Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury.

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA­seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)]were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)­mRNA regulatory network and miRNA­target gene­pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co­expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA­mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were revealed according to the miRNA­target gene­pathway regulatory network to be related to NP. Four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.

Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury.

Our study aimed to explore the molecular mechanisms and novel target genes of neuropathic pain via bioinformatics analysis. Gene expression profiling of GSE30691 which was consisted of sciatic nerve lesion and sham control samples at 3 days, 7 days, 21 days, and 40 days (D3, D7, D21, and D40) after injury were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified for all the four time points. Overlapped DEGs for all the four time points were used for functional and weighted co-expression modular analysis. Afterwards, protein-protein interaction (PPI) network was analyzed by MCODE (Molecular Complex Detection) and BiNGO. Pathway network was constructed according to the enriched pathways of PPI network and relevant pathways selected from the Comparative Toxicogenomics Database. There were 355 overlapped DEGs for all the four time points. Two co-expression modules had significant positive correlations with disease. The top ten hub DEGs in the PPI network were Fos, Tp53, Csk, Map2k2, Stat3, Ccl2, Pxn, Tgfb1, Notch1, and Prkacb. Fos, Dusp1, Tp53, Tgfb1, and Map2k2 participated in MAPK signaling pathway, while Csk participated in chemokine signaling pathway. The expressions of Fos, Tp53, Csk, and Map2k2 were significantly increased at D3. Tp53, Csk, and Map2k2 continued overexpressing until at D7, and an elevated tendency in Csk expression could be observed until at D21. The expression of Fos reached up to the highest at D40. Fos, Tp53, Csk, and Map2k2 might be the potential biomarkers related to neuropathic pain.

Synthesis and biological evaluation of novel oleanolic acid analogues as potential α-glucosidase inhibitors.

Considerable interest has been attracted in oleanolic acid and its analogues because of their hypoglycemic activity. In this study, a series of novel oleanolic acid analogues against α-glucosidase were synthesized and their biological activities were evaluated in vitro and in vivo. In vitro α-glucosidase inhibition activity results indicated that most of the designed analogues exhibited prominent inhibition activities, especially compounds 10, 15, 16 and 26 which with the IC50 values of 0.33 ±â€¯0.01, 0.98 ±â€¯0.06, 0.69 ±â€¯0.01 and 0.72 ±â€¯0.21 µM, respectively. Enzyme kinetic studies on the most potent compounds reveled that derivatives 10, 15, 16 and 26 were noncompetitive inhibitors. Moreover, the docking studies were carried out to prove that the four compounds could interact with the hydrophobic region of the active pocket and form hydrogen bonds to enhance the binding affinity of them with the α-glucosidase. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the active compounds (10, 15, 16 and 26) against normal 3T3 cell line. Furthermore, the in vivo actual pharmacological potential studies on derivatives 10, 15, 16 and 26 showed that the hypoglycemic effects of them were comparable to that of positive control, acarbose.

[Studies on the Analytical Potential Energies for Partial Electronic States of Li(2) with Variational Algebraic Energy Consistent Method].

The full vibrational spectra especially those high-lying vibrational energies in the dissociation region of four specific electronic states 1(3)Δ(g), 33Σ(+)(g), 1(3)Σ-(g) and b(3)Π(u) have been obtained by using the improved variational algebraic method (VAM). The analytical potential energy functions (APEFs) of these electronic states are also determined with corresponding adjustable parameter λ by using the variational algebraic energy consistent method (VAECM) based on the VAM vibrational spectra. The full vibrational energies, vibrational spectroscopic constants, force constants f(n), and expansion coefficients a(n) of the VAECM potential are also tabulated for each electronic state in this study. The results show that the VAECM analytical potentials are superior to some other widely used analytical ones, and do not have the unphysical tiny barriers existing in the precious AECM potentials.