Research progress on the role of ferroptosis in the pathogenesis of non-alcoholic fatty liver disease / 基础医学与临床

Ferroptosis is a new type of cell death proposed in recent years,and its main characteristics are iron overload and lipid peroxidation.Ferroptosis is involved in the occurrence and development of non-alcoholic fatty liv-er disease(NAFLD).Iron overload can generate a large amount of reactive oxygen species through the Fenton reac-tion.Under the action of lipoxygenase,the unsaturated fatty acids on the liver cell membrane undergo lipid peroxi-dation,which induces liver cell death and leads to the occurrence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.Blocking ferroptosis may provide one of the therapeutic strategies to protect liver cells.

Iron overload regulates atherosclerotic activity of foam cells induced by oxLDL / 实用医学杂志

Objective To explore the roles of iron overload in pro-atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK-8 test,DHE probe,ELISA,RT-qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase-1(Arg-1),α-smooth muscle actin(α-SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro-inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL-1β,TNF-α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro-atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.

Protective effect of asiatic acid on brain injury after experimental subarachnoid hemorrhage in rats / 天津医药

Objective To explore the neuroprotective effect of asiatic acid(AA)on brain damage after experimental subarachnoid hemorrhage(SAH)in rats.Methods A total of 108 adult SD rats were divided into the sham1 group,the SAH+vehicle group and the SAH+AA group,with 36 rats in each group.The 42 rats were divided into the sham2 group,3,6,12,24,48 and 72 h after SAH groups,with 6 rats in each group.Except the sham group,SAH model was established by unilateral external carotid artery puncture method in other groups.After modeling,the SAH+AA group was given AA solution(30 mg/kg)by gavage.Neurobehavioral changes were assessed by foot fault test and modified Garcia score.Western blot assay was used to detect the protein level of glutathione peroxidase 4(GPX4)in brain tissue.ELISA was used to detect the concentrations of glutathione(GSH)and malondialdehyde(MDA).Fluoro Jade B(FJB)staining was used to detect the neuronal death.Results Compared with the sham1 group,the SAH+vehicle group showed a significant increase in the proportion of empty steps and a significant decrease in the modified Garcia score,a significant decrease in GPX4 protein levels,a significant increase in MDA concentration(P＜0.05),a decrease in GSH concentration(P＜0.01)and a significant increase in the number of dead neurons(P＜0.05).Compared with the SAH+vehicle group,a significant decrease in the proportion of empty steps,a significant increase in the modified Garcia score,a significant increase in GPX4 protein level,a significant decrease in MDA concentration,a significant increase in GSH concentration(P＜0.05)and a significant decrease in the number of dead neurons in the SAH+AA group(P＜0.05).Conclusion AA may reduce brain injury after SAH in rats by inhibiting lipid peroxidation.

Knockdown of SMARCA4 leads to ferroptosis of HT1080 cells through inhibition of cholesterol synthesis / 中国病理生理杂志

AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P＜0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P＜0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.

Changes in iron content, lipid peroxidation, and ferroptosis-related gene expression in vascular endothelial cells in vitro induced by vibration / 环境与职业医学

Background Vascular endothelial injury is an important pathogenic step of vibration-induced hand arm vibration disease (HAVD), and long-term vibration exposure can lead to vascular endothelial cell dysfunction and cell damage. Cell ferroptosis may be one of the important mechanisms of vibration-induced vascular endothelial cell injury and HAVD. Objective To explore whether vibration can induce changes in ferroptosis-related indicators in vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into four vibrationgroups and two control groups. The vibration groups were exposed to an vibration setting of 125 Hz, 6.5 m·s−2 frequency band and for different durations: 1 d 2 h (total 1 d, 2 h per day), 1 d 4 h (total 1 d, 4 h per day), 2 d 2 h (total 2 d, 2 h per day), and 2 d 4 h (total 2 d, 4 h per day), respectively. All control groups were treated the same as the experimental groups except no vibration exposure. When the cells were 80% confluent, the control groups and the corresponding experimental groups were harvested at the same time. The effects of subgroup treatments on iron, reduced glutathione (GSH), and malondialdehyde (MDA) in HUVEC were detected with a cell ferrous colorimetric test kit, a reduced GSH colorimetric test kit, and a trace MDA test kit, respectively. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of ferroptosis-related genes acyl-CoA synthetase long chain family member 4 (ACSL4), tumor protein 53 (P53), recombinant human ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Western blot (WB) was used to detect the expression levels of ferroptosis-related proteins in HUVEC. Results Compared with the control groups, the vibration induced an increase in the iron content of HUVEC with a dose-response trend. Compared with the control groups, the reduced GSH content of HUVEC in the vibration group decreased with the increase of vibration time and frequency, and there was a dose-response trend. Compared with the control groups, the intracellular MDA content of HUVEC in the 1 d 2 h, 1 d 4 h, and 2 d 4 h vibration groups increased, and the MDA content in the 1 d 2 h and 1 d 4 h vibration group increased with time. The RT-PCR results showed that the mRNA expression levels of ACSL4 and P53 in the 1 d 4 h group increased compared with the 1 d 2 h group. Compared with the 2 d control group, the mRNA expression levels of ACSL4 in the 2 d 2 h vibration group and the 2 d 4 h vibration group increased, and the mRNA expression level of P53 in the 2 d 4 h vibration group increased. Compared with the 1 d control group, the mRNA expression levels of FTH1 and GPX4 in endothelial cells in the vibration 1 d 2 h group decreased. The WB results showed that compared with the control groups, the expression level of ferroptosis-related protein ACSL4 in endothelial cells increased in the vibration 1 d 2 h group; the expression levels of P53 in the 1 d 2 h and 2 d 4 h vibration groups increased; the expression levels of GPX4 decreased in the 1 d 4 h and 2 d 2 h vibration group, and the decrease was more obvious in the 2 d 2 h vibration group than in the 1 d 2 h vibration group; the above differences were statistically significant (P<0.05). Conclusion Vibration induces an increase in iron content, a decrease in GSH, and an increase in MDA in vascular endothelial cells in vitro, as well as mRNA and protein expressions of ferroptosis-related genes ACSL4, P53, FTH1, and GPX4.

The effect of ferroptosis on pancreatic inflammatory injury in acute pancreatitis / 西安交通大学学报(医学版)

【Objective】 To observe the presence of ferroptosis in acute pancreatitis (AP) and the effect of iron ions on the NLRP3 pathway so as to explore the possible mechanisms for the protection of pancreatic alveolar cells. 【Methods】 A total of 45 male C57BL/6 mice were randomly divided into three groups (control, AP, and AP+2′2-bipyridyl). A total of 12 injections (caerulein, 50 μg/kg) were given at one-hour intervals. The AP+2′2-bipyridyl group was pretreated with 2′2-bipyridyl (20 mg/kg) for 1 hour, and then injected with caerulein. The control group was injected with an equal volume of normal saline. All of the mice were killed one hour after the last injection. Their pancreases were harvested for histopathological evaluation, immunohistochemistry analyses, and Western blotting. 【Results】 The ferroptosis inhibitor 2′2-bipyridyl could prevent the accumulation of iron ions, reduce the formation of lipid peroxides and the injury in the process of AP, and it also reduced pancreatic inflammation through NLRP3 pathway. 【Conclusion】 This experiment confirmed the real existence of ferroptosis, a form of cell death, in AP, and revealed that inhibition of ferroptosis can reduce pancreatic inflammatory damage in AP.

Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies / 中草药·英文版

OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.

Progress in ferroptosis and its inhibitors in central nervous system diseases / 中国医科大学学报

The etiology of central nervous system(CNS)diseases is complex and mostly unknown,and patients are often left with sequelae and poor prognosis.Recently,ferroptosis has emerged as a unique oxidative stress-induced cell death pathway and is important in various CNS diseases.It is an important mode of neuronal cell death.This article summarizes the molecular mechanism of ferroptosis,research progress of ferroptosis in CNS diseases,and application of ferroptosis inhibitors in CNS diseases to provide new targets and clini-cal references for CNS disease treatment.

The Role of Ubiquitination in Regulating Ferroptosis / 生物化学与生物物理进展

Ferroptosis is a novel type of iron-dependent cell death driven by lipid peroxidation. More and more evidence shows that ferroptosis is related to various pathological conditions, such as neurodegenerative diseases, diabetic nephropathy, and cancer. Ferroptosis driven by lipid peroxidation may promote or inhibit the occurrence and development of these diseases. The intracellular antioxidant system plays an important role in resisting ferroptosis by inhibiting lipid peroxidation. The key pathways of ferroptosis include the amino acid metabolism pathway with SLC7A11-GPX4 as the key molecule, the iron metabolism pathway with ferritin or transferrin as the main component, and the lipid metabolism pathway. The occurrence of ferroptosis is regulated by intracellular proteins, which undergo various post-translational modifications, including ubiquitination. The ubiquitin-proteasome system (UPS) is one of the main degradation systems in cells. It catalyzes the ubiquitin molecule to label the protein and then the proteasome recognizes and degrades the target protein. UPS promotes ferroptosis by promoting the degradation of key ferroptosis molecules (such as SLC7A11, GPX4, and GSH) and antioxidant systems (such as NRF2). UPS can also inhibit ferroptosis by promoting the degradation of related molecules in the lipid metabolism pathway (such as ACLS4 and ALOX15). In this review, we summarize the latest research progress of ubiquitination modification in the regulation of ferroptosis, generalize the published studies on the regulation of ferroptosis by E3 ubiquitin ligase and deubiquitination, and sum up the targets of ubiquitin ligase and deubiquitination regulating ferroptosis, which is helpful to identify new prognostic indicators in human diseases and provide potential therapeutic strategies for these diseases.

The impact of COVID-19 on vitamin E concentrations and oxidative stress markers in adult subjects: A systematic review

Objective: To determine the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Method: We conducted a systematic review using observational studies published between 2020 and 2023, which addressed the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Review articles, clinical trials, letters to the editor, as well as studies conducted with pregnant women, animals and/or in vitro tests, and in languages other than English were excluded from this search. Studies were selected through a literature search in the following electronic databases: PubMed, Science Direct, and Web of Science, from October 2022 to May 2023. Results: Three articles were included in this review, consisting of patients with mild to severe symptoms, including those hospitalized in the intensive care unit. The reduction in vitamin E concentrations was in all studies accompanied by a reduction in enzymes involved in antioxidant action, such as superoxide dismutase, glutathione peroxidase, and glutathione reductase. In parallel to this, studies showed elevated concentrations of lipid peroxidation markers, such as malondialdehyde and myeloperoxidase. Conclusion: Infection with the SARS-COV-2 alters the activity of antioxidant cells and free radical defense agents.

Objetivo: Determinar el impacto del COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Método: Se trata de una Revisión Sistemática, realizada mediante una prospección de estudios observatorios publicados entre 2020 y 2023, que abordaron el impacto de la COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Se excluyeron de esta búsqueda artículos de revisión, ensayos clínicos, cartas al editor, así como estudios realizados con mujeres embarazadas, animales y/o ensayos in vitro, y en idiomas distintos al inglés. Los estudios se seleccionaron mediante una búsqueda bibliográfica en las siguientes bases de datos electrónicas: PubMed, Science Direct y Web of Science, desde octubre de 2022 hasta mayo de 2023. Resultados: Se incluyeron tres artículos en esta revisión, que consistían en pacientes con síntomas de leves a graves, incluidos los hospitalizados en la unidad de terapia intensiva. La reducción de las concentraciones de vitamina E se acompañó en todos los estudios de una reducción de las enzimas implicadas en la acción antioxidante, como la superóxido dismutasa, la glutatión peroxidasa y la glutatión reductasa. Paralelamente, los estudios mostraron concentraciones elevadas de marcadores de peroxidación lipídica, como el malondialdehído y la mieloperoxidasa. Conclusiones: La infección por el virus del SARS-CoV-2 altera la actividad de las células antioxidantes y de los agentes de defensa contra los radicales libres.

Ameliorative effect of sixteen weeks endurance training on biochemical and oxidative damage in high fat diet induced obese rats

Obesity is mainly caused by consumption of high fat diet (HFD) and a lack of physical activity. Physical activity is an efficient strategy to delay development of obesity. In this studyv we tried to evaluate attenuating properties of 16 weeks endurance training on plasma oxidative stress and some biochemical parameters in HFD induced obese rats. Twenty-four male Wistar rats were randomly divided into four groups: standard diet group (SD), standard diet with endurance training group (ESD), HFD group and HFD with endurance training group (EHFD). After sixteen weeks, plasma was prepared and evaluated for measurement of different parameters. The results showed that HFD significantly decreased the activities of superoxide dismutase (33.58%), catalase (26.51%) and glutathione S-transferase (22.77%), while endurance training increased these enzymes activities. However, exercise ameliorated the increased malondialdehyde level and depletion of glutathione. In addition, it significantly reduced the increased levels of liver enzymes activities and lipid profiles. These findings suggest that endurance training has found to have beneficial effects against HFD-induced oxidative damage through increasing reduced antioxidants levels and inhibition of lipid peroxidation due to its antioxidant property. Thus, it can be considered an interesting strategy for the management of obesity related diseases.

Moringa oleifera seeds attenuate benzene-induced alterations in lipid peroxidation and antioxidant enzymes in liver and kidney tissues of Wistar rats

Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II – VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III – VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO’s pro-active role in attenuating benzene toxicity.

Peroxidación lipídica y estrés laboral en trabajadores de una universidad privada del norte de Perú

Objetivo: Establecer la relación entre los niveles de estrés laboral y la producción de malondialdehído (MDA), como producto de la peroxidación lipídica, en los trabajadores de la Universidad Católica Santo Toribio de Mogrovejo en Chiclayo. Materiales y métodos: Investigación descriptiva, de tipo correlacional. La muestra estuvo conformada por 72 trabajadores, de los cuales 37 eran docentes y 35, administrativos. Se midió espectrofotométricamente el MDA presente en el plasma mediante la reacción con ácido tiobarbitúrico (TBA). Para determinar el estrés se utilizó la Escala de Estrés Laboral, elaborada por Ivancevich y Matteson en 1989, y adaptada por Suárez en 2013. El instrumento consta de 25 ítems y está compuesto por siete dimensiones: clima organizacional, estructura organizacional, territorio organizacional, tecnología, influencia del líder, falta de cohesión y respaldo del grupo. Resultados: En la investigación participaron 23 hombres y 49 mujeres. La edad media fue de 45,1 años y la desviación estándar de 11,33, con un mínimo de 25 y máximo de 68 años. El estrés laboral elevado se observó en mayor porcentaje en las dimensiones influencia del líder (19,40 %), estructura organizacional (16,70 %) y territorio organizacional (16,70 %). El 54 % (39) de los trabajadores presentaron niveles altos del MDA, es decir, valores superiores en plasma a 3,94 µM. De ellos, 17 fueron hombres y 22, mujeres. Al evaluar, con Rho de Spearman al 95 % de significancia, la correlación entre los valores de MDA con el sexo, trabajar en otro centro laboral y la atención de hijos en el hogar, resultaron valores de p = 0,08, p = 0,61 y p = 0,33, respectivamente; por lo tanto, no hubo significancia estadística. Conclusiones: Del total de trabajadores evaluados, el 54 % presentó alta concentración de malondialdehído plasmático. Aunque no hubo correlación estadísticamente significativa, las dimensiones con alto nivel de estrés, según la prueba aplicada, influencia del líder, estructura organizacional y territorio organizacional mostraron niveles de estrés en el orden de 19,40 %, 16,70 % y 16,70 %, respectivamente.

Objective: To establish the relationship between occupational stress levels and the production of malondialdehyde (MDA), as a product of lipid peroxidation, among workers of Universidad Católica Santo Toribio de Mogrovejo in Chiclayo. Materials and methods: A descriptive, correlational research. The sample consisted of 72 workers, 37 of whom were professors and 35 administrative staff members. Plasma MDA was measured spectrophotometrically by thiobarbituric acid (TBA) reaction. To determine stress, the Occupational Stress Scale, developed by Ivancevich and Matteson in 1989 and adapted by Suárez in 2013, was used. The instrument had 25 items and seven dimensions: organizational climate, organizational structure, organizational territory, technology, leadership influence, lack of cohesion and group support. Results: Twenty-three men and 49 women participated in the research. The mean age was 45.1 years and the standard deviation was 11.33, with a minimum of 25 and a maximum of 68 years. The highest percentage of high occupational stress was observed in the dimensions leadership influence (19.40 %), organizational structure (16.70 %) and organizational territory (16.70 %). A total of 39 workers (54 %), 17 of whom were men and 22 were women, had high levels of MDA-i.e., plasma values higher than 3.94 µM. Spearman's Rho at 95 % confidence interval showed that the correlation between MDA values and sex, working in another workplace and childcare at home were p = 0.08, p = 0.61 and p = 0.33, respectively; therefore, there was no statistical significance. Conclusions: Out of all workers, 54 % had high plasma levels of MDA. Although no statistically significant correlation was found, the dimensions leadership influence, organizational structure and organizational territory showed high stress levels on the order of 19.40 %, 16.70 % and 16.70 %, respectively.

Screening for acetylcholinesterase inhibition, lipid peroxidation inhibition and antioxidant activity of medicinal plants from Morocco / Detección de inhibición de acetilcolinesterasa, inhibición de peroxidación de lípidos y actividad antioxidante de plantas medicinales de Marruecos

Acetylcholinesterase (AChE), hydrolyzes acetylcholine to choline and acetate, thereby terminating this neurotransmitter effect at cholinergic synapses. Therefore, AChE inhibition is used for counterbalance the cholinergic deficit in Alzheimer's disease (AD) patients. In the present work, in order to find new plant acetylcholinesterase inhibitors, the hydroalcoholic extracts from seventeen medicinal plant species were screened for their acetylcholinesterase inhibition activity, as well as total phenolic (TPC) and flavonoids contents (TFC) and antioxidant activity using ORAC (Oxygen Radical Absorbance Capacity) assay, and their ability to inhibit lipid peroxidation. The results revealed that Rumex acetosa, Taraxacum officinale and Hypericum perforatum extracts possessing the highest TPC and TFC, were the most effective in terms of ORAC antioxidant activity, and acetylcholinesterase inhibition, in addition to their ability to inhibit liposomes peroxidation, suggesting that those plant species may provide a substantial source of secondary metabolites, which act as natural antioxidants and acetylcholinesterase inhibitors, and may be beneficial in the treatment of AD.

La acetilcolinesterasa (AChE) hidroliza la acetilcolina se hidroliza en colina y acetato, terminando así este efecto neurotransmisor en las sinapsis colinérgicas. Por lo tanto, la inhibición de la AChE se utiliza para contrarrestar el déficit colinérgico en pacientes con enfermedad de Alzheimer (EA). En el presente trabajo, con el fin de encontrar nuevos inhibidores de la acetilcolinesterasa vegetal, se analizaron los extractos hidroalcohólicos de diecisiete especies de plantas medicinales para determinar su actividad inhibidora de la acetilcolinesterasa, así como el contenido total de fenólicos (TPC) y flavonoides (TFC) y la actividad antioxidante utilizando ORAC (Capacidad de absorbancia de radicales de oxígeno) y su capacidad para inhibir la peroxidación de lípidos. Los resultados revelaron que los extractos de Rumexacetosa, Taraxacum officinale e Hypericum perforatum que poseen los más altos TPC y TFC, fueron los más efectivos en términos de actividad antioxidante ORAC e inhibición de acetilcolinesterasa, además de su capacidad para inhibir la peroxidación de los liposomas, sugiriendo que esas especies de plantas puede proporcionar una fuente sustancial de metabolitos secundarios, que actúan como antioxidantes naturales e inhibidores de la acetilcolinesterasa, y puede ser beneficioso en el tratamiento de la EA.

Research progress on ferroptosis regulated by glycolysis-fatty acid metabolism in metabolic diseases / 药学学报

In metabolic diseases, the accumulation of reactive oxygen species and oxidative stress are closely associated with ferroptosis. As a key regulatory factor, the imbalance between glycolysis and fatty acid metabolism can participate in ferroptosis directly or indirectly, thereby regulating the occurrence and development of various metabolic diseases. The essence of ferroptosis is a new regulatory cell death mode, which is caused by the excessive accumulation of iron-dependent lipid peroxide. It is closely related to glycolysis and fatty acid metabolism, which plays an important role in metabolic diseases. This regulatory cell death mode is significantly distinguished from other programmed cell death modes and has unique changes in cell morphology, symbolic characteristics and mechanisms. This paper first illustrates the main mechanism of glycolysis and fatty acid metabolism imbalance in the occurrence of ferroptosis, then reviews the research progress of ferroptosis in tumor, diabetes, rheumatoid arthritis and other metabolic diseases, and finally reveals the internal connection between glycolysis-fatty acid metabolism imbalance and ferroptosis, as well as its impacts on metabolic diseases, which provide new strategies for the prevention and treatment of metabolic diseases.

Research advances in ferroptosis in the pathogenesis and treatment of nonalcoholic fatty liver disease / 临床肝胆病杂志

Ferroptosis is a pattern of non-apoptotic cell death characterized by iron dependence and lipid peroxidation. Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease with fat infiltration as its main pathological feature, and it is closely associated with insulin resistance and genetic susceptibility. The mechanism of transition from hepatic steatosis alone to steatohepatitis remains unclear, and studies have shown that ferroptosis in hepatocytes may be the trigger for the inflammatory initiation of steatohepatitis. This article reviews the role of abnormal iron metabolism and lipid peroxidation in promoting the development and progression of NAFLD and summarizes the application prospect of ferroptosis-related inhibitors in the treatment of NAFLD.

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Exploring the Pathogenesis of T2DM based on the Correlation between “Qi-fire Imbalance” and Ferroptosis / 中医杂志

Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.

Exploring the Pathogenesis of T2DM based on the Correlation between “Qi-fire Imbalance” and Ferroptosis / 中医杂志

@#Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.