A modified 3D stereophotogrammetry-based distraction test for assessing lower eyelid tension.

AIM: To investigate the reliability of a modified three-dimensional distraction test (3D-DT) and three-dimensional pinch test (3D-PT) for assessing lower eyelid tension (LET). METHODS: A cross-sectional study was conducted among 97 volunteers including 97 eyelids with no history of trauma, tumor, or reconstructive surgeries. Six three-dimensional photographs were acquired for each participant, including two photographs obtained in a neutral position (NP), two using a modified 3D-DT with a 15.9-grammes stainless steel eyelid hook performed, and two using 3D-PT. RESULTS: The mean absolute differences between NP, 3D-DT, and 3D-PT measurements varied between 0.07 and 7.42, 0.10 and 13.10, and 0.07 and 15.97, respectively; technical error of measurement varied between 0.05 and 7.81, 0.09 and 10.19, and 0.07 and 12.47, respectively; and relative error measurements varied between 0.10% and 11.50%, 0.16% and 30.51%, and 0.11% and 38.75%, respectively. For intra-rater reliability, the intraclass correlation coefficients (ICCs) were more than 0.80 in seven out of eight measurements obtained in the NP and 3D-DT, whereas those obtained in the 3D-PT were as low as less than 0.30 by rater 1; the ICCs of all the measurements obtained in all the positions (NP, 3D-DT, and 3D-PT) were more than 0.80 by rater 2. For inter-rater reliability six out of eight NP and 3D-DT measurements had an ICC greater than 0.80, whereas those of 3D-PT measurements were less than 0.30. For intra-method reliability, the ICCs of all the NP measurements were more than 0.87, whereas those of the six 3D-DT measurements and four 3D-PT measurements were more than 0.80. CONCLUSION: Our study results prove that the modified 3D-DT, which involves the use of an eyelid hook, can be a highly reliable method for evaluating LET. Furthermore, this novel and simple method may be utilized as the basis for further investigation and routine pre- and postoperative clinical evaluation.

Transcriptional regulation and ubiquitination-dependent regulation of HnRNPK oncogenic function in prostate tumorigenesis.

BACKGROUND: Heterogeneous nuclear ribonucleoprotein K (HnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, HnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis in various types of human cancers and are therefore pursued as attractive therapeutic targets for select patients. However, both the transcriptional regulation and degradation of HnRNPK in prostate cancer remain poorly understood. METHODS: qRT-PCR was used to detect the expression of HnRNPK mRNA and miRNA; Immunoblots and immunohistochemical assays were used to determine the levels of HnRNPK and other proteins. Flow cytometry was used to investigate cell cycle stage. MTS and clonogenic assays were used to investigate cell proliferation. Immunoprecipitation was used to analyse the interaction between SPOP and HnRNPK. A prostate carcinoma xenograft mouse model was used to detect the in vivo effects of HnRNPK and miRNA. RESULTS: In the present study, we noted that HnRNPK emerged as an important player in the carcinogenesis process of prostate cancer. miR-206 and miR-613 suppressed HnRNPK expression by targeting its 3'-UTR in PrCa cell lines in which HnRNPK is overexpressed. To explore the potential biological function, proliferation and colony formation of PrCa cells in vitro and tumor growth in vivo were also dramatically suppressed upon reintroduction of miR-206/miR-613. We have further provided evidence that Cullin 3 SPOP is a novel upstream E3 ubiquitin ligase complex that governs HnRNPK protein stability and oncogenic functions by promoting the degradation of HnRNPK in polyubiquitination-dependent proteolysis in the prostate cancer setting. Moreover, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of HnRNPK proteins. CONCLUSION: Our findings reveal new posttranscriptional and posttranslational modification mechanisms of HnRNPK regulation via miR-206/miR-613 and SPOP, respectively. More importantly, given the critical oncogenic role of HnRNPK and the high frequency of SPOP mutations in prostate cancer, our results provide a molecular rationale for the clinical investigation of novel strategies to combat prostate cancer based on SPOP genetic status.

Low-Rank Constrained Super-Resolution for Mixed-Resolution Multiview Video.

Multiview video allows for simultaneously presenting dynamic imaging from multiple viewpoints, enabling a broad range of immersive applications. This paper proposes a novel super-resolution (SR) approach to mixed-resolution (MR) multiview video, whereby the low-resolution (LR) videos produced by MR camera setups are up-sampled based on the neighboring HR videos. Our solution analyzes the statistical correlation of different resolutions between multiple views, and introduces a low-rank prior based SR optimization framework using local linear embedding and weighted nuclear norm minimization. The target HR patch is reconstructed by learning texture details from the neighboring HR camera views using local linear embedding. A low-rank constrained patch optimization solution is introduced to effectively restrain visual artifacts and the ADMM framework is used to solve the resulting optimization problem. Comprehensive experiments including objective and subjective test metrics demonstrate that the proposed method outperforms the state-of-the-art SR methods for MR multiview video.

The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1.

BACKGROUND: Previous studies report that miR-1-3p, a member of the microRNA-1 family (miR-1), and functions as a tumor suppressor in several different cancers. However, little is known regarding the biological role and intrinsic regulatory mechanisms of miR-1-3p in prostate cancer (PCa). METHODS: In this study, the expression levels of miR-1-3p were first examined in PCa cell lines and tumor tissues by RT-qPCR and bioinformatics. The in vitro and in vivo functional effect of miR-1-3p was examined further. A luciferase reporter assay was conducted to confirm target associations. RESULTS: We found that miR-1-3p was significantly downregulated in advanced PCa tissues and cell lines. Low miR-1-3p levels were strongly associated with aggressive clinicopathological features and poor prognosis in PCa patients. Ectopic expression of miR-1-3p in 22RV1 and LncaP cells was sufficient to prevent tumor cell growth and cell cycle progression in vitro and in vivo. Further mechanistic studies revealed that miR-1-3p could directly target the mRNA 3'- untranslated region (3'- UTR) of two central cell cycle genes, E2F5 and PFTK1, and could suppress their mRNA and protein expression. In addition, knockdown of E2F5 and PFTK1 mimicked the tumor-suppressive effects of miR-1-3p overexpression on PCa progression. Conversely, concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the inhibitory effects of either E2F5 or PFTK1 silencing alone. CONCLUSION: These data highlight an important role for miR-1-3p in the regulation of proliferation and cell cycle in the molecular etiology of PCa and indicate the potential for miR-1-3p in applications furthering PCa prognostics and therapeutics.

Small Activating RNAs: Towards Development of New Therapeutic Agents and Clinical Treatments.

BACKGROUND: Small double-strand RNAs (dsRNAs) molecules are able to activate endogenous genes via an RNA-based promoter-targeting mechanism. Like RNA interference (RNAi), RNA activation (RNAa) is an evolutionarily conserved mechanism that is present in diverse eukaryotic organisms ranging from yeast to humans. METHODS: The small activating RNAs (saRNAs) that are involved in RNAa have been successively used to activate gene expression in cultured cells. Thus, this emergent technique might allow us to develop biotechnological and therapeutic applications without the need to synthesize hazardous construct systems that harbor exogenous DNA sequences. RESULT AND CONCLUSION: Accordingly, this article aims to provide insights into how RNAa cellular machinery can be manipulated to activate gene expression and for more effective clinical treatments of diverse diseases.

Demystifying the mechanistic and functional aspects of p21 gene activation with double-stranded RNAs in human cancer cells.

BACKGROUND: The recently identified phenomenon of double-stranded RNA (dsRNA)-mediated gene activation (RNAa) has been studied extensively, as it is present in humans, mice, and Caenorhabditis elegans, suggesting that dsRNA-mediated RNAa is an evolutionarily conserved mechanism. Previous studies have shown that dsP21-322 can induce tumor suppressor gene p21 expression in several human cancer cells. Nonetheless, the role of dsRNAs in the activation of gene expression, including their target molecules and associated key factors, remains poorly understood. METHODS: Oligonucleotides were used to overexpress dsRNAs and dsControl. Real-time PCR and Western blotting were used to detect corresponding mRNA and protein expression, respectively. Fluorescence microscopy was used to examine the kinetics of dsRNA subcellular distribution. Luciferase reporter assays were performed to verify dsRNA target molecules. Chromatin immunoprecipitation (ChIP) assays were carried out to determine whether histone modification and other associated key factors are involved in saRNA-mediated p21 expression. RESULTS: We demonstrated that dsRNA-mediated p21 induction in human cell lines is a common phenomenon. This process occurs at the transcriptional level, and the complementary p21 promoter is the intended dsRNA target. Additionally, ChIP assays indicated that p21 activation was accompanied by an increased enrichment of AGO1 and the trimethylation of histone H3K4 at dsRNA-targeted genomic sites. CONCLUSION: These data systematically reveal the mechanistic and functional aspects of ncRNA-mediated p21 activation in human cancer cells, which may be a useful tool to analyze gene function and aid in the development of novel drug targets for cancer therapeutics.