Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the progression of human cancers, including colorectal cancer (CRC). The study of genome-wide lncRNA expression patterns in metastatic CRC could provide novel mechanism underlying CRC carcinogenesis. In here, we determined the lncRNA expression profiles correlating to CRC with or without lymph node metastasis (LNM) based on microarray analysis. We found that 2439 lncRNAs and 1654 mRNAs were differentially expressed in metastatic CRC relative to primary CRC. Among these dysregulated lncRNAs, FBXL19-AS1 was the most significantly upregulated lncRNA in metastatic tumors. Functionally, knockdown of FBXL19-AS1 played tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Overexpression of FBXL19-AS1 was markedly correlated with TNM stage and LNM in CRC. Bioinformatics analysis predicted that miR-203 was potentially targeted by FBXL19-AS1, which was confirmed by dual-luciferase reporter assay. Pearson's correlation analysis showed that miR-203 expression was negatively related to FBXL19-AS1 in tumor tissues. Finally, miR-203 inhibition abrogated the effect of FBXL19-AS1 knockdown on the proliferation and invasion of LoVo cells. Our results reveal the cancer-promoting effect of FBXL19-AS1, acting as a molecular sponge in negatively modulating miR-203, which might provide a new insight for understanding of CRC development.Read more
The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3β. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3β, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.Read more
Aldehyde dehydrogenase proteins consist of a superfamily and the family 7 (ALDH7) is a typical group with highly conserved proteins across species. It catalyzes oxidation of α-aminoadipic semialdehyde (AASA) in lysine degradation, participates in protection against hyperosmotic stress, and detoxifies aldehydes in human; however, its function in plants has been much less documented. Here we reported a mutant with yellow-colored endosperm in rice, and showed that the yellow endosperm was caused by mutation of OsALDH7. OsALDH7 is expressed in all tissues detected, with the highest level in mature seeds. We found that oryzamutaic acid A accumulated during late seed development and after a year-long storage in the colored endosperm, whereas it was undetectable in the wild type endosperm. Moreover, lysine degradation was enhanced in yeast over-expressing OsALDH7 and as a result, content of lysine, glutamate and saccharopine was changed, suggesting a role of OsALDH7 in lysine catabolism.Read more
Mental rotation performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. Previous studies suggest depressive patients present the correlates of impaired behavioural performance for mental rotation and psychomotor disturbance. The aim of this study is to compare the mental rotation abilities of patients with a first episode of depression, recurrent depression and healthy control subjects with regard to hand tasks.
We tested 32 first episode of depression, 38 recurrent depression and 36 healthy control subjects by evaluating the performance of depressed patients with regard to the hand mental rotation tasks.
First, the first episode and recurrent depression subjects were significantly slower and made more errors than controls in mentally rotating hands. Second, the first depressive episode but not the recurrent depression displayed the same pattern of response times to stimuli at various orientations relative to control subjects in the hand task. Third, in particular, recurrent depression subjects were significantly slower and made more errors during the mental transformation of hands than first depressive episode relative to control subjects and the differences were significantly larger in female than male subjects in the mental rotation hand task.
Patients were on antidepressant medication.
These results suggest that the impaired behavioural performance for mental representation processing are related to the number of previous episodes. Moreover, the recurrent major depressive episodes may contribute to the reinforcement of cognitive impairments and further the development or maintenance of mental representation dysfunctions, especially in female patients. A deficit on mental rotation in the depressive patients may be potential biomarkers for recurrence chronically.Read more
A number of pathogens for which there are no effective treatments infect the cells via endocytosis. Once in the endosomes, the pathogens complete their life cycle by overriding normal lysosomal functions. Recently, our laboratory identified the lysosomal targeting signal of prosaposin, which is recognized by the sorting receptor "sortilin". Based on this evidence, we tested whether the antimicrobial peptide β-Defensin linked to the targeting sequence of prosaposin (βD-PSAP) could be redirected from its secretory pathway to the endolysosomal compartment. To this effect, βD-PSAP was transfected into COS-7 cells. The sub-cellular distribution of βD-PSAP was analyzed by confocal microscopy and differential centrifugation. Confocal microscopy demonstrated that βD-PSAP overlaid with the lysosomal marker LAMP1, indicating that the construct reached endosomes and lysosomes. Differential centrifugation also showed that βD-PSAP was in the lysosomal fractions. In addition, our binding inhibition assay demonstrated that βD-PSAP bound specifically to sortilin. Similarly, the delivery of βD-PSAP was abolished after overexpressing a truncated sortilin. These results indicate that the prosaposin C-terminus and D/C-domain (prosaposin targeting sequence) was an effective "guidance system" to redirect βD-PSAP to the endolysosomal compartment. In the future, this and other fusion proteins with antimicrobial properties will be assembled to our "biotic vehicle" to target pathogens growing within these compartments.Read more
To examine the altered spontaneous brain activity in patients with social anxiety disorders (SAD) before and after cognitive behavior therapy (CBT),and determine the neuromechanism of formation,treatment and recovery of SAD.
Fifteen SAD patients were treated with an eight-week group CBT.The patients underwent functional magnetic resonance imaging (fMRI) at resting state before and after the treatments.Eighteen healthy controls (HC) were recruited and underwent a baseline fMRI scan.The regional homogeneity (ReHo) of the patients was compared with the healthy controls.Before the baseline scanning,all participants were assessed with the Liebowitz Social Anxiety Scale(LSAS),the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD).
All participants were right-handed.10 males and 4 females were in the patient group,with mean age of (27.07±8.11) years.13 males and 5 females were in the HC group,with mean age of (26.28±2.42) years.There was no difference for gender and age while significant differences were found in LSAS,HAMA,HAMD between patients and controls (P<0.01).After 8 weeks of group CBT,clinical assessments significantly decreased (P<0.05) in patients group.Compared with HC,the pre-treatment SAD patients showed significantly increased ReHo in right cerebellum lobe at baseline [(P<0.05,with Gaussian random field (GRF) correction]; but the difference became insignificant after the group CBT.The post-treatment patients showed increased ReHo in left putamen and right caudate compared with their pre-treatment conditions (P<0.05,with GRF correction).Pre-post ReHo change in right cerebellum posterior in patients was positively correlated with pre-post change of LSAS-fear scores (r=0.62,P=0.015).
The activity of cerebellum might be one of the potential biomakers to modulate the treatment effect of CBT in SAD,which provides a basis for further investigation into the pathophysiology of SAD.Read more
To investigate the expression of advanced glycation end products (AGEs) and the receptor for AGE (RAGEs) in maternal blood, umbilical blood and placental tissues in women with severe preeclampsia (sPE) as well as any association with inflammatory processes.
The expressions of AGEs, RAGE, tumor necrosis factor-alpha (TNF)-α and vascular cell adhesion molecule-1 (VCAM)-1 in placental tissues were measured using immunohistochemistry. The levels of AGEs, RAGE, TNF-α and VCAM-1 in maternal blood, umbilical blood and placental extracts were assessed using enzyme-linked immunosorbent assays. Placental RAGE, TNF-α and VCAM-1 mRNA expression levels were determined by PCR. Placental AGEs, RAGE, TNF-α and VCAM-1 protein levels were determined by western blotting.
The levels of AGEs, TNF-α and VCAM-1 in the maternal tissues and umbilical blood were significantly higher in the sPE group than in the normal pregnancy (NP) controls (p < 0.05). The serum level of sRAGE in the umbilical blood was lower in the sPE group than in the NP controls (p < 0.05), while sRAGE was higher in the maternal blood of sPE than in the NP (p < 0.05). The maternal serum levels of AGEs were positively correlated with that of TNF-α and VCAM-1 in the maternal blood. There were no correlations between the levels of RAGE, TNF-α or VCAM-1 in maternal blood or umbilical serum. There were no correlations between the levels of sRAGE and TNF-α or VCAM-1 in maternal blood or umbilical serum. The levels of AGEs were positively correlated with those of TNF-α and VCAM-1 in placental lysates.
AGEs and RAGE appear to act as important mediators in regulating the inflammatory pathways of preeclampsia.Read more
In this work, by employing halogen elements (fluorine, chlorine, bromine, and iodine) as dopant we demonstrate a unique strategy to enhance the output performance of ZnO-based flexible piezoelectric nanogenerators. For a halogen-doped ZnO nanowire film, dopants and doping concentration dependent lattice strain along the ZnO c-axis are established and confirmed by the EDS, XRD, and HRTEM analysis. Although lattice strain induced charge separation was theoretically proposed, it has not been experimentally investigated for wurtzite structured ZnO nanomaterials. Tuning the lattice strain from compressive to tensile state along the ZnO c-axis can be achieved by a substitution of halogen dopant from fluorine to other halogen elements due to the ionic size difference between dopants and oxygen. With its focus on a group of nonmetal element induced lattice strain in ZnO-based nanomaterials, this work paves the way for enhancing the performance of wurtzite-type piezoelectric semiconductor nanomaterials via lattice strain strategy which can be employed to construct piezoelectric nanodevices with higher efficiency in a cost-effective manner.Read more
The carbon tetrachloride (CCl(4))-treated model involving mature Sprague-Dawley rats has been historically relied upon to study liver injury and regeneration and to test drug efficacy and disposition. However, there few studies about phase II metabolic enzymes changes in CCl(4)-model rats. The metabolic and excretion tests of phenacetin and acetaminophen (APAP), and the mRNA test of cytochrome P4501A2 (CYP1A2) and phase II metabolic enzymes [sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A6 (UGT1A6)] were studied in model rats after CCl(4) pretreatment. The result showed that the function and structure of liver and kidney was impaired by CCl(4) pretreatment, and a significant difference has been observed in the mRNA content of CYP1A2 (p<0.01) in model group, but there was no significant difference on the mRNA content of SULT1A1 and UGT1A6 in both groups. Compared to the control group, a significant higher content of phenacetin (p<0.01) and sulfate-APAP (AS, p<0.01) was observed in the metabolic tests of phenacetin and APAP. Statistically significant differences in cumulative urinary excretion levels of APAP, AG and AS for CCl(4) model rats were observed also. We have shown that impaired disposition of probe drugs in this model was due to both liver and kidney dysfunction in CCl(4)-model rats and we should consider the development of a new liver damage model without renal impairment.Read more