Krüppel-Like Factor 6 Silencing Prevents Oxidative Stress and Neurological Dysfunction Following Intracerebral Hemorrhage via Sirtuin 5/Nrf2/HO-1 Axis

As a severe neurological deficit, intracerebral hemorrhage (ICH) is associated with overwhelming mortality. Subsequent oxidative stress and neurological dysfunction are likely to cause secondary brain injury. Therefore, this study sought to define the role of Krüppel-like factor 6 (KLF6) and underlying mechanism in oxidative stress and neurological dysfunction following ICH. An in vivo model of ICH was established in rats by injection of autologous blood, and an in vitro ICH cell model was developed in hippocampal neurons by oxyhemoglobin (OxyHb) exposure. Next, gain- and loss-of-function assays were performed in vivo and in vitro to clarify the effect of KLF6 on neurological dysfunction and oxidative stress in ICH rats and neuronal apoptosis and mitochondrial reactive oxygen species in OxyHb-induced hippocampal neurons. KLF6, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) were highly expressed in hippocampal tissues of ICH rats, whereas sirtuin 5 (SIRT5) presented a poor expression. Mechanistically, KLF6 bound to the SIRT5 promoter and transcriptionally repressed SIRT5 to activate the Nrf2/HO-1 signaling pathway. KLF6 silencing alleviated neurological dysfunction and oxidative stress in ICH rats and diminished oxidative stress and neuronal apoptosis in OxyHb-induced neurons, whereas SIRT5 overexpression negated its effect. To sum up, KLF6 silencing elevated SIRT5 expression to inactivate the Nrf2/HO-1 signaling pathway, thus attenuating oxidative stress and neurological dysfunction after ICH.

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Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.746964 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu-Qiong He ◽

Can-Can Zhou ◽

Jiu-Ling Deng ◽

Liang Wang ◽

Wan-Sheng Chen

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Inflammatory Responses ◽

Lung Edema ◽

Protective Effects ◽

And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

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Long Noncoding RNA Maternally Expressed Gene 3 Targets miR-30b and Regulates the AKT Serine/Threonine Kinase 1/Phosphoinositide 3-Kinase Signaling Pathway of H2O2-Induced Proliferation, Apoptosis, and Oxidative Stress in Retinal Ganglion Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2412 ◽

2021 ◽

Vol 11 (3) ◽

pp. 351-358

Author(s):

Kai Yan ◽

Lin Niu ◽

Huili Tian ◽

Fanfan Su ◽

Yao Chen

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Noncoding Rna ◽

Retinal Ganglion ◽

Pi3k Signaling Pathway ◽

Related Proteins ◽

And Oxidative Stress ◽

Maternally Expressed Gene 3

Oxidative stress is an important factor affecting retinal ganglion cell (RGC) apoptosis. RGC apoptosis is the main pathophysiological feature of visual impairment as a result of glaucoma. Recently, it has been found that long noncoding RNA (lncRNA) and microRNAs are involved in RGC apoptosis. Here, the function of lncRNA maternally expressed gene 3 (MEG3) and miR-30b in H2 O2-induced RGC proliferation, apoptosis, and oxidative stress was investigated. The expression levels of MEG3 and miR-30b were detected by RT-PCR; the effects of MEG3 and miR-30b on the proliferation and apoptosis of RGCs were observed by flow cytometry; the levels of apoptosis-related proteins and AKT/PI3K signal pathway proteins were detected by protein immunoassay; and the regulation of miR-34a by pvt1 was verified by in vivo and in vitro experiments. The expression of MEG3 and miR-30b increased and decreased significantly in RGCs treated by H2O2. MEG3 expression decreased, apoptosis level-related proteins decreased, the apoptosis rate reduced, and the activity of MDA and SOD decreased. When the expression of miR-34a was inhibited, the proliferation rate of RGCs increased, the apoptosis rate decreased, and the level of apoptosis-related proteins decreased, which reversed MEG3’s effect on RGC apoptosis and proliferation. Furthermore, pvt1 could bind the miR-30b promoter and regulate it with in vitro expression and in vivo expression. Besides, we found that miR-30b can regulate the AKT/PI3K signaling pathway and participate in cell apoptosis and hyperplasia in stress response. LncRNA MEG3 targets miR-30b and regulates the AKT/PI3K signaling pathway on H2 O2-induced cell apoptosis, hyperplasia, and oxidative stress of RGCs.

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CircFNDC3B Regulates Osteoarthritis and Oxidative Stress by Targeting miR-525-5p/HO-1 axis

10.21203/rs.3.rs-827722/v1 ◽

2021 ◽

Author(s):

Shunwu Fan ◽

Zizheng Chen ◽

Yizhen Huang ◽

Yute Yang ◽

Jinjin Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Rabbit Model ◽

Circular Rna ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Luciferase Reporter ◽

And Oxidative Stress

Abstract Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a patient-derived Circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.

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Resveratrol upregulates miR-455-5p to antagonize cisplatin ototoxicity via modulating the PTEN–PI3K–AKT axis

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0459 ◽

2021 ◽

pp. 1-11

Author(s):

Yupeng Liu ◽

Hui Wu ◽

Fan Zhang ◽

Jun Yang ◽

Jingchun He

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Cell Injury ◽

Auditory Brainstem ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Brainstem Response ◽

And Oxidative Stress

Resveratrol is a non-flavonoid polyphenol compound that exists in many plants, and is considered an antitoxin. This study explores the effects from the regulation of miR-455-5p by resveratrol on cisplatin-induced ototoxicity via the PTEN–PI3K–AKT signaling pathway. For this, House Ear Institute–Organ of Corti 1 (HEI-OC1) cells were transfected with miR-455-5p inhibitor and treated with cisplatin and resveratrol, then cell proliferation, apoptosis, and oxidative stress were evaluated. A mouse model of hearing loss was established, and these mice were treated with cisplatin, resveratrol, or cisplatin combined with resveratrol, by intraperitoneal injection. The auditory brainstem response (ABR) threshold was measured, and hair cells were examined using immunofluorescence staining. The expression levels of miR-455-5p, PTEN, and PI3K/Akt proteins were examined. The results from our in-vitro experiments indicate that resveratrol promoted viability and reduced apoptosis and oxidative stress in cisplatin-induced HEI-OC1 cells. Resveratrol upregulated miR-455-5p, downregulated PTEN, and activated the PI3K–Akt axis. These effects of resveratrol were reversed by knock-down of miR-455-5p. The results from our in-vivo experiments indicate that resveratrol protected hearing and inhibited the hair-cell injury caused by cisplatin ototoxicity. Resveratrol also upregulated miR-455-5p, downregulated PTEN, and activated the PTEN–PI3K–Akt axis in cochlear tissues from cisplatin-treated mice. These results indicate that resveratrol upregulates miR-455-5p to target PTEN and activate the PI3K–Akt signaling pathway to counteract cisplatin ototoxicity.

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Bugan Rongjin decoction alleviates inflammation and oxidative stress to treat the postmenopausal knee osteoarthritis through Wnt signaling pathway

BioMedical Engineering OnLine ◽

10.1186/s12938-021-00939-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Sheng Wang ◽

Pei Ding ◽

Xiaopeng Xia ◽

Xuexian Chen ◽

Daguo Mi ◽

...

Keyword(s):

Oxidative Stress ◽

Knee Osteoarthritis ◽

Wnt Signaling ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Cartilage Tissue ◽

Ovx Rats ◽

And Oxidative Stress

Abstract Background Traditional Chinese medicine has been found effective for the therapy of knee osteoarthritis (KOA). This study was aimed at investigating the underlying mechanism of Bugan Rongjin decoction (BGRJ) in treating the postmenopausal KOA. Results Ovariectomized rat model of KOA and LPS-induced chondrocytes were successfully constructed for in vivo and in vitro model of postmenopausal KOA. X-ray and hematoxylin–eosin (H&E) staining showed that BGRJ alleviated pathological damage of articular cartilage in OVX rats with KOA. In addition, BGRJ inhibited inflammation and oxidative stress through decreasing the levels of serum IL-6, IL-1β, TNF-α and NO and regulated Wnt signaling pathway by downregulating the expression of Wnt5a and β-catenin and upregulating the expression of Sox9 and Collagen II in cartilage tissue, detected by immunohistochemistry (IHC) and western blot analysis. Furthermore, Wnt5a silencing reduced the apoptosis of LPS-induced ADTC5 cells, which was further suppressed by the combination of downregulation of Wnt5a and BGRJ. Conclusions In summary, BGRJ alleviates inflammation and oxidative stress to treat the postmenopausal KOA through Wnt signaling pathway.

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Coenzyme Q10 Regulation of Apoptosis and Oxidative Stress in H2O2 Induced BMSC Death by Modulating the Nrf-2/NQO-1 Signaling Pathway and Its Application in a Model of Spinal Cord Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6493081 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Xing Li ◽

Jiheng Zhan ◽

Yu Hou ◽

Yonghui Hou ◽

Shudong Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Signaling Pathway ◽

Coenzyme Q10 ◽

Therapeutic Efficiency ◽

Cord Injury ◽

And Oxidative Stress

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCs in vitro and explored its molecular mechanisms. Furthermore, we investigated the protective effect of CoQ10 combined with BMSCs transplanted into a SCI model to verify its ability. Our results demonstrate that CoQ10 treatment significantly decreases the expression of the proapoptotic proteins Bax and Caspase-3, as shown through TUNEL-positive staining and the products of oxidative stress (ROS), while increasing the expression of the antiapoptotic protein Bcl-2 and the products of antioxidation, such as glutathione (GSH), against apoptosis and oxidative stress, in a H2O2-induced model. We also identified consistent results from the CoQ10 treatment of BMSCs transplanted into SCI rats in vivo. Moreover, the Nrf-2 signaling pathway was also investigated in order to detail its molecular mechanism, and the results show that it plays an important role, both in vitro and in vivo. Thus, CoQ10 exerts an antiapoptotic and antioxidant effect, as well as improves the microenvironment in vitro and in vivo. It may also protect BMSCs from oxidative stress and enhance their therapeutic efficiency when transplanted for SCI treatment.

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Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

International Journal of Molecular Sciences ◽

10.3390/ijms22041514 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1514 ◽

Cited By ~ 1

Author(s):

Akihiro Yachie

Keyword(s):

Oxidative Stress ◽

Animal Models ◽

Heme Oxygenase ◽

Inflammatory Diseases ◽

Cell Types ◽

Pharmacological Intervention ◽

Heme Oxygenase 1 ◽

Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

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Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽

10.3390/antiox10040507 ◽

2021 ◽

Vol 10 (4) ◽

pp. 507

Author(s):

Rosaria Meccariello ◽

Stefania D’Angelo

Keyword(s):

Oxidative Stress ◽

Food Sources ◽

Preventive Action ◽

Nutritional Interventions ◽

Beneficial Effects ◽

Age Related ◽

Macromolecular Damage ◽

And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

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