Abstract:ATP-binding cassette transporters A1(ABCA1) is expressed widely in the brain tissues. It transports intracellular cholesterol to apolipoprotein E(apoE) and apolipoprotein A1(apoA-Ⅰ) to form high-density lipoprotein, thus regulates the balance of brain cholesterol. Research has shown, there is a close relationship between ABCA1 and brain diseases about cholesterol metabolism, including Alzheimer's disease(AD), traumatic brain injury(TBI) and Cerebral infarction. Recently, there are some research progresses about ABCA1 and brain disease, but there are still many problems that has not been clarified. In this paper, the effects of ABCA1 in various related brain diseases are introduced, in order to look for a new target and method for the related brain diseases.

Abstract:Cancer is one kind of diseases which seriously jeopardized the health of human beings. Oncogenic DNA virus is a leading factor for many kinds of cancer. Virus DNA integration could cause host cell organization inflammation and tumorigenesis. Its integration could induce the host genome instability and rearrangement. It could also cause the alterations of host transcriptome such as viral promoter driven human transcription, viral-human transcription fusion and form new fusion gene，and the host gene expression change. Meanwhile, it's one of the mechanisms for virus replication, escape the host immunological recognition and maintain itself. The review focus on the research and the progress of the oncogenic DNA virus integration regulation and the carcinogenic effect of its integration. We also prospect the oncogenic DNA virus integration research direction and the application on the cancer occurrence, development, diagnose and therapy.

Abstract:Runx2 is an osteoblast-specific transcription factor, which regulates osteoblast differentiation and bone formation. In breast cancer, Runx2 activates expression of bone matrix and adhesion proteins, matrix metalloproteinase and angiogenic factors that has long been associated with metastasis. Runx2 forms co-regulatory complexes with some co-activator and co-repressor proteins that are organized in subnuclear domains to regulate gene transcription and mediates the responses of cells to signaling pathways activate in breast tumors. In addition, Runx2 could also interact with the estrogen receptors in some extent to discharge the effect of estrogen and its receptors on the development of breast cancer. This article mainly summarizes Runx2's roles in breast carcinoma and its interaction with estrogen receptors.

Abstract:The nuclear envelope spectrin repeat proteins (Nesprins), connecting the nucleus with many kinds of cytoskeleton and/or organelles, play important roles in nucleus and cytoskeleton positioning, power and material transporting between nucleus and cytoplasm, nuclear envelope constructing, cell migrating, anchoring and polarizing. Their discoveries, encoding genes, structural characters, functions and related diseases were summarized in this review, and their further research pulses are also prospected meanwhile.

Abstract:The filamentous fungus Neurospora crassa is an important model organism for studying genetic regulation, circadian rhythm and light response. This review summarized the structure and functions of WC-1 and VVD, and their participation in regulation of circadian rhythm and photoadaptation. All known light responses in Neurospora are regulated by blue light through two photoreceptors WC-1 and VVD. WC-1 is a transcription factor in this fungus and initiated the light response, generating a lot of light-responded proteins, such as VVD. VVD suppresses the transcription function of WC-1through negative feedback mechanism. In addition, the vvd gene has been applied to construct the photoresponsive elements of various genes in mammalian systems.

Abstract:Gene regulatory networks have an important role in every process of life, including cell differentiation, metabolism, the cell cycle and signal transduction. The RASSF1A is a tumor suppressor gene involved in several growth regulatory and pro-apoptotic pathways. In this study, we have used microarray technology to define differences in the gene expression profiles subsequent to exogenous wild-type RASSF1A in melanoma A375 cells. Gene expression changes were verified in a subset of genes using real time RT-PCR. Association of modulated genes with biological functional groups identified several pathways affected by RASSF1A including cell death, cellular growth and proliferation, and cellular development. GRN of modulated genes were identified using the STRING. Pro-inflammatory factors and transcription factors locates in the center of RASSF1A modulated gene regulatory networks. Our results suggested that RASSF1A might affect melanoma gene regulatory network via modulating the expression and interaction between pro-inflammatory factors and transcription factors.

Abstract:We investigated the inhibitory effect of modified antisense RNA oligonucleotides and cationic liposome-RNA complexes on the repression of hepatitis B virus (HBV) replication and expression. ELISA and quantitative Real-time PCR analysis showed that HBV replication and antigens expression both in pHBV1.3 transduced HepG2 and HepG2.2.15 cells were reduced after treatment with antisense RNA oligonucleotides P-2987, X-60 and X-519. Subsequently, the antisense RNA oligonucleotides and control RNA oligonucleotides were injected via the tail vein into HBV transgenic mice or hydrodynamically injected mice. In the HBV transgenic mice, with the treatment of X-519, HBV pregenomic RNA in the liver decreased by 81%. Cationic liposome further increased the inhibition effectory to 91%. But no significant differences were observed for HBV antigens and HBV DNA copy number in the sera. In acute HBV infection mouse model by hydrodynamic injection, ELISA and quantitative real-time PCR analysis showed that X-519 significantly repressed HBV replication, as measured by HBV pregenomic RNA, antigens expression, and presence of HBV DNA in the sera. Taken together, the synthesized antisense RNA oligonucleotide X-519 repressed HBV replication and antigens expression in vitro and in vivo.

Abstract:Multiple system atrophy (MSA) is a progressive neuron degenerative disease characterized by glial cytoplasmic inclusions containing insoluble α-synuclein and autonomic failure associated with either poorly levodopa-responsive TRPC1-sonism or cerebellar ataxia or both. Studies have shown that α-synuclein plays very important role in the pathogenesis of MSA, but the molecular mechanism of the toxicity is still unclear. On the basis of many previous studies about calcium dyshomeostasis caused by the intracellular oxidative stress conditions, we put forward a new hypothesis of Bergmann glia death which is closely related to the oxidative stress during the progress of MSA. In order to compare the difference between α-synuclein overexpressed U251 cells with or without TRPC1 RNA interference in response to free iron, we investigated the cell apoptosis by Western-blot and measuring activated caspase activity. The interrelations of autophagy and neuron death were studied by assessing the level of LC-3 protein and autophagosomes; and then the cell survival was measured by cell count and MTT assay. In this study, we gave a deep analysis of the molecular mechanism of neuron death in α-synuclein overexpressed U251 cells in some respects of cell apoptosis, autophagy and calcium ion channels and so on. Firstly, we analysed the relation of α-synuclein and overexpressed TRPC1. Our results indicated that α-synuclein overexpression in U251 cells could inhibit cell growth and increase the level of oxidative stress. And then, the expression of some important proteins such as calcium channels protein TRPC1, autophagy related protein LC-3B and death receptor DR5 were increased obviously. Meanwhile, with the downregulation of TRPC1, we investigated the change of cell death and the oxidative level of α-synuclein overexpression U251 cells during the progress, and we can see the cell toxicity of U251 cells with α-synuclein overexpression was effectively changed. All results demonstrated that α-synuclein overexpression can destroy cell calcium homeostasis by increasing the level of membranous calcium channels protein TRPC1. Besides, it can increase the level of apoptosis and autophagy, and the level of oxidative stress which might be the reason of MSA. We tried to give a reasonable explanation and provide a clue for the prevention and treatment of MSA.

Abstract:Improper usage of general anesthesia may cause fatal damage to the central nervous system. Therefore, its safety becomes a major concern. In order to reveal the changing patterns of neuronal activity during the period of increasing anesthetic depth, the present paper investigated the changes of excitability and signal conduction of neurons in the rat hippocampus during deep anesthesia till brain death with urethane. By using the techniques of microelectrode array recording and electrical stimulation, we recorded population spikes (PS) in the pyramidal layer of hippocampal CA1 region that were evoked either by orthodromic stimulation of the Schaffer collateral or by antidromic stimulation of the alveus. The amplitude and latency of PS were used as indices to evaluate the changes of neuronal activity. The results showed that as the urethane concentration in the plasma increased, the amplitudes of PS decreased and the latencies of PS increased, indicating that the urethane suppressed the neuronal excitability as well as the synaptic transmission and axon conduction. Particularly, there was a turning point that divided the whole decline period of neuronal activity into two distinct stages: slow stage and fast stage. The catastrophic decline of fast stage resulted in brain death rapidly. In addition, the urethane concentration in plasma, rather than the duration of anesthesia, might cause the appearance of turning point. However, the prolonged duration of slow stage caused by slower injection rate of urethane could also induce more damage to neuronal functions. These results provide important information for the safe application of narcotics in both animal experiments and clinic usage.

Abstract:Acute alcoholism is a common pathological state caused by excess intake of ethanol in a short period. It leads to multiple organ functional damage such as central nervous system depression, respiratory and circulatory system dysfunction, metabolism and immune system abnormal. In order to study the reason of death caused by acute alcoholism, we developed a mouse model of acute alcoholism by intraperitoneal injection method. We reported for the first time that HMGB1 played an important role in acute alcoholism. HMGB1 was released and detected in the serum as early as 0.5 h after the intraperitoneal injection of ethanol. Then HMGB1 induced subsequent acute systemic inflammatory response. We further provided evidences indicating that anti-HMGB1 antibody could effectively protect mouse from acute alcohol. This protection was achieved by significantly reducing HMGB1 release and suppressing systemic inflammation.

Abstract:Recent studies revealed that heterogeneity is a general phenomenon among microbes with identical genomes, and it is closely related to physiological functions of microbes. The multiple heterogeneous states of microbes requires single-cell level tools to uncover. Flow cytometry is one of the most important methods to obtain accurate information on quantitative distribution of heterogeneous states of microbes. However, the small size, much less biomolecule contents and general lack of specific reagents limit the application of conventional flow cytometry to investigations of the heterogeneity of microbes. In this study, we applied a newly developed flow cytometer with increased resolution and sensitivity on three label-free parameters which include FSC,SSC and autofluorescence level of NAD(P)H to analyse Bacillus subtilis. And for the first time we revealed that the bacterial culture exhibited complicated and dynamically distributed multiple heterogeneous subgroups depended on its growth stage. This method has low background noise, high sensitivity and great resolution. The newly identified multiple subpopulations of Bacillus subtilis and their changes dynamically associated with the biological functions are likely to provide new opportunities to understand physiological change patterns and their underlying molecule mechanisms. We also discussed that the new method based on flow cytometric measurements of non-label parameters with high sensitivity and resolution had great potency for studies on the heterogeneity of various microbes.

Abstract:Glycosylation is one of the most common post-translational modifications in proteins. Current methods for glycan analysis are generally based on multiple preparation processes to separate glycans. However, glycans are continuously lost and the difficulty for accurate quantitative analysis is increased in the procedure. Here, a filter aided sample preparation-based total N-linked glycans from the glycoproteins enrichment and separation method (N-glycan-FASP-T) was developed using ultrafiltration units according to the molecular mass difference among the glycans, the impurities and proteins. The enriched glycans were characterized and confirmed by the MALDI-TOF/TOF-MS. A total of 23 distinctive N-linked glycans were characterized from human serum.