Liraglutide alleviates vascular injury in diabetic rabbits with lower limb vascular stenosis through regulation of RCAN1.

OBJECTIVE: The aim of the present study is to explore the possible mechanism that may have ameliorative effect of liraglutide (Lira) on diabetic lower extremity vascular stenosis. MATERIALS AND METHODS: A diabetic rabbit model of lower extremity stenosis was established and treated with Lira. The intimal hyperplasia of the lower extremity and the oxidative stress level of vascular tissue were observed and examined. Vascular smooth muscle cells (VSMCs) induced by high glucose (HG) were treated with Lira, and RCAN1 overexpressing plasmid was constructed to transfect VCMCs. RESULTS: Lira treatment showed its association in significantly improving the hyperplasia of the intima, the level of oxidative stress, and the level of homeostasis model assessment of insulin resistance (HOMA-IR) in rabbits induced by diabetes and lower limb stenosis. In addition, Lira treatment reduced the elevated expression of RCAN1 in vascular tissues induced by diabetes. Not only could Lira treatment inhibit the increase of ROS level, proliferation and migration of VSMCs induced by HG, but reduce the expression of PCNA, MMP-9 and collagen I induced by HG. Overexpression of RCAN1 in VSMCs counteracted the effect of Lira, suggesting that Lira affected the proliferation and migration of VSMCs by regulating RCAN1. CONCLUSIONS: Our findings have important implications for Lira to exert beneficial outcomes in reducing excessive neointimal formation after lower extremity vascular injury in diabetic rabbits via the regulation of RCAN1.

Long noncoding RNA LINC00858 promotes the proliferation, migration and invasion of gastric cancer cells via the miR-363-3p/FOXP4 axis.

OBJECTIVE: Long non-coding RNA (lncRNA) LINC00858 has been found to exert oncogenic activity in several types of cancers, except gastric cancer (GC). In the present study, we aimed to explore the potential role of LINC00858 in GC and the underlying molecular mechanism. PATIENTS AND METHODS: The expression patterns of LINC00858 were determined using qRT-PCR in GC samples and cell lines. Cell proliferation was examined utilizing CCK-8 assay. Cell migration and invasion were evaluated using transwell assays. We used the bioinformatics software StarBase and TargetScan to predict lncRNA-miRNA and miRNA-mRNA interactions. RESULTS: Our findings revealed that LINC00858 expression was markedly upregulated in GC tissues and cell lines. Loss-of-function experiments demonstrated that LINC00858 silencing inhibited the proliferation, migration and invasion of GC cells. Bioinformatics analysis showed that there were several complementary binding sites between LINC00858 and microRNA (miR)-363-3p, and further Luciferase reporter assay confirmed the interaction between LINC00858 and miR-363-3p. In addition, forkhead box P4 protein (FOXP4) was found to be a target gene of miR-363-3p in GC cells. FOXP4 overexpression reversed the inhibitory effects of miR-363-3p mimics on cell proliferation, migration and invasion of BGC-823 cells. CONCLUSIONS: Collectively, LINC00858 acted as an oncogene in GC via regulating miR-363-3p/FOXP4 axis, which indicated that LINC00858 might be a novel therapeutic target for the treatment of GC.

Molecular genetic map construction and QTL analysis of fruit maturation period in grapevine.

In this study, we aimed at finding the genetic regularity of grape maturation period. Early-maturing grapevine, "87-1", was used as the female parent and late-maturing, "9-22", as the male parent, to create an F1 hybrid population. A total of 149 individual plants and their parents were selected as the mapping population. Sequence-related amplified polymorphism and simple-sequence repeat analyses were performed. We performed a linkage analysis and constructed a molecular genetic map. In the obtained map, the female and male parents each covered 19 linkage groups containing 188 and 175 maker loci, respectively. The total map distances for the female and male parents were 1074.5 and 1100.2 cM, respectively, whereas the average genetic distances between each two loci were 5.7 and 7.8 cM, respectively. The interval-mapping method was used in a quantitative trait locus (QTL) analysis for fruit maturation period. A total of 12 QTLs associated with fruit maturation period were detected. These included four QTLs in the male parent genetic map that were located in linkage groups M5, M11, M14-1, and M16, with a 62.6-75.7% rate of contribution of each QTL. Another three QTLs were found in the female parent genetic map, located in linkage groups F6, F14-1, and F18, with a 72.7-77.7% rate of contribution of each QTL. Five more QTLs were detected in the consensus map, located in linkage groups LG11, LG14-1, LG16, LG17, and LG18, with 8.9-75.7% phenotypic variance explained by each QTL.

Hybrid metamaterial switching for manipulating chirality based on VO2 phase transition.

Polarization manipulations of electromagnetic waves can be obtained by chiral and anisotropic metamaterials routinely, but the dynamic and high-efficiency modulations of chiral properties still remain challenging at the terahertz range. Here, we theoretically demonstrate a new scheme for realizing thermal-controlled chirality using a hybrid terahertz metamaterial with embedded vanadium dioxide (VO2) films. The phase transition of VO2 films in 90° twisted E-shaped resonators enables high-efficiency thermal modulation of linear polarization conversion. The asymmetric transmission of linearly polarized wave and circular dichroism simultaneously exhibit a pronounced switching effect dictated by temperature-controlled conductivity of VO2 inclusions. The proposed hybrid metamaterial design opens exciting possibilities to achieve dynamic modulation of terahertz waves and further develop tunable terahertz polarization devices.

Quantitative trait locus analysis of grape weight and soluble solid content.

A grapevine hybrid population was derived from a crossing of the early-maturing female parent cultivar '87-1' and the late-maturing male parent cultivar '9-22'. A total of 149 plants were selected from the hybrid population as the mapping population, and after sequence-related amplified polymorphism and simple-sequence repeat marker analysis were conducted we constructed molecular genetic maps of the parents. The molecular linkage map of '87-1' had 19 linkage groups that contained 188 markers, with an average interval of 5.7 cM and a total distance of 1074.5 cM; the '9-22' map had 19 linkage groups that contained 175 markers, with an average interval of 7.8 cM and a total distance of 1100.2 cM. The molecular linkage map of both parents had 19 linkage groups that contained 251 markers, with an average interval of 5.0 cM and a total distance of 1264.2 cM. We used the interval mapping method to conduct a quantitative trait locus (QTL) analysis of grape weight and soluble solid content of the mapping population. Six QTLs were related to grape weight, and the average contribution to the phenotypic variance was between 11.3 and 33.0%. Seven QTLs were related to soluble solid content, and the average contribution to the phenotypic variance was between 15.7 and 55.8%.

Association between GSTM1 polymorphisms and lung cancer: an updated meta-analysis.

The relationship between glutathione S-transferase M1 (GSTM1) genetic polymorphisms and lung cancer has been reported previously. However, the results are not consistent. Therefore, to clarify the association between GSTM1 polymorphisms and lung cancer, we performed a meta-analysis based on published studies. We used the Revman 5.0 software to perform literature retrieval, article selection, data collection, and statistical analysis. We utilized a random-effect model to pool the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible studies including 5737 lung cancer patients and 6843 cancer-free control subjects were analyzed. We found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.15, 95%CI = 0.98-1.36, P = 0.08). Including only Chinese individuals, we found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.13, 95%CI = 0.97-1.32, P = 0.13). In conclusion, we found that GSTM1 polymorphisms are not associated with lung cancer risk.

Normal retinal development and retinofugal projections in mice lacking the retina-specific variant of actin-binding LIM domain protein.

The actin-binding LIM domain protein (abLIM) is the mammalian homologue of UNC-115, a protein mediating axon guidance in C. elegans. AbLIM is widely expressed with three isoforms differing from one another by the length of their amino termini. Experiments utilizing dominant-negative mutants in the chick retina suggested a role for abLIM in axon path finding in retinal ganglion cells (RGCs). To investigate which variant is involved in the regulation of mammalian RGC axon guidance, we analyzed their expression profile in mice. The longest variant, abLIM-L, is highly enriched in the ganglion cell layer. AbLIM-L is up-regulated postnatally which temporally overlaps with the period of RGC axon remodeling. In contrast, the abLIM-M and abLIM-S variants are widespread and remain relatively constant through development. By selective gene targeting, we ablated abLIM-L to explore its functional significance in vivo. AbLIM-L mutant mice exhibit no apparent morphological or functional defects in photoreceptors and inner retinal neurons. Retinofugal projections and synaptic maturation also appear normal. These data suggest that abLIM-M is likely the isoform performing the essential function related to axon guidance.

[In situ quantitative analysis of Drosophila histone gene in S-phase].

We used a novel multiparametric microfluorometry analytic system to determine the replication timing of Drosophila histone gene DNA by in situ quantitative analysis of the gene in S-phase under a fluorescent microscope. There are 110 copies of histone genes per genome and each one of them is 5 kb in size. Primary cultured embryo cells were used to make preparations for microscopic analysis. Cells were first stained with DAPI and the total nuclear DNA contents in each nucleus reflected on the fluorescent intensity. We collected data of the fluorescent intensity from 400 of the cells in S-phase (Fig. 4). Then, the very same preparation was subjected to FISH (fluorescent in situ hybridization) using biotinylated DNA probes and FITC, and the fluorescent intensity of the hybridization signals were quantitatively detected from the same 400 cells and in the same order. This data showed the relative quantity of the signals representing the histone genes. From the correlation of fluorescent intensity of DAPI and that of FITC of the cells in S-phase, we found that the histone gene DNA completed its replication during early stage in S-phase (Fig. 5). The method we introduced here is considered to be able to use in many other cases of quantitative analysis directly in cells.