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Objective: The aim of the study was to examine the effects and potential mechanisms of miR-340-5p in Osteosarcoma (OS) progression., Patients and Methods: qRT-PCR was applied to detect expressions of miR-340-5p and NRF2 mRNA. MTT and transwell assay were carried out to determine the roles of miR-340-5p in OS cells viability, invasion and migration. TargetScan and Luciferase reporter assays were performed to search for the candidate target gene of miR-340-5p. The regulatory roles of miR-340-5p in OS PI3K/AKT pathway and EMT were examined by Western blot., Results: MiR-340-5p expressions were decreased in OS tissues and cells. Moreover, the decreased miR-340-5p expressions in OS tissues were frequently accompanied by shorter overall survival and malignant clinicopathologic features of OS patients. MTT assay showed that miR-340-5p upregulation prominently repressed OS cell proliferation. In addition, miR-340-5p restoration could significantly suppress OS cell invasion and migration as demonstrated by transwell assays. Results also revealed that miR-340-5p could directly target NRF2 and regulate PI3K/AKT pathway and EMT, exerting prohibitory functions in OS., Conclusions: MiR-340-5p repressed the malignant phenotypes of OS via targeting NRF2 and regulating PI3K/AKT pathway and EMT. The current study provided preclinical evidence for the potential applications of miR-340-5p/NRF2 axis in OS therapies.

Objective: To explore the expression pattern and diagnostic value of microRNA-122 (miRNA-122) in childhood Kawasaki disease (KD)., Patients and Methods: A total of 150 children with KD were included in the KD group. During the same period, 150 children with respiratory infection complicated with fever and without myocardial involvement were included in the control group.  Serum level of miRNA-122 in children with acute phase of KD and those in the control group was detected. The relationship between serum level of miRNA-122 and clinical features of KD was analyzed by Pearson correlation test. ROC curves were depicted to assess the diagnostic value of miRNA-122 in KD., Results: Serum level of miRNA-122 was higher in the KD group than controls. In the acute phase of KD, the serum level of miRNA-122 was positively correlated to CRP and NT-proBNP, while negatively correlated to the sodium level. The specificity and sensitivity of miRNA-122 in diagnosing KD was 78.67% and 84.67%, respectively (AUC=0.8861, cut-off value=2.905)., Conclusions: Serum level of miRNA-122 is significantly enhanced in the acute phase of KD, and highly expressed miRNA-122 is related to systematic inflammation. MiRNA-122 may be used as a diagnostic hallmark of KD.

Objective: To explore the influence of micro ribonucleic acid (miR)-34a on renal ischemia-reperfusion by regulating Kruppel-like factor 4 (KLF4)., Materials and Methods: A total of 36 Sprague-Dawley (SD) rats weighing 180-200 g were randomly divided into sham operation group (n=12), model group (n=12), and miR-34a inhibitor group (n=12). Renal ischemia-reperfusion modeling was performed in rats of model group and miR-34a inhibitor group. Those in the sham operation group received the same procedures without ligation. 200 μL of miR-34a inhibitor was pre-injected before modeling in rats of miR-34a inhibitor group. An automatic biochemical analyzer was used to detect serum creatinine and urea nitrogen levels in each group of rats, thus reflecting renal functions. The expressions of B-cell lymphoma 2 (Bcl-2), an apoptotic protein, and KLF4, a transcription factor, were detected via Western blotting. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assay was conducted to measure the expression levels of miR-34a and KLF4 in rat renal tissues in each group. Immunohistochemistry was employed to determine the expressions of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Additionally, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining was utilized to determine the apoptotic rate in rat kidney tissues in each group., Results: Compared with those in the sham operation group, serum creatinine level, urea nitrogen level, expressions of miR-34a, TNF-α and Bcl-2 (p<0.05) increased, while the levels of KLF4 and IL-10 (p<0.05) decreased in the model group. Apoptosis rate was also higher in the model group than the controls. In comparison with the model group, miR-34a inhibitor group had lowered serum creatinine level, urea nitrogen level, expressions of miR-34a, TNF-α and Bcl-2, and apoptotic rate (p<0.05), but raised levels of KLF4 and IL-10 (p<0.05), showing statistically significant differences., Conclusions: Downregulation of miR-34a ameliorates inflammatory response and apoptosis induced by renal ischemia-reperfusion by promoting KLF4 level, thus improving renal functions in rats.

Objective: The purpose of this study was to compare the differences of degenerative characteristics of medial, lateral regions, femoral, patellar, and tibia parts of the knee joint in the early stage of knee osteoarthritis (OA)., Patients and Methods: A total of 66 patients with early-stage knee OA and 22 healthy volunteers who have no knee-related clinical symptoms were enrolled in this cross-sectional study. T2 mapping and 3D dual-echo images were acquired with a 3.0T MR scanner. The degenerative changes of the articular cartilage were quantified by a T2 mapping and cartilage thicknesses analysis. Any structural changes were conducted using the Whole Organ Magnetic Resonance Imaging Score (WORMS)., Results: In patients with knee OA, the thicknesses of medial cartilages were significantly thinner than lateral ones (2.13 mm vs. 2.34 mm, p<0.0001), but with higher T2 values (40.38 ms vs. 38.4 ms, p<0.0001) and WORMS scores (12.12 vs. 0.47, p=0.004). No significant differences were observed between medial and lateral cartilage in the healthy volunteers. The T2 values of the femoral (p<0.001) and patellar (p=0.012) cartilages of OA patients were higher than that of the healthy controls. Within OA group, the T2 values of femoral (p<0.0001) and patellar (p<0.0001) cartilages were higher than tibial ones. Moreover, the WORMS scores of femoral (p=0.001) and patellar (p<0.0001) cartilages were higher than that of the tibial ones., Conclusions: This study demonstrates that the medial compartment and patellofemoral knee joint degenerate more severely in patients with early-stage knee OA.

Objective: To investigate the expression characteristics and the potential role of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) in the clinical pathology and prognosis of prostate cancer (PCa)., Patients and Methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of EHMT2 in 55 pairs of PCa tissues and adjacent normal tissues. The relationship between EHMT2 expression and the pathological features, as well as the prognosis of PCa patients was analyzed. EHMT2 expression in PCa cells was determined by qRT-PCR as well. In addition, EHMT2 knockdown model was constructed by transfection of the small interfering RNA in PCa cell lines PC-3 and DU-145. The regulatory effects of EHMT2 on the behaviors of PCa cells were evaluated through cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay and flow cytometry. Finally, we detected the protein levels of relative genes in PI3K/AKT/mTOR pathway through Western blot., Results: QRT-PCR results showed that the expression level of EHMT2 in PCa tissues was markedly higher than that in adjacent normal tissues. Compared with PCa patients with low expression of EHMT2, those with high expression of EHMT2 had higher pathological grade and lower overall survival. EHMT2 was also highly expressed in PCa cell lines. Knockdown of EHMT2 inhibited the proliferative potential and induced apoptosis of PCa cells. Western blot results revealed that PCa cells with EHMT2 knockdown presented downregulated p-PI3K, p-AKT and p-mTOR., Conclusions: EHMT2 was highly expressed in PCa, and its expression is closely correlated with tumor stage and poor prognosis of PCa patients. EHMT2 promoted the malignant progression of PCa by inhibiting PI3K/AKT/mTOR pathway.

Objective: Monomethyl fumarate (MF) exerts anti-inflammatory and antioxidant capacities. Whether microRNA-139 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) are involved in the pharmacological activity of MF remain unclear. We aim to elucidate the potential function of MF in intracerebral hemorrhage (ICH), and its possible mechanism., Materials and Methods: Twenty-four Sprague Dawley (SD) rats were randomly assigned into sham group, ICH group and MF group, with 8 rats in each group. Rats in ICH and MF group were subjected to ICH procedures. Rat brain tissues were harvested at 48 h after ICH procedures. Evans blue extravasation was performed to evaluate ICH-induced rat brain damage. Content of cerebral edema and neurological deficit were examined to reflect the neuronal pathological lesions. Reactive oxygen species (ROS) content in rat brain was examined by immunofluorescence. Activities of oxidative stress indexes in rat brain homogenate were detected using relative commercial kits. MicroRNA-139 expression in rat brain was quantified by quantitative Real-time polymerase chain reaction (qRT-PCR). Finally, protein levels of Nrf2, HO-1, NQO1 and nuclear factor-kappa B (NF-κB) in rat brain tissues were examined by Western blot., Results: Compared with rats in sham group, neurological deficit scores of rats in ICH group were lower. Disruption of blood-brain barrier and brain tissue edema of rats were pronounced in ICH group. However, MF pretreatment markedly alleviated the above mentioned cerebral lesions. In addition, MF pretreatment increased activities of SOD, GSH and CAT, but decreased MDA and ROS contents in rat brain homogenate relative to those in ICH group (p<0.05). Western blot analysis found that expression levels of Nrf2, HO-1 and NQO-1 were markedly upregulated after MF pretreatment, while the expression level of NF-κB was downregulated. At the cellular level, we altered microRNA-139 expression in SH-SY5Y cells by transfection of microRNA-139 mimics or inhibitor. Overexpression of microRNA-139 remarkably increased Nrf2 expression and decreased NF-κB expression. Treatment of high-dose MF upregulated Nrf2, downregulated NF-κB and decreased ROS content in SH-SY5Y cells., Conclusions: MF protects ICH in rats by inhibiting oxidative stress and inflammatory response through activating microRNA-139/Nrf2 axis.

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/β-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/β-catenin signaling. Targeting CENPU could be a promising therapeutic strategy for patients with CENPU.

Objective: To investigate the impact of tissue glue on mast cells (MC) and epidermal growth factor receptor (EGFR) in rat peptic ulcer., Materials and Methods: SD rats were used to establish peptic ulcer model. Cimetidine gavage was adopted in the positive control, while cimetidine and endoscopic tissue glue therapy were applied in the experimental group. The ulcer inhibition rate and ulcer index were measured to evaluate healing quality. Real-time PCR was performed to test EGFR mRNA in the ulcer surrounded gastric mucosa. Immunohistochemistry was selected to determine MC quantity. HE staining and apoptosis detection were used to evaluate cell apoptosis., Results: Tissue glue significantly reduced MC number in the peptic ulcer rat compared with control with dose dependence (p < 0.05). Tissue glue significantly decreased ulcer area, and elevated ulcer index and inhibition rate (p < 0.05). EGFR mRNA in the mucosa markedly declined after modeling. Tissue glue upregulated EGFR mRNA to a certain extent (p > 0.05). Tissue glue induced MC apoptosis with dose dependence., Conclusions: Endoscopic application of tissue glue accelerated ulcer mucosa healing via up-regulating EGFR mRNA, enhancing gastrointestinal mucous membrane regeneration and repair ability, and decreasing MC number.

Objective: Aim of this study was to investigate the association of the FTO rs9939609 polymorphism with the effects of the exercise and dietary intervention on obese adolescents and children in China., Patients and Methods: Total 138 chinese children and adolescents (77 males and 61 females, aged 10-18 years) were recruited in the 2012 summer camp in Shanghai. Dietary and exercise intervention was performed for four weeks. Obesity related parameters were detected by the physical examination before and after four-week's intervention. Genotyping of the FTO rs9939609 was performed by using a TaqMan SNP Genotyping Assay. SPSS 19.0 were used to do the statistical analysis., Results: Finally, 135 campers were investigated in this study. The AA, AT and TT genotype frequencies of rs9939609 were 5.2%, 33.3% and 61.5%, respectively. The BMI in individuals with the genotype AA (or AT) was significantly higher compared with their with TT genotype (p = 0.044). The levels of body mass index (BMI), insulin (INS), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), red blood cell (RBC), Hemoglobin (HB) and hematocrit (HCT) in campers were significantly declined by the combined intervention (p < 0.05). Moreover, the levels of TC, low-density lipoprotein (LDL), RBC, HB, and HCT in the camper with genotype AA (or AT) were significantly decreased by the combined intervention compared with the camper with genotype TT (p < 0.05)., Conclusions: The effects of exercise combined with dietary intervention on obesity were associated with the FTO rs9939609 polymorphism in chinese adolescents and children.