Proteins and DNA Sequences Interacting with Tanshinones and Tanshinone Derivatives

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 848 - 848

Published: Jan. 20, 2025

Tanshinones, biologically active diterpene compounds derived from Salvia miltiorrhiza, interact with specific proteins and DNA sequences, influencing signaling pathways in animals humans. This study highlights tanshinone–protein interactions observed at concentrations achievable vivo, ensuring greater physiological relevance compared to vitro studies that often employ supraphysiological ligand levels. Experimental data suggest while tanshinones multiple proteomic targets, only a few enzymes are significantly affected relevant concentrations. apparent paradox may be resolved by tanshinones’ ability bind influence involved gene expression or mRNA stability, such as RNA polymerase II human antigen R protein. These trigger secondary, widespread changes expression, leading complex alterations. Although the current understanding of remains incomplete, this provides foundation for deciphering molecular mechanisms underlying therapeutic effects S. miltiorrhiza diterpenes. Additionally, numerous tanshinone derivatives have been developed enhance pharmacokinetic properties biological activity. However, their safety profiles remain poorly characterized, limiting comprehensive insights into medicinal potential. Further investigation is essential fully elucidate toxicological both native modified tanshinones.

Language: Английский

---

KLF9, Epigenetic Silenced by DNMT1, Promotes ERK‐Mediated Ferroptosis of Osteoarthritic Chondrocytes Through Transcriptionally Regulating CYP1B1

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: Feb. 27, 2025

ABSTRACT Ferroptosis plays a crucial role in the pathogenesis of osteoarthritis (OA), and inhibition chondrocyte ferroptosis effectively alleviates OA progression. Krüppel‐like factor 9 (KLF9) is demonstrated to be upregulated OA, but its molecular mechanism remains unclear. The study aimed investigate KLF9 Primary chondrocytes were treated with IL‐1β establish an cell model, showed that was highly expressed IL‐1β‐incubated chondrocytes. Knockdown alleviated IL‐1β‐induced degeneration. In addition, decreased methylation proportion gene promoter. DNA methyltransferase 1 (DNMT1) directly bound promoter, overexpression DNMT1 inhibited expression by promoting promoter Subsequently, shRNA pcDNA‐CYP1B1 individually or altogether transfected into Cytochrome P450 1B1 (CYP1B1) chondrocytes, abrogated inhibitory effect on ferroptosis. Moreover, Ferrostatin‐1 (Fer‐1, inhibitor ferroptosis) reversed promotion Finally, vivo experiments significantly suppressed cartilage tissue damage, ferroptosis, IHC scores CYP1B1 rats. conclusion, our results suggested KLF9, epigenetic silenced DNMT1, promoted extracellular signal‐regulated kinase (ERK)‐mediated through transcriptionally regulating CYP1B1. Thus, expected new target for treatment OA.

Language: Английский

---

Cardioprotective potential of transcription factor PRRX1 silencing against myocardial ischemia/reperfusion injury by regulating excessive mitophagy and ferroptosis through FKBP5-p38 MAPK axis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167766 - 167766

Published: March 3, 2025

Language: Английский

---

The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2667 - 2667

Published: March 16, 2025

Cardiovascular disease (CVD) is a serious global health issue with high mortality rates worldwide. Despite the numerous advancements in study of CVD pathogenesis recent years, further summarization and elaboration specific molecular pathways are required. An extensive body research has been conducted to elucidate association between MAPK signaling pathway, which present all eukaryotic organisms, cardiovascular disease. This review aims provide comprehensive summary on over past five years. The primary focus four diseases: heart failure, atherosclerosis, myocardial ischemia–reperfusion injury, cardiac hypertrophy. will also address pathophysiological mechanisms diseases, objective proposing novel clinical treatment strategies for CVD.

Language: Английский

---

NRF2-mediated osteoblast anti-ferroptosis effect promotes induced membrane osteogenesis

Bone, Journal Year: 2024, Volume and Issue: unknown, P. 117384 - 117384

Published: Dec. 1, 2024

Language: Английский

---