Biomedical subjects

Li Cui

Publications and source records attributed to Li Cui.

26 records · Page 2Linked to original sources

PubMed2003

Survival and function of mouse embryonic stem cell-derived cardiomyocytes in ectopic transplants.

OBJECTIVE: Embryonic stem cell-derived cardiomyocytes are a useful source for cell transplantation into the heart, as well as for tissue engineering of the extracardiac vascular system. The present study was designed to investigate the survival and contractile function of embryonic stem cell-derived cardiomyocytes around large blood vessels to assess the feasibility of their ectopic use for future engineering of cardiovascular tissues. METHODS: The mouse embryonic stem cell-derived cardiomyocytes were transplanted into the retroperitoneum of the adult nude mice, and the myocardial tissues that developed were characterized by electrophysiological and histological techniques. RESULTS: Macroscopic and electrophysiological analyses showed spontaneously contracting transplants in the host retroperitoneum 7 and 30 days after transplantation. Immunohistochemistry detected developing cardiomyocytes in the transplants on Day 7, which formed the myocardial tissues. They were positive for cardiac troponin I, cadherin, connexin 43, and proliferating cell nuclear antigen, but negative for alpha-smooth muscle actin. Vascular formation was discernible in the transplant tissues. By Day 30, more mature myocardial tissues had been established in the transplants. Electron microscopic study emphasized that the transplant tissues comprised cardiomyocytes, in which myofibrils with organized sarcomeres were observed. Desmosomes, fasciae adherens and gap junctions were evident in the cellular junctions. CONCLUSIONS: The cardiomyocytes derived from the mouse ES cells were demonstrated to be viable and function in the ectopic site of the host retroperitoneum up to Day 30, following a process of proliferation and differentiation. Vascularization and host perfusion beneficial for the survival of the cardiomyocytes occurred in the transplants.

Animals↗

PubMed2003

Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: relationship to glucose disposal.

The goal of this work was to compare the effects of different antidiabetic therapies on the phenotype of skeletal muscle in type 2 diabetic subjects failing sulfonylurea therapy. Subjects were treated with a thiazolidinedione (troglitazone, TGZ) or a biguanide (metformin, MET) in addition to glyburide for 3 to 4 months. Insulin action was determined with a hyperinsulinemic (300 mU. m(-2). min(-1)) euglycemic (5.0 to 5.5 mmol/L) clamp. Biopsies were obtained from the vastus lateralis muscle for morphological analysis. Despite similar glycemic control, relative increases in the insulin-stimulated glucose disposal rate (GDR) were greater after TGZ treatment (37 +/- 8% increase, P <.05) than after MET (21 +/- 11%, P <.05). Neither treatment had any effect on fiber type composition of the muscle. Capillary density was reduced in diabetic subjects compared to a nondiabetic group (P <.01) and was increased with TGZ treatment (P <.05), while MET was without significant effect. Diabetic muscle also displayed a lower mitochondrial volume density that was unaltered by either treatment. Both TGZ and MET therapy resulted in a reduction in the lipid content of muscle (percent fiber volume as lipid droplets); the relative decrease tended to be greater for TGZ (-33% v -23% for MET). The relative (%) improvement in GDR was correlated with the change in lipid content (r = -0.756, P <.05) after TGZ treatment; no such relationship was observed for MET. From these results we conclude that the higher potency of TGZ to increase capillary density and reduce the lipid content of muscle may contribute to its greater ability to improve glucose disposal in skeletal muscle of type 2 diabetic individuals.

Adult↗

PubMed2003

The permissive effect of zinc deficiency on uroguanylin and inducible nitric oxide synthase gene upregulation in rat intestine induced by interleukin 1alpha is rapidly reversed by zinc repletion.

Deficient intake of zinc from the diet upregulates both uroguanylin (UG) and inducible nitric oxide synthase (iNOS) expression in rats. Because these changes influence intestinal fluid secretion and intestinal cell pathophysiology, they relate to the incidence of diarrheal disease and its reversal by zinc as well as intestinal inflammation in general. A model of moderate zinc deficiency in rats, which changes molecular indices of zinc deficiency, was used to further explore the effects of the proinflammatory cytokine interleukin (IL)-1alpha and zinc repletion on these changes. IL-1alpha has been shown to have a role in the intestinal inflammation that occurs with bacterial infection. Our results showed a permissive effect of zinc deficiency on both UG and iNOS expression. Specifically, UG expression was responsive to zinc deficiency and IL-1alpha challenge, which were additive when combined, whereas iNOS expression was upregulated by IL-1alpha only during the deficiency. Immunohistochemistry showed that the increase in UG was limited to enterocytes of the upper villus but, in contrast, the increase in iNOS was principally in cells of the lamina propria of IL-1alpha-treated rats. Cells exhibiting UG upregulation did not co-express serotonin. Repletion with zinc reversed upregulation of the iNOS gene within 1 d, whereas UG upregulation required 3-4 d to return to normal. This differential response to repletion suggests that mechanisms of UG and iNOS dysregulation are different. Dysregulation of both genes may contribute to the severity of zinc-responsive diarrheal disease and intestinal inflammatory disease.

Animals↗

PubMed2003

Zinc transporters 1, 2 and 4 are differentially expressed and localized in rats during pregnancy and lactation.

Zinc metabolism is controlled within relatively restricted limits throughout the life cycle. Expression and localization of zinc transporters 1, 2 and 4 during pregnancy and lactation in small intestine, mammary gland and liver of the rat were investigated using Northern analysis, Western blotting and immunohistochemistry. In maternal tissues, zinc transporter 4 was the most widely expressed among these zinc transporters in the tissues examined. In small intestine and liver, zinc transporter 4 increased from levels found during late gestation, but zinc transporter 1 did not. Zinc transporter 2 expression in small intestine was transient, being highest around parturition, and was not detected in liver. Immunohistochemistry revealed unique patterns of zinc transporter localization at different stages of development. In the placenta, zinc transporters 1 and 4 were found concentrated along the villous visceral splanchnopleure. In the mammary gland, zinc transporter 4 was most abundant in cells surrounding the alveolar ducts and oriented to the basement lamina. All three transporters were highly expressed in neonatal small intestine, principally near the apical surface, but zinc transporters 1 and 4 increased in abundance at the basolateral surface during development. Zinc transporter 2 was oriented apically, directly adjacent to the microvilli of enterocytes. Within the intestine, expression of each transporter was limited to enterocytes. These results support a role for these transporters in maintaining an adequate zinc supply derived from the maternal diet for zinc acquisition and use by the fetus and neonate.

Analysis of Variance↗

PubMed2003

Regulation of zinc metabolism and genomic outcomes.

Differential mRNA display and cDNA array analysis have identified zinc-regulated genes in small intestine, thymus and monocytes. The vast majority of the transcriptome is not influenced by dietary zinc intake, high or low. Of the genes that are zinc regulated, most are involved in signal transduction (particularly influencing the immune response), responses to stress and redox, growth and energy utilization. Among the genes identified are uroguanylin (UG), cholecystokinin, lymphocyte-specific protein tyrosine kinase (LCK), T-cell cytokine receptor, heat shock proteins and the DNA damage repair and recombination protein-23B. Zinc transporters (ZnT) help regulate the supply of this micronutrient to maintain cellular functions. Expression of ZnT-1 and -2 is regulated by dietary zinc in many organs including small intestine and kidney. ZnT-4 is ubiquitously expressed but is refractory to zinc intake. Expression of ZnT-1, -2 and -4 changes markedly during gestation and lactation from highly abundant to undetectable. Each ZnT has an endosomal-like appearance in the tissues examined. Upregulation of ZnT-1 and ZnT-2 by dietary zinc strongly implicates these transporters in zinc acquisition and/or storage for subsequent systemic needs. THP-1 cells were used as a model to examine the response of human cells to changes in zinc status. Based on mRNA quantities, Zip1 and ZnT-5 were the most highly expressed. Zinc depletion of these cells decreased expression of all transporters except Zip2, where expression increased markedly. Collectively, these findings provide a genomic footprint upon which to address the biological and clinical significance of zinc and new avenues for status assessment.

Animals↗

PubMed2003

Immunohistochemical localization of hepatocyte growth factor activator (HGFA) in developing mouse liver tissues. Heterogeneous distribution of HGFA protein.

Hepatocyte growth factor activator (HGFA) can activate the single-chain hepatocyte growth factor (HGF) required for embryonic development. We studied the immunohistochemical (IHC) localization of HGFA in adult mouse liver and its developmental changes from embryonic day 12 to postnatal day 30. A heterogeneous distribution of HGFA was observed in adult liver tissues. The hepatocytes around the hepatic veins were preferentially positive for HGFA, whereas those in other areas were negative. Depending on the vascular diameter, the hepatic veins were bordered by a one- to three-cell-thick layer of hepatocytes positive for HGFA, which showed evidence of cell-cell heterogeneity in staining intensity. Immunoelectron microscopy detected ubiquitous distribution of the gold particle reaction product for HGFA in the cytoplasm of these hepatocytes, especially in the rough endoplasmic reticulum. Developmental analysis indicated that there was hardly any staining of HGFA until postnatal day 0 and that noticeable staining was initially detected in the pericentral hepatocytes on postnatal day 3. Subsequently, immunoreactivity increased and the distinct staining pattern had been established by postnatal day 30. These results suggest that HGFA proteins are produced in the hepatocytes surrounding the efferent hepatic veins in the mouse and that development of the unique distributing pattern takes place postnatally.

Animals↗

PubMed2002

Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation.

To evaluate the immunological functions of the greater omentum in the peritoneal cavity, the localization of cell adhesion molecules (CAMs) on mesothelial cells and leukocytes in the omental milky spots were studied in normal and lipopolysaccharide (LPS)-stimulated mice by means of immunoelectron microscopy. The milky spots featured numerous leukocytes among the dome-shaped mesothelial cells, even in the normal stable state. Leukocyte integrins LFA-1, Mac-1, and VLA-4 were preferentially localized to microvilli and ruffles of macrophages and lymphocytes. The mesothelial cells of the milky spots showed higher ICAM-1 levels than did those of other omental regions, and fibronectin was detected in the stomata. The number of leukocytes markedly increased following an increase in proliferating cell nuclear antigen (PCNA)-positive cells in the milky spots after LPS stimulation. The mesothelial cells contained VCAM-1 newly restricted to the microvilli and increasing amounts of ICAM-1. These results show that the omental milky spots are active sites for leukocyte migration and peritoneal leukocyte supply because of the presence of adhesion molecules and active cell proliferation. Proliferative active leukocytes and those that have migrated from vessels pass through the stomata via an interaction of VLA-4 and fibronectin, adhere to the microvilli of the activated mesothelial cell surface as the result of an interaction between ICAM-1/VCAM-1 and integrins, and exude into the peritoneal cavity. Much of the exudation and adhesion of leukocytes seen in the milky spots of LPS-stimulated mice may be attributable to an increase in cell proliferation and in the amounts of ICAM-1 and VCAM-1.

Animals↗

PubMedDate not supplied

Embryonic stem cell-derived embryoid bodies in three-dimensional culture system form hepatocyte-like cells in vitro and in vivo.

Pluripotent embryonic stem (ES) cells can be a source of hepatocytes for bioartificial livers or transplantation. In this study, embryoid bodies (EBs) were formed from ES cells cultured in polypropylene conical tubes. The EBs were then inserted into a collagen scaffold three-dimensional culture system and stimulated with exogenous growth factors and hormones to induce hepatic histogenesis. The EB-derived cells expressed liver-specific genes, and albumin-positive cells formed cord-like structures that were not present in two-dimensional monolayer culture systems. However, these albumin- positive cells were not cytokeratin 18 positive. Electron microscopy showed immature hepatocyte- like cells having tight junctions, rough endoplasmic reticulum, and intercellular canaliculi. The scaffold including EB-derived hepatocyte-like cells was transplanted into the median lobes of partially hepatectomized nude mice. After 7 and 14 days, cells positive for both albumin and cytokeratin 18 appeared in the transplant and formed clustered aggregates. Thus the collagen scaffold three-dimensional culture system and the liver regeneration environment induced hepatocyte-like cells and hepatic lobule-like aggregates from EBs. Therefore, differentiating EBs in the scaffold culture system may be useful in developing bioartificial livers, secondary livers, and as pharmaceutical models.

Animals↗