Wen Guo

Abstract Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines. To date, only a few adjuvants have been approved for use in humans, among which aluminum-containing adjuvants are the only ones widely used. However, the medical need for potent and safe adjuvants is currently continuously increasing, especially those triggering cellular immune responses for cytotoxic T lymphocyte activation, which are urgently needed for the development of efficient virus and cancer vaccines. Manganese is an essential micronutrient required for diverse biological activities, but its functions in immunity remain undefined. We previously reported that Mn 2+ is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn 2+ alone directly activates cGAS independent of dsDNA, leading to an unconventional catalytic synthesis of 2′3′-cGAMP. Herein, we found that Mn 2+ strongly promoted immune responses by facilitating antigen uptake, presentation, and germinal center formation via both cGAS-STING and NLRP3 activation. Accordingly, a colloidal manganese salt (Mn jelly, MnJ) was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses, inducing antibody production and CD4 + /CD8 + T-cell proliferation and activation by either intramuscular or intranasal immunization. When administered intranasally, MnJ also worked as a mucosal adjuvant, inducing high levels of secretory IgA. MnJ showed good adjuvant effects for all tested antigens, including T cell-dependent and T cell-independent antigens, such as bacterial capsular polysaccharides, thus indicating that it is a promising adjuvant candidate.

BACKGROUND: The triglyceride-glucose index (TyG) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD). Its association with the severity of hepatic steatosis and liver fibrosis in NAFLD is poorly understood. This study evaluated the relationship between these factors in NAFLD. METHODS: A total of 4784 participants who underwent ultrasonography were enrolled. Anthropometric and biochemical measurements were assessed. Participants with NAFLD were diagnosed by ultrasound. The degree of hepatic steatosis and liver stiffness was evaluated with transient elastography. RESULTS: The TyG index was significantly correlated with the severity of hepatic steatosis and the presence of liver fibrosis in patients with NAFLD. TyG quartile values correlated with increasing prevalence of NAFLD (Q1 30.9%, Q2 53.3%, Q3 71.7%, and Q4 86.4%, P < 0.001) and with the presence of liver fibrosis (Q1 13.5%, Q2 17.6%, Q3 18.8%, and Q4 26.1%, P < 0.001). The AUROC for the TyG index to predict NAFLD was 0.761, resulting in a cut-off value of 8.7. However, the AUC value of the TyG index was 0.589 for liver fibrosis, which was insufficient to predict this condition. The adjusted odds of having hepatic steatosis or liver fibrosis were more strongly associated with TyG values compared with HOMA-IR. CONCLUSION: The TyG index is positively related to the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD. The index also performed better than HOMA-IR.

Background: Insulin resistance (IR) is a significant risk factor for cardiovascular disease (CVD). In this study, the association of the triglyceride glucose (TyG) index, a simple surrogate marker of IR, with arterial stiffness and 10-year CVD risk was evaluated. Methods: A total of 13,706 participants were enrolled. Anthropometric and cardiovascular risk factors were determined in all participants, while serum insulin levels were only measured in 955 participants. Arterial stiffness was measured through brachial-ankle pulse wave velocity (baPWV), and 10-year CVD risk was evaluated using the Framingham risk score. Results: All participants were classified into four groups according to the quartile of the TyG index. BaPWV and the percentage of participants in the 10-year CVD risk categories significantly increased with increasing quartiles of the TyG index. Logistic regression analysis showed that the TyG index was independently associated with a high baPWV and 10-year CVD risk after adjusting for traditional CVD risk factors. The area under the receiver operating characteristics curve (AUROC) of the TyG index for predicting a high baPWV was 0.708 (95% CI 0.693–0.722, P &amp;lt; 0.001) in women, higher than that in men. However, the association of the homeostatic model assessment of IR (HOMA-IR) with a high baPWV and the 10-year CVD risk was absent when adjusting for multiple risk factors in 955 participants. Conclusions: The TyG index is independently associated with arterial stiffness and 10-year CVD risk.