Integrated Bioinformatic Analysis and Validation Identifies Immune Microenvironment-Related Potential Biomarkers in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, accompanied by cognitive and memory impairment, accounting for about 60% - 80% of dementia types. The pathogenesis of AD has not been clarified, and there is no effective therapy to prevent or treat AD. In this study, we aimed to identify the potential biomarkers involved in the brain immune microenvironment in AD. METHODS: AD datasets from GEO database were obtained to identify the differentially expressed disease-related genes (DEDRGs) in AD through weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional Enrichment analysis was performed to explore the potential biological function of DEDRGs. The hub DEDRGs were identified through the protein-protein interaction (PPI) network. Furthermore, the CIBERSORT algorithm was employed to bulk gene expression profiles of AD to depict the immune microenvironment characteristics in AD. Pearson's correlation analysis was utilized to depict the correlation between each of immune cells and hub DEDRGs. RESULTS: A total of 27 DEDRGs were identified through WGCNA and differential expression analysis. Functional enrichment analysis of 27 DEDRGs indicated that chemokine signaling pathway was the most significantly enriched KEGG pathway, response to biotic stimulus was the most significantly enriched GO term, and most of DEDRGs were enriched into urinary system cancer in DO analysis. 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were screened through PPI network and all of them were up-regulated in AD. Immune infiltration analysis revealed that there were higher infiltration levels of T cells CD4 memory activated, T cells gamma delta, NK cells resting and macrophages M0, and lower infiltration level of NK cell activated in AD, and macrophages M2 owned the highest positively association with VCAM1 and CXCR4, but VCAM1 was statistically and negatively correlated to T cells CD8. CONCLUSION: Our study identified 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were statistically associated with immune infiltrating cells, and were significantly related to the pathological development of AD, which may provide a theoretical basis for developing potential biomarkers and implementing effective therapies against AD.

Analysis of risk factors associated with outcomes in road traffic injury patients with acute lung injury.

Over 50% of road traffic injury (RTI) patients experience post-traumatic acute lung injury (ALI) and it is, therefore, extremely important to identify the risk factors related to the poor outcomes associated with ALI in RTI populations. This study evaluated 19 potential risk factors associated with the outcomes of ALI in 366 RTI patients. They were divided into two groups: a 'favourable outcomes group' and an 'unfavourable outcomes group'. The results indicated that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the presence of gastrointestinal haemorrhage may help predict the outcomes of ALI in the early post-trauma phase of treatment. The duration of trauma and sepsis were shown to impact strongly on both the short- and long-term outcomes of ALI. Age (> 65 years) and disseminated intravascular coagulation in the early RTI phase were also independent risk factors for a poorer short- and long-term outcome in ALI.

Impact of ketamine intervention for acute lung injury on RAGE and TLR9.

OBJECTIVE: The purpose of this study was to explore the benefits of ketamine intervention for acute lung injury (ALI) and its effects on the receptor for advanced glycation end-product (RAGE) and toll-like receptor 9 (TLR9). MATERIALS AND METHODS: Lipopolysaccharide (LPS, 3 mg/kg) was used to induce ALI rat model. Forty healthy Sprague-Dawley rats (6-8 weeks) were assigned into control, model, low ketamine (5 mg/kg), and high ketamine (50 mg/kg) groups. After 24 h, these rats were sacrificed and lungs were collected. RESULTS: The pathological score, lung W/D ratio, the percentage of leukocytes and epithelial in bronchoalveolar lavage fluids (BALF), the expression levels of RAGE, TLR9, and other inflammation markers in serum and lungs were significantly higher in the Model group, indicating a good ALI model. Ketamine intervention restored all these parameters, with more benefits in the High dose group. CONCLUSIONS: The high dose ketamine decreased the degree of ALI by inhibiting the expression of RAGE, TLR9, TNF-α, NF-κB, IL-6 and MPO in tissues.