Intrauterine cytomegalovirus infection: a possible risk for cerebral palsy and related to its clinical features, neuroimaging findings: a retrospective study.

BACKGROUND: Abundant clinical evidences indicate that the increased risk of cerebral palsy (CP) may be associated with the intrauterine exposure to maternal infection. Cytomegalovirus (CMV) is a common cause of CP. However, little is known about the relationship between the intrauterine exposure of the fetus to CMV infection and CP. This study aims to explore the relationships between intrauterine CMV infection and clinical symptoms, classification, intelligence development and brain neuroimaging findings in children with CP. METHODS: In this study, 147 children with CP in recent 6 years were retrospectively analyzed (average age: 14.76 ± 3.07months; sex (M/F): 103/44). 148 children had CMV IgG and IgM positive sera identified by TORCH examination were selected as the control group (average age: 15.10 ± 3.21months; sex (M/F): 102/46), which also undergo the examination of CMV-DNA in urine. The age and sex of children in the control group were matched with those in the CP group. CMV-DNA in urine was detected by CMV fluorescence quantitative PCR, and t-test was performed to analyze the number of copies. For the CP group, standardized rehabilitation treatment was performed and the function of gross motor was evaluated by GMFM scale before and after treatment. The Gesell developmental scale (GDS) was used to assess the level of intellectual development. The classification of CP was conducted and the results of magnetic resonance imaging were analyzed. Finally, the correlations between the copy number of CMV-DNA and the clinical characteristics of children with CP were evaluated by the method of Pearson and Spearman correlation analysis. RESULTS: The level of CMV infection was negatively correlated with the developmental quotient (DQ) of children with CP. Negative association was found between the level of CMV infection and the level of the gross motor development. The level of CMV infection was positively related with the occurrence probability of spastic quadriplegia. However, no associations were found between the abnormalities of brain tissue and the number of CMV copies. Moreover, CMV infection might add the difficulty of the rehabilitation treatment. CONCLUSIONS: CMV infection is a risk factor for the occurrence of CP in children. Pregnancy examination should be strengthened. Early detection and control of CMV infection may contribute to the rehabilitation of children with CP and reduce the disability and social burden.

The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus.

The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP-1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL-5, CCL-19 and CCL-21 could be regulated by Fra1 in mTEC and that IL-1ß, IL-6, IL-8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock-down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer.

BACKGROUND: The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood. METHODS: With the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis. RESULTS: DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability. CONCLUSION: DLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC.

Upregulated expression of NKG2D and its ligands give potential therapeutic targets for patients with thymoma.

The activating receptor NKG2D (natural killer group 2, member D) of natural killer (NK) cells promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells, and thus having an important role in antitumor immune response. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present as useful target for immunotherapeutic approaches in cancer. In this study, to elucidate the role of NKG2D-NKG2D ligand interaction in thymoma tissues and to evaluate the potential role of NKG2D ligands as therapeutic target for thymoma, we examined the expression of NKG2D and its specific ligands: MICA (major histocompatibility complex class I chain-related protein A), MICB (major histocompatibility complex class I chain-related protein B) and ULBP (UL16-binding protein) in 36 thymomas (6 subtype A, 6 subtype AB, 8 subtype B1, 5 subtype B2, 6 subtype B3 and 5 subtype C), 15 thymic atrophy and 8 thymic hyperplasia by immunohistochemistry and reverse transcription-real-time-PCR methods. We demonstrated that both mRNA and protein levels of NKG2D, MICA, MICB and ULBP were upregulated in six types of thymomas compared with those in atrophic thymus or proliferating thymus. Furthermore, the NKG2D ligands were found to be frequently coexpressed on thymoma cells. Furthermore, the expression of MICA, MICB and ULBP in subtype C was higher compared with those in subtype A, AB, B1, B2 and B3. Thus, we concluded that high expressions of NKG2D, MICA, MICB and ULBP1 were shown in patients with thymoma, and this may enhance the recognition function of NK cells to eliminate tumor cells. MICA, MICB and ULBP presented an attractive target for thymoma therapy. The abnormal expression of NKG2D, MICA, MICB and ULBP1 can provide us with evidence of the occurrence of thymoma and could also be used as a target in the treatment of thymoma.