Objective To investigate the value of the reverse shock index multiplied by GlasgowComa scale score (rSIG) and serum translocator protein 18000 in the prognosis of patients with severe traumatic brain injury. Methods One hundred and fifteen patients with severe traumatic brain injury were divided into the survival group and death group. SPSS 20.0 software was used to compare the vital signs, rSIG and TSPO between the two groups, and the relationship between rSIG and TSPO was analyzed. Receiver operating characteristic (ROC) curve was used to predict the value of rSIG and TSPO and their combination in the prognosis of patients with severe traumatic brain injury. According to the best cut-off value of rSIG and TSPO of ROC curve, patients were divided into the rSIG ≤ 14.8 group and rSIG>14.8 group, and the TSPO ≤ 1.84 ng/mL group and TSPO>1.84 ng/mL group, and the mortality between the groups was compared. Results In 115 patients, rSIG of the survival group was significantly higher than that of the death group, and TSPO was significantly lower than that of the death group [(10.5±4.4) vs. (6.4±4.1), 1.0(0.3,1.9) ng/mL vs.3.4 (2.0, 4.6) ng/mL, P<0.01]. The ability of rSIG combined with TSPO to forecast the mortality of patients with severe traumatic brain injury is not superior to the predictive power of these two indicators alone. The serum TSPO value and 28-day mortality in the rSIG > 4.15 group were significantly higher than those in the rSIG ≤ 4.15 group. The rSIG value of the TSPO ≤ 1.84 ng/mL group was significantly higher than that of the TSPO>1.84 ng/mL group; the 28-day mortality was significantly lower than that in the TSPO>1.84 ng/mL group. The rSIG value was negatively correlated with serum TSPO value (r=-0.611, P<0.01). Conclusions rSIG value and serum TSPO value have good predictive value for the prognosis of patients with severe traumatic brain injury, and can provide certain guiding significance in clinical practice.

Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed Dcaf8 knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of Dcaf8-deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in Dcaf8 knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and Dcaf8 knockout sperm. More than 40% of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm. In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.
Animals ; Cullin Proteins/genetics* ; DNA-Binding Proteins/genetics* ; Factor VIII ; Male ; Mice ; Mice, Knockout ; Spermatogenesis/genetics* ; Ubiquitin-Protein Ligases

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα_q/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gα_q/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gα_q/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
Humans ; Mice ; Animals ; Lipoylation ; NIH 3T3 Cells ; Uveal Neoplasms/genetics* ; Melanoma/genetics* ; Cell Proliferation ; Proto-Oncogene Proteins c-bcl-2 ; GTP-Binding Protein alpha Subunits, Gq-G11/genetics*