Oxidative Medicine and Cellular Longevity

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ISSN / EISSN : 1942-0900 / 1942-0994
Published by: Hindawi Limited (10.1155)
Total articles ≅ 5,565
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Lin Zhou, Fengjuan Yan, Rui Jiang, Jing Liu, Limin Cai, Yongchen Wang
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-14; https://doi.org/10.1155/2021/9930187

Ulcerative colitis (UC) is a common chronic nonspecific intestinal inflammation of unknown etiology associated with a low cure rate and a high relapse rate. Hair follicle mesenchymal stem cells (HF-MSCs) are a class of pluripotent stem cells that have differentiation potential and strong proliferation ability. Nuclear factor red system related factor (Nrf-2) is a key factor in the oxidative stress response. Dextran sulfate sodium- (DSS-) induced rat UC models closely mimic human UC in terms of symptoms and histological changes. Animals were divided into five groups, including a healthy group and UC model rats treated with normal saline, Nrf-2, HF-MSCs, or Nrf-2-expressing HF-MSC group. Based on the expression of intestinal stem cells, inflammatory factors, anti-inflammatory factors, and disease activity index scores, Nrf-2-expressing HF-MSCs had the most obvious therapeutic effect under the same treatment regimen. This study provided a new potential clinical treatment option for ulcerative colitis.
Han Ki Lee, Hyo Sun Cha, Myeong Jin Nam, Kyungmoon Park, Yung-Hun Yang, ,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-17; https://doi.org/10.1155/2021/2800706

Broussochalcone A (BCA) is a chalcone compound extracted from the cortex of Broussonetiapapyrifera (L.) Ventenat that exerts various effects, such as potent antioxidant, antiplatelet, and anticancer effects. However, the effects of BCA against cancers have been seldom studied. This study is aimed at demonstrating the apoptotic mechanisms of BCA in A498 and ACHN cells, which are two types of human renal cancer cell lines. MTT, cell counting, and colony formation assays indicated that BCA treatment inhibited cell viability and cell growth. Further, cell cycle analysis revealed that BCA induced cell cycle arrest at the G2/M phase. Annexin V/PI staining and TUNEL assays were performed to determine the apoptotic effects and DNA fragmentation after treatment with BCA. Based on western blot analysis, BCA induced the upregulation of cleaved PARP, FOXO3, Bax, p21, p27, p53, phosphorylated p53 (ser15, ser20, and ser46), and active forms of caspase-3, caspase-7, and caspase-9 proteins, but downregulated the proforms of the proteins. The expression levels of pAkt, Bcl-2, and Bcl-xL were also found to be downregulated. Western blot analysis of nuclear fractionation results revealed that BCA induced the nuclear translocation of FOXO3, which might be induced by DNA damage owing to the accumulation of reactive oxygen species (ROS). Elevated intracellular ROS levels were also found following BCA treatment. Furthermore, DNA damage was detected after BCA treatment using a comet assay. The purpose of this study was to elucidate the apoptotic effects of BCA against renal cancer A498 and ACHN cells. Collectively, our study findings revealed that the apoptotic effects of BCA against human renal cancer cells occur via the elevation of ROS level and activation of the FOXO3 signaling pathway.
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-20; https://doi.org/10.1155/2021/2990326

Nanomedicine and plasma medicine are innovative and multidisciplinary research fields aiming to employ nanotechnology and gas plasma to improve health-related treatments. Especially cancer treatment has been in the focus of both approaches because clinical response rates with traditional methods that remain improvable for many types of tumor entities. Here, we discuss the recent progress of nanotechnology and gas plasma independently as well as in the concomitant modality of nanoplasma as multimodal platforms with unique capabilities for addressing various therapeutic issues in oncological research. The main features, delivery vehicles, and nexus between reactivity and therapeutic outcomes of nanoparticles and the processes, efficacy, and mechanisms of gas plasma are examined. Especially that the unique feature of gas plasma technology, the local and temporally controlled deposition of a plethora of reactive oxygen, and nitrogen species released simultaneously might be a suitable additive treatment to the use of systemic nanotechnology therapy approaches. Finally, we focus on the convergence of plasma and nanotechnology to provide a suitable strategy that may lead to the required therapeutic outcomes.
Yanfei Shao, Hongtao Jia, Shuchun Li, Ling Huang, Batuer Aikemu, Guang Yang, Sen Zhang, ,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-29; https://doi.org/10.1155/2021/7007933

Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group ( P < 0.001 ). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.
Ruoyun Wu, , Xiaoqin Ding, Han Lv, Xiuhua Meng, Bingru Ren, Jing Li, , Weilin Li
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-13; https://doi.org/10.1155/2021/4706410

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.
Carla P. Vieira, Anisio Iuri L. S. Rosario, Carini A. Lelis, Bruna Samara S. Rekowsky, , , Thaísa A. Elias, , ,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-34; https://doi.org/10.1155/2021/9081738

Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from in vitro and in vivo studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences ( P < 0.05 ) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential—OR of 8.56 (95% CI: 2.27–32.21, P ≤ .001 )—according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
Ting Hong, Yiyan Chen, Xiaoying Li,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-25; https://doi.org/10.1155/2021/6889533

The overproduction of reactive oxygen species (ROS) and consequent oxidative stress contribute to the pathogenesis of acute and chronic liver diseases. It is now acknowledged that nonalcoholic fatty liver disease (NAFLD) is characterized as a redox-centered disease due to the role of ROS in hepatic metabolism. However, the underlying mechanisms accounting for these alternations are not completely understood. Several nuclear receptors (NRs) are dysregulated in NAFLD, and have a direct influence on the expression of a set of genes relating to the progress of hepatic lipid homeostasis and ROS generation. Meanwhile, the NRs act as redox sensors in response to metabolic stress. Therefore, targeting NRs may represent a promising strategy for improving oxidation damage and treating NAFLD. This review summarizes the link between impaired lipid metabolism and oxidative stress and highlights some NRs involved in regulating oxidant/antioxidant turnover in the context of NAFLD, shedding light on potential therapies based on NR-mediated modulation of ROS generation and lipid accumulation.
Yanni Pan, Yujing Ning, Jing Hu, Zhiying Wang, Xiufeng Chen,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-16; https://doi.org/10.1155/2021/9416794

In this study, we used DSS to establish an IBD mouse model to study the preventive effect of Lactobacillus plantarum (L. plantarum) ZS62 on IBD in the context of oxidative stress and the immune response. We assessed the mitigating effect of this strain on IBD mice by examining the length of and histopathological changes in the colon, determining the serum antioxidant index and the levels of inflammatory cytokines, as well as the mRNA and protein expression levels of relevant genes. The study results showed that L. plantarum ZS62 could inhibit colonic atrophy in IBD mice, reduce the degree of colonic damage, downregulate the serum levels of MDA, MPO, IL-1β, IL-6, IL-12, TNF-α, and IFN-γ and the relative mRNA and protein expression of IL-1β, IL-12, TNF-α, COX-2, iNOS, and NF-κB p65 in mouse colon tissues, and upregulate the serum levels of CAT, T-SOD, and IL-10 and the relative mRNA and protein expression of Cu/Zn SOD, Mn SOD, GSH-Px, CAT, IL-10, and IκB-α in colon tissues. In summary, L. plantarum ZS62 exhibited a good preventive effect on DSS-induced IBD by regulating oxidative stress and the immune response.
Acharya Balkrishna, , Vedpriya Arya, Akansha Rohela, , Eugenie Nepovimova, , Dinesh Kumar, Naveen Thakur,
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-20; https://doi.org/10.1155/2021/3155962

Nanotechnology is gaining significant attention, with numerous biomedical applications. Silver in wound dressings, copper oxide and silver in antibacterial preparations, and zinc oxide nanoparticles as a food and cosmetic ingredient are common examples. However, adverse effects of nanoparticles in humans and the environment from extended exposure at varied concentrations have yet to be established. One of the drawbacks of employing nanoparticles is their tendency to cause oxidative stress, a significant public health concern with life-threatening consequences. Cardiovascular, renal, and respiratory problems and diabetes are among the oxidative stress-related disorders. In this context, phytoantioxidant functionalized nanoparticles could be a novel and effective alternative. In addition to performing their intended function, they can protect against oxidative damage. This review was designed by searching through various websites, books, and articles found in PubMed, Science Direct, and Google Scholar. To begin with, oxidative stress, its related diseases, and the mechanistic basis of oxidative damage caused by nanoparticles are discussed. One of the main mechanisms of action of nanoparticles was unearthed to be oxidative stress, which limits their use in humans. Secondly, the role of phytoantioxidant functionalized nanoparticles in oxidative damage prevention is critically discussed. The parameters for the characterization of nanoparticles were also discussed. The majority of silver, gold, iron, zinc oxide, and copper nanoparticles produced utilizing various plant extracts were active free radical scavengers. This potential is linked to several surface fabricated phytoconstituents, such as flavonoids and phenols. These phytoantioxidant functionalized nanoparticles could be a better alternative to nanoparticles prepared by other existing approaches.
Yisheng Chen, Yaying Sun, , Wei-Wei Lin, Zhiwen Luo, Zhihua Han, Shaohua Liu, Beijie Qi, Chenyu Sun, Ken Go, et al.
Oxidative Medicine and Cellular Longevity, Volume 2021, pp 1-29; https://doi.org/10.1155/2021/7663366

Introduction. Regeneration of fibrochondrocytes is essential for the healing of the tendon-bone interface (TBI), which is similar to the formation of neurogenic heterotopic ossification (HO). Through single-cell integrative analysis, this study explored the homogeneity of HO cells and fibrochondrocytes. Methods. This study integrated six datasets, namely, GSE94683, GSE144306, GSE168153, GSE138515, GSE102929, and GSE110993. The differentiation trajectory and key transcription factors (TFs) for HO occurrence were systematically analyzed by integrating single-cell RNA (scRNA) sequencing, bulk RNA sequencing, and assay of transposase accessible chromatin seq. The differential expression and enrichment pathways of TFs in heterotopically ossified tissues were identified. Results. HO that mimicked pathological cells was classified into HO1 and HO2 cell subsets. Results of the pseudo-temporal sequence analysis suggested that HO2 is a differentiated precursor cell of HO1. The analysis of integrated scRNA data revealed that ectopically ossified cells have similar transcriptional characteristics to cells in the fibrocartilaginous zone of tendons. The modified SCENIC method was used to identify specific transcriptional regulators associated with ectopic ossification. Xbp1 was defined as a common key transcriptional regulator of ectopically ossified tissues and the fibrocartilaginous zone of tendons. Subsequently, the CellPhoneDB database was completed for the cellular ligand-receptor analysis. With further pathway screening, this study is the first to propose that Xbp1 may upregulate the Notch signaling pathway through Jag1 transcription. Twenty-four microRNAs were screened and were found to be potentially associated with upregulation of XBP1 expression after acute ischemic stroke. Conclusion. A systematic analysis of the differentiation landscape and cellular homogeneity facilitated a molecular understanding of the phenotypic similarities between cells in the fibrocartilaginous region of tendon and HO cells. Furthermore, by identifying Xbp1 as a hub regulator and by conducting a ligand–receptor analysis, we propose a potential Xbp1/Jag1/Notch signaling pathway.
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