Identification of a nine-gene prognostic signature for gastric carcinoma using integrated bioinformatics analyses.

BACKGROUND: Gastric carcinoma (GC) is one of the most aggressive primary digestive cancers. It has unsatisfactory therapeutic outcomes and is difficult to diagnose early. AIM: To identify prognostic biomarkers for GC patients using comprehensive bioinformatics analyses. METHODS: Differentially expressed genes (DEGs) were screened using gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases for GC. Overlapping DEGs were analyzed using univariate and multivariate Cox regression analyses. A risk score model was then constructed and its prognostic value was validated utilizing an independent Gene Expression Omnibus dataset (GSE15459). Multiple databases were used to analyze each gene in the risk score model. High-risk score-associated pathways and therapeutic small molecule drugs were analyzed and predicted, respectively. RESULTS: A total of 95 overlapping DEGs were found and a nine-gene signature (COL8A1, CTHRC1, COL5A2, AADAC, MAMDC2, SERPINE1, MAOA, COL1A2, and FNDC1) was constructed for the GC prognosis prediction. Receiver operating characteristic curve performance in the training dataset (The Cancer Genome Atlas-stomach adenocarcinoma) and validation dataset (GSE15459) demonstrated a robust prognostic value of the risk score model. Multiple database analyses for each gene provided evidence to further understand the nine-gene signature. Gene set enrichment analysis showed that the high-risk group was enriched in multiple cancer-related pathways. Moreover, several new small molecule drugs for potential treatment of GC were identified. CONCLUSION: The nine-gene signature-derived risk score allows to predict GC prognosis and might prove useful for guiding therapeutic strategies for GC patients.

Current status and future prospects of stem cell therapy in Alzheimer's disease.

Alzheimer's disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of ß-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only alleviate the symptoms without curing the disease, which is a serious issue and influences the quality of life of the patients and their caregivers. In recent years, stem cell technology has provided new insights into the treatment of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Currently, the main sources of stem cells include neural stem cells, embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells. In this review, we discuss the pathophysiology and general treatment of Alzheimer's disease, and the current state of stem cell transplantation in the treatment of Alzheimer's disease. We also assess future challenges in the clinical application and drug development of stem cell transplantation as a treatment for Alzheimer's disease.

Propofol elicits autophagy via endoplasmic reticulum stress and calcium exchange in C2C12 myoblast cell line.

In this study, we investigated the relationship between propofol and autophagy and examined whether this relationship depends on ER stress, production of ROS (reactive oxygen species), and disruption of calcium (Ca2+) homeostasis. To this end, we measured C2C12 cell apoptosis in vitro, along with Ca2+ levels; ROS production; and expression of proteins and genes associated with autophagy, Ca2+ homeostasis, and ER stress, including LC3 (microtubule-associate protein 1 light chain 3), p62, AMPK (adenosine 5'-monophosphate (AMP)-activated protein kinase), phosphorylated AMPK, mTOR (the mammalian target of rapamycin), phosphorylated mTOR, CHOP (C/BEP homologous protein), and Grp78/Bip (78 kDa glucose-regulated protein). We found that propofol treatment induced autophagy, ER stress, and Ca2+ release. The ratio of phosphorylated AMPK to AMPK increased, whereas the ratio of phosphorylated mTOR to mTOR decreased. Collectively, the data suggested that propofol induced autophagy in vitro through ER stress, resulting in elevated ROS and Ca2+. Additionally, co-administration of an ER stress inhibitor blunted the effect of propofol.

Enhanced differentiation of human amniotic fluid-derived stem cells into insulin-producing cells in vitro.

AIMS/INTRODUCTION: To investigate the ability of human amniotic fluid stem cells (hAFSCs) to differentiate into insulin-producing cells. MATERIALS AND METHODS: hAFSCs were induced to differentiate into pancreatic cells by a multistep protocol. The expressions of pancreas-related genes and proteins, including pancreatic and duodenal homeobox-1, insulin, and glucose transporter 2, were detected by polymerase chain reaction and immunofluorescence. Insulin secreted from differentiated cells was tested by enzyme-linked immunosorbent assay. RESULTS: hAFSCs were successfully isolated from amniotic fluid that expressed the pluripotent markers of embryonic stem cells, such as Oct3/4, and mesenchymal stem cells, such as integrin ß-1 and ecto-5'-nucleotidase. Here, we first obtained the hAFSCs that expressed pluripotent marker stage-specific embryonic antigen 1. Real-time polymerase chain reaction analysis showed that pancreatic and duodenal homeobox-1, paired box gene 4 and paired box gene 6 were expressed in the early phase of induction, and then stably expressed in the differentiated cells. The pancreas-related genes, such as insulin, glucokinase, glucose transporter 2 and Nkx6.1, were expressed in the differentiated cells. Immunofluorescence showed that these differentiated cells co-expressed insulin, C-peptide, and pancreatic and duodenal homeobox-1. Insulin was released in response to glucose stimulation in a manner similar to that of adult human islets. CONCLUSIONS: The present study showed that hAFSCs, under selective culture conditions, could differentiate into islet-like insulin-producing cells, which might be used as a potential source for transplantation in patients with type 1 diabetes mellitus.

Biological roles of microRNA-140 in tumor growth, migration, and metastasis of osteosarcoma in vivo and in vitro.

The objective of this study was to explore the biological roles of microRNA-140 (miR-140) in tumor growth, migration, and metastasis of osteosarcoma (OS) in vivo and in vitro. Between 2007 and 2014, 47 cases of OS samples and normal bone tissue samples adjacent to OS were selected from our hospital. Tissue biopsies from OS patients were used to measure miR-140 levels to obtain a correlation between clinicopathological features and miR-140 expression. In vitro, MG63 human osteosarcoma cells were divided into four groups: blank group, miR-140 mimic group, miR-140 inhibitor group, and negative control (NC; empty plasmid) group. qRT-PCR was used to detect miR-140 expression, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and scratch migration assay was used to detect cell migration. In vivo, the relative expression of miR-140 level in OS tissue was lower than that in the adjacent normal bone tissue. miR-140 expression is inversely correlated with tumor size, Enneking stage, and tumor metastasis. In vitro, compared with blank group and NC group, relative miR-140 expression was increased, cell proliferation was inhibited, cell population in G0/G1 phase was increased, cell population in G2/M phase and S phases and proliferation index (PI), and cell migration distance were decreased in the miR-140 mimic group, but the relative expression and all the cell indexes were found opposite trend in the miR-140 inhibitor group. In conclusion, in vivo and vitro findings provided evidence that miR-140 could inhibit the growth, migration, and metastasis of OS cells.