keyword
https://read.qxmd.com/read/38506417/anti-inflammatory-effect-of-echinacoside-in-collagen-induced-arthritis-via-nrf2-drp1-pathway
#21
JOURNAL ARTICLE
Xiaoyan Wang, Lingxinyu Li, Mengyun Zhang, Ruike Ji, Na Li, Kun Wang, Zhufeng Chen
BACKGROUND: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease. OBJECTIVES: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA. MATERIAL AND METHODS: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0...
March 20, 2024: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://read.qxmd.com/read/38503948/nek2-affects-the-ferroptosis-sensitivity-of-gastric-cancer-cells-by-regulating-the-expression-of-hmox1-through-keap1-nrf2
#22
JOURNAL ARTICLE
Jianyong Wu, Desheng Luo, Laizhen Tou, Hongtao Xu, Chuan Jiang, Dan Wu, Haifeng Que, Jingjing Zheng
NEK2 is a serine/threonine protein kinase that is involved in regulating the progression of various tumors. Our previous studies have found that NEK2 is highly expressed in gastric cancer and suggests that patients have a worse prognosis. However, its role and mechanism in gastric cancer are only poorly studied. In this study, we established a model of ferroptosis induced by RSL3 or Erastin in AGS cells in vitro, and konckdown NEK2, HOMX1, Nrf2 by siRNA. The assay kit was used to analyzed cell viability, MDA levels, GSH and GSSG content, and FeRhoNox™-1 fluorescent probe, BODIPY™ 581/591 C11 lipid oxidation probe, CM-H2DCFDA fluorescent probe were used to detected intracellular Fe2+ , lipid peroxidation, and ROS levels, respectively...
March 19, 2024: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38503237/nrf-2-dependent-antioxidant-and-anti-inflammatory-effects-underlie-the-protective-effect-of-esculeoside-a-against-retinal-damage-in-streptozotocin-induced-diabetic-rats
#23
JOURNAL ARTICLE
Nasser A Alsabaani, Kawther Amawi, Samy M Eleawa, Wisam Nabeel Ibrahim, Walid Aldhaban, Ahmad Mohammad Alaraj, Badr Alkhalaf, Waqas Sami, Hisham Alshaikhli, Mahmoud A Alkhateeb
Esculeoside A (ESA) is a tomato-derived glycoside with antioxidant and anti-inflammatory properties. The protective effect of ESA against diabetic retinopathy is not well-investigated and was the core objective of this study. In addition, we tested if such protection involves the activation of Nrf2 signaling. Type 1 diabetes mellitus (T1DM) was induced in adult Wistar male rats by an intraperitoneal injection of streptozotocin (65 mg/kg). Non-diabetic and T1DM rats were divided into two subgroup groups given either the vehicle or ESA (100 mg)/kg...
March 18, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38503013/irbesartan-ameliorates-diabetic-nephropathy-by-activating-the-nrf2-keap1-pathway-and-suppressing-nlrp3-inflammasomes-in-vivo-and-in-vitro
#24
JOURNAL ARTICLE
Yuan Li, Weihong Long, Haifeng Zhang, Meng Zhao, Menghan Gao, Weiying Guo, Lu Yu
OBJECTIVES: Diabetic nephropathy (DN) is characterized by albuminuria and renal dysfunction caused by diabetes. At present there is no specific treatment for DN. Irbesartan (IRB) is an angiotensin receptor inhibitor indicated for the treatment of hypertension and DN. However, the underlying molecular mechanisms of IRB on DN remains obscure. METHODS: RAW264.7 macrophages were incubated in RPMI-1640, cell viability was evaluated by CCK-8 assays, transcriptional level of proinflammatory cytokines and was measured by ELISA and qPCR, NLRP3 inflammasome and Nrf2/Keap1 related proteins were measured by Western blotting and immunohistochemistry...
March 18, 2024: International Immunopharmacology
https://read.qxmd.com/read/38502885/morusin-alleviates-aortic-valve-calcification-by-inhibiting-valve-interstitial-cell-senescence-through-ccnd1-trim25-nrf2-axis
#25
JOURNAL ARTICLE
Zongtao Liu, Kan Wang, Chen Jiang, Yuqi Chen, Fayuan Liu, Minghui Xie, Wai Yen Yim, Dingyi Yao, Xingyu Qian, Shiqi Chen, Jiawei Shi, Kang Xu, Yixuan Wang, Nianguo Dong
The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro...
March 19, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38501537/homocysteine-potentiated-kelch-like-ech-associated-protein-1-promotes-senescence-of-neuroblastoma-2a-cells-via-inhibiting-ubiquitination-of-%C3%AE-catenin
#26
JOURNAL ARTICLE
Yao Zhang, Jia-Zhao Xie, Yan-Li Jiang, Shao-Juan Yang, Hui Wei, Ying Yang, Jian-Zhi Wang
Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated β-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the β-catenin-WTX interaction...
March 19, 2024: European Journal of Neuroscience
https://read.qxmd.com/read/38499731/de-novo-antioxidant-peptide-design-via-machine-learning-and-dft-studies
#27
JOURNAL ARTICLE
Parsa Hesamzadeh, Abdolvahab Seif, Kazem Mahmoudzadeh, Mokhtar Ganjali Koli, Amrollah Mostafazadeh, Kosar Nayeri, Zohreh Mirjafary, Hamid Saeidian
Antioxidant peptides (AOPs) are highly valued in food and pharmaceutical industries due to their significant role in human function. This study introduces a novel approach to identifying robust AOPs using a deep generative model based on sequence representation. Through filtration with a deep-learning classification model and subsequent clustering via the Butina cluster algorithm, twelve peptides (GP1-GP12) with potential antioxidant capacity were predicted. Density functional theory (DFT) calculations guided the selection of six peptides for synthesis and biological experiments...
March 18, 2024: Scientific Reports
https://read.qxmd.com/read/38499512/hyperoside-inhibits-ehv-8-infection-via-alleviating-oxidative-stress-and-ifn-production-through-activating-jnk-keap1-nrf2-ho-1-signaling-pathways
#28
JOURNAL ARTICLE
Tongtong Wang, Leyu Hu, Ruibo Li, Huiying Ren, Shuwen Li, Qi Sun, Xiangdan Ding, Yubao Li, Changfa Wang, Liangliang Li
Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E...
March 20, 2024: Journal of Virology
https://read.qxmd.com/read/38494201/insights-into-the-molecular-mechanisms-structure-activity-relationships-and-application-prospects-of-polysaccharides-by-regulating-nrf2-mediated-antioxidant-response
#29
REVIEW
Nuo Chen, Meifen Hu, Tingyue Jiang, Ping Xiao, Jin-Ao Duan
The occurrence and development of many diseases are closely related to oxidative stress. In this context, accumulating evidence suggests that Nrf2, as the master switch of cellular antioxidant signaling, plays a central role in controlling the expression of antioxidant genes. The core molecular mechanism of polysaccharides treatment of oxidative stress-induced diseases is to activate Keap1/Nrf2/ARE signaling pathway, promote nuclear translocation of Nrf2, and up-regulate the expression of antioxidant enzymes...
June 1, 2024: Carbohydrate Polymers
https://read.qxmd.com/read/38493156/anti-inflammatory-and-anti-oxidative-electrospun-nanofiber-membrane-promotes-diabetic-wound-healing-via-macrophage-modulation
#30
JOURNAL ARTICLE
Jibing He, Shasha Zhou, Jiaxing Wang, Binbin Sun, Dalong Ni, Jinglei Wu, Xiaochun Peng
BACKGROUND: In the inflammatory milieu of diabetic chronic wounds, macrophages undergo substantial metabolic reprogramming and play a pivotal role in orchestrating immune responses. Itaconic acid, primarily synthesized by inflammatory macrophages as a byproduct in the tricarboxylic acid cycle, has recently gained increasing attention as an immunomodulator. This study aims to assess the immunomodulatory capacity of an itaconic acid derivative, 4-Octyl itaconate (OI), which was covalently conjugated to electrospun nanofibers and investigated through in vitro studies and a full-thickness wound model of diabetic mice...
March 16, 2024: Journal of Nanobiotechnology
https://read.qxmd.com/read/38488001/zmynd8-protects-breast-cancer-stem-cells-against-oxidative-stress-and-ferroptosis-through-activation-of-nrf2
#31
JOURNAL ARTICLE
Maowu Luo, Lei Bao, Yuanyuan Xue, Ming Zhu, Ashwani Kumar, Chao Xing, Jennifer E Wang, Yingfei Wang, Weibo Luo
Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of oxidative stress in BCSCs remains unclear. We recently found that the histone reader ZMYND8 was upregulated in BCSCs. Here, we showed that ZMYND8 reduced ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high (ALDHhi) BCSCs, leading to BCSC expansion and tumor initiation in mice. The underlying mechanism involved a two-fold posttranslational regulation of nuclear factor erythroid 2-related factor 2 (NRF2)...
January 23, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38487897/-bifidobacterium-longum-gl001-alleviates-rat-intestinal-ischemia-reperfusion-injury-by-modulating-gut-microbiota-composition-and-intestinal-tissue-metabolism
#32
JOURNAL ARTICLE
Jilang Tang, Mingchao Zhao, Xue Miao, Hong Chen, Binger Zhao, Yingying Wang, Yingchao Guo, Tiantian Wang, Xin Cheng, Hongri Ruan, Jiantao Zhang
Intestinal ischemia-reperfusion (IIR) injury leads to inflammation and oxidative stress, resulting in intestinal barrier damage. Probiotics, due to their anti-inflammatory and antioxidant properties, are considered for potential intervention to protect the intestinal barrier during IIR injury. Bifidobacterium longum , a recognized probiotic, has targeted effects on IIR injury, but its mechanisms of action are not yet understood. To investigate the mechanism of Bifidobacterium longum intervention in IIR injury, we conducted a study using a rat IIR injury model...
March 15, 2024: Food & Function
https://read.qxmd.com/read/38487538/control-of-immune-cell-signaling-by-the-immuno-metabolite-itaconate
#33
REVIEW
Roland Lang, Md Nur A Alam Siddique
Immune cell activation triggers signaling cascades leading to transcriptional reprogramming, but also strongly impacts on the cell's metabolic activity to provide energy and biomolecules for inflammatory and proliferative responses. Macrophages activated by microbial pathogen-associated molecular patterns and cytokines upregulate expression of the enzyme ACOD1 that generates the immune-metabolite itaconate by decarboxylation of the TCA cycle metabolite cis-aconitate. Itaconate has anti-microbial as well as immunomodulatory activities, which makes it attractive as endogenous effector metabolite fighting infection and restraining inflammation...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38485922/cyclic-peptide-keap1-nrf2-protein-protein-interaction-inhibitors-design-synthesis-and-in-vivo-treatment-of-acute-lung-injury
#34
JOURNAL ARTICLE
Jihua Zou, Jianyu Yan, Yifei Lu, Zhou Yu, Kai Zhang, Qianyu Han, Dan Han, Conghao Gai, Xiaoyun Chai, Qingjie Zhao, Chunlin Zhuang, Yan Zou
Directly blocking the Keap1-Nrf2 pathway is a promising strategy for the mitigation of acute lung injury (ALI). Peptide Keap1-Nrf2 inhibitors have been reported to have a high Keap1 binding affinity. However, these inhibitors showed weak activity in cells and/or animals. In this study, we designed a series of linear peptides from an Nrf2-based 9-mer Ac-LDEETGEFL-NH2 . To improve the cellular activity, we further designed cyclic peptides based on the crystal complex of Keap1 with a linear peptide. Among them, cyclic 9-mer ZC9 targeting Keap1 showed a better affinity ( K D2 = 51 nM)...
March 14, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38484668/physalin-h-ameliorates-lps-induced-acute-lung-injury-via-keap1-nrf2-axis
#35
JOURNAL ARTICLE
Yuxing Cai, Jiangmin Zhu, Ling Zhu, Lihong Hong, Jianfei Zhang, Lingyi Kong, Chen Chen, Jianguang Luo
Physalin H (PH), a withanolide isolated from Physalisangulata L. has been reported to have anti-inflammatory effect. However, its impact on acute lung injury (ALI) remains unexplored. In this study, we observed that PH significantly alleviated inflammation in LPS-stimulated macrophages by suppressing the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and down-regulating the expression of the inflammation-related genes. RNA sequencing analysis revealed a significant up-regulation of the NRF2 pathway by PH...
March 13, 2024: International Immunopharmacology
https://read.qxmd.com/read/38482922/neurotoxic-microglial-activation-via-ifn%C3%AE-induced-nrf2-reduction-exacerbating-alzheimer-s-disease
#36
JOURNAL ARTICLE
You Jung Kang, Seung Jae Hyeon, Amanda McQuade, Jiwoon Lim, Seung Hyun Baek, Yen N Diep, Khanh V Do, Yeji Jeon, Dong-Gyu Jo, C Justin Lee, Mathew Blurton-Jones, Hoon Ryu, Hansang Cho
Microglial neuroinflammation appears to be neuroprotective in the early pathological stage, yet neurotoxic, which often precedes neurodegeneration in Alzheimer's disease (AD). However, it remains unclear how the microglial activities transit to the neurotoxic state during AD progression, due to complex neuron-glia interactions. Here, the mechanism of detrimental microgliosis in AD by employing 3D human AD mini-brains, brain tissues of AD patients, and 5XFAD mice is explored. In the human and animal AD models, amyloid-beta (Aβ)-overexpressing neurons and reactive astrocytes produce interferon-gamma (IFNγ) and excessive oxidative stress...
March 14, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38481699/structure-based-identification-of-kelch-like-ech-associated-protein-1-as-a-pharmacological-target-of-electrophile-containing-catechol-o-methyltransferase-inhibitors
#37
JOURNAL ARTICLE
Ping Wang, Yang Li, Jinyi Yang, Ziwen Li, Xintong Ren, Qingshi Meng, Pengfei Li, Luzhe Qin, Wei Li, Yuting Xie, Nannan Hou, Niu Huang
Entacapone and nitecapone are electrophile-containing catechol- O -methyltransferase (COMT) inhibitors that are used to treat Parkinson's disease in combination with L-DOPA. It is desirable to investigate whether they can covalently bind to cellular protein targets using their reactive electrophilic warheads. We identified Kelch-like ECH-associated protein 1 (KEAP1), a sensor for oxidative and electrophilic stress, as a potential pharmacological target of both drugs by performing covalent-based reverse docking...
March 8, 2024: ACS Pharmacology & Translational Science
https://read.qxmd.com/read/38480798/nortriptyline-hydrochloride-a-potential-candidate-for-drug-repurposing-inhibits-gastric-cancer-by-inducing-oxidative-stress-by-triggering-the-keap1-nrf2-pathway
#38
JOURNAL ARTICLE
Chunyang Zhu, Yangyang Lu, Shasha Wang, Jialin Song, Yixin Ding, Yan Wang, Chen Dong, Jiani Liu, Wensheng Qiu, Weiwei Qi
Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression...
March 13, 2024: Scientific Reports
https://read.qxmd.com/read/38479223/inhibition-of-glycogen-synthase-kinase-3-enhances-nrf2-protein-stability-nuclear-localisation-and-target-gene-transcription-in-pancreatic-beta-cells
#39
JOURNAL ARTICLE
Chinmai Patibandla, Lidy van Aalten, Albena T Dinkova-Kostova, Tadashi Honda, Antonio Cuadrado, Raquel Fernández-Ginés, Alison D McNeilly, John D Hayes, James Cantley, Calum Sutherland
Accumulation of reactive oxygen species (i.e., oxidative stress) is a leading cause of beta cell dysfunction and apoptosis in diabetes. NRF2 (NF-E2 p45-related factor-2) regulates the adaptation to oxidative stress, and its activity is negatively regulated by the redox-sensitive CUL3 (cullin-3) ubiquitin ligase substrate adaptor KEAP1 (Kelch-like ECH-associated protein-1). Additionally, NRF2 is repressed by the insulin-regulated Glycogen Synthase Kinase-3 (GSK3). We have demonstrated that phosphorylation of NRF2 by GSK3 enhances β-TrCP (beta-transducin repeat-containing protein) binding and ubiquitylation by CUL1 (cullin-1), resulting in increased proteasomal degradation of NRF2...
March 7, 2024: Redox Biology
https://read.qxmd.com/read/38479222/gstp-alleviates-acute-lung-injury-by-s-glutathionylation-of-keap1-and-subsequent-activation-of-nrf2-pathway
#40
JOURNAL ARTICLE
Xiaolin Sun, Chaorui Guo, Chunyan Huang, Ning Lv, Huili Chen, Haoyan Huang, Yulin Zhao, Shanliang Sun, Di Zhao, Jingwei Tian, Xijing Chen, Yongjie Zhang
Oxidative stress plays an important role in the pathogenesis of acute lung injury (ALI). As a typical post-translational modification triggered by oxidative stress, protein S-glutathionylation (PSSG) is regulated by redox signaling pathways and plays diverse roles in oxidative stress conditions. In this study, we found that GSTP downregulation exacerbated LPS-induced injury in human lung epithelial cells and in mice ALI models, confirming the protective effect of GSTP against ALI both in vitro and in vivo. Additionally, a positive correlation was observed between total PSSG level and GSTP expression level in cells and mice lung tissues...
March 6, 2024: Redox Biology
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