The mechanism of hypoxia-inducible factor-1α enhancing the transcriptional activity of transferrin ferroportin 1 and regulating the Nrf2/HO-1 pathway in ferroptosis after cerebral ischemic injury.

Cerebral ischemic/reperfusion (I/R) injury has high disability and morbidity. Hypoxia-inducible factor-1α (HIF-1α) may enhance the transcriptional activity of transferrin ferroportin 1 (FPN1) in regulating ferroptosis after cerebral ischemia injury (CII). In this study, cerebral I/R injury rat models were established and treated with pcDNA3.1-HIF-1α, pcDNA3.1-NC lentiviral plasmid, or ML385 (a specific Nrf2 inhibitor). Additionally, oxygen-glucose deprivation/reoxygenation (OGD/R) exposed PC12 cells were used as an in vitro model of cerebral ischemia and treated with pcDNA3.1-HIF-1α, si-FPN1, or ML385. The results elicited that cerebral I/R injury rats exhibited increased Longa scores, TUNEL and NeuN co-positive cells, Fe2+ concentration, ROS and HIF-1α levels, and MDA content, while reduced cell density and number, GSH content, and GPX4 protein level. Morphologically abnormal and disordered hippocampal neurons were also observed in CII rats. HIF-1α inhibited brain neuron ferroptosis and ameliorated I/R injury. HIF-1α alleviated OGD-induced PC12 cell ferroptosis. OGD/R decreased FPN1 protein level in PC12 cells, and HIF-1α enhanced FPN1 transcriptional activity. FPN1 knockdown reversed HIF-1α-mediated alleviation of OGD/R-induced ferroptosis. HIF-1α activated the Nrf2/HO-1 pathway by enhancing FPN1 expression and alleviating OGD/R-induced ferroptosis. Conjointly, HIF-1α enhanced the transcriptional activity of FPN1, activated the Nrf2/HO-1 pathway, and inhibited ferroptosis of brain neurons, thereby improving I/R injury in CII rats.

Association of anion gap and albumin corrected anion gap with acute kidney injury in patients with acute ischemic stroke.

BACKGROUND: Acute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on clinical outcomes. Anion gap (AG)/albumin corrected anion gap (ACAG) are used to assess acid-base balance status and help identify the severity of metabolic acidosis. OBJECTIVES: To explore the association of AG and ACAG with the risk of AKI in AIS patients admitted to the intensive care unit (ICU). MATERIAL AND METHODS: Data of AIS patients in this retrospective cohort study were extracted from the electronic ICU (eICU) databases (2014-2015). The outcome was the occurrence of AKI after ICU admission. The covariates included demographic data, vital signs, comorbidities, laboratory parameters, and medication use. The association of AG and ACAG levels with AKI risk in AIS patients was evaluated using univariate and multivariate logistic regression models with odds ratios (ORs) and 95% confidence intervals (95% CIs). The predictive performance of AG and ACAG for the risk of AKI in AIS patients was assessed with the area under the curve (AUC). To further explore the association of AG and ACAG levels with AKI risk, subgroup analyses were performed according to comorbidities. RESULTS: Of the 1,260 AIS patients, 546 (43%) developed AKI. Elevated AG (OR = 1.73, 95% CI: 1.32-2.29) and ACAG (OR = 1.57, 95% CI: 1.21-2.04) were associated with the risk of AKI in AIS patients. The AUC of ACAG was superior to AG for predicting the risk of AKI (0.581 vs 0.558; p = 0.024). Elevated ACAG levels were associated with the risk of AKI in AIS patients without ischemic heart disease (OR = 1.60, 95% CI: 1.19-2.15), diabetes (OR = 1.58, 95% CI: 1.19-2.10) and hypertension (OR = 1.69, 95% CI: 1.24-2.30). CONCLUSIONS: Albumin corrected anion gap was a better predictor than AG for AKI risk in AIS patients, which may help clinicians identify high-risk patients for AKI.

Extracellular vesicles from bone marrow stromal cells reduce the impact of stroke on glial cell activation and blood brain-barrier permeability via a putative miR-124/PRX1 signalling pathway.

Ischaemic stroke (IS) is a cerebrovascular disease caused by cerebral infarction and cerebral artery occlusion. In this study, we proposed that EVs from bone marrow stromal cells (BMSCs) could reduce the impact of stroke by reducing the resultant glial cell activation and blood-brain barrier (BBB) leak. We furthermore investigated some of the signalling mechanisms. The transient middle cerebral artery occlusion (t-MCAO) mouse model was established. The behavioural deficits and neuronal damage were verified using Bederson's scale and the 28-point neurological score. The area of cerebral infarction was detected. The expressions of astrocytes/microglia markers and BBB permeability were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The internalization of EVs by astrocytes/microglia in the peripheral area was detected by fluorescence labelling. The expressions of astrocyte/microglia markers were measured by RT-qPCR. Levels of TNF-α and IL-1ß in microglia were detected by ELISA. BBB permeability was evaluated. The downstream target genes and pathway of miR-124 were analysed. Microglia/astrocytes were treated by oxygen-glucose deprivation reoxygenation (OGD/R). OGD/R microglia/astrocyte conditioned medium was used to culture bEnd.3 cells. The transendothelial electric resistance (TEER) of bEnd.3 cells was measured, and BBB permeability was characterized. Our results suggested that EVs from BMSCs can indeed reduce the extent of stroke-mediated damage and evidenced that these effects are mediated via expression of the non-coding RNA, miR-124 that may act via the peroxiredoxin 1 (PRX1). Our results provided further motivation to pursue the use of modified EVs as a treatment option for neurological diseases.

Amino-functionalized NH2-MIL-125(Ti)-decorated hierarchical flowerlike Znln2S4 for boosted visible-light photocatalytic degradation.

Developing novel heterojunction photocatalysts with visible-light response and remarkable photocatalytic activity have been verified to applying for the photodegradation of antibiotics in water environment. Herein, NH2-MIL-125(Ti) was integrated with flowerlike ZnIn2S4 to construct NH2-MIL-125(Ti)@ZnIn2S4 heterostructure using a one-pot solvothermal method. The photocatalytic performance was evaluated by the degradation of tetracycline (TC) under visible light illumination. The optimized NM(2%)@ZIS possesses a photodegradation rate (92.8%) and TOC removal efficiency (58.5%) superior to pristine components, which can be principally attributed to the positive cooperative effects of well-matched energy level positions, strong visible-light-harvesting capacity, and abundant coupling interfaces between the two. Moreover, the probable TC degradation mechanism was also clarified using the active species trapping experiments. This study inspires further design and construction of NH2-MIL-125(Ti) and ZnIn2S4 based photocatalysts for effective removal of antibiotics in water environment.

Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits.