Perampanel attenuates oxidative stress and pyroptosis following subarachnoid hemorrhage via the SIRT3/FOXO3α pathway.

Subarachnoid hemorrhage (SAH) occurs most commonly after rupture of an aneurysm, resulting in high disability and mortality due to the absence of effective therapy. Its subsequent stage, early brain injury (EBI), promotes the sustainable development of injury in the brain and ultimately leads to poor prognosis. As a new antiepileptic drug, the effect of perampanel on EBI after SAH is unknown. Pyroptosis, a process of inflammatory programmed cell death, has been confirmed in most studies to play a substantial role in aggravating SAH-post EBI. Similarly, oxidative stress is closely involved in neuronal pyroptosis and the pathophysiological mechanism of SAH-post EBI, leading to a devastating outcome for SAH patients. Nonetheless, no studies have been conducted to determine whether perampanel reduces pyroptosis and oxidative stress in the context of SAH-induced EBI. Rat SAH model via endovascular perforation was constructed in this study, to assess the neuroprotective effect of perampanel on SAH-post EBI, and to clarify the possible molecular mechanism. By means of the neurological score, brain edema detection, FJB staining, immunofluorescence, WB, ELISA, and ROS assay, we found that perampanel can improve neuroscores and reduce brain edema and neuronal degeneration at 24 h after SAH; we also found that perampanel reduced oxidative stress, neuronal pyroptosis, and inhibition of the SIRT3-FOXO3α pathway at 24 h after SAH. When 3-TYP, an inhibitor of SIRT3, was administered, the effects of perampanel on the SIRT3-FOXO3a pathway, antioxidant stress, and neuronal pyroptosis were reversed. Taken together, our data indicate that perampanel attenuates oxidative stress and pyroptosis following subarachnoid hemorrhage via the SIRT3/FOXO3α pathway. This study highlights the application value of perampanel in subarachnoid hemorrhage and lays a foundation for clinical research and later transformation of perampanel in SAH.

A nomogram for predicting the risk of poor prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage following microsurgical clipping.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a common and potentially fatal cerebrovascular disease. Poor-grade aSAH (Hunt-Hess grades IV and V) accounts for 20-30% of patients with aSAH, with most patients having a poor prognosis. This study aimed to develop a stable nomogram model for predicting adverse outcomes at 6 months in patients with aSAH, and thus, aid in improving the prognosis. Method: The clinical data and imaging findings of 150 patients with poor-grade aSAH treated with microsurgical clipping of intracranial aneurysms on admission from December 2015 to October 2021 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO), logistic regression analyses, and a nomogram were used to develop the prognostic models. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow tests were used to assess discrimination and calibration. The bootstrap method (1,000 repetitions) was used for internal validation. Decision curve analysis (DCA) was performed to evaluate the clinical validity of the nomogram model. Result: LASSO regression analysis showed that age, Hunt-Hess grade, Glasgow Coma Scale (GCS), aneurysm size, and refractory hyperpyrexia were potential predictors for poor-grade aSAH. Logistic regression analyses revealed that age (OR: 1.107, 95% CI: 1.056-1.116, P < 0.001), Hunt-Hess grade (OR: 8.832, 95% CI: 2.312-33.736, P = 0.001), aneurysm size (OR: 6.871, 95% CI: 1.907-24.754, P = 0.003) and refractory fever (OR: 3.610, 95% CI: 1.301-10.018, P < 0.001) were independent predictors of poor outcome. The area under the ROC curve (AUC) was 0.909. The calibration curve and Hosmer-Lemeshow tests showed that the nomogram had good calibration ability. Furthermore, the DCA curve showed better clinical utilization of the nomogram. Conclusion: This study provides a reliable and valuable nomogram that can accurately predict the risk of poor prognosis in patients with poor-grade aSAH after microsurgical clipping. This tool is easy to use and can help physicians make appropriate clinical decisions to significantly improve patient prognosis.

Sirtuin-3: A potential target for treating several types of brain injury.

Sirtuin-3 (SIRT3) is responsible for maintaining mitochondrial homeostasis by deacetylating substrates in an NAD+-dependent manner. SIRT3, the primary deacetylase located in the mitochondria, controls cellular energy metabolism and the synthesis of essential biomolecules for cell survival. In recent years, increasing evidence has shown that SIRT3 is involved in several types of acute brain injury. In ischaemic stroke, subarachnoid haemorrhage, traumatic brain injury, and intracerebral haemorrhage, SIRT3 is closely related to mitochondrial homeostasis and with the mechanisms of pathophysiological processes such as neuroinflammation, oxidative stress, autophagy, and programmed cell death. As SIRT3 is the driver and regulator of a variety of pathophysiological processes, its molecular regulation is significant. In this paper, we review the role of SIRT3 in various types of brain injury and summarise SIRT3 molecular regulation. Numerous studies have demonstrated that SIRT3 plays a protective role in various types of brain injury. Here, we present the current research available on SIRT3 as a target for treating ischaemic stroke, subarachnoid haemorrhage, traumatic brain injury, thus highlighting the therapeutic potential of SIRT3 as a potent mediator of catastrophic brain injury. In addition, we have summarised the therapeutic drugs, compounds, natural extracts, peptides, physical stimuli, and other small molecules that may regulate SIRT3 to uncover additional brain-protective mechanisms of SIRT3, conduct further research, and provide more evidence for clinical transformation and drug development.

Electrochemical Behavior and Determination of Chlorogenic Acid Based on Multi-Walled Carbon Nanotubes Modified Screen-Printed Electrode.

In this paper, the multi-walled carbon nanotubes modified screen-printed electrode (MWCNTs/SPE) was prepared and the MWCNTs/SPE was employed for the electrochemical determination of the antioxidant substance chlorogenic acids (CGAs). A pair of well-defined redox peaks of CGA was observed at the MWCNTs/SPE in 0.10 mol/L acetic acid-sodium acetate buffer (pH 6.2) and the electrode process was adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods for the determination of CGA were proposed based on the MWCNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 0.17 to 15.8 µg/mL, and the linear regression equation was Ipa (µA) = 4.1993 C (×10-5 mol/L) + 1.1039 (r = 0.9976) and the detection limit for CGA could reach 0.12 µg/mL. The recovery of matrine was 94.74%-106.65% (RSD = 2.92%) in coffee beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

[Research on multi-agent based modeling and simulation of hospital system].

In this paper, the theory of complex adaptive system (CAS) and its modeling method are introduced. The complex characters of the hospital system is analyzed. The agile manufacturing and cell reconstruction technologies are used to reconstruct the hospital system. Then we set forth a research for simulation of hospital system based on the methodology of Multi-Agent technology and high level architecture (HLA). Finally, a simulation framework based on HLA for hospital system is presented.

[Application of the life sciences platform based on oracle to biomedical informations].

The life sciences platform based on Oracle database technology is introduced in this paper. By providing a powerful data access, integrating a variety of data types, and managing vast quantities of data, the software presents a flexible, safe and scalable management platform for biomedical data processing.