Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms.

The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.

The 3-dimensional miniplate is more effective than the standard miniplate for the management of mandibular fractures: a meta-analysis.

PURPOSE: The study aimed to determine the superiority between 3-dimensional (3D) miniplate and standard miniplate for mandibular fractures (MFs) treatment. BACKGROUND: Controversial results on the use of standard miniplate and 3D miniplate have remained for management of MFs. METHODS: Several electronic databases were retrieved up to September 2014 to identify eligible studies. The quality of studies was assessed, and the relative risk (RR) with its corresponding 95% confidence interval (CI) was assessed to measure the effect size. Subgroup analyses by different fracture regions and different 3D miniplate sizes were performed. Publication bias was measured by a funnel plot. RESULTS: There were 13 studies included for the meta-analysis, consisting of 593 participants. The 3D miniplate achieved significant lower incidences of malocclusion (RR 0.43, 95% CI 0.24-0.77, P = 0.004) and hardware failure (RR 0.31, 95% CI 0.13-0.74, P = 0.008) than the standard miniplate. There were no significant differences between the two miniplates on the incidence of the remaining outcomes: wound dehiscence, infection, paresthesia, and nonunion/malunion. Subgroup analyses indicated that 3D miniplate caused a lower hardware failure than standard with the size of 8 or 10 holes (RR 0.23, 95% CI 0.08-0.66, P = 0.006). Besides, publication bias was not detected. CONCLUSION: The 3D miniplate is superior to the standard miniplate on the reduction of postoperative complication rates for the management of MFs. More holes in the 3D miniplate might contribute to a successful treatment.

Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

The aim of the present study was to identify potential therapeutic target genes and miRNAs for primary myelofibrosis (PMF). The dataset GSE53482 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) of peripheral blood (PB) cluster of differentiation (CD)34+ cells from PMF patients (PB-PMF group) and peripheral blood CD34+ cells from healthy individuals (PB-control group) were analyzed using the Linear Models for Microarray Data package in R. The Kyoto Encyclopedia of Genes and Genomes was used for pathway enrichment analysis. MiRNA-gene joint enrichment analysis was performed by ENViz and a miRNAs-gene regulatory network was constructed. A total of 1,182 DEGs (773 upregulated and 109 downregulated) and 48 DEMs (28 upregulated and 20 downregulated) were identified. According to the pathway enrichment analysis, a number of DEGs were enriched in metabolic pathways, including IDH1 and DNMT1. Other DEGs were enriched in the citrate cycle (tricarboxylic acid cycle; IDH1 and IDH3A) and certain DEGs were enriched in pyrimidine metabolism, including CARD8. For downregulated genes, certain DEGs were enriched in the spliceosome, including SF3B1 and CDC40. Furthermore, hsa-miR-127-3p, hsa-miR-140-3p and hsa-miR345 were associated with cell cycle-related biological processes, signal transduction and cell surface receptor signaling pathway. The DEM-DEG regulatory network indicated that hsa-miR-543 regulated 113 genes, including CARD8 and TIFA. The present study identified a number of genes, including IDH1, DNMT1, SF3B1 and CARD8, and miRNAs, including hsa-miR-127-3p and hsa-miR-140-3p, which may be therapeutic targets in the treatment of PMF.

Investigation of crucial genes and microRNAs in conventional osteosarcoma using gene expression profiling analysis.

The present study aimed to screen potential genes associated with conventional osteosarcoma (OS) and obtain further information on the pathogenesis of this disease. The microarray dataset GSE14359 was downloaded from the Gene Expression Omnibus. A total of 10 conventional OS samples and two non­neoplastic primary osteoblast samples in the dataset were selected to identify the differentially expressed genes (DEGs) using the Linear Models for Microarray Data package. The potential functions of the DEGs were predicted using Gene Ontology (GO) and pathway enrichment analyses. Protein­protein interaction (PPI) data were also obtained using the Search Tool for the Retrieval of Interacting Genes database, and the PPI network was visualized using Cytoscape. Module analysis was then performed using the Molecular Complex Detection module. Additionally, the potential microRNAs (miRNAs) for the upregulated DEGs in the most significant pathway were predicted using the miRDB database, and the regulatory network for the miRNAs­DEGs was visualized in Cytoscape. In total, 317 upregulated and 670 downregulated DEGs were screened. Certain DEGs, including cyclin­dependent kinase 1 (CDK1), mitotic arrest deficient 2 like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine­protein kinase (BUB1), were significantly enriched in the cell cycle phase and oocyte meiosis pathway. DEGs, including replication factor C subunit 2 (RFC2), RFC3, RFC4 and RFC5, were significantly enriched in DNA replication and interacted with each other. RFC4 also interacted with other DEGs, including CDK1, MAD2L1, NDC80 kinetochore complex and BUB1. In addition, RFC4, RFC3 and RFC5 were targeted by miRNA (miR)­802, miR­224­3p and miR­522­3p. The DEGs encoding RFC may be important for the development of conventional OS, and their expression may be regulated by a number of miRNAs, including miR­802, miR­224­3p and miR­522­3p.

Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A.

BACKGROUND: The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. METHODS: The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified. RESULTS: A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). CONCLUSION: Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A.