Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

Bone Microthrombus Promotes Bone Loss in Iron Accumulation Rats

In the present study,we investigated the changes of the coagulation state,bone microthrombus,microvascular bed and bone density levels in iron accumulation rats.Meanwhile,the effect of anticoagulation therapy on bone mineral density was further investigated.We established two groups:a control(Ctrl)group and an iron intervention(FAC)group.Changes in coagulation function,peripheral blood cell counts,bone microthrombus,bone vessels and bone mineral density were compared between the two groups.We designed the non-treatment group and treatment group to study the changes of bone mineral density by preventing microthrombus formation with the anticoagulant fondaparinux.We found that the fbrinogen and D-dimer contents were significantly higher,whereas the thrombin time(TT)and prothrombin time(PT)were significantly shorter in the FAC group.After ink staining,the microvascular bed in the FAC group was significantly reduced compared with that in the Ctrl group.HE and Martius Scarlet Blue(MSB)staining showed microthrombus in the bone marrow of the iron accumulation rats.Following anticoagulation therapy,the bone microcirculation vascular bed areas in the treatment group rats were significantly increased.Furthermore,the bone mineral density was increased in the treatment group compared with that in the non-treatment group.Through experiments,we found that the blood in iron accumulation rat was relatively hypercoagulable;moreover,there was microthrombus in the bone marrow,and the bone vascular bed was reduced.Additionally,anticoagulation was helpful for improving bone microcirculation,reducing microthrombus and decreasing bone loss.

Correction to“Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation”

We found a mistake in Figure 6. Panels A (Sham group) and F (DFX group) (180degrees rotated) is same images. We have replaced the incorrect images (Panels F)with the correct Figure. This error does not change the meaning of the picture orthe conclusion of the manuscript. We apologize for our unintentional mistakes,which caused great inconvenience.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women

Postmenopausal osteoporosis is a kind of degenerative disease,also described as“invisible killer.”Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives.Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000μg/L.It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause.In recent years,many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis,and a significant correlation has been found between iron accumulation and fragility fractures.In this review,we summarize and analyze the relevant literature including randomized controlled trials,systematic reviews,and meta-analyses between January 1996 and July 2022.We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation,osteoporosis,and postmenopausal fragility fractures,as well as the main clinical treatment strategies.We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation,in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Accumulation and elimination of iron oxide nanomaterials in zebrafish(Danio rerio) upon chronic aqueous exposure

A 52-day continuous semi-static waterborne exposure（test media renewed daily） regimen was employed to investigate the accumulation and elimination profiles of two iron oxide nanomaterials（nano-Fe2O3 and nano-Fe3O4） in zebrafish（Danio rerio）. Adult zebrafish were exposed to nanomaterial suspensions with initial concentrations of 4.0 and 10.0 mg/L for28 days and then were moved to clean water for 24 days to perform the elimination experiment. Fe content was measured in fish body and feces to provide data on accumulation and elimination of the two iron oxide nanomaterials in zebrafish. The experiment revealed that：（1） high accumulation of nano-Fe2O3 and nano-Fe3O4 were found in zebrafish, with maximum Fe contents, respectively, of 1.32 and 1.25 mg/g for 4.0 mg/L treatment groups and 1.15 and 0.90 mg/g for 10.0 mg/L treatment groups;（2） accumulated nanoparticles in zebrafish can be eliminated efficiently（the decrease of body burden of Fe conforms to a first-order decay equation） when fish were moved to nanoparticle-free water,and the elimination rates ranged from 86% to 100% by 24 days post-exposure; and（3）according to analysis of Fe content in fish excrement in the elimination phase, iron oxide nanomaterials may be adsorbed via the gastrointestinal tract, and stored for more than12 days.