Lee S, et al. Yonsei Med J. 2022 Jan;63(Suppl):S93-S107. https://doi.org/10.3349/ymj.2022.63.S93

Background: Titanium dioxide nanoparticles (TiO₂ NPs) represent a scientific breakthrough in the areas of biological and medicinal applications. Interaction of TiO₂ NPs with components of innate immune system remains elusive. Aim: This study explored in vitro immunotoxicity of murine macrophage RAW 264.7 to TiO₂ NPs (20 nm, negative charge) and its underlying molecular mechanism by way of immunoredox profiling. Materials and methods: In this study, chemically synthesized BSA-functionalized TiO₂ NPs (20 nm, negative charge) were characterized and immunotoxicity was investigated on RAW 264.7 cells. Results: We found that reactive oxygen species levels significantly increased with increasing nitric oxide production, whereas depleting endogenous antioxidant super oxide dismutase as well as nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels. Furthermore, NPs exposure increased the expression of apoptotic factors such as BAX, BIM, and PUMA with disruption of mitochondrial membrane potential (ΔΨ_m) that lead to decrease in immunocytes. Molecular immune profiling revealed the activation of multiple toll-like receptors (TLRs) 4/9/12/13 simultaneously with the phosphorylation of p-p38MAPK and p-SAPK/c-Jun N-terminal kinase (JNK) compared to untreated control. Conclusion: Collectively, this study shows that the molecular nature of TiO₂^SA20(-) NP-induced immunotoxicity in RAW 264.7 macrophage is simultaneous induction of immunocyte apoptosis and multiple TLRs signaling through oxidative stress-dependent SAPK/JNK and p38 mitogen-associated protein kinase activation. This is the first study to address newer molecular mechanism of TiO₂^SA20(-) NP-induced immunotoxicity.

Objectives: This study aims to investigate the relationship between the total injury experience rate and socioeconomic status based on the fourth Korea National Health and Nutrition Examination Survey (KNHANES).

Several anthropometric indices such as body mass index (BMI) and waist circumference (WC) have been examined as indicators of cardiovascular diseases, in both adults and children. However, the waist-to-height ratio (WHtR) is considered a better predictor for the detection of cardiovascular risk factors, than BMI. We investigated the association between the WHtR and incident hypertension. A total of 1718 participants, aged 39–72 years, were recruited in this longitudinal study. Participants were divided into 2 groups according to the development of hypertension during 2005–2008 (baseline) and 2008–2011 (follow-up). Logistic regression models were used to evaluate the WHtR as a significant predictor of hypertension. During the 2.8 years of follow-up, 185 new cases of hypertension (10.8%) were diagnosed, with an incidence rate of approximately 4% per year. The WHtR was significantly higher in the participants who had developed hypertension than in those who had not (0.54 ± 0.05 vs. 0.51 ± 0.05, p < 0.001). After adjusting for age, sex, smoking status, alcohol intake, regular exercise status, total cholesterol, and systolic blood pressure, at the baseline, the logistic regression analysis indicated that the participants with the highest quartile of the WHtR (WHtR≥0.54) were 4.51 times more likely to have hypertension than those with the lowest quartile (odds ratio 4.51; 95% confidence interval 2.41–8.43; p < .0001). The area under the curve for the WHtR, in identifying hypertension risk, was significantly greater than that for the BMI (p = 0.0233). A positive association between WHtR and the incidence of hypertension was observed in Korean adults. The findings of the present community-based prospective study suggest that the WHtR may be a better predictor of incident hypertension.