Redox Report最新文献

Objectives: Bone remodeling imbalance contributes to osteoporosis. Though current medications enhance osteoblast involvement in bone formation, the underlying pathways remain unclear. This study was aimed to explore the pathways involved in bone formation by osteoblasts, we investigate the protective role of glycolysis and N6-methyladenosine methylation (m6A) against oxidative stress-induced impairment of osteogenesis in MC3T3-E1 cells.

Methods: We utilized a concentration of 200 μM hydrogen peroxide (H₂O₂) to establish an oxidative damage model of MC3T3-E1 cells. Subsequently, we examined the alterations in the m6A methyltransferases (METTL3, METTL14), glucose transporter proteins (GLUT1, GLUT3) and validated m6A methyltransferase overexpression in vitro and in an osteoporosis model. The osteoblast differentiation and osteogenesis-related molecules and serum bone resorption markers were measured by biochemical analysis, Alizarin Red S staining, Western blot and ELISA.

Results: H₂O₂ treatment inhibited glycolysis and osteoblast differentiation in MC3T3-E1 cells. However, when METTL14 was overexpressed, these changes induced by H₂O₂ could be mitigated. Our findings indicate that METTL14 promotes GLUT3 expression via YTHDF1, leading to the modulation of various parameters in the H₂O₂-induced model. Similar positive effects of METTL14 on osteogenesis were observed in an ovariectomized mouse osteoporosis model.

Discussion: METTL14 could serve as a potential therapeutic approach for enhancing osteoporosis treatment.

Background: The most prevalent endocrine disorder affecting women is PCOS. Programmed death of ovarian cells has yet to be elucidated. Ferroptosis is a kind of iron-dependent necrosis featured by significantly Fe⁺²-dependent lipid peroxidation. The ongoing study aimed to reinforce fertility by combining therapy with AgNPs and (Zileuton) in PCOS rats' model.

Methods: The study included 75 adult female rats divided into 5 groups; control, PCOS, PCOS treated with AgNPs, PCOS treated with Zileuton, and PCOS group treated with AgNPs and Zileuton. The study investigated the anti-ferroptotic, anti-inflammatory, antioxidant, antiapoptotic, histopathological and immunohistochemical examinations of COX-2 and VEGF.

Results: The combination of AgNPs and Zileuton showed significant reduction of inflammatory mediators (IL-6, TNF-α, NFk-B) compared with diseased group (P-value < 0.05), regression of ferroptosis marks (Panx1 and TLR4 expression, Fe⁺² levels) compared with diseased group (P-value < 0.05), depression of apoptotic marker caspase 3 level compared with diseased animals (P-value < 0.05), depression of MDA level, elevation of HO-1, GPx4 activity, and reduction of Cox2 and VEGF as compared with the diseased, AgNPs or zileuton-treated groups (P-value < 0.05).

Conclusion: The study showed that the combination of AgNPs and zileuton guards against, inflammation, apoptosis, and ferroptosis in PCO.

Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.

Objectives: Asthma, a prevalent chronic disease, poses significant health threats and burdens healthcare systems. This study focused on the role of bronchial epithelial cells in asthma pathophysiology.

Methods: Bioinformatics was used to identify key asthmarelated genes. An ovalbumin-sensitized mouse model and an IL-13-stimulated Beas-2B cell model were established for further investigation.

Results: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a crucial gene in asthma. CEACAM5 expression was elevated in asthmatic mouse lung tissues and IL-13-stimulated Beas-2B cells, primarily in bronchial epithelial cells. CEACAM5 induced reactive oxygen species (ROS), lipid peroxidation, and ferroptosis. Interfering with CEACAM5 reduced ROS, malondialdehyde levels, and enhanced antioxidant capacity, while inhibiting iron accumulation and autophagy. Overexpression of CEACAM5 in IL-13-stimulated cells activated the JAK/STAT6 pathway, which was necessary for CEACAM5-induced autophagy, ROS accumulation, lipid peroxidation, and ferroptosis.

Conclusion: CEACAM5 promotes ferroptosis and autophagy in airway epithelial cells via the JAK/STAT6 pathway, exacerbating asthma symptoms. It represents a potential target for clinical treatment.

Objective: Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.

Methods: We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model. RT-PCR and Western blot were used to investigate the expression of the fat mass and obesity-associated (FTO) gene. Electrocardiogram, echocardiography, triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to assess the model and the effect of FTO overexpression. The generation of reactive oxygen species (ROS) and the levels of superoxide dismutase (SOD2), mitochondrial transcription factor (TFAM) and cytochrome c oxidase I (COXI) were detected to assess the oxidative stress and mitochondrial biogenesis. RNA immunoprecipitation (RIP) and RNA pulldown assays were used to identify the interaction of FTO and PGC-1a. The m6A dot blot, methylated RNA immunoprecipitation PCR (MeRIP-PCR) and RNA stability analysis were used to analyze the regulation of methylation of PGC-1a by FTO.

Results: FTO was downregulated in MIRI rats and H/R induced cardiomyocytes. Overexpression of FTO inhibited ROS level and increased the expression of SOD2, TFAM and COXI in vitro and in vivo. In addition, PGC-1a was identified as a downstream target of FTO. FTO enhanced the stability of PGC-1a mRNA through removing the m6A modification.

Conclusion: Our study revealed the role of FTO regulates the oxidative stress and mitochondrial biogenesis via PGC-1a in MIRI, which may provide a new approach to mitigating MIRI.

Oxidative stress, characterized by an imbalance between excessive reactive oxygen species (ROS) production and impaired antioxidant defenses, is closely linked to the pathogenesis of various otorhinolaryngological disorders. Mitochondria, as the primary site of cellular energy production, play a crucial role in modulating oxidative stress. Mitochondrial dysfunction exacerbates ROS generation, leading to cellular damage and inflammatory responses. In otorhinolaryngological diseases, oxidative stress is strongly associated with conditions such as hearing loss, allergic rhinitis, and chronic sinusitis, where oxidative damage and tissue inflammation are key pathological features. Recent studies have highlighted the potential of antioxidant therapies to mitigate oxidative stress and restore homeostasis, offering promising avenues for alleviating symptoms in these diseases. However, despite the encouraging results from early-stage research, the clinical efficacy of antioxidant interventions remains to be fully established. This review provides an overview of the role of oxidative stress in otorhinolaryngological diseases and evaluates the therapeutic potential of antioxidant strategies.

Objectives: Cerebral ischemic stroke is a leading cause of death worldwide. Though timely reperfusion reduces the infarction size, it exacerbates neuronal apoptosis due to oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating the expression of antioxidant enzymes. Activating Nrf2 gives a therapeutic approach to ischemic stroke.

Methods: Herein we explored flavonoids identified from Polypodium hastatum as Nrf2 activators and their protective effects on PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R) as well as middle cerebral artery occlusion (MCAO) mice.

Results: The results showed among these flavonoids, AAKR significantly improved the survival of PC12 cells induced by OGD/R and activated Nrf2 in a Keap1-dependent manner. Further investigations have disclosed AAKR attenuated oxidative stress, mitochondrial dysfunction and following apoptosis resulting from OGD/R. Meanwhile, activation of Nrf2 by AAKR was involved in the protective effects. Finally, it was found that AAKR could protect MCAO mice brains against ischemia/reperfusion injury via activating Nrf2.

Discussion: This investigation could provide lead compounds for the discovery of novel Nrf2 activators targeting ischemia/reperfusion injury.

Objective: Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role and mechanism in sepsis-induced cardiac injury and impairment remain unclear.

Methods: Adenoviral and adeno-associated viral vectors were applied to overexpress or knock down the expression of MEGF9 in vivo and in vitro. To stimulate septic injury, cardiomyocytes and mice were treated lipopolysaccharide (LPS). To clarify the necessity of AMP-activated protein kinase (AMPK), global AMPK knockout mice were used.

Results: We found that MEGF9 expressions were reduced in cardiomyocytes and mice by LPS stimulation. Compared with negative controls, plasma MEGF9 levels were also decreased in septic patients, and negatively correlated with LPS-induced cardiac dysfunction. In addition, MEGF9 overexpression attenuated, while MEGF9 knockdown aggravated LPS-induced inflammation and oxidative damage in vivo and in vitro, thereby regulating LPS-induced cardiac injury and impairment. Mechanistic studies revealed that MEGF9 overexpression alleviated LPS-induced cardiac dysfunction through activating AMPK pathway.

Conclusion: We for the first time demonstrate that MEGF9 prevents LPS-related inflammation, oxidative damage and cardiac injury through activating AMPK pathway, and provide a proof-of-concept for the treatment of LPS-induced cardiac dysfunction by targeting MEGF9.

Background: Regenerative medicine researches have shown that mesenchymal stem cells (MSCs) may be an effective treatment method for premature ovarian insufficiency (POI). However, the efficacy of MSCs is still limited.

Purpose: This study aims to explain whether salidroside and MSCs combination is a therapeutic strategy to POI and to explore salidroside-enhanced MSCs inhibiting ferroptosis via Keap1/Nrf2/GPX4 signaling.

Methods: The effect of salidroside and MSCs on ovarian granular cells (GCs) was analyzed. After treatment, hormone levels and -fertility of rats were measured. Lipid peroxidation levels, iron deposition and mitochondrial morphology were detected. The genes and proteins of Keap1/Nrf2/GPX4 signaling were examined.

Results: Salidroside and MSCs were found to inhibit cell death of GCs by reducing peroxidation and intracellular ferrous. Salidroside promotes the proliferation of MSCs and supports cell survival in ovary. Salidroside combined with MSCs therapy restored ovarian function, which was better than MSCs monotherapy. Salidroside-enhanced MSCs to inhibit ferroptosis. The results showed activation of the Keap1/Nrf2/GPX4 signaling and an increase in anti-ferroptosis molecule.

Conclusions: Salidroside-enhanced MSCs as a ferroptosis inhibitor and provide new therapeutic strategies for POI. The possible mechanisms of MSCs were related to maintaining redox homeostasis via a Keap1/Nrf2/GPX4 signaling.

Background: Amiodarone, a common antiarrhythmic drug, is known for its severe side effects, including pulmonary toxicity, which involves oxidative stress and apoptosis. Artemisinin, an antimalarial drug, has shown cytoprotective properties by inhibiting oxidative stress and apoptosis. This study investigated the protective effects of artemisinin against amiodarone-induced toxicity in human bronchial epithelial cells (BEAS-2B) and mouse models.

Results: In vitro experiments revealed that amiodarone decreased cell viability, increased LDH release, ROS generation, caspase 3 activation, and apoptosis in BEAS-2B cells. Artemisinin counteracted these effects by upregulating p-AMPK, CaMKK2, Nrf2, and SOD1 protein levels, thereby protecting the cells from oxidative damage. The protective effect of artemisinin was diminished by the AMPK inhibitor Compound C or AMPKα knockdown. In vivo experiments demonstrated that artemisinin increased p-AMPK and Nrf2 protein levels in lung tissues, protecting against amiodarone-induced apoptosis and bronchial epithelial cell shedding in mice.

Conclusion: These findings suggest that artemisinin protects airway epithelial cells and lung tissue from amiodarone-induced oxidative stress and apoptosis through AMPK activation, offering potential new strategies for preventing and treating amiodarone-induced pulmonary toxicity.