Jiaxin Ren

Oxidative stress is a key cause of ischemic stroke and an initiator of neuronal dysfunction and death, mainly through the overproduction of peroxides and the depletion of antioxidants. Ferroptosis/oxytosis is a unique, oxidative stress-induced cell death pathway characterized by lipid peroxidation and glutathione depletion. Both oxidative stress and ferroptosis/oxytosis have common molecular pathways. This review summarizes the possible targets and the mechanisms underlying the crosstalk between oxidative stress and ferroptosis/oxytosis in ischemic stroke. This knowledge might help to further understand the pathophysiology of ischemic stroke and open new perspectives for the treatment of ischemic stroke.

Ferroptosis is mechanism for non-apoptotic, iron-dependent, oxidative cell death that is characterized by glutathione consumption and lipid peroxides accumulation. Ferroptosis is crucially involved in neurological diseases, including neurodegeneration, stroke and neurotrauma. This review provides detailed discussions of the ferroptosis mechanisms in these neurological diseases. Moreover, it summarizes recent drugs that target ferroptosis for neurological disease treatment. Furthermore, it compares the differences and relationships among the various cell death mechanisms involved in neurological diseases. Elucidating the ferroptosis role in the brain can improve the understanding of neurological disease mechanism and provide potential prevention and treatment interventions for acute and chronic neurological diseases.

BACKGROUNDS: The prevalence of diabetes has increased with the increase of obesity, and finding indicators to predict diabetes risk has become an urgent need. The purpose of this study is to compare the correlation between four anthropometric indices and the prevalence of diabetes. METHODS: A total of 4052 participants aged 40 years and above were selected in Dehui City, Jilin Province, using a multistage stratified whole group sampling method. Face-to-face interviews and physical examinations were conducted. Multivariate logistic analysis was used. The values of BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were divided into quartiles (Q1: <25%; Q2: ~25%; Q3: ~50%; and Q4: ~75%). The median of each quartile was used for a linear trend test. RESULTS: For all four body fat-measuring indices of body mass index (adjusted OR: 3.300, 95% CI: 2.370, 4.595), WC (adjusted OR: 5.131, 95% CI: 3.433, 7.669), WHR (adjusted OR: 3.327, 95% CI: 2.386, 4.638), and WHtR (adjusted OR: 5.959, 95% CI: 3.922, 9.054), patients in the highest quartile were more likely to have diabetes than those in the lowest quartile. The areas under the curve of WHtR, WC, WHR, and BMI for diabetes were 0.683, 0.669, 0.654, and 0.629, respectively. In female participants, the areas under the curve of the waist-height ratio and WC were 0.710 (95% CI: 0.679-0.741) and 0.701 (95% CI: 0.670-0.732), respectively. CONCLUSIONS: The WC and WHtR were more closely related to diabetes than BMI and WHR among study participants ≥ 40 years of age, especially in females.

Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed.

Autophagy is a conserved process to maintains homeostasis via the degradation of toxic cell contents, which can either promote cell survival or accelerate cellular demise. Ferroptosis is a recently discovered iron-dependent cell death pathway associated with the accumulation of lethal reactive lipid species. In the past few years, an increasing number of studies have suggested the crosstalk between autophagy and ferroptosis. Ischemic stroke is a complex brain disease regulated by several cell death pathways, including autophagy and ferroptosis. However, the potential links between autophagy and ferroptosis in ischemic stroke have not yet been explored. In this review, we briefly overview the mechanisms of ferroptosis and autophagy, as well as their possible connections in ischemic stroke. The elucidation of crosstalk between different cell death pathways may provide insight into new future ischemic stroke therapies.