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Diabetes mellitus complicated with cerebral infarction (DMCI) has a high incidence and disability rate. Therefore, identification of biomarkers for the early prediction of the development and progression of cerebral infarction (CI) is of great significance for the prevention and treatment of this disease. The roles of serum homocysteine (Hey), interleukin-1β (IL-1β), and fasting blood glucose (FBG) in DMCI and their correlations with carotid intima-media thickness (CIMT) were explored. A total of 124 patients with DMCI (DMCI group) and 103 patients with diabetes mellitus (DM) (DM group) admitted to the People's Hospital of Liuhe District of Nanjing were enrolled in this study. A further 100 healthy controls undergoing physical examinations during the same period (HC group) were also enrolled. CIMT value was detected by carotid artery ultrasound. Hey and FBG levels were determined by a fully automatic biochemical analyzer. The IL-1β level was detected by enzyme-linked immunosorbent assay (ELISA). The levels of Hey, IL-1β, and FBG and the CIMT value in the DMCI and DM groups were significantly higher than those in the HC group (P<0.001). The levels and the value in the DMCI group were significantly higher than those in the DM group (P<0.001). Hey, IL-1β, and FBG levels were positively correlated with CIMT value (r=0.542, P<0.001; r=0.522, P<0.001; r=0.402, P<0.001). Receiver operating characteristic (ROC) curves showed that the sensitivity and specificity of Hey for diagnosing DMCI were 86.29 and 80.58%; those of IL-1β were 68.55 and 86.41%; those of FBG were 69.35 and 88.35%. Multivariate logistic regression analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Hey, IL-1β, FBG, and CIMT were independent risk factors for DMCI (P<0.05). In conclusion, patients with DMCI have severe atherosclerosis. Hey, IL-1β, and FBG are involved in the development and progression of DMCI, so they can be used as predictive markers for the disease. Hey, IL-1β, FBG, and CIMT are independent risk factors for patients with DMCI. [ABSTRACT FROM AUTHOR]

Guilt by association (GBA) algorithm has been widely used to predict gene functions statistically, and a network-based approach may increase the confidence and veracity of identifying molecular signatures for diseases. The aim of the present study was to suggest a gene ontology (GO)-based method by integrating the GBA algorithm and network, to identify key gene functions for spinal muscular atrophy (SMA). The inference of predicting key gene functions was comprised of four steps, preparing gene lists and sets; extracting differentially expressed genes (DEGs) using microarray data [linear models for microarray data (limma)] package; constructing a co-expression matrix on gene lists using the Spearman correlation coefficient method; and predicting gene functions by GBA algorithm. Ultimately, key gene functions were predicted according to the area under the curve (AUC) index for GO terms and the GO terms with AUC >0.7 were determined as the optimal gene functions for SMA. A total of 484 DEGs and 466 background GO terms were regarded as gene lists and sets for the subsequent analyses, respectively. The predicted results obtained from the network-based GBA approach showed 141 gene sets had a good classified performance with AUC >0.5. Most significantly, 3 gene sets with AUC >0.7 were denoted as seed gene functions for SMA, including cell morphogenesis, which is involved in differentiation and ossification. In conclusion, we have predicted 3 key gene functions for SMA compared with control utilizing network-based GBA algorithm. The findings may provide great insights to reveal pathological and molecular mechanism underlying SMA. [ABSTRACT FROM AUTHOR]

We investigated the correlation between the methylation levels of peroxisome proliferator-activated receptor-α (PPAR-α) in the peripheral blood and atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus (DM). A total of 50 normal subjects (group N) and 50 NAFLD patients with DM (group M) were selected at Qilu Hospital of Shandong University. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in groups N and M were detected. The mRNA and protein expressions of PPAR-α in groups N and M were detected using reverse transcription polymerase chain reaction (PCR) and immunofluorescence. The differences in expression of PPAR-α in group N and M and the correlation between PPAR-α methylation level and atherosclerosis were analyzed using SPSS17.0 statistical software. TC, TG, HDL and LDL in groups N and M were significantly different (P<0.01). Hematoxylin and eosin staining showed that the histopathological damage was severe in group M. PCR and immunofluorescence showed that PPAR-α was significantly higher in N than in group M (P<0.01). The abnormal expression of PPAR-α is closely related to atherosclerosis, indicating that the correlation between PPAR-α methylation levels in peripheral blood and atherosclerosis of NAFLD patients with DM can provide a new direction of diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The correlation between the methylation levels of peroxisome proliferator-activated receptor-α (PPAR-α) in the peripheral blood and the inflammatory factors associated with non-alcoholic fatty liver disease (NAFLD) patients with diabetes mellitus (DM) was investigated. Thirty-two samples of normal liver tissues (group N) and 35 samples of liver tissues from NAFLD patients with DM (group M) were used for the present study. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured using commercially available kits. The accumulation of lipid droplets and glycogen in the two groups was determined through Oil Red O staining and Sudan III staining. mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-1β) and IL-6 in liver tissues of groups N and M were detected using reverse transcription-polymerase chain reaction (RT-PCR). In addition, western blotting was used to detect the protein expression of PPAR-α in liver tissues of both groups. The Statistical Product and Service Solutions (SPSS) 17.0 statistical software was used to analyze the expression difference of PPAR-α in liver tissues in the groups. The high levels of ALT and AST indicated severe liver injury in group M. Oil Red O staining and Sudan III staining showed a large number of lipid droplets and glycogen accumulation in the liver of group M patients. RT-PCR showed that the expression of inflammatory factors was extremely high and that the inflammatory injury was severe in the liver of group M patients. Western blotting showed that the expression of PPAR-α in group N was significantly higher than that in group M. ANOVA results showed that the expression of PPAR-α in liver tissues of groups N and M patients were statistically significantly different (P<0.01). Therefore, the abnormal expression of PPAR-α is closely associated with the occurrence and development of NAFLD complicated with DM, and that the abnormal expression of PPAR-α is closely related to inflammatory factors. Results from the present study suggest PPAR-α has important value in the study on NAFLD complicated with DM. The expression of PPAR-α can be used as a new basis for the diagnosis and treatment of NAFLD complicated with DM. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) represent a promising alternative source of MSCs for effective periodontal regeneration. Scientific evidence has demonstrated that growth/differentiation factor.5 (GDF.5) supports regeneration of periodontal tissues and has a key role in MSC differentiation. The present study investigated the effects of recombinant human GDF.5 (rhGDF.5) on periodontal specific differentiation of iPSC.derived MSCs (iPSC.MSCs) and bone marrow mesenchymal stem cells (BMSCs). rhGDF.5 treatment in vitro significantly enhanced the expression levels of marker genes associated with osteogenesis (OCN), fibrogenesis (periostin) and cementogenesis (CAP) in the iPSC.MSCs compared with untreated controls (all P<0.05). Interestingly, the rhGDF.5.treated BMSCs failed to exhibit overexpression of periostin and CAP despite highly upregulated expression of OCN. In the presence of rhGDF.5, both the iPSC.MSCs and BMSCs demonstrated marked formation of mineralized nodules. Notably, rhGDF.5 greatly promoted periodontal specific differentiation of the iPSC.MSCs encapsulated in hyaluronic acid (HA) hydrogels in vivo as determined by immunohistochemical and immunofluorescence staining. The majority of the PKH67.labeled iPSC.MSCs implanted with rhGDF.5 exhibited strong expression of OCN, periostin and CAP. In conclusion, iPSC.MSCs demonstrate high periodontal specific differentiation potential in response to rhGDF.5 both in vitro and in vivo. The delivery of iPSC.MSCs and rhGDF.5 with HA hydrogel may have beneficial effects in regenerative periodontal therapy. [ABSTRACT FROM AUTHOR]