International Immunopharmacology, Journal Year: 2024, Volume and Issue: 146, P. 113817 - 113817
Published: Dec. 25, 2024
Language: Английский
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 9, 2024
Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains lack effective therapeutic approaches as mechanisms pathogenesis progression have yet to be elucidated. As OA progresses, cellular metabolic profiles energy production are altered, emerging reprogramming highlights importance specific pathways disease progression. crucial part glucose metabolism, glycolysis bridges inflammatory dysfunctions. Moreover, glycolytic pathway is involved different areas metabolism inflammation, associated with variety transcription factors. To date, it not fully elucidated whether changes its key enzymes onset or OA. This review summarizes important role mediating inducing tissue inflammation injury, aim providing further insights into pathological functions proposing new targets for treatment
Language: Английский
Citations
11
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116270 - 116270
Published: Feb. 15, 2024
Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance iron homeostasis involves the process intake, storage output, dependening on iron-regulated protein/iron response element system operate tightly metabolism-related genes, including TFR1, DMT1, Fth, FPN. Dysregulation can lead overload, which increases virulence microbial colonisers occurrence oxidative stress, causing alveolar epithelial cells undergo necrosis apoptosis, form extracellular matrix. Accumulated drive iron-dependent ferroptosis exacerbated pulmonary fibrosis. Notably, chelator deferoxamine lipophilic antioxidant ferritin-1 have been shown attenuate inhibit lipid peroxidation in paper summarises regulatory mechanisms dysregulated metabolism development Targeting may be a potential therapeutic strategy for prevention treatment
Language: Английский
Citations
9
World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(15), P. 2143 - 2154
Published: April 19, 2024
BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic associated with progressive accumulation activated stellate cells (HSCs), which can transdifferentiate into myofibroblasts produce an excess extracellular matrix (ECM). Myofibroblasts are main source excessive ECM responsible for fibrosis. Therefore, (aHSCs), principal producing injured liver, promising therapeutic target treatment AIM To explore effect taurine on aHSC proliferation mechanisms involved. METHODS Human HSCs (LX-2) were randomly divided five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated low, medium, high dosage (10 mmol/L, 50 100 respectively) PDGF-BB group. Cell Counting Kit-8 method was performed evaluate viability aHSCs. Enzyme-linked immunosorbent assay used estimate levels reactive oxygen species (ROS), malondialdehyde, glutathione, iron concentration. Transmission electron microscopy applied observe autophagosomes ferroptosis features Quantitative real-time polymerase chain reaction Western blot analysis detect expression α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin PTGS2, SLC7A11, p62. RESULTS Taurine promoted death aHSCs reduced deposition ECM. Treatment could alleviate autophagy inhibit their activation, by decreasing autophagosome formation, downregulating LC3B 1 protein expression, upregulating p62 expression. Meanwhile, triggered ferritinophagy eliminate characterized overload, lipid ROS accumulation, glutathione depletion, peroxidation. Furthermore, bioinformatics demonstrated that had direct targeting nuclear receptor coactivator 4, exhibiting best average binding affinity -20.99 kcal/mol. CONCLUSION exerts effects via involve inhibition trigger
Language: Английский
Citations
6
Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 25, 2025
This study mainly explores the possible role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in onset development Glucocorticoid-induced osteoporosis (GIOP), seeks potential targets for treatment GIOP. Mesenchymal stem cells (MSCs) were treated with osteogenic induction medium. An vitro damage model was established by exposing MSCs to a high concentration (10− 6 M) dexamethasone (DEX). Osteogenic markers measured real-time quantitative polymerase chain reaction, western blot, alkaline phosphatase staining, Alizarin Red S staining. Ferroptosis assessed through reactive oxygen species (ROS) fluorescent probe, transmission electron microscopy, measurement malondialdehyde (MDA). The investigated using RT-qPCR, lysosomal probes, molecular docking, other analytical approaches. PDK4 validated GIOP rat model, micro-computed tomography Masson's trichrome High concentrations DEX inhibited differentiation C3H10T1/2 cells, exhibited opposite effect. partially reversed inhibitory effect both vivo vitro. caused mitochondrial shrinkage disappearance cristae as well an increase total iron, ROS, MDA contents, level ferroptosis key factors. These changes weakened PDK4. inhibitor ferrostatin-1 blocked DEX, while inducer RSL3 reversal reduced protein PDK4, which Bafilomycin A1. docking results showed that can directly bind enhance ability bone mass rats. may promote degradation via lysosome pathway, weaken increasing ferroptosis. become target improving
Language: Английский
Citations
0
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114341 - 114341
Published: March 1, 2025
Language: Английский
Citations
0
Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103298 - 103298
Published: Aug. 2, 2024
Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, cell death mechanism triggered iron-dependent lipid peroxidation and closely linked to inflammation, has yet be fully understood in context BPH. Using RNA sequencing, we observed significant elevation taurine-upregulated gene 1 (TUG1) long noncoding (lncRNA) BPH tissues compared normal prostate tissue. High levels TUG1 exhibited discernible correlation both volume extent inflammatory infiltration patients. The suppression not only led reduction size but also ameliorated AR-deficiency-induced hyperplasia. Mechanistically, decrease AR luminal cells prompted macrophage aggregation release IL-1β, subsequently fostering transcription via MYC. Induced TUG1, through competitive binding miR-188-3p, facilitated expression GPX4, thereby diminishing intracellular ROS impeding ferroptosis cells. Notably, inducer JKE-1674 alleviated inflammation-induced vivo. Together, these findings suggest that deficiency crucially inhibits ferroptosis, promoting TUG1/miR-188-3p/GPX4 signaling axis, making induction promising therapeutic strategy for patients
Language: Английский
Citations
3
Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 560, P. 119752 - 119752
Published: May 29, 2024
Language: Английский
Citations
1
World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(41), P. 4509 - 4513
Published: Oct. 23, 2024
We summarize the mechanism by which taurine (Tau) inhibits autophagy and induces iron apoptosis in hepatic stellate cells. Tau interacts with regulates multifunctional proteins, microtubule-associated protein 1 light chain 3 Beta, autophagy-related gene 5 to inhibit autophagy, binds ferritin heavy nuclear receptor coactivator 4 trigger glutathione peroxidase promote apoptosis. There is a solid rationale for developing Tau-based therapies targeting ferroptosis regulation. From pharmaceutical point of view, there are certain requirements delivery systems, such as loading efficiency, stability, targeting. Nanomaterials should also contain hydrophilic motif similar optimize efficiency. Since molecule high water solubility, liposomes, micelles, amphiphilic polymer nanoparticles may represent superior choice. The nanostructure liposome includes region lipid membrane sequester hydrophobic drugs, respectively, whereas expected be loaded into region. In addition, representative method actively hematopoietic stem cells introduced. A treatment liver fibrosis proposed based on formulation common liposomes (lecithin plus cholesterol).
Language: Английский
Citations
1
Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12
Published: Dec. 9, 2024
Liver fibrosis represents a reversible pathophysiological process, caused by chronic inflammation stemming from hepatocyte damage. It delineates the initial stage in progression of liver disease. This pathological is characterized excessive accumulation extracellular matrix (ECM), which leads to significant structural disruption and ultimately impairs function. To date, no specific antifibrotic drugs have been developed, advanced remains largely incurable. transplantation sole efficacious intervention for fibrosis; nevertheless, it constrained exorbitant costs risk postoperative immune rejection, underscoring imperative novel therapeutic strategies. Ferroptosis, an emergent form regulated cell death, has identified as pivotal regulatory mechanism development intricately linked with diseases. Recent investigations elucidated that diverse array non-coding RNAs (ncRNAs), including microRNAs, long RNAs, circular are involved ferroptosis pathway, thereby modulating various diseases, fibrosis. In recent years, roles ferroptosis-related ncRNAs attracted escalating scholarly attention. paper elucidates pathophysiology fibrosis, explores mechanisms underlying ferroptosis, involvement ncRNA-mediated pathways pathology aims propose strategies prevention
Language: Английский
Citations
1
CytoJournal, Journal Year: 2024, Volume and Issue: 21, P. 78 - 78
Published: Dec. 30, 2024
Addressing the inhibition and reversal of chronic hepatitis B fibrosis is an urgent global challenge, which highlights critical need to understand its underlying mechanisms. Inhibiting activation hepatic stellate cells (HSCs) important strategy for reversal. In particular, induction ferroptosis in HSCs presents a promising avenue curtailing liver fibrosis. Therefore, this study explores influence PR/SET domain 1 (PRDM1), transcriptional regulator, on progression by regulating HSC through glutathione peroxidase 4 (GPX4). We used protein-protein interaction databases analyze interacting proteins GPX4. The messenger ribonucleic acid levels PRDM1 GPX4 tissues with varying degrees were examined using quantitative polymerase chain reaction. Cell lines interference overexpression PRDM1/GPX4 established. Reactive oxygen species (ROS) activity, malondialdehyde (MDA) concentration, cell proliferation capacity, as well expression GPX4, a-smooth muscle actin, vimentin, desmin, assessed investigate relationship between fibrosis, impact HSCs. A significant negative correlation was observed regulator As degree worsened, decreased significantly, whereas increased significantly. markedly ROS MDA concentrations, but it levels, marker protein levels. Interference yielded opposite results. level did not affect PRMD1 Compared single PRDM1, simultaneous significantly inhibited activity capacity It also elevated concentrations. When inhibitors added, concentrations decreased, increased. Opposite results obtained when overexpressed simultaneously. implicated occurrence may act upstream regulatory factor exerts control over suppressing transcription Ultimately, promoted.
Language: Английский
Citations
1