PRDM16 Acts as a Homeostasis Regulation Factor to Suppress the Transition of AKI to CKD via Upregulation of Eukaryotic Initiation Factor 6

Опубликована: Янв. 1, 2025

Язык: Английский

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PRDM16 suppresses pyroptosis to attenuate the progression of AKI caused by rhabdomyolysis via upregulation of USP10

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Апрель 2, 2025

Previous studies have indicated that PRDM16 suppresses apoptosis and ferroptosis, thereby mitigating the development of AKI triggered by ischemia, cisplatin, sepsis. Nevertheless, exact function control mechanisms in rhabdomyolysis-induced are not fully understood. In this investigation, was found to inhibit ferrous myoglobin-induced pyroptosis Boston University mouse proximal tubule (BUMPT) cells. At molecular level, binds USP10 promoter, enhancing its expression subsequently inhibiting NLRP3-Caspase1-GSDMD Caspase3-GSDME pathways. Rhabdomyolysis-induced alleviated KI mice, whereas KO exacerbated condition. Furthermore, PNPs-encapsulated formononetin significantly attenuated progression AKI. conclusion, ameliorates regulating USP10/NLRP3-Caspase1-GSDMD emerges as a promising therapeutic strategy.

Язык: Английский

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Ferroptosis-related protein biomarkers for diagnosis, differential diagnosis, and short-term mortality in patients with sepsis in the intensive care unit

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Sepsis is a disease with high mortality caused by dysregulated response to infection. Ferroptosis newly discovered type of cell death. Ferroptosis-related genes are involved in the occurrence and development sepsis. However, research on diagnostic value ferroptosis-related protein biomarkers sepsis serum limited. This study aims explore clinical proteins diagnosing predicting risk. A single-center, prospective, observational was conducted from January December 2023, involving 170 patients, 49 non-septic ICU 50 healthy individuals. Upon admission, biochemical parameters, GCS, SOFA, APACHE II scores were recorded, surplus stored at -80°C for biomarker analysis via ELISA. Diagnostic efficacy evaluated using ROC curve analysis. Baseline levels ACSL4, GPX4, PTGS2, CL-11, IL-6, IL-8, PCT, hs-CRP significantly differed among sepsis, non-septic, individuals (all p-value < 0.01). demonstrated differential performance (AUC: 0.6688 0.9945). IL-10 TNF-α showed good (AUC = 0.8955 0.7657, respectively). ACSL4 0.7127) associated mortality. Serum IL-6 above cut-off shorter survival times. positively correlated SOFA (Rho 0.354, 0.0001), 0.317, septic shock 0.274, 0.003) but negatively GCS score -0.218, 0.018). GPX4 0.204, 0.027) 0.233, 0.011) scores. have strong including ability predict 28-day may become new potential markers

Язык: Английский

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The Ferroptosis–Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation

Antioxidants, Год журнала: 2025, Номер 14(5), С. 613 - 613

Опубликована: Май 20, 2025

Emerging evidence links ferroptosis–mitochondrial dysregulation to depression pathogenesis through an oxidative stress–energy deficit–neuroinflammation cycle driven by iron overload. This study demonstrates that accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating AMPK/mTOR signaling imbalance calcium dyshomeostasis synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: peroxidation derivatives oxidize cardiolipin, while ROS overproduction activates ACSL4 amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal–hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show microglial M1 polarization cGAS-STING activation sustains neuroinflammation IL-6/TNF-α release. We propose “ferroptosis–mitochondrial fragmentation–metabolic maladaptation” triad as mechanistic subtyping criteria for depression. Preclinical validation shows combinatorial therapy (iron chelators + SIRT3 agonists) rescues viability restoring energy flux. work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing homeostasis, organelle dynamics, vulnerability—a framework significant implications developing neuroprotective antidepressants.

Язык: Английский

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A Novel Flavonoid Derivative of Icariside II (YS-10) Improves Erectile Dysfunction in a Diabetic Rat Model by Inhibiting Ferroptosis via Activation of the Nrf2/HO-1/GPX4 Pathway

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 4481 - 4500

Опубликована: Май 1, 2025

This study aimed to evaluate the therapeutic potential of YS-10, a novel flavonoid derivative icariside II (ICA II), and explore its mechanism action in diabetic rat model erectile dysfunction (DMED). Twenty-four male Sprague-Dawley rats were divided into four groups: control, DMED, DMED + ICA (2.5 mg/kg/day), YS-10 mg/kg/day). Treatments lasted for 4 weeks followed by 3-day washout. Erectile function was assessed, penile tissues analyzed histology, immunohistochemistry, ELISA, Western blot. In vitro, primary corpus cavernosum endothelial cells (CCECs) treated with advanced glycation end products (AGEs), Fer-1 (ferroptosis inhibitor), or ML385 (Nrf2 inhibitor) oxidative stress ferroptosis. vivo, both mg/kg/day) significantly improved rats, increased smooth muscle content, reduced collagen deposition, enhanced marker (CD31) expression tissue (p < 0.01 vs group). The maximum ICP/MAP ratio markers similarly restored treatment groups, no significant difference between > 0.05). reversed AGEs-induced injury ferroptosis (CCECs), upregulated GPX4, downregulated ACSL4, ROS lipid peroxidation, comparable effects inhibitor Fer-1. also promoted Nrf2 nuclear translocation elevated HO-1 expression. Molecular docking, immunofluorescence, blotconfirmed interaction Nrf2/HO-1/GPX4 signaling pathway. improves reducing inhibiting via activation At 2.5 mg/kg/day, effective, well-tolerated, showed efficacy II. These findings support as promising candidate diabetes-related therapy.

Язык: Английский

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Unveiling the renoprotective mechanisms of self-assembled herbal nanoparticles from Scutellaria barbata and Scleromitrion diffusum in acute kidney injury: A nano-TCM approach

Acta Pharmaceutica Sinica B, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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