Etiología y evolución de la anemia en pacientes sometidos a cirugía cardiovascular / Etiology and evolution of anemia in patients submitted to cardiovascular surgery

Resumen Objetivo: El objetivo del presente estudio es evaluar en nuestro medio la prevalencia de anemia en el preoperatorio de la cirugía cardiovascular, su incidencia postoperatoria y su evolución durante el primer mes. Métodos: Se realizó un estudio de cohorte prospectivo en el que se incluyeron todos los pacientes sometidos a cirugía cardiovascular central intervenidos durante el periodo del 01/09/2021 al 01/09/2022 en un hospital universitario. Se realizó seguimiento clínico y de laboratorio previo a la cirugía, al quinto y al día treinta del postoperatorio. Se comparó a los grupos con y sin anemia preoperatoria. Resultados: La prevalencia de anemia en el preoperatorio fue del 32.1%. La incidencia de anemia en el postoperatorio fue del 96% en el grupo de pacientes sin anemia previa. Al mes de la cirugía un 73 y un 90% de los pacientes, con y sin anemia preoperatoria respectivamente, persistían anémicos. Los pacientes con anemia preoperatoria tuvieron una menor recuperación de sus valores de hemoglobina al mes. Se observó una tendencia a mayor mortalidad y una mayor necesidad de derivación a centros de rehabilitación postegreso hospitalario en aquellos con anemia preoperatoria. Conclusiones: En este trabajo se evidenció una alta prevalencia e incidencia de anemia en el perioperatorio de las cirugías cardiovasculares. Así como su subtratamiento y elevada persistencia durante el mes posterior a la cirugía.

Abstract Objective: The aim of this study is to evaluate the prevalence of anemia in the preoperative period of cardiovascular surgery, its postoperative incidence and its evolution during the first month in our setting. Methods: A prospective cohort study was carried out in which all patients undergoing central cardiovascular surgery operated during the period 09/01/2021-09/01/2022 in a university hospital were included. Clinical and laboratory follow-up was carried out prior to surgery, on the fifth and on the 30th postoperative day. Groups with and without preoperative anemia were compared. Results: The prevalence of anemia in the preoperative period was 32.1%. The incidence of anemia in the postoperative period was 96% in the group of patients without previous anemia. One month after surgery, 73 and 90% of the patients, with and without preoperative anemia, respectively, remained anemic. Patients with preoperative anemia had less recovery of their hemoglobin values at one month. A trend towards higher mortality and a greater need for referral to post-hospital discharge rehabilitation centers was observed in those with preoperative anemia. Conclusions: In this work, a high prevalence and incidence of anemia in the perioperative period of cardiovascular surgeries was evidenced. As well as its subtreatment and high persistence during the month after surgery.

Factores asociados a anemia ferropénica en lactantes y preescolares / Factors associated with iron deficiency anemia in infants and preschoolers

Introducción: La anemia se define como una afección en la cual el número de glóbulos rojos o la concentración de hemoglobina dentro de estos se encuentran por debajo del límite inferior, 11 gr/dl para menores entre 6 a 59 meses. La OMS calcula que a nivel mundial la anemia presenta una prevalencia del 42% en los niños menores de 5 años. Objetivos: Realizar una revisión panorámica de diversas publicaciones científicas acerca de los factores asociados a la anemia ferropénica en preescolares. Materiales y métodos: La revisión se realizó a través de la búsqueda electrónica de diversos artículos científicos relacionados con el tema. Se utilizó la pregunta PEO: ¿Cuáles son los factores asociados a anemia ferropénica en lactantes y preescolares? Se seleccionaron los artículos publicados desde el 2017 hasta el 2022. Resultados: De los 48 artículos encontrados en la revisión, 33 fueron descartados por no cumplir con nuestros criterios de selección, quedando 15 artículos para esta revisión. Basado en 12 artículos revisados, se halló que los factores que se asocian a anemia en menores de 5 años eran por problemas socioeconómicos, déficit de micronutrientes altos en hierro en dieta, madre con antecedente de anemia, la edad materna, falta de educación, entre otros. Conclusión: Los factores predisponentes para la presencia de anemia ferropénica en los menores de 5 años más importantes fueron los relacionados con la edad materna, el nivel socioeconómico y educativo de la madre que conllevan el déficit de hierro del menor.

Introduction: Anemia is defined as a condition in which the number of red blood cells or the hemoglobin concentration within red blood cells is below the lower limit, 11 g/dL for children aged 6-59 months. The WHO estimates that worldwide anemia has a prevalence of 42% in children under 5 years of age. Objectives: To perform an overview review of various scientific publications on the factors associated with iron deficiency anemia in preschoolers. Materials and methods: The review was carried out through an electronic search of various scientific articles related to the subject. The PEO question was used: What are the factors associated with iron deficiency anemia in infants and preschoolers? Articles published from 2017 to 2022 were selected. Results: Of the 48 articles found in the review, 33 were discarded for not meeting our selection criteria, leaving 15 articles for this review. Based on 12 articles reviewed, it was found that the factors associated with anemia in children under 5 years of age were socioeconomic problems, deficiency of micronutrients high in iron in the diet, mothers with a history of anemia, maternal age, lack of education, among others. Conclusion: The most important predisposing factors for the presence of iron deficiency anemia in children under 5 years of age were those related to maternal age, socioeconomic and educational level of the mother that lead to iron deficiency in the child.

Hepcidin and inflammation associated with iron deficiency in childhood obesity - A systematic review

Abstract Objectives: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Data source: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Summary of findings: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Conclusions: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.

Riesgos y beneficios de la profilaxis con sulfato ferroso en lactantes nacidos a término con niveles de hemoglobina y ferremia desconocidos / Risks and benefits of iron supplementation in full-term infants with unknown hemoglobin and ferritin levels

La seguridad y eficacia de los programas de suplementación con hierro a lactantes, está actualmente en discusión. El objetivo de esta revisión fue identificar estudios sobre riesgos y beneficios de la suplementación con hierro profiláctico en lactantes menores de un año, nacidos a término, con niveles de hemoglobina (Hb) y ferremia desconocidos. Se realizó una búsqueda en Pubmed y Cochrane, identificando 3 revisiones sistemáticas y metaanálisis. Estos estudios arrojaron resultados que indican mejoras en los niveles séricos de hierro y hemoglobina como resultado de la suplementación con hierro. Sin embargo, no se observó un beneficio significativo en el desarrollo cognitivo de los lactantes. Los efectos adversos más reportados son los gastrointestinales, efectos en el crecimiento (menor ganancia de talla y peso) y menor absorción de zinc. En resumen, la evidencia en cuanto a la profilaxis con hierro en lactantes es limitada, lo que nos lleva a recomendar un seguimiento cercano de los lactantes que reciben suplementos de hierro, con el objetivo de detectar posibles eventos adversos. Es fundamental evaluar cuidadosamente los riesgos y beneficios de esta intervención antes de su implementación (AU)

The safety and efficacy of iron supplementation programs for infants are currently under discussion. The objective of this review was to identify studies on the risks and benefits of prophylactic iron supplementation in infants under one year of age, born at term, with unknown hemoglobin (Hb) and serum iron levels. The search was conducted on Pubmed and Cochrane, identifying three systematic reviews and meta-analyses. The results indicate improvements in serum iron and hemoglobin levels as a result of iron supplementation. However, a significant benefit in infant cognitive development was not observed. The most reported adverse effects were gastrointestinal, effects on growth (reduced height and weight gain), and reduced zinc absorption. In summary, the evidence regarding iron prophylaxis in infants is limited, leading us to recommend close monitoring of infants receiving iron supplements to detect potential adverse events. It is crucial to carefully assess the risks and benefits of this intervention before implementation (AU)

Is Iron Overload Associated with Worse Outcomes in Patients with Chronic Liver Disease Undergoing Liver Transplantation?

ABSTRACT Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 person-months; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

The role of iron-uptake factor PiuB in pathogenicity of soybean pathogen Xanthomonas axonopodis pv. glycines / 生物工程学报

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe3+, Cu2+, Zn2+ and Mn2+ was significantly enhanced. Additionally, the H2O2 resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe3+ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe3+, and is necessary for Xag to be pathogenic in host soybean.

Quantitative evaluation of gender differences in supraclavicular fat related to fat metabolism with IDEAL-IQ in healthy young adults / 实用放射学杂志

Objective To evaluate the gender differences in fat water fraction(FWF)related to fat metabolism in supraclavicular region of neck with iterative decomposition of water and fat with echo asymmetry and least square estimation iron quantification(IDEAL-IQ)sequence quantitatively.Methods Twenty healthy female and twenty healthy male volunteers were selected for a MRI examination with IDEAL-IQ,then the FWF of R2*,brown adipose tissue(BAT)and white adipose tissue(WAT)were obtained by post-processing.The differences of FWF between the two groups were compared by Mann-Whitney U test.Results There was sig-nificant difference in the FWF of BAT and WAT between the two groups(P＜0.05).The FWF of BAT in the female was higher than that the male,and the FWF of WAT in the male was higher than that the female,there was no significant difference in the R2*between the two groups(P＞0.05).Conclusion IDEAL-IQ sequence can be used to evaluate the FWF in supraclavicular region of neck quantitatively,and classify BAT and WAT,then provide clinical according to the quantitative study of fat content.

Mechanism of iron death induced by high homocysteine via TRPC6/NF-κb in glomerular podiatocytes / 实用医学杂志

Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

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.

Function and advantages of magnetically responsive hydrogel in bone tissue engineering / 中国组织工程研究

BACKGROUND:Magnetically responsive hydrogels have great advantages in bone tissue engineering,which is more conducive to the minimally invasive and efficient promotion of osteogenesis. OBJECTIVE:To review the application advances of magnetically responsive hydrogels in bone tissue engineering. METHODS:PubMed,Web of Science,WanFang and CNKI databases were used to search relevant literature.The English search terms were"Magnetic Hydrogels,Magnetic Nanoparticles,Superparamagnetic Nanoparticles,Fe3O4,SPIONs,Magnetic Fields,Bone Regeneration,Bone Repair,Bone Tissue Engineering".The Chinese search terms were"Magnetic Hydrogel,Magnetic Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Magnetic Field,Iron Oxide Nanoparticles,Bone Regeneration,Bone Reconstruction,Bone Repair,Bone Tissue Engineering".After preliminary screening of all articles according to the inclusion and exclusion criteria,60 articles were finally retained for review. RESULTS AND CONCLUSION:(1)In recent years,due to the emergence of magnetic nanoparticles,more and more magnetic responsive scaffold materials have been developed.Among them,magnetic responsive hydrogels containing iron oxide nanoparticles and superparamagnetic iron oxide nanoparticles have outstanding mechanical properties and good biocompatibility.It can quickly respond to the external magnetic field and provide the magnetic-mechanical signals needed for seed cells to form bone.(2)Magnetic-responsive hydrogel can be used as a carrier to accurately regulate the release time of growth factors.(3)Under the three-dimensional microenvironment culture platform based on magnetically responsive hydrogel,the magnetic force at the interface between the magnetic response hydrogel and cells can activate cell surface sensitive receptors,enhance cell activity,and promote the integration of new bone and host bone.(4)The injectable magnetically responsive hydrogel can be used in the field of magnetic hyperthermia and biological imaging of bone tumors.(5)At present,magnetically responsive hydrogels are expected to mimic the anisotropic layered structure observed in natural bone tissue.However,most of the studies on magnetically responsive hydrogels focus on in vitro studies,and the mechanism of interaction between magnetically responsive hydrogels and the local microenvironment in vivo is still insufficient.(6)Therefore,based on the successful application of magnetic nanoparticles in magnetic resonance imaging,it is expected to optimize the properties of magnetic nanoparticles in the future to construct magnetic responsive hydrogels with suitable degradation properties,mechanical properties,and vascular functionalization,which can monitor changes in vivo in real time.

Research progress on iron metabolism in aging-related diseases / 中华老年医学杂志

With the acceleration of population aging in China, the issue of population aging is becoming increasingly severe.The investigation of the pathogenesis of aging-related diseases has become a focal point in the field of modern geriatrics.Iron is an essential trace element in the human body and plays a crucial role in maintaining normal physiological functions.Numerous studies have demonstrated the association between the disruption of iron metabolism and the occurrence and progression of various aging-related diseases.This review aims to briefly summarize the potential mechanisms of iron metabolism disorders in common aging-related diseases, and provide a theoretical basis for the diagnosis and treatment of such diseases.

Research status of ocular changes in beta-thalassemia major / 国际眼科杂志(Guoji Yanke Zazhi)

Beta-thalassemia major(β-TM)is an inherited disease caused by a defect in the synthesis of globin. The disease requires long-term blood transfusion and iron chelator treatment, which can cause various secondary changes in the body and eye tissues. Compared with normal peers, β-TM patients will show changes in the eye such as steeper corneal curvature, shallower anterior chamber, increased lens thickness, shorter axial length, and reduced tear secretion. At the same time, nutritional deficiencies and the use of iron chelator drugs will increase the risk of complicated cataract and retinal degeneration, thus affecting the quality of life of β-TM patients.This article combines relevant domestic and foreign literatures to explore and review the changes in the eye of β-TM patients, with a view to providing valuable insights for clinical practice.

Active Ingredients of Chinese Medicines Induce Ferroptosis in Tumor Cells： A Review / 中国实验方剂学杂志

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system Xc-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules / 中国药理学通报

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

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.

An insight into the mechanism of iron overload in knee osteoarthritis under the theory of blood stasis / 中国组织工程研究

BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.

Ferroptosis in bone diseases:therapeutic targets of osteoporosis / 中国组织工程研究

BACKGROUND:With the aging of the global population,the incidence rate of osteoporosis is also increasing.It is very important to further understand its pathogenesis and propose new therapeutic targets.Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases,such as inflammatory arthritis,osteoporosis and osteoarthritis. OBJECTIVE:To summarize the previous studies on the mechanism of ferroptosis in osteoporosis,so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS:The first author used the computer to search the documents published from 2000 to 2022 in CNKI,WanFang,VIP,PubMed and Web of Science with the key words of"ferroptosis,osteoporosis,osteoblasts,osteoclasts,iron chelators,reactive oxygen species,nuclear factor erythroid 2-related factor 2,heme oxygenase-1,glutathione peroxidase 4,review"in Chinese and English.A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:Ferroptosis is significantly different from necrosis,apoptosis and autophagy.In terms of cell morphology and function,it does not have the morphological characteristics of typical necrosis,nor does it have the characteristics of traditional apoptosis,such as cell contraction,chromatin condensation,the formation of apoptotic bodies and the disintegration of cytoskeleton.Contrary to autophagy,ferroptosis does not form a classical closed bilayer membrane structure(autophagic vacuole).Morphologically,ferroptosis is mainly manifested by obvious contraction of mitochondria,increased membrane density,and reduction or disappearance of mitochondrial cristae,which are different from other cell death modes.Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation,leading to osteoporosis.Iron overload interferes with the differentiation of stem cells to osteoblasts,leading to a weakened osteoblast function and further imbalance of bone metabolism in the body,which eventually leads to osteoporosis.Stimulated by iron overload,osteoclast bone resorption is enhanced and bone loss exceeds new bone formation.Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts.Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation.Antioxidants can prevent reactive oxygen species production and inhibit bone absorption,thus improving bone metabolism and effectively preventing osteoporosis.

Deferoxamine mesylate improves the repair of jaw bone defects in an ovariectomized rat model of osteoporosis / 中国组织工程研究

BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.