Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Small-Molecule Fluorophores for Near-Infrared IIb Imaging and ImageGuided Therapy of Vascular Diseases

Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged.Here,we report novel benzobis(1,2,5-thiadiazole)-based second near-infrared region(NIR-II)fluorophores HY1-HY4 with highly twisted structures(55°at the S_(0) state),extremely strong aggregation-induced emission(AIE)characteristics(I/I_(0)>13),and remarkably high fluorescence quantum yields(QYs)(up to 14.45%)in the NIR-II region(>1000 nm)and∼0.27%in the nearinfrared IIb window(NIR-IIb,>1500 nm)in aqueous solution.Using NIR-IIb AIE HY4 dots,high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis,and real-time feedback of the therapeutic efficacy of Chinese medicine Dengzhan Xixin injection(DXI)on ischemic stroke,were achieved for the first time.In addition,results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway.These attractive results provide a new perspective for designing ultrabright NIR-IIb probes for vascular-related phenomena,disease assessment,and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.

CD4 T cell deficiency attenuates ischemic stroke, inhibits oxidative stress, and enhances Akt/mTOR survival signaling pathways in mice

Background: Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal survival signaling pathways. In this study, we investigated the effects of CD4 T cell deficits on oxidative stress and on the Akt/mTOR cell signaling pathways after ischemic stroke in mice. Methods: MHC II gene knockout C57/BL6 mice, with significantly decreased CD4 T cells, were used. Stroke was induced by 60-min middle cerebral artery (MCA) occlusion. Ischemic brain tissues were harvested for Western blotting. Results: The impairment of CD4 T cell production resulted in smaller infarction. The Western blot results showed that iNOS protein levels robustly increased at 5 h and 24 h and then returned toward baseline at 48 h in wild-type mice after stroke, and gene KO inhibited iNOS at 5 h and 24 h. In contrast, the anti-inflammatory marker, arginase I, was found increased after stroke in WT mice, which was further enhanced in the KO mice. In addition, stroke resulted in increased phosphorylated PTEN, Akt, PRAS40, P70S6, and S6 protein levels in WT mice, which were further enhanced in the animals whose CD4 T cells were impaired. Conclusion: The impairment of CD4 T cell products prevents ischemic brain injury, inhibits inflammatory signals, and enhances the Akt/mTOR cell survival signaling pathways.

Semi-clathrate hydrate based carbon dioxide capture and separation techniques

CO_(2)is considered as the main contributor to global warming,and hydrate enclathration is an efficient way for carbon capture and separation(CCS).Semi-clathrate hydrate(SCH)is a type of clathrate hydrate capable of encaging CO_(2)molecules under mild temperature and pressure conditions.SCH has numerous unique advantages,including high thermal stability,selective absorption of gas molecules with proper size and recyclable,making it a promising candidate for CCS.While SCH based CCS technology is in the developing stage and great efforts have to be conducted to improve the performance that is determined by their thermodynamical and structural properties.This review summarizes and compares the thermodynamic and structural properties of SCH and quaternary salt hydrates with gas mixtures to be captured and separated.Based on the description of the physical properties of SCH and hydrate of quaternary salts with gas mixture,the CO_(2)capture and separation from fuel gas,flue gas and biogas with SCH are reviewed.The review focuses on the use of tetra-nbutyl ammonium halide and tetra-n-butyl phosphonium halide,which are the current application hotspots.This review aims to provide guidance for the future applications of SCH.