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Biomedical subjects

Song Li

Publications and source records attributed to Song Li.

139 records · Page 8Linked to original sources
PubMed2002

2,4,6-trinitrotoluene-induced reproductive toxicity via oxidative DNA damage by its metabolite.

Several epidemiological studies and animal experiments showed that 2,4,6-trinitrotoluene (TNT), a commonly used explosive, induced reproductive toxicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of TNT on the male reproductive system in Fischer 344 rats. TNT administration induced germ cell degeneration, the disappearance of spermatozoa in seminiferous tubules, and a dramatic decrease in the sperm number in both the testis and epididymis. TNT increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in sperm whereas plasma testosterone levels did not decrease. These results suggest that TNT-induced toxicity is derived from direct damage to spermatozoa rather than testosterone-dependent mechanisms. To determine the mechanism of 8-oxodG formation in vivo, we examined DNA damage induced by TNT and its metabolic products in vitro. 4-Hydroxylamino-2,6-dinitrotoluene, a TNT metabolite, induced Cu(II)-mediated damage to 32P-labeled DNA fragments and increased 8-oxodG formation in calf thymus DNA, although TNT itself did not. DNA damage was enhanced by NADH, suggesting that NADH-mediated redox reactions involving TNT metabolites enhanced toxicity. Catalase and bathocuproine inhibited DNA damage, indicating the involvement of H2O2 and Cu(I). These findings suggest that TNT induces reproductive toxicity through oxidative DNA damage mediated by its metabolite. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by TNT and other nitroaromatic compounds.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Interplay between integrins and FLK-1 in shear stress-induced signaling.

Blood flow can modulate vascular cell functions. We studied interactions between integrins and Flk-1 in transducing the mechanical shear stress due to flow. This application of a step shear stress caused Flk-1. Casitas B-lineage lymphoma (Cbl) activation (Flk-1. Cbl association, tyrosine phosphorylation of the Cbl-bound Flk-1, and tyrosine phosphorylation of Cbl) in bovine aortic endothelial cells (BAECs). The activation of integrins by plating BAECs on vitronectin or fibronectin also induced this Flk-1. Cbl activation. The shear-induced Flk-1. Cbl activation was blocked by inhibitory antibodies for alphavbeta3- or beta1-integrin, suggesting that it is mediated by integrins. Inhibition of Flk-1 by SU1498 also abolished this shear-induced Flk-1. Cbl activation. In contrast to the requirement of integrins for Flk-1. Cbl activation, the Flk-1 blocker SU1498 had no detectable effect on the shear-induced integrin activation, suggesting that integrins and Flk-1 play sequential roles in the signal transduction hierarchy induced by shear stress. Integrins are essential for the mechanical activation of Flk-1 by shear stress but not for the chemical activation of Flk-1 by VEGF.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Lipid-mediated delivery of oligonucleotide to pulmonary endothelium.

Pulmonary endothelium plays an important role in the maintenance of normal pulmonary physiology and its dysfunction is involved in a number of pulmonary diseases. Correction of endothelial dysfunction via antisense oligodeoxyonucleotides (ODN) is dependent on the development of a delivery vehicle that can efficiently deliver the ODN to pulmonary endothelium with minimal toxicity. To this end, we have developed a lipidic vector (LPD) that is composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) liposomes, protamine, and ODN. This formulation is highly efficient in delivering ODN to the lung via the vascular route. The efficiency of delivery is a function of lipid composition and of the charge ratio between lipid and ODN. Immunofluorescence staining of BrdU-labeled ODN suggested efficient accumulation of ODN in the alveolar capillary region. Transmission electron microscopy of immunogold localization of BrdU-labeled ODN confirmed that pulmonary endothelial cells were indeed targeted by the vector. Furthermore, this formulation is associated with minimal proinflammatory cytokine response and other hematologic toxicities when the ODN lack a potent unmethylated CpG motif. Pretreatment of mice with LPD containing an ODN against intercellular adhesion molecule-1 (ICAM-1) significantly decreased ICAM-1 expression in the lung following LPS challenge. These results provide a basis for lipid-mediated delivery of ODN for the treatment of pulmonary diseases.

Animals↗
PubMed2002

Crystallization and preliminary X-ray diffraction analysis of FKBP12 complexed with a novel neurotrophic ligand.

A novel neurotrophic ligand, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-Leucine ethyl ester, has been complexed with FKBP12 and crystallized using the hanging-drop vapor-diffusion method. Crystals belong to P2(1) space group, with unit cell parameters a=41.2, b=29.6, c=41.5 A, beta=114.0 degrees. The crystals diffract to 1.8 A resolution limit.

Crystallography, X-Ray↗
PubMed2002

Prevalence of cerebral palsy in children aged 1 - 6 in Guangxi, China.

OBJECTIVE: To study the prevalence of cerebral palsy (here in after referred to CP) in children aged 1 - 6 in Guangxi, China, and its epidemiologic characteristics and relevant risk factors. METHODS: Investigations on the prevalence and etiology of CP in children at ages of 1 - 6 were conducted in Nanning, Hengxian and Qinzhou of Guangxi from June to December in 1998, with a cluster sampling. RESULTS: Totally, 150 806 children aged 1 - 6 were investigated in Nanning, Hengxian and Qinzhou of Guangxi, with 89 418 boys and 61 388 girls. Among them, 193 children were diagnosed as CP, with a prevalence rate of 1.28 per thousand, higher in boys (136 cases, 1.52 per thousand ) than in girls (57 cases, 0.93 per thousand ), with statistical significance (chi(2) = 9.536 7, P = 0.02). Logistic regression analysis showed that risk factors for CP were children who could not cry after birth (neonatal asphyxia), Apgar score less than eight, delivery at lower level of maternity hospital, number of mother's gravidity, no prenatal checks for mothers, and taking antipyretics and preserved food with salt during pregnancy. CONCLUSIONS: Prevalence of CP in children of Guangxi was at a lower level in comparison with that in other areas at home and abroad, which, maybe, was related with the lower neonatal survival and higher infant mortality.

Cerebral Palsy↗
PubMed2001

[Study on Polyethylene Glycol Modified Porcine Hemoglobin Using Computer Modeling]

The structure analysis of porcine hemoglobin alphabeta dimer and the calculation of solvent accessible surface of the amino acids showed the epsilon-amino groups of the lysine are suitable for modification by polyethylene glycol (PEG). The modification of the lysine residues will not affect the carring oxygen capacity of Hb. Three types of linker have been designed to connect PEG and porcine hemoglobin. The lysines between porcine and bovine hemoglobin (pHb and bHb) are highly conserved, but the solvent accessible surface of conserved lysines are different. These suggested that the properties of homologous proteins are similar in pHb and bHb, but the characteristic derived from the homology analysis will be deviated from the actual status. The results of molecular dynamics simulation suggested that the chemical modified porcine hemoglobin would be no immunogenicity.

Journal Article↗
PubMedDate not supplied

Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles.

In this study, a novel lipid vector has been developed for targeted delivery of oligodeoxynucleotides (ODN) to tumors that overexpress folate receptor. This is based on a method developed by Semple et al. (1), which utilizes an ionizable aminolipid (1,2-dioleoyl-3-(dimethylammonio)propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles. Folate is incorporated into the lipid vesicles via a distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) spacer. These vesicles are around 100-200 nm in diameter with an ODN entrapment efficiency of 60-80%. Folate mediated efficient delivery of ODN to KB cells that overexpress folate receptor. Uptake of folate-targeted lipidic ODN by KB cells is about 8-10-fold more efficient than that of lipidic ODN without a ligand or free ODN. This formulation is resistant to serum. Thus, targeted delivery of ODN via this novel lipid vector may have potential in treating tumors that overexpress folate receptors.

Base Sequence↗
PubMedDate not supplied

Subchronic exposure to arsenic through drinking water alters expression of cancer-related genes in rat liver.

Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in drinking water), by using real-time quantitative RT-PCR and immunohistochemical analyses. Arsenic accumulated in the rat liver dose-dependently and caused hepatic histopathological changes, such as disruption of hepatic cords, sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm), and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta-catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and decreased expression of both PTEN and beta-catenin at all 3 doses. An immunohistochemical study revealed that each protein expression accords closely with each gene expression of mRNA level. In conclusion, subchronic exposure to inorganic arsenate caused pathological changes and altered expression of cyclin D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that arsenic liver toxicity involves disturbances of some cancer-related molecules.

Administration, Oral↗
PubMedDate not supplied

Biomimetic collagen scaffolds for human bone cell growth and differentiation.

Type I collagen provides a structural framework for connective tissues and plays a central role in the temporal cascade of events leading to the formation of new bone from progenitors. The aim of this study was to examine the ability of the cell-binding domain of type I collagen (P-15 peptide) to promote human bone marrow stromal cell adhesion, proliferation, and differentiation on three-dimensional scaffolds. Human bone marrow stromal cells were selected, expanded, and cultured on particulate microporous ABM ("pure" hydroxyapatite) phase adsorbed with or without P-15 under basal or osteogenic conditions. Immobilized P-15 increased alkaline phosphatase activity and bone morphogenetic protein 2 (BMP-2) gene expression after 1 and 5 days as determined by real-time polymerase chain reaction. P-15 promoted human bone marrow stromal cell attachment, spreading, and alignment on ABM as well as alkaline phosphatase-specific activity in basal and osteogenic cultures. The presence of mineralized bone matrix, extensive cell ingrowth, and cellular bridging between three-dimensional matrices adsorbed with P-15 was confirmed by confocal microscopy, scanning electron microscopy, and alizarin red staining. Negligible cell growth was observed on ABM alone. In vivo diffusion chamber studies using MF1-nu/nu mice showed bone matrix formation and organized collagen formation after 6 weeks. These studies indicate the potential of P-15 to generate appropriate biomimetic microenvironments for osteoblasts and demonstrate the potential for the exploitation of extracellular matrix cues for osteogenesis and, ultimately, bone regeneration.

Adsorption↗
PubMedDate not supplied

Injectable biopolymers enhance angiogenesis after myocardial infarction.

Novel strategies by which to repair ischemic myocardium after myocardial infarction include the use of three-dimensional polymer scaffolds. A comparative study was carried out to assess the therapeutic potential of fibrin, collagen I, and Matrigel as injectable biopolymers for repair after myocardial infarction. Using a rat model of left coronary artery occlusion followed by reperfusion, local injection of the biopolymers into the infarct zone yielded significantly higher levels of capillary formation, when compared with the saline control group, at 5 weeks posttreatment. However, the degree of angiogenesis was not significantly different among the biopolymers. In addition, the collagen biopolymer significantly enhanced infiltration of myofibroblasts into the infarct area when compared with the control group. The results of this study highlight the potential clinical benefit of these biopolymers as injectable scaffolds or cell delivery vehicles to the infarct zone after infarction.

Animals↗
PubMedDate not supplied

Roles of microtubule dynamics and small GTPase Rac in endothelial cell migration and lamellipodium formation under flow.

Endothelial cell (EC) migration is required for vascular development and wound healing. We investigated the roles of microtubule (MT) dynamics and the small GTPase Rac in the fluid shear stress-induced protrusion of lamellipodia and enhancement of migration of bovine aortic ECs (BAECs). Shear stress increased lamellipodial protrusion and cell migration. Treating BAECs with paclitaxel (Taxol), an MT-stabilizing agent, inhibited lamellipodial protrusion and reduced migration speed in both the static and sheared groups. After Taxol washout, both lamellipodial protrusion and cell migration increased in the flow direction. Taxol treatment also decreased the shear-induced Rac activation. Transfection of BAECs with a dominant negative mutant of Rac1 inhibited lamellipodial protrusion and cell migration under static and shear conditions. Transfection with an activated mutant of Rac1 induced lamellipodia in all directions and attenuated the shear-induced migration, suggesting that an appropriate level of Rac activity and a polarized lamellipodial protrusion are important for cell migration under static and shear conditions. Our findings suggest that MT dynamics and optimum Rac activation are required for the polarized protrusion of lamellipodia that drives the directional EC migration under flow.

Animals↗