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The role of CD3 + CD56 + natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3 + CD56 + NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ 2  = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3 + CD56 + NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sepsis can cause sepsis-associated encephalopathy (SAE), but whether SAE was induced or exacerbated by ferroptosis remains unknown. In this study, the rat sepsis model was constructed using the cecal ligation and puncture method. The blood-brain barrier (BBB) permeability was measured by Evans blue dye (EBD) in vivo. The levels of ROS, Fe ion, MDA, GSH, and GPX4 were assessed by enzyme-linked immunosorbent assay (ELISA). The exosomes isolated from serum were cultured with bEnd.3 cells for the in vitro analysis. Moreover, bEnd.3 cells cultured with 100 μM FeCl3 (iron-rich) were to simulate ferroptosis stress. The cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-9-5p with NEAT1, TFRC, and GOT1. In vivo, it is found that BBB permeability was damaged in model rats. Level of ROS, Fe ion, and MDA was increased, and level of GSH and GPX4 was decreased, which means ferroptosis was induced by sepsis. Exosome-packaged NEAT1 in serum was significantly upregulated in model rats. In vitro, it is found that NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. In conclusion, these findings suggest that sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate SAE by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis., (© 2022. The Author(s).)

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan–Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis. [ABSTRACT FROM AUTHOR]