Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγ protein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve.

Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis.

Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE-/-) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (ox-LDL) in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3'UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.

To explore potential biomarkers to accurately diagnose patients with acute pancreatitis (AP) at early stage and to auxiliary clinicians implement the best treatment options.

Hydroxyapatite can deliver drugs, and its composite material is capable of repairing bone defects in tumors. This study was conducted to evaluate the effect of composite materials on tumor growth inhibition and bone growth induction. Composites containing drug delivery compounds were synthesized by coprecipitation and freeze-drying and then characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). In addition, the effect of hydroxyapatite nanoparticles (nano-SHAP) on proliferation of an osteosarcoma cell line (MG-63) and an osteoblast cell line (MC3T3-E1) was evaluated, and its mechanism was studied. The use of nano-SHAP alone did not affect the proliferation of normal cell lines. However, nanoparticles containing different amounts of norcantharidin in the composite materials and had different inhibitory effects on osteosarcoma and different effects on osteoblasts. And, with the increase of the content of norcantharidin, the antitumor performance of the composite has been enhanced. In summary, the nano-SHAP system developed in this study is a drug delivery material that can inhibit the growth of tumors and induce the proliferation of osteoblasts.

Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.

Muscle-derived stem cells (MDSCs) possess multipotent differentiation and self-renewal capacities; however, the effects and mechanism in neuron injury remain unclear. The aim of this study was to investigate the effects of MDSCs on neuron secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the Basso, Beattie, and Bresnahan (BBB) score and number of neurons significantly increased after MDSCs' transplantation in spinal cord injury (SCI) rats. An in vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax in the MNT (MDSCs cocultured with injured neurons) group compared with the NT (injured neurons) group. Both LC3II/LC3I and β-catenin were enhanced in the MNT group, while XAV939 (a β-catenin inhibitor) decreased the expression of nuclear erythroid-related factor 2 (Nrf2) and LC3II/LC3I. Moreover, MDSCs became NSE- (neuron-specific enolase-) positive neuron-like cells with brain-derived neurotrophic factor (BDNF) treatment. The correlation analysis indicated that there was a significant relation between the level of BDNF and neuron injury. These findings suggest that MDSCs may protect the spinal cord from injury by inhibiting apoptosis and replacing injured neurons, and the increased BDNF and β-catenin could contribute to MDSCs' effects.

Wilms' tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progression. So far, their roles and related competitive endogenous RNA (ceRNA) network remain unelucidated in nephroblastoma pathogenesis. We comprehensively integrated lncRNA, microRNA (miRNA), and messenger RNA (mRNA) expression profiles from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and screened out differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network based on the information generated from miRcode, miRTarBase, TargetScan, and miRDB. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the functional characteristics of DEMs in the ceRNA network. The interaction between protein molecules was also analyzed by establishing a protein-protein interaction network. Finally, prognosis-related biomarkers were identified via survival analysis. Initially, 1647 DELs, 115 DEMis, and 3280 DEMs (|log FC| > 2; FDR < 0.01) were obtained using the R package. Next, we constructed a lncRNA-miRNA-mRNA network (ceRNA network), in which 176 DELs, 24 DEMis, and 141 DEMs were identified. Furthermore, 148 functional enrichment terms from GO were identified and 29 KEGG pathways were found to be significantly enriched. We also integrated patient clinical information to analyze the association between DERNAs and patient prognosis. We found that high expression of 8 DELs (LINC00473, AL445228.2, DENND5B-AS1, DLEU2, AC123595.1, AC135178.1, LINC00535, and LMO7-AS1) and 4 DEMs (CEP55, DEPDC1, PHF19, and TRIM36) correlated with poor survival in a patient with WT, whereas high expression of 2 DELs (MEG3 and RMST), 1 DEM (KIAA0922), and 1 DEMi (hsa-mir-200a) could possibly lead to better clinical outcomes. For the first time, the present study provided a novel insight into lncRNA-related ceRNA networks and identified potential prognostic biomarkers in Wilms' tumor.

Polycystic ovary syndrome (PCOS) is one of the most common metabolic and reproductive endocrinopathies. However, few studies have tried to develop a diagnostic model based on gene biomarkers. In this study, we applied a computational method by combining two machine learning algorithms, including random forest (RF) and artificial neural network (ANN), to identify gene biomarkers and construct diagnostic model. We collected gene expression data from Gene Expression Omnibus (GEO) database containing 76 PCOS samples and 57 normal samples; five datasets were utilized, including one dataset for screening differentially expressed genes (DEGs), two training datasets, and two validation datasets. Firstly, based on RF, 12 key genes in 264 DEGs were identified to be vital for classification of PCOS and normal samples. Moreover, the weights of these key genes were calculated using ANN with microarray and RNA-seq training dataset, respectively. Furthermore, the diagnostic models for two types of datasets were developed and named neuralPCOS. Finally, two validation datasets were used to test and compare the performance of neuralPCOS with other two set of marker genes by area under curve (AUC). Our model achieved an AUC of 0.7273 in microarray dataset, and 0.6488 in RNA-seq dataset. To conclude, we uncovered gene biomarkers and developed a novel diagnostic model of PCOS, which would be helpful for diagnosis.

To investigate the different effects on osteolysis between commercial pure Ti particles and TiAl6V4 particles obtained from prosthesis of patients with aseptic loosening.

Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs/TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population.

HNSCC is the sixth most frequent type of malignant carcinoma with a low prognosis rate. In addition, autophagy is important in cancer development and progression. The purpose of this study is to investigate the potential significance of ARGs in the diagnosis and treatment of HNSCC.