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The availability of high-throughput sequencing data creates opportunities to comprehensively understand human diseases as well as challenges to train machine learning models using such high dimensions of data. Here, we propose a denoised multi-omics integration framework, which contains a distribution-based feature denoising algorithm, Feature Selection with Distribution (FSD), for dimension reduction and a multi-omics integration framework, Attention Multi-Omics Integration (AttentionMOI) to predict cancer prognosis and identify cancer subtypes. We demonstrated that FSD improved model performance either using single omic data or multi-omics data in 15 The Cancer Genome Atlas Program (TCGA) cancers for survival prediction and kidney cancer subtype identification. And our integration framework AttentionMOI outperformed machine learning models and current multi-omics integration algorithms with high dimensions of features. Furthermore, FSD identified features that were associated to cancer prognosis and could be considered as biomarkers.
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Genômica , Neoplasias , Humanos , Genômica/métodos , Multiômica , Neoplasias/genética , AlgoritmosRESUMO
Acute myocardial ischaemia/reperfusion (MI/R) injury causes severe arrhythmias with a high rate of lethality. Extensive research focus on endoplasmic reticulum (ER) stress and its dysfunction which leads to cardiac injury in MI/R Our study evaluated the effects of sulodexide (SDX) on MI/R by establishing MI/R mice models and in vitro oxidative stress models in H9C2 cells. We found that SDX decreases cardiac injury during ischaemia reperfusion and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase and reduced malondialdehyde in mice plasm, increased Bcl-2 expression, decreased BAX expression in a mouse model of MI/R. In vitro, SDX exerted a protective effect by the suppression of the ER stress which induced by tert-butyl hydroperoxide (TBHP) treatment. Both of the in vivo and in vitro effects were involved in the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. Inhibition of PI3K/Akt pathway by specific inhibitor, LY294002, partially reduced the protective effect of SDX. In short, our results suggested that the cardioprotective role of SDX was related to the suppression of ER stress in mice MI/R models and TBHP-induced H9C2 cell injury which was through the PI3K/Akt signalling pathway.
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Glicosaminoglicanos/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Coração/efeitos dos fármacos , Masculino , Camundongos , Isquemia Miocárdica/genética , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
IMPORTANCE: Identifying pediatric eye diseases at an early stage is a worldwide issue. Traditional screening procedures depend on hospitals and ophthalmologists, which are expensive and time-consuming. Using artificial intelligence (AI) to assess children's eye conditions from mobile photographs could facilitate convenient and early identification of eye disorders in a home setting. OBJECTIVE: To develop an AI model to identify myopia, strabismus, and ptosis using mobile photographs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted at the Department of Ophthalmology of Shanghai Ninth People's Hospital from October 1, 2022, to September 30, 2023, and included children who were diagnosed with myopia, strabismus, or ptosis. MAIN OUTCOMES AND MEASURES: A deep learning-based model was developed to identify myopia, strabismus, and ptosis. The performance of the model was assessed using sensitivity, specificity, accuracy, the area under the curve (AUC), positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (P-LR), negative likelihood ratios (N-LR), and the F1-score. GradCAM++ was utilized to visually and analytically assess the impact of each region on the model. A sex subgroup analysis and an age subgroup analysis were performed to validate the model's generalizability. RESULTS: A total of 1419 images obtained from 476 patients (225 female [47.27%]; 299 [62.82%] aged between 6 and 12 years) were used to build the model. Among them, 946 monocular images were used to identify myopia and ptosis, and 473 binocular images were used to identify strabismus. The model demonstrated good sensitivity in detecting myopia (0.84 [95% CI, 0.82-0.87]), strabismus (0.73 [95% CI, 0.70-0.77]), and ptosis (0.85 [95% CI, 0.82-0.87]). The model showed comparable performance in identifying eye disorders in both female and male children during sex subgroup analysis. There were differences in identifying eye disorders among different age subgroups. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the AI model demonstrated strong performance in accurately identifying myopia, strabismus, and ptosis using only smartphone images. These results suggest that such a model could facilitate the early detection of pediatric eye diseases in a convenient manner at home.
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Inteligência Artificial , Diagnóstico Precoce , Fotografação , Humanos , Feminino , Masculino , Estudos Transversais , Criança , Pré-Escolar , Fotografação/métodos , Miopia/diagnóstico , Aprendizado Profundo , Estrabismo/diagnóstico , Blefaroptose/diagnóstico , Sensibilidade e Especificidade , China/epidemiologia , Oftalmopatias/diagnóstico , AdolescenteRESUMO
Background: Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. Methods: A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Results: Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. Conclusion: This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.
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In this study, twenty-nine coumarin-3-sulfonamide derivatives, twenty-seven of which are original were designed and synthesized. Cytotoxicity assay indicated that most of these derivatives exhibited moderated to good potency against A549 cells. Among them, compound 8q showed potent inhibition against the four tested cancer cell lines, especially A549 cells with IC50 value of 6.01 ± 0.81 µM, and much lower cytotoxicity on the normal cells was observed compared to the reference compounds. Bioinformatics analysis revealed human carbonic anhydrase IX (CAIX) was highly expressed in lung adenocarcinoma (LUAD) and associated with poor prognosis. The inhibitory activity of compound 8q against CAIX was assessed by using molecular docking and molecular dynamics simulations, which revealed prominent interactions of both compound 8q and CAIX at the active site and their high affinity. The results of ELISA assays verified that compound 8q possessed strong inhibitory activity against CAIX and high subtype selectivity, and could also down-regulate the expression of CAIX in A549 cells. Furthermore, the significant inhibitory effects of compound 8q on the migration and invasion of A549 cells were also found. After treatment with compound 8q, intracellular reactive oxygen species (ROS) levels increased and mitochondrial membrane potential (MMP) decreased. Mechanistic investigation using western blotting revealed compound 8q exerted the anti-migrative and anti-invasive effects probably through mitochondria-mediated PI3K/AKT pathway by targeting CAIX. In summary, coumarin-3-sulfonamide derivatives were developed as potential and effective CAIX inhibitors, which were worthy of further investigation.
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Inibidores da Anidrase Carbônica , Cumarínicos , Humanos , Anidrase Carbônica IX , Simulação de Acoplamento Molecular , Cumarínicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Antígenos de Neoplasias/metabolismo , Sulfonamidas/farmacologia , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Background: Type 2 innate lymphoid cells (ILC2s) and NLRP3 inflammasome are related to allergic and inflammatory responses. NLRP3 inflammasome inhibitor MCC950 was demonstrated to ameliorate allergic rhinitis (AR) in animal models. Objective: To elucidate the effect of MCC950 on ILC2 responses in AR. Methods: NLRP3 inflammasome, ILC2s, IL-5+ILC2s, IL-13+ILC2s, and Th2-related factors were examined in 30 AR patients. ILC2s were identified as Lin-CRTH2+CD127+lymphocytes. ILC2s isolated from PBMCs were stimulated with LPS plus ATP. The effect of MCC950, IL-1ß, and IL-18 on ILC2 responses was detected by flow cytometry. AR models were established in 60 BALB/c mice. Nasal symptoms and ILC2 responses in the AR models after MCC950 treatment were detected. Human nasal epithelial cells were stimulated with IL-13 (10 ng/mL) and treated with MCC950 (10 µM). Results: AR patients showed activated NLRP3 inflammasome and increased ILC2 responses compared to controls. NLRP3 inflammasome levels in the AR patients were positively related to the proportion of ILC2s, IL-5+ILC2s, and IL-13+ILC2s in total PBMCs. MCC950 treatment or IL-1ß/IL-18 suppression inhibited ILC2 proliferation and Th2-related factors (GATA3, RORα, IL-5, and IL-13). MCC950 administration alleviated frequencies of nasal rubbing and sneezes in the AR models. ILC2s, IL-5+ILC2s, and IL-13+ILC2s in mice were reduced by MCC950. MCC950 inhibited NLRP3 inflammasome in the in vitro models of AR. Conclusion: MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.
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Imunidade Inata , Rinite Alérgica , Humanos , Animais , Camundongos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Interleucina-18 , Linfócitos/metabolismo , Interleucina-13 , Interleucina-5 , Rinite Alérgica/tratamento farmacológicoRESUMO
Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.
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BACKGROUND: Accurate prediction of prognostic outcomes in patients with COVID-19 could facilitate clinical decision-making and medical resource allocation. However, little is known about the ability of machine learning (ML) to predict prognosis in COVID-19 patients. OBJECTIVE: This study aimed to systematically examine the prognostic value of ML in patients with COVID-19. METHODS: A systematic search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and IEEE Xplore up to December 15, 2021. Studies predicting the prognostic outcomes of COVID-19 patients using ML were eligible for inclusion. Risk of bias was evaluated by a tailored checklist based on Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pooled sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated to evaluate model performance. RESULTS: A total of 33 studies that described 35 models were eligible for inclusion, with 27 models presenting mortality, four intensive care unit (ICU) admission, and four use of ventilation. For predicting mortality, ML gave a pooled sensitivity of 0.86 (95% CI, 0.79-0.90), a specificity of 0.87 (95% CI, 0.80-0.92), and an AUC of 0.93 (95% CI, 0.90-0.95). For the prediction of ICU admission, ML had a sensitivity of 0.86 (95% CI, 0.78-0.92), a specificity of 0.81 (95% CI, 0.66-0.91), and an AUC of 0.91 (95% CI, 0.88-0.93). For the prediction of ventilation, ML had a sensitivity of 0.81 (95% CI, 0.68-0.90), a specificity of 0.78 (95% CI, 0.66-0.87), and an AUC of 0.87 (95% CI, 0.83-0.89). Meta-regression analyses indicated that algorithm, population, study design, and source of dataset influenced the pooled estimate. CONCLUSION: This meta-analysis demonstrated the satisfactory performance of ML in predicting prognostic outcomes in patients with COVID-19, suggesting the potential value of ML to support clinical decision-making. However, improvements to methodology and validation are still necessary before its application in routine clinical practice.
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COVID-19 , Humanos , COVID-19/diagnóstico , Prognóstico , Hospitalização , Unidades de Terapia Intensiva , Aprendizado de MáquinaRESUMO
AIMS/INTRODUCTION: Clinical guidelines for the management of individuals with type 2 diabetes mellitus endorse the systematic assessment of atherosclerotic cardiovascular disease risk for early interventions. In this study, we aimed to develop machine learning models to predict 3-year atherosclerotic cardiovascular disease risk in Chinese type 2 diabetes mellitus patients. MATERIALS AND METHODS: Clinical records of 4,722 individuals with type 2 diabetes mellitus admitted to 94 hospitals were used. The features included demographic information, disease histories, laboratory tests and physical examinations. Logistic regression, support vector machine, gradient boosting decision tree, random forest and adaptive boosting were applied for model construction. The performance of these models was evaluated using the area under the receiver operating characteristic curve. Additionally, we applied SHapley Additive exPlanation values to explain the prediction model. RESULTS: All five models achieved good performance in both internal and external test sets (area under the receiver operating characteristic curve >0.8). Random forest showed the highest discrimination ability, with sensitivity and specificity being 0.838 and 0.814, respectively. The SHapley Additive exPlanation analyses showed that previous history of diabetic peripheral vascular disease, older populations and longer diabetes duration were the three most influential predictors. CONCLUSIONS: The prediction models offer opportunities to personalize treatment and maximize the benefits of these medical interventions.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , População do Leste Asiático , Seguimentos , Aprendizado de Máquina , Aterosclerose/diagnósticoRESUMO
BACKGROUND: Considering the high incidence of medical privacy disclosure, it is of vital importance to study doctors' privacy protection behavior and its influencing factors. OBJECTIVE: We aim to develop a scale for doctors' protection of patients' privacy in Chinese public medical institutions, following construction of a theoretical model framework through grounded theory, and subsequently to validate the scale to measure this protection behavior. METHODS: Combined with the theoretical paradigm of protection motivation theory (PMT) and semistructured interview data, the grounded theory research method, followed by the Delphi expert and group discussion methods, a theoretical framework and initial scale for doctors in Chinese public medical institutions to protect patients' privacy was formed. The adjusted scale was collected online using a WeChat electronic survey measured using a 5-point Likert scale. Exploratory and confirmatory factor analysis (EFA and CFA) and tests to analyze reliability and validity were performed on the sample data. SPSS 19.0 and Amos 26.0 statistical analysis software were used for EFA and CFA of the sample data, respectively. RESULTS: According to the internal logic of PMT, we developed a novel theoretical framework of a "storyline," which was a process from being unaware of patients' privacy to having privacy protection behavior, that affected doctors' cognitive intermediary and changed the development of doctors' awareness, finally affecting actual privacy protection behavior in Chinese public medical institutions. Ultimately, we created a scale to measure 18 variables in the theoretical model, comprising 63 measurement items, with a total of 208 doctors participating in the scaling survey, who were predominantly educated to the master's degree level (n=151, 72.6%). The department distribution was relatively balanced. Prior to EFA, the Kaiser-Meyer-Olkin (KMO) value was 0.702, indicating that the study was suitable for factor analysis. The minimum value of Cronbach α for each study variable was .754, which met the internal consistency requirements of the scale. The standard factor loading value of each potential measurement item in CFA had scores greater than 0.5, which signified that all the items in the scale could effectively converge to the corresponding potential variables. CONCLUSIONS: The theoretical framework and scale to assess doctors' patient protection behavior in public medical institutions in China ï¬lls a significant gap in the literature and can be used to further the current knowledge of physicians' thought processes and adoption decisions.
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Introduction: With the spread of the epidemic worldwide, an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019 (COVID-19): olfactory or taste disorders. Therefore, clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID-19 patients is of great significance and urgency. Materials and Methods: A retrospective study was conducted, which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients, through face-to-face interviews and telephone follow-up. Following the completion of questionnaires, the patients participating in the study, were categorized according to the degree of olfactory and taste disorders experienced, and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded. Results: Among the 229 patients, 31 (13.54%) had olfactory dysfunction, and 44 (19.21%) had gustatory dysfunction. For the patients with olfactory dysfunction, 6 (19.35%) developed severe disease and became critically ill. Olfactory dysfunction appeared before the other symptoms in 21.43% of cases. The proportion of females with olfactory and gustatory dysfunction was higher than that of males (P < 0.001). Conclusions: The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad; the prognosis of patients with olfactory dysfunction is relatively favorable; olfactory and gustatory dysfunction can be used as a sign for early screening; females are more prone to olfactory and gustatory dysfunction.
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Food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC50 values of the five top-rated tripeptides ranged from 5.86 to 21.84 µM. Five hundred top-ranked tripeptides were chosen for detailed structure-activity analysis, and a significant preference for aromatic amino acids at both C- and N-terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity.
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To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.
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COVID-19/complicações , Transtornos do Olfato/etiologia , Olfato , Distúrbios do Paladar/etiologia , Paladar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/epidemiologia , Prevalência , SARS-CoV-2 , Fatores Sexuais , Distúrbios do Paladar/epidemiologia , Adulto JovemRESUMO
As the prevalence of systemic fungal infections caused by Candida albicans gradually increases, it is necessary to explore potential and effective antifungals. Carvacrol is reported to be lethally toxic to C. albicans, involving several potential mechanisms. However, the form and specific mechanism of cell death caused by this compound has not been delineated. In this study, we found that carvacrol could significantly decrease C. albicans survival rates, consistent with previous researches. Further examination proved that carvacrol treatment caused cell membrane permeability and depolarization. To elucidate the association between cell death and apoptosis, DNA fragmentation and metacaspase activation were determined; as expected, these two apoptosis-related markers were clearly observed. Moreover, total and mitochondrial reactive oxygen species (ROS) levels were elevated, and both mitochondrial transmembrane potential and morphology were disrupted. Additionally, cytosolic and mitochondrial calcium levels were also increased by carvacrol. Calcineurin inhibition experiments revealed cyclosporine A (CsA) addition notably rescued cell growth and inhibited metacaspase activation, indicating that carvacrol triggered C. albicans apoptosis through inducing calcineurin activation. Carvacrol was demonstrated to both have low toxicity and be effective in alleviating systemic infections with C. albicans, which might be via its antifungal and immunomodulation activities. This study suggests that carvacrol has excellent potential as a natural protective compound against C. albicans infections.
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Calcineurina , Candida albicans , Antifúngicos/farmacologia , Apoptose , Calcineurina/farmacologia , Cimenos , Espécies Reativas de OxigênioRESUMO
Long noncoding RNAs (lncRNAs) play important roles in the development of vascular diseases. However, the effect of lncRNA NORAD on atherosclerosis remains unknown. This study aimed to investigate the effect NORAD on endothelial cell injury and atherosclerosis. Ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE-/- mice were used as in vitro and in vivo models. Results showed that NORAD-knockdown induced cell cycle arrest in G0/G1 phase, aggravated ox-LDL-induced cell viability reduction, cell apoptosis, and cell senescence along with the increased expression of Bax, P53, P21 and cleaved caspase-3 and the decreased expression of Bcl-2. The effect of NORAD on cell viability was further verified via NORAD-overexpression. NORAD- knockdown increased ox-LDL-induced reactive oxygen species, malondialdehyde, p-IKBα expression levels and NF-κB nuclear translocation. Proinflammatory molecules ICAM, VCAM, and IL-8 were also increased by NORAD- knockdown. Additionally, we identified the strong interaction of NORAD and IL-8 transcription repressor SFPQ in HUVECs. In ApoE-/- mice, NORAD-knockdown increased the lipid disorder and atherosclerotic lesions. The results have suggested that lncRNA NORAD attenuates endothelial cell senescence, endothelial cell apoptosis, and atherosclerosis via NF-κB and p53-p21 signaling pathways and IL-8, in which NORAD-mediated effect on IL-8 might through the direct interaction with SFPQ.
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Aterosclerose/genética , Células Endoteliais/metabolismo , Interleucina-8/metabolismo , Lipoproteínas LDL/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Senescência Celular , Regulação para Baixo , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , NF-kappa B/metabolismo , Oxirredução , Transdução de SinaisRESUMO
Kawasaki disease (KD) is an acute, selflimited vasculitis that predominantly affects mediumsized arteries, particularly the coronary arteries. Recent studies have indicated that microRNAs are involved in many diseases, including KD. However, the detailed mechanism remains unclear. The aim of the present study was to explore the role of miR186 in KD and potentially discover a new target for KD treatment. The results demonstrated that miR186 was upregulated in serum from patients with KD and KD serum could increase miR186 transcript levels in endothelial cells (HUVECs). Overexpression of miR186 mimic induced HUVEC apoptosis through mitogenactivated protein kinase (MAPK) activation by targeting and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC apoptosis through miR186. In conclusion, the present results suggested that KD serumassociated miR186 has an essential role in endothelial cell apoptosis by activating the MAPK pathway through targeting the SMAD6 gene.