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Biomedical subjects

Jing Liu

Publications and source records attributed to Jing Liu.

At least 73 records · Page 4Linked to original sources
PubMed2006

The third 20 amino acid repeat is the tightest binding site of APC for beta-catenin.

Adenomatous polyposis coli (APC) plays a critical role in the Wnt signaling pathway by tightly regulating beta-catenin turnover and localization. The central region of APC is responsible for APC-beta-catenin interactions through its seven 20 amino acid (20aa) repeats and three 15 amino acid (15aa) repeats. Using isothermal titration calorimetry, we have determined the binding affinities of beta-catenin with an APC 15aa repeat fragment and each of the seven 20aa repeats in both phosphorylated and unphosphorylated states. Despite sequence homology, different beta-catenin binding repeats of APC have dramatically different binding affinities with beta-catenin and thus may play different biological roles. The third 20aa repeat is by far the tightest binding site for beta-catenin among all the repeats. The fact that most APC mutations associated with colon cancers have lost the third 20aa repeat underlines the importance of APC-beta-catenin interaction in Wnt signaling and human diseases. For every 20aa repeat, phosphorylation dramatically increases its binding affinity for beta-catenin, suggesting phosphorylation has a critical regulatory role in APC function. In addition, our CD and NMR studies demonstrate that the central region of APC is unstructured in the absence of beta-catenin and Axin, and suggest that beta-catenin may interact with each of the APC 15aa and 20aa repeats independently.

Adenomatous Polyposis Coli↗
PubMed2006

Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rats.

Chronic cerebral hypoperfusion, a mild ischemic condition, is associated with the cognitive deficits of AD. Paeoniflorin (PF), a major constituent of peony root, was proved to be neuroprotective in middle cerebral artery occlusion model. In this study, we investigated whether PF could attenuate chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rat. Seven weeks after permanent bilateral occlusion of the common carotid arteries, the rats were tested in the Morris water maze. Subsequently, the animals were sacrificed and neurons, astrocytes and microglias were labeled with immunocytochemistry in hippocampus. PF at the dose of 2.5 mg/kg ameliorated cerebral hypoperfusion-related learning dysfunction and prevented CA1 neuron damage. Chronic cerebral hypoperfusion increased the immunoreactivity of astrocytes and microglias in hippocampus. The increase was prevented by PF at the dose of 2.5 mg/kg. Cerebral hypoperfusion also increased expression of nuclear factor-kappaB (NF-kappaB), mostly in astrocytes, but not in neurons. With the treatment of PF (2.5 mg/kg), NF-kappaB immunostaining was diminished in hippocampus. Our results demonstrated that PF could attenuate cognitive deficit and brain damage induced by chronic cerebral hypoperfusion and that suppression of neuroinflammatory reaction in brain might be involved in PF-induced neuroprotection.

Animals↗
PubMed2006

TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material.

In histology and cell block sections, antibodies to thyroid transcription factor-1 (TTF-1) and p63 have been demonstrated to be useful markers for distinguishing between small-cell lung carcinoma and poorly differentiated pulmonary squamous cell carcinoma. In this study, we assessed the utility of TTF-1 and p63, as an antibody panel, for differentiating between these two neoplasms in previously Papanicolaou (Pap)-stained cytologic smears and cytospin slides. Twenty-six lung carcinomas (13 small-cell lung carcinomas, 13 poorly differentiated pulmonary squamous cell carcinomas) were evaluated. One or two previously 95% ethanol-fixed, Pap-stained smears or cytospin slides were selected from each case. The cytologic material from these slides was transferred to positively charged slides. Unstained recuts were obtained from the corresponding histologic specimens or cell blocks. Immunohistochemical staining for TTF-1 and p63 was performed on the paired samples from each tumor. All (13/13) small-cell lung carcinomas were negative for p63 and 92% (12/13) were positive for TTF-1. Conversely, all (13/13) poorly differentiated pulmonary squamous cell carcinomas expressed p63 and did not express TTF-1. Immunoreactivity for p63 was also noted in bronchial reserve cells and metaplastic squamous cells. The immunostaining results obtained from the cytology slides were concordant with those of the histology or cell block sections in all cases. The results of this study show that TTF-1 and p63 immunostaining can be successfully applied to previously Pap-stained cytologic material, as an antibody panel, to facilitate pathologic differentiation between small-cell lung carcinomas and poorly differentiated pulmonary squamous cell carcinomas. p63 immunostaining, however, must be interpreted in conjunction with cytomorphology to distinguish between poorly differentiated pulmonary squamous cell carcinomas and benign cellular constituents of the lung.

Adult↗
PubMed2006

Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia cell lines.

Thymosin alpha1 (Talpha1), a 28-amino acid peptide, is a well-known immune system enhancer for the treatment of various diseases. In the present investigation, the effects of Talpha1 on the proliferation and apoptosis of human leukemia cell lines (HL-60, K562 and K562/ADM) were studied. The proliferation was significantly depressed after 96 h of treatment with Talpha1, and obvious signs of apoptosis, i.e., cell morphology, nuclei condensation and Annexin V binding, were observed thereafter. Moreover, the up-regulation of Fas/Apol (CD95) and decrease in bcl-2 anti-apoptotic gene expression were observed in apoptotic cells. The expression and the function of P-glycoprotein (P-gp) can be slightly inhibited by Talpha1. It is noteworthy that K562 and K562/ADM were more sensitive than HL-60 cells when subjected to Talpha1. Furthermore, HepG-2, the human hepatoma cell line, displayed significant less sensitivity to Talpha1 than all the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine receptors (nAChRs) antagonist, significantly antagonized the inhibition effects induced by Talpha1, whereas atropine, a muscarinic acetylcholine receptor antagonist, did not exhibit such effects. All the results indicate that Talpha1 was able to significantly suppress proliferation and induce apoptosis in human leukemia cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

The DNA sequence, annotation and analysis of human chromosome 3.

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.

Animals↗
PubMed2006

Mild hypoxia promotes survival and proliferation of SOD2-deficient astrocytes via c-Myc activation.

Mouse astrocytes deficient in the mitochondrial form of manganese superoxide dismutase (SOD2) do not survive in culture under atmospheric air with 20% oxygen (O2), which is a common condition for cell cultures. Seeding the cells and maintaining them under mild hypoxic conditions (5% O2) circumvents this problem and allows the cells to grow and become confluent. Previous studies from our laboratory showed that this adaptation of the cells was not attributable to compensation by other enzymes of the antioxidant defense system. We hypothesized that transcriptional activity and upregulation of genes other than those with an antioxidant function are involved. Our present study shows that c-Myc was significantly induced and that it inhibited p21 and induced proteins such as cyclin-dependent kinases, cyclin D, and cyclin E, which are involved in the cell cycle process, along with phosphorylation of the retinoblastoma protein and Cdc2 (cell division cycle 2). These mechanisms contribute to cell proliferation. Small interfering RNA of c-Myc, however, blocked proliferation of SOD2 homozygous (SOD2-/-) astrocytes under mild hypoxia consisting of 5% O2, whereas it did not affect the growth of wild-type astrocytes. Our results indicate that c-Myc plays a critical role in hypoxia-induced proliferation and survival of SOD2-/- astrocytes by overcoming injury caused by oxidative stress.

Animals↗
PubMed2006

Theoretical evaluation of burns to the human respiratory tract due to inhalation of hot gas in the early stage of fires.

A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.

Burns, Inhalation↗
PubMed2006

Induced fit of passenger proteins fused to Archaea maltose binding proteins.

Maltose binding proteins (MBPs) are used as carriers for improving the solubility of passenger proteins. Our results indicate that the higher solubility of the fusions correlates with their elevated heat stability. Fusions of the otherwise thermo-sensitive GFP with MBPs from Archaea, but not GST-GFP and Escherichia coli MBP-GFP, maintained their fluorescence and structure after 10min incubation at 100 degrees C and could be purified by heating the bacteria lysate, with yields even higher than those obtained using metal affinity chromatography. Furthermore, only correctly folded proteins could stand the heating treatment and, therefore, the heat-purification method can be used as a quality control step to select homogeneous monodispersed material whereas soluble aggregates are removed by precipitation.

Archaeal Proteins↗
PubMed2006

Endomorphin1 and endomorphin2, endogenous potent inhibitors of electrical field stimulation (EFS)-induced cholinergic contractions of rat isolated bronchus.

In the present study, we determined whether endomorphin1 (EM1) and endomorphin2 (EM2), selective endogenous mu-opioid receptor (MOR) agonists, inhibited the response to EFS in rat isolated bronchus in a concentration- and frequency-dependent manner. EM1 (1 microM) produced significant inhibition at relatively low frequencies (< 5 Hz) (74.02 +/- 5.53%, 56.16 +/- 10.24% and 37.64 +/- 5.92% inhibition at 1, 2 and 4 Hz, respectively, p < 0.05 versus control), but no significant inhibition at 8, 16, 32 and 64 Hz (17.15 +/- 9.4%, 14.51 +/- 4.23%, 9.11 +/- 2.38% and 5.93 +/- 3.5%, respectively, p > 0.05 versus control). Similar modulations were observed in response to EM2 (1 microM). It is therefore considered that the inhibition effects of EM1 and EM2 may take place at frequencies under physiological conditions. Furthermore, EM1 and EM2 (0.01-10 microM) induced inhibition of cholinergic constriction in a dose-dependent manner at 1, 2 and 4 Hz. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10 microM), indicating that opioid receptors were involved. Neither EM1 nor EM2 (1 microM) had an effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. All the results indicate that EM1 and EM2 are potent inhibitors of EFS-induced cholinergic bronchoconstriction. These also imply that EM1 and EM2 may modulate cholinergic bronchoconstriction under physiological conditions and that these tetrapeptides could have therapeutic potential in the treatment of airway diseases.

Animals↗
PubMed2006

The finished DNA sequence of human chromosome 12.

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

Animals↗
PubMed2006

Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless.

The discovery of direct downstream targets of transcription factors (TFs) is necessary for understanding the genetic mechanisms underlying complex, highly regulated processes such as development. In this report, we have used a combinatorial strategy to conduct a genome-wide search for novel direct targets of Eyeless (Ey), a key transcription factor controlling early eye development in Drosophila. To overcome the lack of high-quality consensus binding site sequences, phylogenetic shadowing of known Ey binding sites in sine oculis (so) was used to construct a position weight matrix (PWM) of the Ey protein. This PWM was then used for in silico prediction of potential binding sites in the Drosophila melanogaster genome. To reduce the false positive rate, conservation of these potential binding sites was assessed by comparing the genomic sequences from seven Drosophila species. In parallel, microarray analysis of wild-type versus ectopic ey-expressing tissue, followed by microarray-based epistasis experiments in an atonal (ato) mutant background, identified 188 genes induced by ey. Intersection of in silico predicted conserved Ey binding sites with the candidate gene list produced through expression profiling yields a list of 20 putative ey-induced, eye-enriched, ato-independent, direct targets of Ey. The accuracy of this list of genes was confirmed using both in vitro and in vivo methods. Initial analysis reveals three genes, eyes absent, shifted, and Optix, as novel direct targets of Ey. These results suggest that the integrated strategy of computational biology, genomics, and genetics is a powerful approach to identify direct downstream targets for any transcription factor genome-wide.

Animals↗
PubMed2006

In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury.

AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction,Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury. METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD)and TNF-alpha were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H and E) for histological evaluation and examined under light microscope. RESULTS: We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride (CCl4) through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-alpha level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-alpha level and the free radical scavenging activity.

Alanine Transaminase↗
PubMed2006

Protein repertoire of double-stranded DNA bacteriophages.

The complexity and diversity of phage gene sets, which are produced by rapid evolution of phage genomes and rampant gene exchanges among phages, hamper the efforts to decipher the evolutionary relationships between individual phage proteins and reconstruct the complete set of evolutionary events leading to the known phages. To start unraveling the natural history of phages, we built the phage orthologous groups (POGs), a natural system of phage protein families that includes 6378 genes from 164 complete genome sequences of double-stranded DNA bacteriophages. Phage proteomes have high POG coverage: on average, 39 genes per phage genome belong to POGs, which is close to half of all genes in most phages. In an agreement with the notion of phage role in horizontal gene transfer, we see many cases of likely gene exchange between phages and their microbial hosts. At the same time, about 80% of all POGs are highly specific to phage genomes and are not commonly found in microbial genomes, indicating coherence and large degree of evolutionary independence of phage gene sets. The information on orthologous genes is essential for evolutionary classification of known bacteriophages and for reconstruction of ancestral phage genomes.

Bacteriophages↗
PubMed2006

Association of IL-7 with disease progression in Chinese HIV-1 seropositive individuals.

BACKGROUND: Elevated levels of interleukin-7 (IL-7) have been correlated with CD4(+) T cell depletion and the emergence of syncytium-inducing (SI) variants in human immunodeficiency virus type-1 (HIV-1) infection, and suggested as an indicator of acquired immunodeficiency syndrome (AIDS) disease progression. Therefore, we investigated the effects of IL-7 on disease progression and virus phenotype in Chinese HIV/AIDS patients. METHODS: In a cross-sectional study of 71 untreated HIV-1 seropositive individuals and 12 healthy donors, plasma IL-7 levels were determined by an ultra sensitive enzyme-linked immunosorbent assay (ELISA), and its relations to CD4(+) T cells, CD8(+) T cells, plasma viral loads and HIV phenotypes were analyzed. RESULTS: Significant higher IL-7 levels were found in Chinese HIV/AIDS patients [(3.33 +/- 3.60) pg/ml] than those of health controls [(1.2 +/- 0.81) pg/ml] (P < 0.05), and IL-7 levels were inversely associated with CD4(+) T cell counts (r = -0.497, P < 0.01). Furthermore, IL-7 levels were significant higher in patients with SI variants [(9.12 +/- 4.55) pg/ml] than those with non-syncytium-inducing variants [(1.50 +/- 2.69) pg/ml] (P < 0.01). CONCLUSIONS: Increased IL-7 levels were found in Chinese HIV/AIDS patients and significantly associated with disease progression, thus increased IL-7 plasma levels may indicate disease progression.

Adult↗
PubMed2006

Expression of mouse liver receptor homologue 1 in embryonic stem cells is directed by a novel promoter.

Liver receptor homologue 1 (LRH-1) plays important roles in many physiological processes and embryogenesis. However, little is known about the developmental regulation of lrh-1 expression. We identified a novel transcript of mouse lrh-1 (mlrh-1v2) from embryonic stem (ES) cells. mlrh-1v2 is expressed throughout embryogenesis and in several adult tissues, while the known transcript (mlrh-1v1) appears later during embryogenesis. mlrh-1v2 expression is directed by a new promoter which displays a strong activity in ES cells. The generation of the new transcript is conserved in rats. The identification of novel mlrh-1 variant and promoter is critical for elucidating LRH-1 functions in development and adult tissues.

Animals↗
PubMed2006

NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta.

Ultraviolet (UV) exerts its biological activities by activating downstream effectors, including NF-kappaB, JNK, and caspases. Activation of JNK is required for UV-induced apoptosis. It is unknown whether any crosstalk occurs between NF-kappaB and JNK in response to UV and, if so, how it affects UV killing. Here we report that NF-kappaB promotes UV-induced JNK activation, thereby contributing to UV-induced apoptosis. UV-induced JNK activation is impaired in RelA/NF-kappaB null murine embryonic fibroblasts. In resting cells, the preexisting nuclear RelA has already been recruited to PKCdelta promoter and is essential for its expression. UV-induced rapid and robust activation of JNK requires PKCdelta, which augments JNK phosphorylation-activation by its upstream kinases. The RelA/NF-kappaB-PKCdelta-JNK pathway is critical for UV-induced apoptosis, as it induces the immediate expression of the proapoptotic Fas ligand. Thus, our results demonstrate that RelA/NF-kappaB via PKCdelta positively regulates UV-induced JNK activation and provide a mechanism by which NF-kappaB promotes UV-induced apoptosis.

Animals↗
PubMed2006

Apoptosis of HL-60 cells induced by extracts from Narcissus tazetta var. chinensis.

Narcissus tazetta var. chinensis is one member of the Amaryllidaceae family. We found that extracts from N. tazetta var. chinensis (ENT) strongly decreased the survival rate of the following tumor cell lines: HL-60, K562, KT1/A3, and A3R. The cytotoxic effects of ENT on non-cancer cells lines (NHBE and NIH3T3) were smaller than on leukemia cell lines. AO/EB staining and flow cytometry assays showed that ENT induced HL-60 cell apoptosis. Furthermore, the release of cytochrome c and the increase of caspase-8, -9, and -3 activities were tested after HL-60 cells were treated with ENT, which indicated that the mitochondrial pathway and cell death receptor pathway were both involved in the apoptosis signal pathways induced by ENT. Upregulation of Bax showed that the Bcl-2 family was involved in the control of apoptosis. Our results suggest that apoptosis activity can be mediated by ENT in HL-60 cells.

Antineoplastic Agents↗