Effect of esketamine pretreatment on acute sepsis-associated encephalopathy.

PURPOSE: Esketamine, the S(+) enantiomer of ketamine, exhibits good anesthetic efficacy and controllability; however, its potential clinical applications, particularly in sepsis-associated encephalopathy (SAE), remain underexplored. SAE involves the development of diffuse brain dysfunction after sepsis, leading to markedly increased sepsis-related disability and mortality. In this study, we investigated the effects of esketamine pretreatment on acute SAE. METHODS: Mice were randomly divided into four groups: control (C, n = 22), acute SAE (L, n = 22), esketamine pretreatment + acute SAE (EL, n = 22), and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) + esketamine pretreatment + acute SAE (N + EL, n = 22). Acute SAE was established using intraperitoneal (i.p.) injection of lipopolysaccharide (LPS; 10 mg/kg), while controls received equal amounts of saline. The EL group received daily i.p. injections of esketamine (10 mg/kg) for 5 consecutive days, followed by LPS on day 6. The N + EL group received i.p. injections of ML385 (30 mg/kg) 1 h before esketamine pretreatment. The remainder of treatment followed the same protocol as the EL group. Behavioral tests were performed 24 h post-LPS injection, and whole blood and brain tissues were collected for further analysis. RESULTS: Esketamine improved sepsis symptoms, 7-day survival, and spatial cognitive impairment, without altering locomotor activity. Moreover, esketamine reversed the LPS-induced increase in serum S100 calcium-binding protein ß and neuron-specific enolase levels and reduced hippocampal neuroinflammation, oxidative stress, and neuronal apoptosis in the EL group. However, these neuroprotective effects of esketamine were reversed by ML385. CONCLUSION: The results of our study suggest that esketamine pretreatment mitigates acute SAE, highlighting the involvement of the Nrf2/heme oxygenase-1 pathway in mediating its neuroprotective effects.

Copper metabolism-related Genes in entorhinal cortex for Alzheimer's disease.

The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the formation of amyloid plaques. However, their role has been controversial. The aim of this study was to explore the role of Cu in AD. We applied the "R" software for our differential analysis. Differentially expressed genes were screened using the limma package. Copper metabolism-related genes and the intersection set of differential genes with GSE5281 were searched; functional annotation was performed. The protein-protein interaction network was constructed using several modules to analyse the most significant hub genes. The hub genes were then qualified, and a database was used to screen for small-molecule AD drugs. We identified 87 DEGs. gene ontology analysis focused on homeostatic processes, response to toxic substances, positive regulation of transport, and secretion. The enriched molecular functions are mainly related to copper ion binding, molecular function regulators, protein-containing complex binding, identical protein binding and signalling receptor binding. The KEGG database is mainly involved in central carbon metabolism in various cancers, Parkinson's disease and melanoma. We identified five hub genes, FGF2, B2M, PTPRC, CD44 and SPP1, and identified the corresponding small molecule drugs. Our study identified key genes possibly related to energy metabolism in the pathological mechanism of AD and explored potential targets for AD treatment by establishing interaction networks.

Constructing and Validating a Network of Potential Olfactory Sheathing Cell Transplants Regulating Spinal Cord Injury Progression.

The pathology of spinal cord injury (SCI), including primary and secondary injuries, primarily involves hemorrhage, ischemia, edema, and inflammatory responses. Cell transplantation has been the most promising treatment for SCI in recent years; however, its specific molecular mechanism remains unclear. In this study, bioinformatics analysis verified by experiment was used to elucidate the hub genes associated with SCI and to discover the underlying molecular mechanisms of cell intervention. GSE46988 data were downloaded from the Gene Expression Omnibus dataset. In our study, differentially expressed genes (DEGs) were reanalyzed using the "R" software (R v4.2.1). Functional enrichment and protein-protein interaction network analyses were performed, and key modules and hub genes were identified. Network construction was performed for the hub genes and their associated miRNAs. Finally, a semi-quantitative analysis of hub genes and pathways was performed using quantitative real-time polymerase chain reaction. In total, 718 DEGs were identified, mainly enriched in immune and inflammation-related functions. We found that Cd4, Tp53, Rac2, and Akt3 differed between vehicle and transplanted groups, suggesting that these genes may play an essential role in the transplantation of olfactory ensheathing cells, while a toll-like receptor signaling pathway was significantly enriched in Gene set enrichment analysis, and then, the differences were statistically significant by experimentally verifying the expression of their associated molecules (Tlr4, Nf-κb, Ikkß, Cxcl2, and Tnf-α). In addition, we searched for upstream regulatory molecules of these four central genes and constructed a regulatory network. This study is the first to construct a regulatory network for olfactory ensheathing cell transplantation in treating SCI, providing a new idea for SCI cell therapy.

Effects of Pharmacological Intervention on Recovery After Sevoflurane Anesthesia in Children: a Network Meta-analysis of Randomized Controlled Trials.

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD), especially in elderly patients, is a serious complication characterized by impairment of cognitive and sensory modalities after surgery. The pathogenesis of POCD mainly includes neuroinflammation, neuronal apoptosis, oxidative stress, accumulation of Aß, and tau hyperphosphorylation; however, the exact mechanism remains unclear. Non-coding RNA (ncRNA) may play an important role in POCD. Some evidence suggests that microRNA, long ncRNA, and circular RNA can regulate POCD-related processes, making them promising biomarkers in POCD diagnosis, treatment, and prognosis. This article reviews the crosstalk between ncRNAs and POCD, and systematically discusses the role of ncRNAs in the pathogenesis and diagnosis of POCD. Additionally, we explored the possible mechanisms of ncRNA-associated POCD, providing new knowledge for developing ncRNA-based treatments for POCD.

Regulation of neuropeptide Y in body microenvironments and its potential application in therapies: a review.

Neuropeptide Y (NPY), one of the most abundant neuropeptides in the body, is widely expressed in the central and peripheral nervous systems and acts on the cardiovascular, digestive, endocrine, and nervous systems. NPY affects the nutritional and inflammatory microenvironments through its interaction with immune cells, brain-derived trophic factor (BDNF), and angiogenesis promotion to maintain body homeostasis. Additionally, NPY has great potential for therapeutic applications against various diseases, especially as an adjuvant therapy for stem cells. In this review, we discuss the research progress regarding NPY, as well as the current evidence for the regulation of NPY in each microenvironment, and provide prospects for further research on related diseases.

Update on the Mechanism and Treatment of Sevoflurane-Induced Postoperative Cognitive Dysfunction.

Sevoflurane is one of the most widely used anesthetics for the induction and maintenance of general anesthesia in surgical patients. Sevoflurane treatment may increase the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD exhibit lower cognitive abilities than before the operation. POCD affects the lives of patients and places an additional burden on patients and their families. Understanding the mechanism of sevoflurane-induced POCD may improve prevention and treatment of POCD. In this paper, we review the diagnosis of POCD, introduce animal models of POCD in clinical research, analyze the possible mechanisms of sevoflurane-induced POCD, and summarize advances in treatment for this condition.

Transplantation of mesenchymal stem cells for spinal cord injury: a systematic review and network meta-analysis.

Spinal cord injury (SCI) is a severe traumatic disease of the central nervous system, with a global prevalence of 236-4187 per million people. This meta-analysis aimed to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) in treating patients with SCI as well as the optimal source and transplantation method of MSCs. PubMed, OVID, Cochrane, Web of Science, and China Biomedical Database were searched up until April 01, 2021. The study was conducted for five endpoints: American Spinal Injury Association (ASIA) motor and sensory score, ASIA grade improvement, Barthel Index (BI), and adverse reactions. Standard meta-analysis and network meta-analysis were performed using Stata 14.0. Eighteen studies with a total of 949 patients, were included in the meta-analysis. Standard meta-analysis showed that MSCs significantly improved ASIA motor score (P < 0.001), sensory score (P < 0.001), ASIA grade (P < 0.001), and BI (P < 0.001) compared to rehabilitation. In addition, in the network meta-analysis, autologous MSCs significantly improved the ASIA motor [MD = 8.01, 95% CI (4.27, 11.76)], sensory score [MD = 17.98, 95% CI (10.04, 25.91)], and BI [MD = 7.69, 95% CI (2.10, 13.29)] compared to rehabilitation. Similarly, compared to rehabilitation, intrathecal injection (IT) of MSCs significantly improved the ASIA motor [MD = 7.97, 95% CI (4.40, 11.53)] and sensory score [MD = 19.60, 95% CI (9.74, 29.46)]. Compared to rehabilitation, however, only the IL of MSCs was associated with more adverse reactions [OR = 17.82, 95% CI (2.48, 128.22)]. According to the results of SUCRA, both autologous MSCs and IT transplantation approaches most improved the neurological function in SCI patients. Cell transplantation using MSCs is effective in patients with SCI and IT of autologous MSCs may be more beneficial.

High bone turnover of type I collagen depends on fetal growth.

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E2 and CT both showed a significant positive correlation with Ca (P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.