Down-regulation of Stargazin Inhibits the Enhanced Surface Delivery of α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor GluR1 Subunit in Rat Dorsal Horn and Ameliorates Postoperative Pain

Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Yet, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development

The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease.</jats:p

Understanding the heterogeneity in liver hepatocellular carcinoma with a special focus on malignant cell through single-cell analysis

Abstract Introduction Hepatocellular carcinoma (HCC) is the most common form of liver cancer globally and remains a major cause of cancer-related deaths. HCC exhibits significant intra-tumoral and interpatient heterogeneity, impacting treatment efficacy and patient prognosis. Methods We acquired transcriptome data from the TCGA and ICGC databases, as well as liver cancer chip data from the GEO database, and processed the data for subsequent analysis. We also obtained single cell data from the GEO database and performed data analysis using the Seurat package. To further investigate epithelial cell subgroups and their copy number variations, we used the Seurat workflow for subgroup classification and the InferCNV software for CNV analysis, utilizing endothelial cells as a reference. Pseudo-time analysis and transcription factor analysis of epithelial cells were performed using the monocle2 and SCENIC software, respectively. To assess intercellular communication, we employed the CellChat package to identify potential ligand-receptor interactions. We also analyzed gene expression differences and conducted enrichment analysis using the limma and clusterProfiler packages. Additionally, we established tumor-related risk characteristics using Cox analysis and Lasso regression, and predicted immunotherapy response using various datasets. Results The samples were classified into 23 clusters, with malignant epithelial cells being the majority. Trajectory analysis revealed the differentiation states of the malignant epithelial cells, with cluster 1 being in the terminal state. Functional analysis revealed higher aggressiveness and epithelial-mesenchymal transition (EMT) scores in cluster 1, indicating a higher propensity for metastasis. RBP4+ tumor cells were highly enriched with hypoxia process and intensive cell-to-cell communication. A prognostic model was established, and immune infiltration analysis showed increased infiltration in the high-risk group. TP53 demonstrated significant differences in mutation rate between the two risk groups. Validation analysis confirmed the up-regulation of model genes, including AKR1B10, ARL6IP4, ATP6V0B, and BSG in tumor tissues. Conclusion A prognostic model was established based on HCC malignant cell associated gene signature, displaying decent prognosis guiding effectiveness in the multiple cohorts. The study provided comprehensive insights into the heterogeneity and potential therapeutic targets of LIHC

Endothelial Glycocalyx Layer: A Possible Therapeutic Target for Acute Lung Injury during Lung Resection

Background. Shedding of the endothelial glycocalyx layer (EGL) is known to occur during major surgery, but its degradation associated with minimally invasive video-assisted thoracoscopy (VATS) remains unclear. We investigated if serum biomarkers of EGL disruption were elevated during VATS lobectomy, and whether the urinary trypsin inhibitor (UTI) ulinastatin exerted a protective effect during this procedure. Materials and Methods. Sixty ASA II-III lung cancer patients undergoing elective VATS lobectomy were divided equally into UTI and control groups. UTI group patients received intravenous UTI during surgery. Serum levels of syndecan-1 and heparan sulfate were examined before (T0) and at the end of surgery (T1). Serum albumin and hemoglobin were measured before surgery (BOD) and on the first postoperative day (POD1). Results. In control group, syndecan-1 levels were significantly elevated at T1 compared with T0 (3.77±3.15 versus 4.28±3.30, P=0.022⁎) and increased even more significantly in patients whose surgery lasted >3 h (3.28±2.84 versus 4.31±3.39, P=0.003⁎⁎). Serum albumin levels on POD1 were significantly lower in control group compared with UTI group (32.63±4.57 versus 35.76±2.99, P=0.031⁎). Conclusion. EGL degradation occurs following VATS lobectomy. UTI can alleviate this shedding, thus helping preserve normal vascular permeability. Trail Registration. This trial is registered with ChiCTR-IOC-17010416 (January 13, 2017)

Actin Reorganization in Hippocampal Neurons May Play Roles in Early Impairment of Learning and Memory in Rats After Propofol Anesthesia

Abstract Background Perioperative neurocognitive disorder (PND) is a kind of neuronal complication especially observed in elderly patients. The present study was conducted to observe the changes of actin in hippocampus after propofol anesthesia, and to evaluate their roles in consequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats.Methods Double-shuttle box was used to learning evaluation since1, 3, 7 or 14d after anesthesia. Hippocampi were removed after evaluations. F-actin content and the spines were observed through immunofluorescence and laser scanning confocal microscope (LSCM).Results In young rats, latency of escape response (LER) was prolonged within 3 days after anesthesia. However, LER was significantly prolonged until 7days after anesthesia in elderly rats. Moreover, the learning curves were also shift in old rats. Dendritic spines became smaller in anesthesia groups of aged rats within 3 days, where the F-actin contents were significantly increased until 14d post anesthesia.Conclusion Our results indicate that learning ability could be inhibited until after propofol anesthesia especially in old rats. The over-polymerization of actin and the consequent reorganization of dendrite spines in hippocampus may be responsible, which provides fresh evidence in aspect of synaptic plasticity for PND mechanism.</jats:p

Dexmedetomidine as a neuraxial adjuvant for prevention of perioperative shivering: Meta-analysis of randomized controlled trials.

Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has been investigated for anti-shivering effects in some trials. This current meta-analysis was conducted to evaluate the effectiveness of dexmedetomidine as a neuraxial adjuvant in preventing perioperative shivering.This systematic review and meta-analysis was registered in PROSPERO [www.crd.york.ac.uk/PROSPERO] with the unique identification number CRD42017055991. The electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) were searched to select high-quality randomized controlled trials (RCTs) that evaluated the anti-shivering efficacy for neuraxial application dexmedetomidine as local anesthetic adjuvant. Effects were summarized using pooled risk ratios (RRs), weighed mean differences (MDs), or standardized mean differences (SMDs) and corresponding 95% confidence intervals (Cls) with random effect model. Heterogeneity assessment, sensitivity analysis, and publication bias were performed. The primary outcome was perioperative shivering.A total of 1760 patients from 24 studies were included in this meta-analysis. Compared with the placebo, dexmedetomidine reduced the incidence of perioperative shivering (RR: 0.34; 95% Cl: 0.21 to 0.55; P < 0.00001), with a maximum effective dose of 5μg via subarachnoid space injection (RR: 0.55; 95% CI: 0.32 to 0.92; P = 0.02), especially in cesarean section (RR: 0.20; 95% CI: 0.09 to 0.45; P = 0.0001). Dexmedetomidine also could improve the characteristics of the block, with an increase only in the incidence of bradycardia (RR: 2.11; 95% CI: 1.23 to 3.60; P = 0.006). No significant difference could be found compared dexmedetomidine with other adjuvants, except morphine.This meta-analysis shows that dexmedetomidine as a neuraxial adjuvant had statistically significant efficacy on prevention of perioperative shivering. Moreover, dexmedetomidine could improve the characteristics of the block. However, the potential induction of bradycardia should be taken seriously