Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway.

The article "Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway, by Q. Zhang, T.-Y. Len, S.-X. Zhang, Q.-H. Zhao, L.-H. Yang, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 43-54-DOI: 10.26355/eurrev_202001_19894-PMID: 31957817" has been withdrawn from the authors stating that "after the manuscript has been accepted, we are ready to continue to study the exosomes and their mechanism of action. Before the research, we read the latest guideline of exosomes research, MISEV2018. This guideline first suggests that extracellular vesicles should be used to refer to these cell-derived noncellular membrane structures, while exosomes are only applicable to those vesicles released from intracellular sources to extracellular cells by special means. Secondly, the guidelines suggest that when performing key functional verification experiments with extracellular vesicles, methods such as density gradient centrifugation should be used to purify the vesicles. Thirdly, strict negative control should be set up in the functional study of cells, such as cell-conditioned medium treated with extracellular vesicle production inhibitor (GW4869), so as to exclude the false positive of other non-extracellular vesicle components in functional analysis. In our published manuscripts, we called extracellular vesicles as exosomes, and used exosomes separation kit with low purity to separate the exosomes. No appropriate negative control is used in the functional analysis. Most importantly, the conclusion we made in our study is "SKOV3-secreted exosomes inhibited the PTEN/AKT signaling pathway by transferring lncRNA FAL1, thus inhibiting OC cell metastasis in vitro and in vivo". However, the study did not confirm whether lncRNA FAL1 was encapsulated by extracellular vesicles and transferred to OC cells or induced by extracellular vesicles to upregulate its expression in OC cells. Based on the above reasons, we believe that our understanding of extracellular vesicles is not deep enough, which leads to the inaccuracy and over-interpretation of the experimental results. In order to avoid the readers' misunderstanding of extracellular vesicles and ensure the preciseness of scientific research, all of our authors decided to withdraw this article. We will conduct our research again according to MISEV2018, interpret the experimental results and write articles again, and will submit to ERMPS in the near future". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19894.

Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway.

OBJECTIVE: Tumor-derived exosomes have been repeatedly studied as tumor antigens, suppressing T-cell signaling molecules and promoting apoptosis in ovarian cancer (OC). Long non-coding RNAs (lncRNAs) have been recognized as major regulators in tumorigenesis, including OC. For this study, we try to find out the mechanism of exosomes and lncRNA FAL1 in OC. MATERIALS AND METHODS: After the extraction and identification of exosomes, the internalization of exosomes was observed. Invasion and migration experiments were conducted to investigate the effect of SKOV3 cells-secreted exosomes on OC tumorigenesis and metastasis. Furthermore, the in vivo findings were verified via xenograft tumors in nude mice. FAL1 was knocked out on exosomes. OC cells treated with exosomes were co-cultured with lncRNA FAL1 or/and PTEN to measure cell invasion and migration. RESULTS: SKOV3-secreted exosomes were absorbed and internalized by OC cells. After exosome treatment, the migration and invasion of OC cells were enhanced, tumors in nude mice were larger and heavier, metastasis was increased, and lncRNA FAL1 expression was increased. When lncRNA FAL1 was knocked out, the promoting effects of SKOV3 cells-secreted exosomes on OC cell metastasis were weakened, along with increased PTEN level and decreased AKT phosphorylation level. In HO-8910PM cells treated with siRNA-FAL1 exosomes and siRNA-PTEN, cell invasion and migration, and AKT phosphorylation were restored. CONCLUSIONS: SKOV3-secreted exosomes inhibited the PTEN/AKT signaling pathway by transferring lncRNA FAL1, thus inhibiting OC cell metastasis in vitro and in vivo.

Centromere protein U promotes cell proliferation, migration and invasion involving Wnt/ß-catenin signaling pathway in non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to examine centromere protein U (CENPU) expression in non-small cell lung cancer (NSCLC) and identify the clinical values of CENPU, as well as investigate the potential molecular mechanisms in NSCLC. PATIENTS AND METHODS: The expression levels and clinical significance of CENPU were systematically evaluated in human protein atlas datasets and TCGA datasets. CENPU protein expression was studied by Western blotting. CENPU mRNA expression was studied by Real Time-Polymerase Chain Reaction (RT-PCR). Proliferation, migration, and invasion capacities of CENPU cells were assessed after silencing CENPU. Apoptosis was determined using flow cytometry. Western blotting was performed to assess the protein expression levels. RESULTS: We found that the expression of CENPU at mRNA and protein levels was significantly up-regulated in both NSCLC tissues and cell lines. Overexpression of CENPU was significantly associated with poor prognosis of NSCLC patients. Knockdown of CENPU significantly suppressed proliferation, migration, and invasion, and caused apoptosis of NSCLC cells in vitro. In addition, knockdown of CENPU suppressed epithelial-mesenchymal transition (EMT). Furthermore, our results revealed that the abnormal expression of CENPU could influence the Wnt/ß-catenin signaling pathway. CONCLUSIONS: CENPU was highly expressed in NSCLC tissues and its knockdown of CENPU strongly suppressed NSCLC cell proliferation and metastasis through modulating Wnt/ß-catenin signaling. Targeting CENPU could be a promising therapeutic strategy for patients with CENPU.

The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats.

OBJECTIVE: This study aims to explore the role and the mechanism of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction (MI) rats, and to provide a new sight for the treatment of myocardial infarction. MATERIALS AND METHODS: Fifty Sprague- Dawley (SD) male rats were randomly divided into 5 groups: sham operation group (Sham group), model group (MI group), low-dose Parkin group (L-Parkin group), middle-dose Parkin group (M-Parkin group) and high-dose Parkin group (H-Parkin group). The rat model of myocardial infarction was established by ligation of the anterior descending branch. Small animal ultrasound was used to measure cardiac function. The myocardial infarct size was observed by triphenyltetrazolium chloride (TTC) staining. The pathological changes of myocardial tissues were observed by hematoxylin-eosin (HE) staining. The myocardial cell apoptosis was detected by TUNEL assay. The mRNA expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) were detected by qRT-PCR. The expression of Parkin protein in myocardial tissue of rats was detected by Western-blot. RESULTS: Compared with MI group, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) in Parkin overexpressing group were significantly decreased (p<0.05), while the value of left ventricular short axis shortening (FS) and left ventricular ejection fraction (EF %) in Parkin overexpression group were significantly increased (p<0.05). Overexpression of Parkin improved abnormal structure of myocardial tissue, reduced the size of myocardial infarct, made the arrangement of myocardium fibers more neatly and made the stain of myocardial cells more uniformly. Apoptosis index (AI) values were significantly decreased (p<0.05), and MMP2, MMP9, TIMP1 and TIMP2 mRNA levels were significantly decreased (p<0.05), while Parkin protein expression was significantly elevated in a dose-dependent manner (p<0.05). CONCLUSIONS: After treatment with Parkin in myocardial infarction rats, the relevant mRNA levels decreased, the number of apoptotic cells decreased, the myocardial fiber morphology returned to normal, the myocardial infarct size decreased, and the cardiac function of rats improved. Therefore, Parkin therapy plays an active role in cardiac function and ventricular remodeling in myocardial infarction rats.

The protective effects of taurine on experimental autoimmune myocarditis.

OBJECTIVE: To investigate the protective effects of taurine on experimental autoimmune myocarditis and its mechanisms. BALB/c mice were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM). MATERIALS AND METHODS: We administered taurine (5 mg/kg, 10 mg/kg or 20 mg/kg) or vehicle to EAM mice daily. On day 21, the severity of myocarditis was evaluated by determination of heart weight/body weight ratio (Hw/Bw), histopathological and echocardiographic examination of heart tissue. The levels of Th1 and Th2 cytokines in serum were measured by ELISA. Moreover, ELISA was also used to determine the levels of MDA, SOD and GSH-Px in heart homogenates. RESULTS: The mice treated with taurine had significantly decreased Hw/Bw (p < 0.05). Treatment with 10 or 20 mg/ kg taurine prevented the LV dysfunction, significantly increased the LVEDs, LVEDd and LVPW. Furthermore, Th1 cytokines (TNF-α, IFN-γ and IL-2) were significantly downregulated, accompanied by Th2 cytokines (IL-4 and IL-10) markedly upregulated after treatment with taurine. Meanwhile, the activities of SOD and GSH-Px in heart tissues significantly increased, while the content of MDA significantly decreased after treatment with taurine. CONCLUSIONS: The results indicated that taurine has a protective effect against EAM by modulating Th1/Th2 cytokine balance and suppressing of oxidative stress.

Knockdown of tripartite motif 59 (TRIM59) inhibits tumor growth in prostate cancer.

OBJECTIVE: Members of the tripartite motif (TRIM) protein family contain a highly conserved N-terminal really interesting new gene (RING) domain that is involved in regulating transcriptional factors and tumor suppressors. In this study, the effects of TRIM59 expression on tumor growth were investigated in prostate cancer. MATERIALS AND METHODS: The expression of TRIM59 in prostate cancer tissues (n = 15) and prostate cancer cell lines was determined by quantitative reverse transcriptase-PCR (qRT-PCR), Western blotting, and immunohistochemistry. A specific shRNA targeting TRIM59 was employed to knockdown TRIM59 expression in the prostate cancer cell lines PC3 and DU145. The effects of TRIM59 knockdown on cell proliferation were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The effects on cell cycle progression were determined by flow cytometry, and a xenograft mouse model of prostate cancer was generated to determine the in vivo effects of TRIM59 knockdown. The effects on cell cycle regulators were determined by Western blotting. RESULTS: TRIM59 was highly expressed in prostate cancer tissues. Knockdown of TRIM59 significantly inhibited cell proliferation and colony formation, and cell cycle analysis showed that TRIM59-depleted cells accumulated in S-phase. TRIM59 knockdown was shown to inhibit tumorigenesis in mice. In addition, the cell cycle regulators CDC25A, CDC2, and cyclin B1 were decreased by TRIM59 shRNA-mediated knockdown. CONCLUSIONS: Our study suggests that TRIM59 promotes prostate cancer cell proliferation, possibly through its effects on cell cycle progression.

Effects of silencing PTTG expression by small interference RNA.

OBJECTIVE: We investigated the effects of small interference RNA (siRNA) on the cell proliferation inhibition, sensitivity to radiotherapy effects and cell apoptosis. The siRNA used here was specific to the pituitary tumor transforming gene (PTTG). MATERIALS AND METHODS: Vectors containing the specific functional siRNAs for PTTG were designed and constructed. Cells were divided into four groups: (I) blank control group; (II) radiotherapy group: cells were exposed to X-ray radiation; (III) Group PTTG siRNA: transfected with PTTG siRNA; (IV) PTTG siRNA+ radiotherapy group: transfected with PTTG siRNA and then were exposed to X-ray radiation. HEC-1A cells were transfected by the specific interfering plasmids using Lipofectamine 2000 transfection reagent. The PTTG protein expression levels were analyzed using Western blot Cell proliferation was examined by MTT assay and the HEC-1A cell line apoptosis was evaluated by flow cytometry. RESULTS: Recombinant small interference RNA (siRNA) expression vectors targeting PTTG were successfully constructed. The results of MTT showed that the growth of the HEC-1A cell was negatively influenced after cells were transfected with PTTG siRNA. Furthermore, PTTG siRNA combined with radiotherapy demonstrated more powerful inhibitory effects. Cell apoptosis rates were significantly increased in the radiotherapy group and the PTTG siRNA transfection group when compared to the control group. A more pronounced cell apoptosis rate was observed in the group that was treated with PTTG siRNA combined with radiotherapy. CONCLUSIONS: Recombinant small interference RNA (siRNA) expression vector targeting PTTG successfully inhibited the cell proliferation and induced apoptosis in endometrial carcinoma cells and increased the cancer cells vulnerability to the effects of radiation.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

STUDY DESIGN: This is a randomized controlled prospective trial with two parallel groups. OBJECTIVES: The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. SETTING: This study was conducted in SCS Research Center in Colorado, USA. METHODS: A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). RESULTS: Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. CONCLUSION: TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

Clinical significance of sCIP2A levels in breast cancer.

OBJECTIVE: It has previously found that human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) was overexpressed in breast cancer, and was positively correlated with lymph node metastasis of the patients. This study aimed to investigate the association between serum CIP2A and prognosis of breast cancer. Then, we investigated whether CIP2A could be as a therapeutic target in breast cancer treatment. PATIENTS AND METHODS: Preoperative CIP2A levels of 240 patients with breast cancer and 480 cases of controls were measured by ELISA method. The association of CIP2A levels with clinicopathological outcomes was investigated by univariate and multivariate analyses. The effect of CIP2A on breast cancer MDA-MB-231 cells was evaluated by CIP2A siRNA-mediated depletion of the CIP2A protein followed by an analysis of cell proliferation, invasion, colony growth, and xenograft growth and metastasis. RESULTS: The serum CIP2A levels in patients with breast cancer were (79.0 ± 74.2) ng/mL, which was significantly higher than that in those controls (25.6 ± 21.4) ng/mL for male and (24.8 ± 20.6) ng/mL for female control. Higher preoperative CIP2A levels were significantly associated with the American Joint Committee on Cancer (AJCC) stage, histological grade and lymph node metastasis. Patients with elevated CIP2A levels showed worse survival. In multivariate analysis, elevated preoperative CIP2A levels were independent prognostic factors. Patients with high CIP2A levels had significantly shorter overall survival (OS) and disease-free survival (DFS) times. Knockdown of CIP2A by stable CIP2A siRNA transfection inhibited MDA-MB-231 cell proliferation, invasion, colony growth in vitro, and xenograft growth and metastasis in vivo. CONCLUSIONS: Our results suggest that serum CIP2A is significantly higher in patients with breast cancer, which is a potential biomarker to make a distinction between breast cancer patients and healthy controls. Higher serum CIP2A levels positively associated with the aggressive phenotype of breast cancer, and forecasts poor prognosis for patients with breast cancer. Knockdown of CIP2A may be a novel target for prevention and treatment of breast cancer.

Lixisenatide rescues spatial memory and synaptic plasticity from amyloid ß protein-induced impairments in rats.

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by cognitive impairment, but effective strategies against AD are currently not available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, the neuroprotective effects of lixisenatide in the brain remain to be clarified. In the present study, we report for the first time the effects of lixisenatide on the amyloid ß (Aß) protein-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms. We found that: (1) bilateral intrahippocampal injection of Aß25-35 resulted in a significant decline in spatial learning and memory of rats, as well as a suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide treatment effectively prevented the Aß25-35-induced impairments; (3) lixisenatide inhibited the Aß25-35 injection-induced activation of glycogen synthase kinase 3ß (GSK3ß), with a significant increase in the phosphorylation of ser9 and a significant decrease in the phosphorylation of Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt-GSK3ß pathway, can prevent Aß-related impairments in synaptic plasticity and spatial memory of rats, suggesting that lixisenatide may be a novel and effective treatment for AD.

The application of chromosome abnormality chip detection in male infertility / Aplicación de la detección de la anormalidad del cromosoma mediante biochips genéticos en la infertilidad masculina

OBJECTIVE: To discuss the application of microarray technology in the diagnosis of male infertility. METHODS: Sixteen loci, including a sex-determining region on the Y chromosome, were investigated by polymerase chain reaction (PCR) in infertile male patients. Chromosome abnormality chip with 180 000 probes was used to detect small deletion, small amplification and loss of heterozygosity. RESULTS: By PCR, nine of 103 infertile patients were found to have sequence-tagged site microdeletions. Microdeletions were not observed in control samples. The deletions detected by PCR were present in six azoospermic men (6/44, 13.6%) and in three oligoasthenoteratozoospermic (OATS) men (3/59, 5%). The overall frequency of microdeletions in infertile men was 8.7% (9/103). Chromosome abnormality chip detection 500+ detected more amplification or deletion in 51 infertile patients and the overall frequency of microdeletions in infertile men was 49.5% (51/103). CONCLUSION: Chromosome abnormality chip detection system provides a sensitive, economic and high-throughput method for detecting the deletion or amplification of genomic DNA sequences of infertile patients. Not only can it identify Yq deletions, but it can also find other chromosome abnormalities and facilitate the understanding of male infertility.

OBJETIVO: Analizar la aplicación de la tecnología de los microarreglos en el diagnóstico de la infertilidad masculina. MÉTODOS: Dieciséis loci, incluyendo una región determinante del sexo en el cromosoma Y, fueron investigados mediante reacción en cadena de la polimerasa (RCP) en pacientes hombres con problemas de infertilidad. Un biochip de la anormalidad cromosómica, con 180000 sondas, fue utilizado a fin de detectar pequeñas delecciones, pequeñas amplificaciones y pérdidas de heterocigosidad. RESULTADOS: Por medio de la RCP, se halló que nueve de 103 pacientes con infertilidad presentaban microdelecciones de sitios de secuencia marcada. Las microdelecciones no fueron observadas en las muestras de control. Las delecciones detectadas mediante RCP, estuvieron presentes en seis hombres azoospérmicos (6/44, 13.6%) y en tres hombres con oligoastenoteratozoospermia (OAT) (3/59, 5%). La frecuencia general de las microdelecciones en los hombres infértiles fue 8.7% (9/103). La detección con biochip de la anormalidad cromosómica de 500+ detectó más amplificación y delección en 51 pacientes, y la frecuencia general de microdelecciones en los hombres infértiles fue 49.5% (51/103). CONCLUSIÓN: El sistema de detección de la anormalidad del cromosoma mediante biochips genéticos representa un método sensible, económico, y de alto rendimiento, para detectar la delección o amplificación de las secuencias genómicas de ADN de pacientes infértiles. Este método puede no sólo identificar las delecciones Yq, sino también hallar otras anormalidades cromosómicas, facilitando así la comprensión de la infertilidad en los hombres.

The application of chromosome abnormality chip detection in male infertility.

OBJECTIVE: To discuss the application of microarray technology in the diagnosis of male infertility. METHODS: Sixteen loci, including a sex-determining region on the Y chromosome, were investigated by polymerase chain reaction (PCR) in infertile male patients. Chromosome abnormality chip with 180 000 probes was used to detect small deletion, small amplification and loss of heterozygosity. RESULTS: By PCR, nine of 103 infertile patients were found to have sequence-tagged site microdeletions. Microdeletions were not observed in control samples. The deletions detected by PCR were present in six azoospermic men (6/44, 13.6%) and in three oligoasthenoteratozoospermic (OATS) men (3/59, 5%).The overall frequency of microdeletions in infertile men was 8.7% (9/103). Chromosome abnormality chip detection 500+ detected more amplification or deletion in 51 infertile patients and the overall frequency of microdeletions in infertile men was 49.5% (51/103). CONCLUSION: Chromosome abnormality chip detection system provides a sensitive, economic and high-throughput method for detecting the deletion or amplification of genomic DNA sequences of infertile patients. Not only can it identify Yq deletions, but it can also find other chromosome abnormalities and facilitate the understanding of male infertility.

α4 is highly expressed in carcinogen-transformed human cells and primary human cancers.

A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.

Thin sectional anatomy, three-dimensional reconstruction and visualization of the heart from the Chinese Visible Human.

The research aimed to provide sectional anatomic and three-dimensional (3D) virtual anatomic bases for imaging diagnosis and surgical operation by the use of data from the heart of the first Chinese digitized Visible Human. Data from the series of thin sections of the heart were analyzed and input into an SGI workstation, and 3D reconstruction and virtualization of the heart were performed. Each image of sectional anatomy was clear and the 3D structures of the heart were reconstructed in their entirety. All reconstructed structures can be displayed by multiple structural and color modes, individually or jointly, and can be rotated continuously in any plane. The model of the virtual heart clearly showed fine structures of the heart in random orientation. The dataset of the sectional anatomy provides a fine and integrated morphologic base for imaging diagnosis. The 3D reconstructed images clearly show the internal and entire structures of the heart.

Visualization of the temporal bone of the Chinese Visible Human.

Temporal bone anatomy is very difficult to understand. After dataset acquisition of the first Chinese Visible Human, we processed the two-dimensional images to build a digitized visible model of the temporal bone and explore the role of virtual endoscopy in the inner ear. On a SGI workstation three-dimensional computer reconstructions of the ear were generated from the Chinese visible human dataset, viewing the middle and inner ear imitating the traditional otoscopy. The three-dimensional data of the temporal bone were then converted to STL format, and the temporal bone replica were fabricated with rapid prototyping by laminated object manufacturing. The virtual model of the ear was successfully completed, and the virtual endoscopy improved three-dimensional visualization of the middle and inner ear. Physical replica of the temporal bone were built with paper; the accuracy was +/-0.2 mm. The reconstructed model and the replica of the temporal bone can be used to make preoperative plans in the complicated otoneurosurgical operations, allowing various surgical exercises to be carried out on the three-dimensional stereophysical model. The virtual endoscopy stands as a promising new visualization technique for elucidation of the middle and inner ear and reveals a tremendous potential in both clinical and educational settings, providing morphological data for the image diagnosis and otoneurosurgery.