Gene expression profile of the hippocampus of rats subjected to traumatic brain injury

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.     

Particulate matter 2.5 induced bronchial epithelial cell injury via activation of 5′-adenosine monophosphate-activated protein kinase-mediated autophagy

The impact of particulate matter 2.5 (PM2.5) on the respiratory system is a worldwide concern. However, the mechanisms by which PM2.5 causes disease are still unclear. In this study, we investigated the effect of PM2.5 on autophagy and studied the effect of PM2.5-induced autophagy and 5′-adenosine monophosphate-activated protein kinase (AMPK) on cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS), and airway inflammation using human bronchial epithelial cells 16HBE140 cells. Results showed that exposure of cells to PM2.5 at a concentration of 100 μg/mL for 24 hours was most effective for inhibiting cell viability. PM2.5 induced cell arrest in the G0/G1 phase and increased mitochondrial membrane potential, ROS, and cell apoptosis with increasing concentration. PM2.5 downregulated cyclin D and matrix metallopeptidase-9 (MMP-9) expression but upregulated tissue inhibitor of metalloproteinases-1 (TIMP-1) expression, significantly promoted interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and enhanced the level and activation of AMPK. The levels of autophagy-related protein 5 (ATG5), Beclin-1, and LC3II/I were significantly increased by PM2.5. The activation of Unc-51-like autophagy activating kinase 1 was significantly inhibited by PM2.5. Moreover, ATG5 knockdown inhibited PM2.5-induced autophagy, ROS, and cell apoptosis significantly. The expression of cyclin D, MMP-9, and TIMP-1 was reversed by ATG5 suppression. PM2.5-induction of IL-6 and TNF-α was significantly inhibited by knockdown of ATG5. Thus, inhibition of autophagy protected the cells from PM2.5-induced injury. PM2.5 induced injury in human bronchial epithelial cells via activation of AMPK-mediated autophagy, suggesting possible therapeutic targets for the treatment of respiratory diseases.     

GDF-15 promotes mitochondrial function and proliferation in neuronal HT22 cells

The neuronal cell line HT22 is an excellent model for studying Parkinson's disease. Growth differentiation factor 15 (GDF15) plays a critical role in Parkinson's disease, but the molecular mechanism involved are not well understood. We constructed the GDF15 overexpression HT22 cells and detected the effects of overexpression of GDF15 on the viability, oxygen consumption, mitochondrial membrane potential of oligomycin-treated HT22 cells. In addition, we used a high-throughput RNA-sequencing to study the lncRNA and mRNA expression profiling and obtained key lncRNAs, mRNA, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway. The expression of selected DElncRNAs was validated by quantitative real-time PCR (qRT-PCR). Our results showed that overexpression of GDF15 significantly reversed the cells viability, oxygen consumption, and mitochondrial membrane potential effect caused by oligomycin in HT22 cells. The 1093 DEmRNAs and 395 DElncRNAs in HT22 cells between GDF15-oligomycin non-intervention group and a normal control-oligomycin un-intervention group were obtained, and 394 DEmRNAs and 271 DElncRNAs in HT22 cells between GDF15-oligomycin intervention group and normal control-oligomycin intervention group were identified. Base on the GO and KEGG enrichment analysis of between GDF15-oligomycin intervention group and normal control-oligomycin intervention group, positive regulation of cell proliferation was most significantly enriched GO terms, and Cav1 was enriched in positive regulation of cell proliferation pathway. PI3K-Akt signaling pathway was one significantly enriched pathway in GDF15-oligomycin intervention group. The qRT-PCR results were consistent with RNA-sequencing, generally. GDF15 might promote mitochondrial function and proliferation of HT22 cells by regulating PI3K/Akt signaling pathway. Our study may be helpful in understanding the potential molecular mechanism of GDF15 in Parkinson's disease.     

Structure and function insights garnered from in silico modeling of the thrombospondin type-1 domain-containing 7A antigen

The thrombospondin type-1 domain containing 7A (THSD7A) protein is known to be one of the antigens responsible for the autoimmune disorder idiopathic membranous nephropathy. The structure of this antigen is currently unsolved experimentally. Here we present a homology model of the extracellular portion of the THSD7A antigen. The structure was evaluated for folding patterns, epitope site prediction, and function was predicted. Results show that this protein contains 21 extracellular domains and with the exception of the first two domains, has a regular repeating pattern of TSP-1-like followed by F-spondin-like domains. Our results indicate the presence of a novel Trp-ladder sequence of WxxxxW in the TSP-1-like domains. Of the 21 domains, 18 were shown to have epitope binding sites as predicted by epitopia. Several of the F-spondin-like domains have insertions in the canonical TSP fold, most notably the coiled coil region in domain 4, which may be utilized in protein-protein binding interactions, suggesting that this protein functions as a heparan sulfate binding site.     

Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and the Wnt signaling pathway

Breast cancer (BC)-related mortality is associated with the potential metastatic properties of the primary breast tumors. The following study was conducted with the main focus on the effect of LINC00518 on the growth and metastasis of BC epithelial cells via the Wnt signaling pathway through regulation of the methylation of CDX2 gene. Initially, differentially expressed long intergenic non-protein coding RNAs (lincRNAs) related to BC were screened out in the Cancer Genome Atlas (TCGA) database, after which we detected the LINC00518 expression and localization in BC tissues and cells. Then the CDX2 positive expression and methylation level were identified. The targeting relationship of LINC00518 and CDX2, and binding methyltransferase in the promoter region were examined. BC epithelial cell proliferation, colony formation ability, invasion, migration and apoptosis were further evaluated. The lincRNA expression data related to BC downloaded from the TCGA database revealed that there was a high expression of LINC00518 in BC, and a negative correlation between LINC00518 and CDX2. In addition, LINC00518 promotes CDX2 methylation by recruiting DNA methyltransferase through activating the Wnt signaling pathway. The down-regulation of LINC00518 inhibited proliferation, invasion, migration, and EMT of BC epithelial cells while enhancing apoptosis. The inhibitory effects of LINC00518 down-regulation was reversed by CDX2 down-regulation. In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells.     

Neurons-on-a-Chip: In Vitro NeuroTools

Neurons-on-a-Chip technology has been developed to provide diverse in vitro neuro-tools to study neuritogenesis, synaptogensis, axon guidance, and network dynamics. The two core enabling technologies are soft-lithography and microelectrode array technology. Soft lithography technology made it possible to fabricate microstamps and microfluidic channel devices with a simple replica molding method in a biological laboratory and innovatively reduced the turn-around time from assay design to chip fabrication, facilitating various experimental designs. To control nerve cell behaviors at the single cell level via chemical cues, surface biofunctionalization methods and micropatterning techniques were developed. Microelectrode chip technology, which provides a functional readout by measuring the electrophysiological signals from individual neurons, has become a popular platform to investigate neural information processing in networks. Due to these key advances, it is possible to study the relationship between the network structure and functions, and they have opened a new era of neurobiology and will become standard tools in the near future.     

Contributions of source population and incubation temperature to phenotypic variation of hatchling Chinese skinks

Phenotypic plasticity and local adaptation are viewed as the main factors that result in between-population variation in phenotypic traits,but contributions of ...     

The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin’s ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.     

基因外显子连接序列与相应内含子序列的相互作用

剪接后的内含子与相应mRNA序列的相互作用在基因表达调控过程中起着非常重要的作用。基于27个物种的核糖核蛋白基因序列,采用Smith—Waterman局域比对方法得到外显子连接序列与相应内含子序列的最佳匹配片段,分析了外显子连接序列上的匹配频率分布和匹配片段的序列特征。发现一些低等真核生物EJC结合区域的匹配频率明显低于其它区域,所有物种EJC结合区域的序列构成呈现出相对低的结构序。最佳匹配片段的平均长度和配对率分布与siRNA和miRNA的结合特征相同。推测EJC和内含子在与外显子序列结合的过程中存在相互竞争和相互协作的关系,内含子中部序列在基因表达调控过程中起着重要的作用。