Clinical Evaluation of FOXO1 as a Tumor Suppressor in Prostate Cancer.

OBJECTIVE: Prostate cancer (PCa) is considered the most serious cancer in the world. Nevertheless, the accuracy of current biomarkers, such as pathological staging, Gleason's score, and serum prostate-specific antigen (PSA) levels, is limited. FOXO1 is a key downstream effector of PTEN and a tumor suppressor in PCA, which has been reported extensively. However, the clinical relevance of FOXO1 in PCa remains unclear. METHODS: In this study, we first detected its expression in four public databases to explore the clinical role of FOXO1. Verification of the knockdown effect of FOXO1 siRNA was performed by real-time PCR analysis. Changes in cell viability were assessed using cell counting kit-8 (CCK-8) assays. In addition, we verified the effect of FOXO1 on the PCa cell cycle using a cell cycle assay. RESULTS: Herein, we found that FOXO1 was significantly downregulated in PCa tissues and was significantly associated with Gleason's score, age, biochemical recurrence (BCR), and lymph node (LN) status, while FOXO1 expression was independent of pathological staging and preoperative PSA levels. The Kaplan-Meier survival analysis showed that PCA patients with high FOXO1 expression were less likely to develop BCR compared with patients with low FOXO1 expression. In terms of function, FOXO1 inhibition significantly promoted the proliferation and cell cycle progression of PCa cells. CONCLUSIONS: In summary, our study suggests that FOXO1 may be one of the prognostic factors that describe the risk of PCa for BCR. These results suggest that FOXO1 may be a therapeutic target for PCa.

MicroRNA-96-5p Facilitates the Viability, Migration, and Invasion and Suppresses the Apoptosis of Cervical Cancer Cells byNegatively Modulating SFRP4.

PURPOSE: The current study was intended to research the functional role and regulatory mechanism of microRNA-96-5p in the progression of cervical cancer. METHODS: MicroRNA-96-5p expression in cervical cancer tissues was assessed by quantitative real-time polymerase chain reaction. The association between microRNA-96-5p expression and clinicopathological features of patients with cervical cancer was analyzed. MTT, flow cytometry, wound healing, and transwell assay were performed to evaluate the viability, apoptosis, migration, and invasion of Hela and SiHa cells. Targetscan, dual-luciferase reporter gene assay, and RNA pull-down analysis were constructed to evaluate the target relationship between microRNA-96-5p and secreted frizzled-related protein 4. RESULTS: MicroRNA-96-5p was overexpressed in cervical cancer tissues, and microRNA-96-5p expression was markedly associated with the clinical stage and lymph node metastasis of patients with cervical cancer. Overexpressed microRNA-96-5p facilitated the viability, migration, invasion, and inhibited the apoptosis of Hela and SiHa cells, whereas suppression of microRNA-96-5p exerted the opposite trend. Secreted frizzled-related protein 4 was proved to be a target of microRNA-96-5p. Silencing of secreted frizzled-related protein 4 eliminated the anti-tumor effect of microRNA-96-5p on cervical cancer cells. CONCLUSIONS: MicroRNA-96-5p facilitated the viability, migration, and invasion and inhibited the apoptosis of cervical cancer cells via negatively regulating secreted frizzled-related protein 4.

Down-regulation of LncRNA CRNDE aggravates kidney injury via increasing MiR-181a-5p in sepsis.

Long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is reported to be linked to inflammation and cell apoptosis. However its role in sepsis induced kidney injury remains unclear. This study aims to explore the possible mechanism of CRNDE in kidney injury induced by sepsis. In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 and HEK293 cells were established. Kidney function was measured in rats from different groups. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß(IL-1ß) in kidney tissue were detected via Enzyme-linked immune sorbent assay (ELISA). Then we up- or down-regulated CRNDE and miRNA-181a-5p expression in the cells. The biological influence of CRNDE and miR-181a-5p on cells was studied using CCK-8 assay and Annexin V assay. Interaction between CRNDE and miR-181a-5p was determined by bioinformatics analysis, RT-PCR, and dual luciferase reporter assay. Peroxisome proliferator-activated receptor-α (PPARα) and cell apoptosis related molecules were detected by western blot. We demonstrated that CRNDE was markedly down-regulated while miR-181a-5p was significantly up-regulated in sepsis models. CRNDE interacted with miR-181a-5p, and negatively regulated its expression level. CRNDE knockdown in rats increased the urea nitrogen and serum creatinine in plasma. Knockdown of CRNDE or transfection of miR-181a-5p significantly inhibited proliferation and promoted apoptosis of HK-2 and HEK293 cells, while overexpression of CRNDE and transfection of miR-181a-5p inhibitors had opposite effects. For mechanism, miR-181a-5p directly targeted the 3' untranslated region of PPARα, and depressed its protein level, and PPARα was regulated indirectly by CRNDE. We concluded that CRNDE protected renal cell from sepsis-induced injury via miR-181a-5p/PPARα pathway.

Gender Differences in the Symptoms, Signs, Disease History, Lesion Position and Pathophysiology in Patients with Pulmonary Embolism.

Advances in research relating to pulmonary embolisms (PE) can assist physicians in selecting the best management strategies for PE patients. However, the symptoms, signs, disease history, lesion position and pathophysiology linked to different genders in patients with PE have rarely been evaluated. One hundred and forty-nine PE patients (73 males and 76 females) were sequentially recruited to this study over the last five years whilst attending our Emergency Department. Data relating to the symptoms, signs, disease history, biochemical testing, cardiac electrophysiology, imaging detection, treatment and outcome were collected and the gender differences were analyzed. We found that embolisms occurred significantly more frequently in the right lung (89.7%) than in the left lung (42.6%). The presence of dyspnea, the number of patients presenting with tumors, the number of patients with chronic pulmonary disease, those with emboli in the right pulmonary artery and emboli in the right lung, as well as the average systolic and diastolic blood pressure were: 78.1%, 15.1%, 31.5%, 32.9%, 94.5%, 129.9+20.0 and 75.0+11.2 in the male patients and 59.2%, 1.3%, 14.5%, 17.1%, 69.7%, 125.1+14.6 and 69.3+11.0 in the female patients. These indicators were found to be significantly higher in male patients. In contrast, the rate of V1-V4 T-wave inversion and level of D-dimer in the blood were significantly lower in males than in females. No significant difference was observed in the remaining observational indicators. Gender differences regarding the symptoms, signs, disease history, lesion position and pathophysiology exist in patients with PE and should be considered in clinical practice.

Analysis of the dynamic relationships between the lingual artery and lingual markers in patients with obstructive sleep apnea.

PURPOSE: To determine the relationships between the lingual artery and the lingual markers in tongue resting and extended positions in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) for the clinical application of functional tongue surgery. METHOD: Computed tomography angiography (CTA) of the lingual artery was performed on 30 OSAHS patients using a 16-slice spiral CT scanner. The anatomical relationships between the lingual artery and the lingual markers were analyzed with the tongue in resting and extended positions using the CTA images. RESULTS: The course of the lingual artery resembled the configuration of the Big Dipper constellation when the tongue was in a resting position. When the tongue was in a full-extended position, the majority of the lingual artery moved forward and upward with the hyoid and formed a "√" fashion. The positions of the tip of the greater horn of the hyoid changed with the tongue positions. While the relationship between the main lingual artery and the tip of the greater horn of the hyoid, as well as the distances between bilateral lingual arteries, remained constant in both tongue positions. CONCLUSIONS: In conditions of dynamic tongue movement, the tip of the great horn of the hyoid and the lingual midline are constant anatomical markers to indicate the course of the lingual artery.

Therapy effects of gold nanorods on the CNE-1 nasopharyngeal carcinoma cell line.

The use of nanocarriers to deliver drugs to tumor tissue is one of the most important strategies in cancer therapeutics. Recently, gold nanorods (GNRs) have begun to be used in cancer therapy because of their unique properties. The purpose of this study was to show the potential that GNRs have against human nasopharyngeal carcinoma CNE-1 cells, using near-infrared (NIR) laser light. Transmission electron microscopic and ultraviolet-visible spectroscopic investigations confirmed the efficient uptake of the GNRs by CNE-1 and human rhinal epithelia cells. The in vitro NIR photothermal therapy for the CNE-1 and rhinal epithelia cells was designed in three groups: (1) control, (2) laser alone, and (3) GNRs with laser. Fluorescence microscopy images indicated that, at some GNR concentrations and some intensities of NIR laser, GNRs with laser therapy could induce cell death for CNE-1 cells while keeping the rhinal epithelia cells healthy. Therefore, the results of this study suggest that using GNRs with NIR laser therapy can selectively destruct CNE-1 cells while having no effect on normal (rhinal epithelia) cells.

The definition of the V zone for the safety space of functional surgery of the tongue.

OBJECTIVES/HYPOTHESIS: To define safety space for functional surgery of the tongue. STUDY DESIGN: Prospective nonrandomized study. METHODS: Computed tomographic angiography of the lingual artery was performed in 107 in-patients with obstructive sleep apnea syndrome and 17 controls. The safety space was ascertained according to the course of lingual artery. RESULTS: The course of the lingual artery, termed the Big Dipper bowl of the tongue, was similar in each group. The tissue above the lingual artery and the vacuity of the hypoglossal/lingual artery neurovascular bundle (HLNVB) formed a three-dimensional structure. The anterior part was named the V prozone. Its anterior border was the tangent plane of the deep lingual artery, its posterior border the circumvallate papilla, its width the interval of bilateral margins at the corresponding parts of the tongue, and its height the level of the middle lingual frenulum. The posterior portion between the bilateral dorsal arteries in the tongue base was named the V postzone. Its width was 31.42±3.82 mm when the tongue was in a resting position, and its height was the distance from the foramen cecum to the bottom of the epiglottic vallecula. The inferior part under the intrinsic lingual muscles was named the hypoglossal floor. It is a relatively restricted surgery zone. CONCLUSIONS: The V zone of the tongue without HLNVB travelling provides enough of safety space for functional surgery on the tongue.

Zwitterionic phosphorylcholine as a better ligand for gold nanorods cell uptake and selective photothermal ablation of cancer cells.

The conjugation of zwitterionic phosphorylcholine onto gold nanorods leads to enhanced and selective uptake within cancer cells.