Objective: We aimed to evaluate the activity of the human glymphatic system in type 2 diabetes mellitus (T2DM) using diffusion tensor image analysis along with the perivascular space (DTI-ALPS). Methods: Diffusion tensor images were acquired to calculate the diffusivities in the direction of the x-axis (right-to-left; Dx), y-axis (anterior-to-posterior; Dy), and z-axis (inferior-to-superior; Dz) of the plane of the lateral ventricle body in 20 patients with type 2 diabetes and 10 people in a control group. We evaluated the diffusivity along with the perivascular spaces, as well as the projection fibers and association fibers, separately. The analysis along the perivascular space (ALPS-index) was defined as the mean (Dxpro, Dypro)/mean (Dypro, Dzasc), where the Dxpro and Dxasc were the Dx values in the projection and association fiber areas, respectively. Results: There were significant differences in diffusivity along the projection fibers and the association fibers among the groups. The significant differences among the groups along the perivascular spaces, shown as the ALPS-index and medical history of T2DM, indicating lower water diffusivity along the perivascular space concerning type 2 diabetes severity, was also observed. Conclusion: Lower diffusivity along the perivascular space on DTI-APLS can reflect impairment of the glymphatic system in T2DM. This study showed that the activity of the glymphatic system could be evaluated by diffusion tensor image analysis.

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Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of the three loci among 236 patients with NPC and 287 healthy controls were determined by PCR-RFLP. Cytokines and chemokines mRNA and protein in NPC biopsies were measured by real-time quantitative PCR and ELISA, respectively. Results showed that the combined CT/TT genotype of T399I was associated with increased NPC risk, with an odds ratio of 1.853 (95% confidence interval: 1.184-2.961). Also, individuals with the T allele of T399I showed a 1.842-fold increase in NPC risk compared to those with the T399I C allele (95% confidence interval: 1.213-3.015). Messenger RNA levels of interleukin (IL)-1a, tumor necrosis factor-a and IL-10 were significantly elevated in patients with T399I combined CT/ TT genotype; IL-1a and IL-10 protein concentration significantly increased in NPC patients with T399I combined CT/TT genotype compared to those with the T399I CC genotype. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC. (Cancer Sci 2012; 103: 653-658)