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Biomedical subjects

He Meng

Publications and source records attributed to He Meng.

16 recordsLinked to original sources
PubMed2026

DAZL-targeted inducible kill switches enable efficient ablation of chicken primordial germ cells.

Competition from endogenous primordial germ cells (PGCs) in recipient embryos limits the generation of fully donor-derived offspring in avian surrogate-host systems. An inducible and germline-restricted ablation strategy is therefore needed to create sterile recipients without compromising somatic development. Using CRISPR/Cas9-mediated homology-directed repair, we inserted three inducible suicide-gene cassettes (iCaspase9, RapaCasp9, and CD) into the endogenous DAZL locus of chicken PGCs. All knock-in lines showed stable reporter expression and retained typical PGC morphology. Comparative functional analyses identified iCaspase9 activated by AP20187 as the most sensitive and specific ablation system, achieving near-complete killing at nanomolar concentrations without detectable toxicity in control cells. RapaCasp9 induced with rapamycin also ablated engineered PGCs efficiently, but rapamycin caused marked non-specific growth inhibition in control cells. Replacing rapamycin with the synthetic A/C heterodimerizer AP21967 largely eliminated this off-target toxicity while preserving rapid and robust killing. By contrast, yeast-derived CD variants did not substantially improve 5-fluorocytosine sensitivity in chicken PGCs. DAZL-restricted iCaspase9/AP20187 and the optimized RapaCasp9/AP21967 system provide efficient inducible kill switches for chicken PGCs in vitro. These platforms establish a practical genetic toolkit for generating sterile surrogate hosts to support avian genome editing, germline replacement, and Sire Dam Surrogate breeding.

CRISPR/Cas9↗
PubMed2006

MRI detects white matter reorganization after neural progenitor cell treatment of stroke.

We evaluated the effects of neural progenitor cell treatment of stroke on white matter reorganization using MRI. Male Wistar rats (n = 26) were subjected to 3 h of middle cerebral artery occlusion and were treated with neural progenitor cells (n = 17) or without treatment (n = 9) and were sacrificed at 5-7 weeks thereafter. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. White matter reorganization, confirmed histologically, was coincident with increases of fractional anisotropy (FA, P < 0.01) after stroke in the ischemic recovery regions compared to that in the ischemic core region in both treated and control groups. Immunoreactive staining showed axonal projections emanating from neurons and extruding from the corpus callosum into the ipsilateral striatum bounding the lesion areas after stroke. Fiber tracking (FT) maps derived from diffusion tensor imaging revealed similar orientation patterns to the immunohistological results. Complementary measurements in stroke patients indicated that FT maps exhibit an overall orientation parallel to the lesion boundary. Our data demonstrate that FA and FT identify and characterize cerebral tissue undergoing white matter reorganization after stroke and treatment with neural progenitor cells.

Algorithms↗
PubMed2006

Protection of adult mouse progenitor cells and human glioma cells by de novo decorin expression in an oxygen- and glucose-deprived cell culture model system.

We employed an in vitro hypoxia cell culture model system and gene transfer technology to examine the effect of the decorin gene on cell survival against oxygen and glucose deprivation (OGD). Ectopic expression of decorin in subventricular zone (SVZ) cells from adult male mouse brain and human glioblastoma U-87 cells kept the cells viable against 24 h of OGD. Fewer than 1% of decorin-synthesizing cells were apoptotic after 12 h of OGD. In contrast, 100% of the control cells were apoptotic even after 4 h of OGD. De novo decorin synthesis in SVZ and U-87 cells induced expression of p21, p27 and Ras, AKT (acutely transforming retrovirus AKT8 in rodent T-cell lymphoma), and phosphorylated AKT. Blocking of phosphoinositide 3-kinase (PI-3K), Ras, and the epidermal growth factor receptor with specific inhibitors had no effect on induction of Ras, p21, and p27 at the messenger RNA level in decorin-synthesizing SVZ and U-87 cells. PI-3K inhibitors significantly increased apoptosis in decorin-expressing cells. Our data indicate that induction of p21, p27, Ras, AKT, and phosphorylated AKT by decorin inhibits apoptosis and protects U-87 and SVZ cells against OGD. Therefore, our data suggest that decorin is a potent trophic factor that protects neuronal progenitor cells and glioma cells from OGD.

Aging↗
PubMed2006

[Distributions of polymorphism of ADD1, MC4R, H-FABP gene, associated with IMF and BF in 3 populations in pig].

Different breeds of pigs varied in traits of meat quality, especially between local abroad varieties. Intramuscular fat content (IMF) and back fat thickness (BF) have extra difference between Chinese breeds and foreign breeds. We have known that polymorphism of H-FABP, MC4R and ADD1 gene associated relation with IMF or BF in recent research. The Meishan, Sutai and Duroc x Landrace x Yorkshair become experimental animal in this research. Result show three breeds have different IMF and BF because different distributions of polymorphism three genes. Meishan has particular genetic background, so it should be protected. The results of associated analysis show that the polymorphism of three genes was associated traits of IMF and BF, polymorphism of MC4R gene was not associated traits BF. The molecular marker can apply to pig breeding by molecular marker-assisted selection (MAS).

Animals↗
PubMed2005

Multitargeted effects of statin-enhanced thrombolytic therapy for stroke with recombinant human tissue-type plasminogen activator in the rat.

BACKGROUND: Microvascular dysfunction posttreatment of stroke with recombinant human tissue-type plasminogen activator (rht-PA) constrains the therapeutic window to 3 hours. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) promote vascular thrombolysis and reduce the inflammation response. We therefore investigated the neuroprotective effects of a combination of atorvastatin and delayed rht-PA treatment in a rat model of embolic stroke. METHODS AND RESULTS: Rats subjected to embolic middle cerebral artery occlusion were treated with atorvastatin in combination with rht-PA 4 hours after stroke. Magnetic resonance imaging measurements revealed that combination treatment with atorvastatin and rht-PA blocked the expansion of the ischemic lesion, which improved neurological function compared with saline-treated rats. Real-time reverse transcription-polymerase chain reaction analysis of single endothelial cells isolated by laser-capture microdissection from brain tissue and immunostaining showed that combination treatment downregulated expression of tissue factor, von Willebrand factor, protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, which concomitantly reduced cerebral microvascular thrombosis and enhanced microvascular integrity. Combination treatment did not increase cerebrovascular endothelial nitric oxide synthase (eNOS) levels or eNOS activity, and inhibition of NOS activity with N-nitro-L-arginine methyl ester did not block the beneficial effects of combination treatment on stroke. Furthermore, combination treatment compared with thrombolytic monotherapy increased cerebral blood flow and reduced infarct volume in eNOS-null mice. CONCLUSIONS: These data demonstrate that combination treatment with atorvastatin and rht-PA exerts a neuroprotective effect when administered 4 hours after stroke and that the therapeutic benefits are likely attributed to its multitargeted effects on cerebrovascular patency and integrity.

Animals↗
PubMed2005

Biphasic effects of exogenous VEGF on VEGF expression of adult neural progenitors.

Vascular endothelial growth factor (VEGF) regulates neurogenesis. The present study investigated the direct effect of VEGF on the enhancement of proliferation and differentiation of the adult mouse subventricular zone (SVZ) neural progenitors in vitro. A high dose (500 ng/ml) of VEGF significantly downregulated endogenous VEGF receptors 1 and 2, which was associated with significantly reduced neural progenitor cell proliferation and enhancement of neuronal differentiation. A low dose (50 ng/ml) of VEGF significantly upregulated endogenous VEGF receptors 1 and 2 but did not increase proliferation and differentiation. These data suggest that exogenous VEGF has a biphasic effect on the expression of endogenous VEGF receptors, and the high dose of VEGF enhances adult neural progenitor cell differentiation into neurons.

Animals↗
PubMed2005

Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI.

Using MRI, we investigated dynamic changes of brain angiogenesis after neural progenitor cell transplantation in the living adult rat subjected to embolic stroke. Neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat were labeled by superparamagnetic particles and intracisternally transplanted into the adult rat 48 h after stroke (n = 8). Before and after the transplantation, an array of MRI parameters were measured, including high resolution 3D MRI and quantitative T1, T1sat (T1 in the presence of an off-resonance irradiation of the macromolecules of brain), T2, the inverse of the apparent forward transfer rate for magnetization transfer (kinv), cerebral blood flow (CBF), cerebral blood volume (CBV), and blood-to-brain transfer constant (Ki) of Gd-DTPA. The von Willerbrand factor (vWF) immunoreactive images of coronal sections obtained at 6 weeks after cell transplantation were used to analyze vWF immunoreactive vessels. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. In the ischemic boundary regions, angiogenesis confirmed by an increase in vascular density and the appearance of large thin wall mother vessels was coincident with increases of CBF and CBV (CBF, P < 0.01; CBV, P < 0.01) at 6 weeks after treatment, and coincident with transient increases of K(i) with a peak at 2 to 3 weeks after cell therapy. Relative T1, T1sat, T2, and kinv decreased in the ischemic boundary regions with angiogenesis compared to that in the non-angiogenic ischemic region (T1, P < 0.01 at 6 weeks; T1sat, P < 0.05 at 2 to 6 weeks; T2, P < 0.05 at 3 to 6 weeks; kinvP < 0.05 at 6 weeks). Of these methods, Ki appear to be the most useful MR measurements which identify and predict the location and area of angiogenesis. CBF, CBV, T1sat, T1, T2, and kinv provide complementary information to characterize ischemic tissue with and without angiogenesis. Our data suggest that select MRI parameters can identify the cerebral tissue destined to undergo angiogenesis after treatment of embolic stroke with cell therapy.

Algorithms↗
PubMed2005

Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor.

BACKGROUND AND PURPOSE: Advanced age is associated with a decrease in brain plasticity compared with the young adult. Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor promotes brain plasticity and improves functional outcome after stroke in the young animal. Here, we test the hypothesis that sildenafil provides restorative therapeutic benefit to the aged animal. METHODS: Male Wistar rats (aged, 18-month old; young, 3-month old) were subjected to embolic stroke. Saline or sildenafil was administered daily at a dose of 2 mg/kg orally or 10 mg/kg subcutaneously for 7 consecutive days starting 24 hour after stroke onset. RESULTS: Aged rats exhibited significant impairment of functional recovery and reductions of vascular density, and endothelial cell proliferation compared with young rats. Aged rats treated with sildenafil at a dose of 10 mg/kg but not 2 mg/kg, showed significant improvements of functional recovery and concomitant increases in cortical cyclic guanosine 3',5'-cyclic monophosphate (cGMP) level, vascular density, endothelial cell proliferation, and synaptogenesis compared with aged rats treated with saline. In young rats, treatment with sildenafil at a dose of 2 or 10 mg/kg significantly enhanced functional recovery and amplified brain plasticity compared with young rats treated with saline. CONCLUSIONS: Age is associated with reduction of angiogenesis, and poor neurological functional recovery after stroke. However, treatment of aged stroke rats with sildenafil improves functional recovery that is likely fostered by enhancement of angiogenesis and synaptogenesis.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Molecular cloning and characterization of monoamine oxidase A and B genes in pig.

Monoamine oxidase (MAO) is a key enzyme in the degradation of monoamine neurotransmitters, which are physiologically and pathologically important for animals and humans. MAO exists in two forms, coded by separate genes. Here we cloned and sequenced full length cDNAs of MAO-A and MAO-B in pig. The putative proteins include 527 and 520 amino acids, respectively. The sequences alignment and homology analysis showed that MAO-A and MAO-B are conserved among mammals. The amino acid residues and domains, which have been demonstrated to be important for MAO-A and MAO-B binding of ligands, substrates and inhibitors, were conserved in the pig.

Amines↗
PubMed2004

A novel chainlike As-V-O polymer based on a transition metal complex and a dimeric polyoxoanion.

The novel polyoxometalate ([As(8)V(13)NiClO(41)][Ni(en)(2)(H(2)O)][Ni(en)(2)])([Ni(en)(2)(H(2)O)(2)](0.5)).4H(2)O (1), which is the first example of a chainlike inorganic-organic hybrid polymer based on dimeric polyoxoanions linked by nickel complex fragments, has been synthesized in the system of As(2)O(3)-V(2)O(5)-H(2)C(2)O(4)-en-NiCl(2).6H(2)O-H(2)O under hydrothermal conditions and characterized by IR, TGA, elemental analysis, single crystal X-ray diffraction, XPS, and magnetic susceptibility studies, respectively. This compound crystallized in the triclinic space group P with a = 13.358(3) angstroms, b = 14.198(3) angstroms, c = 19.723(4) angstroms, alpha = 83.88(3) degrees, beta = 86.04(3) degrees, gamma = 64.66(3) degrees, V = 3360.2(2) angstroms(3), and Z = 2. Interestingly, the dimeric polyoxoanion contains two ([Ni(en)(2)(H(2)O)][As(8)V(13)NiClO(41)]) cluster units linked by Ni-O-As bonds and is a Ni-substituted [As(8)V(13)NiClO(41)] cluster supported by [Ni(en)(2)(H(2)O)] coordination fragment. The chainlike structure consists of ([Ni(en)(2)(H(2)O)][As(8)V(13)NiClO(41)])(2) dimeric polyoxoanions and [Ni(en)(2)] groups which are linked together through vertexes forming a unique one-dimensional polymer. The study of the magnetic susceptibility of 1 demonstrates the presence of antiferromagnetic interaction in 1.

Journal Article↗
PubMed2004

[Characterization of tissue expression of peroxisome proliferator activated receptors in the chicken].

The peroxisome proliferator activated receptor (PPAR) is the member of super family of nuclear receptors. A great number of researches in rodent and human have showed that PPARs are involved in the lipids metabolism, especially in regulating the microsome,expression of genes coding the various enzymes during the beta-oxidation of peroxisome and the differentiation of adipose cell. The PPARs are one of the important gene clusters that are viewed as the objective genes correlated with the lipids metabolism and corresponding diseases. Great differences in lipids metabolism are existed between the poultry and mammals. The mechanism of the lipids metabolism in poultry is not completely understood. The current study was designed to investigate the expression characterization of PPAR genes in chicken in order to understand the effects of PPAR gene on adipose and other tissues. The eight weeks age Arber Acres broilers were used and quantitative RT-PCR and Northern blot were developed to analyze the expression characterization of PPAR-alpha and PPAR-gamma gene in heart, liver, spleen, lung, kidney, stomach, intestine, brain, muscle and adipose tissues. Results of the quantitative RT-PCR showed that the expression level of PPAR-alpha gene was higher in brain, lung, kidney, heart and intestine, medium in stomach, liver and adipose, and lower in spleen. But did no expression was detected in breast muscle. The expression level of PPAR-gamma gene was higher in adipose, medium in brain and kidney, lower in spleen, heart, lung, stomach and intestine, but no expression was detected in liver and breast muscle. Northern blot results showed that PPAR-alpha gene expressed in heart, liver, kidney and stomach, and the intensity of hybridization signal was the greatest in liver tissue; PPAR-gamma gene only expressed in adipose and kidney tissues, and the intensity of hybridization signal was greater in adipose tissue. The present study results showed that the tissue expression characterization of PPARs gene in chicken was almost consistent with that in rodent and human, but, in chicken, PPAR-alpha did not expressed in breast muscle and PPAR-gamma gene expressed in kidney. The results of current research indicated simultaneously that the PPAR genes were related with the growth and development of various tissues and organs.

Animals↗
PubMed2004

[Cloning and sequence analysis of cDNA encoding PPAR from goose].

The peroxisome proliferator activated receptor (PPAR) belongs to a large family of nuclear receptors. This study was designed to clone and sequence analysis of cDNA encoding PPAR from goose. The RT-PCR method was developed to clone the cDNA, and the lengths of cDNA encoding PPARalpha and PPARgamma were 1407bp and 1428bp respectively. The cDNAs of the two genes were cloned and sequenced for the first time. The identities of CDS of PPARalpha and PPARgamma gene were 87.43% and 92.00% by homologous comparison among goose and other five species, and that were 93.38% and 96.95% in amino acid sequences. The further analysis among seventeen species including goose showed that the identities of PPAR genes were low(66.18%) among different sub-type (alpha,gamma,beta) of PPAR genes and that was high for the same sub-type of PPAR genes: PPARalpha, PPARgamma and PPARbeta (or PPARdelta) were 84.80%, 86.23% and 87.36% respectively. The results showed that these two genes are conservative in the process of evolution and has important physiological function for the growth and development of birds and mammals. The results of the present study will benefit the further study of relationship between PPAR genes and the growth and development, especially in fat metabolism of goose.

Amino Acid Sequence↗
PubMed2002

[Studies of single nucleotide polymorphism of PPAR gene and its associations with fattiness trait in chicken].

In this experiment, the AA broiler fat traits and three Chinese special breeds (Shiqiza, Beijing youji and Baier) were used to study the effect of PPAR-alpha gene on fat trait. Coding region of the gene was amplified by seven pairs of primers, and then single nucleotide polymorphisms (SNPs) were detected by the technique of single strand conformation polymorphism (SSCP) and finally confirmed by sequencing. One nucleotide variation was found, the result of chi 2 analysis showed that the distribution of three genotypes was very different among different breeds(P < 0.01). The result of variance analysis showed that the birds with BB genotype had a higher abdominal fat weight than the birds with other genotypes (AA and AB). It implied that PPAR-alpha gene could be a candidate locus or linked to a major gene to significantly affect abdominal fat traits in chicken.

Abdomen↗
PubMed2002

[The study of the uncoulping protein gene as the candidate gene for fatness traits in chicken].

The UCPs are integral membrane proteins of the mitochondrial respiration from oxidative phosphorylation, diminishing the resulting production of ATP and instead yielding dissipative heat. The action of those proteins creates a futile cycle that decreases the metabolic efficiency of the organism. Thus UCPs provide new clue to obesity's causes. This study was designed to investigate the effect of UCP gene on chicken fatness traits. The fifth generation population of divergent selection broiler line, Hyline Brown layer and three native breeds (shiqiza, Beijing You, baier) were used in this research. Body weight and body composition traits were measured in broiler lines at 7 weeks of age. Primers for the 3'-untranslator region in UCP were designed from database of chicken genomic sequence. Polymorphisms were detected by PCR-SSCP and DNA sequencing. The results showed that there was significant difference (P < 0.01) in the frequency of genotype among breeds except broiler vs Beijing You and Baier vs Hyline Brown layer in mutation sites detected by the two pairs of primers. The distribution of genotype in Beijing You and broiler had no difference. It deduced that Beijing You belongs to the native breed that has dominant meat type traits and has the same genetic background with broiler. Baier and Hyline Brown Layer have no difference in the genotype, it can be viewed as they have same genetic background. A A/C mutation at base position 1197 was found among individuals in broiler line and the least square analysis showed that BB birds had significant lower (P < 0.01) abdominal fat weight and percentage of abdominal fat than AB or AA birds. From the results we can putatively draw the conclusion that UCP gene is the major gene to affect the fatness traits or it links with the major gene.

Animals↗
PubMed2002

[Single nucleotide polymorphism analysis in chicken leptin receptor exon 9].

Leptin receptor is a type I cytokine super family member and plays an important role in leptin functioning signal transduction. This study was designed to investigate the single nucleotide polymorphism (SNP) of OBR gene in various breeds, including Fatness Line (FL), Leanness Line (LL), Beijing Youji, Baierji, Shiqiza, Dwarf Yellow Chickens, Mini Yellow Chickens, Huiyang Huxuji, Recessive White Chickens and Hyline Layer. The primers for exon 9 in OBR gene were designed from the database of chicken genomic sequence and the SNPs were detected by PCR-SSCP method. One SNP (C/A at 1167 in cds) was found among individuals within all breeds. However, the amino acid was not changed because it was a silence mutation. The result of population genetics analyses showed that the frequency of AA genotype in Beijing Youji was significantly higher than that in other lines. Also, the frequency of A allele in FL was significantly higher than that in LL.

English Abstract↗