Search

Search Results

9 results found. Results per page: [ 20 ][ 40 ][ 60 ][ 80 ][ 100 ][ 200 ][ 300 ]

Sort by: [ Publication Date ][ Score ]

Year of publication: [ 2025 ][ 2024 ][ 2023 ][ 2022 ][ 2021 ][ 2020 ][ 2019 ][ 2018 ][ 2017 ][ 2016 ][ 2015 ][ 2014 ][ 2013 ][ 2012 ][ 2011 ][ 2010 ][ 2009 ][ Any ]

Direction: [ Desc ][ Asc ]

• Research Paper Volume 14, Issue 7 pp 3216-3232

  Trehalose inhibits ferroptosis via NRF2/HO-1 pathway and promotes functional recovery in mice with spinal cord injury

  Relevance score: 13.839455

  Fangyi Gong, Ting Ge, Jing Liu, Jin Xiao, Xiaochuan Wu, Hehui Wang, Yingchun Zhu, Dongdong Xia, Baiwen Hu

  Keywords: spinal cord injury, trehalose, ferroptosis, NRF2/HO-1, neuroinflammation

  Published in Aging on April 10, 2022

  Show abstract
  Hide abstract

  Spinal cord injury (SCI) is the main cause of severe damage to the central nervous system and leads to irreversible tissue loss and neurological dysfunction. Ferroptosis is a cell death pattern, newly discovered in recent years. Ferroptosis is an oxidizing cell death induced by small molecules, and is an iron-dependent process caused by the imbalance between the generation and degradation of lipid reactive oxygen species (ROS) in cells. As an antioxidant, trehalose can effectively prevent lipid peroxidation. Studies have reported that trehalose can improve the prognosis of SCI. However, it is unclear whether these benefits are related to ferroptosis. In this study, we demonstrated for the first time that trehalose reduces the degeneration and iron accumulation of neurons by inhibiting the production of ROS and ferroptosis caused by lipid peroxides after SCI, thus promoting the survival of neurons and improving the recovery of motor function. More specifically, we found that trehalose inhibited the expansion of cavities in the nerve tissue of mice with SCI, inhibited neuron loss, and improved functional recovery. In terms of mechanism, our results indicate that the neuroprotective effect of trehalose is due to the activation of the NRF2/HO-1 pathway, which in turn inhibits ferroptosis and ferroptosis-related inflammation. Our findings provide important insights into the previously unknown role of trehalose in SCI, as well as new evidence supporting the hypothesis that suppression of ferroptosis plays a key neuroprotective role in SCI.

• Research Paper Volume 13, Issue 22 pp 24640-24654

  PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway

  Relevance score: 10.500784

  Haocong Zhang, Dulei Xiang, Xinwei Liu, Liangbi Xiang

  Keywords: PPARα agonist PEA, spinal cord injury, Nrf2/HO-1, Raf-1/MEK/ERK, TUNEL staining

  Published in Aging on November 19, 2021

  Show abstract
  Hide abstract

  Objective: To observe the inhibitory effects of the peroxisome proliferator-activated receptor alpha (PPARα) agonist palmitoylethanolamide (PEA) on inflammatory responses and oxidative stress injury in rats with spinal cord injury (SCI).

  Methods: The SCI rat model was established using modified Allen's method and the changes in rats’ joint motion were observed by Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) at 1, 3 and 7 days after modeling, HE Staining and Nissl Staining has been carried out to evaluate the pathological lesion of spinal cords in rats. Besides, Immunohistochemical (IHC) was performed to detect the reactive oxygen species (ROS), expression levels of acrylamide (ACR) and manganese superoxide dismutase (MnSOD) in rat spinal cords, and Western Blotting was applied to measure protein expression levels of nuclear factor-kappa B (NF-κB), B cell lymphoma-2 (Bcl-2), BCL-2 associated X (BAX), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), phosphorylated (p)-Akt, HO-1, Nrf2, trithorax-1 (TRX-1), Raf-1, MEK, ERK, p-MEK and p-ERK.

  Results: The PPARα agonist PEA could alleviate SCI in rats, inhibit inflammatory responses, mitigate oxidative stress injury, reduce the apoptotic rate and promote SCI rats motor function recovery. In addition, the PPARα agonist PEA was able to activate the phosphorylation of MEK and ERK, stimulate Nrf-2 translocation into the nucleus and up-regulate the expressions of HO-1 and TRX-1.

  Conclusion: PPARα agonist PEA can relieve SCI in rats by inhibiting inflammatory responses and oxidative stress, which may involve a mechanism associated with the activation of Nrf2/HO-1 via the Raf-1/MEK/ERK pathway.

• Research Paper Volume 12, Issue 21 pp 21344-21354

  Soy isoflavones ameliorate the cognitive dysfunction of Goto-Kakizaki rats by activating the Nrf2-HO-1 signalling pathway

  Relevance score: 13.222513

  Boxi Ke, Tianmeng Zhang, Tianyang An, Rong Lu

  Keywords: cognitive decline, soy isoflavones, ROS, Nrf2-HO-1 signal pathway

  Published in Aging on November 7, 2020

  Show abstract
  Hide abstract

  Soy isoflavones (SIF) are soybean phytochemicals that are considered to be biologically active components that protect from neurodegenerative diseases. In this study, the therapeutic effect of SIF was evaluated in a diabetic Goto-Kakizaki (GK) rat model. Twenty male GK rats were randomly divided into diabetes mellitus (DM) model group and SIF+DM group (n=10 in each group). Twenty age-matched male Wistar rats were randomly divided into control group (CON group) and CON+SIF group, with 10 rats in each group. The learning and memory functions of the animals were determined by the Morris water maze (MWM) test. Hematoxylin-eosin staining (HE) was performed to examine pyramidal neuron loss in the CA1 area of the hippocampus. Markers of oxidative stress (OS) were measured to evaluate oxidative stress-mediated injury. RT-PCR and western blotting were used to analyze the expression of nuclear factorerythroid2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone1 (NQO1). Treatment with SIF for 4 weeks alleviated the cognitive dysfunction of the GK rats as determined by the MWM test. Moreover, SIF treatment also reduced diabetes-related oxidative reactions. In addition, SIF enhanced the expression of Nrf2, HO-1 and NQO1, suggesting a potential antioxidation mechanism for the effect of SIF. These findings suggest that SIF can be considered candidates for inhibiting the progression of diabetes-induced cognitive dysfunction, provide novel insights into the antioxidant effect of SIF and further strengthen the link between oxidative stress and diabetes.

• Research Paper Volume 12, Issue 3 pp 2992-3009

  EGF released from human placental mesenchymal stem cells improves premature ovarian insufficiency via NRF2/HO-1 activation

  Relevance score: 10.504669

  Chenyue Ding, Qinyan Zou, Yifei Wu, Jiafeng Lu, Chunfeng Qian, Hong Li, Boxian Huang

  Keywords: human placental mesenchymal stem cells, premature ovarian insufficiency, epidermal growth factor, oxidative stress, NRF2/HO-1

  Published in Aging on February 10, 2020

  Show abstract
  Hide abstract

  Human placental mesenchymal stem cells (hPMSCs) have the ability to release cytokines and to differentiate into the three germ layers. To date, the relevance of hPMSCs for the treatment of premature ovarian insufficiency (POI) disease through the regulation of oxidative stress is still unclear. Therefore, to evaluate the therapeutic efficiency and investigate the mechanism of hPMSCs, we generated a mouse model of POI and collected human ovarian granule cells (hGCs) from patients with POI. hPMSCs displayed therapeutic effects on POI ovarian function, including recovered follicular numbers and increased expression of oocyte markers. Furthermore, secretion of the cytokine EGF (epidermal growth factor) was higher from hPMSCs than it was from other cells. FACS and Western blot analyses showed that EGF elevated the proliferation and reduced the apoptosis in hGCs. hPMSCs and EGF inhibited oxidative stress levels. Protein assays demonstrated that EGF suppressed oxidative stress by dose-dependently upregulating the expression of the NRF2/HO-1 pathway, and it inhibited the apoptosis by regulating the PTEN/PI3K/AKT pathway. These findings provide an experimental foundation for hPMSCs in improving ovarian function through the secretion of EGF. The mechanism of action of EGF is related to protection from oxidative stress by activation of the NRF2/HO-1.

  

  hPMSCs improved the function of a POI mouse model. (A) The number of primordial follicles recovered to normal levels four weeks after hPMSC transplantation. (B) hPMSC transplantation restored the primary follicle numbers. (C) hPMSC elevated the number of secondary follicles to the WT group level (D) hPMSC transplantation elevated the number of antral follicles to the WT group level. (E) ELISA results indicated that hPMSC transplantation increased the levels of E2. (F) hPMSC transplantation improved the levels of AMH. (G) hPMSC transplantation decreased the levels of FSH to the WT group level. All experiments were carried out three times; error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency, hPMSC = human placental mesenchymal stem cell.

  
  
  

  

  hPMSCs upregulated the marker expression level of hGCs with POI. (A) FACS results indicated that hPMSCs increased the number of FSHR⁺AMH⁺ positive hGCs. (B) FACS results indicated that hPMSCs increased the number of CYP19A1⁺FOXL2⁺ positive hGCs. (C) Western blot results showed that hPMSCs increased the protein levels of FSHR, AMH, CYP19A1 and FOXL2 in POI hGCs to the normal level. All experiments were carried out three times; error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency, hPMSC = human placental mesenchymal stem cell, hGCs = human ovarian granule cells.

  
  
  

  

  EGF derived from hPMSCs was observed at higher levels than other growth factors. (A) Antibody microarray analysis of growth factor secretion from the hPMSC and control groups (293T cell line). Four growth factors were selected in accordance with standard criteria: the fold change was greater than or equal to sixteen, and there was statistical significance (p< 0.01). (B) EGF derived from hPMSCs was secreted at higher levels than other growth factors. (C) EGF was highly expressed in the POI mouse model after hPMSC transplantation. All experiments were carried out three times. hPMSC = human placental mesenchymal stem cell.

  
  
  

  

  EGF derived from hPMSCs improved the proliferation rate and inhibited the apoptosis rate in POI hGCs. (A) FACS results indicated that hPMSCs, hPMSC-CM or EGF treatment improved the proliferation rate (Ki67) in POI hGCs. (B) FACS results indicated that hPMSCs, hPMSC-CM or EGF treatment inhibited the rate of apoptosis (Annexin V) in POI hGCs. (C) Western blot results demonstrated that hPMSCs, hPMSC-CM or EGF treatment increased the expression of apoptosis resistance genes (Bcl2 and Survivin) and reduced the expression levels of apoptosis genes (Caspase 3 and Caspase 9). All of the experiments were carried out three times; the error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency.

  
  
  

  

  EGF derived from hPMSCs suppressed ROS in POI hGCs. (A) hPMSC, hPMSC-CM or EGF treatment suppressed ROS in vitro to normal levels (POI hGCs). (B) ELISA results revealed that hPMSCs, hPMSC-CM or EGF treatment inhibited MDA expression to the WT group level. (C) hPMSC, hPMSC-CM or EGF treatment suppressed the level of SOD expression in vitro. (D) ELISA results indicated that hPMSCs, hPMSC-CM or EGF treatment elevated CAT expression in POI hGCs. (E) hPMSC, hPMSC-CM or EGF treatment increased LDH expression to the WT group level in vitro. (F) ELISA results demonstrated that hPMSCs, hPMSC-CM or EGF improved the level of GR in vitro. (G) hPMSC, hPMSC-CM or EGF treatment increased GPx expression to normal levels in POI hGCs. All of the experiments were carried out three times. The error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency.

  
  
  

  

  EGF derived from hPMSCs suppressed ROS by upregulating the NRF2/HO-1 pathway in vitro. (A) qPCR analysis of the mRNA expression levels of PI3K, AKT and PTEN in POI hGCs after hPMSC or EGF (with 10 ng/ml, 20 ng/ml, and 40 ng/ml) treatment. (B) Western blot analysis of the protein levels of PI3K, AKT and PTEN in POI hGCs after hPMSC and EGF (with 10 ng/ml, 20 ng/ml, and 40 ng/ml) treatment. (C) qPCR analysis of the mRNA levels of NRF2 and HO-1 in POI hGCs after hPMSC or EGF (with 10 ng/ml, 20 ng/ml, and 40 ng/ml) treatment. (D) Western blot analysis of the protein levels of NRF2 and HO-1 in POI hGCs after hPMSC or EGF (with 10 ng/ml, 20 ng/ml, and 40 ng/ml) treatment. (E) Western blot analysis of the protein levels of NRF2, HO-1, CASPASE 3 and CASPASE 9 in H₂O₂-treated hGCs after EGF (with different concentrations) coculture. All experiments were carried out three times. The error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency. The qPCR primer sequences used are listed in Supplementary Table 1.

  
  
  

  

  EGF derived from hPMSCs suppressed ROS by upregulating the NRF2/HO-1 pathway in a POI mouse model. (A) qPCR analysis of the mRNA expression levels of PI3K, AKT and PTEN in POI hGCs after in vivo treatment with hPMSC or EGF (with 0.1 μg/ml, 0.5 μg/ml, and 1.0 μg/ml). (B) Western blot analysis of the protein expression levels of PI3K, AKT and PTEN in POI hGCs after hPMSC or EGF (with 0.1 μg/ml, 0.5 μg/ml, 1.0 μg/ml) treatment. (C) qPCR analysis of the mRNA levels of NRF2 and HO-1 in POI hGCs after hPMSC and EGF (with 0.1 μg/ml, 0.5 μg/ml, and 1.0 μg/ml) treatment. (D) Western blot analysis of the protein levels of NRF2 and HO-1 in POI hGCs after hPMSC and EGF (with 0.1 μg/ml, 0.5 μg/ml, and 1.0 μg/ml) treatment. All experiments were carried out three times. The error bars indicate the SD; *** p < 0.001 (compared with the POI group). POI = premature ovarian insufficiency. The qPCR primer sequences used are listed in Supplementary Table 1.

  
  
  

  

  EGF affected ROS levels by regulating the NRF2/HO-1 signaling pathway but not the PI3K/AKT signaling pathway. (A) qPCR analysis of the expression levels of PTEN, NRF2, HO-1, PI3K and AKT in hGCs-NRF2^KD after treatment with EGF. (B) Western blot analysis of the expression levels of PTEN, NRF2, HO-1, PI3K and AKT in hGCs-NRF2^KD after treatment with EGF. (C) ROS levels were measured in hGCs-NRF2^KD after treatment with hPMSCs and EGF. (D) qPCR analysis of the expression levels of PTEN, NRF2, HO-1, PI3K and AKT in hGCs-PTEN^KD after treatment with EGF. (E) Western blot analysis of the expression levels of PTEN, NRF2, HO-1, PI3K and AKT in hGCs-PTEN^KD after treatment with EGF. (F) ROS levels were measured in hGCs-PTEN^KD after treatment with hPMSCs and EGF. All experiments were carried out three times. The error bars indicate the SD; **, p < 0.01; *** p < 0.001 (compared with the NRF2 or PTEN knockdown group, respectively). The qPCR primer sequences used are listed in Supplementary Table 1.

  
  
  

• Research Paper Volume 11, Issue 24 pp 12361-12374

  A phenolic amide (LyA) isolated from the fruits of Lycium barbarum protects against cerebral ischemia–reperfusion injury via PKCε/Nrf2/HO-1 pathway

  Relevance score: 13.58243

  Kai Gao, Meiyou Liu, Yi Ding, Minna Yao, Yanrong Zhu, Jinyi Zhao, Lianghua Cheng, Juan Bai, Fan Wang, Jinyi Cao, Jiankang Li, Haifeng Tang, Yanyan Jia, Aidong Wen

  Keywords: ischemic stroke, Lyciumamide A, oxidative stress, PKCε, Nrf2, HO-1

  Published in Aging on December 26, 2019

  Show abstract
  Hide abstract

  Lyciumamide A (LyA), a dimer of phenolic amide isolated from the fruits of Lycium barbarum, has been confirmed to possess potent antioxidant activity. This study was aimed to investigate the neuroprotection and molecular mechanisms of LyA against cerebral ischemia/reperfusion (I/R) injury via improving antioxidant activity. The model of middle cerebral artery occlusion (MCAO) and SH-SY5Y cells induced by oxygen and glucose deprivation (OGD) were adopted to verify the neuroprotective effects and the potential pharmacology mechanisms of LyA in vivo and in vitro. In MCAO model, treatment with LyA significantly improved neurologic score, reduced infarct volume, and relieved oxidative stress injury at 48 h after reperfusion. Meanwhile, LyA markedly increased the transcription Nrf2 and HO-1 expressions in the ischemic cerebral cortex. In vitro results showed that LyA protected differentiated SH-SY5Y cells against OGD-induced injury. LyA significantly decreased the expression of caspase-3 and the Bax/Bcl-2 ratio. But knockdown of Nrf2 or HO-1 attenuated the protective effect of LyA. Similarly, knockdown of protein kinase Cε (PKCε) inhibited LyA-induced Nrf2/HO-1 activation, and abated its protective effects. In conclusion, this study firstly demonstrated that LyA protects against cerebral I/R injury, ameliorates oxidative damage and neuronal apoptosis, partly via activation of PKCε/Nrf2/HO-1 pathway.

  

  Effects of phenolic amides and OGD on cell viability. (A) Chemical structure of phenolic amides (1-5). Thereinto, the compound 3 is Lyciumamide A (LyA). (B) MTT assay was employed to investigate the protective effects of phenolic amides against OGD-induced cytotoxicity. The concentrations of these compounds is 40 μM. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with control group; ^#p < 0.05 compared with OGD group.

  
  
  

  

  LyA protects against cerebral ischemic-reperfusion injury. (A) TTC staining of the cerebral infarct in the sham, control and treatment with LyA groups. (B) The columnar diagram for the infarct volume of brains in each group (n=6). (C) Neurological scores of rats at 48 h after cerebral I/R for each group (n=8). (D) H-E stains of coronal sections from the ischemic cerebral cortex (scale bar 100 μm). (E) Necrotic neurons were counted and analyzed in each group (n=6). All data, except for neurological scores, were expressed as mean ± SD. ^*p < 0.05 compared with sham group; ^#p < 0.05 compared with I/R group.

  
  
  

  

  LyA Promoted the Expression of Nrf2 and HO-1. (A) Protein expressions of Nuclear Nrf2, Cytoplasmic Nrf2 and HO-1 were evaluated by Western blot analysis. (B) The immunofluorescence staining of Nrf2 with DAPI (400 x). Data were presented as mean ± SD (n = 6). ^*p < 0.05 compared with I/R group.

  
  
  

  

  Effects of LyA and OGD on cell viability. (A) Cells were incubated in different concentrations of LyA alone. (B) MTT assay was employed to investigate the protective effect of LyA against OGD-induced cytotoxicity. (C) Cell death was further confirmed by measuring LDH leakage. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with control group; ^#p < 0.05 compared with OGD group.

  
  
  

  

  Effects of LyA on apoptotic in SH-SY5Y cells. (A) Hoechst 33342 staining (scale bar 100 μm). (B) Effects of LyA on OGD-induced apoptosis after AV-PI double stain. (C) The quantitative analysis of apoptotic cells. (D) Protein expressions of bax, bcl-2 and cleaved caspase-3 were evaluated by western blot analysis. (E) Relative expressions are calculated and are shown here. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with control group; ^#p < 0.05 compared with OGD group.

  
  
  

  

  Effect of LyA treatment on PKCε phosphorylation, activation of Nrf2/HO-1 pathway in SH-SY5Y cells. (A) Representative bands of each protein are presented. (B) Relative expressions are calculated and are shown here. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with control group; ^#p < 0.05 compared with OGD group.

  
  
  

  

  The neuroprotection of LyA involved the Nrf2/HO-1 pathway. (A–C) Cells were transfected with control or HO-1 and Nrf2 siRNA for 48 h, followed by treatment with 40 μM LyA for 8 h. HO-1 and Nrf2 expression levels were analyzed by western blotting. Data were presented as mean ± SD (n =6). ^*p < 0.05 vs si-control group without LyA; ^#p < 0.05 vs si-control group with LyA. (D) Cells were treated for 48 h with control or siRNA, and then treated with 40 μM LyA for 8 h before being subjected to 60 min OGD followed at 24 h by the MTT assay. (E) Intracellular ROS level. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with OGD group; ^#p < 0.05 compared with OGD + LyA group.

  
  
  

  

  PKCε mediated LyA-induced neuroprotection, Nrf2 nuclear translocation, and HO-1 upregulation. (A–C) Cells were transfected with control or PKCε siRNA for 48 h, followed by treatment with 40 μM LyA for 8 h. p-PKCε, PKCε, HO-1, Nrf2, bax, bcl-2 and cleaved caspase-3 expression levels were analyzed by western blotting. Data were presented as mean ± SD (n =6). ^*p < 0.05 vs si-control group without LyA; ^#p < 0.05 vs si-control group with LyA. (D) Cells were treated for 48 h with control or siRNA, and then treated with 40 μM LyA for 8 h before being subjected to 60 min OGD followed at 24 h by the MTT assay. (E) Intracellular ROS level. Data were represented as means ± SD (n=6). ^*p < 0.05 compared with OGD group; ^#p < 0.05 compared with OGD + LyA group.

  
  
  

• Research Paper Volume 10, Issue 8 pp 2016-2036

  Lycopene ameliorates oxidative stress in the aging chicken ovary via activation of Nrf2/HO-1 pathway

  Relevance score: 13.839455

  Xingting Liu, Xin Lin, Siyu Zhang, Changquan Guo, Jian Li, Yuling Mi, Caiqiao Zhang

  Keywords: lycopene,ovarian aging, oxidative stress, Nrf2/HO-1, chicken

  Published in Aging on August 16, 2018

  Show abstract
  Hide abstract

  After 480 days of age, high-producing hens are likely to be subject to ovarian aging, mainly due to oxidative stress. In this study, the amelioration of ovarian aging in chickens, using a plant antioxidant, lycopene, was investigated. The activity of the Nrf2/HO-1 pathway in chicken ovaries at different ages (90, 150, 280 and 580 days old) were compared to elucidate any age-related changes. Subsequently, the putative attenuating effect of lycopene (100 ng/mL) on ovarian aging was evaluated through the establishment of a D-gal-induced aging ovarian culture model. The cultured ovarian tissues of young (280 days) and old (580 days) hens were treated with lycopene for 72 h to verify protective effects of lycopene on naturally aged ovaries. Results showed that the Nrf2/HO-1 pathway was down-regulated during the ovarian aging process. Lycopene rescued the decreased antioxidant capacity by increasing the activities of antioxidases and activating the Nrf2/HO-1 pathway in both D-gal-induced and naturally aged ovaries. Moreover, lycopene promoted cell proliferation and inhibited apoptosis in both D-gal-induced and naturally aged ovaries. Lycopene also alleviated D-gal-induced mitochondrial damage in the living granulosa cells. In conclusion, lycopene can effectively ameliorate the oxidative stress in aging hen ovaries via the activation of the Nrf2/HO-1 pathway.

  

  Age-related changes in the activity of the Nrf2/HO-1 pathway. (A) Immunohistochemistry of Nrf2 in the ovaries of hens aged 90, 150, 280 and 580 days, scale bar: 10 μm, black arrowheads: Nrf2 located in the nucleus. (B) Age-related changes in relative expression levels of Nrf2, pNrf2, Keap1, HO-1 and NQO1. (C) Age-related changes in transcription levels of Nrf2/HO-1 downstream genes: Gclc, Gclm, Glrx, Gpx1, Txn, Txnrd. Values are expressed as the means±s.e.. The relative abundance of each transcript was normalized to a β-actin and expressed as fold change over D90 ovaries. Different lowercase letters indicate significant differences (P < 0.05).

  
  
  

  

  Protective effects of lycopene on D-gal-induced aged ovaries. (A) Effect of lycopene on D-gal-induced morphological changes of ovarian tissues, scale bar: 50 µm. (B) Effect of lycopene on D-gal-induced ultrastructural changes of granulosa cells: the four pictures in the lower row are the higher magnifications of the red squares from the four pictures in the upper row, respectively, scale bar: 2 µm (upper); 1 µm (lower), red arrowheads: fragmented mitochondria. (C) Effect of lycopene on D-gal-induced decline of BrdU index, scale bar: 20 µm; (D) Relative expression of proteins related to cell proliferation. (E) Effect of lycopene on D-gal-induced increase of TUNEL index, scale bar: 20 µm. (F) Relative expression of proteins related to pro-apoptosis (Bax) and anti-apoptosis (Bcl-xL). Values are expressed as the means±s.e.. Different lowercase letters indicate significant differences (P < 0.05).

  
  
  

  

  Effects of lycopene on decreased antioxidant status in D-gal-induced aged ovarian tissues and the activities of Nrf2/HO-1 pathway. (A) Effect of lycopene on decreased antioxidants status in the D-gal-induced aged ovarian tissues. (B) Effect of lycopene on the down-regulated expression of Nrf2, pNrf2 and HO-1, and the mRNA abundance of Nrf2 and HO-1. (C) Effect of lycopene on down-regulated mRNA abundance of Nrf2/HO-1 downstream genes. Values are expressed as the means±s.e.. Different lowercase letters indicate significant differences (P < 0.05).

  
  
  

  

  Protective effect of lycopene on oxidative stress in aged ovarian tissues was similar to the effects of DMF. (A) Relative changes in the expression of Nrf2, pNrf2 and HO-1 after treatment with D-gal alone or combined with DMF or lycopene. (B) Changes in the morphology of ovarian tissues after treatment with D-gal alone or combined with DMF or lycopene, scale bar: 50 µm. (C and E) Changes in BrdU index in ovarian tissues after treatment with D-gal alone or combined with DMF or lycopene, scale bar: 20 µm. (D) Relative changes in the expression of proteins related to cell proliferation and cell apoptosis in ovarian tissues after treatment with D-gal alone or combined with DMF or lycopene. (E and G) Changes in TUNEL index in ovarian tissues after treatment with D-gal alone or combined with DMF or lycopene, scale bar: 20 µm. (F) Changes in ROS levels of the ovarian tissues after treatment with D-gal alone or combined with DMF or lycopene. Values are expressed as the means±s.e.. Different lowercase letters indicate significant differences (P < 0.05).

  
  
  

  

  Protective effect of lycopene on the oxidative stress in the aging ovarian tissues was abolished by ML385. (A) Relative changes in the expression of Nrf2, pNrf2 and HO-1 after treatment with D-gal, ML385 alone or combined with lycopene. (B) Changes in the morphology of ovarian tissues after treatment with D-gal, ML385 alone or combined with lycopene, scale bar: 50 µm. (C and E) Changes in BrdU index in ovarian tissues after treatment with D-gal, ML385 alone or combined with lycopene, scale bar: 20 µm. (D) Relative changes in the expression of proteins related to cell proliferation and cell apoptosis in ovarian tissues after treatment with D-gal, ML385 alone or combined with lycopene. (E and G) Changes in TUNEL index in ovarian tissues after treatment with D-gal, ML385 alone or combined with lycopene, scale bar: 20 µm. (F) Changes in the levels of ROS in ovarian tissues after treatment with D-gal, ML385 alone or combined with lycopene. Values are expressed as the means±s.e.. Different lowercase letters indicate significant differences (P < 0.05).

  
  
  

  

  Effects of lycopene on the antioxidant capacity, cell proliferation and apoptosis in the ovarian tissues of D280 and D580 hens in vitro. (A) Effect of lycopene on antioxidant capacity in ovarian tissues of D280 and D580 hens in vitro. (B) Effect of lycopene on expression of Nrf2, pNrf2 and HO-1, and the mRNA abundance of Nrf2 and HO-1 in ovarian tissues of D280 and D580 hens in vitro. (C) Effect of lycopene on the mRNA abundance of Nrf2/HO-1 downstream genes in the ovarian tissues of D280 and D580 hens in vitro. (D) Effect of lycopene on the expression of proteins related to cell proliferation and apoptosis in the ovarian tissues of D280 and D580 hens in vitro. Each parameter was determined after 72 h of treatment with lycopene (100 ng/mL). Values are expressed as the means±s.e.. Different lowercase letters indicate significant differences (P < 0.05) for the same age.

  
  
  

  

  Schematic diagram summarizing the mechanisms underlying the attenuating effect of lycopene against ovarian oxidative stress during the aging process in chickens. The Nrf2/HO-1 pathway was down-regulated in the natural aging process in the laying hens. Lycopene attenuated the oxidative stress in aging ovaries via the activation of Nrf2/HO-1 pathway.

  
  
  

• Research Paper pp undefined-undefined

  Tremella fuciformis polysaccharides induce ferroptosis in Epstein–Barr virus-associated gastric cancer by inactivating NRF2/HO-1 signaling

  Relevance score: 12.010382

  Wencheng Kong, Xinchun Liu, Hangzhang Zhu, Sixing Zheng, Guang Yin, Panpan Yu, Yuqiang Shan, Shenglin Ma, Rongchao Ying, Huicheng Jin

  Keywords: Tremella fuciformis polysaccharides, ferroptosis, Epstein-Barr virus-associated gastric cancer, NRF2/HO-1

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Approximately 10% of gastric cancers are associated with Epstein–Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT–qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.

• Research Paper pp undefined-undefined

  Exploring anti- acute kidney injury mechanism of Dahuang-Gancao decoction by network pharmacology and experimental validation

  Relevance score: 10.500784

  Rui Wang, Yi An, Yifang Xu, Chengyin Li, Qiyuan Wang, Yinshui Zou, Guangzhi Wang

  Keywords: acute kidney injury, network pharmacology, Dahuang-Gancao decoction, experimental validation, SIRT3/NRF2/HO-1 signaling pathway

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  This study aimed to investigate the pharmacological effects and molecular mechanisms of Dahuang-Gancao Decoction (DHGC) on acute kidney injury (AKI). Network pharmacology was utilized to analyze the key targets of DHGC against AKI. These targets were used to construct a protein-protein interaction (PPI) network, which was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict the mechanism of action. Based on the network pharmacological analysis, Sirtuin 3 (SIRT3) was identified as a key target, and apoptosis was suggested as a mechanism of DHGC for AKI treatment. Subsequently, an AKI mouse model was induced using lipopolysaccharide (LPS), and the study demonstrated that DHGC gradient intervention significantly reduced plasma urea and creatinine levels in AKI mice, ameliorated renal pathological changes, reduced apoptosis, and lowered serum inflammatory factors. The mechanism of DHGC’s anti-AKI effect may lie in the activation of the SIRT3/NRF2/HO-1 signaling pathway, which plays an antiapoptotic role in renal cells. In summary, DHGC improved LPS-induced AKI in mice by activating the SIRT3/NRF2/HO-1 signaling pathway. These findings shed light on the potential clinical application of DHGC for the treatment of nephropathy.

• Research Paper pp undefined-undefined

  Moxibustion prevents tripterygium glycoside-induced oligoasthenoteratozoospermia in rats via reduced oxidative stress and modulation of the Nrf2/HO-1 signaling pathway

  Relevance score: 14.489309

  Shangjie Liang, Yaqun Yin, Zhizi Zhang, Yansu Fang, Ge Lu, Hongxiao Li, Yaoli Yin, Meihong Shen

  Keywords: moxibustion, oligoasthenoteratozoospermia, sperm quality, oxidative stress, Nrf2, HO-1

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.