[Impact of anterior lobe thickness of the prostate on the clinical progression of benign prostatic hyperplasia].

OBJECTIVE: To investigate the correlation of the anterior lobe thickness of the prostate (ALTP) with bladder outlet obstruction (BOO), and evaluate the effect of ALTP on the clinical progression of BPH. METHODS: This retrospective study included 159 cases of BPH. We obtained the clinical indicators of the patients, including ALTP, prostate volume (PV), postvoid residual urine (PVR), maximum urinary flow rate (Qmax), BOO index (BOOI) and IPSS, and analyzed the correlations of ALTP with IPSS, PV, Qmax, age, PVR and BOOI. Using the ROC curve and cut-off point of ALTP, we compared the clinical indicators between the small and large ALTP groups, and analyzed the correlation between ALTP and the clinical progression of BPH. RESULTS: IPSS was not significantly correlated with ALTP (P > 0.05), nor was ALTP with PV and Qmax (P > 0.05). The area under the ROC curve was 0.742 (95% CI: 0.656－0.828) and the cut-off point of ALTP was 0.65 cm. Statistically significant differences were observed in PV, Qmax, IPSS and the rate of surgery between the small ALTP (<0.65 cm) and large ALTP (≥0.65 cm) groups (P < 0.05). CONCLUSION: ALTP is not proportional to PV or to IPSS. ALTP ≥ 0.65 cm increases the incidence of BOO, and may be a risk factor for the clinical progression of BPH.

Human Herpesvirus 6A U4 Inhibits Proteasomal Degradation of the Amyloid Precursor Protein.

Human herpesvirus 6 (HHV-6) belongs to the betaherpesvirus subfamily and is divided into two distinct species, HHV-6A and HHV-6B. HHV-6 can infect nerve cells and is associated with a variety of nervous system diseases. Recently, the association of HHV-6A infection with Alzheimer's disease (AD) has been suggested. The main pathological phenomena of AD are the accumulation of ß-amyloid (Aß), neurofibrillary tangles, and neuroinflammation; however, the specific molecular mechanism of pathogenesis of AD is not completely clear. In this study, we focused on the effect of HHV-6A U4 gene function on Aß expression. Coexpression of HHV-6A U4 with amyloid precursor protein (APP) resulted in inhibition of ubiquitin-mediated proteasomal degradation of APP. Consequently, accumulation of ß-amyloid peptide (Aß), insoluble neurofibrillary tangles, and loss of neural cells may occur. Immunoprecipitation coupled with mass spectrometry (IP-MS) showed that HHV-6A U4 protein interacts with E3 ubiquitin ligase composed of DDB1 and cullin 4B, which is also responsible for APP degradation. We hypothesize that HHV-6A U4 protein competes with APP for binding to E3 ubiquitin ligase, resulting in the inhibition of APP ubiquitin modification and clearance. Finally, this leads to an increase in APP expression and Aß deposition, which are the hallmarks of AD. These findings provide novel evidence for the etiological hypothesis of AD, which can contribute to the further analysis of the role of HHV-6A in AD. IMPORTANCE The association of HHV-6A infection with Alzheimer's disease has attracted increasing attention, although its role and molecular mechanism remain to be established. Our results here indicate that HHV-6A U4 inhibits amyloid precursor protein (APP) degradation. U4 protein interacts with CRLs (cullin-RING E3 ubiquitin-protein ligases), which is also responsible for APP degradation. We propose a model in which U4 competitively binds to CRLs with APP, resulting in APP accumulation and Aß generation. Our findings provide new insights into the etiological hypothesis of HHV-6A in AD that can help further analyses.

Human Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling Pathway.

U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection.

Long Non-Coding RNA SNHG1 Regulates the Wnt/ß-Catenin and PI3K/AKT/mTOR Signaling Pathways via EZH2 to Affect the Proliferation, Apoptosis, and Autophagy of Prostate Cancer Cell.

BACKGROUND: Prostate cancer (PCa) is the most common malignant cancer in western developed countries, which has seriously threatened the life style and life quality of men. Its pathogenesis and causes remain indistinct. Currently, it is found that lncRNA-SNHG1 (SNHG1) is highly expressed in multiple tumors with proto-oncogene effect, but its function and mechanism in PCa need to be further studied. METHODS: The expression of SNHG1 and EZH2 was detected by RT-qPCR in the 20 pairs of PCa tissue, adjacent tissue and PCa cell lines. They were transfected with siRNA NC, SNHG1 siRNA, EZH2 siRNA, SNHG1 siRNA+empty, and SNHG1 siRNA+EZH2 overexpression. Then, MTT and colony formation assay were used to detect the proliferation and cloning ability of PCa cells LNCaP and PC3. Transwell and flow cytometry were used to measure cell migration and invasion ability and apoptosis level respectively. Immunofluorescence was used to detect the LC3 spot formation. Western blot was used to detect the expression of the autophagy-related proteins, and PI3K/AKT/mTOR and Wnt/ß-catenin signaling pathway related proteins. Finally, in vivo nude mice tumorigenesis experiment to explore the effect of SNHG1 expression on PCa. RESULTS: We found that SNHG1 and EZH2 were up-regulated in PCa tissue and cells. The expression of SNHG1 and EZH2 was positively correlated. RNA pull down and RNA IP assay further confirmed that SNHG1 bound to EZH2. The proliferation, colony formation, migration and invasion of LNCaP and PC3 cells were significantly reduced with the interference with SNHG1or EZH2 compared with the control group. The related proteins of Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathway were significantly reduced after the interference with SNHG1 or EZH2; after simultaneous interference with SNHG1 and overexpression of EZH2, the functional effects on LNCaP and PC3 cells interfered with SNHG1 were reversed. These results were also confirmed in vivo nude mice tumor formation experiments. CONCLUSIONS: This study reveals that lncRNA-SNHG1 regulates Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways via EZH2 gene to affect proliferation, apoptosis and autophagy of PCa cells. This experiment provides ideas and experimental basis for the improvement and treatment of PCa.