Wei Zhang

BACKGROUND: Although peripheral blood adipokines and insulin levels have been considered to be biomarkers of Alzheimer's disease (AD), previous researches about levels of adipokines and insulin in blood are no conclusive. We designed this meta-analysis to validate whether peripheral adipokines and insulin can be used as a candidate biomarker in AD diagnosis. METHODS: We carried out a replication study in serum by ourselves and further conducted a meta-analysis to estimate the different levels of peripheral blood adipokines and insulin between AD patients and controls. In the section of meta-analysis, the pooled weighted mean difference (WMD) and 95% confidence interval (CI) was used to compare the levels of adipokines and insulin in different groups. RESULTS: According to our replication study, there is statistically significant lower in the levels of leptin, but conspicuous higher in the levels of adiponectin and insulin in the blood of AD patients than controls. We finally identified four studies for leptin, four studies for adiponectin and eleven studies for insulin. From the random-effect model, the pooled WMD of the levels of leptin, adiponectin and insulin of AD subjects compared with the controls was -3.90 ng/ml (95% CI: [-5.68, -2.13]), 9.42 µg/mL (95% CI: [4.21, 14.62]), and 2.86 µIU/ml (95% CI: [1.21, 4.50]), respectively. CONCLUSION: Our replication study and meta-analysis support lower levels of leptin and higher levels of adiponectin and insulin in AD patients with respect to controls, and indicate their potential values as important risk factors for AD. Further researches that using standardized assay for leptin, adiponectin, and insulin measurement are still needed to reveal the potential change of peripheral blood leptin, adiponectin, and insulin levels in AD participants.

Extranodal nasal-type natural killer/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma that progresses rapidly and relapses frequently. Advanced ENKTL is multidrug chemoresistant and has a poor prognosis. In this study, we aim to develop a novel hexokinase domain component 1 (HKDC1)-based antitumor target for ENKTL that is involved with the antimetabolic signaling pathway, EBV replication, and P-glycoprotein (P-gp) expression. We showed that HKDC1 is highly upregulated in ENKTL cells and HKDC1 knockdown significantly suppresses ENKTL tumor growth. In addition, HKDC1 is highly identical with four other hexokinase isoforms, with the only difference being in the last eight amino acids (aa) at the C-terminal. Further investigation showed that peptide delivery of the last eight aa of HKDC1 at the C-terminal (HKC8) with D-configuration using transferrin (Tf) receptor internalization sequence (Tf-D-HKC8) inhibits HKDC1 association with vascular endothelial growth factor 1 (VDAC1), resulting in mitochondrial dysfunction and reactive oxygen species (ROS) overgeneration and subsequently suppressing EBV replication and P-gp expression, making it very effective in killing EBV-positive ENKTL cells. Further in vivo experiments showed that local injection of Tf-D-HKC8 peptide significantly suppresses ENKTL tumor growth and EBV replication in ENKTL xenograft mouse models. We conclude that HKDC1 C-terminal-based peptides inhibit ENKTL by modulation of mitochondrial function and EBV suppression.