keyword
https://read.qxmd.com/read/37149844/the-synthetic-oleanane-triterpenoid-cddo-2p-im-binds-grp78-bip-to-induce-unfolded-protein-response-mediated-apoptosis-in-myeloma
#21
JOURNAL ARTICLE
George Luo, Kristin Aldridge, Toby Chen, Vivek Aslot, Byung-Gyu Kim, Eun Hyang Han, Neelima Singh, Sai Li, Tsan Sam Xiao, Michael B Sporn, John J Letterio
Synthetic oleanane triterpenoids (SOTs) are small molecules with broad anti-cancer properties. A recently developed SOT, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole (CDDO-2P-Im or '2P-Im'), exhibits enhanced activity and improved pharmacokinetics over CDDO-Im, a previous generation SOT. However, the mechanisms leading to these properties are not defined. Here we show synergy of 2P-Im and the proteasome inhibitor ixazomib in human multiple myeloma (MM) cells, and 2P-Im activity in a murine model of plasmacytoma...
May 7, 2023: Molecular Oncology
https://read.qxmd.com/read/36982949/cddo-me-abrogates-aberrant-mitochondrial-elongation-in-clasmatodendritic-degeneration-by-regulating-nf-%C3%AE%C2%BAb-pdi-mediated-s-nitrosylation-of-drp1
#22
JOURNAL ARTICLE
Duk-Shin Lee, Tae-Hyun Kim, Hana Park, Ji-Eun Kim
Clasmatodendrosis is a kind of astroglial degeneration pattern which facilitates excessive autophagy. Although abnormal mitochondrial elongation is relevant to this astroglial degeneration, the underlying mechanisms of aberrant mitochondrial dynamics are still incompletely understood. Protein disulfide isomerase (PDI) is an oxidoreductase in the endoplasmic reticulum (ER). Since PDI expression is downregulated in clasmatodendritic astrocytes, PDI may be involved in aberrant mitochondrial elongation in clasmatodendritic astrocytes...
March 20, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36900370/orthogonal-optimization-characterization-and-in-vitro-anticancer-activity-evaluation-of-a-hydrogen-peroxide-responsive-and-oxygen-reserving-nanoemulsion-for-hypoxic-tumor-photodynamic-therapy
#23
JOURNAL ARTICLE
Liang Hong, Jianman Wang, Yi Zhou, Guofu Shang, Tao Guo, Hailong Tang, Jiangmin Li, Yali Luo, Xiangyu Zeng, Zhu Zeng, Zuquan Hu
Tumor hypoxia can seriously impede the effectiveness of photodynamic therapy (PDT). To address this issue, two approaches, termed in situ oxygen generation and oxygen delivery, were developed. The in situ oxygen generation method uses catalysts such as catalase to decompose excess H2 O2 produced by tumors. It offers specificity for tumors, but its effectiveness is limited by the low H2 O2 concentration often present in tumors. The oxygen delivery strategy relies on the high oxygen solubility of perfluorocarbon, etc...
March 3, 2023: Cancers
https://read.qxmd.com/read/36835414/rta-dh404-induces-cell-cycle-arrest-apoptosis-and-autophagy-in-glioblastoma-cells
#24
JOURNAL ARTICLE
Tai-Hsin Tsai, Yu-Feng Su, Cheng-Yu Tsai, Chieh-Hsin Wu, Kuan-Ting Lee, Yi-Chiang Hsu
RTA dh404 is a novel synthetic oleanolic acid derivative that has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory properties, and exerts therapeutic effects on various cancers. Although CDDO and its derivatives have anticancer effects, the actual anticancer mechanism has not been fully explored. Therefore, in this study, glioblastoma cell lines were exposed to different concentrations of RTA dh404 (0, 2, 4, and 8 µM). Cell viability was evaluated using the PrestoBlue™ reagent assay...
February 16, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36798782/bardoxolone-methyl-ameliorates-osteoarthritis-by-inhibiting-osteoclastogenesis-and-protecting-the-extracellular-matrix-against-degradation
#25
JOURNAL ARTICLE
Ruijia Yang, Yanjing Guo, Sujing Zong, Zhou Ma, Zhenyu Wang, Jiyu Zhao, Jinmei Yang, Liping Li, Chongwei Chen, Shaowei Wang
Inflammation and oxidative damage are closely related to the development of osteoarthritis. Bardoxolone methyl (CDDO-Me), a semisynthetic oleanane triterpenoid, plays a strong anti-inflammatory and antioxidant role. The purpose of our research was to explore fundamental mechanisms of CDDO-Me in orthopaedics development. The results showed that CDDO-Me inhibited nuclear factor-κB ligand (RANKL)-induced osteoclast formation and extracellular matrix (ECM) degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-κB pathway activation and excess ROS production...
February 2023: Heliyon
https://read.qxmd.com/read/36730842/nuclear-factor-erythroid-2-related-factor-regulates-systemic-and-pulmonary-barrier-function-and-immune-programming-after-burn-and-inhalation-injury
#26
JOURNAL ARTICLE
Roland F Seim, Michelle Mac, Lucas M Sjeklocha, Alex J Kwiatkowski, Ben G Keselowsky, Shannon M Wallet, Bruce A Cairns, Robert Maile
Major burn injury is associated with systemic hyper-inflammatory and oxidative stresses that encompass the wound, vascular, and pulmonary systems that contribute to complications and poor outcomes. These stresses are exacerbated if there is a combined burn and inhalation injury (B + I), which leads to increases in morbidity and mortality. Nuclear Factor-Erythroid-2-Related Factor (NRF2) is a transcription factor that functions to maintain homeostasis during stress, in part by modulating inflammation and oxidative injury...
November 3, 2022: Shock
https://read.qxmd.com/read/36693016/role-of-human-aldo-keto-reductases-and-nuclear-factor-erythroid-2-related-factor-2-in-the-metabolic-activation-of-1-nitropyrene-via-nitroreduction-in-human-lung-cells
#27
JOURNAL ARTICLE
Anthony L Su, Trevor M Penning
1-Nitropyrene (1-NP) is a constituent of diesel exhaust and classified as a group 2A probable human carcinogen. The metabolic activation of 1-NP by nitroreduction generates electrophiles that can covalently bind DNA to form mutations to contribute to cancer causation. NADPH-dependent P450 oxidoreductase (POR), xanthine oxidase (XO), aldehyde oxidase (AOX), and NAD(P)H/quinone oxidoreductase 1 (NQO1) may catalyze 1-NP nitroreduction. We recently found that human recombinant aldo-keto reductases (AKRs) 1C1-1C3 catalyze 1-NP nitroreduction...
January 24, 2023: Chemical Research in Toxicology
https://read.qxmd.com/read/36670978/the-triterpenoid-cddo-methyl-ester-redirects-macrophage-polarization-and-reduces-lung-tumor-burden-in-a-nrf2-dependent-manner
#28
JOURNAL ARTICLE
Jessica A Moerland, Ana S Leal, Beth Lockwood, Elena Y Demireva, Huirong Xie, Teresa Krieger-Burke, Karen T Liby
The NRF2/KEAP1 pathway protects healthy cells from malignant transformation and maintains cellular homeostasis. Up to 30% of human lung tumors gain constitutive NRF2 activity which contributes to cancer cell survival and chemoresistance, but the effects of NRF2 activation in immune cells within the tumor microenvironment are underexplored. Macrophages can promote cancer progression or regression depending on context, and NRF2 activation affects macrophage activity. The NRF2 activator CDDO-Methyl ester (CDDO-Me or bardoxolone methyl) reprogrammed Nrf2 wild-type (WT) tumor-educated bone marrow-derived macrophages (TE-BMDMs) from a tumor-promoting to a tumor-inhibiting phenotype, marked by an increase in M1 markers TNFα, IL-6, and MHC-II and a decrease in the tumor-promoting factors VEGF, CCL2, and CD206...
January 3, 2023: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/36661241/triterpenoid-cddo-ea-inhibits-lipopolysaccharide-induced-inflammatory-responses-in-skeletal-muscle-cells-through-suppression-of-nf-%C3%AE%C2%BAb
#29
JOURNAL ARTICLE
Phoebe Fang-Mei Chang, Daniel Acevedo, Lawrence J Mandarino, Sara M Reyna
Chronic inflammation is a major contributor to the development of obesity-induced insulin resistance, which then can lead to the development of type 2 diabetes (T2D). Skeletal muscle plays a pivotal role in insulin-stimulated whole-body glucose disposal. Therefore, dysregulation of glucose metabolism by inflammation in skeletal muscle can adversely affect skeletal muscle insulin sensitivity and contribute to the pathogenesis of T2D. The mechanism underlying insulin resistance is not well known; however, macrophages are important initiators in the development of the chronic inflammatory state leading to insulin resistance...
January 20, 2023: Experimental Biology and Medicine
https://read.qxmd.com/read/36587836/lonp1-and-sig-1r-contribute-to-the-counteraction-of-ursolic-acid-against-ochratoxin-a-induced-mitochondrial-apoptosis
#30
JOURNAL ARTICLE
Qipeng Zhang, Wenying Chen, Boyang Zhang, Yiwen Zhang, Yuqing Xiao, Yichen An, Lingyun Han, Huiqiong Deng, Song Yao, Hongwei Wang, Xiao Li Shen
Ochratoxin A (OTA), a secondary fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food materials and medicinal plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1...
February 2023: Food and Chemical Toxicology
https://read.qxmd.com/read/36497112/induction-of-cardiac-pathology-endogenous-versus-exogenous-nrf2-upregulation
#31
REVIEW
Bryan J Mathis, Hideyuki Kato, Yuji Hiramatsu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results...
November 30, 2022: Cells
https://read.qxmd.com/read/36462163/25-hydroxycholesterol-induces-odontoclastic-differentiation-through-rank-rankl-upregulation-and-nf-%C3%AE%C2%BAb-activation-in-odontoblast-like-mdpc-23-cells-an-in-vitro-study
#32
JOURNAL ARTICLE
HyangI Lim, Ji-Su Oh, Kyeong-Rok Kang, Jeong-Yeon Seo, Do Kyung Kim, Sun-Kyoung Yu, Heung-Joong Kim, Joo-Cheol Park, Jae-Sung Kim
AIM: The physiological effects and cellular mechanism of 25-hydroxycholesterol (25-HC), which is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase (CH25H) expressed under inflammatory conditions, are still largely unknown during odontoclastogenesis. This study aimed to evaluate 25-HC-induced odontoclastogenesis and its cellular mechanisms in odontoblast-like MDPC-23 cells. METHODOLOGY: To investigate 25-HC-induced odontoclastogenesis of MDPC-23 cells and its cellular mechanism, haemotoxylin and eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, dentine resorption assay, zymography, reactive oxygen species (ROS) detection, immunocytochemistry, and nuclear translocation were performed...
April 2023: International Endodontic Journal
https://read.qxmd.com/read/36368569/establishment-of-neh2-cre-tdtomato-reporter-mouse-for-monitoring-the-exposure-history-to-electrophilic-stress
#33
JOURNAL ARTICLE
Hiroshi Kitamura, Tetsuya Oishi, Shohei Murakami, Tomoe Yamada-Kato, Isao Okunishi, Masayuki Yamamoto, Yukio Katori, Hozumi Motohashi
Cells are often exposed to exogenous and endogenous redox disturbances and exert their protective mechanisms in response to stimuli. The KEAP1-NRF2 system plays pivotal roles in counteracting oxidative damage. Due to the transient nature of NRF2 activation, the identification of cells in which NRF2 is activated in response to systemic stimuli is sometimes not easy. To examine the electrophilic stress response at a single-cell resolution, we aimed to develop a new reporter mouse in this study. A cell-tracing strategy exploiting Cre recombinase-mediated activation of a reporter gene was chosen for stable detection of reporter expression instead of real-time monitoring of the cellular response...
November 8, 2022: Free Radical Biology & Medicine
https://read.qxmd.com/read/36336370/countermeasure-development-against-space-radiation-induced-gastrointestinal-carcinogenesis-current-and-future-perspectives
#34
REVIEW
Shubhankar Suman, Albert J Fornace
A significantly higher probability of space radiation-induced gastrointestinal (GI) cancer incidence and mortality after a Mars mission has been projected using biophysical and statistical modeling approaches, and may exceed the current NASA mandated limit of less than 3% REID (risk of exposure-induced death). Since spacecraft shielding is not fully effective against heavy-ion space radiation, there is an unmet need to develop an effective medical countermeasure (MCM) strategy against heavy-ion space radiation-induced GI carcinogenesis to safeguard astronauts...
November 2022: Life Sciences in Space Research
https://read.qxmd.com/read/36324037/dna-methylome-and-transcriptome-study-of-triterpenoid-cddo-in-tpa-mediated-skin-carcinogenesis-model
#35
JOURNAL ARTICLE
Hsiao-Chen Dina Kuo, Renyi Wu, Md Shahid Sarwar, Meinizi Zheng, Chao Wang, Davit Sargsyan, Nanjoo Suh, Ah-Ng Tony Kong
Overexposure to ultraviolet radiation and environmental carcinogens drive skin cancer development through redox imbalance and gene mutation. Antioxidants such as triterpenoids have exhibited anti-oxidative and anti-inflammatory potentials to alleviate skin carcinogenesis. This study investigated the methylome and transcriptome altered by tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or TPA with 2-cyano 2,3-dioxoolean-1,9-dien-28-oic acid (CDDO). The results show that CDDO blocks TPA-induced transformation dose dependently...
November 2, 2022: AAPS Journal
https://read.qxmd.com/read/36290607/sp1-mediated-prdx6-upregulation-leads-to-clasmatodendrosis-by-increasing-its-aipla2-activity-in-the-ca1-astrocytes-in-chronic-epilepsy-rats
#36
JOURNAL ARTICLE
Ji-Eun Kim, Duk-Shin Lee, Tae-Cheon Kang
Clasmatodendrosis is an autophagic astroglial degeneration (a non-apoptotic (type II) programmed cell death) whose underlying mechanisms are fully understood. Peroxiredoxin-6 (Prdx6), the "non-selenium glutathione peroxidase (NSGPx)", is the only member of the 1-cysteine peroxiredoxin family. Unlike the other Prdx family, Prdx6 has multiple functions as glutathione peroxidase (GPx) and acidic calcium-independent phospholipase (aiPLA2). The present study shows that Prdx6 was upregulated in CA1 astrocytes in chronic epilepsy rats...
September 23, 2022: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/36288851/15-prostaglandin-dehydrogenase-inhibition-enhances-colon-cancer-metastasis-by-up-regulation-of-epithelial-to-mesenchymal-transition-genes
#37
JOURNAL ARTICLE
Sun-Hee Kim, Seong Eun Song, Hyungjoo Baik, Dae Young Hur, Mi Seon Kang, Ki Beom Bae
BACKGROUND/AIM: Most deaths from colon cancer are due to metastasis. Recently, PGE2 was found to influence colon cancer invasion and metastasis. 15-PGDH, an enzyme that metabolizes PGE2, is known as a tumor suppressor in colonic carcinogenesis. This study investigated the effect of 15-PGDH on colon cancer metastasis. MATERIALS AND METHODS: 15-PGDH expression by immunohistochemical staining, clinicopathologic features, and 5-year cancer-specific survival were investigated in colon cancer patients...
November 2022: Anticancer Research
https://read.qxmd.com/read/36233013/genetic-ablation-of-nrf2-exacerbates-neuroinflammation-in-ocular-autoimmunity
#38
JOURNAL ARTICLE
Yasuhiko Sato, Shoko Saito, Makiko Nakayama, Sunao Sugita, Akihiko Kudo, Hiroshi Keino
Experimental autoimmune uveoretinitis (EAU) is an animal model of non-infectious uveitis and is developed by immunization with retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2) is responsible for regulating antioxidant and inflammatory responses. In this study, we investigated the role of Nrf2 on the development of EAU. Clinical and pathological examination demonstrated that retinal inflammation was exacerbated in Nrf2 knockout (Nrf2 KO) mice compared to wild type (WT) mice, and the expression of inflammatory cytokines (IFN-γ, IL-6, and IL-17) in the retina was significantly elevated in Nrf2 KO mice...
October 3, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36168309/cddo-a-ppar-%C3%AE-ligand-inhibits-tpa-induced-cell-migration-and-invasion-through-a-ppar-%C3%AE-independent-mechanism
#39
JOURNAL ARTICLE
Hye-Yeon Jang, On-Yu Hong, Hyun Jo Youn, Jaeuk Jung, Eun Yong Chung, Sung Hoo Jung, Jong-Suk Kim
Peroxisome proliferator-activated receptor-γ (PPAR-γ) acts as a key factor in breast cancer metastasis. Notably, PPAR-γ can inhibit metalloproteinase (MMP), which is involved in cancer metastasis. Our previous study revealed that PPAR-γ was related to breast cancer metastasis. The present study aimed to investigate whether the PPAR-γ ligand 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) mediated suppression of cell invasion and reduced the expression of MMP-9 in breast cancer cells. The results indicated that CDDO reduced MMP-9 expression, cell migration and invasion of breast cancer cells by inhibiting TPA-induced phosphorylation of mitogen-activated protein kinases, and downregulating the activities of activator protein-1 and nuclear factor κB...
October 2022: Oncology Letters
https://read.qxmd.com/read/35929395/synthetic-oleanane-triterpenoid-derivative-cddo-me-disrupts-cellular-bioenergetics-to-suppress-pancreatic-ductal-adenocarcinoma-via-targeting-slc1a5
#40
JOURNAL ARTICLE
Percy D P Akuetteh, Huimin Huang, Shijia Wu, Hongfei Zhou, Guihua Jin, Welong Hong, Hongbao Yang, Linhua Lan, Fugen Shangguan, Qiyu Zhang
To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes...
August 5, 2022: Journal of Biochemical and Molecular Toxicology
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