Esketamine ameliorates post-stroke anxiety by modulating microglial HDAC3/NF-κB/COX1 inflammatory signaling in ischemic cortex.

Post-stroke anxiety (PSA) is a kind of affective disorder occurring after a stroke, with anxiety as the primary clinical manifestation. PSA's mechanism is unclear, and there are few prevention and treatment measures. Our previous study found that HDAC3 could activate NF-κB signaling through mediated p65 deacetylation, which further influenced microglia activation. That implies HDAC3 may be the key mediator in ischemic stroke mice and modulates anxiety susceptibility to stress. This study established a PSA model in male C57BL/6 mice through photothrombotic stroke combined with chronic restrain stress. We focused on exploring whether esketamine administration can alleviate anxiety-like behavior and neuroinflammation, which may be associated with inhibiting HDAC3 expression and NF-κB pathway activation. The results showed that esketamine administration alleviated anxiety-like behavior in PSA mice. And the results showed that esketamine alleviated cortical microglial activation, altered microglial number, and kept morphology features. Furthermore, the results showed that the expression of HDAC3, phosphor-p65/p65, and COX1 significantly decreased in esketamine-treated PSA mice. Besides, we also found that esketamine reduced PGE2 expression, one of the primary regulators of negative emotions. Interestingly, our results indicate that esketamine reduced the perineuronal net (PNN) number in the pathological process of PSA. In conclusion, this study suggests esketamine could alleviate microglial activation, reduces inflammatory cytokine, and inhibits the expression of HDAC3 and NF-κB in the cortex of PSA mice to attenuate anxiety-like behavior. Our results provided a new potential therapeutic target for applying esketamine to PSA.

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment.

Gamma oscillation is the synchronization with a frequency of 30-90 Hz of neural oscillations, which are rhythmic electric processes of neuron groups in the brain. The inhibitory interneuron network is necessary for the production of gamma oscillations, but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this network to malfunction. Gamma oscillations specifically control the connectivity between different brain regions, which is crucial for perception, movement, memory, and emotion. Studies have linked abnormal gamma oscillations to conditions of the central nervous system, including Alzheimer's disease, Parkinson's disease, and schizophrenia. Evidence suggests that gamma entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses the function of gamma oscillations in advanced brain activities from both a physiological and pathological standpoint, and it emphasizes gamma entrainment as a potential therapeutic approach for a range of neuropsychiatric diseases.

Effect of erythromycin on the ultrastructure of human macrophages exposed to cigarette smoke extract in vitro.

Macrophages serve an active role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been verified as an effective treatment for COPD. However, there are few studies on the effect of EM on the ultrastructure of macrophages exposed to cigarette smoke extract (CSE). In the present study, human macrophages were randomly divided into three groups: The control, CSE and the CSE+EM group, using electron microscopy, the effect of EM was evaluated by comparing the ultrastructural changes between these groups. The macrophages were additionally divided into a further four groups: The control, CSE, CSE+EM 24 h and CSE+EM 48 h groups. The generation of reactive oxygen species (ROS) in each group was evaluated by detecting fluorescence intensity. It was observed that the cellular ultrastructure of the CSE group exhibited abnormal changes, though this effect was reversed back to the level of the control in the CSE+EM group. Compared with the control group, the ROS expression level was significantly increased in the CSE group (P < .05); however, compared with the CSE group, the ROS concentration was decreased in the CSE+EM 24 h (P < .05) and CSE+EM 48 h groups (P < .05), though this was more apparent in the EM 48 h group. It was concluded that EM protects human macrophages against CSE. Moreover, it was hypothesized that EM may reduce the symptoms of patients with COPD by protecting the macrophage ultrastructure from the effects of CSE, resulting in the decreased generation of ROS, inhibiting autophagy and reducing endoplasmic reticulum stress.

Omarigliptin Mitigates Lipopolysaccharide-Induced Neuroinflammation and Dysfunction of the Integrity of the Blood-Brain Barrier.

The blood-brain barrier (BBB) is an important barrier that separates brain tissue from peripheral blood. The permeability of the BBB can be destroyed by external harmful factors, such as lipopolysaccharide (LPS), which contributes to neuroinflammation and central nervous system diseases. The present study aims to investigate the protective effects of Omarigliptin against LPS-induced neuroinflammation and the underlying mechanism using a series of both in vivo and in vitro experiments. A neuroinflammation model was established by intraperitoneal injection of LPS into mice. We found that administration of Omarigliptin reduced LPS-induced inflammatory responses by inhibiting the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Importantly, we found that Omarigliptin protected the integrity of the BBB against LPS by increasing the expression of the tight junction proteins claudin-1 and claudin-5. Our results also demonstrate that Omarigliptin reduced LPS-induced increase in expressions of matrix matalloproteinases-2 (MMP-2) and matrix matalloproteinases-9 (MMP-9) at both the mRNA and protein levels. Notably, Omarigliptin showed a powerful beneficial effect against LPS-induced cell damage in bEnd.3 brain endothelial cells by reducing the release of high mobility group box chromosomal protein 1 (HMGB-1). Consistently, Omarigliptin ameliorated LPS-induced exacerbation of endothelial permeability by increasing the expressions of claudin-1 and claudin-5 and reducing the expression of MMP-2 and MMP-9. Mechanistically, Omarigliptin inhibited the activation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor κB (TLR4/Myd88/NF-κB) signaling pathway. On the basis of these findings, we concluded that Omarigliptin might mitigate LPS-induced neuroinflammation and dysfunction of the integrity of the blood-brain barrier.

From Patient-Controlled Analgesia to Artificial Intelligence-Assisted Patient-Controlled Analgesia: Practices and Perspectives.

Pain relief is a major concern for patients who have undergone surgery, and it is an eternal pursuit for anesthesiologists. However, postoperative pain management is far from satisfactory, though the past decades have witnessed great progress in the development of novel analgesics and analgesic techniques. A Cochrane systematic review showed that patient-controlled analgesia (PCA) achieved better pain relief and greater patient satisfaction than traditional "on-demand" parenteral analgesia, suggesting that it might be the manner of analgesia implementation that matters for effective postoperative pain management. A wireless intelligent PCA (Wi-PCA) system that incorporated remote monitoring, an intelligent alarm, intelligent analysis and assessment of the PCA equipment, as well as automatically recording and reserving key information functions under a wireless environment was introduced in our department in 2018. The practice showed that the Wi-PCA system significantly reduced the incidence of moderate to severe postoperative pain and relevant adverse effects, shortened hospital stays, and improved patient satisfaction with postoperative pain relief. Nevertheless, for both traditional and Wi-PCA, analgesics are only administered when pain occurs, leaving behind a realm of possibilities for better postoperative pain management. With the rapid development of machinery and deep learning algorithms, artificial intelligence (AI) is changing the mode of clinical decision making. Integrating the big data collected by state-of-the-art monitoring sensors, the Internet of Things and AI algorithms, an AI-assisted PCA (Ai-PCA) may be a promising future direction for postoperative pain management.