Xiao-Yan Jiang

A novel role of phospholipase A2 in mediating spinal cord secondary injury

To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI).

Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway

Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is unclear. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes. Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted in a significant increase in the expression of the oligodendrocyte-specific transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of oligodendrogliogenesis. Together, our studies provide cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is mediated by the activation of Erk pathway which involves the downstream upregulation of transcriptional factor Olig2.

Panaxydol and panaxynol protect cultured cortical neurons against Aβ25–35-induced toxicity

Amyloid beta protein (Abeta), the central constituent of senile plaques in Alzheimers disease (AD), is known to exert toxic effects on cultured neurons. In the present study, the protective effect of panaxydol (PND) and panaxynol (PNN) on Abeta25-35-induced neuronal apoptosis and potential mechanisms were investigated in primary cultured rat cortical neurons. Pretreatment of the cells with PND or PNN prior to 10 microM Abeta25-35 exposure resulted significantly in elevation of cell survival determined by MTT assay, TUNEL/Hoechst staining and western blot. Furthermore, a marked increase in calcium influx and intracellular free radical generation was found after Abeta25-35 exposure, which could be almost completely reversed by pretreatment of PND or PNN. PND and PNN could also alleviate Abeta25-35-induced early-stage neuronal degeneration. These results indicated that inhibition of calcium influx and free radical generation is a mechanism of the anti-apoptotic action of PND and PNN. Since Abeta plays critical roles in the pathogenesis of AD, these findings raise the possibility that PND and PNN reduce neurodegeneration in AD.

Methods for isolating highly-enriched embryonic spinal cord neurons: A comparison between enzymatic and mechanical dissociations

Spinal cord neuronal culture is a useful system to study normal and abnormal functions of the spinal cord. For many bioassays, obtaining large quantities of highly purified spinal cord neurons is required. However, technical difficulties exist in obtaining these cells reliably and consistently. By comparing two dissociation methods, mechanical and enzymatic dissociations, we found that the enzymatic dissociation of embryonic day 14-15 spinal cords resulted in significantly higher cell yield than the mechanical dissociation (25.40 +/- 5.41 x 10(6) versus 3.43 +/- 0.52 x 10(6) cells per 12 embryos; n = 6/group; p < 0.01). Furthermore, cell viability was significantly higher after the enzymatic than the mechanical dissociation (83.40 +/- 3.08% versus 32.81 +/- 3.49%, n = 4/group; p < 0.01). In both methods, highly purified populations of primary neurons were obtained (mechanical: 85.17 +/- 2.84%; enzymatic: 87.67 +/- 2.52%; n = 3/group). Critical measures that affect culture outcomes include, but not limited to, the age of embryo, cell seeding density, dissociation time, and elimination of non-neuronal cells. Thus, the present study has identified the enzymatic dissociation method to be a preferred method for obtaining large quantity of highly-enriched embryonic spinal cord neurons.

Low Expression of lncRNA-GAS5 Is Implicated in Human Primary Varicose Great Saphenous Veins

The cellular mechanisms of primary varicose great saphenous veins (GSVs) involve inflammation, apoptosis, and proliferation of local cells and extracellular matrix degradation. Long non-coding RNAs (lncRNAs) play important roles in these cellular processes; however, which and how lncRNAs related to these mechanisms take effect on GSVs remain unclear. By screening lncRNAs that might experience changes in GSV varicosities, we selected the lower expressed lncRNA-GAS5 (growth arrest specific transcript 5) for functional assessments. Silencing of lncRNA-GAS5 promoted cell proliferation and migration, and cell cycle of the human saphenous vein smooth muscle cells (HSVSMCs), whereas overexpressing it inhibited these cellular behaviors and reduced apoptosis of HSVSMCs. RNA pull-down experiment revealed a direct bind of lncRNA-GAS5 to a Ca2+-dependent RNA-binding protein, Annexin A2. Further experiments showed that silencing of Annexin A2 reduced the HSVSMCs proliferation and vice versa. In the context of lncRNA-GAS5 knockdown, silencing of Annexin A2 reduced the proliferation of HSVSMCs while overexpression of Annexin A2 increased the proliferation. Thus, the low expression of lncRNA-GAS5 may facilitate HSVSMCs proliferation and migration through Annexin A2 and thereby the pathogenesis of GSV varicosities.

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

The Kazakh inhabitants living in Barkol pasture of northeast China belong to a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. To investigate whether the polymorphisms in the G-protein β-3 subunit (GNB3) gene and angiotensin-converting enzyme (ACE) gene are associated with essential hypertension (EH), we carried out a case–control study of 290 hypertensive subjects and 244 normotensive (NT) controls randomly selected from Kazakh populations of Barkol. A previous medical history of diabetes and hypertension, and body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The insertion/deletion (I/D) polymorphism of the ACE gene and the C825T polymorphism of the GNB3 gene were determined by the polymerase chain reaction (PCR) technique. The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of EH related to the ACE gene D allele and GNB3 gene T allele was not significantly different from 1.0. Logistic regression analysis shows the variation at the GNB3 and ACE did not have any statistically significant synergistic effect on blood pressure (BP). Stratification of NT and untreated hypertensives according to I/D polymorphism of ACE gene and C825T polymorphism of GNB3 gene disclosed no significant difference across genotypes with respect to BMI, glucose, triglyceride, cholesterol, systolic and diastolic BP. In conclusion, the polymorphisms in the GNB3 gene and ACE gene, solely or combined, did not confer a significantly increased risk for the development of EH in the Kazakh isolate of northeast China.

Association of LPR5 polymorphism with bone mass density and cholesterol level in population of Chinese Han.

Recently, two single nucleotide polymorphisms, rs4355801 near the osteoprotegerin (OPG) gene and rs3736228 in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, were found to be associated with osteoporosis and osteoporotic fractures in Caucasians in a genome wide association study. In the present study, we investigated the association between these two SNPs (rs4355801 and rs3736228) and bone mass density (BMD), whole body T score and metabolic phenotypes (e. g., body mass index, glucose, triglyceride, and total cholesterol) in 425 Chinese Han subjects. We observed a significant association between rs3736228 in LRP5 and hip BMD, total BMD, and T score. The level of hip BMD, total BMD, and T score was significantly reduced with the number of at risk T alleles (p=0.006, p=0.003, and p=0.006, respectively). This finding was still significant after accounting for gender and age. We also observed a significant association between rs3736228 and total cholesterol (CHO) levels in our sample. The CHO levels of the CC, CT, and TT genotypes were 4.71, 4.76, and 5.24, respectively (p=0.031). For OPG rs4355801, the level of hip BMD, spine BMD, and total BMD was consistently reduced in persons with the copy of A allele, but none of these findings were statistically significant. We also did not observe a significant association between the above two polymorphisms and body mass index, glucose, and triglyceride levels in Chinese Han subjects. Thus, our observations support the association between rs3736228 and BMD in Han subjects. We also provide first evidence that the T allele of rs3736228 increases the total cholesterol level in a general Han population.

CYP7A1 polymorphism influences the LDL cholesterol-lowering response to atorvastatin.

What is known and Objective:  Response to the lipid‐lowering effect of the statins is known to show significant inter‐individual variability. Our aim was to investigate whether genetic variants of the CYP3A5 gene, CYP7A1 gene and ABCG8 gene influence the lipid‐lowering response to atorvastatin.

Associations of sleep duration and sleep quality with life satisfaction in elderly Chinese: The mediating role of depression

This study investigated whether sleep duration and quality were related to life satisfaction (LS) among older Chinese adults and whether depression mediated those relationships. Cross-sectional data from the aging arm of the Rugao Longevity and Aging Study were used. Sleep duration, sleep quality, depression, LS and covariates were analyzed using logistic regressions. To assess the potential mediation of depression on the association between sleep duration and quality and LS, Aroian tests were used. Of 1756 older Chinese adults aged 70-84 years, 90.7% of the men and 83.3% of the women reported being satisfied with their lives. After adjusting for covariates, older adults who slept ≤6h per night were more likely to suffer from life dissatisfaction compared with those who slept 7-8h (OR=2.67, 95% CI 1.86-3.79), and individuals who slept poorly were almost 2 times (OR=2.91, 95% CI 2.16-3.91) more likely to have life dissatisfaction. The Aroian tests confirmed that these relationships were partially mediated by depression (p<0.001). Between short sleep and LS, the mediating effect of depression accounted for 13.9% of the total effects. Moreover, the mediating effect of depression on the association between sleep quality and LS was 13.3%. Short sleep duration and poor sleep quality were inversely associated with LS, and the relationships were partially mediated by depression. Our study suggests that both sleep and depression status are important factors for LS among the elderly.

Aberrantly expressed lncRNAs in primary varicose great saphenous veins.

Long non-coding RNAs (lncRNAs) are key regulatory molecules involved in a variety of biological processes and human diseases. However, the pathological effects of lncRNAs on primary varicose great saphenous veins (GSVs) remain unclear. The purpose of the present study was to identify aberrantly expressed lncRNAs involved in the prevalence of GSV varicosities and predict their potential functions. Using microarray with 33,045 lncRNA and 30,215 mRNA probes, 557 lncRNAs and 980 mRNAs that differed significantly in expression between the varicose great saphenous veins and control veins were identified in six pairs of samples. These lncRNAs were sub-grouped and mRNAs expressed at different levels were clustered into several pathways with six focused on metabolic pathways. Quantitative real-time PCR replication of nine lncRNAs was performed in 32 subjects, validating six lncRNAs (AF119885, AK021444, NR_027830, G36810, NR_027927, uc.345-). A coding-non-coding gene co-expression network revealed that four of these six lncRNAs may be correlated with 11 mRNAs and pathway analysis revealed that they may be correlated with another 8 mRNAs associated with metabolic pathways. In conclusion, aberrantly expressed lncRNAs for GSV varicosities were here systematically screened and validated and their functions were predicted. These findings provide novel insight into the physiology of lncRNAs and the pathogenesis of varicose veins for further investigation. These aberrantly expressed lncRNAs may serve as new therapeutic targets for varicose veins. The Human Ethnics Committee of Shanghai East Hospital, Tongji University School of Medicine approved the study (NO.: 2011-DF-53).