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  • Frontiers Media SA  (9)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Pathology and Oncology Research Vol. 27 ( 2021-4-29)
    In: Pathology and Oncology Research, Frontiers Media SA, Vol. 27 ( 2021-4-29)
    Abstract: Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3′ untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
    Type of Medium: Online Resource
    ISSN: 1532-2807
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2002501-4
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  • 2
    In: Frontiers in Earth Science, Frontiers Media SA, Vol. 10 ( 2022-7-8)
    Abstract: The Kuqa Depression boasts rich cretaceous ultra-deep hydrocarbon resources. However, it is in complex geological conditions. At present, sufficient understandings on the in situ stress distribution and influencing factors are lacking, which restricts the process of hydrocarbon exploitation. Therefore, in this study, the Bozi gas field is selected as an example, and a 1D mechanical earth model (1D MEM) is established with the drilling data and logging data through the geomechanical method to clarify the in situ stress distribution of the wellbore. A 3D heterogeneous geomechanical model (3D HGM) is established with the constraint of 1D HEM to clarify the distribution characteristics of the 3D in situ stress field in the Bozi gas field and discuss its influencing factors. The results show that: 1) the Bozi gas field is in an extremely strong in situ stress condition with high stress values. The minimum horizontal principal stress (S h ) of the cretaceous system is 153∼180 MPa, and the maximum horizontal principal stress (S H ) is nearly 200 MPa; 2) the in situ stress in the Bozi gas field has obvious vertical stratification characteristics, which can be divided into three stress sequences of “low–high–low”, with great differences in interlayer stress; 3) the in situ stress distribution of the Bozi gas field is greatly affected by the types of faulted anticline. Different types indicate different stress distribution; 4) within the influence range of overthrusts, the in situ stress in the footwall is lower than that of the hanging wall. The greater the fault offset, the greater the in situ stress difference between the hanging wall and footwall. Moreover, the lower the stress in the footwall, the higher is the degree of overthrust, and the larger is the range of footwall stress area; and 5) the means of highly deviated wells is more helpful to the Bozi gas field for hydrocarbon exploitation.
    Type of Medium: Online Resource
    ISSN: 2296-6463
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2741235-0
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Molecular Biosciences Vol. 9 ( 2022-4-8)
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 9 ( 2022-4-8)
    Abstract: Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disorder affecting epidemic proportion at global scope. Defective insulin secretion by pancreatic β -cells and the inability of insulin-sensitive tissues to respond effectively to insulin are the underlying biology of T2DM. However, circulating biomarkers indicative of early diabetic onset at the asymptomatic stage have not been well described. We hypothesized that global and targeted mass spectrometry (MS) based metabolomic discovery can identify novel serological metabolic biomarkers specifically associated with T2DM. We further hypothesized that these markers can have a unique pattern associated with latent or early asymptomatic stage, promising an effective liquid biopsy approach for population T2DM risk stratification and screening. Methods: Four independent cohorts were assembled for the study. The T2DM cohort included sera from 25 patients with T2DM and 25 healthy individuals for the biomarker discovery and sera from 15 patients with T2DM and 15 healthy controls for the testing. The Pre-T2DM cohort included sera from 76 with prediabetes and 62 healthy controls for the model training and sera from 35 patients with prediabetes and 27 healthy controls for the model testing. Both global and targeted (amino acid, acylcarnitine, and fatty acid) approaches were used to deep phenotype the serological metabolome by high performance liquid chromatography-high resolution mass spectrometry. Different machine learning approaches (Random Forest, XGBoost, and ElasticNet) were applied to model the unique T2DM/Pre-T2DM metabolic patterns and contrasted with their effectiness to differentiate T2DM/Pre-T2DM from controls. Results: The univariate analysis identified unique panel of metabolites ( n = 22) significantly associated with T2DM. Global metabolomics and subsequent structure determination led to the identification of 8 T2DM biomarkers while targeted LCMS profiling discovered 14 T2DM biomarkers. Our panel can effectively differentiate T2DM (ROC AUC = 1.00) or Pre-T2DM (ROC AUC = 0.84) from the controls in the respective testing cohort. Conclusion: Our serological metabolite panel can be utilized to identifiy asymptomatic population at risk of T2DM, which may provide utility in identifying population at risk at an early stage of diabetic development to allow for clinical intervention. This early detection would guide ehanced levels of care and accelerate development of clinical strategies to prevent T2DM.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2814330-9
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2018
    In:  Frontiers in Genetics Vol. 9 ( 2018-9-4)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 9 ( 2018-9-4)
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606823-0
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-12-5)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-12-5)
    Abstract: Obstructive sleep apnea (OSA) is a globally prevalent disease closely associated with hypertension. To date, no predictive model for OSA-related hypertension has been established. We aimed to use machine learning (ML) to construct a model to analyze risk factors and predict OSA-related hypertension. Materials and methods We retrospectively collected the clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 and randomly divided them into training and validation sets. A total of 1,493 OSA patients with 27 variables were included. Independent risk factors for the risk of OSA-related hypertension were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and the multilayer perceptron (MLP), were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model. We compared the accuracy and discrimination of the models to identify the best machine learning algorithm for predicting OSA-related hypertension. In addition, a web-based tool was developed to promote its clinical application. We used permutation importance and Shapley additive explanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results A total of 18 variables were selected for the models. The GBM model achieved the most extraordinary discriminatory ability (area under the receiver operating characteristic curve = 0.873, accuracy = 0.885, sensitivity = 0.713), and on the basis of this model, an online tool was built to help clinicians optimize OSA-related hypertension patient diagnosis. Finally, age, family history of hypertension, minimum arterial oxygen saturation, body mass index, and percentage of time of SaO 2 & lt; 90% were revealed by the SHAP method as the top five critical variables contributing to the diagnosis of OSA-related hypertension. Conclusion We established a risk prediction model for OSA-related hypertension patients using the ML method and demonstrated that among the six ML models, the gradient boosting machine model performs best. This prediction model could help to identify high-risk OSA-related hypertension patients, provide early and individualized diagnoses and treatment plans, protect patients from the serious consequences of OSA-related hypertension, and minimize the burden on society.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-8-26)
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-8-26)
    Abstract: Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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  • 7
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-12-19)
    Abstract: A high body mass index (BMI) is a major risk factor for hypertension. The purpose of this study was to investigate the association between the BMI and hypertension in children and adolescents. Methods We analyzed physical examination data from 29,810 students aged 6–14 years old. A restricted cubic spline (RCS) function was used to investigate the dose-response relationship between the BMI and hypertension. Results The prevalence of hypertension was 9.91%, followed by 11.71% in males and 7.9% in females, respectively. Compared to the normal weight group, the odds risk (OR) for hypertension in the overweight group was 1.729, and the OR for hypertension in the obesity group was 3.089. After adjusting for potential confounders, the adjusted ORs were 1.620 [95% confidence interval (CI): 1.457–1.800] in the overweight group and 3.092 (95% CI: 2.824–3.385) in the obesity group. According to the multivariate RCS regression analysis, there was a significant non-linear dose-response association between the BMI and the risk of hypertension (all P-values for non-linear & lt; 0.001). Conclusion The dose-response relationship analysis showed that the association strength of hypertension increased non-linearly along with the continuous change of BMI in children and adolescents.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 8
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 10 ( 2023-1-5)
    Abstract: As an important neuroprotective factor, the brain-derived neurotrophic factor (BDNF) may have a key role in cognitive impairment in children with sleep-disordered breathing (SDB). The main aim of this study was to compare the levels of BDNF and tyrosine kinase receptor B (TrkB) in normal children and those with obstructive sleep apnea (OSA) and primary snoring (PS) and to explore a possible link between BDNF/TrkB, inflammation, and SDB with cognitive impairment in children. Methods A total of 44 OSA children and 35 PS children who completed polysomnography between October 2017 and October 2019 were enrolled. At the same time, 40 healthy children during the same period were included as a control. Enzyme-linked immunosorbent assay was used to measure serum indices of BDNF, TrkB, interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). Correlation and pooled analyses were performed between the cognitive scores and four serological indicators. Logistic regression was used to analyze the risk factors for cognitive impairment. Results Significant differences were found in serum BDNF, TrkB, IL-1β, and TNF-α between the three groups (all P   & lt; 0.01). The serum BDNF and TrkB in the OSA and PS groups were lower than those in the control group, whereas the serum IL-1β and TNF-α were higher than those in the control group (all P   & lt; 0.05). Moreover, among these four indices, the strongest correlation was found between BDNF and the Chinese Wechsler Intelligence Scale (all P   & lt; 0.05). Logistic regression analysis revealed a correlation between OSA status, TrkB, and course of mouth breathing and cognitive status. Conclusion The levels of serum BDNF and TrkB were related to cognitive impairment in children with SDB. Also, BDNF and TrkB could be used as noninvasive and objective candidate markers and predictive indices of cognitive impairment in children with SDB.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711999-3
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  • 9
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-9-21)
    Abstract: Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. Methods The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. Results A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. Conclusion The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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