miRNA-142-3p aggravates hydrogen peroxide-induced human umbilical vein endothelial cell premature senescence by targeting SIRT1.

Vascular endothelial cell premature senescence plays an important part in stroke. Many microRNAs (miRNAs) are known to be involved in the pathological process of vascular endothelial cell premature senescence. The present study aimed to investigate the mechanism of hydrogen peroxide (H2O2)-induced premature senescence in human umbilical vein endothelial cells (HUVECs) and effect of miR-142-3p on hydrogen peroxide (H2O2)-induced premature senescence. HUVECs were exposed to H2O2 to establish a model premature senescence in endothelial cells. CCK-8 assay was performed to detect cell viability. Senescence-associated ß-galactosidase staining assay and senescence-related proteins p16 and p21 were used to detect changes in the degree of cell senescence. RT-qPCR and Western blot were conducted to measure mRNA and protein levels, respectively. The scratch wound-healing assay, transwell assay, and EdU assay were performed to evaluate the ability of migration and proliferation, respectively. miRNA-142-3p and silencing information regulator 2 related enzyme 1 (SIRT1) binding was verified using Targetscan software and a dual-luciferase assay. We found that miRNA-142-3p is abnormally up-regulated in HUVECs treated with H2O2. Functionally, miRNA-142-3p inhibition may mitigate the degree of HUVEC senescence and improve HUVEC migration and proliferation. Mechanistically, SIRT1 was validated to be targeted by miRNA-142-3p in HUVECs. Moreover, SIRT1 inhibition reversed the effects of miRNA-142-3p inhibition on senescent HUVECs exposed to H2O2. To our knowledge, this is the first study to show that miRNA-142-3p ameliorates H2O2-induced HUVECs premature senescence by targeting SIRT1 and may shed light on the role of the miR-142-3p/SIRT1 axis in stroke treatment.

Gastrodin alleviates premature senescence of vascular endothelial cells by enhancing the Nrf2/HO-1 signalling pathway.

Endothelial dysfunction is an independent risk factor for stroke. The dysfunction of endothelial cells (EC) is closely concerned with EC senescence. Gastrodin (GAS) is an organic compound extracted from the dried root mass of the Orchidaceae plant Gastrodiae gastrodiae. It is used clinically to treat diseases such as vertebrobasilar insufficiency, vestibular neuronitis and vertigo. In the present study, we used hydrogen peroxide (H2 O2 )-induced human umbilical vein endothelial cells (HUVECs) to establish an in vitro EC senescence model and to investigate the role and mechanism of GAS in EC senescence. It's found that H2 O2 -treated HUVECs increased the proportion of senescence-associated ß-galactosidase (SA ß-gal) positive cells and the relative protein expression levels of senescence-associated cyclin p16 and p21. In addition, GAS reduced the proportion of SA ß-gal positive cells and the relative protein expression levels of p16 and p21, and increased the proliferation and migration ability of HUVECs. Meanwhile, GAS increased the expression of the anti-oxidative stress protein HO-1 and its nuclear expression level of Nrf2. The anti-senescence effect of GAS was blocked when HO-1 expression was inhibited by SnPPIX. Furthermore, absence of HO-1 abolished the effect of GAS on HUVEC proliferation and migration. In conclusion, GAS ameliorated H2 O2 -induced cellular senescence and enhanced cell proliferation and migration by enhancing Nrf2/HO-1 signalling in HUVECs. These findings of our study expanded the understanding of GAS pharmacology and suggested that GAS may offer a potential therapeutic agent for stroke.

Biparametric magnetic resonance imaging-based radiomics features for prediction of lymphovascular invasion in rectal cancer.

BACKGROUND: Preoperative assessment of lymphovascular invasion(LVI) of rectal cancer has very important clinical significance. However, accurate preoperative imaging evaluation of LVI is highly challenging because the resolution of MRI is still limited. Relatively few studies have focused on prediction of LVI of rectal cancer with the tool of radiomics, especially in patients with negative statue of MRI-based extramural vascular invasion (mrEMVI).The purpose of this study was to explore the preoperative predictive value of biparametric MRI-based radiomics features for LVI of rectal cancer in patients with the negative statue of mrEMVI. METHODS: The data of 146 cases of rectal adenocarcinoma confirmed by postoperative pathology were retrospectively collected. In the cases, 38 had positive status of LVI. All patients were examined by MRI before the operation. The biparametric MRI protocols included T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). We used whole-volume three-dimensional method and two feature selection methods, minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO), to extract and select the features. Logistics regression was used to construct models. The area under the receiver operating characteristic curve (AUC) and DeLong's test were used to evaluate the diagnostic performance of the radiomics based on T2WI and DWI and the combined models. RESULTS: Radiomics models based on T2WI and DWI had good predictive performance for LVI of rectal cancer in both the training cohort and the validation cohort. The AUCs of the T2WI model were 0.87 and 0.87, and the AUCs of the DWI model were 0.94 and 0.92. The combined model was better than the T2WI model, with AUCs of 0.97 and 0.95. The predictive performance of the DWI model was comparable to that of the combined model. CONCLUSIONS: The radiomics model based on biparametric MRI, especially DWI, had good predictive value for LVI of rectal cancer. This model has the potential to facilitate the clinical recognition of LVI in rectal cancer preoperatively.

Analysis of Clinical Characteristic and Risk Factors for Short-Term Prognosis of Moyamoya Disease with Intraventricular Hemorrhage in Adults.

BACKGROUND: Intraventricular hemorrhage (IVH) is the most common type of hemorrhage in moyamoya disease (MMD) with intracerebral hemorrhage (ICH), but the risk factors affecting the short-term prognosis of MMD with IVH in adults are still unclear. METHODS: We retrospectively analyzed patients of MMD with IVH between January 1, 2018 and January 31, 2020 in the First Affiliated Hospital of Zhengzhou University. According to the modified Rankin Scale (mRS) score at 3 months after discharge, the patients were divided into mRS score ≤2 (good prognosis) group and mRS score >2 (poor prognosis) groups. Univariate and multivariate logistics regression analysis was used to analyze the risk factors affecting the short-term prognosis of adult MMD with IVH. RESULTS: Univariable analyses showed that patients in the poor prognosis group had a significantly older age of onset (48.48 ± 8.34 vs. 43.74 ± 5.44 years; P = 0.002), a higher percentage of hypertension (57.97% vs. 33.33%; P = 0.014), a higher percentage of tracheotomy (23.19% vs. 2.56%; P = 0.005), a lower Glasgow Coma Scale (GCS) score (7.90 ± 3.58 vs. 11.19 ± 2.56; P = 0.000), a higher Graeb score (7.46 ± 4.04 vs. 5.23 ± 1.93; P = 0.002), and treatment methods (P = 0.000). Multiple logistic regression analysis showed that the lower GCS score (odds ratio [OR], 1.761; P = 0.001) and higher Graeb score (OR, 1.767; P = 0.002) were independently associated with the poor prognosis of MMD with IVH, and surgery treatment (OR, 0.032; P = 0.000) was independently related to the good prognosis of MMD with IVH. CONCLUSIONS: Among patients with MMD with IVH, the lower GCS score and higher Graeb score are independent risk factors for poor prognosis, whereas in patients with MMD with IVH, surgery treatment acts as a protective factor.

A Multicomponent Polymer-Metal-Enzyme System as Electrochemical Biosensor for H2O2 Detection.

Herein, an Au nanoparticles-polydopamine-poly acrylic acid-graphene (Au NPs-PDA-PAA-graphene) multicomponent nanohybrid is fabricated by surface functionalization of graphene alongside extensive in-situ growth of Au nanoparticles. The as-obtained nanocomposite possesses good hydrophilicity, excellent biocompatibility and high biomolecules loading capacity, which acts as an ideal platform for enzyme modification. Considering this fact, Horseradish peroxidase is expressively immobilized upon Au NPs-PDA-PAA-graphene surface, in order to lay the foundations of a biosensor that is majorly based on enzymatic activity. The biosensor exhibits higher sensitivity towards the determination of H2O2 with linearity ranging from 0.1 µm upto 20 mm, and the limit of detection going down to 0.02 µm. Encouraged by its acceptable electrocatalytic performance, this multicomponent system can also be easily employed for carrying out the real-time tracking of H2O2 coming out of Macrophage cells. Therefore, this work designs an extraordinarily updated platform for biosensing related applications, and also presents a reliable platform for the direct detection of H2O2 in vivo and in vitro, which show great potential in bioelectroanalytical chemistry, cellular biology, and pathophysiology.

Molecular mechanisms of osteoarthritis using gene microarrays.

This study aimed to investigate the molecular mechanisms of osteoarthritis (OA) by microarray analysis. Three gene expression datasets GSE1919, 19664 and 55235 were downloaded from the Gene Expression Omnibus, and data of OA samples and healthy controls were used. After data preprocessing, differential expression analysis between the OA group and controls was performed using LIMMA (Linear Models for Microarray Data) package and genes with |log2FC (fold change)|>1 and P<0.05 were screened as DEGs (differentially expressed genes). The screened DEGs were then subject to functional annotation and pathway enrichment analysis using DAVID (Database for Annotation Visualization and Integrated Discovery). Next, gene-set enrichment analysis was performed using Enrichment map Cytoscape plug-in, followed by detecting sub-networks using clusterONE. Finally, risk subpathways were screened using iSubpathwayMiner package. A total of 141 DEGs were screened, including 52 up-regulated ones and 89 down-regulated ones. These DEGs were enriched in 48 GO terms that were mainly related to locomotory behavior, taxis, adhesion, and 11 pathways that were related to cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, as well as several signaling pathways. The enrichment map enriched gene-sets mainly related to cell death and apoptosis, and extracellular components. The risk pathways up-regulated DEGs were exclusively related to arachidonic acid metabolism and glycosphingolipid biosynthesis, and the top two risk pathways were tyrosine metabolism for the down-regulated ones. From this study we conclude that genes involved in cell death and apoptosis, as well as cell-extracellular matrix interaction, may be essential for OA pathogenesis by altering multiple signaling pathways.