Selective recruitment of host factors by HSV-1 replication centers.

Herpes simplex virus type 1 (HSV-1) enters productive infection after infecting epithelial cells, where it controls the host nucleus to make viral proteins, starts viral DNA synthesis and assembles infectious virions. In this process, replicating viral genomes are organized into replication centers to facilitate viral growth. HSV-1 is known to use host factors, including host chromatin and host transcription regulators, to transcribe its genes; however, the invading virus also encounters host defense and stress responses to inhibit viral growth. Recently, we found that HSV-1 replication centers recruit host factor CTCF but exclude γH2A.X. Thus, HSV-1 replication centers may selectively recruit cellular factors needed for viral growth, while excluding host factors that are deleterious for viral transcription or replication. Here we report that the viral replication centers selectively excluded modified histone H3, including heterochromatin mark H3K9me3, H3S10P and active chromatin mark H3K4me3, but not unmodified H3. We found a dynamic association between the viral replication centers and host RNA polymerase II. The centers also recruited components of the DNA damage response pathway, including 53BP1, BRCA1 and host antiviral protein SP100. Importantly, we found that ATM kinase was needed for the recruitment of CTCF to the viral centers. These results suggest that the HSV-1 replication centers took advantage of host signaling pathways to actively recruit or exclude host factors to benefit viral growth.

In situ hybridization analysis of the expression of miR-106b in colonic cancer.

BACKGROUND: MicroRNA-106b (miR-106b) is thought to be an oncogenic microRNA that promotes tumor growth and metastasis. The potential predictive value of miR-106b was studied in colonic cancer patients. METHODS: The expression of miR-106b was examined in 180 colonic cancer cases using in situ hybridization (ISH) technique and was evaluated semi-quantitatively by examining the staining index. The Correlation of miR-106b expression and clinic-pathological features was analyzed by Spearman Rank Correlation. Wilcoxon signed rank test was used for assessing the expression difference of miRNA-106b between colonic cancerous and para-cancerous ones, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. RESULTS: MiR-106b was higher expressed in para-cancerous tissues, compared with colonic cancerous ones (P < 0.001). A positive correlation of miR-106b levels between colonic and para-cancerous tissues was also observed (CC = 0.523, P < 0.001). Furthermore, the expression of miR-106b was not significantly correlated with clinic-pathological parameters, including gender, age, histological grade, tumor size, pT stage, pN stage, pM stage and pTNM stage of the patients. Histological grade was positively correlated with pT stage (P = 0.011), pN stage (P = 0.036) and pTNM stage (P = 0.009). Patients expressing high levels of miR-106b both in colonic cancer tissues and para-cancerous ones have a relatively longer survival time but the difference is not statistically significant (P = 0.16). CONCLUSIONS: The expression difference of miR-106b levels between colonic tissues and para-cancerous tissues is statistically significant, but the miR-106b levels were not quite correlated with clinic-pathological characteristics and overall survival times of patients with colonic cancer. Lower levels of miR-106b may be connected with neoplastic effects due to interference with TGF-ß signaling, providing evidence that down-regulation of miR-106b might also play an important role in the progression of the disease. The study results are consistent with the literature and support the notion that miR-106b is an oncogenic microRNA.

Alterations of dendritic cell subsets and TH1/TH2 cytokines in the peripheral circulation of patients with superficial transitional cell carcinoma of the bladder.

BACKGROUND: Dendritic cells (DCs) and cytokines play an important role in the tumor growth and recurrence. METHODS: Sixty-six patients with superficial transitional cell carcinoma of the bladder (STCCB) and 38 healthy controls were studied to investigate the percentages of DC subsets, monocyte-derived DC (MoDC) function, and alterations of Th1 and Th2 cytokines. MoDCs were generated and three-color flow cytometry was used for determining the phenotype of MoDCs and DC subsets. The ability to stimulate autologous T cells was tested in mixed leukocyte reaction (MLR). The levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit. RESULTS: The myeloid DC (mDC) counts, MoDC surface molecular expression, and stimulatory capacity to T cells were impaired in STCCB patients than in controls. The percentage of mDC and the expression of CD80, CD83, and CD86 were lower in patients showing recurrence. The serum levels of IL-2 and IFN-γ were found to be significantly lower while IL-4, IL-6, and IL-10 were significantly higher in STCCB patients than in controls. IL-6 was found to be significantly higher in recurrent patients. CONCLUSION: The impairment of mDC counts and MoDC function with imbalance of Th1/Th2 cytokines was closely associated with proliferation and recurrence of STCCB.

[Clinical observation on treatment of Stein-Leventhal syndrome caused sterility by combined use of clomiphene and Chinese nourishing shen and activating blood circulation drugs].

OBJECTIVE: To observe the efficacy of combination therapy of clomiphene and Chinese drugs for nourishing Shen and activating blood circulation (NSABC) in treating Stein-Leventhal syndrome caused sterility. METHODS: Sixty-two patients with anovulation caused sterility were randomly divided into the treated group (n = 32) and the control group (n = 30). The treated grop was treated with the combination therapy and the control group treated by the same dosage of clomiphene alone. RESULTS: After treatment, when comparing with that before treatment, the endocrine hormones in the treated group improved significantly, showing a markedly decrease of androgen and luteotropic hormone, and increase of estrogen (P < 0.001). The periodic ovulation rate in the treated group reached 87%, the total pregnancy rate being 65.6%, with no occurrence of ovarian hyperstimulation syndrome (OHSS) and luteinized unruptured follicle syndrome (LUFS), while in the control group, the periodic ovulation rate was 66%, the total pregnancy rate 36.6%, with LUFS occurred in 4 patients. Comparison of the therapeutic effects between the two groups showed significant difference (P < 0.05). CONCLUSION: The combination therapy of clomiphene and NSABC has a better therapeutic effect in treating Stein-Leventhal syndrome caused sterility than that of using clomiphene alone.