation and detection of chlorogenic acid and caffeic acid in TCMs.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36423319

RESUMO

Cardiac troponin (cTnI) is a biomarker with high sensitivity and specificity for acute myocardial infarction (AMI). Rapid and accurate detection of cTnI can effectively reduce the mortality of AMI. Aiming at the problems of complex operation and low sensitivity of traditional methods used to detect cTnI, an Alphalisa immunoassay enabled centrifugal microfluidic system (AIECMS) is designed to detect cTnI quickly with high sensitivity, and good accuracy is achieved in the linear range of 0.1 ng/mL-50 ng/mL. However, in order to realize the detection of hypersensitive cTnI (the definition standard of weak positive and negative is 0.08 ng/mL), it is necessary to further improve the accuracy of qualitative detection. Since the signal curve of the system for reagents of low concentration range is relatively close, the system can not accurately distinguish weak positive and negative samples, which is easy to cause misjudgment of detection results. In order to solve this problem, this paper proposes to apply machine learning to the signal processing detected by AIECMS for the first time. Firstly, different pre-processing is done according to the characteristics of biological signals; Secondly, different machine learning algorithms are used to train and test the data, and the classification of four clinically significant concentrations (0.02 ng/mL, 0.04 ng/mL, 0.08 ng/mL and 0.1 ng/mL) is realized. Finally, combining the performance of various algorithms, algorithm cost and clinical requirements for the accuracy of low concentration classification, we choose random forest (accuracy 92%) to accurately distinguish the weak positive and negative samples of cTnI.

15.
Heliyon ; 8(10): e11016, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36276742

RESUMO

Pulmonary arterial remodeling at an early stage, including excessive proliferation and migration of smooth muscle cells, is a hallmark of pulmonary arterial hypertension (PAH). Salt-inducible kinases (SIKs) have been increasingly reported to play a key role in smooth muscle cell proliferation and phenotype switching, which may be associated with arterial remodeling. However, the potential effects of SIK1 in PAH and the underlying mechanisms have not been explored. The aim of this study was to determine whether reduced expression or inactivation of SIK1 is associated with pulmonary arterial remodeling in PAH and to elucidate whether it is related to the Hippo/Yes-associated protein (YAP) pathway. Using mouse models of PAH and hypoxia-stimulated hPASMCs, we observed that SIK1 expression was robustly reduced in lung tissues of PAH mice and hPASMCs cultured under hypoxia. In hypoxia-induced PAH mice, pharmacological SIK inhibition or AAV9-mediated specific smooth muscle SIK1 knockdown strongly aggravated pathological changes caused by hypoxia, including right ventricular hypertrophy and small pulmonary arterial remodeling. Meanwhile, in hypoxia-stimulated hPASMCs, SIK1 knockdown or inhibition promoted proliferation and migration under hypoxia, accompanied by decreased phosphorylation and increased nuclear accumulation of YAP, while SIK1 overexpression inhibited hypoxia-induced proliferation, migration and nuclear translocation of YAP in hPASMCs. YAP knockdown attenuated the increase in cell proliferation induced by HG-9-91-01 treatment or SIK1 siRNA transfection under hypoxia in hPASMCs. Here, we identified SIK1 as an antiproliferative factor in hypoxia-induced pulmonary arterial remodeling via YAP-mediated mechanisms. These results show that targeting SIK1 may be a promising therapeutic strategy for the treatment of PAH.

16.
Can Respir J ; 2022: 9656278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311545

RESUMO

Background: Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods: Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results: We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001; COPD: P = 0.001); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001; COPD: p = 0.012). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO (p < 0.001). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions: In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Masculino , Feminino , Humanos , Eosinófilos , Asma/epidemiologia , Contagem de Leucócitos , Citocinas
17.
Front Cardiovasc Med ; 9: 974035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312232

RESUMO

Cardiovascular disease is the leading cause of death globally among non-communicable diseases, which imposes a serious socioeconomic burden on patients and the healthcare system. Therefore, finding new strategies for preventing and treating cardiovascular diseases is of great significance in reducing the number of deaths and disabilities worldwide. Dipeptidyl peptidase 3 (DPP3) is the first zinc-dependent peptidase found among DPPs, mainly distributes within the cytoplasm. With the unique HEXXGH catalytic sequence, it is associated with the degradation of oligopeptides with 4 to 10 amino acids residues. Accumulating evidences have demonstrated that DPP3 plays a significant role in almost all cellular activities and pathophysiological mechanisms. Regarding the role of DPP3 in cardiovascular diseases, it is currently mainly used as a biomarker for poor prognosis in patients with cardiovascular diseases, suggesting that the level of DPP3 concentration in plasma is closely linked to the mortality of diseases such as cardiogenic shock and heart failure. Interestingly, it has been reported recently that DPP3 regulates blood pressure by interacting with the renin-angiotensin system. In addition, DPP3 also participates in the processes of pain signaling, inflammation, and oxidative stress. But the exact mechanism by which DPP3 affects cardiovascular function is not clear. Hence, this review summarizes the recent advances in the structure and catalytic activity of DPP3 and its extensive biological functions, especially its role as a therapeutic target in cardiovascular diseases. It will provide a theoretical basis for exploring the potential value of DPP3 as a therapeutic target for cardiovascular diseases.

18.
Oxid Med Cell Longev ; 2022: 1200602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246398

RESUMO

P300/CBP-Associated Factor (PCAF), one of the histone acetyltransferases (HATs), is known to be involved in cell growth and/or differentiation. PCAF is reported to be involved in atherosclerotic plaques and neointimal formation. However, its role in cellular senescence remains undefined. We investigated the potential mechanism for PCAF-mediated cellular senescence. Immunohistochemical (IHC) analysis showed PCAF was distinctly increased in the endothelia of aorta in aged mice. Palmitate acid (PA) or X radiation significantly induced the expression of senescence-associated markers and PCAF in human umbilical vein endothelial cells (HUVECs). PCAF silence in PA-treated HUVECs significantly rescued senescence-associated phenotypes, while PCAF overexpression accelerated it. Additionally, our results showed that Yes1 Associated Transcriptional Regulator (YAP) that acts as end effector of the Hippo signaling pathway is crucial in PCAF-mediated endothelial senescence. YAP activity declining was observed in aged vascular endothelia. Overexpression of YAP partially ameliorated PCAF-induced endothelial senescence. In vivo, endothelial-(EC-) specific PCAF downregulation in aged mice using adeno-associated virus revealed less vascular senescence-associated phenotypes. These results suggested that PCAF mediated endothelial senescence through the Hippo signaling pathway, implying that PCAF may become a potential target for the prevention and treatment of vascular aging.


Assuntos
Células Endoteliais , Via de Sinalização Hippo , Idoso , Animais , Humanos , Camundongos , Senescência Celular , Histona Acetiltransferases , Palmitatos
19.
Biomed Res Int ; 2022: 9294148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246958

RESUMO

Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Hipertensão Arterial Pulmonar , Angiotensina II/metabolismo , Animais , Antagomirs , Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar/metabolismo , Hipóxia/genética , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Monocrotalina , Hipertensão Arterial Pulmonar/genética , Ratos , Regulação para Cima/genética , Remodelação Ventricular/genética
20.
Neurosci Lett ; 791: 136917, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36252850

RESUMO

Circadian rhythm plays a significant role in maintaining the function of the cardiovascular system. Emerging studies have demonstrated that circadian disruption enhances the risk of cardiovascular diseases by activating the sympathetic nervous system; however, the underlying mechanisms remain unknown. Therefore, this study aimed to clarify the role of oxidative stress in the rostral ventrolateral medulla (RVLM) in sympathetic hyperactivity induced by circadian disruption. Rats were randomly divided into two groups: the normal light and dark (LD) group and the circadian disruption (CD) group. Sympathetic nerve activity of rats was assessed by recording renal sympathetic nerve activity (RSNA) and indirect methods such as plasma level of norepinephrine (NE). The level of oxidative stress in the RVLM was detected by dihydroethidium probes. Moreover, the expression levels of the oxidative stress-related proteins in the RVLM were detected by Western blotting. Circadian disruption significantly increased blood pressure (BP), RSNA, and plasma levels of NE. Compared to the LD group, the CD group exhibited a more significant depressor response to i.v. hexamethonium bromide, a ganglionic blocker. Furthermore, the reactive oxygen species (ROS) production in the RVLM of rats with circadian disruption was significantly increased. In addition, BP and RSNA of rats with circadian disruption exhibited a greater decrease in the effects of microinjection of tempol, a superoxide scavenger, into the RVLM, compared to artificial cerebrospinal fluid (aCSF). Further investigation of the molecular mechanism by Western blotting showed that nuclear factor-erythroid-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO1)/NAD(P)H: quinone oxidoreductase 1 (NQO1) signaling was down-regulated in the RVLM of circadian disruption rats. These data suggest that oxidative stress in the RVLM mediates sympathetic hyperactivity induced by circadian disruption and possibly by down-regulating Nrf2/HO1/NQO1 signaling.


Assuntos
Hipertensão , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Bulbo , Sistema Nervoso Simpático , Estresse Oxidativo/fisiologia , Superóxidos/metabolismo , Superóxidos/farmacologia , Pressão Sanguínea , Hipertensão/metabolismo , Frequência Cardíaca
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