The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells DOI Open Access
Hunter R. Ford, Massimo Bionaz

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4264 - 4264

Published: April 12, 2024

Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, periparturient period, when cows must rapidly adapt sudden metabolic demands lactation, is a period damaging free radicals overwhelm natural systems, potentially leading tissue damage milk production. Central protection against radical defense transcription factor NRF2, which activates an array genes associated with functions cell survival. The objective this study was evaluate effect that two NRF2 modulators, agonist sulforaphane (SFN) antagonist brusatol (BRU), have on transcriptome immortalized bovine mammary alveolar cells (MACT) using both RT-qPCR putative target genes, as well RNA sequencing approaches. treatment SFN resulted in activation many upregulation pathways involved survival, metabolism, function while suppressing expression related cellular senescence DNA repair. contrast, BRU inflammation, stress, apoptosis various processes. analysis also revealed several novel bovine. conclusion, data indicate may be effective at modulating transcriptional network, but additional effects metabolism complicate effectiveness compounds improve health via nutrigenomic

Language: Английский

Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis DOI Creative Commons
Giovanni Tossetta, Sonia Fantone, Lucrezia Togni

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1270 - 1270

Published: Oct. 18, 2024

Periodontitis affects up to 40% of adults over 60 years old and is a consequence gingivitis. characterized by chronic inflammation, periodontal damage, alveolar bone resorption. The nuclear factor erythroid 2-related 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays key role in periodontitis modulating redox balance inflammation the periodontium. However, NRF2 expression decreased gingival tissues patients with while oxidative stress significantly increased this pathology. Oxidative lipopolysaccharide (LPS) produced gram-negative bacteria favor production inflammatory causing favoring bone. In review, we analyzed current literature regarding natural synthetic compounds NRF2/KEAP1 vitro vivo models order evaluate new potential treatments that can improve outcome disease.

Language: Английский

Citations

15

The Multifaceted Role of Endothelial Sirt1 in Vascular Aging: An Update DOI Creative Commons
Roberto Campagna, Laura Mazzanti, Veronica Pompei

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1469 - 1469

Published: Sept. 1, 2024

NAD+-dependent deacetylase sirtuin-1 (Sirt1) belongs to the sirtuins family, known be longevity regulators, and exerts a key role in prevention of vascular aging. By aging, expression levels Sirt1 decline with severe impact on function, such as rise endothelial dysfunction, which turn promotes development cardiovascular diseases. In this context, activity preventing senescence is particularly important. Given counteracting senescence, great efforts have been made deepen knowledge about intricate cross-talks interactions other molecules, order set up possible strategies boost prevent or treat The aim review provide proper background regulation function endothelium discuss recent advances regarding therapeutic targeting counteract

Language: Английский

Citations

11

The Cancer Antioxidant Regulation System in Therapeutic Resistance DOI Creative Commons

Xuanhao Gu,

Chunyang Mu,

Rujia Zheng

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 778 - 778

Published: June 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Language: Английский

Citations

9

Naringin Suppresses CoCl2-Induced Ferroptosis in ARPE-19 Cells DOI Creative Commons
Yuchang Yang,

Manting Liu,

Xiaoxv Dong

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 236 - 236

Published: Feb. 18, 2025

Hypoxic damage to retinal pigment epithelial (RPE) cells and subsequent neovascularization are key factors in the pathogenesis of branch vein occlusion (BRVO). Naringin (NG), a naturally occurring flavanone glycoside, has demonstrated significant antioxidant anti-neovascular activities. However, regulatory effects mechanisms NG on ferroptosis BRVO yet be explored. Our study aimed investigate protective RPE under hypoxic stress elucidate underlying molecular mechanisms. findings revealed that significantly reduced cytotoxicity induced by cobaltous chloride (CoCl2) also inhibited vascular proliferation retina, thereby attenuating choroidal neovascularization. pretreatment largely countered overproduction reactive oxygen species (ROS) malondialdehyde (MDA) triggered damage, while restoring levels antioxidants glutathione (GSH) superoxide dismutase (SOD). Furthermore, activated expression hypoxia-inducible factor-1 alpha (HIF-1α) its downstream heme oxygenase-1 (HO-1) NADPH dehydrogenase (NQO1). In conclusion, not only inhibits but alleviates inflammation modulating HO-1/GPX4 pathway inhibit ferroptosis. These highlight potential as promising therapeutic agent for treatment BRVO.

Language: Английский

Citations

1

From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS DOI Creative Commons

Jie An,

Qin Zhou, Xiaojing Guo

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 17, 2025

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology PCOS multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, dysregulation. Iron, critical mineral, not only plays role regulating female physiological functions the progression but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, form nonapoptotic cell death characterized by accumulation lipid peroxides. While numerous studies have explored ferroptosis patients animal models, precise mechanisms therapeutic implications remain inadequately understood. This review seeks elucidate pathophysiology contributory factors ferroptosis. Additionally, we examine diverse manifestations evaluate its role. Furthermore, introduce ferroptosis-related traditional Chinese medicines that may enhance understanding pathogenesis aid development targeted therapies for PCOS.

Language: Английский

Citations

1

Targeting catalase in cancer DOI Creative Commons
Christophe Glorieux, Pedro Buc Calderón

Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103404 - 103404

Published: Oct. 19, 2024

Language: Английский

Citations

6

NFE2L2 and ferroptosis resistance in cancer therapy DOI Open Access
Daolin Tang, Rui Kang

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

NFE2-like basic leucine zipper transcription factor 2 (NFE2L2, also known as NRF2), is a key in the cellular defense against oxidative stress, playing crucial role cancer cell survival and resistance to therapies. This review outlines current knowledge on link between NFE2L2 ferroptosis - form of regulated death characterized by iron-dependent lipid peroxidation within cells. While activation can protect normal cells from damage, its overexpression contributes drug upregulating antioxidant defenses inhibiting ferroptosis. We delve into molecular pathways ferroptosis, highlighting involvement target genes, such

Language: Английский

Citations

6

Glutathione-Dependent Pathways in Cancer Cells DOI Open Access
Elena Kalinina

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8423 - 8423

Published: Aug. 1, 2024

The most abundant tripeptide—glutathione (GSH)—and the major GSH-related enzymes—glutathione peroxidases (GPxs) and glutathione S-transferases (GSTs)—are highly significant in regulation of tumor cell viability, initiation development, its progression, drug resistance. high level GSH synthesis different cancer types depends not only on increasing expression key enzymes γ-glutamyl cycle but also changes transport velocity precursor amino acids. ability GPxs to reduce hydroperoxides is used for cellular each member GPx family has a mechanism action site maintaining redox balance. GSTs catalyze conjugation electrophilic substances reduction organic take part signaling pathways. By catalyzing S-glutathionylation target proteins, are involved processes, including metabolism (e.g., glycolysis PPP), signal transduction, transcription regulation, development resistance anticancer drugs. In this review, recent findings synthesis, roles functions GPxs, GST isoforms discussed, along with search inhibitors treatment.

Language: Английский

Citations

5

The molecular mechanism of gemcitabine in inhibiting the HIF-1α/VEGFB/FGF2/FGFR1 signaling pathway for ovarian cancer treatment DOI Creative Commons
Liangliang Wang, Shanshan Ma, H. Su

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 3, 2025

Language: Английский

Citations

0

Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis DOI

Shrouk M Basiouny,

Hala F. Zaki,

Shimaa M. Elshazly

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110295 - 110295

Published: Jan. 1, 2025

Language: Английский

Citations

0