Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

[Correlation of K-ras Gene Mutations with the Protein Expressions of TAK1 and MAP4K2 in Colorectal Cancer].

OBJECTIVE: To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-ß activating kinase 1 (TAK1) protein and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) protein in colorectal cancer. METHODS: K-ras gene mutations were detected by DNA sequencing analysis, and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues. RESULTS: In 76 cases of colorectal cancer tissues, the mutation rate of K-ras gene was 32.89% (25 cases), and K-ras gene mutations were correlated with the degrees of cell differentiation ( P<0.05). The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%, respectively. The protein expressions of TAK1 and MAP4K2 were positively correlated with the degrees of cell differentiation and lymph node metastases, respectively ( P<0.05). There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression ( P>0.05). In 25 cases of colorectal cancer with K-ras mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein ( P<0.05). CONCLUSION: K-ras gene mutation, TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer, but not to the depth of invasion. In colorectal cancer with K-ras gene mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Male adolescents with Interleukin 10 rs1800872 AA genotype had higher prevalence and slower recoveries of post-traumatic stress disorder at late stage of a follow-up.

BACKGROUND: Pathophysiological mechanisms of post-traumatic stress disorder (PTSD) are elusive and heterogeneous relationships have been reported among PTSD, Interleukin 10 (IL-10), and other factors after stresses. The present study aimed to longitudinally investigate associations of PTSD with environmental factors and genetic variation of rs1800872 at IL-10 gene. METHODS: Symptoms of PTSD were measured by PTSD Checklist-Civilian Version (PCL-C) in 462 high school students at 6, 12, and 18 months after Wenchuan earthquake in China. Genotypes of IL-10 rs1800872 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and verified by DNA sequencing. RESULTS: AA homozygotes had higher PTSD prevalence than C allele carriers only at 18 months in male, but not female subjects. PTSD prevalence at 18 months was lowered in all subjects except male AA homozygotes when compared to that at 6 months, and only in female C allele carriers when compared to that at 12 months. PCL-C scores at 18 months were decreased in all students but not in male AA homozygotes when compared to those at 6 months. IL-10 rs1800872 was associated with PTSD at 18 months. Patterns of predictors of PCL-C scores were different between AA homozygotes and C allele carriers at different times during the follow-up. CONCLUSION: There were different reciprocal actions of IL-10 rs1800872 with other potential factors or predictors on PTSD in a time-course and gender-dependent manner. Male students with IL-10 rs1800872 AA genotype had higher prevalence and slower recoveries of PTSD at late stage of the follow-up, suggesting requirements of special psychiatric care or drug supplementation at this stage.