Biomedical subjects

Jian Guo

Publications and source records attributed to Jian Guo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Lentiviral shRNA silencing of murine bone marrow cell CCR2 leads to persistent knockdown of CCR2 function in vivo.

A major barrier in hematopoietic gene function studies is posed by the laborious and time-consuming generation of knockout mice with an appropriate genetic background. Here we present a novel lentivirus-based strategy for the in situ generation of hematopoietic knockdowns. A short hairpin RNA (shRNA) was designed targeting murine CC-chemokine receptor 2 (CCR2), which was able to specifically blunt CCR2 expression at the mRNA, protein, and functional levels in vitro. Reconstitution of irradiated recipient mice with autologous bone marrow that had been ex vivo transduced with shRNA lentivirus led to persistent down-regulation of CCR2 expression, which translated into a 70% reduction in CCR2-dependent recruitment of macrophages to an inflamed peritoneal cavity without noticeable side effects on related chemokine receptors or general inflammation status. These findings clearly demonstrate the potential of shRNA lentivirus-infected bone marrow transplantation as a rapid and effective method to generate hematopoietic knockdowns for leukocyte gene function studies.

Animals↗

PubMed2005

Repopulation of apolipoprotein E knockout mice with CCR2-deficient bone marrow progenitor cells does not inhibit ongoing atherosclerotic lesion development.

OBJECTIVE: Using bone marrow transplantation, we have previously demonstrated the critical role that hematopoietic CCR2 plays in early atherogenesis. Reconstitution of irradiated apolipoprotein (apo) E3-Leiden mice with CCR2-deficient bone marrow progenitor cells resulted in 86% reduction on overall atherosclerotic lesion development. However, no data on CCR2 in the cause of established atherosclerosis have been reported so far. METHODS AND RESULTS: To study the role of CCR2 in established atherosclerotic lesions, bone marrow progenitor cells harvested from apoE-/- and apoE-/-/CCR2-/- mice were transplanted into lethally irradiated 16-week-old apoE-/- mice with established atherosclerotic lesions. No significant differences were found in serum total cholesterol and triglycerides levels at different time points after transplantation. At age 16 weeks, lesion size in control apoE-/- mice was 3.28+/-1.06x10(5) microm2. At 9 weeks after transplantation, apoE-/---> apoE-/- and apoE-/-/CCR2-/---> apoE-/- mice had developed significantly larger atherosclerotic lesions (4.49+/-0.92x10(5) microm2, P<0.02 and 4.15+/-0.62x10(5) microm2, P<0.04 compared with controls, respectively). However, no significant effect of disruption of hematopoietic CCR2 was observed on the progression of lesions. Furthermore, the macrophage positive area (78+/-4% versus 72+/-9%) and collagen content (11+/-6% versus 15+/-3%) of the lesions were similar as well. CONCLUSIONS: In contrast to the critical role of CCR2 in the initiation of atherogenesis, bone marrow progenitor cell-derived CCR2 does not influence the progression of established atherosclerotic lesions, pointing to additional mechanisms for recruitment of monocytes at later stages of lesion development.

Animals↗

PubMed2005

Comparison of Gd [DTPA-bis (2-aminoethoxy) ethane] polymeric contrast agent with gadodiamide injection for interstitial MR lymphography: experimental study with rabbits.

PURPOSE: To compare the differences between macromolecular and small molecular contrast agents in interstitial magnetic resonance (MR) lymphography. MATERIALS AND METHODS: In two groups of rabbits (N = 12 each), 0.5-mL volumes of 0.5 M and 0.1 M gadodiamide, respectively, were injected subcutaneously into the dorsal feet of both hind legs. After a 24-hour interval, 0.5 mL of Gd [DTPA-bis (2-aminoethoxy) ethane] polymeric contrast agent (Gd-poly-DTPA-EOEA) injection (0.1 M) was injected into the same sites in each rabbit. T1-weighted three-dimensional gradient-echo and maximum intensity projection (MIP) images were obtained before and after the administration of each agent. The nodal maximum short-axis diameter (MSAD) and signal-to-noise ratio (SNR) at each time point were measured. Postmortem measurements of nodal MSADs were also performed. The nodal MSAD measurements obtained by MR lymphography were compared with the postmortem measurements. As an additional control experiment, six rabbits received a subcutaneous injection of 0.5 mL of 0.1 M gadodiamide at the same sites as those described above. This procedure was repeated after a 24-hour interval to determine whether the first injected gadodiamide had any effect on the performance of the subsequently injected agent, by comparing the differences in nodal MSADs obtained by MR lymphography after each injection. RESULTS: Gd-poly-DTPA-EOEA showed a significantly longer enhancement plateau compared to gadodiamide. In comparison with postmortem measurements, nodal measurements by MR lymphography with Gd-poly-DTPA-EOEA at the peak-enhancement phase revealed no significantly different MSADs (P > 0.05), whereas nodal measurements by MR lymphography with gadodiamide showed significantly smaller MSADs (P < 0.05). A comparison of the nodal MSADs measured in two gadodiamide-enhanced MR examinations after the 24-hour interval showed no significant difference (P > 0.05). CONCLUSION: Interstitial MR lymphography with polymeric Gd-poly-DTPA-EOEA enhancer enables more sufficient and reliable visualization of lymph nodes compared to small molecular gadodiamide.

Animals↗

PubMed2005

Distribution of rDNA in the nucleus of Giardia lamblia: detection by Ag-I silver stain.

OBJECTIVE: To determine whether rDNA of Giardia lamblia forms a nucleolus organizer region (NOR)-like structure and is in a very primitive state. STUDY DESIGN: G lamblia was used as the experimental animal, with Euglena gracilis as the control. The distribution was demonstrated indirectly by the modified Ag-I silver technique, which can specifically indicate the NOR under both light and electron microscopes. RESULTS: In the ultrathin sections of silver-stained Euglena cells, all the silver grains were concentrated in the fibrosa of the nucleolus, while no grains found in the cytoplasm, nucleoplasm, condensed chromosomes or pars granulosa of the nucleus. In the silver-stained Giardia cells, no nucleolus was found; a few silver grains were scattered in the nucleus but were not concentrated in any specific region. CONCLUSION: The distribution of silver grains in G lamblia showed that the transcription of rDNA occurs inside the nucleus, though no nucleolus is present. It is possible that chromosomes are in a very primitive state in diplomonad cells; as each chromosome has few prRNA genes, the transcription is independent of a nucleolus. These results imply that the rDNA of Giardia does not form a NOR-like structure and seems to represent a very primitive state in the evolution of the nucleolus.

Animals↗

PubMed2004

The presence of leukocyte CC-chemokine receptor 2 in CCR2 knockout mice promotes atherogenesis.

OBJECTIVE: To selectively determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in atherogenesis. METHODS AND RESULTS: Bone marrow progenitor cells harvested from CCR2(+/+) mice were transplanted into irradiated CCR2(-/-) mice, representing the whole-body absence of CCR2 except in leukocytes. Transplantation of CCR2(-/-) bone marrow into CCR2(-/-) mice served as control. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet for another 10 weeks in order to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the two groups. However, the mean cross-sectional aortic root lesion area of CCR2(+/+)-->CCR2(-/-) mice amounted up to 12.28+/-3.28x10(4) microm(2), compared with only 3.08+/-0.74 x 10(4) microm(2) observed in the CCR2(-/-)-->CCR2(-/-) group. Thus, the presence of CCR2 exclusively on leukocytes induces a fourfold increase in aortic lesion area. This extent of lesion development was comparable to C57Bl/6 mice receiving CCR2(+/+) bone marrow (10.08+/-3.30x10(4) microm(2)). CONCLUSION: These results point at a dominant role of leukocyte CCR2 in atherogenesis, implying that CCR2 from nonleukocyte sources, like endothelial cells or smooth muscle cells, is less critical in the initiation of atherosclerosis. Pharmacological inhibition of leukocyte CCR2 function might be a promising strategy to prevent atherosclerosis.

Animals↗

PubMed2004

A novel method for protein secondary structure prediction using dual-layer SVM and profiles.

A high-performance method was developed for protein secondary structure prediction based on the dual-layer support vector machine (SVM) and position-specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI-BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three-state overall per-residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available at http://www.bioinfo.tsinghua.edu.cn/pmsvm.

Computational Biology↗

PubMed2004

[Epidemiological study on semen quality of 562 volunteers aged 22-30].

OBJECTIVE: This study is to understand the difference of semen quality among the different areas and the related factors. METHODS: Five hundred and sixty-two people were under from seven provinces. RESULTS: Results showed that the quantity and density of semen, the rate of moving forward semen, livability, percent age of normal formed semen and the total number of semen were statistically different among the seven areas. The difference was ranged as 28.82%, with the highest 2.95 ml in Shanxi province and the lowest 2.29 ml in Henan province. Geometric mean of semen density was found the lowest 36.27 x 10(6)/ml in Guizhou province, next to it was 42.52 x 10(6)/ml in Shandong province and the highest was 74.77 x 10(6)/ml in Hebei province. The percent age with forward progression of semen was seen the lowest 44.40% in Henan province, followed by 51.88% in Hebei province and 52.88% in Zhejiang province and the highest were 76.50% in Shanghai, 75.24% in Shanxi province, with a range of 72.30%. The highest semen viability was 85.89% in Shanghai, while the lowest 72.35% in Henan, with a range of 18.71%. Normal sperm morphology was seen the lowest 68.45% in Hebei province, with the highest 88.06% in Guizhou province, and the range was 28.65%. The geometric mean of total sperm count was seen the highest 204.23 x 10(6)/ml in Hebei province and the lowest 77.69 x 10(6)/ml in Guizhou province. Results showed through analysis of variance that some indexes were different in some provinces. CONCLUSION: The results indicated that the semen quality was different in different regions in China and its influential factors may be region and geography environment.

Adult↗

PubMed2004

Effect of artemether on Schistosoma mansoni: dose-efficacy relationship, and changes in worm morphology and histopathology.

OBJECTIVE: To investigate the effects of artemether on Schistosoma mansoni harboured in mice, with particular consideration on single dose-efficacy relationship, hepatic shift and artemether-induced alterations in worm morphology and histopathology. METHODS: Groups of mice, infected with 21 d old S. mansoni, were treated with artemether at single oral doses of 12.5 mg/kg to 600 mg/kg. Worm burden reduction was assessed 28 d post-treatment. The hepatic shift was investigated in mice infected with 46 d old S. mansoni and treated with artemether at a single oral dose of 400 mg/kg within a period of 14 d post-treatment. Morphological and histopathological observations were made in adult worms in mice, subject to single oral dose of artemether at 400 mg/kg. RESULTS: The minimum effective dose of oral artemether against juvenile worms in mice was 200 mg/kg, resulting in a worm burden reduction of 81%. The hepatic shift commenced 8 h post-treatment, and all worms shifted to the liver 3-7 d post-treatment. Fourteen days post-treatment, 31% of the worms returned to the mesenteric veins. Treatment with artemether resulted in decreased worm body size, expansion of the pharynx and dilation of the gut with marked reduction in pigment. Focal tegumental damage was observed among female worms with adherence of host leukocytes and degeneration of ovary and vitelline glands, as well as atrophy of testis in male worms. Artemether-damaged worms were surrounded and infiltrated by eosinophils. CONCLUSION: The minimum effective dosage of artemether against 21 d old S. mansoni in mice is 200 mg/kg. Artemether also exhibits effect against adult schistosomes, including shrinkage and degeneration, and can lead to worm death. The predominant inflammatory cell surrounded and infiltrated into the artemether-damaged worm is eosinophil.

Animals↗

PubMed2004

[Additive therapeutic effect of a combination of artemether and daphnetin against Plasmodium berghei in mice].

OBJECTIVE: To investigate the therapeutic effect of a combination of artemether and daphnetin against Plasmodium berghei ANKA strain in mice. METHODS: Groups of P. berghei infected mice were treated with various oral doses of artemether and daphnetin according to "4-day suppress assay". Thin blood smears were made on the fifth day after inoculation of parasites and the parasitemia reduction rate was calculated. The ED50 values obtained were plotted on isobolograms. A combined action of artemether and daphnetin was assessed. RESULTS: Artemether 0.4 mg/(kg x d) x 4d exhibited no detectable antimalarial effect, while artemether 0.4 mg/(kg x d) x 4d combined with daphnetin 7.7 mg/kg. d x 4d showed potent antiparasile efficacy. The ED50s of artemether in combination with daphnetin were lower than that of single artemether or daphnetin. The R-values were higher than 0.4, but lower than 2.7. CONCLUSION: The combination of artemether with daphnetin showed an additive antiparasile effect.

Animals↗

PubMed2004

Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites.

OBJECTIVE: To compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo. METHODS: Schizontocidal activity of recrystallized or crude daphnetin at various dosages was assessed in mice infected with Plasmodium berghei ANKA using a "4-day suppress assay". RESULTS: The comparison of the reduction rate of parasitemia caused by either recrystallized or crude dephnetin showed that ED(50) of crude daphnetin was 18.36 mg/kg, with 95% confidence limit of 5.96-56.54 mg/kg while ED50 of recrystallized daphnetin was 11.46 mg/kg, with 95% confidence limit of 8.63-15.22 mg/kg. CONCLUSION: The results indicate that the efficacy of recrystallized daphnetin is 37.6% higher than that of crude daphnetin.

Animals↗

PubMed2003

The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens.

Microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. However, ECM components can also serve as an integral part of the innate immunity. Mice lacking expression of mindin (spondin 2), a highly conserved ECM protein, have an impaired ability to clear bacterial infection, and mindin-deficient macrophages show defective responses to a broad spectrum of microbial stimuli. Moreover, mindin binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Thus, mindin is essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens.

Amino Acid Sequence↗

PubMed2003

Lymphocyte accumulation in the spleen of retinoic acid receptor-related orphan receptor gamma-deficient mice.

The hormone nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORgamma) plays important roles in thymocyte development and lymphoid organogenesis. RORgamma and its thymus-specific isoform RORgammat are expressed in the thymus, but not in the spleen and bone marrow (BM). However, RORgamma(-/-) mice have 2- to 3-fold more splenocytes than wild-type controls due to an accumulation of conventional resting B lymphocytes. The increase in B lymphocytes in RORgamma(-/-) mice is caused neither by abnormal B cell development in the BM nor by an obvious defect in the peripheral T cell compartment. Furthermore, analyses of BM chimeras using either RORgamma(-/-) or recombinase-activating gene-2(-/-) mice as recipients and wild-type or RORgamma(-/-) mice as donors, respectively, demonstrate that the splenic microenvironment of RORgamma(-/-) mice is defective, since wild-type T and B lymphocytes accumulated in these chimeric mice. In addition, T lymphocyte homeostasis was altered due to a lowered thymic output in RORgamma(-/-) mice. Collectively, these results suggest that RORgamma regulates lymphocyte homeostasis at multiple levels.

Animals↗

PubMed2003

Transplantation of monocyte CC-chemokine receptor 2-deficient bone marrow into ApoE3-Leiden mice inhibits atherogenesis.

OBJECTIVE: To determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in the early development of atherosclerosis METHODS AND RESULTS: Bone marrow cells harvested from CCR2 (-/-) and CCR2 (+/+) mice were transplanted into ApoE3-Leiden mice, a mouse strain susceptible for diet-induced atherosclerosis. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet (1% cholesterol, 15% fat, 0.5% cholate) for another 8 weeks to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the CCR2 (+/+) --> ApoE3-Leiden and CCR2 (-/-) --> ApoE3-Leiden mice. However, the mean cross-sectional aortic root lesion area of CCR2 (-/-) --> ApoE3-Leiden mice was only 2.94+/-1.94x10(4) microm2 compared with 20.94+/-12.71x10(4) microm2, for CCR2 (+/+) --> ApoE3-Leiden mice. Thus, the absence of CCR2 on leukocytes induces an 86% reduction of aortic lesion area as compared with controls (n=10, P<0.01). CONCLUSIONS: These results provide direct evidence that CCR2 expressed by leukocytes plays a critical role in the initiation of early atherosclerosis and that pharmacological intervention in CCR2 function represents an attractive target to inhibit atherogenesis.

Animals↗

PubMed2003

Preparation of Gd3+-containing polymer complex as a novel magnetic resonance signal-enhancing coating material.

This study investigated the suitability of a Gd(3+)-containing polymer complex used as a magnetic resonance (MR) signal-enhancing coating material. The synthesis of the Gd>(3+)-containing polymer complex was done by conjugating N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA) with poly (styrene-maleic acid) copolymer (SMA), followed by coordinating with Gd(3+). The characterizations of FT-IR, NMR and XPS confirmed that HEDTA was covalently attached to SMA and Gd(3+)-containing polymer complex was formed. Coating such Gd(3+)-containing polymer complex on the surface of polypropylene (PP) catheter was performed by solution coating method. The results of MR imaging experiments in vitro indicated that the PP catheter coated with this coating material showed strong MR signal in the vicinity of the catheter surface and a clear contrast between the catheter surface and background. Based on these results, a novel MR signal-enhancing coating material, which showed the great potentialities in making catheters for endovascular intervention, visible by MR imaging, can be developed.

Journal Article↗

PubMed2002

Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary V(alpha) to J(alpha) rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias towards 3' J(alpha) usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the J(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire.

Animals↗

PubMed2002

RRR-alpha-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest.

AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-alpha-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest. METHODS: Human gastric cancer SGC-7901 cells were regularly incubated in the presence of VES at 5, 10 and 20mg x L(-1) (VES was dissolved in absolute ethanol and diluted in RPMI 1640 complete condition media correspondingly to a final concentration of VES and 1 mL x L(-1) ethanol), succinic acid and ethanol equivalents as vehicle (VEH) control and condition media only as untreated (UT) control. Trypan blue dye exclusion analysis and MTT assay were applied to detect the cell proliferation. Cells were pulsed with 37kBq of tritiated thymidine and (3H) TdR uptake was measured to observe DNA synthesis. Apoptotic morphology was observed by electron microscopy and DAPI staining. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect VES-triggered apoptosis. RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppression by 24.7%, 49.2% and 68.7% following 24h of VES treatment at 5, 10 and 20 mg x L(-1), respectively, similar to the findings from MTT assay. DNA synthesis was evidently reduced by 35%, 45% and 98% after 24h VES treatment at 20mg x L(-1) and 48 h at 10 and 20mg x L(-1), respectively. VES induced SGC-7901 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation/margination, nucleus fragmentation and apoptotic body formation, typical apoptotic sub-G1 peak by flow cytometry and increase of apoptotic cells by TUNEL assay in which 90% of cells underwent apoptosis after 48 h of VES treatment at 20 mg x L(-1). CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest. Inhibition of SGC-7901 cell growth by VES is dose- and time-dependent. Therefore VES can function as a potent chemotherapeutic agent against human gastric carcinogenesis.

Apoptosis↗

PubMed2002

Potential long-term toxicity of repeated orally administered doses of artemether in rats.

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.

Administration, Oral↗

PubMed2002

[Determination of p-tert-butylcatechol in styrene monomer by gas chromatography/mass spectrometry].

An efficient method for the determination of p-tert-butylcatechol (TBC) in styrene monomer by gas chromatography/mass spectrometry (GC/MS) has been established. The sample was injected directly, and separated by gas chromatography with capillary column (HP-1, 30 m x 0.32 mm i.d. x 0.25 micron), then determined by a mass-spectrometer with electron impact (EI) at selected ion monitoring (SIM) mode. There was a good linear relationship within the range of 5 mg/kg-50 mg/kg (r2 = 0.9987). Compared with the colorimetric determination by a spectrophotometer (ASTM D4590), the method was proved to be fast and accurate.

English Abstract↗