Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils.

AIMS: To evaluate the impact of galangin treatment on cerebral ischemia-reperfusion (I/R) injury in gerbils and to identify potential mechanisms of the protective effect of galangin on hippocampal neurons after I/R injury. PRINCIPAL METHODS: A cerebral ischemia model using bilateral common carotid artery ligation in gerbils was established. The Morris water maze (MWM) test was used to evaluate the learning and memory ability of gerbils. The cell viability was evaluated with an MTT assay. The levels of lipid peroxide biomarkers were measured to estimate the injury due to lipid peroxide. The morphology was detected by electron micrography, immunofluorescence and Nissl staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to measure the molecular characteristics. KEY FINDINGS: In the MWM, gerbils treated with galangin after I/R injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4). Furthermore, the expression of the marker of ferroptosis was decreased in galangin-treated gerbils, and the effect of galangin was weakened when SLC7A11 was knocked down. These results show that galangin can inhibit ferroptosis by enhancing the expressions of SLC7A11 and GPX4 as well as reduce neuronal cell death. SIGNIFICANCE: Galangin inhibits ferroptosis through activation of the SLC7A11/GPX4 axis and has a protective effect on hippocampal neurons in gerbils after I/R.

Transplantation of Stem Cells from Human Exfoliated Deciduous Teeth Decreases Cognitive Impairment from Chronic Cerebral Ischemia by Reducing Neuronal Apoptosis in Rats.

Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic.

Early changes in pulmonary function and intrarenal haemodynamics and the correlation between these sets of parameters in patients with T2DM.

PURPOSE: The main objectives of this study were to assess the early changes in pulmonary function and intrarenal haemodynamics and to determine the correlation between pulmonary function and intrarenal haemodynamics in patients with type 2 diabetes mellitus (T2DM). METHODS: 96 patients with T2DM (diabetes group) without diabetes kidney disease (DKD) and 33 healthy subjects (control group) were enrolled in studies intended to assess the early changes in pulmonary function and intrarenal haemodynamics associated with diabetes, as well as to determine the correlation between pulmonary function and intrarenal haemodynamics. RESULTS: Pulmonary functional parameters were negatively correlated with HbA1c levels and diabetes duration (P< 0.05). Moreover, renal functional parameters were positively correlated with HbA1c levels and diabetes duration (P<0.05). Additionally, pulmonary functional parameters were negatively correlated with renal functional parameters (P<0.05). Multiple linear regression analysis of the relationship between pulmonary functional parameters and the bilateral kidney arterial resistivity index (RI) showed that all the pulmonary functional parameters were significantly correlated with the arterial RI (P< 0.05). CONCLUSIONS: Patients displayed changes in pulmonary function and intrarenal haemodynamics during the preclinical stages of DKD. Regulating glycaemia may improve intrarenal haemodynamics in the bilateral interlobular renal arteries. Moreover, during the preclinical stages of DKD, the right kidney RI is a effective predictor of early changes in pulmonary function in adult T2DM patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02798198); registered 8 June 2016.