Activation of TLR4-Mediated NFκB Signaling in Hemorrhagic Brain in Rats

Inflammation and immunity play a crucial role in the pathogenesis of Intracerebral hemorrhage (ICH). Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa-B (NFκB) signaling plays critical roles in the activation and regulation of inflammatory responses in injured brain. However, the involvement of TLR4-mediated NFκB signaling in the pathogenesis of ICH remains unknown. The present study was to evaluate the temporal profile of the expression of TLR4 and the activation of TLR4-mediated NFκB signaling in brain tissues of Wistar rats after ICH. TLR4 mRNA and protein, the phosphorylation of inhibitors of kappa B (p-IκBα), and the activity of NFκB were examined in hemorrhagic cerebral tissue by Rt-PCR, Western blots, immunohistochemistry staining, and EMSA. Compared with saline control, the TLR4 mRNA and protein significantly increased starting at 6 hours after ICH, peaked on the 3rd day after ICH, and then decreased but still maintained at a higher level on the 7th day after ICH (P < .05). The level of p-IκBα and the activity of NFκB also increased in the brain after ICH compared with saline control. The present study firstly suggests that TLR4-mediated NFκB signaling participates in the pathogenesis of ICH, which may become a therapeutic target for ICH-induced brain damage

25-Hydroxyvitamin D Levels and the Risk of Dementia and Alzheimer's Disease: A Dose–Response Meta-Analysis

Background and Purpose: Conclusions of previous cohort studies on the relationship between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease were not consistent. Thus, we performed a dose–response meta-analysis to evaluate this relationship by summarizing cohort studies.Methods: Pubmed, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Cohort studies concerning the association between 25-hydroxyvitamin D level and dementia or Alzheimer's disease were included. Results of studies were pooled and the dose–response relationship was determined using a random-effect model.Results: Ten cohort studies, with 28,640 participants were included. A significant inverse relationship was found between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease. In addition, we found a linear dose–response relationship in that a 10 nmol/L increase in 25-hydroxyvitamin D level may lead to a 5% decrease in the risk of dementia (relative risk, 0.95; 95% confidence interval, 0.93–0.98) and 7% in the risk of Alzheimer's disease (relative risk, 0.93; 95% confidence interval, 0.89–0.97).Conclusion: Plasma or serum 25-hydroxyvitamin D concentration was inversely related to the risk of dementia and Alzheimer's disease, consistent with a linear dose–response relationship

Overexpression of TRIM24 Stimulates Proliferation and Glucose Metabolism of Head and Neck Squamous Cell Carcinoma

TRIM24 (Tripartite Motif Containing 24) is a recently identified oncogene overexpressed in various cancers. However, the molecular mechanism of TRIM24 in the progression of head and neck squamous cell carcinoma (HNSCC) remains ambiguous. In the present study, we analyzed the expression pattern of TRIM24 in 100 HNSCC tissues and found that TRIM24 was overexpressed in 43/100 HNSCC cases. Significant association was found between TRIM24 overexpression and tumor-node-metastasis (TNM) stage (p=0.0034) and T stage (p=0.0048). Furthermore, we overexpressed and knocked down TRIM24 in Detroit 562 and FaDu cell lines, respectively. TRIM24 overexpression promoted proliferation, colony formation, and invasion, while TRIM24 depletion inhibited proliferation, colony formation, and invasion. Further studies showed that TRIM24 facilitated cell cycle transition and upregulated cyclin D1 and p-Rb. In addition, we found that GLUT3, a key protein involved in regulating glucose metabolism, was altered in HNSCC cells overexpressing TRIM24. We demonstrated that TRIM24 overexpression increased glucose uptake ATP production. Overexpression of TRIM24 increases cell sensitivity to glucose deprivation in Detroit cells. Depleting TRIM24 in FaDu cells demonstrated the opposite results. We also showed that TRIM24 could bind to the promoter region of cyclin D1. In conclusion, TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC

Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments

Preparation of Chitosan-Composite-Film-Supported Copper Nanoparticles and Their Application in 1,6-Hydroboration Reactions of p-Quinone Methides

Here, we describe the preparation of copper nanoparticles that are stabilized on a chitosan composite film (CP@Cu). This material could catalyze the 1,6-hydroboration reactions of p-quinone methides with B2pin2 as a boron source under mild conditions. This reaction exhibited very good functional group compatibility, and the organoboron compounds that were formed could easily be converted into corresponding hydroxyl products with good to excellent yields. This newly developed methodology provides an efficient and sequential pathway for the synthesis of gem-disubstituted methanols