m6A Modification Mediates Endothelial Cell Responses to Oxidative Stress in Vascular Aging Induced by Low Fluid Shear StressRead the full article
Oxidative Medicine and Cellular Longevity publishes research involving cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, and metabolism.
Chief Editor Dr Vasquez-Vivar has experience in free radical and redox biology research including the discovery of the role of tetrahydrobiopterin in the regulation of superoxide generation by endothelial and neuronal nitric oxide synthase.
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Cryptotanshinone Attenuated Pathological Cardiac Remodeling In Vivo and In Vitro Experiments
Objective. Cardiac remodeling has been demonstrated to be the early stage and common pathway for various types of cardiomyopathy, but no specific treatment has been suggested to prevent its development and progress. This study was aimed at assessing whether Cryptotanshinone (CTS) treatment could effectively attenuate cardiac remodeling in vivo and in vitro. Methods. Aortic banding (AB) surgery was performed to establish a pressure-overload-induced mouse cardiac remodeling model. Echocardiography and pressure-volume proof were used to examine mouse cardiac function. Hematoxylin and eosin (HE) and Picro-Sirius Red (PSR) staining were used to assess cardiac remodeling in vivo. Mouse hearts were collected to analysis signaling pathway and cardiac remodeling markers, respectively. Furthermore, neonatal rat cardiomyocyte (NRCMs) and cardiac fibroblast (CF) were isolated to investigate the roles and mechanisms of CTS treatment in vitro. Results. CTS administration significantly alleviated pressure-overload-induced mouse cardiac dysfunction, inhibited cardiac hypertrophy, and reduced cardiac fibrosis. Mechanically, CTS treatment significantly inhibited the STAT3 and TGF-β/SMAD3 signaling pathways. In vitro experiments, CTS treatment markedly inhibited AngII-induced cardiomyocyte hypertrophy and TGF-β-induced myofibroblast activation via inhibiting STAT3 phosphorylation and its nuclear translocation. Finally, CTS treatment could not protect against pressure overload-induced mouse cardiac remodeling after adenovirus-associated virus (AAV)9-mediated STAT3 overexpression in mouse heart. Conclusion. CTS treatment might attenuate pathological cardiac remodeling via inhibiting STAT3-dependent pathway.
lncRNA CRNDE Affects Th17/IL-17A and Inhibits Epithelial-Mesenchymal Transition in Lung Epithelial Cells Reducing Asthma Signs
Background. Asthma treatment is difficult due to disease heterogeneity and comorbidities. In addition, the development of drugs targeting the underlying mechanisms of asthma remains slow. We planned to identify the most upregulated differentially expressed long noncoding RNA in asthma to explore its regulatory patterns and pathways in asthma. Methods. We sensitized mice using a mixture of ovalbumin, house dust mites, and lipopolysaccharide to establish an asthma mouse model. We also sensitized asthma cells with TGF-β1 in an in vitro model. We performed a microarray analysis to identify the lncRNA with the differential expression level in model mice. We applied hematoxylin and eosin and Masson’s trichrome stainings to mouse tissues to quantify the tissue damage extent. Next, we assess the levels of lncRNA CRNDE, miR-29a-3p, TGF-β1, MCL-1, E-cadherin, vimentin, and snail. We counted the percentages of Th17 cells using flow cytometry. Finally, we performed a dual-luciferase reporter assay to assess the association between lncRNA CRNDE and miR-29a-3p. Results. We successfully established asthma mouse/cell models and selected the lncRNA CRNDE for our study. Transfection of si-CRNDE reduced the degree of injury and inflammation in the mouse model and reversed the TGF-β1-induced epithelial-mesenchymal transition (EMT) in the cell model. Moreover, the E-cadherin level was upregulated, and the levels of IL-17A, vimentin, snail, and α-SMA were downregulated. We also discovered that lncRNA CRNDE negatively regulated miR-29a-3p and that this one in turn inhibited MCL-1 in mice. After lncRNA CRNDE expression downregulation, the level of miR-29a-3p was increased, and we detected reduced levels of MCL-1 and EMTs. Conclusions. lncRNA CRNDE expression downregulation led to reduced inflammation and reduced lung damage in mice with induced asthma, it inhibited the EMTs of lung epithelial cells via the miR-29a-3p/MCL-1 pathway, and it reduced the levels of Th17/IL-17A cells to reduce asthma signs.
A Novel Scientometrics Research on the Interaction between Oxidative Stress and Hematopoietic Stem Cell Transplantation Complications: From Graft-versus-Host Disease to Sepsis
As major and serious complications after hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) and sepsis are the chief causes of low survival rates as well as mortality and for HSCT recipients. Although the overall treatment outcomes of HSCT have improved significantly in recent years, there is still an increased incidence rate of complications and mortality after transplantation. In the immediate past, with a deeper understanding of oxidative stress, more and more shreds of evidence have shown that it is closely related to transplantation-related sepsis. However, there is currently a precious little research on the interaction between oxidative stress and complications after HSCT, and the major mechanism has not yet been clarified. The objective of this study was to assess the internal connection between and potential mechanisms as well as visualized the scientometrics results of all important literature related to the topic. Through exhaustive scientometrics analysis, we searched and carefully screened 286 related publications from the Web of Science Core Collection (WoSCC) with “((HSCT) OR (hematopoietic stem cell transplantation)) AND (oxidative stress)” as the search strategy. Then, detailed visualization of the overall information analysis was made by scientific and rigorous bibliometrics software or website. Next, we analyzed retrieved articles extensively and then 59 publications that are relevant to this topic were selected for nuanced analysis and summary. The assessment of these studies proved the validity of the interaction between oxidative stress and complications after HSCT objectively and directly.
Oxidative Stress Response Biomarkers of Ovarian Cancer Based on Single-Cell and Bulk RNA Sequencing
Background. The occurrence and development of ovarian cancer (OV) are significantly influenced by increased levels of oxidative stress (OS) byproducts and the lack of an antioxidant stress repair system. Hence, it is necessary to explore the markers related to OS in OV, which can aid in predicting the prognosis and immunotherapeutic response in patients with OV. Methods. The single-cell RNA-sequencing (scRNA-seq) dataset GSE146026 was retrieved from the Gene Expression Omnibus (GEO) database, and Bulk RNA-seq data were obtained from TCGA and GTEx databases. The Seurat R package and SingleR package were used to analyze scRNA-seq and to identify OS response-related clusters based on ROS markers. The “limma” R package was used to identify the differentially expressed genes (DEGs) between normal and ovarian samples. The risk model was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. The immune cell infiltration, genomic mutation, and drug sensitivity of the model were analyzed using the CIBERSORT algorithm, the “maftools,” and the “pRRophetic” R packages, respectively. Results. Based on scRNA-seq data, we identified 12 clusters; OS response-related genes had the strongest specificity for cluster 12. A total of 151 genes were identified from 2928 DEGs to be significantly correlated with OS response. Finally, nine prognostic genes were used to construct the risk score (RS) model. The risk score model was an independent prognostic factor for OV. The gene mutation frequency and tumor immune microenvironment in the high- and low-risk score groups were significantly different. The value of the risk score model in predicting immunotherapeutic outcomes was confirmed. Conclusions. OS response-related RS model could predict the prognosis and immune responses in patients with OV and provide new strategies for cancer treatment.
Mitochondrial Dysfunction and Increased DNA Damage in Vascular Smooth Muscle Cells of Abdominal Aortic Aneurysm (AAA-SMC)
There is increasing evidence for enhanced oxidative stress in the vascular wall of abdominal aortic aneurysms (AAA). Mitochondrial damage and dysfunction are hypothesized to be actors in altered production of reactive oxygen species (ROS) and oxidative stress. However, the role of mitochondria and oxidative stress in vascular remodelling and progression of AAA remains uncertain. We here addressed whether mitochondrial dysfunction is persistently increased in vascular smooth muscle cells (VSMCs) isolated from AAA compared to healthy VSMC. AAA-derived VSMC cultures (AAA-SMC, ) and normal VSMC cultures derived from healthy donors () were grown in vitro and analysed for four parameters, indicating mitochondrial dysfunction: (i) mitochondrial content and morphology, (ii) ROS production and antioxidative response, (iii) NADP+/NADPH content and ratio, and (iv) DNA damage, in the presence or absence of angiotensin II (AngII). AAA-SMC displayed increased mitochondrial circularity (rounded shape), reduced mitochondrial area, and reduced perimeter, indicating increased fragmentation and dysfunction compared to healthy controls. This was accompanied by significantly increased O2- production, reduced NADP+/NADPH levels, a lower antioxidative response (indicated by antioxidative response element- (ARE-) driven luciferase reporter assays), more DNA damage (determined by percentage of γ-H2A.X-positive nuclei), and earlier growth arrest in AAA-SMC. Our data suggest that mitochondrial dysfunction and oxidative stress are persistently increased in AAA-SMC, emphasizing their implication in the pathophysiology of AAA.
Investigation of Anti-Inflammatory Properties, Phytochemical Constituents, Antioxidant, and Antimicrobial Potentials of the Whole Plant Ethanolic Extract of Achillea santolinoides subsp. wilhelmsii (K. Koch) Greuter of Balochistan
Medicinal plants are rich source of phytochemical constitutes and can be used to treat many human diseases. Infectious diseases have always been a major source of concern. Globally, the medicinal plant Achillea wilhelmsii locally known as Bohe Madran is extensively dispersed and widely used as traditional medicine. The aim of this present work is to investigate phytochemical constituents and antimicrobial, antioxidant, and anti-inflammatory properties of the whole plant ethanolic extract of Achillea santolinoides subsp. wilhelmsii (WEEAW) from Balochistan region. The total phenolic content was mg GAE/g of the extract whereas the total flavonoid content was mg QE/g of the extract. The antioxidant ability of the extract was analyzed by DPPH (2,2-diphenyl-1-picryl-hydrazyl) scavenging assay and FRAP (ferric reducing antioxidant power) assay in terms of concentration having 50% inhibition (IC50). Results showed that IC50 value for DPPH% inhibition was mg/mL while FRAP assay represented with IC50 value of mg/mL. In antileishmanial bioassay, the extract was analyzed against Leishmania major and showed good activity with IC50 value of mg/mL. Antibacterial assay revealed that Staphylococcus aureus was highly sensitive with the diameter of inhibition zone ( mm) followed by Salmonella typhi ( mm), Pseudomonas aeruginosa ( mm), and Escherichia coli ( mm) while Klebsiella pneumoniae showed minimum inhibition ( mm). Antifungal activity was tested against Aspergillus flavus with 89% of inhibition zone and 77% against Mucor mucedo and Aspergillus niger with 74% of inhibition zone. The anti-inflammatory assay was carried out by inhibiting protein denaturation, proteinase inhibitory activity, and heat-induced hemolysis. The IC50 value for protein denaturation was mg/mL, proteinase inhibitory with IC50 value of mg/mL, and heat-induced hemolysis assay with IC50 value mg/mL by comparing to the standard drug aspirin having IC50 value mg/mL. Results of the current work showed that whole plant ethanolic extract of Achillea wilhelmsii exhibited substantial anti-inflammatory action, thus can be utilized as a traditional treatment. Furthermore, overall finding of this research suggested that the antioxidant potential of the plant aids to prevent free radical damage and reduce the incidence of chronic disease. More research is needed to find out more active compounds present in the extract that are responsible for their pharmacological effects.