Background: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil—an acetylcholinesterase (AChE) inhibitor—on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. Methods: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 μM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. Results: In vitro, donepezil was found to lead to increased cell viability and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1β), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. Conclusions: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy.

Macrophages become activated by a variety of stimuli such as lipopolysaccharide (LPS) and participate in the process of immune responses. Activated macrophages produce various inflammatory mediators. In the present study, we investigated the anti-inflammatory mechanism of a serotonin derivative, N-feruloylserotonin, isolated from safflower seeds in RAW 264.7 macrophages. N-Feruloylserotonin treatment significantly attenuated these effects on LPS-induced reactive oxygen species, nitric oxide, and prostaglandin E2 production in RAW 264.7 macrophages. Furthermore, N-feruloylserotonin significantly decreased the abnormal expression of mitogen-activated protein kinase, such as phosphor (p)-c-Jun N-terminal kinase and p-extracellular-signal regulated kinase activation. Further research revealed that N-feruloylserotonin could stimulate sirtuin1 (SIRT1), then promote the forkhead box protein O1 (FOXO1), and suppress nuclear factor-kappa B (NF-kB) signaling pathways. The present study suggests that N-feruloylserotonin may be a new anti-inflammatory component and a promising candidate for anti-inflammatory therapeutic agents through the regulation of SIRT1-stimulated FOXO1 and NF-kB signaling pathways.

This study develops a predictive model for video laryngoscopic views using advanced machine learning techniques, aiming to enhance airway management’s efficiency and safety. A total of 212 participants were involved, with 169 in the training set and 43 in the test set. We assessed outcomes using the percentage of glottic opening (POGO) score and considered factors like the modified Mallampati classification, thyromental height and distance, sternomental distance, mouth opening distance, and neck circumference. A range of machine learning algorithms was employed for data analysis, including Random Forest, Light Gradient Boosting Machine, K-Nearest Neighbors, Support Vector Regression, Ridge Regression, and Lasso Regression. The models’ performance was evaluated on the test set, with Root Mean Squared Error values ranging from 20.4 to 21.9. SHapley Additive exPlanations value analysis revealed that age is a consistent and significant predictor of POGO score across all models, highlighting its critical role in the predictive accuracy of these techniques.

Advanced glycation end-products (AGEs) and their receptor cause diabetic liver disease by increasing oxidative stress and inflammation. We investigate the potential therapeutic benefits of Cirsium japonicum (CJ) in preventing the progression of diabetes, focusing on complications for both liver and kidney health associated with AGEs. Streptozotocin (STZ, 30 mg/kg) was injected into SD rats and CJ (50, 100 mg/kg) was orally administered for 4 weeks. CJ treatment led to a marked reduction in key diabetic markers (glucose, reaction oxygen species, and lactate dehydrogenase), compared with the rats treated only with STZ. Moreover, the hepatic tissues of STZ-treated rats exhibited heightened biomarkers associated with AGE induction and formation, and these were notably attenuated in the CJ-treated rats. This effectively alleviated oxidative stress, inflammation, and AGE accumulation in the liver. Similarly, in the context of diabetic nephropathy, CJ treatment resulted in significant improvements in the rats with STZ-induced diabetes. Biomarkers associated with AGE induction and formation were significantly reduced in CJ-treated rats, demonstrating the ability of CJ to combat renal oxidative stress, inflammation, and AGE-related complications in diabetic nephropathy. CJ thus shows potential as a promising natural remedy that might mitigate the detrimental effects of diabetes on both the liver and kidneys through its anti-oxidation, anti-inflammation, and anti-AGE activities. These findings suggest that CJ is a beneficial agent for preventing and treating diabetic complications.

Post-craniotomy headache (PCH) is a common postoperative complication, and some of these patients progress to chronic PCH (CPCH). We aimed to identify clinical variables associated with PCH and its progression to CPCH, especially possible associations between age and sex differences. Therefore, we examined clinical information on PCH using the Clinical Data Warehouse over 10 years. Of the 1326 patients included, 927 patients (69.9%) experienced PCH. In multivariate analysis for PCH, age was inversely related to risk (p = 0.003), and being female showed a significant association with an increased risk of PCH (p = 0.002). There was also a significant inverse relationship between age and severity of the worst headache, with younger female patients reporting greater severity of the worst headache (p < 0.001). Of the 927 patients who experienced PCH, 319 (34.4%) progressed to CPCH. Sex was a significant factor, with females having a higher risk of developing CPCH compared to males (p < 0.001). In addition, the presence of preoperative headaches significantly increased the risk of CPCH (p = 0.001). The occurrence of PCH is associated with younger age and female sex. In particular, female sex and preoperative headaches increased the risk of developing CPCH. These clinical factors should be considered in patients undergoing neurosurgery.

One of the major obstacles to neural recovery following intracerebral hemorrhage (ICH) is the cavity-like lesion that occurs at the site of the hemorrhage, which impedes axonal regeneration. Here, we aim to address this challenge by investigating the migratory mechanisms of neural stem cells (NSCs) within the cavity in vitro using a hydrogel and endothelial cells. Mouse NSCs (mNSCs) isolated from the subventricular and subgranular zones using the 3D hydrogel culture were evaluated for their neurogenic, extracellular matrix (ECM), and adhesion-related mRNA expression compared to microglia (BV2) and secretory factors of human umbilical vein endothelial cells (HUVECs) in vitro and in vivo conditions. A hydrogel mesh combining mNSCs and HUVECs was developed for its therapeutic potential. mNSCs exhibit high stemness, neurogenesis, and ECM remodeling capabilities. mNSCs demonstrated close interaction with HUVECs and the surrounding vascular structures in in vitro and in vivo studies. Furthermore, mNSCs could degrade high concentrations of fibrin to facilitate migration and adhesion. mNSCs and HUVECs formed mesh networks through cell–cell contacts and maintained the structure through Matrigel support, potentially ensuring sufficient survival and regeneration capabilities. Our proposed hydrogel mesh platform with mNSCs and HUVECs demonstrated successful maintenance of cell survival and provision of structural support for the delivered cells by promoting ECM remodeling and neurogenesis, which may aid in axonal regeneration in the cavity lesions following ICH.