Biomedical subjects

Ying Qian

Publications and source records attributed to Ying Qian.

16 recordsLinked to original sources

PubMed2006

Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway.

To investigate the possibility that natural medicines affect lipid metabolism by regulating lipoprotein lipase (LPL) expression, a green fluorescent protein (GFP) gene was constructed downstream of the peroxisome proliferator response element (PPRE) and the constructed plasmid was microinjected into Xenopus oocytes to establish a PPRE regulatory reporter system. Using this system, hawthorn flavonoids were quickly selected from a panel of natural medicines and found to up-regulate GFP expression by an effect on PPRE. To confirm the effect of hawthorn flavonoids, we treated mice orally with water (control), hawthorn flavonoids, and pioglitazone and measured the LPL levels in serum, adipose tissue, and muscle by an enzyme-linked immunosorbent assay. The serum LPL levels were no different from the controls after treatment with either hawthorn flavonoids or pioglitazone, but LPL increased significantly in muscular tissues and decreased in adipose tissues. These results demonstrate that hawthorn flavonoids meditate LPL expression in mice with tissue-specific differences. A novel PPRE regulatory report system was established for rapid and effective selection and evaluation of LPL-mediating drugs.

Adipose Tissue↗

PubMed2006

Changes of skeletal muscle adiponectin content in diet-induced insulin resistant rats.

The current study examined the relationship between skeletal muscle levels of adiponectin and parameters of insulin sensitivity. A high fat/sucrose diet (HFD) for 20 weeks resulted in significant increases in body weight, serum insulin, triglycerides (TG), and free fatty acids (FFA) (all p < 0.01). Interestingly, this diet leads to a slight increase in serum adiponectin, but significant decreases in gastrocnemius muscle and white adipose adiponectin (all p < 0.05). HFD for 4 weeks also resulted in a significant decrease in muscle adiponectin, which correlated with serum insulin, TG, and FFA (all p < 0.05). Treatment of the 4-week HFD rats with a PPARgamma agonist GI262570 ameliorated the diet-induced hyperinsulinemia and dyslipidemia, and effectively restored muscle adiponectin (all p < 0.05). This study demonstrated that HFD-induced hyperinsulinemia and dyslipidemia appeared without changes in serum adiponectin, but were associated with decreased tissue adiponectin. This provides the first evidence for a connection between tissue adiponectin and diet-induced hyperinsulinemia and dyslipidemia.

Adiponectin↗

PubMed2006

Effect of curcumin on the expression of LDL receptor in mouse macrophages.

To investigate the molecular mechanisms of lipid-lowering drug, Rhizoma Curcumae Longae, we treated the mouse macrophages with curcumin, which was purified from the ethanol extraction of Rhizoma Curcumae Longae. The LDL receptors expressed in the macrophages were determined by ELISA, FLISA and assay of LDL uptake. Here for the first time, we found that curcumin obviously up-regulated the expression of LDL receptor in mouse macrophages, and the dose-effect relationship was demonstrated.

Animals↗

PubMed2006

Keratoprosthesis: current techniques.

PURPOSE: To compare and contrast the techniques and results of keratoprosthesis (KPro) using the Cardona device (1975-1985) with those related to the use of the Dohlman-Doane type 1 device (2003-2005). METHODS: We conducted a retrospective review of 31 cases of Cardona KPro implanted between 1975 and 1981 and a review of 25 cases of Dohlman-Doane type 1 KPro implanted between 2003 and 2005. Procedures were limited to eyes with a poor prognosis for traditional penetrating keratoplasty. RESULTS: In the Cardona cases, 39% (12/31) of patients achieved a visual acuity of 20/40 or better at some point postoperatively, degrading to 16% (5/31) at the end of the observation period. Fifty percent (15/31) required subsequent surgical revision of the KPro. Sixteen percent of cases (5/31) developed endophthalmitis, and 58% (18/31) developed retroprosthetic membranes. There were 5 dislocations of the prosthesis and an additional 3 frank extrusions (26%). Of the 25 Dohlman-Doane cases, there have been no reoperations, endophthalmitis, dislocations, or extrusions to date (8/15/05). Forty-eight percent (12/25) achieved 20/200 acuity or better, and 12% (3/25) achieved 20/40 or better. Retroprosthetic membranes formed in 3 cases. CONCLUSION: Although KPro remains a technique to be used in poor prognosis keratoplasty, improvements in the design of the device and surgical technique over the past 30 years have reduced the overall morbidity and severity of complications and improved the prognosis for visual rehabilitation.

Adolescent↗

PubMed2006

Retinal localization and copper-dependent relocalization of the Wilson and Menkes disease proteins.

PURPOSE: Menkes and Wilson diseases are associated with retinal degeneration. The Menkes and Wilson genes are homologous copper transporters, but differences in their expression pattern lead to different disease manifestations. To determine whether the Wilson and Menkes genes may act locally in the retina, this study was undertaken to assess retinal Wilson and Menkes expression and localization. METHODS: RT/PCR was used to test for the presence of Wilson and Menkes mRNAs in mouse and human retinas and retinal pigment epithelial cell lines. The Menkes and Wilson proteins were immunolocalized in human and mouse retinas and in the ARPE-19 cell line. RESULTS: The Menkes mRNA and protein were present in the RPE and neurosensory retina whereas the Wilson mRNA and protein were limited to the RPE. In the RPE, both proteins localized to the Golgi. Increased copper concentration led to relocalization of the Wilson protein to a diffuse cytoplasmic distribution. CONCLUSIONS: Both the Menkes and Wilson proteins are present in the RPE. Since the RPE is a blood-brain barrier, these proteins most likely regulate not only their own copper levels but also copper levels of the overlying photoreceptors. Because the Wilson protein delivers copper to the ferroxidase ceruloplasmin in the liver, it is likely that the Wilson and/or Menkes proteins provide copper to ceruloplasmin made in the RPE. Retinopathy in Wilson and Menkes diseases may result not only from abnormal systemic copper levels but also from loss of retinal Wilson or Menkes protein.

Adenosine Triphosphatases↗

PubMed2005

[Effect of curcumin on the gene expression of low density lipoprotein receptors].

OBJECTIVE: To investigate the molecular mechanisms and effective target points of lipid-lowering drug, Rhizoma Curcumae Longae, and study the effect of curcumin on the expression of low density lipoprotein (LDL) receptors in macrophages in mice. METHODS: Macrophages in mice were treated with curcumin, which was purified from the ethanolly extraction of Rhizoma Curcumae Longae for 24 h. The LDL receptors expressed in the macrophages were determined by enzyme-linked immunosorbent assay (ELISA) and assay of DiI labeled LDL uptake by flow cytometer. RESULTS: It was found for the first time that 10 micromol/L-50 micromol/L curcumin could obviously up-regulate the expression of LDL receptor in macrophages in mice, and a dose-effect relationship was demonstrated. CONCLUSION: One of the lipid-lowering mechanisms of traditional Chinese medicine, Rhizoma Curcumae Longae, was completed by the effect of curcumin through the up-regulation of the expression of LDL receptor.

Animals↗

PubMed2005

Keratoprosthesis: the Dohlman-Doane device.

PURPOSE: To determine the usefulness of the Dohlman-Doane type I keratoprosthesis for visual rehabilitation in cases of poor prognosis for traditional penetrating keratoplasty. DESIGN: A retrospective, noncomparative interventional series of 25 patients who had sustained multiple graft failure or who were otherwise deemed poor candidates for conventional keratoplasty. METHODS: Candidates were evaluated for potential acuity, intraocular pressure, inflammation, the quality of the ocular surface, and overall prognosis for penetrating keratoplasty. The keratoprosthesis was assembled and mounted on an 8.5- or 9.0-mm diameter donor corneal button and sutured into an 8.0- or 8.5-mm diameter recipient bed with 12 to 16 9-0 nylon sutures. Patients were examined on the first day and subsequently in 1 week and 1 month and then at 3-month intervals. RESULTS: All devices were retained without dislocation or extrusion. There were no instances of endophthalmitis or surface infection. Fundus details were visible on the first postoperative day. Patients achieved their best acuity in an average of 2 months (range, 1 to 180 days). Improvement in acuity was observed in an average of 13 days (range, 1 to 60 days). Retroprosthetic membranes occurred in three cases, with multiple recurrences in one instance. Visual acuity ranged from no light perception to 20/25. CONCLUSION: We conclude that this prosthesis can be implanted routinely and maintained with minimal complications in poor prognosis keratoplasty, which presents the potential for visual rehabilitation.

Adult↗

PubMed2004

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration.

Mechanisms of brain and retinal iron homeostasis have become subjects of increased interest after the discovery of elevated iron levels in brains of patients with Alzheimer's disease and retinas of patients with age-related macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and its homolog hephaestin (Heph) are important for retinal iron homeostasis, we studied retinas from mice deficient in Cp and/or Heph. In normal mice, Cp and Heph localize to Müller glia and retinal pigment epithelium, a blood-brain barrier. Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron. The iron storage protein ferritin was also increased in Cp-/-Heph-/Y retinas. After retinal iron levels had increased, Cp-/-Heph-/Y mice had age-dependent retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor degeneration, and subretinal neovascularization, providing a model of some features of the human retinal diseases aceruloplasminemia and age-related macular degeneration. This pathology indicates that Cp and Heph are critical for CNS iron homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent retinal neurodegeneration, providing a model that can be used to test the therapeutic efficacy of iron chelators and antiangiogenic agents.

Animals↗

PubMed2004

Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina.

PURPOSE: CNS iron accumulation is associated with several neurodegenerative diseases, including age-related macular degeneration. Intracellular overload of free iron is prevented, in part, by the iron export protein, ferroportin, and the iron storage protein, ferritin. The purpose of this study was to assess retinal localization and regulation of ferroportin and ferritin. METHODS: Normal murine retinas were analyzed by immunohistochemistry to localize ferroportin, cytosolic ferritin, and mitochondrial ferritin, with double-labeling using cell-specific markers to identify cell types. Retinas deficient in the ferroxidases, ceruloplasmin and hephaestin, accumulate iron in their retinas and RPE, while retinas deficient in iron regulatory proteins (IRPs) lack the ability to regulate several proteins involved in iron metabolism; retinas from these knockout mice along with their age matched wild type littermates were also examined to study regulation of ferritin and ferroportin. To enable visualization of label in the retinal pigment epithelial cells, sections from pigmented mice were bleached with H2O2 prior to IHC, a novel use of this technique for study of the RPE. RESULTS: In normal retinas, cytosolic ferritins were found predominantly in rod bipolar cells and photoreceptors. Ferroportin was found in RPE and Müller cells. Iron accumulation in mice deficient in ceruloplasmin and hephaestin was associated with upregulation of ferritin and ferroportin. Mice deficient in IRPs showed upregulation of ferritin and ferroportin, likely because of their inability to repress translation. CONCLUSIONS: Normal retinas contain ferritin and ferroportin, whose levels are regulated by iron-responsive, iron regulatory proteins. Ferroportin colocalizes with ceruloplasmin and hephaestin to RPE and Müller cells, supporting a potential cooperation between these ferroxidases and the iron exporter. Cytosolic ferritin accumulates in rod bipolar synaptic terminals, suggesting that ferritin may be involved in axonal iron transport. Mitochondrial ferritin increases with iron accumulation, suggesting a role in iron storage.

Animals↗

PubMed2004

Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates.

Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord. First, we found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons. Both generic and region-specific glutamatergic markers, including VGLUT2 and the AMPA receptor Gria2, were absent in Tlx mutant dorsal horn. Second, spinal GABAergic markers were derepressed in Tlx mutants, including Pax2 that is necessary for GABAergic differentiation, Gad1/2 and Viaat that regulate GABA synthesis and transport, and the kainate receptors Grik2/3. Third, ectopic expression of Tlx3 was sufficient to suppress GABAergic differentiation and induce formation of glutamatergic neurons. Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice.

Amino Acid Transport Systems↗

PubMed2004

Effect of acute and chronic olanzapine treatment on phencyclidine-induced behavioral sensitization in rats with neonatal dopamine loss.

In agreement with previous work, adult rats given selective lesions to dopamine (DA)-containing neurons as neonates exhibited a greater behavioral sensitization to repeated phencyclidine (PCP) treatment in comparison to sham-lesioned controls. Acute administration of olanzapine (1-5 mg/kg ip) or clozapine (15 mg/kg ip) decreased sensitized PCP-induced activity in both lesioned and control animals. Acute haloperidol (0.5 mg/kg ip) had no impact on PCP responsiveness in lesioned animals, but significantly antagonized PCP effects in sham-lesioned controls. Ketanserin, a selective 5-HT(2A)/5-HT(2C)-receptor antagonist, significantly reduced PCP activation in both lesioned and control rats, suggesting that the efficacy of atypical antipsychotics against PCP-induced sensitized responses may be mediated by one of the 5-HT(2)-receptor subtypes. A 6-week chronic regimen of orally administered olanzapine, clozapine, or haloperidol failed to block the sensitization induced by repeated PCP exposure. However, a 10-month oral olanzapine treatment significantly blunted the behavioral sensitization to repeated PCP exposure in lesioned animals, even after withdrawal from chronic olanzapine for more than 3 weeks. A 10-month oral haloperidol treatment had no effect on the sensitization induced by repeated PCP dosing. The persistent effect of chronic olanzapine administration on PCP sensitization may be relevant to the chronic therapeutic efficacy of atypical antipsychotics treating schizophrenia-a clinical syndrome linked to enhanced sensitivity to N-methyl-d-aspartate (NMDA)-receptor antagonists.

Animals↗

PubMed2004

Ex vivo adenovirus-mediated gene transfer to corneal graft endothelial cells in mice.

PURPOSE: Genetic modulation of donor tissue before corneal transplantation may have the potential to modulate alloimmunity and/or to prevent corneal endothelial cell death. This study was conducted to optimize adenovirus-mediated gene transfer to donor corneal endothelium and to delineate the kinetics of marker gene expression in syngeneic and allogeneic corneal grafts. METHODS: BALB/c mouse corneas were incubated with replication-deficient adenovirus encoding green fluorescent protein (GFP) or empty vector ex vivo at a dose of 6 x 10(7) or 6 x 10(6) PFU at temperatures of 4 degrees C or 37 degrees C. After ex vivo infection, the donor corneas were transplanted orthotopically to BALB/c or C57BL/6 recipients. After transplantation, localization of GFP in the grafts was determined in cryosections of enucleated eyes, and GFP expression in the grafts was visualized in vivo by using epifluorescence microscopy over 12 weeks. All grafts were evaluated clinically by slit lamp biomicroscopy. RESULTS: GFP expression was found to be restricted to the corneal endothelium. In vivo expression of GFP in syngeneic corneal grafts was demonstrated for up to 12 weeks. Syngeneic grafts incubated with the vector at 4 degrees C exhibited a more extensive and longer duration of expression of green fluorescence than grafts incubated at 37 degrees C. Moreover, the syngeneic grafts infected at 4 degrees C maintained their transparency, whereas those infected at 37 degrees C displayed a high degree of opacity. Corneal allogeneic grafts infected with a low dose of the vector displayed longer GFP expression and graft survival than the allogeneic grafts infected with a high dose of the viral vector. CONCLUSIONS: Adenoviral vector can selectively and efficiently deliver exogenous gene(s) to the endothelium of corneal grafts during hypothermic organ preservation. Gene expression is retained in vivo in corneal syngeneic grafts for longer periods than are allogeneic grafts.

Adenoviridae↗

PubMed2002

Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.

Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation. Rnx and Tlx-1 maintain expression of Drg11, a homeobox gene critical for the development of pain circuitry, and are essential for the ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. We showed previously that Rnx is necessary for proper formation of the nucleus of solitary tract, the target for visceral sensory afferents. Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral.

Animals↗

PubMed2002

Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.

Animals↗

PubMed2002

Effect of locally administered anti-CD154 (CD40 ligand) monoclonal antibody on survival of allogeneic corneal transplants.

PURPOSE: To determine the effect of ocular administration of anti-CD154 monoclonal antibody on the survival of orthotopic murine corneal transplants. METHODS: BALB/c mice were used as recipients of multiple minor H- and MHC-mismatched orthotopic corneal transplants. Recipient beds were either avascular (normal-risk) or neovascularized (high-risk) at the time of surgery. Mice were randomized to receive either anti-CD154 antibody or control immunoglobulin by subconjunctival injection. All grafts were evaluated for signs of rejection by slitlamp biomicroscopy until week 20-24 with the therapy tapered and discontinued after week 8 and week 12, respectively. RESULTS: In normal-risk transplantation, the 8-week survival rate improved from 30% in control mice to 90% in anti-CD154 treated mice (p= 0.0061). In high-risk transplantation, the survival rate of anti-CD154-treated mice was enhanced to 55% compared with 0% in control mice at week 8 (p= 0.0184); however, tapering and termination of anti-CD154 led to some loss in graft survival, with a survival rate of 56% in normal-risk recipients, and 22% in high-risk recipients by week 20. Anti-CD40L treated animals displayed lower grades of postoperative corneal neovascularization (p<0.05), in particular in normal-risk recipients. CONCLUSIONS: Local ocular administration of anti-CD154 is effective in the prevention of corneal allograft rejection in normal-risk recipients, and in delaying the incidence of rejection in high-risk recipients. Long-term graft survival may not be fully achieved following termination of the CD40-CD154 pathway blockade.

Administration, Topical↗

PubMedDate not supplied

Regulation of LDL receptor expression by the effect of curcumin on sterol regulatory element pathway.

To investigate the molecular mechanisms of the effect of curcumin on up-regulation of LDL receptor expression, a sterol regulatory report system was established in Xenopus laevis oocytes by microinjection of a plasmid pLXRN-4SRE-fPA, in which green fluorescence protein (GFP) gene was constructed downstream from the sterol regulatory element-1 (SRE-1), in the nucleus of the oocytes. The oocytes were treated with different kinds of natural medicines: curcumin, tea polyphenols, tanshinone, ligustrazine, ginkgolide, astragalosides. The expression of GFP was induced only by curcumin. In addition, it was also proved that the curcumin can increase the expression of functional LDL receptors in human liver hepatoma cell line HepG2. In conclusion, curcumin may up-regulate the expression of LDL receptor by its effect on SRE pathway.

Animals↗