Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Flower-like tin oxide membranes with robust three-dimensional channels for efficient removal of iron ions from hydrogen peroxide

Membrane technology has become the mainstream process for the production of electronic grade hydrogen peroxide(H_(2)O_(2)).But due to the oxidation degradation of the organic membranes(e.g.polyamide)by the strong oxidative radicals(e.g.OH)generated via the activation of H_(2)O_(2)by iron ions(Fe^(3+)),the short effective lifetime of membranes remains a challenge.Inorganic nano tin oxide(SnO_(2))has great potential for the removal of Fe^(3+)in strongly oxidative H_(2)O_(2)because of its ability to stabilize H2O_(2)and preferentially adsorb Fe^(3+).Herein,we have designed for the first time a flower-like robust SnO_(2)membrane on the ceramic support by in situ template-free one-step hydrothermal method.The three-dimensional loose pore structure in the membrane built by interlacing SnO_(2)nanosheets endows the SnO_(2)membrane with a high specific surface area and abundant adsorption sites(AOH).Based on the coordination complexation and electrostatic attraction between the SnO_(2)surface and Fe^(3+),the membrane shows a high Fe3+removal efficiency(83%)and permeability(24 L·m^(-2)·h^(-1)·MPa^(-1))in H_(2)O_(2).This study provides an innovative and simple approach to designing robust SnO_(2)membranes for highly efficient removal of Fe^(3+)in harsh environments,such as strong oxidation conditions.

Pilot Test of Preparing 2-Alkylanthraquinone Using Alkylation-Oxidation Technology

To expedite the development of industrial technology for producing 2-alkylanthraquinone,a novel pilot test of alkylation-oxidation technology was conducted.The process mainly included anthracene alkylation,separation of anthracene and 2-alkylanthracene,oxidation of 2-alkylanthracene,and product purification.Optimal alkylation conditions yielded a 91.1%conversion of anthracene and a 71.73%selectivity for 2-alkylanthracene.To address the separation problem of anthracene and 2-alkylanthracene,solvent-assisted distillation technology was developed,resulting in a 98.9%purity of 2-alkylanthracene and a 91.82%separation yield.When the molar ratio of H2O_(2) to 2-alkylanthracene was 7:1,a 98.96%conversion of 2-alkylanthracene and a 99.94%selectivity for 2-alkylanthraquinone were achieved.A novel composition of 2-alkylanthraquinone,including 2-tert-butylanthraquinone,2-tert-amylanthraquinone,and 2-hexylanthraquinone,was developed.This composition could be effectively separated and purified through a combination of crystallization and washing processes.The elemental composition of the product met the existing standards,and its hydrogenation performance closely matched that of commercially available 2-tert-amylanthraquinone products.

Suppressing a mitochondrial calcium uniporter activates the calcium signaling pathway and promotes cell elongation in cotton

Mitochondrial calcium uniporter(MCU)is a conserved calcium ion(Ca^(2+))transporter in the mitochondrial inner membrane of eukaryotic cells.How MCU proteins regulate Ca^(2+)flow and modulate plant cell development remain largely unclear.Here,we identified the gene GhMCU4 encoding a MCU protein that negatively regulates plant development and fiber elongation in cotton(Gossypium hirsutum).GhMCU4expressed constitutively in various tissues with the higher transcripts in elongating fiber cells.Knockdown of GhMCU4 in cotton significantly elevated the plant height and root length.The calcium signaling pathway was significantly activated and calcium sensor genes,including Ca^(2+)dependent modulator of interactor of constitutively active ROP(GhCMI1),calmodulin like protein(GhCML46),calciumdependent protein kinases(GhCPKs),calcineurin B-like protein(GhCBLs),and CBL-interacting protein kinases(GhCIPKs),were dramatically upregulated in GhMCU4-silenced plants.Metabolic processes were preferentially enriched,and genes related to regulation of transcription were upregulated in GhMCU4-silenced plants.The contents of Ca^(2+)and H_(2)O_(2)were significantly increased in roots and leaves of GhMCU4-silenced plants.Fiber length and Ca^(2+)and H_(2)O_(2)contents in fibers were significantly increased in GhMCU4-silenced plants.This study indicated that GhMCU4 plays a negative role in regulating cell elongation in cotton,thus expanding understanding in the role of MCU proteins in plant growth and development.

High-rate electrochemical H_(2)O_(2) production over multimetallic atom catalysts under acidic–neutral conditions

Hydrogen peroxide(H_(2)O_(2))production by the electrochemical 2-electron oxygen reduction reaction(2e−ORR)is a promising alternative to the energy-intensive anthraquinone process,and single-atom electrocatalysts show the unique capability of high selectivity toward 2e−ORR against the 4e−one.The extremely low surface density of the single-atom sites and the inflexibility in manipulating their geometric/electronic configurations,however,compromise the H_(2)O_(2) yield and impede further performance enhancement.Herein,we construct a family of multiatom catalysts(MACs),on which two or three single atoms are closely coordinated to form high-density active sites that are versatile in their atomic configurations for optimal adsorption of essential*OOH species.Among them,the Cox–Ni MAC presents excellent electrocatalytic performance for 2e−ORR,in terms of its exceptionally high H_(2)O_(2) yield in acidic electrolytes(28.96 mol L^(−1) gcat.^(−1) h^(−1))and high selectivity under acidic to neutral conditions in a wide potential region(>80%,0–0.7 V).Operando X-ray absorption and density functional theory analyses jointly unveil its unique trimetallic Co2NiN8 configuration,which efficiently induces an appropriate Ni–d orbital filling and modulates the*OOH adsorption,together boosting the electrocatalytic 2e−ORR capability.This work thus provides a new MAC strategy for tuning the geometric/electronic structure of active sites for 2e−ORR and other potential electrochemical processes.

Preparation of PrFe_(x)Co_(1-x)O_(3)/Mt catalyst and study on degradation of 2-hydroxybenzoic acid wastewater by catalytic wet peroxide oxidation

In this study,the perovskite nanocomposite PrFe_(x)Co_(1-x)O_(3)(Pr(S))was successfully synthesized by the sol-gel method;PrFe_(x)Co_(1-x)O_(3)/Al-pillared montmorillonite(Pr(S)/Mt)catalysts were prepared by impregnation(D)method and solid-melting(G)method,respectively,with Pr(S)as the active component and Al-pillared montmorillonite as the carrier.The catalysts were applied to treat the 2-hydroxybenzoic acid(2-HA)-simulated wastewater by catalytic wet peroxide oxidation(CWPO)technique,and the chemical oxygen demand(COD)removal rate and the 2-HA degradation rate were used as indicators to evaluate the catalytic performance.The results of the experiment indicated that the solid-melting method was more conducive to preparing the catalyst when the Co/Fe molar ratio of 7:3 and the optimal structural properties of the catalysts were achieved.The influence of operating parameters,including reaction temperature,catalyst dosage,H_(2)O_(2)dosage,pH,and initial 2-HA concentration,were optimized for the degradation of 2-HA by CWPO.The results showed that 97.64%of 2-HA degradation and 75.23%of COD removal rate were achieved under more suitable experimental conditions.In addition,after the catalyst was used five times,the degradation rate of 2-HA could still reach 76.93%,which implied the high stability and reusability of the catalyst.The high catalytic activity of the catalyst was due to the doping of Co into PrFeO_(3),which could promote the generation of HO·,and the high stability could be attributed to the loading of Pr(S)onto Al-Mt,which reduced the leaching of reactive metals.The study of reaction mechanism and kinetics showed that the whole degradation process conformed to the pseudo-firstorder kinetic equation,and the Langmuir-Hinshelwood method was applied to demonstrate that catalysis was dominant in the degradation process.

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

One stone two birds:electrochemical and colorimetric dual-mode biosensor based on copper peroxide/covalent organic framework nanocomposite for ultrasensentive norovirus detection

Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH_(2)nanocomposite(CuO_(2)@COF-NH_(2)).For the colorimetric detection,NoV can be directly detected by the naked eye based on CuO_(2)@COF-NH_(2)as a laccase-like nonazyme using“peptide-NoV-antibody”recognition mode.The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection(LOD)of 0.125 copy/mL.For the electrochemical detection of NoV,CuO_(2)@COF-NH_(2)showed an oxidation peak of copper ion from Cu^(+)to Cu^(2+)using“peptide-NoV-antibody”recognition mode.The electrochemical assay showed a linear detection range was 1-5000 copies/mL with a LOD of 0.152 copy/mL.It's worthy to note that this assay does not need other electrical signal molecule,which provide the stable and sensitive electrochemial detection for NoV.The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples,which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer

BACKGROUND Gastric cancer is one of the most common malignant tumors in the world,and its occurrence and development involve complex biological processes.Iron death,as a new cell death mode,has attracted wide attention in recent years.However,the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear.AIM To explore the role of iron death in the development of gastric cancer,reveal its relationship with lipid peroxidation,and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer.METHODS The process of iron death in gastric cancer cells was simulated by cell culture model,and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry.The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology.In addition,a mouse model of gastric cancer was established,and the role of iron death in vivo was studied by histology and immunohistochemistry,and the level of lipid peroxidation was detected.These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer.RESULTS Iron death was significantly activated in gastric cancer cells,and at the same time,associated lipid peroxidation levels increased significantly.Through high-throughput sequencing analysis,it was found that iron death regulated the expression of several genes related to lipid metabolism.In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation.CONCLUSION This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.The activation of iron death significantly increased lipid peroxidation levels,revealing its regulatory mechanism inside the cell.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Protective Effect of Naringenin on Acute Myocardial Ischemia-reperfusion Injury in Rats

[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.

Research progress on the anti-colorectal cancer effect of traditional Chinese medicine active ingredients based on ferroptosis

Ferroptosis is defined as an iron-dependent form of regulated cell death that is initiated by the toxic accumulation of lipid peroxides on cellular membranes.In the past decade,ferroptosis has aroused considerable interest in comprehensive treatment of colorectal cancer,mainly as it is a specific cell death mode that is mechanistically and morphologically differ from other forms of cell death such as autophagy,apoptosis,and pyroptosis,following by holding a giant potential for the therapy of colorectal cancer.Research has found that various active ingredients in traditional Chinese medicine possess the ability of inducing ferroptosis in colorectal cancer cells through pathways such as lipid metabolism,iron metabolism,or cysteine/glutamate transporter system,which demonstrating enormous clinical therapeutic potential.In this review,the metabolic regulatory network of ferroptosis is introduced from the perspective of ferroptosis mechanism,and the information on the induction of ferroptosis in colorectal cancer cells by active ingredients of traditional Chinese medicine is also be retrospected,which the purpose is to provide novel strategies for the anti-colorectal cancer therapy of active ingredients in traditional Chinese medicine.

A Natural Catalytic Converter® for Continuously Inactivating Air and Surface Pathogens with More Effect than Ventilation and Filtration

Study Objective: The purpose of the study is to present independent laboratory testing for a novel technology in air and on surfaces. Since 2020, public health goals have focused on improving indoor air quality. This includes protection from airborne pathogens, such as tuberculosis, RSV, SARS-CoV-2, common cold or influenza viruses, measles, and others. Engineering controls are highly effective at reducing hazardous pathogens found in indoor air and from recontamination of surfaces. This occurs from a continuous cycle of settling of small, sustained airborne pathogens, which may become dehumidified, becoming airborne again, carried by room air currents around indoor spaces, then repeating the cycle. Methods: The novel technology utilizes a catalytic process to produce safe levels of hydrogen peroxide gas that are effective in reducing pathogens in the air and on surfaces. Air testing was performed with the MS2 bacteriophage, the test organism for ASHRAE standard 241, and methicillin-Resistant Staphylococcus aureus (MRSA). Surface testing was performed with SARS-COV-2 (Coronavirus COVID-19) and H1N1 (Influenza). Typical ventilation and filtration does not effectively remove disbursed pathogens from the entire facility, due to inconsistent air circulation and surface deposits of pathogens. Results: MS2 was reduced by 99.9%;MRSA was reduced by 99.9%;SARS-CoV-2 was reduced by 99.9%;H1N1 was reduced by 99.9%. Conclusion: This novel catalytic converter reduces a variety of pathogens in the air (99%) and on surfaces (99%), by actively disinfecting with the introduction of gaseous hydrogen peroxide. This active disinfection provides a strong solution for protecting the entire facility and its occupants.

Optimization of the Gas Generator in Composite Power System with Tip-Jet Rotor

The key and bottleneck of research on the tip-jet rotor compound helicopter lies in the power system. Computational Fluid Dynamics (CFD) was used to numerically simulate the gas generator and rotor inner passage of the tip-jet rotor composite power system, studying the effects of intake mode, inner cavity structure, propellant components, and injection amount on the characteristics of the composite power system. The results show that when a single high-temperature exhaust gas enters, the gas generator outlet fluid is uneven and asymmetric;when two-way high-temperature exhaust gas enters, the outlet temperature of the gas generator with a tilted inlet is more uniform than that with a vertical inlet;adding an inner cavity improves the temperature and velocity distribution of the gas generator's internal flow field;increasing the energy of the propellant is beneficial for improving the available moment.

Fighting age-related orthopedic diseases: focusing on ferroptosis

Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis,particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.

Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury

Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.