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Biomedical subjects

Na Liu

Publications and source records attributed to Na Liu.

At least 19 recordsLinked to original sources

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ&#x2265;8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p&#x202f;<&#x202f;0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p&#x202f;<&#x202f;0.01), and TCM syndrome score (69.23% vs 30.13%, p&#x202f;<&#x202f;0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

Molecular mechanisms involved in self-renewal and pluripotency of embryonic stem cells.

Embryonic stem cells (ES cells) are derived from inner cell mass (ICM). The self-renewal and pluripotency are the main specificities of ES cells, which are likely to reveal a deeper understanding of human cellular biology and which are considered to be promising sources for cell therapy to treat patients with degenerative diseases in clinical. Growth of ES cells as a pluripotent population requires a balance between survival, proliferation, and self-renewal signals. In fact, the precise mechanism that regulates stem cell self-renewal and pluripotency remains largely unknown. Recently, in vitro and in vivo studies have identified several genetic regulators that may play important roles in the self-renewal and pluripotency process of human and mouse ES cells, including extracellular signaling factors, transcription factors, cell-cycle regulators, microRNA, genes implicated in chromosomal stability, and DNA methylation. In this review, we will summarize the currently known molecular regulators for ES cells self-renewal, and we will propose some possibilities to explain the ways in which these distinct pathways might interact.

Animals↗

A method for rapid similarity analysis of RNA secondary structures.

BACKGROUND: Owing to the rapid expansion of RNA structure databases in recent years, efficient methods for structure comparison are in demand for function prediction and evolutionary analysis. Usually, the similarity of RNA secondary structures is evaluated based on tree models and dynamic programming algorithms. We present here a new method for the similarity analysis of RNA secondary structures. RESULTS: Three sets of real data have been used as input for the example applications. Set I includes the structures from 5S rRNAs. Set II includes the secondary structures from RNase P and RNase MRP. Set III includes the structures from 16S rRNAs. Reasonable phylogenetic trees are derived for these three sets of data by using our method. Moreover, our program runs faster as compared to some existing ones. CONCLUSION: The famous Lempel-Ziv algorithm can efficiently extract the information on repeated patterns encoded in RNA secondary structures and makes our method an alternative to analyze the similarity of RNA secondary structures. This method will also be useful to researchers who are interested in evolutionary analysis.

Algorithms↗

The physical and functional interaction of NDRG2 with MSP58 in cells.

NDRG2, a member of N-Myc downstream regulated gene family, exerts the important functions in cell differentiation and tumor suppression. Although the ectopic expressed Ndrg2 inhibits the proliferation of tumor cells, its intracellular signal transduction pathway is hardly known. Here, we identified MSP58, a 58-kDa microspherule protein, as an interacting partner of human Ndrg2 by using yeast two-hybrid screening. The interaction was confirmed by glutathione S-transferase pull-down assay in vitro and by co-immune-precipitation assay in vivo. The forkhead associated domain of MSP58 is essential for its interaction with Ndrg2. Ndrg2 could co-localize with MSP58 in nuclear of HeLa cell during cell stress. Furthermore, the modulation of Ndrg2 level influences the cell cycle process together with MSP58. In conclusion, the findings offered a novel insight into the physiological roles of Ndrg2.

Animals↗

The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter.

The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.

Animals↗

Protein-based phylogenetic analysis by using hydropathy profile of amino acids.

So far, various approaches for phylogenetic analysis have been developed. Almost all of them put stress on analyzing nucleic acid sequences or protein primary structures. In this paper, we take the physicochemical properties of amino acids into account and introduce the hydropathy profile of amino acids into phylogenetic analysis. We find that this introduction is effectual and our method may be used to complement phylogenetic analysis.

Amino Acids↗

A simple method for protein structural classification.

Since the concept of structural classes of proteins was proposed, the problem of protein classification has been tackled by many groups. Most of their classification criteria are based only on the helix/strand contents of proteins. In this paper, we proposed a method for protein structural classification based on their secondary structure sequences. It is a classification scheme that can confirm existing classifications. Here a mathematical model is constructed to describe protein secondary structure sequences, in which each protein secondary structure sequence corresponds to a transition probability matrix that characterizes and differentiates protein structure numerically. Its application to a set of real data has indicated that our method can classify protein structures correctly. The final classification result is shown schematically. So it is visual to observe the structural classifications, which is different from traditional methods.

Algorithms↗

Cellular prion protein promotes invasion and metastasis of gastric cancer.

Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI) -anchored membrane protein that is highly conserved in mammalian species. PrPc has the characteristics of adhesive molecules and is thought to play a role in cell adhesion and membrane signaling. Here we investigated the possible role of PrPc in the process of invasiveness and metastasis in gastric cancers. PrPc was found to be highly expressed in metastatic gastric cancers compared to nonmetastatic ones by immunohistochemical staining. PrPc significantly promoted the adhesive, invasive, and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45. PrPc also increased promoter activity and the expression of MMP11 by activating phosphorylated ErK1/2 in gastric cancer cells. MEK inhibitor PD98059 and MMP11 antibody (Ab) significantly inhibited in vitro invasive and in vivo metastatic abilities induced by PrPc. N-terminal fragment (amino acid 24-90) was suggested to be an indispensable region for signal transduction and invasion-promoting function of PrPc. Taken together, the present work revealed a novel function of PrPc that the existence of N-terminal region of PrPc could promote the invasive and metastatic abilities of gastric cancer cells at least partially through activation of MEK/ERK pathway and consequent transactivation of MMP11.

Animals↗

Role of Rac1 and Cdc42 in hypoxia induced p53 and von Hippel-Lindau suppression and HIF1alpha activation.

Low oxygen tension can influence tumor progression by enhancing angiogenesis, a process that may involve Rho GTPases whose activities have been implicated in tumorigenesis and metastasis. In the present study, we show that hypoxia can increase the mRNA levels and intracellular activities of Rac1 and Cdc42 in a time-dependent manner. The hypoxia-stimulated activities of Rac1 and Cdc42 could be blocked by the phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and the protein tyrosine kinase (PTK) inhibitor genistein but were not affected by the p38MAPK inhibitor SB203580 or the MEK-1 inhibitor PD98059, suggesting that the hypoxia-mediated signals were through PI3K and PTK. Correlating with the increased activities of Rac1 and Cdc42, the expression of the pro-angiogenesis factors HIF-1alpha and vascular endothelial growth factor (VEGF) was upregulated by hypoxia, whereas the expression of the tumor suppressors von Hippel-Lindau and p53 was down-regulated. Dominant negative N17Rac1 and N17Cdc42 could upregulate the expression of p53 and pVHL but downregulate that of HIF-1alpha and VEGF under hypoxia. Furthermore, the preconditioned medium from N17Rac1 or N17Cdc42-expressing gastric cancer cells was able to inhibit the proliferation of HUVECs. Our results indicate that PI3K and PTK-mediated activations of Rac1 and Cdc42 are involved in the hypoxia-induced production of angiogenesis-promoting factors and tumor suppressors, and suggest that the Rho family GTPases Rac1 and Cdc42 may contribute to the hypoxia-mediated angiogenesis.

Blotting, Western↗

Li-biphenyl-1,2-dimethoxyethane solution: calculation and its application.

Metallic lithium reacts with biphenyl in 1,2-dimethoxyethane (DME) solvent at room temperature. This reaction has been studied using density functional theory (DFT) at the B3LYP level together with the 6-311++G (d,p) basis set. From the energy results of the corresponding optimized geometries for intermediate complexes, the reaction can be interpreted as a charge-transfer process between lithium and biphenyl followed by Li+ coordination with ether oxygens in DME. In addition, the experimentally observed vibrational bands can be unambiguously assigned and interpreted according to the normal modes calculated for the biphenyl-Li-DME complex. This organic complex solution has been demonstrated as a very effective chemical lithiation agent. V2O5 can be lithiated up to 1.45 lithium ions per formula. The lithiated V2O5 shows a high Li-extraction capacity of 173 mAh/g as cathode material for lithium ion batteries.

Journal Article↗

ATM controls c-Myc and DNA synthesis during postnatal thymocyte development through regulation of redox state.

The oncoprotein c-Myc is essential for thymocyte development, and its dysregulation causes lymphoid malignancies. We have demonstrated previously that spontaneous DNA synthesis in Atm(-/-) thymocytes is markedly increased over that of Atm(+/+) thymocytes and that glucocorticoid dexamethasone suppresses thymocyte DNA synthesis and prevents the ultimate development of thymic lymphoma in Atm(-/-) mice. Recently, we reported that in Atm(-/-) thymic lymphoma cells c-Myc is overexpressed compared with the levels of c-Myc in primary thymocytes from wild-type or Atm(-/-) mice. In this study, we show that c-Myc expression progressively increases with age in primary thymocytes from Atm(-/-) mice and that the upregulation of c-Myc parallels the elevated DNA synthesis in the cells, suggesting that deregulation of c-Myc may drive the uncontrolled proliferation of thymocytes in Atm(-/-) mice. Here we also demonstrate that Atm(-/-) thymocytes exhibit increased levels of hydrogen peroxide, NF-E2-related factor (Nrf-2), peroxiredoxin-1, and intracellular glutathione relative to thymocytes from Atm(+/+) mice. Importantly, reduction of hydrogen peroxide by administration of the antioxidant N-acetylcysteine to Atm(-/-) mice attenuates the elevation of Nrf-2, c-Myc, and DNA synthesis in their thymocytes, suggesting that ATM may control c-Myc and DNA synthesis during postnatal thymocyte development by preventing accumulation of reactive oxygen species.

Animals↗

Effects of heat shock protein gp96 on human dendritic cell maturation and CTL expansion.

We reported previously that heat shock protein gp96 and its N-terminal fragment were able to stimulate CTL expansion specific for a HBV peptide (SYVNTNMGL) in BALB/c mice. Here we characterized the adjuvant effects of gp96 on human HLA-A2 restricted T cells. Full-length gp96 isolated from healthy human liver and recombinant fragments both from prokaryotic cells and eukaryotic cells were analyzed for their ability to stimulate maturation of human dendritic cells. It was found that in vitro these proteins were capable of maturating human monocyte-derived dendritic cells (MDDC) isolated from healthy donors as well as from HBV-positive, hepatocellular carcinoma (HCC) patients. In HLA-A2.1/Kb transgenic mice, gp96 and the recombinant fragments were found to augment CTL response specific for the HBcAg(18-27) FLPSDFFPSV peptide of hepatitis B virus.

Animals↗

A weighted measure for the similarity analysis of DNA sequences.

Here we propose a weighted measure for the similarity analysis of DNA sequences. It is based on LZ complexity and (0,1) characteristic sequences of DNA sequences. This weighted measure enables biologists to extract similarity information from biological sequences according to their requirements. For example, by this weighted measure, one can obtain either the full similarity information or a similarity analysis from a given biological aspect. Moreover, the length of DNA sequence is not problematic. The application of the weighted measure to the similarity analysis of beta-globin genes from nine species shows its flexibility.

Animals↗

Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes.

The murine retrovirus, MoMuLV-ts1, induces progressive paralysis and immune deficiency in FVB/N mice. We have reported previously that ts1 infection causes apoptosis in astrocytes via endoplasmic reticulum (ER) and mitochondrial stress (Liu, N., Kuang, X., Kim, H.T., Stoica, G., Qiang, W., Scofield, V.L., Wong, P.K.Y. Wong. 2004. Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes. J. NeuroVirol. 10, 189-198). In the present study, we show that caspase 8 activation in these cells is mediated through ER stress-associated elevation of death receptor DR5 and the C/EBP homologous protein (GADD153/CHOP), an ER stress-initiated transcription factor, rather than through TNFalpha and TNF-R1 interactions on the cell surface. Treatment with Z-IETD-FMK, a specific inhibitor of caspase 8 enzymatic activity, reduced ER stress by two mechanisms: by inhibiting caspase 8 activation, and by preventing cleavage of the ER-associated membrane protein BAP31 into BAP20, which exacerbates the ER stress response. These findings suggest that caspase 8- and ER stress-associated apoptotic pathways are linked in ts1-infected astrocytes.

Animals↗

Cloning of mpd gene from a chlorpyrifos-degrading bacterium and use of this strain in bioremediation of contaminated soil.

An effective chlorpyrifos-degrading bacterium (named strain YC-1) was isolated from the sludge of the wastewater treating system of an organophosphorus pesticides manufacturer. Based on the results of phenotypic features, phylogenetic similarity of 16S rRNA gene sequences and BIOLOG test, strain YC-1 was identified as the genus Stenotrophomonas. The isolate utilized chlorpyrifos as the sole source of carbon and phosphorus for its growth and hydrolyzed chlorpyrifos to 3,5,6-trichloro-2-pyridinol. Parathion, methyl parathion, and fenitrothion also could be degraded by strain YC-1 when provided as the sole source of carbon and phosphorus. The gene encoding the organophosphorus hydrolase was cloned using a PCR cloning strategy based on the known methyl parathion degrading (mpd) gene of Plesiomonas sp. M6. Sequence blast result indicated this gene has 99% similar to mpd. The inoculation of strain YC-1 (10(6) cells g(-1)) to soil treated with 100 mg kg(-1) chlorpyrifos resulted in a higher degradation rate than in noninoculated soils. Theses results highlight the potential of this bacterium to be used in the cleanup of contaminated pesticide waste in the environment.

Biodegradation, Environmental↗

Astrocytes survive chronic infection and cytopathic effects of the ts1 mutant of the retrovirus Moloney murine leukemia virus by upregulation of antioxidant defenses.

The ts1 mutant of Moloney murine leukemia virus (MoMuLV) induces a neurodegenerative disease in mice, in which glial cells are infected by the retrovirus but neurons are not. ts1 infection of primary astrocytes, or of the immortalized astrocytic cell line C1, results in accumulation of the ts1 gPr80(env) envelope protein in the endoplasmic reticulum (ER), with ER and oxidative stress. Notably, only about half of the infected astrocytes die in these cultures, while the other half survive, continue to proliferate, and continue to produce virus. To determine how these astrocytes survive ts1 infection in culture, we established a chronically infected subline of the living cells remaining after the death of all acutely infected cells in an infected C1 cell culture (C1-ts1-S). We report here that C1-ts1-S cells proliferate more slowly, produce less virus, show reduced H2O2 levels, increase their uptake of cystine, and maintain higher levels of intracellular GSH and cysteine compared to acutely infected or uninfected C1 cells. C1-ts1-S cells also upregulate their thiol antioxidant defenses by activation of the transcription factor NF-E2-related factor 2 (Nrf2) and its target genes. Interestingly, despite maintenance of higher levels of intracellular reduced thiols, C1-ts1-S cells are more sensitive to cystine deprivation than uninfected C1 cells. We conclude that some ts1-infected astrocytes survive and adapt to virus-induced oxidative stress by successfully mobilizing their thiol redox defenses.

Animals↗

Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium alpha-luminol (Galavit).

Oxidative stress is involved in many human neuroimmunodegenerative diseases, including human immunodeficiency virus disease/AIDS. The retrovirus ts1, a mutant of Moloney murine leukemia virus, causes oxidative stress and progressive neuro- and immunopathology in mice infected soon after birth. These pathological changes include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell depletion. Astrocytes and thymocytes are directly infected and killed by ts1. Neurons are not infected, but they also die, most likely as an indirect result of local glial infection. Cytopathic effects of ts1 infection in cultured astrocytes are associated with accumulation of the viral envelope precursor protein gPr80env in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress. We have reported (i) that activation of the Nrf2 transcription factor and upregulation of antioxidative defenses occurs in astrocytes infected with ts1 in vitro and (ii) that some ts1-infected astrocytes survive infection by mobilization of these pathways. Here, we show that treatment with a refined monosodium alpha-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2 activation in cultured ts1-infected astrocytes. GVT treatment also inhibits the development of spongiform encephalopathy and gliosis in the central nervous system (CNS) in ts1-infected mice, preserves normal cytoarchitecture in the thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment of infected mice reduces ts1-induced oxidative stress, cell death, and pathogenesis in both the CNS and thymus of treated animals. These studies suggest that oxidative stress mediates ts1-induced neurodegeneration and T-cell loss.

Active Transport, Cell Nucleus↗