Metformin Inhibits the Estrogen-mediated Epithelial-Mesenchymal Transition of Ectopic Endometrial Stromal Cells in Endometriosis.

BACKGROUND/AIM: Endometriosis is an estrogen-dependent disease characterized by the ectopic implantation and growth of endometrial tissue outside the uterus. Endometrial stromal cells (ESCs) play a crucial role in the pathogenesis of endometriosis. Epithelial-mesenchymal transition (EMT) has recently been described in endometriosis and was induced by estrogen. Metformin has been shown to inhibit EMT in various diseases, but its role in endometriosis remains unclear. MATERIALS AND METHODS: We collected endometrial tissue samples from patients with endometriosis and healthy controls and isolated primary ESCs. We performed gene expression analysis using the Gene Expression Omnibus (GEO) dataset and validated the results by immunohistochemistry in tissue samples. We also assessed the effects of metformin on the proliferation, migration and invasion of ectopic ESCs (EESCs) by Cell Counting Kit-8 and Transwell migration and invasion assays, respectively. We analyzed the protein expression of EMT-related markers (N-cadherin, vimentin, twist, and snail) and ß-catenin by Western blotting and immunohistochemistry. RESULTS: We found that vimentin was highly expressed in ectopic endometrial tissues compared to normal endometrial tissues. Metformin treatment inhibited the proliferation, migration and invasion of EESCs in a dose-dependent manner. Metformin treatment also downregulated the expression of EMT-related markers and reduced the expression and nuclear translocation of ß-catenin in EESCs. CONCLUSION: Our results suggest that metformin inhibits estrogen-induced EMT and regulates the expression of ß-catenin in EESCs. This study provides new insights into the potential therapeutic role of metformin in endometriosis.

Ovarian Clear Cell Carcinoma: Genomic Characterization, Pathogenesis and Targeted Therapy.

Ovarian clear cell carcinomas (OCCCs) are a subtype of ovarian epithelial tumors that arise from the malignant transformation of endometriosis (EMs). These tumors have distinctive molecular features, high malignant potential, low sensitivity to conventional chemotherapy, and poor prognosis. The process and mechanism of malignant transformation from EMs to OCCCs remains elusive. Elucidation of the molecular pathogenesis and drug resistance mechanism of OCCCs is essential to guide the clinical management and basic research of this disease. This paper provides a comprehensive review of the mechanisms of malignant transformation, genomic characteristics, drug resistance and targeted therapy of OCCCs. The review aims to provide new insights for the clinical management of advanced OCCCs.

A new species of bush frog (Anura, Rhacophoridae, Raorchestes) from southern Xizang, China.

Based on molecular evidence and morphological data, we describe a new species Raorchestes yadongensis sp. nov. from Yadong County, Xizang Autonomous Region, China. The new species can be distinguished based on a combination of the following characters: (1) small body size, SVL 17.8-24.1 mm in adult males; (2) head wider than long; (3) eye diameter about three times as much as tympanum diameter; (4) tympanum distinct; (5) fingers with rudimentary webbing and narrow lateral dermal fringes; relative finger lengths I < II < IV < III; number of subarticular tubercles in fingers 1, 1, 2, 1; (6) toes with rudimentary webbing and narrow lateral dermal fringes; relative toe lengths I < II < III < V < IV; number of subarticular tubercles in toes 1, 1, 2, 3, 2; inner metatarsal tubercle distinct, outer metatarsal tubercle absent; (7) tips of fingers and toes present discs, and discs pale brown or yellow in life; (8) tibiotarsal articulation reaching the tip of snout when adpressed; (9) milky nuptial pad present on the dorsal surface of first finger; (10) dorsal surface light brown with white warts, ventral surface with irregular white patches. The new species is currently known in Yadong County, Xizang, China, but may also occur in neighboring Bhutan and India. A key to Chinese species of the genus Raorchestes is also provided.

Plane-Aided Visual-Inertial Odometry for 6-DOF Pose Estimation of a Robotic Navigation Aid.

The classic visual-inertial odometry (VIO) method estimates the 6-DOF pose of a moving camera by fusing the camera's ego-motion estimated by visual odometry (VO) and the motion measured by an inertial measurement unit (IMU). The VIO attempts to updates the estimates of the IMU's biases at each step by using the VO's output to improve the accuracy of IMU measurement. This approach works only if an accurate VO output can be identified and used. However, there is no reliable method that can be used to perform an online evaluation of the accuracy of the VO. In this paper, a new VIO method is introduced for pose estimation of a robotic navigation aid (RNA) that uses a 3D time-of-flight camera for assistive navigation. The method, called plane-aided visual-inertial odometry (PAVIO), extracts planes from the 3D point cloud of the current camera view and track them onto the next camera view by using the IMU's measurement. The covariance matrix of each tracked plane's parameters is computed and used to perform a plane consistent check based on a chi-square test to evaluate the accuracy of VO's output. PAVIO accepts a VO output only if it is accurate. The accepted VO outputs, the information of the extracted planes, and the IMU's measurements over time are used to create a factor graph. By optimizing the graph, the method improves the accuracy in estimating the IMU bias and reduces the camera's pose error. Experimental results with the RNA validate the effectiveness of the proposed method. PAVIO can be used to estimate the 6-DOF pose for any 3D-camera-based visual-inertial navigation system.

Downhill Running Acutely Elicits Mitophagy in Rat Soleus Muscle.

PURPOSE: This study aimed to investigate the effects of downhill treadmill running on mitochondrial structure/function and expression levels of mitophagy-related proteins in rat skeletal muscle. METHODS: A total of 48 male adult Sprague-Dawley rats were randomly divided into a control group (C, n = 8) and an exercise group (E, n = 40). Rats in the E group were exercised on a treadmill down a 16° decline at 16 m·min for 90 min and were further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48), and 72 h (E72) postexercise subgroups (n = 8 each). At each time point, the soleus muscle was collected under full anesthesia. Mitochondrial ultrastructural changes in skeletal muscle were observed by a transmission electron microscope. The content of quantitative enzyme citrate synthase and the activities of mitochondrial respiratory chain complex II and complex IV were measured by enzyme-linked immunosorbent assay. Protein expressions of skeletal muscle cytochrome c oxidase subunit 1 (COX1), PTEN-induced putative kinase 1 (PINK1), and mitochondrial Parkin microtubule-associated protein 1 light chain 3 (LC3) were determined by Western blot. Mitochondrial colocalizations with Parkin, ubiquitin (Ub), p62/sequestosome 1 (p62), and LC3 were measured by the immunofluorescence double labeling technique. RESULTS: After downhill treadmill running, the skeletal muscle mitochondrial structure changed dramatically, and a large amount of mitophagosomes were observed; the citrate synthase content and complex II activity were significantly lower (P < 0.05), whereas complex IV activity and COX1 protein level remained unchanged; the expression levels of PINK1, Parkin, Ub, p62, and LC3 were significantly higher than those in the C group (P < 0.05 or P < 0.01). CONCLUSION: A session of downhill treadmill running activated the PINK1/Parkin pathway and facilitated mitochondrial colocalizations with Ub, p62, and LC3, causing mitophagy and mitochondrial damage within the skeletal muscle.

MicroRNA-147 suppresses proliferation, invasion and migration through the AKT/mTOR signaling pathway in breast cancer.

The Akt/mTOR pathway is considered to be the most frequently aberrantly activated pathway in human tumors. It is activated in a variety of types of tumor, and is therefore an attractive target for study, including it's potential regulation by microRNAs. A number of microRNAs (miRs) have been demonstrated to target the Akt/mTOR pathway. A previous study reported that miR-147 targets the EGFR-driven cell-cycle protein network in breast cancer. EGFR serves a crucial role upstream to Akt/mTOR. To define the function and mechanism of miR-147 in breast cancer, the present study assessed miR-147 expression in a normal mammary epithelial cell line and three breast cancer cell lines, and observed that miR-147 expression was markedly low in the highly invasive cell line, MDA-MB-231. Ectopic expression of miR-147 in MDA-MB-231 resulted in a reduction of the phosphorylation of crucial molecules in the Akt/mTOR pathway and the proliferation, invasion and migration of the cell line was also reduced. The effects of miR-147 expression are similar to that of shRNA which is specifically designed to silence the expression of Akt. The findings of the present study indicate that miR-147 suppressed the proliferation, invasion and migration of breast cancer cells through targeting the Akt/mTOR signaling pathway. As a new microRNA targeting Akt/mTOR pathway. Using miR-147 may therefore provide an effective therapeutic approach to suppress tumorigenicity in breast cancer.

Effect of bone marrow stem cell mobilisation on the expression levels of cellular growth factors in a rat model of acute tubular necrosis.

The aim of the present study was to observe the mobilisation effects of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells (BMSCs) in rats with renal ischaemia-reperfusion injury. In addition, the effects of the BMSCs on the expression levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were investigated, with the aim to further the understanding of the protective mechanisms of SCF and G-CSF in renal ischaemia-reperfusion injury. The model and treatment groups were established using a model of unilateral renal ischaemia-reperfusion injury, in which the treatment group and the treatment control group were subcutaneously injected once a day with 200 µg/kg SCF and 50 µg/kg G-CSF, 24 h after the modelling, for five consecutive days. The CD34+ cell count was measured in the peripheral blood using flow cytometry. The mRNA expression levels of HGF and EGF were determined using polymerase chain reaction analysis, while the protein expression levels of HGF and EGF were detected using immunohistochemistry. The CD34+ cell count in the peripheral blood of the treatment and treatment control groups was significantly higher compared with that in the model group (P<0.05). However, CD34 expression levels in the cells from the renal tissues of the model and treatment groups were significantly higher compared with that of the control and treatment control groups (P<0.05), with the greatest increase observed in the treatment group. The mRNA and protein expression levels of HGF and EGF in the treatment group were significantly higher compared with the model group (P<0.05). Therefore, the results indicated that a combination of SCF and G-CSF can promote the repair of acute tubular necrosis. This combination, which can mobilise sufficient numbers of BMSCs to migrate back to the injured site, is a key factor in promoting the repair of renal tubular injury. Upregulation of HGF and EGF was also shown to promote the repair of renal tubular injury.

Localization by chromosome microdissection of a recurrent breakpoint region on chromosome 6 in human B-cell lymphoma.

Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal alterations in human B-cell lymphomas. Conventional cytogenetic banding analysis and loss-of-heterozygosity (LOH) studies have detected several common regions of deletion ranging across the entire long arm (6q), with no defined recurrent breakpoint yet identified. We describe here a strategy combining chromosome microdissection and fluorescence in situ hybridization (Micro-FISH) to determine a minimal region of deletion along chromosome 6. Seven clinical cases and one cell line of follicular lymphoma containing a t(14;18) and one case of diffuse lymphoma, also with a t(14;18), were used for this study. All nine cases had previously defined abnormalities of chromosome 6 determined by cytogenetic analysis. The results of chromosome dissection were unexpected and in contrast to the suggestion of disparate breakpoints by conventional chromosome banding. Specifically, Micro-FISH analysis provided evidence for a common breakpoint at 6q11 in seven of nine cases. After Micro-FISH analysis, all of the presumed simple deletions of chromosome 6 were carefully reanalyzed and shown to actually represent either nonreciprocal translocations (three cases), interstitial deletions (five cases), or isochromosome (one case). The recurrent proximal breakpoint (6q11) was detected in seven of nine cases, with the minimal region of deletion encompassing 6q11 to 6q21. By analogy to other tumor systems, the identification of recurring breakpoints within 6q11 may suggest that a gene(s) important to the genesis or progression of follicular lymphoma can be localized to this band region.