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.

Changes in erythrocyte membrane ATPases and plasma lipid peroxides in upper abdominal surgery under intravenous procaine-balanced anesthesia

AIM To observe the changes in erythrocyte membrane ATPases and plasma lipid peroxides (LPO) patients with in abdominal surgery under intravenous procaine-balanced anesthesia.METHODS By determining the ATPase activities of erythrocyte membrane, effects of upper abdominal surgery under intravenous procaine-balanced anesthesia on the function of erythrocytes were observed in 15 patients undergoing cholecystectomy and gastrectomy (5 males and 10 females, aged 45.9±10.20 years and weighed 60.60kg±11.93kg). All patients were free from severe renal, hepatic, pulmonary, cardiac, metabolic and endocrinological diseases and acute infection for at least 2 weeks before surgery. Patients receiving any drug known to affect carbohydrate metabolism prior to anesthesia were excluded from the study.RESULTS Erythrocyte membrane Na+, K+-ATPase, Mg2+-ATPase, Ca2+, Mg2+-ATPase activities were not significantly changed 60min-90min after incision as compared with 30min before anesthesia, but were decreased markedly 10min and 24 hours after completion of operation (P＜0.01). Plasma lipid peroxides (LPO) were increased significantly 24 hours after surgery (P＜0.01) following an initially marked but transient reduction. Plasma LPO changes were not correlated with erythrocyte membrane ATPase activities, r=-0.0396, -0.0097 and 0.4383, respectively (P＞0.05).CONCLUSION Abdominal surgical trauma under intravenous procaine-balanced anesthesia may be associated with the decreased ATPase activities of erythrocyte membrane and increased LPO in plasma.

Adiabatic Decomposition of Two Kinds of Organic Peroxides by Accelerating Rate Calorimeter

The accelerating rate calorimeter was applied to study the thermal hazard of two kinds of organic peroxides, i.e. methyl ethyl ketone peroxide (MEKPO) and benzoyl peroxide (BPO). And their thermal decomposition characteristics were discussed. Meanwhile, thermal decomposition characteristics of MEKPO and BPO vvere compared. The result indicated that MEKPO is more sensitive to thermal effect than BPO. While once the thermal decomposition takes place. BPO will be more hazardous than MEKPO due to its serious pressure effect. Thermal kinetic analysis of these two kinds of organic peroxides was also taken, and the kinetic parameters for them were calculated. The study of thermal decomposition of MEKPO solution with different initial concentrations indicated that, the lower concentration MEKPO solution is, the higher onset temperature will be. And with the addition of organic solvent, it becomes more difficult for MEKPO to reach a thermal decomposition. Therefore, its thermal hazard is reduced.

Effects of Organic Peroxides on the Curing Behavior of EVA Encapsulant Resin

Compounds of poly(ethylene-co-vinyl acetate) (EVA with vinyl acetate content 33%) with three different organic per- oxides, namely, dialkyl peroxide, peroxyester peroxide, and peroxyketal peroxide, were prepared with a twin screws extruder and a two-roll mixing mill. The cure behavior of the EVA compounds was analyzed from rheographs, which were obtained by a moving die rheometer (MDR) at various curing temperatures between 150?C to 170?C. The effects of organic peroxides on cure behavior were examined. The dynamic curing obtained by the torque rheometer provided sufficient experimental data to show that dialkyl peroxide is not suitable because it has a high half-life temperature and its by-products can discolor the final product. Peroxyester peroxide is good for curing at temperatures in the range of 150?C to 160?C, which accomplished an ultimate cure within 5 to 8 minutes. Also, the peroxyketal peroxide has higher performance, which decreased the optimum cure time to 3 minutes. The thermal decomposition mechanism of organic peroxide was applied to explain how the cure behavior is affected by generated free radicals.

NMR used to study the side-reactions between peroxides and antioxidants during the reactive extrusion process of the impact polypropylene

Side reaction pathways are observed to occur between antioxidants and peroxide during the processing of multiple resin grades mediated by controlled peroxide-induced degradation of impact polypropylene.In the present work,the reaction mechanism and main by-products between antioxidants and peroxides were investigated.The results demonstrate that peroxides greatly accelerate the decomposition reactions,and the free radicals formed from peroxide decomposition react with,for example,the antioxidant AO1010 to produce dehydrogenation of phenyl propionic unit(s)at the a position(cinnamic acid ester moiety),which generates a conjugated system leading to the increased color of the product.It is the first time to confirm the cinnamic acid moiety's existence and report its NMR data.Further,this work confirms the dehydrogenation mechanism by comparison with different sterically hindered phenolic antioxidants.It also systematically summarizes the oxidation and degradation mechanism of AO168 and AO1010 under air and peroxide environments,respectively.Based on present study,clear guidelines are obtained to improve the quality of polymeric products,especially the appearance and stability,during product development.

AN AB INITIO STU DY ON THE CORELATION BETWEEN THE ABSOLUTE CONFIGURATION AND THE CD SPECTRA OF ORGANIC PEROXIDES

Correlation between the absolute configuration and the CD spectra of organic peroxides was studied by ab initio method with a mo- d el moleeule CH_3-O-O-CH_3.For P form when 0°≤θ(twist angle of C-O-O-C) <90°, there is positive Cotton effect;when 90°<θ≤180°, there is nega- tive Cotton effect;the curve is bisignate at θ=90°.

Level of lipid peroxides and cuprozinc superoxide dismutase in gastric mucosa and serum of gastrectomized patients

The level of lipid peroxides (LPO) and copper-zinc containing superoxide dismutase (SOD-Ⅰ) in the gastric mucosa and serum was determined in 141 samples from 25 patients after con-ventional subtotal gastrectomy (11 cases of Billroth Ⅰ and 14 cases of Billroth Ⅱ) and 11 patientsafter pylorus and antroseromuscular flap preserving gastrectomy (PAFPG).Those of 11 normal subjects were examined likewise to serve as control.It was found that:(1) The average LPO levelwas much higher and the average SOD-Ⅰ level much lower in the gastric mucosa of the patientsafter conventional subtotal gastrectomy especially the Billroth Ⅱ type than in that of those afterPAFPG.(2) In 36 specimens of stump mucosa,the average LPO level was significantly higher inthe tissue around the anastomotic ring than in that of the body of the stump;no marked differ-ence of SOD-Ⅰ level between the 2 was revealed.(3) The LPO value in the stump mucosa waspositively correlated to and the SOD-Ⅰ value negatively correlated to the pH value of gastric juice.These rindings suggest that the reation of oxygen free radicals in the stump mucosa may be influ-enced by the intragastric pH or by the type of digestive continuity reconstruction,and that thereaction of oxygen free radicals especially the lipid peroxidation may play a role in the pathogenesisof the lesions in the anastomotic stoma.

Changes in erythrocyte membrane ATPase and plasma lipid peroxides during perioperative period

Changes in erythrocyte membrane ATPases and plasma lipid peroxides（LPO） were studiedperioperatively in 15 abdominal surgical patients under intravenous procaine-balanced anesthesia.The resultsrevealed that erythrocyte membrne Na+-K+ATPase,Mg2+ATPase and Ca2+-Mg2+ATPase activities werenot significantly changed at 60～90 min after incision as compared with 30 min before anesthesia,but weredecreased markedly at 10 rain and 24 hours after completion of operation（P【0.01）.Plasma LPO wereincreased significantly by 24 hours after surgery（P【0.01） following an initially marked but transientreduction.Plasma LPO changes were not correlated with erythrocyte membrane ATPase activities,r=-0.0396,-0.0097 and-0.4383 respeetively（P】0.05）.These correlations are suggested to be inducedby neuroendoerine responses after anesthesia and/or surgical trauma.

Changes of Selenium Metabolism Glutathione Peroxidase Activity and Lipid Peroxides Content in Severely Scalding-injured Rats

The changes of sclenium metabolism, glutathione peroxidase activity and lipid peroxidescontent in the tissues of rats suffering from 30% TBSA full thickness scalding were observed in thefirst 7 days after injury. It was found that selenium content in the rat tissues decreased remarkably af-ter injury, which in turn resulted in serious reduction of glutathione peroxidasc activity and significantincrease of lipid peroxides in the scrum, crythrocytcs and liver. However the muscular tissue showedno significant changes. These facts imply that after burn injury, the body is in a state of selenium deficiency, the lossof selenium might be responsible for the reduction of anti - peroxidation ability of glutathioneperoxidase, and conscqucntly there is an increase of lipid peroxides in the tissues. Only the musculartissue is insensitive to lipid peroxidation. It is believed that the reduction of anti-peroxidation abilityof glutathione peroxidasc after bum injury might be one of the main causes to intensify, the injury re-suiting from free radicals.

Exogenous Vitamin K3 and Peroxides Can Alleviate Hypoxia in Bean Seedlings (<i>Phaseolus vulgaris</i>L.)

Oxygen limiting conditions are a common occurrence in root zones of most crop plants and can adversely affect nearly all aspects of plant growth and development including its survival. The objective of this study was to determine the effectiveness of a novel redox cycling agent, vitamin K3, and various peroxides including hydrogen peroxide, calcium peroxide and magnesium peroxide in alleviating the effects of hypoxia in bean seedlings grown in nutrient culture. All the anti-hypoxic agents including vitamin K3 had a positive impact on the overall growth of bean seedlings under hypoxic conditions, but their responses were variable depending on the concentration. With regard to shoot growth, vitamin K3 (5 μM) increased the leaf area significantly, by more than 58% over the hypoxic control plants and produced the highest stem fresh weight similar to calcium peroxide (20 μM) and magnesium peroxide (10 μM). In addition, the use of vitamin K3 resulted in the highest accumulation of chlorophyll (chla + chlb) in the leaves, an increase of nearly two-fold over the hypoxic control plants. Furthermore under hypoxia, calcium peroxide (20 μM) and magnesium peroxide (10 μM) produced the highest leaf biomass (FW) followed by vitamin K3. Vitamin K3 (1 μM) also favored root growth in bean seedlings under hypoxia;it produced the largest increase in root length and root biomass (DW) similar to calcium peroxide and magnesium peroxide. Based on the overall shoot and root growth response of bean seedlings to various anti-hypoxic substances under hypoxic conditions, calcium peroxide, magnesium peroxide and vitamin K3 performed better than hydrogen peroxide. These findings show that vitamin K3 and peroxide salts are effective in alleviating hypoxic stress in bean seedlings and also, further highlight their potential for dealing with hypoxia in wide ranging situations.

Amperometric Biosensors Sensitive to Organic Peroxides Based on Immobilization of Redox Organic Dyes and Horseradish Peroxidase in Polyester Ionomer Film

Simple and effective organic biosensors sensitive to organic peroxides such as 2 butanone per oxide and tertbutyl hydroperoxide are constructed by immobilizing a series of redox organic dyes and horseradish peroxidase in Eastman AQ polymer film. The organic dyes are methylene blue, methylene green, meldola blue, new methylene blue N and N methyl phenazine methosulphate. The biosensors display high sensitivity and fast response to tertbutyl hydroperoxide and 2 butanone peroxide because of high efficiency of electron transfer between immobilized horseradish peroxidase and the electrode via the redox organic dyes. The comparison of the biosensors employing different organic dyes is made in formal potential, linear range and response time.

Apple Peel Biochemical Changes after Foliar Application of Combined Boron and Calcium II. Photosynthetic Pigments, Total Peroxides and Photochemical Efficiency

Understanding of the physiological effect of post-full-bloom foliar boron combined with calcium (B+Ca) on apple (Malus domestica) peel tissues is envisaged to give way to the unknown mode-of-action by which these mineral regimens suppress fruit sunburn-browning incidence in orchards. Promotion of this mineral approach among growers, as a certainly cheaper alternative to mitigate fruit sunburn-browning incidence in apple orchards necessitates clear elucidation of its mode-of-action. This study investigated peel photosynthetic pigments and total peroxides (as a measure of oxidative stress) in three apple cultivars, ‘Cripps Pink’, ‘Golden Delicious’ and ‘Granny Smith’ which were treated with four B+Ca treatments varying in levels of B and Ca as well as inclusion of zinc (Zn) in one treatment. Randomized complete block design experiments with five replications were conducted at commercial farms in Western Cape, South Africa. Significant (p < 0.05) treatment effect for major pigment aspects and total peroxides occurred in all cultivars, but with strong influence of cultivar and fruit age. For instance, effect of varying B, Ca and possible B+Ca duet-effect on photosynthetic pigments occurred in ‘Cripps Pink’, whereas the Zn-treatment was mainly responsible for significant treatment effects in both ‘Golden Delicious’ and ‘Granny Smith’ apples. Significant treatment effect for total peroxides occurred in ‘Cripps Pink’ and ‘Granny Smith’, yet significant interaction effect occurred with ‘Golden Delicious’, however, these significant results did not yield meaningful peel oxidative stress differences among the treatments. Foliar treatment differences in photochemical efficiency (Fv/Fm) were not significant. The study concludes with firm evidence that foliar B+Ca treatment composition has a significant effect on apple peel photosynthetic pigments depending on cultivar, and Zn is not desirable in the formulation of these treatments.

Relative Explosive Strength of Some Explosive Mixtures Containing Urea and/or Peroxides

Several mixtures,based on urea derivatives and some inorganic oxidants,including also alumina,were studied by means of ballistic mortar techniques with TNT as the reference standard.The detonation pressure(P),detonation velocity(D),detonation energy(Q),and volume of gaseous product at standard temperature and pressure(STP),V,were calculated using EXPLO5V6.3 thermochemical code.The performance of the mixtures studied was discussed in relation to their thermal reactivity,determined by means of differential thermal analysis(DTA).It is shown that the presence of hydrogen peroxide in the form of its complex with urea(i.e.as UHP)has a positive influence on the explosive strength of the corresponding mixtures which is linked to the hydroxy-radical formation in the mixtures during their initiation reaction.These radicals might initiate(at least partially)powdered aluminum into oxidation in the CJ plane of the detonation wave.Mixtures containing UHP and magnesium are dangerous because of potential auto-ignition.

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.

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.

Flavonoids Reduce Lipid Peroxides and Increase Glutathione Levels in Pooled Human Liver Microsomes (HLMs)

The effects of each of the flavonoids;genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.

Estimation of thermal decomposition temperatures of organic peroxides by means of novel local and global descriptors

The thermal decomposition temperature is one of the most important parameters to evaluate fire hazard of organic peroxide. A quantitative structure-property relationship model was proposed for estimating the thermal decomposition temperatures of organic peroxides. The entire set of 38 organic peroxides was at random divided into a training set for model development and a prediction set for external model validation. The novel local molecular descriptors of AT1, AT2, AT3, AT4, AT5, AT6 and global molecular descriptor of ATC have been proposed in order to character organic peroxides’ molecular structures. An accurate quantitative structure-property relationship （QSPR） equation is developed for the thermal decomposition temperatures of organic peroxides. The statistical results showed that the QSPR model was obtained using the multiple linear regression （MLR） method with correlation coefficient （R）, standard deviation （S）, leave-one-out validation correlation coefficient （RCV） values of 0.9795, 6.5676 ℃ and 0.9328, respectively. The average absolute relative deviation （AARD） is only 3.86% for the experimental values. Model test by internal leave-one-out cross validation and external validation and molecular descriptor interpretation were discussed. Comparison with literature results demonstrated that novel local and global descriptors were useful molecular descriptors for predicting the thermal decomposition temperatures of organic peroxides.

Synthesis of Antimalarial Bicyclic Hemiketal Peroxides Belonging to the G-factor Family

Structural analogues of bicyclic peroxides belonging to the G factors family have been synthesised under Mannieh type conditions, followed by an autoxidation step furnishing exclusively the peroxide. As electron transfer from heine or free iron to peroxide is the first step in the mode of action ofartemisinin -like compound, Fe（fl） induced reduction was studied and the reactivity of the intermediate C-centered radical formed was correlated to the antimalarial activity. Dissociative electron transfer was studied by electrochemistry and allowed the evaluation of the standard reduction potentials and other pertinent thermochemical information. These bicyclic peroxides were evaluated in vitro against Plasmodium falciparum and revealed moderate to good activity.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

Multidimensionally Nano‑topologized Polycaprolactone Fibrous Membrane Anchored with Bimetallic Peroxide Nanodots for Microenvironment‑Switched Treatment on Infected Diabetic Wounds

Delayed healing of diabetic wounds poses a major challenge to human health due to severe vascular dysfunction,sustained inflammation,and vulnerability to microbial infection.Herein,we constructed multidimensionally nano-topologized elec-trospun polycaprolactone(PCL)fibrous membranes with shish-kebab nanoarrays on each fiber through self-induced crys-tallization,on which the CuO2-MgO2 bimetallic peroxide nanodots(BPNs)were anchored by polydopamine(PDA)as the bridging layer.When activated by the acidic microenvironment(typically infected diabetic wound),BPNs on fibers reacted immediately to release Cu2+and Mg2+ions together with hydrogen peroxide(H2O2)molecules,which were then transferred into·OH radicals through Fenton-type reactions catalyzed by Cu2+for instant bacteria elimination.At the same time,the released Cu2+and Mg2+ions were retained to improve the angiogenesis and suppress the inflammation infiltration,thus remodeling the wound microenvironment.Meanwhile,the one-dimensional(1D)-constructed nano shish-kebabs and PDA coating on fibers provided additional topological activation for cell adhesion and directed migration along the aligned fiber orientation.Through the meticulous design,the resultant membranes markedly accelerated the infected wound healing in the diabetic rat model.This study pioneers a unique design to develop a nanocomposite fibrous membrane that combines multidimensional topologies with chemodynamic therapy(CDT),for efficiently combating infected diabetic wounds.